Sesquiterpene Lactones with Anti-Hepatitis C Virus Activity Using Molecular Descriptors

Hepatitis C is a worldwide public health problem. The available therapies are limited by their partial effectiveness and with meaningful side-effects. Sesquiterpene lactones (SLs) are a group of natural products with a wide variety of chemical structures and biological activities associated. There are few studies about the influence of the molecular structure of SLs for the anti-hepatitis C virus activity. In the present work, SLs are investigated in a subgenomic RNA replicon assay system and were analyzed using multiple linear regression along with self-organizing maps with DRAGON descriptors in order to identify the structural requirements for their biological activity and to predict the inhibitory potency of SLs. Characteristics such as stereochemistry and electronic effects demonstrated to be important for their anti-HCV activity, and the SOM produced a clear separation betwenn active and inactive compounds. Therefore, it is possible to use this map as a filter for virtual screening to predict the anti-HCV activity of SLs.

On the radial expansion of tubular structures in a quark-gluon plasma

We study the radial expansion of cylindrical tubes in a hot QGP. These tubes are treated as perturbations in the energy density of the system which is formed in heavy ion collisions at RHIC and LHC. We start from the equations of relativistic hydrodynamics in two spatial dimensions and cylindrical symmetry and perform an expansion of these equations in a small parameter, conserving the nonlinearity of the hydrodynamical formalism. We consider both ideal and viscous fluids and the latter are studied with a relativistic Navier-Stokes equation. We use the equation of state of the MIT bag model. In the case of ideal fluids we obtain a breaking wave equation for the energy density fluctuation, which is then solved numerically. We also show that, under certain assumptions, perturbations in a relativistic viscous fluid are governed by the Burgers equation. We estimate the typical expansion time of the tubes. (C) 2012 Elsevier B.V. All rights reserved.

Different protocols to produce artificial dentine carious lesions in vitro and in situ: hardness and mineral content correlation

This study compared dentine demineralization induced by in vitro and in situ models, and correlated dentine surface hardness (SH), cross-sectional hardness (CSH) and mineral content by transverse microradiography (TMR). Bovine dentine specimens (n = 15/group) were demineralized in vitro with the following: MC gel (6% carboxymethylcellulose gel and 0.1 m lactic acid, pH 5.0, 14 days); buffer I (0.05 m acetic acid solution with calcium, phosphate and fluoride, pH 4.5, 7 days); buffer II (0.05 m acetic acid solution with calcium and phosphate, pH 5.0, 7 days), and TEMDP (0.05 m lactic acid with calcium, phosphate and tetraethyl methyl diphosphonate, pH 5.0, 7 days). In an in situ study, 11 volunteers wore palatal appliances containing 2 bovine dentine specimens, protected with a plastic mesh to allow biofilm development. The volunteers dripped a 20% sucrose solution on each specimen 4 times a day for 14 days. In vitro and in situ lesions were analyzed using TMR and statistically compared by ANOVA. TMR and CSH/SH were submitted to regression and correlation analysis (p < 0.05). The in situ model produced a deep lesion with a high R value, but with a thin surface layer. Regarding the in vitro models, MC gel produced only a shallow lesion, while buffers I and II as well as TEMDP induced a pronounced subsurface lesion with deep demineralization. The relationship between CSH and TMR was weak and not linear. The artificial dentine carious lesions induced by the different models differed significantly, which in turn might influence further de- and remineralization processes. Hardness analysis should not be interpreted with respect to dentine mineral loss

The photosynthetic bacterial reaction center in native and artificial envirnoments: effects on light-induced electron transfer

