Role of CIP2A in carcinogenesis

Worldwide and notably in the developed countries, cancer is an increasing cause of morbidity and mortality, being the second most common cause of death after ischemic heart disease. Now and in the future new cancer cases need to be diagnosed earlier. Prognostic factors may be helpful in recognizing and handling those patients who need more aggressive therapy, and it is also desirable to predict treatment response accurately. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein predominantly expressed in malignant tissues and inhibiting protein phosphatase 2A (PP2A) activity; it is a promising target for cancer therapy. The aim of this thesis was to evaluate the prognostic role of CIP2A in solid cancers, and for this purpose to explore expression of CIP2A, and investigating regulation of CIP2A in order to gain insight into signalling pathways leading to alteration in prognosis. Patients diagnosed with gastric, serous ovarian, tongue, or colorectal cancer at Helsinki University Central Hospital were included. Tumour tissue microarrays assembled from specimens from these patients were prepared and stained immunohistochemically for CIP2A protein expression. Associations with clinicopathologic parameters and other biomarkers were explored, and survival analyses were done according to the Kaplan-Meier method. Study of the role of CIP2A in intracellular signalling in vitro involved gastric, ovarian, and tongue cancer cell lines. We found CIP2A to be highly expressed in gastric, ovarian, tongue, and colorectal cancer specimens. CIP2A was associated with clinicopathologic parameters characterizing an aggressive disease, namely advanced stage, high grade, p53 immunopositivity, and high proliferation index. CIP2A led to recognition of gastric, ovarian, and tongue cancer patients with poor prognosis, however, with a cancer type-specific cut-off level for prognostic significance. In tongue cancer, it served as an independent prognostic marker. In contrast, in colorectal cancer, CIP2A provided no prognostic value. In cancer cell lines, CIP2A was highly expressed at both protein and mRNA levels, and promoted cell proliferation and anchorage-independent growth. In gastric cancer, we demonstrated with a MYCER construct in mouse embryo fibroblasts that activation of MYC led to increased CIP2A mRNA expression, and hence we suggested that a positive feedback mechanism between CIP2A and MYC may potentiate and prolong the oncogenic activity of these proteins. We demonstrated in ovarian cancer an association between CIP2A and EGFR protein overexpression and EGFR gene amplification. In ovarian and tongue cancer cells we showed that depletion of EGFR downregulates CIP2A expression. In conclusion, high CIP2A expression occurred frequently among patients with aggressive disease. CIP2A may serve as a prognostic marker in gastric, ovarian, and tongue cancer and thus may help in tailoring therapy for cancer patients. The positive feedback mechanism between CIP2A and MYC, as well as the positive regulation of CIP2A by EGFR, are a few signalling pathways regulating and regulated by CIP2A. These and other mechanisms need to be studied further, however. CIP2A is a potential target for therapy, and its potential role as predictive marker and as a tumour marker in serum requires exploration.

Engineered Biferroic 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3/La0.6Sr0.4MnO3 Epitaxial Superlattices

Symmetric and asymmetric superlattices (SLs) composed of ferromagnetic La0.6Sr0.4MnO3 (LSMO) and ferroelectric 0.7Pb(Mg1/3Nb2/3)O3 – 0.3PbTiO3 (PMN-PT) with different periodicities have been fabricated on LaNiO3 (LNO) coated LaAlO3 (100) (LAO) substrates by pulsed laser ablation deposition. Structural, ferromagnetic and ferroelectric properties have been studied for all the SLs. All the heterostructures exhibited good ferromagnetic response over a wide range of temperatures (10K – 300K), whereas only the asymmetric SLs exhibited reasonably good ferroelectric behaviour. Ferromagnetic and ferroelectric hysteresis loops observed in the asymmetric SLs confirmed their biferroic nature. Studies were conducted towards understanding the influence of LSMO layers on the electrical responses of the heterostructures. Absence of ferroelectricity in the symmetric SL structures has been attributed to their high leakage characteristics. Strong influence of an applied magnetic field of 1.2T was observed on the ferroelectric properties of the asymmetric SLs. The effect of magnetic field on the ferroelectric properties of the SLs indicated possibility of strong interfacial effect.

