An experimentally validated finite element method for augmented vertebral bodies

Background Finite element models of augmented vertebral bodies require a realistic modelling of the cement infiltrated region. Most methods published so far used idealized cement shapes or oversimplified material models for the augmented region. In this study, an improved, anatomy-specific, homogenized finite element method was developed and validated to predict the apparent as well as the local mechanical behavior of augmented vertebral bodies. Methods Forty-nine human vertebral body sections were prepared by removing the cortical endplates and scanned with high-resolution peripheral quantitative CT before and after injection of a standard and a low-modulus bone cement. Forty-one specimens were tested in compression to measure stiffness, strength and contact pressure distributions between specimens and loading-plates. From the remaining eight, fourteen cylindrical specimens were extracted from the augmented region and tested in compression to obtain material properties. Anatomy-specific finite element models were generated from the CT data. The models featured element-specific, density-fabric-based material properties, damage accumulation, real cement distributions and experimentally determined material properties for the augmented region. Apparent stiffness and strength as well as contact pressure distributions at the loading plates were compared between simulations and experiments. Findings The finite element models were able to predict apparent stiffness (R2 > 0.86) and apparent strength (R2 > 0.92) very well. Also, the numerically obtained pressure distributions were in reasonable quantitative (R2 > 0.48) and qualitative agreement with the experiments. Interpretation The proposed finite element models have proven to be an accurate tool for studying the apparent as well as the local mechanical behavior of augmented vertebral bodies.

A urokinase receptor promoter element (-152/-135) bound with an AP-2-alpha-related protein and SP1 is required for the induction of gene expression by PMA and SRC

The urokinase-type plasminogen activator receptor (u-PAR) promotes extracellular matrix degradation, invasion and metastasis. A first objective of this dissertation was to identify cis-elements and trans-acting factors activating u-PAR gene expression through a previously footprinted (–148/–124) promoter region. Mobility shifting experiments on nuclear extracts of a high u-PAR-expressing colon cancer cell line (RKO) indicated Sp1, Sp3 and a factor similar to, but distinct from, AP-2α bound to an oligonucleotide spanning –152/–135. Mutations preventing the binding of the AP-2α-related factor reduced u-PAR promoter activity. In RKO, the expression of a dominant negative AP-2 (AP-2αB) diminished u-PAR promoter activity, protein and u-PAR mediated laminin degradation. Conversely, u-PAR promoter activity in low u-PAR-expressing GEO cells was increased by AP-2αA expression. PMA treatment, which induces u-PAR expression, caused an increased amount of the AP-2α-related factor-containing complex in GEO, and mutations preventing AP-2α-like and Sp1/Sp3 binding reduced the u-PAR promoter stimulation by PMA. In resected colon cancers, u-PAR protein amounts were related to the amount of the AP-2α-related factor-containing complex. In conclusion, constitutive and PMA- inducible u-PAR gene expression and -proteolysis are mediated partly through transactivation via a promoter sequence (–152/435) bound with an AP-2α-related factor and Sp1/Sp3. ^ A second interest of this dissertation was to determine if a constitutively active Src regulates the transcription of the u-PAR gene, since c-src expression increases invasion in colon cancer. Increased u-PAR protein and laminin degradation paralleling elevated Src activity was evident in SW480 colon cancer cells stably expressing a constitutively active Src (Y- c-src527F). Nuclear run-on experiments indicated that this was due largely to transcriptional activation. While transient transfection of SW480 cells with Y-c-src527F induced a u-PAR-CAT-reporter, mutations preventing Sp1-binding to promoter region –152/435 abolished this induction. Mobility shift assays revealed increased Sp1 binding to region –152/135 with nuclear extracts of Src-transfected SW480 cells. Finally, the amounts of endogenous u-PAR in resected colon cancers significantly correlated with Src-activity. These data suggest that u-PAR gene expression and proteolysis are regulated by Src, this requiring the promoter region (–152/–135) bound with Sp1, thus, demonstrating for the first time that transcription factor Sp1 is a downstream effector of Src. ^

Stable two-element control of dTph1 transposition in mutator strains of Petunia by an inactive ACT1 introgression from a wild species

