Technical innovations for the diagnosis and the rehabilitation of motor and perceptive impairments of the child with Cerebral Palsy

The treatment of the Cerebral Palsy (CP) is considered as the “core problem” for the whole field of the pediatric rehabilitation. The reason why this pathology has such a primary role, can be ascribed to two main aspects. First of all CP is the form of disability most frequent in childhood (one new case per 500 birth alive, (1)), secondarily the functional recovery of the “spastic” child is, historically, the clinical field in which the majority of the therapeutic methods and techniques (physiotherapy, orthotic, pharmacologic, orthopedic-surgical, neurosurgical) were first applied and tested. The currently accepted definition of CP – Group of disorders of the development of movement and posture causing activity limitation (2) – is the result of a recent update by the World Health Organization to the language of the International Classification of Functioning Disability and Health, from the original proposal of Ingram – A persistent but not unchangeable disorder of posture and movement – dated 1955 (3). This definition considers CP as a permanent ailment, i.e. a “fixed” condition, that however can be modified both functionally and structurally by means of child spontaneous evolution and treatments carried out during childhood. The lesion that causes the palsy, happens in a structurally immature brain in the pre-, peri- or post-birth period (but only during the firsts months of life). The most frequent causes of CP are: prematurity, insufficient cerebral perfusion, arterial haemorrhage, venous infarction, hypoxia caused by various origin (for example from the ingestion of amniotic liquid), malnutrition, infection and maternal or fetal poisoning. In addition to these causes, traumas and malformations have to be included. The lesion, whether focused or spread over the nervous system, impairs the whole functioning of the Central Nervous System (CNS). As a consequence, they affect the construction of the adaptive functions (4), first of all posture control, locomotion and manipulation. The palsy itself does not vary over time, however it assumes an unavoidable “evolutionary” feature when during growth the child is requested to meet new and different needs through the construction of new and different functions. It is essential to consider that clinically CP is not only a direct expression of structural impairment, that is of etiology, pathogenesis and lesion timing, but it is mainly the manifestation of the path followed by the CNS to “re”-construct the adaptive functions “despite” the presence of the damage. “Palsy” is “the form of the function that is implemented by an individual whose CNS has been damaged in order to satisfy the demands coming from the environment” (4). Therefore it is only possible to establish general relations between lesion site, nature and size, and palsy and recovery processes. It is quite common to observe that children with very similar neuroimaging can have very different clinical manifestations of CP and, on the other hand, children with very similar motor behaviors can have completely different lesion histories. A very clear example of this is represented by hemiplegic forms, which show bilateral hemispheric lesions in a high percentage of cases. The first section of this thesis is aimed at guiding the interpretation of CP. First of all the issue of the detection of the palsy is treated from historical viewpoint. Consequently, an extended analysis of the current definition of CP, as internationally accepted, is provided. The definition is then outlined in terms of a space dimension and then of a time dimension, hence it is highlighted where this definition is unacceptably lacking. The last part of the first section further stresses the importance of shifting from the traditional concept of CP as a palsy of development (defect analysis) towards the notion of development of palsy, i.e., as the product of the relationship that the individual however tries to dynamically build with the surrounding environment (resource semeiotics) starting and growing from a different availability of resources, needs, dreams, rights and duties (4). In the scientific and clinic community no common classification system of CP has so far been universally accepted. Besides, no standard operative method or technique have been acknowledged to effectively assess the different disabilities and impairments exhibited by children with CP. CP is still “an artificial concept, comprising several causes and clinical syndromes that have been grouped together for a convenience of management” (5). The lack of standard and common protocols able to effectively diagnose the palsy, and as a consequence to establish specific treatments and prognosis, is mainly because of the difficulty to elevate this field to a level based on scientific evidence. A solution aimed at overcoming the current incomplete treatment of CP children is represented by the clinical systematic adoption of objective tools able to measure motor defects and movement impairments. A widespread application of reliable instruments and techniques able to objectively evaluate both the form of the palsy (diagnosis) and the efficacy of the treatments provided (prognosis), constitutes a valuable method able to validate care protocols, establish the efficacy of classification systems and assess the validity of definitions. Since the ‘80s, instruments specifically oriented to the analysis of the human movement have been advantageously designed and applied in the context of CP with the aim of measuring motor deficits and, especially, gait deviations. The gait analysis (GA) technique has been increasingly used over the years to assess, analyze, classify, and support the process of clinical decisions making, allowing for a complete investigation of gait with an increased temporal and spatial resolution. GA has provided a basis for improving the outcome of surgical and nonsurgical treatments and for introducing a new modus operandi in the identification of defects and functional adaptations to the musculoskeletal disorders. Historically, the first laboratories set up for gait analysis developed their own protocol (set of procedures for data collection and for data reduction) independently, according to performances of the technologies available at that time. In particular, the stereophotogrammetric systems mainly based on optoelectronic technology, soon became a gold-standard for motion