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Julie Brault,1,2 Guillaume Vaganay,3 Aline Le Roy,4–6 Jean-Luc Lenormand,1 Sandra Cortes,3 Marie José Stasia1,2 1UMR CNRS 5525, University of Grenoble Alpes, Grenoble, France; 2CGD Diagnosis and Research Centre, University Hospital Centre of Grenoble Alpes, Grenoble, France; 3Synthelis SAS, La Tronche, France; 4IBS, University of Grenoble Alpes, Grenoble, France; 5CNRS, IBS, University Grenoble Alpes, Grenoble, France; 6CEA, IBS, University of Grenoble Alpes, Grenoble, France Abstract: Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency due to dysfunction of the phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex leading to severe and recurrent infections in early childhood. The main genetic form is the X-linked CGD leading to the absence of cytochrome b558 composed of NOX2 and p22phox, the membrane partners of the NADPH oxidase complex. The first cause of death of CGD patients is pulmonary infections. Recombinant proteoliposome-based therapy is an emerging and innovative approach for membrane protein delivery, which could be an alternative local, targeted treatment to fight lung infections in CGD patients. We developed an enzyme therapy using recombinant NOX2/p22phox liposomes to supply the NADPH oxidase activity in X0-linked CGD (X0-CGD) macrophages. Using an optimized prokaryotic cell-free protein synthesis system, a recombinant cytochrome b558 containing functional hemes was produced and directly inserted into the lipid bilayer of specific liposomes. The size of the NOX2/p22phox liposomes was estimated to be around 700 nm. These proteoliposomes were able to generate reactive oxygen species (ROS) in an activated reconstituted cell-free NADPH oxidase activation assay in the presence of recombinant p47phox, p67phox and Rac, the cytosolic components of the NADPH oxidase complex. Furthermore, using flow cytometry and fluorescence microscopy, we demonstrated that cytochrome b558 was successfully delivered to the plasma membrane of X0-CGD-induced pluripotent stem cell (iPSC)-derived macrophages. In addition, NADPH oxidase activity was restored in X0-CGD iPSC-derived macrophages treated with NOX2/p22phox liposomes for 8 h without any toxicity. In conclusion, we confirmed that proteoliposomes provide a new promising technology for the delivery of functional proteins to the membrane of targeted cells. This efficient liposomal enzyme replacement therapy will be useful for future treatment of pulmonary infections in CGD patients refractory to conventional anti-infectious treatments. Keywords: protein therapy, proteoliposomes, chronic granulomatous disease, NADPH oxidase, induced pluripotent stem cells, macrophages

AlGaN-based heterostructures are promising candidates for the fabrication of ultraviolet light-emitting diodes. The analysis of the atomic composition of the grown epitaxial films is important from a technological point of view, allowing precise control over the wavelength and intensity of the emitted light. In this work, the depth profiling of AlN(0001), AlGaN(0001), and AlGaN quantum dot surfaces grown by molecular beam epitaxy was carried out by using angle-resolved x-ray photoelectron spectroscopy (XPS) combined with Ar gas cluster ion source (GCIS) sputtering. Core level shifts in XPS spectra measured by Al Kα and Ag Lα photon sources were determined. We found that sputtering by Ar1000+ ion clusters with an energy of 10 keV creates disorder on the surface and induces changes in surface atomic composition. As a result, depth profiling with a typical surface-sensitive Al Kα photon source is affected by the damaged layer. The application of a less surface-sensitive Ag Lα photon source with high photon energy could suppress the contribution from the damaged surface layer. Combining GCIS sputtering with Ag Lα line XPS measurements is, therefore, very promising for the quantification of atomic composition in the buried epitaxial layers or heterostructures with thicknesses of several tens of nm. [ABSTRACT FROM AUTHOR]

