Matériaux Ingénierie et Science

We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.

BACKGROUND: In patients who have chronic heart failure with reduced left ventricular ejection fraction, severe secondary mitral-valve regurgitation is associated with a poor prognosis. Whether percutaneous mitral-valve repair improves clinical outcomes in this patient population is unknown. METHODS: or a regurgitant volume of >30 ml per beat), a left ventricular ejection fraction between 15 and 40%, and symptomatic heart failure, in a 1:1 ratio, to undergo percutaneous mitral-valve repair in addition to receiving medical therapy (intervention group; 152 patients) or to receive medical therapy alone (control group; 152 patients). The primary efficacy outcome was a composite of death from any cause or unplanned hospitalization for heart failure at 12 months. RESULTS: At 12 months, the rate of the primary outcome was 54.6% (83 of 152 patients) in the intervention group and 51.3% (78 of 152 patients) in the control group (odds ratio, 1.16; 95% confidence interval [CI], 0.73 to 1.84; P=0.53). The rate of death from any cause was 24.3% (37 of 152 patients) in the intervention group and 22.4% (34 of 152 patients) in the control group (hazard ratio, 1.11; 95% CI, 0.69 to 1.77). The rate of unplanned hospitalization for heart failure was 48.7% (74 of 152 patients) in the intervention group and 47.4% (72 of 152 patients) in the control group (hazard ratio, 1.13; 95% CI, 0.81 to 1.56). CONCLUSIONS: Among patients with severe secondary mitral regurgitation, the rate of death or unplanned hospitalization for heart failure at 1 year did not differ significantly between patients who underwent percutaneous mitral-valve repair in addition to receiving medical therapy and those who received medical therapy alone. (Funded by the French Ministry of Health and Research National Program and Abbott Vascular; MITRA-FR ClinicalTrials.gov number, NCT01920698 .).

Zirconia ceramics have found broad applications in a variety of energy and biomedical applications because of their unusual combination of strength, fracture toughness, ionic conductivity, and low thermal conductivity. These attractive characteristics are largely associated with the stabilization of the tetragonal and cubic phases through alloying with aliovalent ions. The large concentration of vacancies introduced to charge compensate of the aliovalent alloying is responsible for both the exceptionally high ionic conductivity and the unusually low, and temperature independent, thermal conductivity. The high fracture toughness exhibited by many of zirconia ceramics is attributed to the constraint of the tetragonal‐to‐monoclinic phase transformation and its release during crack propagation. In other zirconia ceramics containing the tetragonal phase, the high fracture toughness is associated with ferroelastic domain switching. However, many of these attractive features of zirconia, especially fracture toughness and strength, are compromised after prolonged exposure to water vapor at intermediate temperatures (∼30°–300°C) in a process referred to as low‐temperature degradation (LTD), and initially identified over two decades ago. This is particularly so for zirconia in biomedical applications, such as hip implants and dental restorations. Less well substantiated is the possibility that the same process can also occur in zirconia used in other applications, for instance, zirconia thermal barrier coatings after long exposure at high temperature. Based on experience with the failure of zirconia femoral heads, as well as studies of LTD, it is shown that many of the problems of LTD can be mitigated by the appropriate choice of alloying and/or process control.

X-ray computer tomography (CT) is fast becoming an accepted tool within the materials science community for the acquisition of 3D images. Here the authors review the current state of the art as CT transforms from a qualitative diagnostic tool to a quantitative one. Our review considers first the image acquisition process, including the use of iterative reconstruction strategies suited to specific segmentation tasks and emerging methods that provide more insight (e.g. fast and high resolution imaging, crystallite (grain) imaging) than conventional attenuation based tomography. Methods and shortcomings of CT are examined for the quantification of 3D volumetric data to extract key topological parameters such as phase fractions, phase contiguity, and damage levels as well as density variations. As a non-destructive technique, CT is an ideal means of following structural development over time via time lapse sequences of 3D images (sometimes called 3D movies or 4D imaging). This includes information needed to optimise manufacturing processes, for example sintering or solidification, or to highlight the proclivity of specific degradation processes under service conditions, such as intergranular corrosion or fatigue crack growth. Besides the repeated application of static 3D image quantification to track such changes, digital volume correlation (DVC) and particle tracking (PT) methods are enabling the mapping of deformation in 3D over time. Finally the use of CT images is considered as the starting point for numerical modelling based on realistic microstructures, for example to predict flow through porous materials, the crystalline deformation of polycrystalline aggregates or the mechanical properties of composite materials.