analysis. They have been successfully applied especially for scientific purposes. Nowadays the optoelectronic systems have significantly improved their performances in term of spatial and temporal resolution, however many laboratories continue to use the protocols designed on the technology available in the ‘70s and now out-of-date. Furthermore, these protocols are not coherent both for the biomechanical models and for the adopted collection procedures. In spite of these differences, GA data are shared, exchanged and interpreted irrespectively to the adopted protocol without a full awareness to what extent these protocols are compatible and comparable with each other. Following the extraordinary advances in computer science and electronics, new systems for GA no longer based on optoelectronic technology, are now becoming available. They are the Inertial and Magnetic Measurement Systems (IMMSs), based on miniature MEMS (Microelectromechanical systems) inertial sensor technology. These systems are cost effective, wearable and fully portable motion analysis systems, these features gives IMMSs the potential to be used both outside specialized laboratories and to consecutive collect series of tens of gait cycles. The recognition and selection of the most representative gait cycle is then easier and more reliable especially in CP children, considering their relevant gait cycle variability. The second section of this thesis is focused on GA. In particular, it is firstly aimed at examining the differences among five most representative GA protocols in order to assess the state of the art with respect to the inter-protocol variability. The design of a new protocol is then proposed and presented with the aim of achieving gait analysis on CP children by means of IMMS. The protocol, named ‘Outwalk’, contains original and innovative solutions oriented at obtaining joint kinematic with calibration procedures extremely comfortable for the patients. The results of a first in-vivo validation of Outwalk on healthy subjects are then provided. In particular, this study was carried out by comparing Outwalk used in combination with an IMMS with respect to a reference protocol and an optoelectronic system. In order to set a more accurate and precise comparison of the systems and the protocols, ad hoc methods were designed and an original formulation of the statistical parameter coefficient of multiple correlation was developed and effectively applied. On the basis of the experimental design proposed for the validation on healthy subjects, a first assessment of Outwalk, together with an IMMS, was also carried out on CP children. The third section of this thesis is dedicated to the treatment of walking in CP children. Commonly prescribed treatments in addressing gait abnormalities in CP children include physical therapy, surgery (orthopedic and rhizotomy), and orthoses. The orthotic approach is conservative, being reversible, and widespread in many therapeutic regimes. Orthoses are used to improve the gait of children with CP, by preventing deformities, controlling joint position, and offering an effective lever for the ankle joint. Orthoses are prescribed for the additional aims of increasing walking speed, improving stability, preventing stumbling, and decreasing muscular fatigue. The ankle-foot orthosis (AFO), with a rigid ankle, are primarily designed to prevent equinus and other foot deformities with a positive effect also on more proximal joints. However, AFOs prevent the natural excursion of the tibio-tarsic joint during the second rocker, hence hampering the natural leaning progression of the whole body under the effect of the inertia (6). A new modular (submalleolar) astragalus-calcanear orthosis, named OMAC, has recently been proposed with the intention of substituting the prescription of AFOs in those CP children exhibiting a flat and valgus-pronated foot. The aim of this section is thus to present the mechanical and technical features of the OMAC by means of an accurate description of the device. In particular, the integral document of the deposited Italian patent, is provided. A preliminary validation of OMAC with respect to AFO is also reported as resulted from an experimental campaign on diplegic CP children, during a three month period, aimed at quantitatively assessing the benefit provided by the two orthoses on walking and at qualitatively evaluating the changes in the quality of life and motor abilities. As already stated, CP is universally considered as a persistent but not unchangeable disorder of posture and movement. Conversely to this definition, some clinicians (4) have recently pointed out that movement disorders may be primarily caused by the presence of perceptive disorders, where perception is not merely the acquisition of sensory information, but an active process aimed at guiding the execution of movements through the integration of sensory information properly representing the state of one’s body and of the environment. Children with perceptive impairments show an overall fear of moving and the onset of strongly unnatural walking schemes directly caused by the presence of perceptive system disorders. The fourth section of the thesis thus deals with accurately defining the perceptive impairment exhibited by diplegic CP children. A detailed description of the clinical signs revealing the presence of the perceptive impairment, and a classification scheme of the clinical aspects of perceptual disorders is provided. In the end, a functional reaching test is proposed as an instrumental test able to disclosure the perceptive impairment. References 1. Prevalence and characteristics of children with cerebral palsy in Europe. Dev Med Child Neurol. 2002 Set;44(9):633-640. 2. Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N, Dan B, et al. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005 Ago;47(8):571-576. 3. Ingram TT. A study of cerebral palsy in the childhood population of Edinburgh. Arch. Dis. Child. 1955 Apr;30(150):85-98. 4. Ferrari A, Cioni G. The spastic forms of cerebral palsy : a guide to the assessment of adaptive functions. Milan: Springer; 2009. 5. Olney SJ, Wright MJ. Cerebral Palsy. Campbell S et al. Physical Therapy for Children. 2nd Ed. Philadelphia: Saunders. 2000;:533-570. 6. Desloovere K, Molenaers G, Van Gestel L, Huenaerts C, Van Campenhout A, Callewaert B, et al. How can push-off be preserved during use of an ankle foot orthosis in children with hemiplegia? A prospective controlled study. Gait Posture. 2006 Ott;24(2):142-151.

