Complementary ab initio and X-ray nanodiffraction studies of Ta2O5.

The complex structure of Ta2O5 led to the development of various structural models. Among them, superstructures represent the most stable configurations. However, their formation requires kinetic activity and long-range ordering processes, which are hardly present during physical vapor deposition. Based on nano-beam X-ray diffraction and concomitant ab initio studies, a new metastable orthorhombic basic structure is introduced for Ta2O5 with lattice parameters a = 6.425 Å, b = 3.769 Å and c = 7.706 Å. The unit cell containing only 14 atoms, i.e. two formula unit blocks in the c direction, is characterized by periodically alternating the occupied oxygen site between two possible positions in succeeding 002-planes. This structure can be described by the space group 53 (Pncm) with four Wyckoff positions, and exhibits an energy of formation of -3.209 eV atom-1. Among all the reported basic structures, its energy of formation is closest to those of superstructures. Furthermore, this model exhibits a 2.5 eV band gap, which is closer to experimental data than the band gap of any other basic-structure model. The sputtered Ta2O5 films develop only a superstructure if annealed at temperatures >800 °C in air or vacuum. Based on these results and the conveniently small unit cell size, it is proposed that the basic-structure model described here is an ideal candidate for both structure and electronic state descriptions of orthorhombic Ta2O5 materials.

Circular test structure for the determination of piezoelectric constants of Sc x Al1-x N thin films applying Laser Doppler Vibrometry and FEM simulations.

Piezoelectric scandium aluminium nitride (Sc x Al1-x N) thin films offer a large potential for the application in micro electromechanical systems, as advantageous properties of pure AlN thin films are maintained, but combined with an increased piezoelectric actuation and sensing potential. Sc x Al1-x N thin films with x = 27% have been prepared by DC reactive magnetron sputtering to find optimized deposition parameters to maximize the piezoelectric constants d33 and d31. For the accurate and simultaneous measurement of these constants Laser Doppler Vibrometry has been applied and compared to finite element (FEM) simulations. The electrode design has been optimized to rotational symmetric structures enabling a 180° phase shifted excitation, so that a straight-forward comparison of experimental displacement curves with those obtained from FEM is feasible.

Designing thin film materials - Ternary borides from first principles.

Exploiting the mechanisms responsible for the exceptional properties of aluminum based nitride coatings, we apply ab initio calculations to develop a recipe for designing functional thin film materials based on ternary diborides. The combination of binary diborides, preferring different structure types, results in supersaturated metastable ternary systems with potential for phase transformation induced effects. For the exemplary cases of M x W1 - x B2 (with M = Al, Ti, V) we show by detailed ab initio calculations that the respective ternary solid solutions are likely to be experimentally accessible by modern depositions techniques.

Vacancy-dependent stability of cubic and wurtzite Ti1-x Al x N.

While it is well-known that supersaturated cubic-structured Ti1-x Al x N can be prepared by physical vapor deposition, the impact of point defects on formation process and cubic to wurtzite transition is largely unexplored. Irrespective of point defects, ab initio calculations correctly predict the Al concentration of the cubic to wurtzite transition. By means of density functional theory we show that vacancies on metal and/or non-metal sites only slightly affect the cubic to wurtzite transition region, whereas they clearly affect the physical properties.

Structural and mechanical evolution of reactively and non-reactively sputtered Zr-Al-N thin films during annealing.

The influence of reactive and non-reactive sputtering on structure, mechanical properties, and thermal stability of Zr1 - xAlxN thin films during annealing to 1500 °C is investigated in detail. Reactive sputtering of a Zr0.6Al0.4 target leads to the formation of Zr0.66Al0.34N thin films, mainly composed of supersaturated cubic (c) Zr1 - xAlxN with small fractions of (semi-)coherent wurtzite (w) AlN domains. Upon annealing, the formation of cubic Zr-rich domains and growth of the (semi-)coherent w-AlN domains indicate spinodal-like decomposition. Loss of coherency can only be observed for annealing temperatures above 1150 °C. Following these decomposition processes, the hardness remains at the as-deposited value of ~ 29 GPa with annealing up to 1100 °C. Using a ceramic (ZrN)0.6(AlN)0.4 target and sputtering in Ar atmosphere allows preparing c-Zr0.68Al0.32N coatings with a well-defined crystalline single-phase cubic structure combined with higher hardnesses of ~ 31 GPa. Due to the absence of (semi-)coherent w-AlN domains in the as-deposited state, which could act as nucleation sites, the decomposition process of c-Zr1 - xAlxN is retarded. Only after annealing at 1270 °C, the formation of incoherent w-AlN can be detected. Hence, their hardness remains very high with ~ 33 GPa even after annealing at 1200 °C. The study highlights the importance of controlling the deposition process to prepare well-defined coatings with high mechanical properties and thermal stability.