X-ray computed tomography (CT) can reveal the internal details of objects in three dimensions non-destructively. In this Primer, we outline the basic principles of CT and describe the ways in which a CT scan can be acquired using X-ray tubes and synchrotron sources, including the different possible contrast modes that can be exploited. We explain the process of computationally reconstructing three-dimensional (3D) images from 2D radiographs and how to segment the 3D images for subsequent visualization and quantification. Whereas CT is widely used in medical and heavy industrial contexts at relatively low resolutions, here we focus on the application of higher resolution X-ray CT across science and engineering. We consider the application of X-ray CT to study subjects across the materials, metrology and manufacturing, engineering, food, biological, geological and palaeontological sciences. We examine how CT can be used to follow the structural evolution of materials in three dimensions in real time or in a time-lapse manner, for example to follow materials manufacturing or the in-service behaviour and degradation of manufactured components. Finally, we consider the potential for radiation damage and common sources of imaging artefacts, discuss reproducibility issues and consider future advances and opportunities. This Primer on X-ray computed tomography explores the different experimental configurations for three-dimensional data acquisition as well as the fundamentals of three-dimensional data reconstruction, segmentation and analysis with examples across the physical and life sciences.

This review describes the mechanisms responsible for low-temperature degradation (LTD) of zirconia ceramics and its detrimental consequences for biomedical devices. Special emphasis is given to the critical issue of zirconia degradation actually observed for hip prostheses. Experimental methods to accurately measure and predict LTD in a given zirconia ceramic are presented. Different solutions to inhibit LTD or at least reduce its kinetics are reviewed, with the objective of highlighting alternative options for the generation of new zirconia-based biomedical ceramic devices.

Nondestructive three-dimensional mapping of grain shape, crystallographic orientation, and grain boundary geometry by diffraction contrast tomography (DCT) provides opportunities for the study of the interaction between intergranular stress corrosion cracking and microstructure. A stress corrosion crack was grown through a volume of sensitized austenitic stainless steel mapped with DCT and observed in situ by synchrotron tomography. Several sensitization-resistant crack-bridging boundaries were identified, and although they have special geometric properties, they are not the twin variant boundaries usually maximized during grain boundary engineering.

The principles of a novel technique for nondestructive and simultaneous mapping of the three-dimensional grain and the absorption microstructure of a material are explained. The technique is termed X-ray diffraction contrast tomography, underlining its similarity to conventional X-ray absorption contrast tomography with which it shares a common experimental setup. The grains are imaged using the occasionally occurring diffraction contribution to the X-ray attenuation coefficient each time a grain fulfils the diffraction condition. The three-dimensional grain shapes are reconstructed from a limited number of projections using an algebraic reconstruction technique. An algorithm based on scanning orientation space and aiming at determining the corresponding crystallographic grain orientations is proposed. The potential and limitations of a first approach, based on the acquisition of the direct beam projection images only, are discussed in this first part of the paper. An extension is presented in the second part of the paper [Johnson, King, Honnicke, Marrow & Ludwig (2008). J. Appl. Cryst. 41 , 310–318], addressing the case of combined direct and diffracted beam acquisition.

