A mesoscopic simulation method for electrolyte solutions

This thesis deals with the development of a novel simulation technique for macromolecules in electrolyte solutions, with the aim of a performance improvement over current molecular-dynamics based simulation methods. In solutions containing charged macromolecules and salt ions, it is the complex interplay of electrostatic interactions and hydrodynamics that determines the equilibrium and non-equilibrium behavior. However, the treatment of the solvent and dissolved ions makes up the major part of the computational effort. Thus an efficient modeling of both components is essential for the performance of a method. With the novel method we approach the solvent in a coarse-grained fashion and replace the explicit-ion description by a dynamic mean-field treatment. Hence we combine particle- and field-based descriptions in a hybrid method and thereby effectively solve the electrokinetic equations. The developed algorithm is tested extensively in terms of accuracy and performance, and suitable parameter sets are determined. As a first application we study charged polymer solutions (polyelectrolytes) in shear flow with focus on their viscoelastic properties. Here we also include semidilute solutions, which are computationally demanding. Secondly we study the electro-osmotic flow on superhydrophobic surfaces, where we perform a detailed comparison to theoretical predictions.

One dimensional extended Hubbard model: two-particle bound states and resonances.

In questo lavoro di tesi è stato svolto uno studio analitico sul modello di Hubbard esteso unidimensionale al fine di osservare la presenza di eventuali risonanze che possano dare origine alla formazione di stati legati di due particelle. L'esistenza di uno stato legato stabile ha suscitato grande interesse negli ultimi anni, sia in ambito teorico che sperimentale, poichè è alla base di molti fenomeni che vengono osservati nei sistemi a molti corpi a basse temperature, come il BCS-BEC crossover. Pertanto si è ritenuto utile studiare il problema a due corpi nel modello di Hubbard esteso, che in generale non è integrabile. Il modello considerato contiene interazioni a primi e secondi vicini, in aggiunta all'interazione di contatto presente nel modello di Hubbard. Il problema è stato indagato analiticamente attraverso il Bethe ansatz, che consente di trovare tutti gli autovalori e le autofunzioni dell'Hamiltoniana. L'ansatz di Bethe sulla funzione d'onda è stato generalizzato per poter tener conto dei termini di interazione a più lungo raggio rispetto all'interazione di contatto. Si trova che, in questo modello, nel limite termodinamico, possono avvenire delle risonanze (o quasi-risonanze) in cui la lunghezza di scattering diverge, contrariamente a quanto avviene nel modello di Hubbard. Tale fenomeno si verifica quando il livello energetico discreto degli stati legati “tocca” la banda di scattering. Inoltre, con l'aggiunta di nuovi termini di interazione emergono nuovi stati legati. Nel caso in esame, si osservano due famiglie di stati legati, se lo spin totale delle due particelle è 1, e tre famiglie di stati legati, se lo spin totale è 0.

Probing quantum chromodynamics with the ATLAS detector : charged-particle event shape variables and the dijet cross-section

Die Quantenchromodynamik ist die zugrundeliegende Theorie der starken Wechselwirkung und kann in zwei Bereiche aufgeteilt werden. Harte Streuprozesse, wie zum Beispiel die Zwei-Jet-Produktion bei hohen invarianten Massen, können störungstheoretisch behandelt und berechnet werden. Bei Streuprozessen mit niedrigen Impulsüberträgen hingegen ist die Störungstheorie nicht mehr anwendbar und phänemenologische Modelle werden für Vorhersagen benutzt. Das ATLAS Experiment am Large Hadron Collider am CERN ermöglicht es, QCD Prozesse bei hohen sowie niedrigen Impulsüberträgen zu untersuchen. In dieser Arbeit werden zwei Analysen vorgestellt, die jeweils ihren Schwerpunkt auf einen der beiden Regime der QCD legen:rnDie Messung von Ereignisformvariablen bei inelastischen Proton--Proton Ereignissen bei einer Schwerpunktsenergie von $sqrt{s} = unit{7}{TeV}$ misst den transversalen Energiefluss in hadronischen Ereignissen. rnDie Messung des zweifachdifferentiellen Zwei-Jet-Wirkungsquerschnittes als Funktion der invarianten Masse sowie der Rapiditätsdifferenz der beiden Jets mit den höchsten Transversalimpulsen kann genutzt werden um Theorievorhersagen zu überprüfen. Proton--Proton Kollisionen bei $sqrt{s} = unit{8}{TeV}$, welche während der Datennahme im Jahr 2012 aufgezeichnet wurden, entsprechend einer integrierten Luminosität von $unit{20.3}{fb^{-1}}$, wurden analysiert.rn