In this thesis we focussed on the characterization of the reaction center (RC) protein purified from the photosynthetic bacterium Rhodobacter sphaeroides. In particular, we discussed the effects of native and artificial environment on the light-induced electron transfer processes. The native environment consist of the inner antenna LH1 complex that copurifies with the RC forming the so called core complex, and the lipid phase tightly associated with it. In parallel, we analyzed the role of saccharidic glassy matrices on the interplay between electron transfer processes and internal protein dynamics. As a different artificial matrix, we incorporated the RC protein in a layer-by-layer structure with a twofold aim: to check the behaviour of the protein in such an unusual environment and to test the response of the system to herbicides. By examining the RC in its native environment, we found that the light-induced charge separated state P+QB - is markedly stabilized (by about 40 meV) in the core complex as compared to the RC-only system over a physiological pH range. We also verified that, as compared to the average composition of the membrane, the core complex copurifies with a tightly bound lipid complement of about 90 phospholipid molecules per RC, which is strongly enriched in cardiolipin. In parallel, a large ubiquinone pool was found in association with the core complex, giving rise to a quinone concentration about ten times larger than the average one in the membrane. Moreover, this quinone pool is fully functional, i.e. it is promptly available at the QB site during multiple turnover excitation of the RC. The latter two observations suggest important heterogeneities and anisotropies in the native membranes which can in principle account for the stabilization of the charge separated state in the core complex. The thermodynamic and kinetic parameters obtained in the RC-LH1 complex are very close to those measured in intact membranes, indicating that the electron transfer properties of the RC in vivo are essentially determined by its local environment. The studies performed by incorporating the RC into saccharidic matrices evidenced the relevance of solvent-protein interactions and dynamical coupling in determining the kinetics of electron transfer processes. The usual approach when studying the interplay between internal motions and protein function consists in freezing the degrees of freedom of the protein at cryogenic temperature. We proved that the “trehalose approach” offers distinct advantages with respect to this traditional methodology. We showed, in fact, that the RC conformational dynamics, coupled to specific electron transfer processes, can be modulated by varying the hydration level of the trehalose matrix at room temperature, thus allowing to disentangle solvent from temperature effects. The comparison between different saccharidic matrices has revealed that the structural and dynamical protein-matrix coupling depends strongly upon the sugar. The analyses performed in RCs embedded in polyelectrolyte multilayers (PEM) structures have shown that the electron transfer from QA - to QB, a conformationally gated process extremely sensitive to the RC environment, can be strongly modulated by the hydration level of the matrix, confirming analogous results obtained for this electron transfer reaction in sugar matrices. We found that PEM-RCs are a very stable system, particularly suitable to study the thermodynamics and kinetics of herbicide binding to the QB site. These features make PEM-RC structures quite promising in the development of herbicide biosensors. The studies discussed in the present thesis have shown that, although the effects on electron transfer induced by the native and artificial environments tested are markedly different, they can be described on the basis of a common kinetic model which takes into account the static conformational heterogeneity of the RC and the interconversion between conformational substates. Interestingly, the same distribution of rate constants (i.e. a Gamma distribution function) can describe charge recombination processes in solutions of purified RC, in RC-LH1 complexes, in wet and dry RC-PEM structures and in glassy saccharidic matrices over a wide range of hydration levels. In conclusion, the results obtained for RCs in different physico-chemical environments emphasize the relevance of the structure/dynamics solvent/protein coupling in determining the energetics and the kinetics of electron transfer processes in a membrane protein complex.

Improved ground motion intensity measures for reliability-based demand analysis of structures

In Performance-Based Earthquake Engineering (PBEE), evaluating the seismic performance (or seismic risk) of a structure at a designed site has gained major attention, especially in the past decade. One of the objectives in PBEE is to quantify the seismic reliability of a structure (due to the future random earthquakes) at a site. For that purpose, Probabilistic Seismic Demand Analysis (PSDA) is utilized as a tool to estimate the Mean Annual Frequency (MAF) of exceeding a specified value of a structural Engineering Demand Parameter (EDP). This dissertation focuses mainly on applying an average of a certain number of spectral acceleration ordinates in a certain interval of periods, Sa,avg (T1,…,Tn), as scalar ground motion Intensity Measure (IM) when assessing the seismic performance of inelastic structures. Since the interval of periods where computing Sa,avg is related to the more or less influence of higher vibration modes on the inelastic response, it is appropriate to speak about improved IMs. The results using these improved IMs are compared with a conventional elastic-based scalar IMs (e.g., pseudo spectral acceleration, Sa ( T(¹)), or peak ground acceleration, PGA) and the advanced inelastic-based scalar IM (i.e., inelastic spectral displacement, Sdi). The advantages of applying improved IMs are: (i ) "computability" of the seismic hazard according to traditional Probabilistic Seismic Hazard Analysis (PSHA), because ground motion prediction models are already available for Sa (Ti), and hence it is possibile to employ existing models to assess hazard in terms of Sa,avg, and (ii ) "efficiency" or smaller variability of structural response, which was minimized to assess the optimal range to compute Sa,avg. More work is needed to assess also "sufficiency" and "scaling robustness" desirable properties, which are disregarded in this dissertation. However, for ordinary records (i.e., with no pulse like effects), using the improved IMs is found to be more accurate than using the elastic- and inelastic-based IMs. For structural demands that are dominated by the first mode of vibration, using Sa,avg can be negligible relative to the conventionally-used Sa (T(¹)) and the advanced Sdi. For structural demands with sign.cant higher-mode contribution, an improved scalar IM that incorporates higher modes needs to be utilized. In order to fully understand the influence of the IM on the seismis risk, a simplified closed-form expression for the probability of exceeding a limit state capacity was chosen as a reliability measure under seismic excitations and implemented for Reinforced Concrete (RC) frame structures. This closed-form expression is partuclarly useful for seismic assessment and design of structures, taking into account the uncertainty in the generic variables, structural "demand" and "capacity" as well as the uncertainty in seismic excitations. The assumed framework employs nonlinear Incremental Dynamic Analysis (IDA) procedures in order to estimate variability in the response of the structure (demand) to seismic excitations, conditioned to IM. The estimation of the seismic risk using the simplified closed-form expression is affected by IM, because the final seismic risk is not constant, but with the same order of magnitude. Possible reasons concern the non-linear model assumed, or the insufficiency of the selected IM. Since it is impossibile to state what is the "real" probability of exceeding a limit state looking the total risk, the only way is represented by the optimization of the desirable properties of an IM.