The principle of the tomography technique and the different possible set-ups, which can be used to obtain medium-(10 μm) and high-(1 μm) resolution, three-dimensional, non-destructive images, are shown in this paper. Illustrations are made of the applications of the technique in the field of materials science. Examples are given for medium-resolution images of metallic foams and model metal matrix composites that are reinforced with spherical particles. High-resolution examples are shown for aluminium alloys. For low-absorbent materials we show that the phase contrast obtained using synchrotron radiation can provide a valuable solution. The quantitative use of these images, coupled with in-situ tensile tests or used for the simple analysis of the initial microstructure of several structural materials, is also described.

Abstract A dynamic structural behavior of Pt nanoparticles on the ceria surface under reducing/oxidizing conditions was found at moderate temperatures (<500 °C) and exploited to enhance the catalytic activity of Pt/CeO 2 ‐based exhaust gas catalysts. Redispersion of platinum in an oxidizing atmosphere already occurred at 400 °C. A protocol with reducing pulses at 250–400 °C was applied in a subsequent step for controlled Pt‐particle formation. Operando X‐ray absorption spectroscopy unraveled the different extent of reduction and sintering of Pt particles: The choice of the reductant allowed the tuning of the reduction degree/particle size and thus the catalytic activity (CO>H 2 >C 3 H 6 ). This dynamic nature of Pt on ceria at such low temperatures (250–500 °C) was additionally confirmed by in situ environmental transmission electron microscopy. A general concept is proposed to adjust the noble metal dispersion (size, structure), for example, during operation of an exhaust gas catalyst.

Many physical and mechanical properties of crystalline materials depend strongly on their internal structure, which is typically organized into grains and domains on several length scales. Here we present dark-field X-ray microscopy; a non-destructive microscopy technique for the three-dimensional mapping of orientations and stresses on lengths scales from 100 nm to 1 mm within embedded sampling volumes. The technique, which allows 'zooming' in and out in both direct and angular space, is demonstrated by an annealing study of plastically deformed aluminium. Facilitating the direct study of the interactions between crystalline elements is a key step towards the formulation and validation of multiscale models that account for the entire heterogeneity of a material. Furthermore, dark-field X-ray microscopy is well suited to applied topics, where the structural evolution of internal nanoscale elements (for example, positioned at interfaces) is crucial to the performance and lifetime of macro-scale devices and components thereof.

Harvesting energy from environmental sources has been of particular interest these last few years. Microgenerators that can power electronic systems are a solution for the conception of autonomous, wireless devices. They allow the removal of bulky and costly wiring, as well as complex maintenance and environmental issues for battery-powered systems. In particular, using piezoelectric generators for converting vibrational energy to electrical energy is an intensively investigated field. In this domain, it has been shown that the harvested energy can be greatly improved by the use of an original non-linear treatment of the piezoelectric voltage called SSHI (Synchronized Switch Harvesting on Inductor), which consists in intermittently switching the piezoelectric element on a resonant electrical network for a very short time. However, the integration of miniaturized microgenerators with low voltage output (e.g. MEMS microgenerators) has not been widely studied. In the case of low voltage output, the losses introduced by voltage gaps of discrete components such as diodes or transistors can no longer be neglected. Therefore the purpose of this paper is to propose a model that takes into account such losses as well as a new architecture for the SSHI energy harvesting circuit that limits such losses in the harvesting process. While most of the study uses an externally powered microcontroller for the non-linear treatment, this circuit is fully self-powered, thus providing an enhanced autonomous microgenerator. In particular this circuit aims at limiting the effect of non-linear components with a voltage gap such as diodes. It is shown both theoretically and experimentally that the harvested power can be significantly increased using such a circuit. In particular, experimental measurements performed on a cantilever beam show that the circuit allows a 160% increase of the harvested power compared to a standard energy harvesting circuit, while the classical implementation of the SSHI shows an increase of only 100% of the output power in the classical case.