Hydrodynamics and solid dosage form disintegration/dissolution : immediate release tablets and novel in situ polyelectrolyte gastroretentive drug delivery systems

Solid oral dosage form disintegration in the human stomach is a highly complex process dependent on physicochemical properties of the stomach contents as well as on physical variables such as hydrodynamics and mechanical stress. Understanding the role of hydrodynamics and forces in disintegration of oral solid dosage forms can help to improve in vitro disintegration testing and the predictive power of the in vitro test. The aim of this work was to obtain a deep understanding of the influence of changing hydrodynamic conditions on solid oral dosage form performance. Therefore, the hydrodynamic conditions and forces present in the compendial PhEur/USP disintegration test device were characterized using a computational fluid dynamics (CFD) approach. Furthermore, a modified device was developed and the hydrodynamic conditions present were simulated using CFD. This modified device was applied in two case studies comprising immediate release (IR) tablets and gastroretentive drug delivery systems (GRDDS). Due to the description of movement provided in the PhEur, the movement velocity of the basket-rack assembly follows a sinusoidal profile. Therefore, hydrodynamic conditions are changing continually throughout the movement cycle. CFD simulations revealed that the dosage form is exposed to a wide range of fluid velocities and shear forces during the test. The hydrodynamic conditions in the compendial device are highly variable and cannot be controlled. A new, modified disintegration test device based on computerized numerical control (CNC) technique was developed. The modified device can be moved in all three dimensions and radial movement is also possible. Simple and complex moving profiles can be developed and the influence of the hydrodynamic conditions on oral solid dosage form performance can be evaluated. Furthermore, a modified basket was designed that allows two-sided fluid flow. CFD simulations of the hydrodynamics and forces in the modified device revealed significant differences in the fluid flow field and forces when compared to the compendial device. Due to the CNC technique moving velocity and direction are arbitrary and hydrodynamics become controllable. The modified disintegration test device was utilized to examine the influence of moving velocity on disintegration times of IR tablets. Insights into the influence of moving speed, medium viscosity and basket design on disintegration times were obtained. An exponential relationship between moving velocity of the modified basket and disintegration times was established in simulated gastric fluid. The same relationship was found between the disintegration times and the CFD predicted average shear stress on the tablet surface. Furthermore, a GRDDS was developed based on the approach of an in situ polyelectrolyte complex (PEC). Different complexes composed of different grades of chitosan and carrageenan and different ratios of those were investigated for their swelling behavior, mechanical stability, and in vitro drug release. With an optimized formulation the influence of changing hydrodynamic conditions on the swelling behavior and the drug release profile was demonstrated using the modified disintegration test device. Both, swelling behavior and drug release, were largely dependent on the hydrodynamic conditions. Concluding, it has been shown within this thesis that the application of the modified disintegration test device allows for detailed insights into the influence of hydrodynamic conditions on solid oral dosage form disintegration and dissolution. By the application of appropriate test conditions, the predictive power of in vitro disintegration testing can be improved using the modified disintegration test device. Furthermore, CFD has proven a powerful tool to examine the hydrodynamics and forces in the compendial as well as in the modified disintegration test device. rn

Fast frontend electronics for high rate particle detectors

Future experiments in nuclear and particle physics are moving towards the high luminosity regime in order to access rare processes. In this framework, particle detectors require high rate capability together with excellent timing resolution for precise event reconstruction. In order to achieve this, the development of dedicated FrontEnd Electronics (FEE) for detectors has become increasingly challenging and expensive. Thus, a current trend in R&D is towards flexible FEE that can be easily adapted to a great variety of detectors, without impairing the required high performance. This thesis reports on a novel FEE for two different detector types: imaging Cherenkov counters and plastic scintillator arrays. The former requires high sensitivity and precision for detection of single photon signals, while the latter is characterized by slower and larger signals typical of scintillation processes. The FEE design was developed using high-bandwidth preamplifiers and fast discriminators which provide Time-over-Threshold (ToT). The use of discriminators allowed for low power consumption, minimal dead-times and self-triggering capabilities, all fundamental aspects for high rate applications. The output signals of the FEE are readout by a high precision TDC system based on FPGA. The performed full characterization of the analogue signals under realistic conditions proved that the ToT information can be used in a novel way for charge measurements or walk corrections, thus improving the obtainable timing resolution. Detailed laboratory investigations proved the feasibility of the ToT method. The full readout chain was investigated in test experiments at the Mainz Microtron: high counting rates per channel of several MHz were achieved, and a timing resolution of better than 100 ps after walk correction based on ToT was obtained. Ongoing applications to fast Time-of-Flight counters and future developments of FEE have been also recently investigated.