De Novo Design of secondary structures: Synthesis and conformational studies

Chemists have long sought to extrapolate the power of biological catalysis and recognition to synthetic systems. These efforts have focused largely on low molecular weight catalysts and receptors; however, biological systems themselves rely almost exclusively on polymers, proteins and RNA, to perform complex chemical functions. Proteins and RNA are unique in their ability to adopt compact, well-ordered conformations, and specific folding provides precise spatial orientation of the functional groups that comprise the “active site”. These features suggest that identification of new polymer backbones with discrete and predictable folding propensities (“foldamers”) will provide a basis for design of molecular machines with unique capabilities. The foldamer approach complements current efforts to design unnatural properties into polypeptides and polynucleotides. The aim of this thesis is the synthesis and conformational studies of new classes of foldamers, using a peptidomimetic approach. Moreover their attitude to be utilized as ionophores, catalysts, and nanobiomaterials were analyzed in solution and in the solid state. This thesis is divided in thematically chapters that are reported below. It begins with a very general introduction (page 4) which is useful, but not strictly necessary, to the expert reader. It is worth mentioning that paragraph I.3 (page 22) is the starting point of this work and paragraph I.5 (page 32) isrequired to better understand the results of chapters 4 and 5. In chapter 1 (page 39) is reported the synthesis and conformational analysis of a novel class of foldamers containing (S)-β3-homophenylglycine [(S)-β3-hPhg] and D- 4-carboxy-oxazolidin-2-one (D-Oxd) residues in alternate order is reported. The experimental conformational analysis performed in solution by IR, 1HNMR, and CD spectroscopy unambiguously proved that these oligomers fold into ordered structures with increasing sequence length. Theoretical calculations employing ab initio MO theory suggest a helix with 11-membered hydrogenbonded rings as the preferred secondary structure type. The novel structures enrich the field of peptidic foldamers and might be useful in the mimicry of native peptides. In chapter 2 cyclo-(L-Ala-D-Oxd)3 and cyclo-(L-Ala-DOxd) 4 were prepared in the liquid phase with good overall yields and were utilized for bivalent ions chelation (Ca2+, Mg2+, Cu2+, Zn2+ and Hg2+); their chelation skill was analyzed with ESI-MS, CD and 1HNMR techniques and the best results were obtained with cyclo-(L-Ala-D-Oxd)3 and Mg2+ or Ca2+. Chapter 3 describes an application of oligopeptides as catalysts for aldol reactions. Paragraph 3.1 concerns the use of prolinamides as catalysts of the cross aldol addition of hydroxyacetone to aromatic aldeydes, whereas paragraphs 3.2 and 3.3 are about the catalyzed aldol addition of acetone to isatins. By means of DFT and AIM calculations, the steric and stereoelectronic effects that control the enantioselectivity in the cross-aldol addition of acetone to isatin catalysed by L-proline have been studied, also in the presence of small quantities of water. In chapter 4 is reported the synthesis and the analysis of a new fiber-like material, obtained from the selfaggregation of the dipeptide Boc-L-Phe-D-Oxd-OBn, which spontaneously forms uniform fibers consisting of parallel infinite linear chains arising from singleintermolecular N-H···O=C hydrogen bonds. This is the absolute borderline case of a parallel β-sheet structure. Longer oligomers of the same series with general formula Boc-(L-Phe-D-Oxd)n-OBn (where n = 2-5), are described in chapter 5. Their properties in solution and in the solid state were analyzed, in correlation with their attitude to form intramolecular hydrogen bond. In chapter 6 is reported the synthesis of imidazolidin-2- one-4-carboxylate and (tetrahydro)-pyrimidin-2-one-5- carboxylate, via an efficient modification of the Hofmann rearrangement. The reaction affords the desired compounds from protected asparagine or glutamine in good to high yield, using PhI(OAc)2 as source of iodine(III).