Surface-Bound Selectin-Ligand Binding Is Regulated By Carrier Diffusion

Two-dimensional (2D) kinetics of receptor-ligand interactions governs cell adhesion in many biological processes. While the dissociation kinetics of receptor-ligand bond is extensively investigated, the association kinetics has much less been quantified. Recently receptor-ligand interactions between two surfaces were investigated using a thermal fluctuation assay upon biomembrane force probe technique (Chen et al. in Biophys J 94:694-701, 2008). The regulating factors on association kinetics, however, are not well characterized. Here we developed an alternative thermal fluctuation assay using optical trap technique, which enables to visualize consecutive binding-unbinding transition and to quantify the impact of microbead diffusion on receptor-ligand binding. Three selectin constructs (sLs, sPs, and PLE) and their ligand P-selectin glycoprotein ligand 1 were used to conduct the measurements. It was indicated that bond formation was reduced by enhancing the diffusivity of selectin-coupled carrier, suggesting that carrier diffusion is crucial to determine receptor-ligand binding. It was also found that 2D forward rate predicted upon first-order kinetics was in the order of sPs > sLs > PLE and bond formation was history-dependent. These results further the understandings in regulating association kinetics of surface-bound receptor-ligand interactions.

InAs/GaSb superlattices for photodetection in short wavelength infrared range

The first report of a short wavelength infrared detector based on type II InAs/GaSb superlattices is presented. Very short period superlattices containing InAs (2ML)/GaSb (8ML) superlattices (SLs) were grown by molecular-beam epitaxy on GaSb substrates. The photoluminescence showed a cut-off wavelength at 2.1 mu m at 10 K and 2.6 mu m at 300 K. Room-temperature optical transmittance spectra shows obvious absorption in InAs (2ML)/GaSb (8ML) SL in the range of 450-680 meV, i.e. 1.8-2.7 mu m. The cut-off wavelength moved from 2.3 mu m to 2.6 mu m with temperature rising from 77 K to 300 K in photoresponse spectra. The blackbody response R-v exponentially decreased as a function of 1/T in two temperature sections (130-200 K and 230-300 K). The blackbody detectivity D-bb(center dot) was beyond 1 x 10(8) cmHz(1/2)/W at room temperature. (C) 2009 Elsevier B.V. All rights reserved.

SHORT PERIOD InAs/GaSb SUPERLATTICE INFRARED DETECTOR ON GaAs SUBSTRATES

Two type II superlattices (SLs) InAs(2ML)/GaSb(8ML) and InAs(8ML)/GaSb(8ML) were grown on GaAs substrates by molecular-beam epitaxy. High resolution X-ray diffraction showed the periods of the two SLs were 31.2 angstrom and 57.3 angstrom, respectively. Room-temperature optical transmittance spectra showed that there were clear absorption edges at 2.1 mu m and 5 mu m for the two SLs. The SWIR and MWIR photoconductor devices were fabricated by standard lithography and etched by tartaric acid solution. The spectral response and blackbody tests were carried out at low and room temperatues. The results show that the 50% cutoff wavelengths of the two photoconductors are 2.1 mu m and 5.0 mu m respectively and D-bb* is above 2 x 10(8) cmHz(1/2)/W for two kinds of photoconductors at 77K. D-bb* is above 10(8) cmHz(1/2)/W for SWIR photoconductor at room temperature.

Interfaces in InAs/GaSb Superlattices Grown by Molecular Beam Epitaxy

Short period InAs(4 ML)/GaSb(8 ML) superlattices (SLs) with InSb- and mixed-like (or Ga(1-x)In(x)As(1-)ySb(y)-like) interfaces (IFs) are grown by molecular-beam epitaxy (MBE) on (001) GaSb substrates at optimized growth temperature. Raman scattering reveals that two kinds of IFs can be formed by controlling shutter sequences. X-ray diffraction (XRD) and atomic force microscopy (AFM) demonstrate that SLs with mixed-like IFs are more sensitive to growth temperature than that with InSb-like IFs. The photoluminescence (PL) spectra of SLs with mixed-like IFs show a stronger intensity and narrower line width than with InSb-like IFs. It is concluded that InAs/GaSb SLs with mixed-like IFs have better crystalline and optical properties.

