Spectral estimates and preconditioning for saddle point systems arising from optimization problems

In this thesis, we consider the problem of solving large and sparse linear systems of saddle point type stemming from optimization problems. The focus of the thesis is on iterative methods, and new preconditioning srategies are proposed, along with novel spectral estimtates for the matrices involved.

Mesozoic fold structure of the Otago and Alpine Schist Belt and its implications on the tectonic evolution of South Island, New Zealand

Erneute Untersuchungen der mesozoischen Faltenstruktur des Otago Schiefergürtels, Südinsel, Neuseeland, zeigen, dass diese aus zwei aufeinander folgenden, ähnlichen, asymmetrischen, offenen bis mäßig engen Großfaltengenerationen im km- Größenbereich besteht anstatt aus den vorher angenommenen Decken- oder Halbfalten. Hauptproblem der Großfaltenstruktur sind Zonen von durchgreifender Boudinage, die in der Nähe der Großfaltenscharniere entstanden sind. Vorherige Bearbeiter deuteten diese Zonen als 'starke Verformungszonen' oder Überschiebungszonen. Diese Arbeit zeigt, dass in diesen Zonen nur durch die asymmetrische Faltung die unteren liegenden Schenkel der Großfalten boudiniert und somit häufig die ansonsten typischen Faltenstrukturen des liegenden Schenkels einer symmetrischen Faltung überprägt wurden. Ein weiteres Problem dieser mesozoischen Großfaltenstruktur ist die Überprägung einer Faltengeneration auf eine frühere. Weil die Verkürzungsrichtung der überprägenden Faltengeneration nicht subparallel zur älteren Faltenachse ist, sondern einen Winkel von rund 30 Grad einschließt, ist ein Wechsel von orthogonalen zu koaxialen Interferenzmustern der Kleinfalten beobachtbar. Folglich ist die Orientierung der Scheitellinie einer überprägenden und überprägten Kleinfalte nicht unbedingt subparallel zur Orientierung der Faltenachse der Großfalte trotz zylindrischer Faltung. Im letzten Teil dieser Arbeit wird die Überprägung der mesozoischen Großfaltenstruktur durch das känozoisch entstandene, transpressionale Alpine Störungssystem, das einen zweiseitigen Falten- und Überschiebungsgürtel im Otago und im Nordwesten anschließenden Alpinen Schiefergürtel bildet, beschrieben.

The intracellular Ig fold: a robust protein scaffold for the engineering of molecular recognition

Protein scaffolds that support molecular recognition have multiple applications in biotechnology. Thus, protein frames with robust structural cores but adaptable surface loops are in continued demand. Recently, notable progress has been made in the characterization of Ig domains of intracellular origin--in particular, modular components of the titin myofilament. These Ig belong to the I(intermediate)-type, are remarkably stable, highly soluble and undemanding to produce in the cytoplasm of Escherichia coli. Using the Z1 domain from titin as representative, we show that the I-Ig fold tolerates the drastic diversification of its CD loop, constituting an effective peptide display system. We examine the stability of CD-loop-grafted Z1-peptide chimeras using differential scanning fluorimetry, Fourier transform infrared spectroscopy and nuclear magnetic resonance and demonstrate that the introduction of bioreactive affinity binders in this position does not compromise the structural integrity of the domain. Further, the binding efficiency of the exogenous peptide sequences in Z1 is analyzed using pull-down assays and isothermal titration calorimetry. We show that an internally grafted, affinity FLAG tag is functional within the context of the fold, interacting with the anti-FLAG M2 antibody in solution and in affinity gel. Together, these data reveal the potential of the intracellular Ig scaffold for targeted functionalization.

Structural analysis of B-Box 2 from MuRF1: identification of a novel self-association pattern in a RING-like fold

The B-box motif is the defining feature of the TRIM family of proteins, characterized by a RING finger-B-box-coiled coil tripartite fold. We have elucidated the crystal structure of B-box 2 (B2) from MuRF1, a TRIM protein that supports a wide variety of protein interactions in the sarcomere and regulates the trophic state of striated muscle tissue. MuRF1 B2 coordinates two zinc ions through a cross-brace alpha/beta-topology typical of members of the RING finger superfamily. However, it self-associates into dimers with high affinity. The dimerization pattern is mediated by the helical component of this fold and is unique among RING-like folds. This B2 reveals a long shallow groove that encircles the C-terminal metal binding site ZnII and appears as the defining protein-protein interaction feature of this domain. A cluster of conserved hydrophobic residues in this groove and, in particular, a highly conserved aromatic residue (Y133 in MuRF1 B2) is likely to be central to this role. We expect these findings to aid the future exploration of the cellular function and therapeutic potential of MuRF1.