The high copy dTph1 transposon system of Petunia (Solanaceae) is one of the most powerful insertion mutagens in plants, but its activity cannot be controlled in the commonly used mutator strains. We analysed the regulation of dTph1 activity by QTL analysis in recombinant inbred lines of the mutator strain W138 and a wild species (P. integrifolia spp. inflata). Two genetic factors were identified that control dTph1 transposition. One corresponded to the ACT1 locus on chromosome I. A second, previously undescribed locus ACT2 mapped on chromosome V. As a 6-cM introgression in W138, the P. i. inflata act1(S6) allele behaved as a single recessive locus that fully eliminated transposition of all dTph1 elements in all stages of plant development and in a heritable fashion. Weak dTph1 activity was restored in act1(S6)/ACT2(S6) double introgression lines, indicating that the P. i. inflata allele at ACT2 conferred a low level of transposition. Thus, the act1(S6) allele is useful for simple and predictable control of transposition of the entire dTph1 family when introgressed into an ultra-high copy W138 mutator strain. We demonstrate the use of the ACT1(W138)/act1(S6) allele pair in a two-element dTph1 transposition system by producing 10 000 unique and fixed dTph1 insertions in a population of 1250 co-isogenic lines. This Petunia system produces the highest per plant insertion number of any known two-element system, providing a powerful and logistically simple tool for transposon mutagenesis of qualitative as well as quantitative traits.

Finite element analysis in asymptomatic, symptomatic, and ruptured abdominal aortic aneurysms: in search of new rupture risk predictors.

OBJECTIVES To compare biomechanical rupture risk parameters of asymptomatic, symptomatic and ruptured abdominal aortic aneurysms (AAA) using finite element analysis (FEA). STUDY DESIGN Retrospective biomechanical single center analysis of asymptomatic, symptomatic, and ruptured AAAs. Comparison of biomechanical parameters from FEA. MATERIALS AND METHODS From 2011 to 2013 computed tomography angiography (CTA) data from 30 asymptomatic, 15 symptomatic, and 15 ruptured AAAs were collected consecutively. FEA was performed according to the successive steps of AAA vessel reconstruction, segmentation and finite element computation. Biomechanical parameters Peak Wall Rupture Risk Index (PWRI), Peak Wall Stress (PWS), and Rupture Risk Equivalent Diameter (RRED) were compared among the three subgroups. RESULTS PWRI differentiated between asymptomatic and symptomatic AAAs (p < .0004) better than PWS (p < .1453). PWRI-dependent RRED was higher in the symptomatic subgroup compared with the asymptomatic subgroup (p < .0004). Maximum AAA external diameters were comparable between the two groups (p < .1355). Ruptured AAAs showed the highest values for external diameter, total intraluminal thrombus volume, PWS, RRED, and PWRI compared with asymptomatic and symptomatic AAAs. In contrast with symptomatic and ruptured AAAs, none of the asymptomatic patients had a PWRI value >1.0. This threshold value might identify patients at imminent risk of rupture. CONCLUSIONS From different FEA derived parameters, PWRI distinguishes most precisely between asymptomatic and symptomatic AAAs. If elevated, this value may represent a negative prognostic factor for asymptomatic AAAs.

In search of the "why" behind campaign professionalisation: explaining the degree and profile of campaign professionalisation by an empirical analysis of 23 Swiss cantonal election campaigns