Bonded structures for enhanced damage tolerant pressurized fuselages

Adhesive bonding provides solutions to realize cost effective and low weight aircraft fuselage structures, in particular where the Damage Tolerance (DT) is the design criterion. Bonded structures that combine Metal Laminates (MLs) and eventually Selective Reinforcements can guarantee slow crack propagation, crack arrest and large damage capability. To optimize the design exploiting the benefit of bonded structures incorporating selective reinforcement requires reliable analysis tools. The effect of bonded doublers / selective reinforcements is very difficult to be predicted numerically or analytically due to the complexity of the underlying mechanisms and failures modes acting. Reliable predictions of crack growth and residual strength can only be based on sound empirical and phenomenological considerations strictly related to the specific structural concept. Large flat stiffened panels that combine MLs and selective reinforcements have been tested with the purpose of investigating solutions applicable to pressurized fuselages. The large test campaign (for a total of 35 stiffened panels) has quantitatively investigated the role of the different metallic skin concepts (monolithic vs. MLs) of the aluminum, titanium and glass-fiber reinforcements, of the stringers material and cross sections and of the geometry and location of doublers / selective reinforcements. Bonded doublers and selective reinforcements confirmed to be outstanding tools to improve the DT properties of structural elements with a minor weight increase. However the choice of proper materials for the skin and the stringers must be not underestimated since they play an important role as well. A fuselage structural concept has been developed to exploit the benefit of a metal laminate design concept in terms of high Fatigue and Damage Tolerance (F&DT) performances. The structure used laminated skin (0.8mm thick), bonded stringers, two different splicing solutions and selective reinforcements (glass prepreg embedded in the laminate) under the circumferential frames. To validate the design concept a curved panel was manufactured and tested under loading conditions representative of a single aisle fuselage: cyclic internal pressurization plus longitudinal loads. The geometry of the panel, design and loading conditions were tailored for the requirements of the upper front fuselage. The curved panel has been fatigue tested for 60 000 cycles before the introduction of artificial damages (cracks in longitudinal and circumferential directions). The crack growth of the artificial damages has been investigated for about 85 000 cycles. At the end a residual strength test has been performed with a “2 bay over broken frame” longitudinal crack. The reparability of this innovative concept has been taken into account during design and demonstrated with the use of an external riveted repair. The F&DT curved panel test has confirmed that a long fatigue life and high damage tolerance can be achieved with a hybrid metal laminate low weight configuration. The superior fatigue life from metal laminates and the high damage tolerance characteristics provided by integrated selective reinforcements are the key concepts that provided the excellent performances. The weight comparison between the innovative bonded concept and a conventional monolithic riveted design solution showed a significant potential weight saving but the weight advantages shall be traded off with the additional costs.

Seismic mitigation of existing masonry structures by means of added damping and stiffness

In this work seismic upgrading of existing masonry structures by means of hysteretic ADAS dampers is treated. ADAS are installed on external concrete walls, which are built parallel to the building, and then linked to the building's slab by means of steel rod connection system. In order to assess the effectiveness of the intervention, a parametric study considering variation of damper main features has been conducted. To this aim, the concepts of equivalent linear system (ELS) or equivalent viscous damping are deepen. Simplified equivalent linear model results are then checked respect results of the yielding structures. Two alternative displacement based methods for damper design are herein proposed. Both methods have been validated through non linear time history analyses with spectrum compatible accelerograms. Finally ADAS arrangement for the non conventional implementation is proposed.