Modelling and analysis of internally BFRP reinforced beams at elevated temperatures

The aim of the work is to conduct a finite element model analysis on a small – size concrete beam and on a full size concrete beam internally reinforced with BFRP exposed at elevated temperatures. Experimental tests performed at Kingston University have been used to compare the results from the numerical analysis for the small – size concrete beam. Once the behavior of the small – size beam at room temperature is investigated and switching to the heating phase reinforced beams are tested at 100°C, 200°C and 300°C in loaded condition. The aim of the finite element analysis is to reflect the three – point bending test adopted into the oven during the exposure of the beam at room temperature and at elevated temperatures. Performance and deformability of reinforced beams are straightly correlated to the material properties and a wide analysis on elastic modulus and coefficient of thermal expansion is given in this work. Develop a good correlation between the numerical model and the experimental test is the main objective of the analysis on the small – size concrete beam, for both modelling the aim is also to estimate which is the deterioration of the material properties due to the heating process and the influence of different parameters on the final result. The focus of the full – size modelling which involved the last part of this work is to evaluate the effect of elevated temperatures, the material deterioration and the deflection trend on a reinforced beam characterized by a different size. A comparison between the results from different modelling has been developed.

Partial reconstruction of the trajectories of a discretely observed branching diffusion with immigration and an application to inference

In this treatise we consider finite systems of branching particles where the particles move independently of each other according to d-dimensional diffusions. Particles are killed at a position dependent rate, leaving at their death position a random number of descendants according to a position dependent reproduction law. In addition particles immigrate at constant rate (one immigrant per immigration time). A process with above properties is called a branching diffusion withimmigration (BDI). In the first part we present the model in detail and discuss the properties of the BDI under our basic assumptions. In the second part we consider the problem of reconstruction of the trajectory of a BDI from discrete observations. We observe positions of the particles at discrete times; in particular we assume that we have no information about the pedigree of the particles. A natural question arises if we want to apply statistical procedures on the discrete observations: How can we find couples of particle positions which belong to the same particle? We give an easy to implement 'reconstruction scheme' which allows us to redraw or 'reconstruct' parts of the trajectory of the BDI with high accuracy. Moreover asymptotically the whole path can be reconstructed. Further we present simulations which show that our partial reconstruction rule is tractable in practice. In the third part we study how the partial reconstruction rule fits into statistical applications. As an extensive example we present a nonparametric estimator for the diffusion coefficient of a BDI where the particles move according to one-dimensional diffusions. This estimator is based on the Nadaraya-Watson estimator for the diffusion coefficient of one-dimensional diffusions and it uses the partial reconstruction rule developed in the second part above. We are able to prove a rate of convergence of this estimator and finally we present simulations which show that the estimator works well even if we leave our set of assumptions.

Design and optimization of components and processes for plasma sources in advanced material treatments

The research activities described in the present thesis have been oriented to the design and development of components and technological processes aimed at optimizing the performance of plasma sources in advanced in material treatments. Consumables components for high definition plasma arc cutting (PAC) torches were studied and developed. Experimental activities have in particular focussed on the modifications of the emissive insert with respect to the standard electrode configuration, which comprises a press fit hafnium insert in a copper body holder, to improve its durability. Based on a deep analysis of both the scientific and patent literature, different solutions were proposed and tested. First, the behaviour of Hf cathodes when operating at high current levels (250A) in oxidizing atmosphere has been experimentally investigated optimizing, with respect to expected service life, the initial shape of the electrode emissive surface. Moreover, the microstructural modifications of the Hf insert in PAC electrodes were experimentally investigated during first cycles, in order to understand those phenomena occurring on and under the Hf emissive surface and involved in the electrode erosion process. Thereafter, the research activity focussed on producing, characterizing and testing prototypes of composite inserts, combining powders of a high thermal conductibility (Cu, Ag) and high thermionic emissivity (Hf, Zr) materials The complexity of the thermal plasma torch environment required and integrated approach also involving physical modelling. Accordingly, a detailed line-by-line method was developed to compute the net emission coefficient of Ar plasmas at temperatures ranging from 3000 K to 25000 K and pressure ranging from 50 kPa to 200 kPa, for optically thin and partially autoabsorbed plasmas. Finally, prototypal electrodes were studied and realized for a newly developed plasma source, based on the plasma needle concept and devoted to the generation of atmospheric pressure non-thermal plasmas for biomedical applications.

Diffusion of laser polarized gases in MRI

The use of Magnetic Resonance Imaging (MRI) as a diagnostic tool is increasingly employing functional contrast agents to study or contrast entire mechanisms. Contrast agents in MRI can be classified in two categories. One type of contrast agents alters the NMR signal of the protons in its surrounding, e.g. lowers the T1 relaxation time. The other type enhances the Nuclear Magnetic Resonance (NMR) signal of specific nuclei. For hyperpolarized gases the NMR signal is improved up to several orders of magnitude. However, gases have a high diffusivity which strongly influences the NMR signal strength, hence the resolution and appearance of the images. The most interesting question in spatially resolved experiments is of course the achievable resolution and contrast by controlling the diffusivity of the gas. The influence of such diffusive processes scales with the diffusion coefficient, the strength of the magnetic field gradients and the timings used in the experiment. Diffusion may not only limit the MRI resolution, but also distort the line shape of MR images for samples, which contain boundaries or diffusion barriers within the sampled space. In addition, due to the large polarization in gaseous 3He and 129Xe, spin diffusion (different from particle diffusion) could play a role in MRI experiments. It is demonstrated that for low temperatures some corrections to the NMR measured diffusion coefficient have to be done, which depend on quantum exchange effects for indistinguishable particles. Physically, if these effects can not change the spin current, they can do it indirectly by modifying the velocity distribution of the different spin states separately, so that the subsequent collisions between atoms and therefore the diffusion coefficient can eventually be affected. A detailed study of the hyperpolarized gas diffusion coefficient is presented, demonstrating the absence of spin diffusion (different from particle diffusion) influence in MRI at clinical conditions. A novel procedure is proposed to control the diffusion coefficient of gases in MRI by admixture of inert buffer gases. The experimental measured diffusion agrees with theoretical simulations. Therefore, the molecular mass and concentration enter as additional parameters into the equations that describe structural contrast. This allows for setting a structural threshold up to which structures contribute to the image. For MRI of the lung this allows for images of very small structural elements (alveoli) only, or in the other extreme, all airways can be displayed with minimal signal loss due to diffusion.