X-ray diffraction contrast tomography (DCT) is a technique for mapping grain shape and orientation in plastically undeformed polycrystals. In this paper, we describe a modified DCT data acquisition strategy which permits the incorporation of an innovative Friedel pair method for analyzing diffraction data. Diffraction spots are acquired during a 360 degrees rotation of the sample and are analyzed in terms of the Friedel pairs ((hkl) and (hkl) reflections, observed 180 degrees apart in rotation). The resulting increase in the accuracy with which the diffraction vectors are determined allows the use of improved algorithms for grain indexing (assigning diffraction spots to the grains from which they arise) and reconstruction. The accuracy of the resulting grain maps is quantified with reference to synchrotron microtomography data for a specimen made from a beta titanium system in which a second phase can be precipitated at grain boundaries, thereby revealing the grain shapes. The simple changes introduced to the DCT methodology are equally applicable to other variants of grain mapping.

Ultrasmall gadolinium-based nanoparticles (GBNs) induce both a positive contrast for magnetic resonance imaging and a radiosentizing effect. The exploitation of these characteristics leads to a greater increase in lifespan of rats bearing brain tumors since the radiosensitizing effect of GBNs can be activated by X-ray microbeams when the gadolinium content is, at the same time, sufficiently high in the tumor and low in the surrounding healthy tissue. GBNs exhibit therefore an interesting potential for image-guided radiotherapy.

In this work, we studied the aptitude to sintering green bodies using γ-Al2O3 transition alumina as raw powder. We focused on the influence of the heating rate on densification and microstructural evolution. Phase transformations from transition alumina γ → δ → θ → α-Al2O3 were studied by in situ X-rays diffraction from the ambient to 1200 °C. XRD patterns revealed coexistence of various phase transformations during the heating cycle. DTA and dilatometry results showed that low heating rate leads to a significant reduction of the temperature of the α-Al2O3 alumina formation. Around 1190, 1217 and 1240 °C were found when using 5, 10 and 20 °C/min of heating rate, respectively. The activation energy for θ-Al2O3 → α-Al2O3 transformation calculated by Kissinger and JMA equations using dilatometry method were 464.29 and 488.79 kJ/mol, respectively and by DTA method were 450.72 and 475.49 kJ/mol, respectively. In addition, the sintering of the green bodies with low heating rate promotes the rearrangement of the grains during θ-Al2O3 → α-Al2O3 transformation, enhancing the relative density to 95% and preventing the development of a vermicular structure. En este trabajo, se ha estudiado la capacidad de sinterización de muestras en verde a partir de γ-Al2O3 de transición en forma de polvo. El trabajo se ha focalizado en la influencia de la velocidad de calentamiento sobre la densificación y la evolución microestructural. Las transformaciones de fase de alúminas de transición γ→δ→θ→α-Al2O3 se han estudiado in situ mediante Difracción de Rayos X (DRX) desde temperatura ambiente hasta 1.200 °C. Los diagramas de XRD han revelado la coexistencia de diversas transformaciones de fase durante el ciclo de calentamiento. Los Análisis Térmicos Diferenciales (ATD) realizados y los datos de dilatometría han mostrado que velocidades de calentamiento bajas conducen a una reducción significativa de la temperatura de formación de α-Al2O3. Detectándose alrededor de 1.190, 1.217 y 1.240 °C cuando se utilizan 5, 10 y 20 °C/min como velocidad de calentamiento, respectivamente. La Energía de Activación para la transformación θ-Al2O3→α-Al2O3 calculada mediante las ecuaciones de Kissinger y JMA usando métodos dilatometricos han sido 464,29 y 488,79 kJ/mol, respectivamente, y mediante ATD 450,72 y 475,49 kJ/mol, respectivamente. Además, la sinterización con velocidad de calentamiento baja promueve la reorganización de los granos durante la transformación θ-Al2O3 → α-Al2O3, el aumento de la densidad relativa al 95% y la prevención del desarrollo de una estructura vermicular.