Die Organisation und die strategische Kommunikation von Wahlkämpfen haben sich in den letzten Jahrzehnten in den meisten westeuropäischen Staaten gewandelt, so auch in der Schweiz. Die Kommunikationswissenschaft hat dafür den Begriff der „Professionalisierung“ geprägt und Eigenschaften zusammengetragen, die zu einem „professionalisierten“ Wahlkampf gehören – wie z.B. die Beauftragung von externen Expertinnen und Experten oder die direkte Ansprache von Wählerinnen und Wählern („narrowcasting“). Welche Hintergründe diese Professionalisierung aber hat und wie das Phänomen nicht nur praktisch zu beschreiben, sondern auch theoretisch zu begründen ist, wurde bisher kaum diskutiert. Hier setzt die vorliegende Dissertation an. Basierend auf einer Analyse von 23 Wahlkämpfen aus den Kantonen Aargau, Appenzell Ausserrhoden, Bern, Neuchâtel und Zürich mithilfe der Methode Fuzzy Set Qualitative Comparative Analysis (fsQCA) kommt sie zum Schluss, dass die Professionalisierung der Wahlkämpfe vor dem theoretischen Hintergrund des soziologischen Neo-Institutionalismus als Anpassung von Wahlkämpfen an sich verändernde Bedingungen, Erwartungen und Anforderungen in den wichtigsten Anspruchsgruppen oder „Umwelten“ für den Wahlkampf (Wählerinnen und Wähler, Mitglieder, Medien, andere Parteien) definiert werden kann. Daraus folgt, dass es nicht nur „die“ Professionalisierung gibt, sondern dass jeder Wahlkampf an jene Umwelten angepasst wird, wo diese Anpassung den Wahlkampfverantwortlichen am dringlichsten erscheint. Daher sollte Professionalisierung mit vier einzelnen Messinstrumenten bzw. Professionalisierungsindices – einem pro Umwelt – gemessen werden. Misst man Professionalisierung wie bisher üblich nur mit einem einzigen Messinstrument, gibt der resultierende Wert nur ein ungenaues Bild vom Grad der Professionalisierung des Wahlkampfs wieder und verschleiert, als Anpassung an welche Umwelt die Professionalisierung geschieht. Hat man ermittelt, wie professionalisiert ein Wahlkampf im Hinblick auf jede der vier relevantesten Umwelten ist, können dann auch zuverlässiger die Gründe analysiert werden, die zur jeweiligen Professionalisierung geführt haben. Die empirische Analyse der kantonalen Wahlkämpfe bestätigte, dass hinter der Professionalisierung in Bezug auf jede der vier Umwelten auch tatsächlich unterschiedliche Gründe stecken. Wahlkämpfe werden in Bezug auf die Ansprache der Wähler angepasst („professionalisiert“), wenn sie in urbanen Kontexten stattfinden. Den Wahlkampf im Hinblick auf die Mitglieder zu professionalisieren ist besonders wichtig, wenn die Konkurrenz zwischen den Parteien gross ist oder wenn eine Ansprache der Gesamtwählerschaft für eine Partei wenig gewinnbringend erscheint. Die Professionalisierung des Wahlkampfes in Bezug auf die Medien erfolgt dann, wenn er eine grosse, regional stark verteilte oder aber eine urbane Wählerschaft ansprechen muss. Für die Professionalisierung der Wahlkämpfe gegenüber anderen Parteien kann kein aussagekräftiger Schluss gezogen werden, da nur wenige der untersuchten Kantonalparteien ihre Wahlkämpfe überhaupt im Hinblick auf andere Parteien professionalisierten, indem sie die gegnerischen Wahlkämpfe beobachteten und den eigenen wenn nötig entsprechend anpassten.

Comparison of proximal femur and vertebral body strength improvements in the FREEDOM trial using an alternative finite element methodology

Denosumab reduced the incidence of new fractures in postmenopausal women with osteoporosis by 68% at the spine and 40% at the hip over 36 months compared with placebo in the FREEDOM study. This efficacy was supported by improvements from baseline in vertebral (18.2%) strength in axial compression and femoral (8.6%) strength in sideways fall configuration at 36 months, estimated in Newtons by an established voxel-based finite element (FE) methodology. Since FE analyses rely on the choice of meshes, material properties, and boundary conditions, the aim of this study was to independently confirm and compare the effects of denosumab on vertebral and femoral strength during the FREEDOM trial using an alternative smooth FE methodology. Unlike the previous FE study, effects on femoral strength in physiological stance configuration were also examined. QCT data for the proximal femur and two lumbar vertebrae were analyzed by smooth FE methodology at baseline, 12, 24, and 36 months for 51 treated (denosumab) and 47 control (placebo) subjects. QCT images were segmented and converted into smooth FE models to compute bone strength. L1 and L2 vertebral bodies were virtually loaded in axial compression and the proximal femora in both fall and stance configurations. Denosumab increased vertebral body strength by 10.8%, 14.0%, and 17.4% from baseline at 12, 24, and 36 months, respectively (p < 0.0001). Denosumab also increased femoral strength in the fall configuration by 4.3%, 5.1%, and 7.2% from baseline at 12, 24, and 36 months, respectively (p < 0.0001). Similar improvements were observed in the stance configuration with increases of 4.2%, 5.2%, and 5.2% from baseline (p ≤ 0.0007). Differences between the increasing strengths with denosumab and the decreasing strengths with placebo were significant starting at 12 months (vertebral and femoral fall) or 24 months (femoral stance). Using an alternative smooth FE methodology, we confirmed the significant improvements in vertebral body and proximal femur strength previously observed with denosumab. Estimated increases in strength with denosumab and decreases with placebo were highly consistent between both FE techniques.