This paper discusses the results of high temperature resistivity and Hall effect studies of Mg-doped GaN and AlxGa1−xN epilayers (0.05 < x < 0.23). The studied samples were grown by molecular beam epitaxy on low temperature buffers of GaN and AlN deposited on a sapphire substrate. The experiments were carried out at temperatures ranging from 300 up to 1000 K. Up to a certain critical temperature TC (around 800 K), a typical increase of the conduction processes due to the excitation of impurity states has been observed with an activation energy of about EA = 200 meV. However, at this critical temperature TC, an annealing effect was observed in all the investigated samples. At this critical temperature, the increase in the free carrier concentration as a function of time leads to an irreversible decrease in the samples' resistivity of more than 60%. The observed temperature dependences of the electrical transport properties are analyzed in the frame of an impurity model including shallow donors and Mg-related acceptors (with EA ∼ 200 meV). In some cases, an additional conduction channel not related to free carriers in the valence band must be taken into account. This can lead to an incorrect determination of hole concentration in the valence band, an important parameter in the process of radiative recombination. [ABSTRACT FROM AUTHOR]

Nanoporous GaN layers were fabricated using selective area sublimation through a self-organized AlN nanomask in a molecular beam epitaxy reactor. The obtained pore morphology, density and size were measured using plan-view and cross-section scanning electron microscopy experiments. It was found that the porosity of the GaN layers could be adjusted from 0.04 to 0.9 by changing the AlN nanomask thickness and sublimation conditions. The room temperature photoluminescence properties as a function of the porosity were analysed. In particular, a strong improvement (>100) of the room temperature photoluminescence intensity was observed for porous GaN layers with a porosity in the 0.4–0.65 range. The characteristics of these porous layers were compared to those obtained with a Si x N y nanomask. Furthermore, the regrowth of p-type GaN on light emitting diode structures made porous by using either an AlN or a Si x N y nanomask were compared. [ABSTRACT FROM AUTHOR]

AlyGa1−yN quantum dots (QDs) have been grown by molecular beam epitaxy on AlxGa1−xN (0001) using a 2-dimensional–3-dimensional growth mode transition that leads to the formation of QDs. QDs have been grown for Al compositions y varying between 10% and 40%. The influence of the active region design [composition y, QD height, and bandgap difference (ΔEg) between the AlxGa1−xN cladding layer and the AlyGa1−yN QDs] is discussed based on microscopy, continuous wave photoluminescence (PL), and time-resolved PL (TRPL) measurements. In particular, increasing y leads to a shift of the QD emission toward shorter wavelengths, allowing covering a spectral range in the UV from 332 nm (UVA) to 276 nm (UVC) at room temperature (RT). The low-temperature (LT) internal quantum efficiency of the QD ensembles was estimated from TRPL experiments at 8 K and values between 11% and 66% were deduced. The highest internal quantum efficiency (IQE)-LT is found for the QDs with higher Al content y. Then, the PL spectrally integrated intensity ratios between RT and LT were measured to estimate the IQE of the samples at RT. The PL ratio is higher for larger ΔEg, for QDs with y of 0.1 or 0.2, and high PL intensity ratios up to 30% were also measured for QDs with larger y of 0.3 and 0.4. RT IQE values between 5% and 20% are deduced for AlyGa1−yN QDs emitting in the 276–308 nm range. [ABSTRACT FROM AUTHOR]

An optical microsource consisting of InAs/InP quantum wires in a suspended microdisk is reported.

Self-assembled GaN quantum dots (QDs) in AlxGa1-xN (0.3≤×≤1) were grown on c-plane sapphire and Si (111) substrates by molecular beam epitaxy using ammonia as nitrogen source. The QD formation temperature was varied from 650 °C to 800 °C. Surprisingly, the density and size of QDs formed in this temperature range are very similar. This has been explained by considering together experimental results obtained from reflection high-energy electron diffraction, atomic force microscopy, and photoluminescence to discuss the interplay between thermodynamics and kinetics in the QD formation mechanisms. Finally, possible ways to better control the QD optical properties are proposed. [ABSTRACT FROM AUTHOR]