Lessons learned from merging wet lab experiments with molecular simulation to improve mAb humanization.

Humanized monoclonal antibodies (mAbs) are among the most promising modern therapeutics, but defined engineering strategies are still not available. Antibody humanization often leads to a loss of affinity, as it is the case for our model antibody Ab2/3H6 (PDB entry 3BQU). Identifying appropriate back-to-mouse mutations is needed to restore binding affinity, but highly challenging. In order to get more insight, we have applied molecular dynamics simulations and correlated them to antibody binding and expression in wet lab experiments. In this study, we discuss six mAb variants and investigate a tyrosine conglomeration, an isopolar substitution and the improvement of antibody binding towards wildtype affinity. In the 3D structure of the mouse wildtype, residue R94h is surrounded by three tyrosines which form a so-called 'tyrosine cage'. We demonstrate that the tyrosine cage has a supporting function for the CDRh3 loop conformation. The isopolar substitution is not able to mimic the function appropriately. Finally, we show that additional light chain mutations can restore binding to wildtype-comparable level, and also improve the expression of the mAb significantly. We conclude that the variable light chain of Ab2/3H6 is of underestimated importance for the interaction with its antigen mAb 2F5.

Tuning structure and mechanical properties of Ta-C coatings by N-alloying and vacancy population.

Tailoring mechanical properties of transition metal carbides by substituting carbon with nitrogen atoms is a highly interesting approach, as thereby the bonding state changes towards a more metallic like character and thus ductility can be increased. Based on ab initio calculations we could prove experimentally, that up to a nitrogen content of about 68% on the non-metallic sublattice, Ta-C-N crystals prevail a face centered cubic structure for sputter deposited thin films. The cubic structure is partly stabilized by non-metallic as well as Ta vacancies - the latter are decisive for nitrogen rich compositions. With increasing nitrogen content, the originally super-hard fcc-TaC0.71 thin films soften from 40 GPa to 26 GPa for TaC0.33N0.67, accompanied by a decrease of the indentation modulus. With increasing nitrogen on the non-metallic sublattice (hence, decreasing C) the damage tolerance of Ta-C based coatings increases, when characterized after the Pugh and Pettifor criteria. Consequently, varying the non-metallic sublattice population allows for an effective tuning and designing of intrinsic coating properties.

Ab initio inspired design of ternary boride thin films.

The demand to discover new materials is scientifically as well as industrially a continuously present topic, covering all different fields of application. The recent scientific work on thin film materials has shown, that especially for nitride-based protective coatings, computationally-driven understanding and modelling serves as a reliable trend-giver and can be used for target-oriented experiments. In this study, semi-automated density functional theory (DFT) calculations were used, to sweep across transition metal diborides in order to characterize their structure, phase stability and mechanical properties. We show that early transition metal diborides (TiB2, VB2, etc.) tend to be chemically more stable in the AlB2 structure type, whereas late transition metal diborides (WB2, ReB2, etc.) are preferably stabilized in the W2B5-x structure type. Closely related, we could prove that point defects such as vacancies significantly influence the phase stability and even can reverse the preference for the AlB2 or W2B5-x structure. Furthermore, investigations on the brittle-ductile behavior of the various diborides reveal, that the metastable structures are more ductile than their stable counterparts (WB2, TcB2, etc.). To design thin film materials, e.g. ternary or layered systems, this study is important for application oriented coating development to focus experimental studies on the most perspective systems.

Fracture toughness and structural evolution in the TiAlN system upon annealing.