Active tectonics in the NW-German Basin: Evidence from correlations between the modern landscape and deep geological structures (Lower Saxony, river Hunte)

KurzfassungIm Einzugsgebiet der Hunte (NW-Deutsches Becken, Niedersachsen) wurde untersucht, ob die Landschaftsgenese durch tektonische Bewegungen der Oberkruste beeinflußt ist. Krustenbewegungen führten im Bereich einer Hauptschollengrenze zu einer Hebung der weichselzeitlichen Niederterrasse (durchschnittliche Hebungssrate von ~0,5 mm/a über die letzten 12000 Jahre). Tektonischer Einfluß auf die heutige Landoberfläche ist über einem permischen Salzkissen zu verzeichnen, wo sich das Gefälle der holozänen Aue umkehrt. Krustenbewegungen haben mit großer Wahrscheinlichkeit Vorzugsrichtungen verursacht, die an der Tertiärbasis und in der heutigen Landschaft nachweisbar sind (0-5° und 90-95°). Das Abfließen der Hunte nach Norden scheint durch eine aktive, nordwärts gerichtete Kippung des NW-Deutschen Beckens verursacht zu sein. Hohe lineare Korrelationskoeffizienten zwischen Tiefenlage der Tertiärbasis und Höhenlage der heutigen Landoberfläche weisen auf eine aktive Kippung des Beckens hin. Beckensubsidenz hat möglicherweise die Akkumulation der weichselzeitlichen Niederterrasse gesteuert, da eine Übereinstimmung zwischen rezenter Beckensubsidenz und durchschnittlicher Sedimentationsrate des Niederterrassenkörpers besteht. Untersuchungen an einer geschlossenen Hohlform deuten auf eine aktive Sackungsstruktur hin, da sich Anomalien des geologischen Untergrundes mit der topographischen Lage der Struktur decken.

Effects of artificial defences and flooding on coastal habitats and assemblages

Since large stretches of European coasts are already retreating and projected scenarios are worsening, many artificial structures, such as breakwaters and seawalls, are built as tool against coastal erosion. However artificial structures produce widespread changes that alter the coastal zones and affect the biological communities. My doctoral thesis analyses the consequences of different options for coastal protection, namely hard engineering ‘artificial defences’ (i.e. impact of human-made structures) and ‘no-defence’ (i.e. impact of seawater inundation). I investigated two new aspects of the potential impact of coastal defences. The first was the effect of artificial hard substrates on the fish communities structure. In particular I was interested to test if the differences among breakwaters and natural rocky reef would change depending on the nature of the surrounding habitat of the artificial structure (prevalent sandy rather than rocky). The second was the effect on the native natural sandy habitats of the organic detritus derived from hard-bottom species (green algae and mussels) detached from breakwaters. Furthermore, I investigated the ecological implication of the “no-defend” option, which allow the inundation of coastal habitats. The focus of this study was the potential effect of seawater intrusion on the degradation process of marine, salt-marsh and terrestrial detritus, including changes on the breakdown rates and the associated macrofauna. The PhD research was conducted in three areas along European coasts: North Adriatic sea, Sicilian coast and South-West England where different habitats (coastal, estuarine), biological communities (soft-bottom macro-benthos; rocky-coastal fishes; estuarine macro-invertebrates) and processes (organic enrichment; assemblage structure; leaf-litter breakdown) were analyzed. The research was carried out through manipulative and descriptive field-experiments in which specific hypothesis were tested by univariate and multivariate analyses.

Anatomic study of the feline bronchial and vascular structures with a 64 detector-row computed tomography

Multidetector row computed tomography over the last decade is commonly used in veterinary medicine. This new technology has an increased spatial and temporal resolution, could evaluate wider scanning range in shorter scanning time, providing an advanced imaging modality. Computed tomography angiographic studies are commonly used in veterinary medicine in order to evaluate vascular structures of the abdomen and the thorax. Pulmonary pathology in feline patients is a very common condition and usually is further evaluating with computed tomography. Up to date few references of the normal computed tomographic aspects of the feline thorax are reported. In this study a computed tomographic pulmonary angiography (CTPA) protocol is reported in normal cats and is compared with the up to date anatomical references. A CTPA protocol using a 64 MDCT in our study achieved high resolution images of the pulmonary arteries, pulmonary veins and bronchial lumen till the level of minor segmental branches. Feline pulmonary bronchial parenchyma demonstrates an architecture of mixed type with a monopedial model observed in the most anatomical parts and the dichotomic aspect is seen at the accessory lobe. The arterial and venous architecture is similar to the bronchial. Statistical analysis demonstrates the linear correlation of tracheal diameter to the felines weight. Vascular variations were noticed. The pulmonary venous system enters into the left atrium through three ostia (left cranial ostia: consisted of the anastomosis of the cranial and caudal portion of the left cranial pulmonary vein; right ostia: consisted of the anastomosis of the right cranial and middle pulmonary vein; and the caudal ostia: consisted of the anastomosis of the right and left caudal pulmonary vein). In conclusion CTPA is applicable in feline patients and provides an excellent imaging of the pulmonary arterial, venous and bronchial system till the level of minor segmental branches.

