Growth of GaN films on porous SiC substrate by molecular-beam epitaxy

Porous SiC (PSiC) substrates were used for the growth of GaN by reactive molecular-beam epitaxy with ammonia as the nitrogen source. Improved quality of GaNfilms has been demonstrated for growth on PSiC substrates, as compared to that on standard 6H–SiC substrates. Cross-sectional transmission electron microscopy and electron diffraction showed a reduction in dislocation density and a higher degree of lattice and thermal relaxation in the GaNfilmsgrown on porous substrates. The submicron GaNfilms exhibit a rocking curve linewidth of 3.3 arcmin for (0002) diffraction and 13.7 arcmin for (101̄2) diffraction. Low-temperature photoluminescence showed an excitonic transition with a full width at half maximum of 9.5 meV at 15 K, as well as high quantum efficiency, on the GaN layer grown on PSiC when the thin skin layer on porous SiC was removed before growth

Efficacy of single and double SiNx interlayers on defect reduction in GaN overlayers grown by organometallic vapor-phase epitaxy

We report on the growth of and evolution of defects in GaN epilayers having single- and double-layer SiNx nanoporous insertion layers. The SiNx was formed in situ in the growth chamber of an organometallic vapor-phase epitaxy system by simultaneous flow of diluted silane and ammonia. The GaN epilayers and SiNx interlayers were grown on 6H-SiC substrates using three different nucleation layers, namely, low-temperature GaN, high-temperature GaN, and high-temperature AlN nucleation layers. X-ray-diffraction rocking curves and cross-sectional and plan-view transmission electron microscope analyses indicated that a nanoporous SiNx layer can reduce the dislocations density in the GaN overgrown layer to ∼3×108cm−2 range; below this level the defect blocking effect of SiNx would saturate. Therefore the insertion of a second SiNx layer becomes much less effective in reducing dislocations, although it continues to reduce the point defects, as suggested by time-resolved photoluminescence measurements. The insertion of SiNx interlayers was found to improve significantly the mechanical strength of the GaN epilayers resulting in a much lower crack line density

Low dislocation densities and long carrier lifetimes in GaN thin films grown on a SiNx nanonetwork

Significant improvement of structural and optical qualities of GaNthin films on sapphire substrates was achieved by metal organic chemical vapor deposition with in situ SiNxnanonetwork. Transmission electron microscope (TEM) studies revealed that screw- and edge-type dislocations were reduced to 4.4×107 and 1.7×107cm−2, respectively, for a ∼5.5-μm-thick layer. Furthermore, room temperature carrier lifetimes of 2.22 and 2.49ns were measured by time-resolved photoluminescence(TRPL) for samples containing single and double SiNx network layers, respectively, representing a significant improvement over the previous studies. The consistent trends among the TEM,x-ray diffraction, and TRPL measurements suggest that in situ SiNx network reduces line defects effectively as well as the point-defect-related nonradiative centers

Effectiveness of TiN porous templates on the reduction of threading dislocations in GaN overgrowth by organometallic vapor-phase epitaxy

We report on the reduction of threading dislocations in GaN overlayers grown by organometallic vapor phase epitaxy on micro-porous TiN networks. These networks were obtained by in situannealing of thin Ti layers deposited in a metalization chamber, on the (0001) face of GaN templates. Observations by transmission electron microscopy indicate dislocation reduction by factors of up to 10 in GaN layers grown on TiN networks compared with the control GaN.X-ray diffraction shows that GaNgrown on the TiN network has a smaller (102) plane peak width (4.6 arcmin) than the control GaN (7.8 arcmin). In low temperature photoluminescence spectra, a narrow excitonic full-width-at-half-maximum of 2.4 meV was obtained, as compared to 3.0 meV for the control GaN, confirming the improved crystalline quality of the overgrown GaN layers

Dislocation reduction in GaN grown on porous TiN networks by metal-organic vapor-phase epitaxy

We report on the effectiveness of porous TiN nanonetworks on the reduction of threading dislocations (TDs) in GaN grown by metal-organic vapor-phase epitaxy (MOVPE). The porous TiN networks were formed by in situ annealing of thin-deposited Ti films deposited ex situ on GaN templates within the MOVPE growth chamber. Different annealing parameters in relation to surface porosity of TiN networks were investigated. Transmission electron micrographs indicated dislocation reduction by factors of up to 10 in GaN layers grown on the TiN nanonetwork, compared with a control sample. TiN prevented many dislocations present in the GaN templates from penetrating into the upper layer. Microscale epitaxial lateral overgrowth of GaN above TiN also contributed to TD reduction. The surface porosity of the TiN network had a strong impact on the efficiency of TD reduction. X-ray-diffraction and time-resolved photoluminescence measurements further confirmed the improved GaN quality

AKT overactivation can suppress DNA repair via p70S6 kinase-dependent downregulation of MRE11