Hard coatings used to protect engineering components from external loads and harsh environments should ideally be strong and tough. Here we study the fracture toughness, K IC, of Ti1-xAlxN upon annealing by employing micro-fracture experiments on freestanding films. We found that K IC increases by about 11% when annealing the samples at 900 °C, because the decomposition of the supersaturated matrix leads to the formation of nanometer-sized domains, precipitation of hexagonal-structured B4 AlN (with their significantly larger specific volume), formation of stacking faults, and nano-twins. In contrast, for TiN, where no decomposition processes and formation of nanometer-sized domains can be initiated by an annealing treatment, the fracture toughness K IC remains roughly constant when annealed above the film deposition temperature. As the increase in K IC found for Ti1-xAlxN upon annealing is within statistical errors, we carried out complementary cube corner nanoindentation experiments, which clearly show reduced (or even impeded) crack formation for annealed Ti1-xAlxN as compared with their as-deposited counterpart. The ability of Ti1-xAlxN to maintain and even increase the fracture toughness up to high temperatures in combination with the concomitant age hardening effects and excellent oxidation resistance contributes to the success of this type of coatings.

EBRA-FCA for measurement of migration of the femoral component in surface arthroplasty of the hip.

Studies on the migration of an implant may be the only way of monitoring the early performance of metal-on-metal prostheses. The Ein Bild Roentgen Analyse--femoral component analysis (EBRA-FCA) method was adapted to measure migration of the femoral component in a metal-on-metal surface arthroplasty of the hip using standard antero-posterior radiographs. In order to determine the accuracy and precision of this method a prosthesis was implanted into cadaver bones. Eleven series of radiographs were used to perform a zero-migration study. After adjustment of the femoral component to simulate migration of 3 mm the radiographs were repeated. All were measured independently by three different observers. The accuracy of the method was found to be +/- 1.6 mm for the x-direction and +/- 2 mm for the y-direction (95% percentile). The method was validated using 28 hips with a minimum follow-up of 3.5 years after arthroplasty. Seventeen were sound, but 11 had failed because of loosening of the femoral component. The normal (control) group had a different pattern of migration compared with that of the loose group. At 29.2 months, the control group showed a mean migration of 1.62 mm and 1.05 mm compared with 4.39 mm and 4.05 mm in the failed group, for the centre of the head and the tip of the stem, respectively (p = 0.001). In the failed group, the mean time to migration greater than 2 mm was earlier than the onset of clinical symptoms or radiological evidence of failure, 19.1 versus 32.2 months (p = 0.001) and 24.8 months (p = 0.012), respectively. EBRA-FCA is a reliable and valid tool for measuring migration of the femoral component after surface arthroplasty and can be used to predict early failure of the implant. It may be of value in determining the long-term performance of surface arthroplasty.

A software tool for prediction of prosthesis failure at the carpometacarpal joint of the thumb.

Early recognition of prosthesis failure is difficult. A tool that helps to identify faulty prosthesis - a cause of early implant loosening - is needed. The aim of this study was to detect early implant loosening by applying a software program EBRA (Ein-Bild-Röntgen-Analyse). EBRA was applied to the radiographs of a series of 76 patients, with a total of 102 thumb carpometacarpal joint de la Caffinière prostheses, with an average follow-up of 14.5 months (range 0.5-24). The data were used to draw graphs of cup migration and inclination over time. Corresponding regression lines of migration and inclination in relation to time were made up to the point of loosening. The gradient of regression was calculated for all implants. The gradient of regression on the x and y axes differed significantly between stable and loose implants. Loose and stable implants showed significantly different cup migration on the x and y axes over time. EBRA proved to be a reliable tool to visualize cup migration in the trapeziometacarpal joint and to predict implant failure.

Extended recombinant bacterial ghost system.