Non linear response of planar asymmetric systems

The seismic behaviour of one-storey asymmetric structures has been studied since 1970s by a number of researches studies which identified the coupled nature of the translational-to-torsional response of those class of systems leading to severe displacement magnifications at the perimeter frames and therefore to significant increase of local peak seismic demand to the structural elements with respect to those of equivalent not-eccentric systems (Kan and Chopra 1987). These studies identified the fundamental parameters (such as the fundamental period TL normalized eccentricity e and the torsional-to-lateral frequency ratio Ωϑ) governing the torsional behavior of in-plan asymmetric structures and trends of behavior. It has been clearly recognized that asymmetric structures characterized by Ωϑ >1, referred to as torsionally-stiff systems, behave quite different form structures with Ωϑ <1, referred to as torsionally-flexible systems. Previous research works by some of the authors proposed a simple closed-form estimation of the maximum torsional response of one-storey elastic systems (Trombetti et al. 2005 and Palermo et al. 2010) leading to the so called “Alpha-method” for the evaluation of the displacement magnification factors at the corner sides. The present paper provides an upgrade of the “Alpha Method” removing the assumption of linear elastic response of the system. The main objective is to evaluate how the excursion of the structural elements in the inelastic field (due to the reaching of yield strength) affects the displacement demand of one-storey in-plan asymmetric structures. The system proposed by Chopra and Goel in 2007, which is claimed to be able to capture the main features of the non-linear response of in-plan asymmetric system, is used to perform a large parametric analysis varying all the fundamental parameters of the system, including the inelastic demand by varying the force reduction factor from 2 to 5. Magnification factors for different force reduction factor are proposed and comparisons with the results obtained from linear analysis are provided.

Hyperbranched polyglycerols as building blocks for complex amphiphilic structures: synthesis, characterization and applications

Among hyperbranched polymers, polyglycerol is one of the most promising and commonly used macromolecules due to its biocompatibility and versatility. However, the synthesis of high molecular weight polyglycerols still involves many intricacies and has only been understood to a limited extent. Furthermore, only few complex structures like star or block copolymers incorporating polyglycerol have been realized so far. Particularly biocompatible block copolymers are considered promising candidates for biomedical applications.rnThe scope of this thesis was the enhancement of the synthetic process leading to polyglycerol derivatives which implies improved molecular weight control for a broad molecular weight range as well as the assembly of more complex structures like amphiphilic block copolymers. Further insight into the relation between reaction solvent, degree of deprotonation during the ring-opening multibranching polymerization of glycidol and the characteristics of the obtained polymers were achieved within the scope of this work. Based on these results, a novel concept for the preparation of hyperbranched polyglycerols with molecular weights up to 20,000 g/mol was developed, applying a two step synthesis pathway. Starting from a partially deprotonated TMP core, low molecular weight hb-PGs were prepared using the known synthetic protocol that has been established since the late 1990ies. In a subsequent reaction sequence, these well defined polymers were used as hyperbranched macroinitiator cores in order to obtain high molecular weight hb-PGs with remarkably low polydispersity (Mw/Mn < 1.8). Molecular weight control was shown to be excellent and undesired low molecular weight side products were absent. Furthermore, the technique of continuous spin fractionation has been discovered as an efficient method for polyglycerol work-up to remove quantitatively residual monomer- and oligomer traces from hb-PG compositions to result in samples with significantly reduced polydispersities. Based on these results the synthesis of amphiphilic block copolymers containing hydrophilic hyperbranched polyglycerol blocks and linear, apolar poly(propylene oxide) blocks has been significantly improved and augmented to hb-PG-b-l-PPO-b-hb-PG ABA block copolymers. The influence of different polyglycerol-based amphiphiles on the fibril formation was studied by Thioflavin T Fluorescence showing remarkable increasing lag times which is promising in order to enhance the stability of this protein. In addition the first synthesis of poly(glyceryl glycerols) (PGG), introducing a new solketyl glycidyl ether monomer (IGG) was shown. It was furthermore demonstrated that core-functional carbosilane wedges allow application in block copolymer synthesis. Bisglycidolized amine functional polymers were successfully employed as macroinitiators for glycidol polymerization. This resulted in the first example of amphiphilic hyperbranched-hyperbranched polymer structures. Finally, it has been shown that the previously reported synthetic pathway to carboxylated hyperbranched polyglycerol polyelectrolytes can also be applied for the amphiphilic linear-hyperbranched block copolymers. These novel biocompatible and highly amphiphilic polyelectrolytes offer great potential for further investigations. rnrn