Deregulated AKT kinase activity due to PTEN deficiency in cancer cells contributes to oncogenesis by incompletely understood mechanisms. Here, we show that PTEN deletion in HCT116 and DLD1 colon carcinoma cells leads to suppression of CHK1 and CHK2 activation in response to irradiation, impaired G2 checkpoint proficiency and radiosensitization. These defects are associated with reduced expression of MRE11, RAD50 and NBS1, components of the apical MRE11/RAD50/NBS1 (MRN) DNA damage response complex. Consistent with reduced MRN complex function, PTEN-deficient cells fail to resect DNA double-strand breaks efficiently after irradiation and show greatly diminished proficiency for DNA repair via the error-free homologous recombination (HR) repair pathway. MRE11 is highly unstable in PTEN-deficient cells but stability can be significantly restored by inhibiting mTORC1 or p70S6 kinase (p70S6K), downstream kinases whose activities are stimulated by AKT, or by mutating a residue in MRE11 that we show is phosphorylated by p70S6K in vitro. In primary human fibroblasts, activated AKT suppresses MRN complex expression to escalate RAS-induced DNA damage and thereby reinforce oncogene-induced senescence. Taken together, our data demonstrate that deregulation of the PI3K-AKT/ mTORC1/ p70S6K pathways, an event frequently observed in cancer, exert profound effects on genome stability via MRE11 with potential implications for tumour initiation and therapy

Metformin as an Adjunctive Therapy for Pancreatic Cancer: A Review of the Literature on Its Potential Therapeutic Use

Pancreatic ductal adenocarcinoma has the worst prognosis of any cancer. New adjuvant chemotherapies are urgently required, which are well tolerated by patients with unresectable cancers. This paper reviews the existing proof of concept data, namely laboratory, pharmacoepidemiological, experimental medicine and clinical trial evidence for investigating metformin in patients with pancreatic ductal adenocarcinoma. Laboratory evidence shows metformin inhibits mitochondrial ATP synthesis which directly and indirectly inhibits carcinogenesis. Drug–drug interactions of metformin with proton pump inhibitors and histamine H2-receptor antagonists may be of clinical relevance and pertinent to future research of metformin in pancreatic ductal adenocarcinoma. To date, most cohort studies have demonstrated a positive association with metformin on survival in pancreatic ductal adenocarcinoma, although there are many methodological limitations with such study designs. From experimental medicine studies, there are sparse data in humans. The current trials of metformin have methodological limitations. Two small randomized controlled trials (RCTs) reported null findings, but there were potential inequalities in cancer staging between groups and poor compliance with the intervention. Proof of concept data, predominantly from laboratory work, supports assessing metformin as an adjunct for pancreatic ductal adenocarcinoma in RCTs. Ideally, more experimental medicine studies are needed for proof of concept. However, many feasibility criteria need to be answered before such trials can progress

Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL)

Modern treatment strategies have improved the prognosis of childhood ALL; however, treatment still fails in 25–30% of patients. Further improvement of treatment may depend on the development of targeted therapies. mTOR kinase, a central mediator of several signaling pathways, has recently attracted remarkable attention as a potential target in pediatric ALL. However, limited data exists about the activity of mTOR. In the present study, the amount of mTOR activity dependent phospho-proteins was characterized by ELISA in human leukemia cell lines and in lymphoblasts from childhood ALL patients (n = 49). Expression was measured before and during chemotherapy and at relapses. Leukemia cell lines exhibited increased mTOR activity, indicated by phospho-S6 ribosomal protein (p-S6) and phosphorylated eukaryotic initiation factor 4E binding protein (p-4EBP1). Elevated p-4EBP1 protein levels were detected in ALL samples at diagnosis; efficacy of chemotherapy was followed by the decrease of mTOR activity dependent protein phosphorylation. Optical density (OD) for p-4EBP1 (ELISA) was significantly higher in patients with poor prognosis at diagnosis, and in the samples of relapsed patients. Our results suggest that measuring mTOR activity related phospho-proteins such as p-4EBP1 by ELISA may help to identify patients with poor prognosis before treatment, and to detect early relapses. Determining mTOR activity in leukemic cells may also be a useful tool for selecting patients who may benefit from future mTOR inhibitor treatments

AMPK:a nutrient and energy sensor that maintains energy homeostasis

AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production by increasing the activity or expression of proteins involved in catabolism while conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole-body level. For example, it mediates the effects of agents acting on the hypothalamus that promote feeding and entrains circadian rhythms of metabolism and feeding behaviour. Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability

AMP-activated protein kinase - not just an energy sensor

Orthologues of AMP-activated protein kinase (AMPK) occur in essentially all eukaryotes as heterotrimeric complexes comprising catalytic α subunits and regulatory β and γ subunits. The canonical role of AMPK is as an energy sensor, monitoring levels of the nucleotides AMP, ADP, and ATP that bind competitively to the γ subunit. Once activated, AMPK acts to restore energy homeostasis by switching on alternate ATP-generating catabolic pathways while switching off ATP-consuming anabolic pathways. However, its ancestral role in unicellular eukaryotes may have been in sensing of glucose rather than energy. In this article, we discuss a few interesting recent developments in the AMPK field. Firstly, we review recent findings on the canonical pathway by which AMPK is regulated by adenine nucleotides. Secondly, AMPK is now known to be activated in mammalian cells by glucose starvation by a mechanism that occurs in the absence of changes in adenine nucleotides, involving the formation of complexes with Axin and LKB1 on the surface of the lysosome. Thirdly, in addition to containing the nucleotide-binding sites on the γ subunits, AMPK heterotrimers contain a site for binding of allosteric activators termed the allosteric drug and metabolite (ADaM) site. A large number of synthetic activators, some of which show promise as hypoglycaemic agents in pre-clinical studies, have now been shown to bind there. Fourthly, some kinase inhibitors paradoxically activate AMPK, including one (SU6656) that binds in the catalytic site. Finally, although downstream targets originally identified for AMPK were mainly concerned with metabolism, recently identified targets have roles in such diverse areas as mitochondrial fission, integrity of epithelial cell layers, and angiogenesis