Growth and characterization of AlGaN/GaN heterostructure using unintentionally doped AlN/GaN superlattices as barrier layer

AlGaN/GaN heterostructure using unintentionally doped AlN/GaN superlattices (SLs) as barrier layer is grown on C-plane sapphire by metal organic vapor deposition (MOCVD). Compared with the conventional Si-doped structure, electrical property is improved. An average sheet resistance of 287.1 Omega/square and high resistance uniformity of 0.82% are obtained across the 2-inch epilayer wafer with an equivalent Al composition of 38%. Hall measurement shows that the mobility of two-dimensional electron gas (2DEG) is 1852 cm(2)/V s with a sheet carrier density of 1.2 x 10(13) cm(-2) at room temperature. The root mean square roughness (RMS) value is 0.159 nm with 5 x 5 mu m(2) scan area and the monolayer steps are clearly observed. The reason for the property improvement is discussed. (c) 2008 Elsevier Ltd. All rights reserved.

Comparison of short period InAs/GaSb superlattices on GaSb and GaAs substrates

Type II superlattices (SLs) short period InAs(4ML)/GaSb(8ML) were grown by molecular-beam epitaxy on lattice-mismatched GaAs substrates and on GaSb substrates. A smooth GaSb epilayer was formed on GaAs substrates by inserting mulit-buffer layers including an interfacial misfit mode AlSb quantum dot layer and AlSb/GaSb superlattices smooth layer. SLs grown on GaAs substrates (GaAs-based SLs) showed well-resolved satellite peaks in XRD. GaSb-based SLs with better structural quality and smoother surface showed strong photoluminescence at 2.55 mu m with a full width at half maximum (FWHM) of 20 meV, narrower than 31 meV of GaAs-based SLs. Inferior optical absorption of GaAs-based SL was observed in the range of 2-3 mu m. Photoresponse of GaSb-based SLs showed the cut-off wavelength at 2.6 mu m.

Optical characteristics of InAs quantum dots capped with short period GaAs/InAs superlattices and InGaAs combination layers

Long wavelength light emission was realized by capping InAs quantum dots (QDs) with short period GaAs/InAs superlattices (SLs) and an InGaAs strain-reducing layer (SRL). The optical properties were systematically investigated by photoluminescence tests. With increasing the periods of SLs, the emission wavelength of InAs QDs shifts from 1.27 to 1.53 mum. We explain the redshift as a result of the increased QD height with the SLs and the reduced strain in the dot caused by InGaAs SRL. (C) 2004 Published by Elsevier Ltd.

Self-organized superlattices along the [001] growth direction in In0.52Al0.48As layers grown on nominally (001) InP substrates by molecular beam epitaxy

Horizontal self-organized superlattice structures consisting of alternating In-rich and Al-rich layers formed naturally during solid-source molecular beam epitaxy (MBE) growth of In0.52Al0.48As on exactly (001) InP substrates, with In and At fluxes unchanged. The growth temperatures were changed from 490 to 510 degrees C, the most commonly used growth temperature for In0.52Al0.48As alloy. No self-organized superlattices (SLs) were observed at the growth temperature 490 degrees C, and self-organized SLs were observed in InAlAs layers at growth temperatures ranging from 498 to 510 degrees C. The results show that the period of the SLs is very highly regular, with the value of similar to 6 nm, and the composition of In or Al varies approximately sinusoidally along the [001] growth direction. The theoretical simulation results confirm that the In composition modulation amplitude is less than 0.02 relative the In composition of the In0.52Al0.48As lattice matched with the InP substrate. The influence of InAs self-organized quantum wires on the spontaneously formed InxAl1-xAs/InyAl1-yAs SLs was also studied and the formation of self-organized InxAl1-xAs/InyAl1-yAs SLs was attributed to the strain-mediated surface segregation process during MBE growth of In0.52Al0.48As alloy. (C) 2005 Published by Elsevier Ltd.