The Interplay between Melting, Refertilization and Carbonatite Metasomatism in Off-Cratonic Lithospheric Mantle under Zealandia: an Integrated Major, Trace and Platinum Group Element Study

It is widely accepted that stabilization of the continental crust requires the presence of sub-continental lithospheric mantle. However, the degree of melt depletion required to stabilize the lithosphere and whether widespread refertilization is a significant process remain unresolved. Here, major and trace element, including platinum group elements (PGE), characterization of 40 mantle xenoliths from 13 localities is used to constrain the melt depletion, refertilization and metasomatic history of lithospheric mantle underneath the micro-continent Zealandia. Our previously published Re–Os isotopic data for a subset of these xenoliths indicate Phanerozoic to Paleoproterozoic ages and, reinterpreted with the new major and trace element data presented here, demonstrate that a large volume (>2 million km3) of lithospheric mantle with an age of 1·99 ± 0·21 Ga is present below the much younger crust of Zealandia. A peritectic melting model using moderately incompatible trace elements (e.g. Yb) in bulk-rocks demonstrates that these peridotites experienced a significant range of degrees of partial melting, between 3 and 28%. During subsolidus equilibration clinopyroxene gains significant rare earth elements (REE), which then leads to the underestimation of the degree of partial melting by ≤12% in fertile xenoliths. A new approach taking into account the effects of subsolidus re-equilibration on clinopyroxene composition effectively removes discrepancies in the calculated degree of melting and provides consistent estimates of between 4 and 29%. The estimated amount of melting is independent of the Re–Os model ages of the samples. The PGE patterns record simple melt depletion histories and the retention of primary base metal sulfides in the majority of the xenoliths. A rapid decrease in Pt/IrN observed at c. 1·0 wt % Al2O3 is a direct result of the exhaustion of sulfide in the mantle residue at c. 20–25% partial melting and the inability of Pt to form a stable alloy phase. Major elements preserve evidence for refertilization by a basaltic component that resulted in the formation of secondary clinopyroxene and low-forsterite olivine. The majority of xenoliths show the effects of cryptic metasomatic overprinting, ranging from minor to strong light REE enrichments in bulk-rocks (La/YbN = 0·16–15·9). Metasomatism is heterogeneous, with samples varying from those with weak REE enrichment and notable positive Sr and U–Th anomalies and negative Nb–Ta anomalies in clinopyroxene to those that have extremely high concentrations of REE, Th–U and Nb. Chemical compositions are consistent with a carbonatitic component contributing to the metasomatism of the lithosphere under Zealandia. Notably, the intense metasomatism of the samples did not affect the PGE budget of the peridotites as this was controlled by residual sulfides.

Search, Seizure and (False?) Arrest: An Analysis of Fourth Amendment Remedies when Police can Plant Evidence

The Fourth Amendment prohibits unreasonable searches and seizures in criminal investigations. The Supreme Court has interpreted this to require that police obtain a warrant prior to search and that illegally seized evidence be excluded from trial. A consensus has developed in the law and economics literature that tort liability for police officers is a superior means of deterring unreasonable searches. We argue that this conclusion depends on the assumption of truth-seeking police, and develop a game-theoretic model to compare the two remedies when some police officers (the bad type) are willing to plant evidence in order to obtain convictions, even though other police (the good type) are not (where this type is private information). We characterize the perfect Bayesian equilibria of the asymmetric-information game between the police and a court that seeks to minimize error costs in deciding whether to convict or acquit suspects. In this framework, we show that the exclusionary rule with a warrant requirement leads to superior outcomes (relative to tort liability) in terms of truth-finding function of courts, because the warrant requirement can reduce the scope for bad types of police to plant evidence