Identification of bracovirus particle proteins and analysis of their transcript levels at the stage of virion formation

http://www.ncbi.nlm.nih.gov/pubmed/20554796

Alpha- versus beta-particle radiopeptide therapy in a human prostate cancer model (213Bi-DOTA-PESIN and 213Bi-AMBA versus 177Lu-DOTA-PESIN)

Recurrent prostate cancer presents a challenge to conventional treatment, particularly so to address micrometastatic and small-volume disease. Use of α-radionuclide therapy is considered as a highly effective treatment in such applications due to the shorter range and exquisite cytotoxicity of α-particles as compared with β-particles. (213)Bi is considered an α-emitter with high clinical potential, due to its short half-life (45.6 minutes) being well matched for use in peptide-receptor radionuclide α-therapy; however, there is limited knowledge available within this context of use. In this study, two novel (213)Bi-labeled peptides, DOTA-PEG(4)-bombesin (DOTA-PESIN) and DO3A-CH(2)CO-8-aminooctanoyl-Q-W-A-V-G-H-L-M-NH(2) (AMBA), were compared with (177)Lu (β-emitter)-labeled DOTA-PESIN in a human androgen-independent prostate carcinoma xenograft model (PC-3 tumor). Animals were injected with (177)Lu-DOTA-PESIN, (213)Bi-DOTA-PESIN, or (213)Bi-AMBA to determine the maximum tolerated dose (MTD), biodistribution, and dosimetry of each agent; controls were left untreated or were given nonradioactive (175)Lu-DOTA-PESIN. The MTD of (213)Bi-DOTA-PESIN and (213)Bi-AMBA was 25 MBq (0.68 mCi) whereas (177)Lu-DOTA-PESIN showed an MTD of 112 MBq (3 mCi). At these dose levels, (213)Bi-DOTA-PESIN and (213)Bi-AMBA were significantly more effective than (177)Lu-DOTA-PESIN. At the same time, (177)Lu-DOTA-PESIN showed minimal, (213)Bi-DOTA-PESIN slight, and (213)Bi-AMBA marked kidney damage 20 to 30 weeks posttreatment. These preclinical data indicate that α-therapy with (213)Bi-DOTA-PESIN or (213)Bi-AMBA is more efficacious than β-therapy. Furthermore, (213)Bi-DOTA-PESIN has a better safety profile than (213)Bi-AMBA, and represents a possible new approach for use in peptide-receptor radionuclide α-therapy treating recurrent prostate cancer.

Hydrodynamic correlation functions of a driven granular fluid in steady state

We study a homogeneously driven granular fluid of hard spheres at intermediate volume fractions and focus on time-delayed correlation functions in the stationary state. Inelastic collisions are modeled by incomplete normal restitution, allowing for efficient simulations with an event-driven algorithm. The incoherent scattering function Fincoh(q,t ) is seen to follow time-density superposition with a relaxation time that increases significantly as the volume fraction increases. The statistics of particle displacements is approximately Gaussian. For the coherent scattering function S(q,ω), we compare our results to the predictions of generalized fluctuating hydrodynamics, which takes into account that temperature fluctuations decay either diffusively or with a finite relaxation rate, depending on wave number and inelasticity. For sufficiently small wave number q we observe sound waves in the coherent scattering function S(q,ω) and the longitudinal current correlation function Cl(q,ω). We determine the speed of sound and the transport coefficients and compare them to the results of kinetic theory.

Unexpected Polymorphism and Unique Particle Morphologies from Monodisperse Droplet Evaporation

The particle sizes, morphologies, and structures are presented for succinic acid particles formed from the evaporation of uniform droplets created with a vibrating orifice aerosol generator. Particle sizes are monodisperse, and solvent choice is found to be the dominant factor in determining the final morphology and structure. The external particle morphologies range from round to cap shaped, while the surface roughness ranges from fairly smooth to extremely rough and pitted. Internally, the particles have significant void space and noticeable crystals. X-ray diffraction confirms that the particles are crystalline. Thus, the morphologies of the particles take on a crystal filled structure that is unique in comparison to previous particles formed through droplet evaporation. The structure of the particles contains β succinic acid; however, the particles formed from water also contain α succinic acid. α Succinic acid has not previously been able to be formed from solution at near atmospheric conditions. The unique morphologies and ability to identify unexpected polymorphs provide for a potential tool to not only enhance particle engineering but also to identify metastable polymorphs.