Pore structure and column efficiency of silica monoliths in high performance liquid chromatography (HPLC)

Five different methods were critically examined to characterize the pore structure of the silica monoliths. The mesopore characterization was performed using: a) the classical BJH method of nitrogen sorption data, which showed overestimated values in the mesopore distribution and was improved by using the NLDFT method, b) the ISEC method implementing the PPM and PNM models, which were especially developed for monolithic silicas, that contrary to the particulate supports, demonstrate the two inflection points in the ISEC curve, enabling the calculation of pore connectivity, a measure for the mass transfer kinetics in the mesopore network, c) the mercury porosimetry using a new recommended mercury contact angle values. rnThe results of the characterization of mesopores of monolithic silica columns by the three methods indicated that all methods were useful with respect to the pore size distribution by volume, but only the ISEC method with implemented PPM and PNM models gave the average pore size and distribution based on the number average and the pore connectivity values.rnThe characterization of the flow-through pore was performed by two different methods: a) the mercury porosimetry, which was used not only for average flow-through pore value estimation, but also the assessment of entrapment. It was found that the mass transfer from the flow-through pores to mesopores was not hindered in case of small sized flow-through pores with a narrow distribution, b) the liquid penetration where the average flow-through pore values were obtained via existing equations and improved by the additional methods developed according to Hagen-Poiseuille rules. The result was that not the flow-through pore size influences the column bock pressure, but the surface area to volume ratio of silica skeleton is most decisive. Thus the monolith with lowest ratio values will be the most permeable. rnThe flow-through pore characterization results obtained by mercury porosimetry and liquid permeability were compared with the ones from imaging and image analysis. All named methods enable a reliable characterization of the flow-through pore diameters for the monolithic silica columns, but special care should be taken about the chosen theoretical model.rnThe measured pore characterization parameters were then linked with the mass transfer properties of monolithic silica columns. As indicated by the ISEC results, no restrictions in mass transfer resistance were noticed in mesopores due to their high connectivity. The mercury porosimetry results also gave evidence that no restrictions occur for mass transfer from flow-through pores to mesopores in the small scaled silica monoliths with narrow distribution. rnThe prediction of the optimum regimes of the pore structural parameters for the given target parameters in HPLC separations was performed. It was found that a low mass transfer resistance in the mesopore volume is achieved when the nominal diameter of the number average size distribution of the mesopores is appr. an order of magnitude larger that the molecular radius of the analyte. The effective diffusion coefficient of an analyte molecule in the mesopore volume is strongly dependent on the value of the nominal pore diameter of the number averaged pore size distribution. The mesopore size has to be adapted to the molecular size of the analyte, in particular for peptides and proteins. rnThe study on flow-through pores of silica monoliths demonstrated that the surface to volume of the skeletons ratio and external porosity are decisive for the column efficiency. The latter is independent from the flow-through pore diameter. The flow-through pore characteristics by direct and indirect approaches were assessed and theoretical column efficiency curves were derived. The study showed that next to the surface to volume ratio, the total porosity and its distribution of the flow-through pores and mesopores have a substantial effect on the column plate number, especially as the extent of adsorption increases. The column efficiency is increasing with decreasing flow through pore diameter, decreasing with external porosity, and increasing with total porosity. Though this tendency has a limit due to heterogeneity of the studied monolithic samples. We found that the maximum efficiency of the studied monolithic research columns could be reached at a skeleton diameter of ~ 0.5 µm. Furthermore when the intention is to maximize the column efficiency, more homogeneous monoliths should be prepared.rn