Controlled expression of cloned PhiX174 gene E in Gram-negative bacteria results in lysis of the bacteria by formation of an E-specific transmembrane tunnel structure built through the cell envelope complex. Bacterial ghosts from a variety of bacteria are used as non-living candidate vaccines. In the recombinant ghost system, foreign proteins are attached on the inside of the inner membrane as fusions with specific anchor sequences. Ghosts have a sealed periplasmic space and the export of proteins into this space vastly extends the capacity of ghosts or recombinant ghosts to function as carriers of foreign antigens. In addition, S-layer proteins forming shell-like self assembly structures can be expressed in candidate vaccine strains prior to E-mediated lysis. Such recombinant S-layer proteins carrying foreign epitopes further extend the possibilities of ghosts as carriers of foreign epitopes. As ghosts have inherent adjuvant properties, they can be used as adjuvants in combination with subunit vaccines. Subunits or other ligands can also be coupled to matrixes like dextran which are used to fill the internal lumen of ghosts. Oral, aerogenic or parenteral immunization of experimental animals with recombinant ghosts induced specific humoral and cellular immune responses against bacterial and target components including protective mucosal immunity. The most relevant advantage of recombinant bacterial ghosts as immunogens is that no inactivation procedures that denature relevant immunogenic determinants are employed in this production. This fact explains the superior quality of ghosts when compared to other inactivated vaccines. The endotoxic component of the outer membrane does not limit the use of ghosts as vaccine candidates but triggers the release of several potent immunoregulatory cytokines. As carriers, there is no limitation in the size of foreign antigens that can be inserted in the membrane and the capacity of all spaces including the membranes, peri-plasma and internal lumen of the ghosts can be fully utilized. This extended recombinant ghost system represents a new strategy for adjuvant free combination vaccines.

EBRA: a method to measure migration of acetabular components.

In orthopedics there is a demand for determining migration of hip sockets by evaluation of standard radiographs. In this case problems are caused mainly by changing pelvis positions on the X-ray table at successive exposures. A method (EBRA) is described that evaluates standard AP radiographs without requiring additional means at exposure (e.g. ball markers). Simulating the spatial situation it computes parameters of longitudinal and transverse migration of prosthetic cup and femoral head. A comparability algorithm using a grid of transverse and longitudinal tangents of the pelvis contour divides serial radiographs into sets of comparable ones. Comparability of serial radiographs takes place if the distances of corresponding grid lines do not transcend a given limit L. Migration is measured only between comparable radiographs. Different studies are described concerning the interdependence of pelvis rotations and changes of the grid lines, the degree of pelvis rotations appearing in practice, the choice of the limit L, the properties of the comparability algorithm and the accuracy of EBRA. The 95% confidence limits for EBRA results are 1.0 mm for longitudinal and 0.8 mm for transverse migration.

[Idiopathic, muscular, hypertrophic, sub-aortic stenosis]. / Die idiopathische muskuläre hypertrophe Subaortenstenose

The authors have seen 14 cases of idiopathic, hypertrophic, subaortic stenosis and they describe the pathology, the clinical and radiological diagnosis and the differential diagnosis of this condition. Their own findings are compared with those in the literature and substantial agreement is found. Some uncharacteristic clinical and radiological findings are associated with typical pressure curves in the left ventricle and marked abnormalities in the laevocardiogram. Variations in ventricular filling due to the difference in severity of the disease are discussed. The importance of a correct diagnosis is stressed, since the use of inotropic substance is this condition is contra-indicated.

[Measurement of migration of acetabular components in cementless hip replacement]. / Messung der Pfannenwanderung bei zementfreien Hüftimplantaten.

PURPOSE: Migration measurements of acetabular components using a special computer aided method (EBRA = abbreviation for the German term "Ein-Bild-Röntgenanalyse") were performed to evaluate early results of the implants and predict aseptic loosening. METHODS: Standard ap-radiographs of the pelvis were marked, specific points were digitised. Simulating the spatial situation the programme computes longitudinal and vertical migration of the cup. 74 acetabular components in 71 patients could be studied by migration measurements. RESULTS: 14 patients showed migration of more than 1 mm, which is the confidence limit of this method. Each of these patients showed diverse reasons for the migration, i.e. osteoporosis of the acetabular bone stock or problems concerning the surgical technique which means malposition of the cup or insufficient reaming of the bone. There were some patients with severe congenital dysplasia of the hip and in some cases the inclination angle of the cup was too great. CONCLUSION: The technique applied for measuring migration of acetabular components can be useful for evaluating early instability of the implant and can be helpful in detecting problems concerning the surgical technique.

Early migration predicts late aseptic failure of hip sockets.