The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure

Aggretin is a C-type lectin purified from Calloselasma rhodostoma snake venom. It is a potent activator of platelets, resulting in a collagen-like response by binding and clustering platelet receptor CLEC-2. We present here the crystal structure of aggretin at 1.7 A which reveals a unique tetrameric quaternary structure. The two alphabeta heterodimers are arranged through 2-fold rotational symmetry, resulting in an antiparallel side-by-side arrangement. Aggretin thus presents two ligand binding sites on one surface and can therefore cluster ligands in a manner reminiscent of convulxin and flavocetin. To examine the molecular basis of the interaction with CLEC-2, we used a molecular modeling approach of docking the aggretin alphabeta structure with the CLEC-2 N-terminal domain (CLEC-2N). This model positions the CLEC-2N structure face down in the "saddle"-shaped binding site which lies between the aggretin alpha and beta lectin-like domains. A 2-fold rotation of this complex to generate the aggretin tetramer reveals dimer contacts for CLEC-2N which bring the N- and C-termini into the proximity of each other, and a series of contacts involving two interlocking beta-strands close to the N-terminus are described. A comparison with homologous lectin-like domains from the immunoreceptor family reveals a similar but not identical dimerization mode, suggesting this structure may represent the clustered form of CLEC-2 capable of signaling across the platelet membrane.

Bifurcation and singularity analysis of a molecular network for the induction of long-term memory.

Withdrawal reflexes of the mollusk Aplysia exhibit sensitization, a simple form of long-term memory (LTM). Sensitization is due, in part, to long-term facilitation (LTF) of sensorimotor neuron synapses. LTF is induced by the modulatory actions of serotonin (5-HT). Pettigrew et al. developed a computational model of the nonlinear intracellular signaling and gene network that underlies the induction of 5-HT-induced LTF. The model simulated empirical observations that repeated applications of 5-HT induce persistent activation of protein kinase A (PKA) and that this persistent activation requires a suprathreshold exposure of 5-HT. This study extends the analysis of the Pettigrew model by applying bifurcation analysis, singularity theory, and numerical simulation. Using singularity theory, classification diagrams of parameter space were constructed, identifying regions with qualitatively different steady-state behaviors. The graphical representation of these regions illustrates the robustness of these regions to changes in model parameters. Because persistent protein kinase A (PKA) activity correlates with Aplysia LTM, the analysis focuses on a positive feedback loop in the model that tends to maintain PKA activity. In this loop, PKA phosphorylates a transcription factor (TF-1), thereby increasing the expression of an ubiquitin hydrolase (Ap-Uch). Ap-Uch then acts to increase PKA activity, closing the loop. This positive feedback loop manifests multiple, coexisting steady states, or multiplicity, which provides a mechanism for a bistable switch in PKA activity. After the removal of 5-HT, the PKA activity either returns to its basal level (reversible switch) or remains at a high level (irreversible switch). Such an irreversible switch might be a mechanism that contributes to the persistence of LTM. The classification diagrams also identify parameters and processes that might be manipulated, perhaps pharmacologically, to enhance the induction of memory. Rational drug design, to affect complex processes such as memory formation, can benefit from this type of analysis.

(Table 1) Geochemical and geothermometry data from fibrous calcite vein fills in the Dabashan Fold Belt, China

Fibrous calcite veins with organic inclusions have been widely considered as indicators of oil and gas generation and migration under overpressure. Abundant fibrous calcite veins containing organic-bearing inclusions occur in faulted Lower Paleozoic through Triassic hydrocarbon source rocks in the Dabashan Foreland Belt (DBF). d13CPDB and d18OPDB values of the fibrous calcite range from - 4.8 to -1.9 to per mil and - 12.8 to - 8.4 per mil respectively, which is lighter than that of associated carbonate host rocks ranging from - 1.7 to + 3.1 per mil and - 8.7 to - 4.5 per mil. A linear relationship between d13CPDB and d18OPDB indicates that the calcite veins were precipitated from a mixture of basinal and surface fluids. The fibrous calcite contains a variety of inclusions, such as solid bitumen, methane bearing all-liquid inclusions, and vapor-liquid aqueous inclusions. Homogenization temperatures of aqueous inclusions range from 140 to 196° with an average of 179°. Salinities of aqueous inclusions average 9.7 wt% NaCl. Independent temperatures from bitumen reflectance and inclusion phase relationships of aqueous and methane inclusions were used to determine fluid pressures. Results indicate high pressures, elevated above typical lithostatic confining pressure, from 150 to 200 MPa. The elevated salinity and high temperature and pressure conditions of the fibrous calcite veins argue against an origin solely from burial overpressure resulting from clay transformation and dehydration reactions. Instead fluid inclusion P-T data and geochemistry results and regional geology indicate abnormally high pressures during fluid migration. These findings indicate that tectonic stress generated fracture and fault fluid pathways and caused migration of organic bearing fluids from the DBF during the Yanshan orogeny.