Molecular dynamics simulations of sheared brush-like systems

Mit Hilfe von Molekulardynamik-Simulationen untersuchen wir bürstenartige Systeme unter guten Lösungsmittelbedingungen. Diese Systeme sind, dank ihren vielfältigen Beschaffenheiten, die von Molekularparametern und äußeren Bedingungen abhängig sind, wichtig für viele industrielle Anwendungen. Man vermutet, dass die Polymerbürsten eine entscheidende Rolle in der Natur wegen ihrer einzigartigen Gleiteigenschaften spielen. Ein vergröbertes Modell wird verwendet, um die strukturellen und dynamischen Eigenschaften zweier hochkomprimierter Polymerbürsten, die eine niedrige Reibung aufweisen, zu untersuchen. Allerdings sind die Lubrikationseigenschaften dieser Systeme, die in vielen biologischen Systemen vorhanden sind, beeinflußt. Wir untersuchen so-genannte "weiche Kolloide", die zwischen den beiden Polymerbürsten eingebettet sind, und wie diese Makroobjekte auf die Polymerbürsten wirken.rnrnNicht-Gleichgewichts-Molekulardynamik-Simulationen werden durchgeführt, in denen die hydrodynamischen Wechselwirkungen durch die Anwendung des DPD-Thermostaten mit expliziten Lösungsmittelmolekülen berücksichtigt werden. Wir zeigen, dass die Kenntnis der Gleichgewichtseigenschaften des Systems erlaubt, dynamische Nichtgleichgewichtsigenschaften der Doppelschicht vorherzusagen.rnrnWir untersuchen, wie die effektive Wechselwirkung zwischen kolloidalen Einschlüßen durch die Anwesenheit der Bürsten (in Abhängigkeit der Weichheit der Kolloide und der Pfropfdichte der Bürsten) beeinflußt wird. Als nächsten Schritt untersuchen wir die rheologische Antwort von solchen komplexen Doppelschichten auf Scherung. Wir entwickeln eine Skalen-Theorie, die die Abhängigkeit der makroskopischen Transporteigenschaften und der lateralen Ausdehnung der verankerten Ketten von der Weissenberg Zahl oberhalb des Bereichs, in dem die lineare Antwort-Theorie gilt, voraussagt. Die Vorhersagen der Theorie stimmen gut mit unseren und früheren numerischen Ergebnissen und neuen Experimenten überein. Unsere Theorie bietet die Möglichkeit, die Relaxationszeit der Doppelschicht zu berechnen. Wenn diese Zeit mit einer charakteristischen Längenskala kombiniert wird, kann auch das ''transiente'' (nicht-stationäre) Verhalten beschrieben werden.rnrnrnWir untersuchen die Antwort des Drucktensors und die Deformation der Bürsten während der Scherinvertierung für grosse Weissenberg Zahlen. Wir entwickeln eine Vorhersage für die charakteristische Zeit, nach der das System wieder den stationären Zustand erreicht.rnrnrnElektrostatik spielt eine bedeutende Rolle in vielen biologischen Prozessen. Die Lubrikationseigenschaften der Polymerbürsten werden durch die Anwesenheit langreichweitiger Wechselwirkungen stark beeinflusst. Für unterschiedliche Stärken der elektrostatischen Wechselwirkungen untersuchen wir rheologische Eigenschaften der Doppelschicht und vergleichen mit neutralen Systemen. Wir studieren den kontinuierlichen Übergang der Systemeigenschaften von neutralen zu stark geladenen Bürsten durch Variation der Bjerrumlänge und der Ladungsdichte.

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.

Aggregation of hybrid molecules and film formation of colloidal monolayers

A unique characteristic of soft matter is its ability to self-assemble into larger structures. Characterizing these structures is crucial for their applications. In the first part of this work, I investigated DNA-organic hybrid material by means of Fluorescence Correlation Spectroscopy (FCS) and Fluorescence Cross-Correlation Spectroscopy (FCCS). DNA-organic hybrid materials, a novel class of hybrid materials composed of synthetic macromolecules and oligodeoxynucleotide segmenta, are mostly amphiphilic and can self-assemble into supramolecular structures in aqueous solution. A hybrid material of a fluorophore, perylenediimide (PDI), and a DNA segment (DNA-PDI) has been developed in Prof. A. Hermann’s group (University of Groningen). This novel material has the ability to form aggregates through pi-pi stacking between planar PDIs and can be traced in solution due to the fluorescence of PDI. I have determined the diffusion coefficient of DNA-PDI conjugates in aqueous solution by means of FCS. In addition, I investigated whether such DNA-PDIs form aggregates with certain structure, for instance dimers. rnOnce the DNA hybrid material self-assemble into supermolecular structures for instance into micelles, the single molecules do not necessarily stay in one specific micelle. Actually, a single molecule may enter and leave micelles constantly. The average residence time of a single molecule in a certain micelle depends on the nature of the molecule. I have chosen DNA-b-polypropylene oxide (PPO) as model molecules and investigated the residence time of DNA-b-PPO molecules in their according micelles by means of FCCS.rnBesides the DNA hybrid materials, polymeric colloids can also form ordered structures once they are brought to an air/water interface. Here, hexagonally densely packed monolayers can be generated. These monolayers can be deposited onto different surfaces as coating layers. In the second part of this work, I investigated the mechanical properties of such colloidal monolayers using micromechanical cantilevers. When a coating layer is deposited on a cantilever, it can modify the elasticity of the cantilever. This variation can be reflected either by a deflection or by a resonance frequency shift of the cantilever. In turn, detecting these changes provides information about the mechanical properties of the coating layer. rnIn the second part of this work, polymeric colloidal monolayers were coated on a cantilever and homogenous polymer films of a few hundred nanometers in thickness were generated from these colloidal monolayers by thermal annealing or organic vapor annealing. Both the film formation process and the mechanical properties of these resulting homogenous films were investigated by means of cantilever. rnElastic property changes of the coating film, for example upon absorption of organic vapors, induce a deflection of the cantilever. This effect enables a cantilever to detect target molecules, when the cantilever is coated with an active layer with specific affinity to target molecules. In the last part of this thesis, I investigated the applicability of suitably functionalized micromechanical cantilevers as sensors. In particular, glucose sensitive polymer brushes were grafted on a cantilever and the deflection of this cantilever was measured during exposure to glucose solution. rn