Abflusslose Senken – Instrumente in der Landschaftsanalyse und Indikatoren rezenter Krustenbewegungen

Innerhalb des Untersuchungsgebiets Schleswig-Holstein wurden 39.712 topographische Hohlformen detektiert. Genutzt wurden dazu ESRI ArcMap 9.3 und 10.0. Der Datenaufbereitung folgten weitere Kalkulationen in MATLAB R2010b. Jedes Objekt wurde räumlich mit seinen individuellen Eigenschaften verschnitten. Dazu gehörten Fläche, Umfang, Koordinaten (Zentroide), Tiefe und maximale Tiefe der Hohlform und Formfaktoren wie Rundheit, Konvexität und Elongation. Ziel der vorgestellten Methoden war die Beantwortung von drei Fragestellungen: Sind negative Landformen dazu geeignet Landschaftseinheiten und Eisvorstöße zu unterscheiden und zu bestimmen? Existiert eine Kopplung von Depressionen an der rezenten Topographie zu geologischen Tiefenstrukturen? Können Senken unterschiedlicher Entstehung anhand ihrer Formcharakteristik unterteilt werden? Die vorgenommene Klassifikation der großen Landschaftseinheiten basiert auf der Annahme, dass sowohl Jungmoränengebiete, ihre Vorflächen als auch Altmoränengebiete durch charakteristische, abflusslose Hohlformen, wie Toteislöcher, Seen, etc. abgegrenzt werden können. Normalerweise sind solche Depressionen in der Natur eher selten, werden jedoch für ehemalige Glaziallandschaften als typisch erachtet. Ziel war es, die geologischen Haupteinheiten, Eisvorstöße und Moränengebiete der letzten Vereisungen zu differenzieren. Zur Bearbeitung wurde ein Detektionsnetz verwendet, das auf quadratischen Zellen beruht. Die Ergebnisse zeigen, dass durch die alleinige Nutzung von Depressionen zur Klassifizierung von Landschaftseinheiten Gesamtgenauigkeiten von bis zu 71,4% erreicht werden können. Das bedeutet, dass drei von vier Detektionszellen korrekt zugeordnet werden können. Jungmoränen, Altmoränen, periglazialeVorflächen und holozäne Bereiche können mit Hilfe der Hohlformen mit großer Sicherheit voneinander unterschieden und korrekt zugeordnet werden. Dies zeigt, dass für die jeweiligen Einheiten tatsächlich bestimmte Senkenformen typisch sind. Die im ersten Schritt detektierten Senken wurden räumlich mit weiterreichenden geologischen Informationen verschnitten, um zu untersuchen, inwieweit natürliche Depressionen nur glazial entstanden sind oder ob ihre Ausprägung auch mit tiefengeologischen Strukturen in Zusammenhang steht. 25.349 (63,88%) aller Senken sind kleiner als 10.000 m² und liegen in Jungmoränengebieten und können vermutlich auf glaziale und periglaziale Einflüsse zurückgeführt werden. 2.424 Depressionen liegen innerhalb der Gebiete subglazialer Rinnen. 1.529 detektierte Hohlformen liegen innerhalb von Subsidenzgebieten, von denen 1.033 innerhalb der Marschländer im Westen verortet sind. 919 große Strukturen über 1 km Größe entlang der Nordsee sind unter anderem besonders gut mit Kompaktionsbereichen elsterzeitlicher Rinnen zu homologisieren.344 dieser Hohlformen sind zudem mit Tunneltälern im Untergrund assoziiert. Diese Parallelität von Depressionen und den teils über 100 m tiefen Tunneltälern kann auf Sedimentkompaktion zurückgeführt werden. Ein Zusammenhang mit der Zersetzung postglazialen, organischen Materials ist ebenfalls denkbar. Darüber hinaus wurden in einer Distanz von 10 km um die miozän aktiven Flanken des Glückstadt-Grabens negative Landformen detektiert, die Verbindungen zu oberflächennahen Störungsstrukturen zeigen. Dies ist ein Anzeichen für Grabenaktivität während und gegen Ende der Vereisung und während des Holozäns. Viele dieser störungsbezogenen Senken sind auch mit Tunneltälern assoziiert. Entsprechend werden drei zusammenspielende Prozesse identifiziert, die mit der Entstehung der Hohlformen in Verbindung gebracht werden können. Eine mögliche Interpretation ist, dass die östliche Flanke des Glückstadt-Grabens auf die Auflast des elsterzeitlichen Eisschilds reagierte, während sich subglazial zeitgleich Entwässerungsrinnen entlang der Schwächezonen ausbildeten. Diese wurden in den Warmzeiten größtenteils durch Torf und unverfestigte Sedimente verfüllt. Die Gletschervorstöße der späten Weichselzeit aktivierten erneut die Flanken und zusätzlich wurde das Lockermaterial exariert, wodurch große Seen, wie z. B. der Große Plöner See entstanden sind. Insgesamt konnten 29 große Depressionen größer oder gleich 5 km in Schleswig-Holstein identifiziert werden, die zumindest teilweise mit Beckensubsidenz und Aktivität der Grabenflanken verbunden sind, bzw. sogar auf diese zurückgehen.Die letzte Teilstudie befasste sich mit der Differenzierung von Senken nach deren potentieller Genese sowie der Unterscheidung natürlicher von künstlichen Hohlformen. Dazu wurde ein DEM für einen Bereich im Norden Niedersachsens verwendet, das eine Gesamtgröße von 252 km² abdeckt. Die Ergebnisse zeigen, dass glazial entstandene Depressionen gute Rundheitswerte aufweisen und auch Elongation und Exzentrizität eher kompakte Formen anzeigen. Lineare negative Strukturen sind oft Flüsse oder Altarme. Sie können als holozäne Strukturen identifiziert werden. Im Gegensatz zu den potentiell natürlichen Senkenformen sind künstlich geschaffene Depressionen eher eckig oder ungleichmäßig und tendieren meist nicht zu kompakten Formen. Drei Hauptklassen topographischer Depressionen konnten identifiziert und voneinander abgegrenzt werden: Potentiell glaziale Senken (Toteisformen), Flüsse, Seiten- und Altarme sowie künstliche Senken. Die Methode der Senkenklassifikation nach Formparametern ist ein sinnvolles Instrument, um verschiedene Typen unterscheiden zu können und um bei geologischen Fragestellungen künstliche Senken bereits vor der Verarbeitung auszuschließen. Jedoch zeigte sich, dass die Ergebnisse im Wesentlichen von der Auflösung des entsprechenden Höhenmodells abhängen.