Seismic data from Colle Gnifetti glacie saddle around borehole KCI, Swiss Alps

Two seismic surveys were carried out on the high-altitude glacier saddle, Colle Gnifetti, Monte Rosa, Italy/Switzerland. Explosive and vibroseismic sources were tested to explore the best way to generate seismic waves to deduce shallow and intermediate properties (<100 m) of firn and ice. The explosive source (SISSY) excites strong surface and diving waves, degrading data quality for processing; no englacial reflections besides the noisy bed reflector are visible. However, the strong diving waves are analyzed to derive the density distribution of the firn pack, yielding results similar to a nearby ice core. The vibrator source (ElViS), used in both P- and SH-wave modes, produces detectable laterally coherent reflections within the firn and ice column. We compare these with ice-core and radar data. The SH-wave data are particularly useful in providing detailed, high-resolution information on firn and ice stratigraphy. Our analyses demonstrate the potential of seismic methods to determine physical properties of firn and ice, particularly density and potentially also crystal-orientation fabric.

9-fold Fresnel-Köhler concentrator for increased uniform irradiance on high concentrations

Non-uniform irradiance patterns created by Concentrated Photovoltaics (CPV) concentrators over Multi-Junction Cells (MJC) can originate significant power losses, especially when there are different spectral irradiance distributions over the different MJC junctions. This fact has an increased importance considering the recent advances in 4 and 5 junction cells. The spectral irradiance distributions are especially affected with thermal effects on Silicone-on-Glass (SoG) CPV systems. This work presents a new CPV optical design, the 9-fold Fresnel Köhler concentrator, prepared to overcome these effects at high concentrations while maintaining a large acceptance angle, paving the way for a future generation of high efficiency CPV systems of 4 and 5 junction cells.

New Fresnel Köhler optical design: 9-fold photovoltaic concentrator

Non-uniform irradiance patterns created by Concentrated Photovoltaics (CPV) concentrators over Multi-Junction Cells (MJC) can originate significant power losses, especially when there are different spectral irradiance distributions over the different MJC junctions. This fact has an increased importance considering the recent advances in 4 and 5 junction cells. This work presents a new CPV optical design, the 9-fold Fresnel Köhler concentrator, prepared to overcome these effects at high concentrations while maintaining a large acceptance angle, paving the way for a future generation of high efficiency CPV systems of 4 and 5 junction cells.

Estimating tremor in Vocal Fold Biomechanics for Neurological Disease characterisation

Neurological Diseases (ND) are affecting larger segments of aging population every year. Treatment is dependent on expensive accurate and frequent monitoring. It is well known that ND leave correlates in speech and phonation. The present work shows a method to detect alterations in vocal fold tension during phonation. These may appear either as hypertension or as cyclical tremor. Estimations of tremor may be produced by auto-regressive modeling of the vocal fold tension series in sustained phonation. The correlates obtained are a set of cyclicality coefficients, the frequency and the root mean square amplitude of the tremor. Statistical distributions of these correlates obtained from a set of male and female subjects are presented. Results from five study cases of female voice are also given.

Monitoring treatment of vocal fold paralysis by biomechanical analysis of voice

A case study of vocal fold paralysis treatment is described with the help of the voice quality analysis application BioMet®Phon. The case corresponds to a description of a 40 - year old female patient who was diagnosed of vocal fold paralysis following a cardio - pulmonar intervention which required intubation for 8 days and posterior tracheotomy for 15 days. The patient presented breathy and asthenic phon ation, and dysphagia. Six main examinations were conducted during a full year period that the treatment lasted consisting in periodic reviews including video - endostroboscopy, voice analysis and breathing function monitoring. The phoniatrician treatment inc luded 20 sessions of vocal rehabilitation, followed by an intracordal infiltration with Radiesse 8 months after the rehabilitation treatment started followed by 6 sessions of rehabilitation more. The videondoscopy and the voicing quality analysis refer a s ubstantial improvement in the vocal function with recovery in all the measures estimated (jitter, shimmer, mucosal wave contents, glottal closure, harmonic contents and biomechanical function analysis). The paper refers the procedure followed and the results obtained by comparing the longitudinal progression of the treatment, illustrating the utility of voice quality analysis tools in speech therapy.

Vocal fold biomechanical analysis for the singing voice

Teaching the adequate use of the singing voice conveys a lot of knowledge in musical performance as well as in objective estimation techniques involving the use of air, muscles, room and body acoustics, and the tuning of a fine instrument as the human voice. Although subjective evaluation and training is a very delicate task to be carried out only by expert singers, biomedical engineering may help contributing with well - funded methodologies developed for the study of voice pathology. The present study is a preliminary study of exploratory character describing the performance of a student singer in a regular classroom under the point of view of vocal fold biomechanics. Estimate s of biomechanical parameters obtained from singing voice are given and their use i n the classroom is discussed.