Atmospheric heterogeneous reactions of N 2 O 5 and NO 3 radicals with mineral dust particles

Die heterogenen Reaktionen von N2O5 bzw. NO3 auf mineralischen Staubpartikeln wurden untersucht, um deren Einfluss auf den Abbau atmosphärischer Stickoxide (NOx) sowie auf die chemische Veränderung der Staubpartikel während ihres Transportes durch die Atmosphäre besser verstehen zu können. Die experimentellen Studien wurden bei Atmosphärendruck, Raumtemperatur und unterschiedlichen relativen Luftfeuchten durchgeführt. Der Aufnahmekoeffizient γ(N2O5) von N2O5 auf dispergiertem Staub aus der Sahara wurde zu 0,020 ± 0,002 (1σ) bestimmt, unabhängig von der relativen Feuchte (0 - 67 %) sowie der N2O5-Konzentration (5x1011 - 3x1013 Moleküle cm-3).rnDie Analyse der Reaktionsprodukte in der Gasphase sowie auf der Partikeloberfläche führt zu der Annahme, dass N2O5 auf der Staubpartikeloberfläche zu Nitrat hydrolysiert wird. Es konnte kein Einfluss der relativen Feuchte auf den Aufnahmekoeffizienten ermittelt werden, was durch das vorhandene interlamellare Wasser, welches bis zu 10 % der Partikelmasse betragen kann, erklärbar ist. Der gemessene Wert des Aufnahmekoeffizienten ist unabhängig von der Eingangs-N2O5-Konzentration, was sich über die sehr große innere Oberfläche der Partikel erklären lässt. Dennoch ließ sich durch eine vorherige Konditionierung der Partikel mit gasförmigem HNO3, was eine Nitratanreicherung an der Oberfläche bewirkt, die Effizienz der N2O5-Aufnahme auf die Staubpartikel reduzieren. Zusätzliche Studien befassten sich mit der Bestimmung des Aufnahmekoeffizienten von N2O5 auf Illit-Partikeln und auf Teststaub aus Arizona. Bei einer relativen Luftfeuchte von 0 % wurden für γ(N2O5) Werte von 0,084 ± 0,019 (1σ) für Illit und von 0,010 ± 0,001 (1σ) für Arizona Teststaub ermittelt.rnUnter Anwendung einer neuartigen Messmethode, die auf der zeitgleichen Messung der Konzentrationsabnahme von NO3 und N2O5 relativ zueinander beruht, wurde das Verhältnis γ(NO3)/γ(N2O5) der Aufnahmekoeffizienten von NO3 und N2O5 auf Saharastaub zu 0,9 ± 0,4 (1σ) bestimmt. Dieser Wert war unabhängig von der relativen Feuchte, den NO3- und N2O5-Konzentrationen sowie der Reaktionszeit, obwohl eine Oberflächendeaktivierung für beide Spurenstoffe beobachtet wurde.

Electronic structure and physical properties of Heusler compounds for thermoelectric and spintronic applications

This thesis focuses on synthesis as well as investigations of the electronic structure and properties of Heusler compounds for spintronic and thermoelectric applications.rnThe first part reports on the electronic and crystal structure as well as the mechanical, magnetic, and transport properties of the polycrystalline Heusler compound Co2MnGe. The crystalline structure was examined in detail by extended X-ray absorption fine structure spectroscopy and anomalous X-ray diffraction. The low-temperature magnetic moment agrees well with the Slater-Pauling rule and indicates a half-metallic ferromagnetic state of the compound, as is predicted by ab-initio calculations. Transport measurements and hard X-ray photoelectron spectroscopy (HAXPES) were performed to explain the electronic structure of the compound.rnA major part of the thesis deals with a systematical investigation of Heusler compounds for thermoelectric applications. Few studies have been reported on thermoelectric properties of p-type Heusler compounds. Therefore, this thesis focuses on the search for new p-type Heusler compounds with high thermoelectric efficiency. The substitutional series NiTi1−xMxSn and CoTi1−xMxSb (where M = Sc, V and 0 ≤ x ≤ 0.2) were synthesized and investigated theoretically and experimentally with respect to electronic structure and transport properties. The results show the possibility to create n-type and p-type thermoelectrics within one Heusler compound. The pure compounds showed n-type behavior, while under Sc substitution the system switched to p-type behavior. A maximum Seebeck coefficient of +230 μV/K (at 350 K) was obtained for NiTi0.26Sc0.04Zr0.35Hf0.35Sn, which is one of the highest values for p-type thermoelectric compounds based on Heusler alloys up to now. HAXPES valence band measurement show massive in gap states for the parent compounds NiTiSn, CoTiSb and NiTi0.3Zr0.35Hf0.35Sn. This proves that the electronic states close to the Fermi energy play a key role for the behavior of the transport properties. Furthermore, the electronic structure of the gapless Heusler compounds PtYSb, PtLaBi and PtLuSb were investigated by bulk sensitive HAXPES. The linear behavior of the spectra close to εF proves the bulk origin of Dirac-cone type density of states. Furthermore, a systematic study on the optical and transport properties of PtYSb is presented. The compound exhibits promising thermoelectric properties with a high figure of merit (ZT = 0.2) and a Hall mobility μh of 300 cm2/Vs at 350 K.rnThe last part of this thesis describes the linear dichroism in angular-resolved photoemission from the valence band of NiTi0.9Sc0.1Sn and NiMnSb. High resolution photoelectron spectroscopy was performed with an excitation energy of hν = 7.938 keV. The linear polarization of the photons was changed using an in-vacuum diamond phase retarder. Noticeable linear dichroism is found in the valence bands and this allows for a symmetry analysis of the contributing states. The differences in the spectra are found to be caused by symmetry dependent angular asymmetry parameters, and these occur even in polycrystalline samples without preferential crystallographic orientation.rnIn summary, Heusler compounds with 1:1:1 and 2:1:1 stoichiometry were synthesized and examined by chemical and physical methods. Overall, this thesis shows that the combination of first-principle calculations, transport measurements and high resolution high energy photoelectron spectroscopy analysis is a very powerful tool for the design and development of new materials for a wide range of applications from spintronic applications to thermoelectric applications.rn