A numerical discrete element study on the influence of an embedded viscoelastic-plastic layer at different viscosity values

The major aim of this study was to examine the influence of an embedded viscoelastic-plastic layer at different viscosity values on accretionary wedges at subduction zones. To quantify the effects of the layer viscosity, we analysed the wedge geometry, accretion mode, thrust systems and mass transport pattern. Therefore, we developed a numerical 2D 'sandbox' model utilising the Discrete Element Method. Starting with a simple pure Mohr Coulomb sequence, we added an embedded viscoelastic-plastic layer within the brittle, undeformed 'sediment' package. This layer followed Burger's rheology, which simulates the creep behaviour of natural rocks, such as evaporites. This layer got thrusted and folded during the subduction process. The testing of different bulk viscosity values, from 1 × 10**13 to 1 × 10**14 (Pa s), revealed a certain range where an active detachment evolved within the viscoelastic-plastic layer that decoupled the over- and the underlying brittle strata. This mid-level detachment caused the evolution of a frontally accreted wedge above it and a long underthrusted and subsequently basally accreted sequence beneath it. Both sequences were characterised by specific mass transport patterns depending on the used viscosity value. With decreasing bulk viscosities, thrust systems above this weak mid-level detachment became increasingly symmetrical and the particle uplift was reduced, as would be expected for a salt controlled forearc in nature. Simultaneously, antiformal stacking was favoured over hinterland dipping in the lower brittle layer and overturning of the uplifted material increased. Hence, we validated that the viscosity of an embedded detachment strongly influences the whole wedge mechanics, both the respective lower slope and the upper slope duplex, shown by e.g. the mass transport pattern.

An efficient ‘a priori’ model reduction for boundary element models

The Boundary Element Method (BEM) is a discretisation technique for solving partial differential equations, which offers, for certain problems, important advantages over domain techniques. Despite the high CPU time reduction that can be achieved, some 3D problems remain today untreatable because the extremely large number of degrees of freedom—dof—involved in the boundary description. Model reduction seems to be an appealing choice for both, accurate and efficient numerical simulations. However, in the BEM the reduction in the number of degrees of freedom does not imply a significant reduction in the CPU time, because in this technique the more important part of the computing time is spent in the construction of the discrete system of equations. In this way, a reduction also in the number of weighting functions, seems to be a key point to render efficient boundary element simulations.

Modelling of corrosion-induced cover cracking in reinforced concrete by an embedded cohesive crack finite element

Corrosion of a reinforcement bar leads to expansive pressure on the surrounding concrete that provokes internal cracking and, eventually, spalling and delamination. Here, an embedded cohesive crack 2D finite element is applied for simulating the cracking process. In addition, four simplified analytical models are introduced for comparative purposes. Under some assumptions about rust properties, corrosion rate, and particularly, the accommodation of oxide products within the open cracks generated in the process, the proposed FE model is able to estimate time to surface cracking quite accurately. Moreover, emerging cracking patterns are in reasonably good agreement with expectations. As a practical case, a prototype application of the model to an actual bridge deck is reported.

An efficient nonlinear transformation for the numerical computation of the singular integrals appearing in the 2-D Boundary Element Method

We discuss several methods, based on coordinate transformations, for the evaluation of singular and quasisingular integrals in the direct Boundary Element Method. An intrinsec error of some of these methods is detected. Two new transformations are suggested which improve on those currently available.

A method for incorporating residual stresses into patient-specific finite element simulations of arteries with an example on AAAs

Through progress in medical imaging, image analysis and finite element (FE) meshing tools it is now possible to extract patient-specific geometries from medical images of abdominal aortic aneurysms(AAAs), and thus to study clinically-relevant problems via FE simulations. Such simulations allow additional insight into human physiology in both healthy and diseased states. Medical imaging is most often performed in vivo, and hence the reconstructed model geometry in the problem of interest will represent the in vivo state, e.g., the AAA at physiological blood pressure. However, classical continuum mechanics and FE methods assume that constitutive models and the corresponding simulations begin from an unloaded, stress-free reference condition.