AIMS: The MITRA-FR trial showed that among symptomatic patients with severe secondary mitral regurgitation, percutaneous repair did not reduce the risk of death or hospitalization for heart failure at 12 months compared with guideline-directed medical treatment alone. We report the 24-month outcome from this trial. METHODS AND RESULTS: or regurgitant volume >30 mL), and left ventricular ejection fraction between 15% and 40% to undergo percutaneous valve repair plus medical treatment (intervention group, n = 152) or medical treatment alone (control group, n = 152). The primary efficacy outcome was the composite of all-cause death and unplanned hospitalization for heart failure at 12 months. At 24 months, all-cause death and unplanned hospitalization for heart failure occurred in 63.8% of patients (97/152) in the intervention group and 67.1% (102/152) in the control group [hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.77-1.34]. All-cause mortality occurred in 34.9% of patients (53/152) in the intervention group and 34.2% (52/152) in the control group (HR 1.02, 95% CI 0.70-1.50). Unplanned hospitalization for heart failure occurred in 55.9% of patients (85/152) in the intervention group and 61.8% (94/152) in the control group (HR 0.97, 95% CI 0.72-1.30). CONCLUSIONS: In patients with severe secondary mitral regurgitation, percutaneous repair added to medical treatment did not significantly reduce the risk of death or hospitalization for heart failure at 2 years compared with medical treatment alone.

The anomalous low friction of diamondlike carbon coated surfaces lubricated by pure glycerol was observed at $80\text{ }\ifmmode^\circ\else\textdegree\fi{}\text{C}$. Steel surfaces were coated with an ultrahard 1 \textmu{}m thick hydrogen-free tetrahedral coordinated carbon (ta-C) layer produced by physical vapor deposition. In the presence of glycerol, the friction coefficient is below 0.01 at steady state, corresponding to the so-called superlubricity regime (when sliding is then approaching pure rolling). This new mechanism of superlow friction is attributed to easy glide on triboformed OH-terminated surfaces. In addition to the formation of OH-terminated surfaces but at a lower temperature, we show here some evidence, by coupling experimental and computer simulations, that superlow friction of polyhydric alcohols could also be associated with triboinduced degradation of glycerol, producing a nanometer-thick film containing organic acids and water. Second, we show outstanding superlubricity of steel surfaces directly lubricated by a solution of myo-inositol (also called vitamin Bh) in glycerol at ambient temperature $(25\text{ }\ifmmode^\circ\else\textdegree\fi{}\text{C})$. For the first time, under boundary lubrication at high contact pressure, friction of steel is below 0.01 in the absence of any long chain polar molecules. The mechanism is still unknown but could be associated with friction-induced dissociation of glycerol and interaction of waterlike species with steel surface.

To overcome the limitations in terms of spatial resolution and field of view of existing tomography techniques, a hard x-ray projection microscope is realized based on the sub-100-nm focus produced by Kirkpatrick-Baez optics. The sample is set at a small distance downstream of the focus and Fresnel diffraction patterns with variable magnification are recorded on a medium-resolution detector. While the approach requires a specific phase retrieval procedure and correction for mirror imperfections, it allows zooming nondestructively into bulky samples. Quantitative three-dimensional nanoscale microscopy is demonstrated on an aluminum alloy in local tomography mode.

A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed.

Abstract The propagation of small cracks contributes to the majority of the fatigue lifetime for structural components. Despite significant interest, criteria for the growth of small cracks, in terms of the direction and speed of crack advancement, have not yet been determined. In this work, a new approach to identify the microstructurally small fatigue crack driving force is presented. Bayesian network and machine learning techniques are utilized to identify relevant micromechanical and microstructural variables that influence the direction and rate of the fatigue crack propagation. A multimodal dataset, combining results from a high-resolution 4D experiment of a small crack propagating in situ within a polycrystalline aggregate and crystal plasticity simulations, is used to provide training data. The relevant variables form the basis for analytical expressions thus representing the small crack driving force in terms of a direction and a rate equation. The ability of the proposed expressions to capture the observed experimental behavior is quantified and compared to the results directly from the Bayesian network and from fatigue metrics that are common in the literature. Results indicate that the direction of small crack propagation can be reliably predicted using the proposed analytical model and compares more favorably than other fatigue metrics.