We report a prospective, stratified study of 60 PCA-cups and 60 RM-polyethylene cups which have been followed for a median time of 90 months, with annual radiography. The radiological migration of cups was measured by the computer-assisted EBRA method. A number of threshold migration rates from 1 mm in the first year to 1 mm in five years have been assessed and related to clinically determined revision rates. A total of 28 cups showed a total migration of 1 mm or more within the first two years; 13 of these cups have required revision and been exchanged. The survival curves of cups which had previously shown early migration were considerably different from those without early migration. For cups with a migration of less than 1 mm within the first two years the mean survival at 96 months was 0.96 +/- 0.02; for migrating cups, it was 0.63 +/- 0.11 (log-rank test, p=0.0001; chi-square value=39.4). Early migration is a good predictor for late loosening of hip sockets.

Evaluation of accuracy and precision of bone markers for the measurement of migration of hip prostheses. A comparison of conventional measurements.

Our aim was to determine whether tantalum m arkers improved the accuracy and/or precision of methods for the measurement of migration in total hip replacement based on conventional measurements without mathematical correction of the data, and with Ein Bild Roentgen Analyse - Femoral Component Analysis (EBRA-FCA) which allows a computerised correction. Three observers independently analysed 13 series of roentgen-stereophotogrammetric-analysis (RSA)-compatible radiographs (88). Data were obtained from conventional measurements, EBRA-FCA and the RSA method and all the results were compared with the RSA data. Radiological evaluation was also used to quantify in how many radiographs the intraosseous position of the bone markers had been simulated. The results showed that tantalum markers improve reliability whereas they do not affect accuracy for conventional measurements and for EBRA-FCA. Because of the danger of third-body wear their implantation should be avoided unless they are an integral part of the method.

Accuracy of EBRA-FCA in the measurement of migration of femoral components of total hip replacement. Einzel-Bild-Röntgen-Analyse-femoral component analysis.

Several methods of measuring the migration of the femoral component after total hip replacement have been described, but they use different reference lines, and have differing accuracies, some unproven. Statistical comparison of different studies is rarely possible. We report a study of the EBRA-FCA method (femoral component analysis using Einzel-Bild-Röntgen-Analyse) to determine its accuracy using three independent assessments, including a direct comparison with the results of roentgen stereophotogrammetric analysis (RSA). The accuracy of EBRA-FCA was better than +/- 1.5 mm (95% percentile) with a Cronbach's coefficient alpha for interobserver reliability of 0.84; a very good result. The method had a specificity of 100% and a sensitivity of 78% compared with RSA for the detection of migration of over 1 mm. This is accurate enough to assess the stability of a prosthesis within a relatively limited period. The best reference line for downward migration is between the greater trochanter and the shoulder of the stem, as confirmed by two experimental analyses and a computer-assisted design.

Low Friction CrNMPP/TiNDCMS Multilayer Coatings.

Transition metal nitrides like CrN and TiN are widely used in automotive applications due to their high hardness and wear resistance. Recently, we showed that a multilayer architecture of CrN and TiN, deposited using the hybrid-high power impulse magnetron sputtering (HIPIMS) and direct current magnetron sputtering (DCMS)-HIPIMS/DCMS deposition technique, results in coatings which indicate not only increased mechanical and tribological properties but also friction coefficients in the range of diamond-like-carbon coatings when tested at RT and ambient air conditions. The modulated pulsed power (MPP) deposition technique was used to replace the HIPIMS powered cathode within this study to allow for a higher deposition rate, which is based on the complex MPP pulse configuration. Our results on MPP/DCMS deposited CrN/TiN multilayer coatings indicate excellent mechanical and tribological properties, comparable to those obtained for HIPIMS/DCMS. Hardness values are around 25 GPa with wear rates in the range of 2 × 10-16 Nm/m3 and a coefficient of friction around 0.05 when preparing a superlattice structure. The low friction values can directly be correlated to the relative humidity in the ambient air during dry sliding testing. A minimum relative humidity of 13% is necessary to guarantee such low friction values, as confirmed by repeated tests, which are even obtained after vacuum annealing to 700 °C. Our results demonstrate that the co-sputtering of high metal ion sputtering techniques and conventional DC sputtering opens a new field of applications for CrN/TiN coatings as high wear resistance and low friction coatings.