Site controlling of InAs quantum wires on cleaved edges of AlGaAs/GaAs superlattices

Site-controlled InAs quantum wires were fabricated on cleaved edges of AlGaAs/GaAs superlattices (SLs) by solid source molecular beam epitaxy. The cleaved edge of AlGaAs/GaAs SLs acted as a nanopattern for selective overgrowth after selective etching. By just growing 2.0 ML InAs without high temperature degassing, site-controlled InAs quantum wires were fabricated on the cleaved edge. Furthermore, atomic force microscopy demonstrates the diffusion of In atoms is strong toward the [00 (1) over bar] direction on the (110) surface.

MBE growth of very short period InAs/GaSb type-II superlattices on (001) GaAs substrates

First, GaSb epilayers were grown on (001) GaAs substrates by molecular beam epitaxy. We determined that the GaSb layers had very smooth surfaces using atomic force microscopy. Then, very short period InAs/ GaSb superlattices (SLs) were grown on the GaSb buffer layer. The optical and crystalline properties of the superlattices were studied by low-temperature photoluminescence spectra and high resolution transition electron microscopy. In order to determine the interface of SLs, the samples were tested by Raman-scattering spectra at room temperature. Results indicated that the peak wavelength of SLs with clear interfaces and integrated periods is between 2.0 and 2.6 mu m. The SL interface between InAs and GaSb is InSb-like.

Influence of InAs deposition. thickness on the structural and optical properties of InAs quantum wires

The influence of InAs deposition thickness on the structural and optical properties of InAs/InAlAs quantum wires (QWR) superlattices (SLS) was studied. The transmission electron microscopy (TEM) results show that with increasing the InAs deposited thickness, the size uniformity and spatial ordering of InAs QWR SLS was greatly improved, but threading dislocations initiated from InAs nanowires for the sample with 6 monolayers (MLs) InAs deposition. In addition, the zig-zag features along the extending direction and lateral interlink of InAs nanowires were also observed. The InAs nanowires, especially for the first period, were laterally compact. These structural features may result in easy tunneling and coupling of charge carriers between InAs nanowires and will hamper their device applications to some extent. Some suggestions are put forward for further improving the uniformity of the stacked InAs QWRs, and for suppressing the formation of the threading dislocations in InAs QWR SLS.

Structural characterization of AlGaN/GaN superlattices by x-ray diffraction and Rutherford backscattering

We report on structural characterization of AlGaN/GaN superlattices grown on sapphire. The superlattice formation is evidenced by high-resolution x-ray diffraction and transmission electron microscopy. The high resolution x-ray diffraction spectra exhibit a pattern of satellite peaks. The in-plane lattice constants of the superlattices indicate the coherent growth of the AlGaN layer onto GaN. The average At composition in the superlattices is determined to be 0.08 by Rutherford backscattering spectroscopy. The average parallel and perpendicular elastic strains for the SLs are determined to be (e(parallel to)) = +0.25% and (e(perpendicular to)) = -0.17%. (c) 2006 Elsevier Ltd. All rights reserved.

Role of different cap layers tuning the wavelength of self-assembled InAs/GaAs quantum dots

We have investigated the effect of different cap layers on the photoluminescence (PL) of self-assembled InAs/GaAs quantum dots (QDs). Based upon different cap layers, the wavelength of InAs QDs can be tuned to the range from 1.3 to 1.5 mum. An InAlAs and InGaAs combination layer can enlarge the energy separation between the ground and first excited radiative transition. GaAs/InAs short period superlattices (SLs) make the emission wavelength shift to 1.53 mum. The PL intensity of InAs QDs capped with GaAs/InAs SLs shows an anomalous increase with increasing temperature. We attribute this to the transfer of carriers between different QDs.