We investigate the electrical and thermal conductivities of the two-dimensional electron gas (2DEG) confined in the quantum well formed at the heterojunction between a thin GaN layer and an AlN layer strained by an AlxGa1−xN capping layer in the temperature range from 10 to 360 K. The experimental protocol developed to deduce from calorimetric and Hall-effect measurements at a variable temperature the critical characteristics and transport properties of the confined 2DEG is presented. It is found that, in the measured temperature range (10–360 K), the electrical conductivity of the 2DEG is temperature-independent, due to the predominance of scattering processes by interface defects. However, the thermal conductivity shows a linear temperature dependence, mirroring the specific heat of free electrons. The temperature-independent relaxation time associated with the overall electron scattering means that the values obtained for electrical and thermal conductivities are in excellent agreement with those stipulated by the Weidemann–Franz law. It is also found that for weak strain fields in the AlN layer, both the electrical and thermal conductivities of the two-dimensional interfacial electrons increase exponentially with strain. The importance of 2DEG in AlN/GaN quantum wells lies in the fact that the strong piezoelectricity of AlN allows the transport properties of the 2DEG to be tuned or modulated by a weak electric field even with the high density of lattice mismatch induced defects at the AlN-GaN interface. [ABSTRACT FROM AUTHOR]

This work presents a continuous-wave photoluminescence study of Al0.5Ga0.5N/GaN quantum dots grown by ammonia-assisted molecular beam epitaxy on sapphire, either on the wurtzite polar (0001) or the semipolar (11-22) plane. Due to interface polarization discontinuities, the polar dots are strongly red-shifted by the Stark effect and emit in the visible range. Carrier injection screening of the polarization charges has been studied. A model relying on average dot heights and dot height variances, as measured by transmission electron microscopy, is proposed. It can account for the injection dependent luminescence energies and efficiencies. The electric field discontinuity deduced from the fittings is in good agreement with theoretical expectations for our barrier composition. On the contrary, semipolar quantum dot ensembles always emit above the gap of GaN strained to Al0.5Ga0.5N. Their luminescence linewidth is significantly lower than that of polar ones, and their energy does not shift with injection. Our study then confirms the expected strong decrease of the Stark effect for (11-22) grown (Al,Ga)N/GaN heterostructures. [ABSTRACT FROM AUTHOR]

A theoretical interpretation of the photoluminescence excitation spectra of self-organized polar GaN/(Al,Ga)N quantum dots is presented. A numerical method assuming a realistic shape of the dots and including the built-in electric field effects is developed to calculate their energy structure and hence their optical absorption. The electron and hole spectra show the existence of a set of quasi-bound states that does not originate from the wetting layer and plays a crucial role in the observed absorption spectrum of the GaN/(Al,Ga)N dots. Transitions involving these quasi-bound states and wetting layer states give a sufficient explanation for the observed continuum absorption background. The properties of this absorption band, especially its extension, depend strongly on the dot's size. Our simulation provides a natural explanation of the experimental luminescence excitation spectra of ensembles of dots of different heights. Our theoretical model can be convenient for future optical studies including systems with more complicated potentials. [ABSTRACT FROM AUTHOR]

Summary: Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The most common form is the X‐linked CGD (X91‐CGD), caused by mutations in the CYBB gene. Clinical, functional and genetic characterizations of 16 CGD cases of male patients and their relatives were performed. We classified them as suffering from different variants of CGD (X910, X91− or X91+), according to NADPH oxidase 2 (NOX2) expression and NADPH oxidase activity in neutrophils. Eleven mutations were novel (nine X910‐CGD and two X91−‐CGD). One X910‐CGD was due to a new and extremely rare double missense mutation Thr208Arg‐Thr503Ile. We investigated the pathological impact of each single mutation using stable transfection of each mutated cDNA in the NOX2 knock‐out PLB‐985 cell line. Both mutations leading to X91−‐CGD were also novel; one deletion, c.‐67delT, was localized in the promoter region of CYBB; the second c.253‐1879A>G mutation activates a splicing donor site, which unveils a cryptic acceptor site leading to the inclusion of a 124‐nucleotide pseudo‐exon between exons 3 and 4 and responsible for the partial loss of NOX2 expression. Both X91−‐CGD mutations were characterized by a low cytochrome b558 expression and a faint NADPH oxidase activity. The functional impact of new missense mutations is discussed in the context of a new three‐dimensional model of the dehydrogenase domain of NOX2. Our study demonstrates that low NADPH oxidase activity found in both X91−‐CGD patients correlates with mild clinical forms of CGD, whereas X910‐CGD and X91+‐CGD cases remain the most clinically severe forms. [ABSTRACT FROM AUTHOR]