Hundertneunundzwanzig Xe NMR for investigations of complex and dynamic systems

In this work, the remarkable versatility and usefulness of applications of Xe-129 NMR experiments is further extended. The application of Xe-129 NMR spectroscopy to very different system is studied, including dynamic and static, solid and liquid, porous and non-porous systems. Using the large non-equilibrium polarization created by hyperpolarization of Xe-129, time-resolved NMR measurements can be used for the online-monitoring of dynamic systems. In the first part of this work, several improvements for medical applications of hyperpolarized Xe-129 are achieved and their feasibility shown experimentally. A large gain in speed and reproducibility of the accumulation process of Xe-129 as ice and an enhancement of the usable polarization in any experiment requiring prior accumulation are achieved. An enhancement of the longitudinal relaxation time of Xe-129 is realized by admixture of a buffer gas during the storage of hyperpolarized Xe-129. Pursuing the efforts of simplifying the accumulation process and enhancing the storage time of hyperpolarized Xe-129 will allow for a wider use of the hyperpolarized gas in (medical) MRI experiments. Concerning the use of hyperpolarized Xe-129 in MRI, the influence of the diffusion coefficient of the gas on parameters of the image contrast is experimentally demonstrated here by admixture of a buffer gas and thus changing the diffusion coefficient. In the second part of this work, a polymer system with unique features is probed by Xe-129 NMR spectroscopy, proving the method to be a valuable tool for the characterization of the anisotropic properties of semicrystalline, syndiotactic polystyrene films. The polymer films contain hollow cavities or channels with sizes in the sub-nanometer range, allowing for adsorption of Xe-129 and subsequent NMR measurements. Despite the use of a ’real-world’ system, the transfer of the anisotropic properties from the material to adsorbed Xe-129 atoms is shown, which was previously only known for fully crystalline materials. The anisotropic behavior towards atomar guests inside the polymer films is proven here for the first time for one of the phases. For the polymer phase containing nanochannels, the dominance of interactions between Xe-129 atoms in the channels compared to interactions between Xe atoms and the channel walls are proven by measurements of a powder sample of the polymer material and experiments including the rotation of the films in the external magnetic field as well as temperature-dependent measurements. The characterization of ’real-world’ systems showing very high degrees of anisotropy by Xe-129 are deemed to be very valuable in future applications. In the last part of this work, a new method for the online monitoring of chemical reactions has been proposed and its feasibility and validity are experimentally proven. The chemical shift dependence of dissolved Xe-129 on the composition of a reaction mixture is used for the online monitoring of free-radical miniemulsion polymerization reactions. Xe-129 NMR spectroscopy provides an excellent method for the online monitoring of polymerization reactions, due to the simplicity of the Xe-129 NMR spectra and the simple relationship between the Xe-129 chemical shift and the reaction conversion. The results of the time-resolved Xe-129 NMR measurements are compared to those from calorimetric measurements, showing a good qualitative agreement. The applicability of the new method to reactions other than polymerization reactions is investigated by the online monitoring of an enzymatic reaction in a miniemulsion. The successful combination of the large sensitivity of Xe-129, the NMR signal enhancements due to hyperpolarization, and the solubility of Xe-129 gives access to the large new field of investigations of chemical reaction kinetics in dynamic and complex systems like miniemulsions.

Thermoelectric properties of TiNiSn and Zr 0.5 Hf 0.5 NiSn thin films and superlattices with reduced thermal conductivities

