Free carrier effects in gallium nitride epilayers: the valence band dispersion

The dispersion of the A-valence-band in GaN has been deduced from the observation of high-index magneto-excitonic states in polarised interband magneto-reflectivity and is found to be strongly non-parabolic with a mass in the range 1.2-1.8 m_{e}. It matches the theory of Kim et al. [Phys. Rev. B 56, 7363 (1997)] extremely well, which also gives a strong k-dependent A-valence-band mass. A strong phonon coupling leads to quenching of the observed transitions at an LO-phonon energy above the band gap and a strong non-parabolicity. The valence band was deduced from subtracting from the reduced dispersion the electron contribution with a model that includes a full treatment of the electron-phonon interaction.Comment: Revtex, 4 pages, 5 figure

Mie-resonances, infrared emission and band gap of InN

Mie resonances due to scattering/absorption of light in InN containing clusters of metallic In may have been erroneously interpreted as the infrared band gap absorption in tens of papers. Here we show by direct thermally detected optical absorption measurements that the true band gap of InN is markedly wider than currently accepted 0.7 eV. Micro-cathodoluminescence studies complemented by imaging of metallic In have shown that bright infrared emission at 0.7-0.8 eV arises from In aggregates, and is likely associated with surface states at the metal/InN interfaces.Comment: 4 pages, 5 figures, submitted to PR

Strain-free bulk-like GaN grown by hydride-vapor-phase-epitaxy on two-step epitaxial lateral overgrown GaN template

Crack-free bulk-like GaN with high crystalline quality has been obtained by hydride-vapor-phase-epitaxy (HVPE)growth on a two-step epitaxial lateral overgrown GaN template on sapphire. During the cooling down stage, the as-grown 270-μm-thick GaN layer was self-separated from the sapphire substrate. Plan-view transmission electron microscopyimages show the dislocation density of the free-standing HVPE-GaN to be ∼2.5×10 exp 7  cm exp −2 on the Ga-polar face. A low Ga vacancy related defect concentration of about 8×10 exp 15 cm exp−3 is extracted from positron annihilation spectroscopy data. The residual stress and the crystalline quality of the material are studied by two complementary techniques. Low-temperature photoluminescence spectra show the main neutral donor bound exciton line to be composed of a doublet structure at 3.4715 (3.4712) eV and 3.4721 (3.4718) eV for the Ga- (N-) polar face with the higher-energy component dominating. These line positions suggest virtually strain-free material on both surfaces with high crystalline quality as indicated by the small full width at half maximum values of the donor bound exciton lines. The E1(TO) phonon mode position measured at 558.52 cm exp −1 (Ga face) by infrared spectroscopic ellipsometry confirms the small residual stress in the material, which is hence well suited to act as a lattice-constant and thermal-expansion-coefficient matched substrate for further homoepitaxy, as needed for high-quality III-nitride device applications.Peer reviewe

Raman scattering by longitudinal optical phonons in InN nanocolumns grown on Si(111) and Si(001) substrates

Raman measurements in high-quality InN nanocolumns and thin films grown on both Si(1 1 1) and Si(1 0 0) substrates display a low-energy coupled LO phonon–plasmon mode together with uncoupled longitudinal optical (LO) phonons. The coupled mode is attributed to the spontaneous accumulation of electrons on the lateral surfaces of the nanocolumns, while the uncoupled ones originates from the inner part of the nanocolumns. The LO mode in the columnar samples appears close to the E1(LO) frequency. This indicates that most of the incident light is entering through the lateral surfaces of the nanocolumns, resulting in pure longitudinal–optical mode with quasi-E1 symmetry. For increasing growth temperature, the electron density decreases as the growth rate increases. The present results indicate that electron accumulation layers do not only form on polar surfaces of InN, but also occur on non-polar ones. According to recent calculations, we attribute the electron surface accumulation to the temperature dependent In-rich surface reconstruction on the nanocolumns sidewalls

Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor

Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity. For sensing EGFR activity in cells, we used a genetically encoded CrkII-based biosensor which undergoes conformational changes upon tyrosine-221 phosphorylation by EGFR. We transfected this biosensor into EGFR-positive tumour cells using targeted lipopolyplexes bearing EGFR-binding peptides at their surfaces. In a murine model of basal-like breast cancer, we demonstrated a significant degree of intratumoral heterogeneity in EGFR activity, as well as the pharmacodynamic effect of a radionuclide-labeled EGFR inhibitor in situ. Furthermore, a significant correlation between high EGFR activity in tumour cells and macrophage-tumour cell proximity was found to in part account for the intratumoral heterogeneity in EGFR activity observed. The same effect of macrophage infiltrate on EGFR activation was also seen in a colorectal cancer xenograft. In contrast, a non-small cell lung cancer xenograft expressing a constitutively active EGFR conformational mutant exhibited macrophage proximity-independent EGFR activity. Our study validates the use of this methodology to monitor therapeutic response in terms of EGFR activity. In addition, we found iNOS gene induction in macrophages that are cultured in tumour cell-conditioned media as well as an iNOS activity-dependent increase in EGFR activity in tumour cells. These findings point towards an immune microenvironment-mediated regulation that gives rise to the observed intratumoral heterogeneity of EGFR signalling activity in tumour cells in vivo

A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary

BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease

Mutations in the nuclear localization sequence of the Aristaless related homeobox; sequestration of mutant ARX with IPO13 disrupts normal subcellular distribution of the transcription factor and retards cell division

The electronic version of this article is the complete one and can be found online at: http://www.pathogeneticsjournal.com/content/3/1/1Background: Aristaless related homeobox (ARX) is a paired-type homeobox gene. ARX function is frequently affected by naturally occurring mutations. Nonsense mutations, polyalanine tract expansions and missense mutations in ARX cause a range of intellectual disability and epilepsy phenotypes with or without additional features including hand dystonia, lissencephaly, autism or dysarthria. Severe malformation phenotypes, such as X-linked lissencephaly with ambiguous genitalia (XLAG), are frequently observed in individuals with protein truncating or missense mutations clustered in the highly conserved paired-type homeodomain. Results: We have identified two novel point mutations in the R379 residue of the ARX homeodomain; c.1135C>A, p.R379S in a patient with infantile spasms and intellectual disability and c.1136G>T, p.R379L in a patient with XLAG. We investigated these and other missense mutations (R332P, R332H, R332C, T333N: associated with XLAG and Proud syndrome) predicted to affect the nuclear localisation sequences (NLS) flanking either end of the ARX homeodomain. The NLS regions are required for correct nuclear import facilitated by Importin 13 (IPO13). We demonstrate that missense mutations in either the N- or C-terminal NLS regions of the homeodomain cause significant disruption to nuclear localisation of the ARX protein in vitro. Surprisingly, none of these mutations abolished the binding of ARX to IPO13. This was confirmed by co-immunoprecipitation and immmuno fluorescence studies. Instead, tagged and endogenous IPO13 remained bound to the mutant ARX proteins, even in the RanGTP rich nuclear environment. We also identify the microtubule protein TUBA1A as a novel interacting protein for ARX and show cells expressing mutant ARX protein accumulate in mitosis, indicating normal cell division may be disrupted. Conclusions: We show that the most likely, common pathogenic mechanism of the missense mutations in NLS regions of the ARX homeodomain is inadequate accumulation and distribution of the ARX transcription factor within the nucleus due to sequestration of ARX with IPO13.Cheryl Shoubridge, May Huey Tan, Tod Fullston, Desiree Cloosterman, David Coman, George McGillivray, Grazia M Mancini, Tjitske Kleefstra and Jozef Géc