Higher-order molecular properties and excitation energies in single-reference and multireference coupled-cluster theory

Coupled-cluster (CC) theory is one of the most successful approaches in high-accuracy quantum chemistry. The present thesis makes a number of contributions to the determination of molecular properties and excitation energies within the CC framework. The multireference CC (MRCC) method proposed by Mukherjee and coworkers (Mk-MRCC) has been benchmarked within the singles and doubles approximation (Mk-MRCCSD) for molecular equilibrium structures. It is demonstrated that Mk-MRCCSD yields reliable results for multireference cases where single-reference CC methods fail. At the same time, the present work also illustrates that Mk-MRCC still suffers from a number of theoretical problems and sometimes gives rise to results of unsatisfactory accuracy. To determine polarizability tensors and excitation spectra in the MRCC framework, the Mk-MRCC linear-response function has been derived together with the corresponding linear-response equations. Pilot applications show that Mk-MRCC linear-response theory suffers from a severe problem when applied to the calculation of dynamic properties and excitation energies: The Mk-MRCC sufficiency conditions give rise to a redundancy in the Mk-MRCC Jacobian matrix, which entails an artificial splitting of certain excited states. This finding has established a new paradigm in MRCC theory, namely that a convincing method should not only yield accurate energies, but ought to allow for the reliable calculation of dynamic properties as well. In the context of single-reference CC theory, an analytic expression for the dipole Hessian matrix, a third-order quantity relevant to infrared spectroscopy, has been derived and implemented within the CC singles and doubles approximation. The advantages of analytic derivatives over numerical differentiation schemes are demonstrated in some pilot applications.