Durch steigende Energiekosten und erhöhte CO2 Emission ist die Forschung an thermoelektrischen (TE) Materialien in den Fokus gerückt. Die Eignung eines Materials für die Verwendung in einem TE Modul ist verknüpft mit der Gütezahl ZT und entspricht α2σTκ-1 (Seebeck Koeffizient α, Leitfähigkeit σ, Temperatur T und thermische Leitfähigkeit κ). Ohne den Leistungsfaktor α2σ zu verändern, soll ZT durch Senkung der thermischen Leitfähigkeit mittels Nanostrukturierung angehoben werden.rnBis heute sind die TE Eigenschaften von den makroskopischen halb-Heusler Materialen TiNiSn und Zr0.5Hf0.5NiSn ausgiebig erforscht worden. Mit Hilfe von dc Magnetron-Sputterdeposition wurden nun erstmals halbleitende TiNiSn und Zr0.5Hf0.5NiSn Schichten hergestellt. Auf MgO (100) Substraten sind stark texturierte polykristalline Schichten bei Substrattemperaturen von 450°C abgeschieden worden. Senkrecht zur Oberfläche haben sich Korngrößen von 55 nm feststellen lassen. Diese haben Halbwertsbreiten bei Rockingkurven von unter 1° aufgewiesen. Strukturanalysen sind mit Hilfe von Röntgenbeugungsexperimenten (XRD) durchgeführt worden. Durch Wachstumsraten von 1 nms 1 konnten in kürzester Zeit Filmdicken von mehr als einem µm hergestellt werden. TiNiSn zeigte den höchsten Leistungsfaktor von 0.4 mWK 2m 1 (550 K). Zusätzlich wurde bei Raumtemperatur mit Hilfe der differentiellen 3ω Methode eine thermische Leitfähigkeit von 2.8 Wm 1K 1 bestimmt. Es ist bekannt, dass die thermische Leitfähigkeit mit der Variation von Massen abnimmt. Weil zudem angenommen wird, dass sie durch Grenzflächenstreuung von Phononen ebenfalls reduziert wird, wurden Übergitter hergestellt. Dabei wurden TiNiSn und Zr0.5Hf0.5NiSn nacheinander abgeschieden. Die sehr hohe Kristallqualität der Übergitter mit ihren scharfen Grenzflächen konnte durch Satellitenpeaks und Transmissionsmikroskopie (STEM) nachgewiesen werden. Für ein Übergitter mit einer Periodizität von 21 nm (TiNiSn und Zr0.5Hf0.5NiSn jeweils 10.5 nm) ist bei einer Temperatur von 550 K ein Leistungsfaktor von 0.77 mWK 2m 1 nachgewiesen worden (α = 80 µVK 1; σ = 8.2 µΩm). Ein Übergitter mit der Periodizität von 8 nm hat senkrecht zu den Grenzflächen eine thermische Leitfähigkeit von 1 Wm 1K 1 aufgewiesen. Damit hat sich die Reduzierung der thermischen Leitfähigkeit durch die halb-Heusler Übergitter bestätigt. Durch die isoelektronischen Eigenschaften von Titan, Zirkonium und Hafnium wird angenommen, dass die elektrische Bandstruktur und damit der Leistungsfaktor senkrecht zu den Grenzflächen nur schwach beeinflusst wird.rn

Variability of lung function predicts loss of asthma control following withdrawal of inhaled corticosteroid treatment

BACKGROUND One aspect of a multidimensional approach to understanding asthma as a complex dynamic disease is to study how lung function varies with time. Variability measures of lung function have been shown to predict response to beta(2)-agonist treatment. An investigation was conducted to determine whether mean, coefficient of variation (CV) or autocorrelation, a measure of short-term memory, of peak expiratory flow (PEF) could predict loss of asthma control following withdrawal of regular inhaled corticosteroid (ICS) treatment, using data from a previous study. METHODS 87 adult patients with mild to moderate asthma who had been taking ICS at a constant dose for at least 6 months were monitored for 2-4 weeks. ICS was then withdrawn and monitoring continued until loss of control occurred as per predefined criteria. Twice-daily PEF was recorded during monitoring. Associations between loss of control and mean, CV and autocorrelation of morning PEF within 2 weeks pre- and post-ICS withdrawal were assessed using Cox regression analysis. Predictive utility was assessed using receiver operator characteristics. RESULTS 53 out of 87 patients had sufficient PEF data over the required analysis period. The mean (389 vs 370 l/min, p<0.0001) and CV (4.5% vs 5.6%, p=0.007) but not autocorrelation of PEF changed significantly from prewithdrawal to postwithdrawal in subjects who subsequently lost control, and were unaltered in those who did not. These changes were related to time to loss of control. CV was the most consistent predictor, with similar sensitivity and sensitivity to exhaled nitric oxide. CONCLUSION A simple, easy to obtain variability measure of daily lung function such as the CV may predict loss of asthma control within the first 2 weeks of ICS withdrawal.

Test-retest reliability of the nociceptive withdrawal reflex and electrical pain thresholds after single and repeated stimulation in patients with chronic low back pain

Recent studies have shown that the nociceptive withdrawal reflex threshold (NWR-T) and the electrical pain threshold (EP-T) are reliable measures in pain-free populations. However, it is necessary to investigate the reliability of these measures in patients with chronic pain in order to translate these techniques from laboratory to clinic. The aims of this study were to determine the test-retest reliability of the NWR-T and EP-T after single and repeated (temporal summation) electrical stimulation in a group of patients with chronic low back pain, and to investigate the association between the NWR-T and the EP-T. To this end, 25 patients with chronic pain participated in three identical sessions, separated by 1 week in average, in which the NWR-T and the EP-T to single and repeated stimulation were measured. Test-retest reliability was assessed using intra-class correlation coefficient (ICC), coefficient of variation (CV), and Bland-Altman analysis. The association between the thresholds was assessed using the coefficient of determination (r (2)). The results showed good-to-excellent reliability for both NWR-T and EP-T in all cases, with average ICC values ranging 0.76-0.90 and average CV values ranging 12.0-17.7%. The association between thresholds was better after repeated stimulation than after single stimulation, with average r (2) values of 0.83 and 0.56, respectively. In conclusion, the NWR-T and the EP-T are reliable assessment tools for assessing the sensitivity of spinal nociceptive pathways in patients with chronic pain.