127 research outputs found
The deleted in brachydactyly B domain of ROR2 is required for receptor activation by recruitment of Src
The transmembrane receptor 'ROR2' resembles members of the receptor tyrosine kinase family of signalling receptors in sequence but its' signal transduction mechanisms remain enigmatic. This problem has particular importance because mutations in ROR2 are associated with two human skeletal dysmorphology syndromes, recessive Robinow Syndrome (RS) and dominant acting Brachydactyly type B (BDB). Here we show, using a constitutive dimerisation approach, that ROR2 exhibits dimerisation-induced tyrosine kinase activity and the ROR2 C-terminal domain, which is deleted in BDB, is required for recruitment and activation of the non-receptor tyrosine kinase Src. Native ROR2 phosphorylation is induced by the ligand Wnt5a and is blocked by pharmacological inhibition of Src kinase activity. Eight sites of Src-mediated ROR2 phosphorylation have been identified by mass spectrometry. Activation via tyrosine phosphorylation of ROR2 receptor leads to its internalisation into Rab5 positive endosomes. These findings show that BDB mutant receptors are defective in kinase activation as a result of failure to recruit Src
Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells.
ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→︀A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration
Optical gain in 1.3-μm electrically driven dilute nitride VCSOAs
We report the observation of room-temperature optical gain at 1.3 μm in electrically driven dilute nitride vertical cavity semiconductor optical amplifiers. The gain is calculated with respect to injected power for samples with and without a confinement aperture. At lower injected powers, a gain of almost 10 dB is observed in both samples. At injection powers over 5 nW, the gain is observed to decrease. For nearly all investigated power levels, the sample with confinement aperture gives slightly higher gain
Triple‐crystal x‐ray diffraction analysis of reactive ion etched gallium arsenide
This is the published version. Copyright 1994 American Institute of PhysicsThe effect of BCl3 reactive ion etching on the structural perfection of GaAs has been studied with diffuse x‐ray scattering measurementsconducted by high‐resolution triple‐crystal x‐ray diffraction. While using a symmetric 004 diffraction geometry revealed no discernible differences between etched and unetched samples, using the more surface‐sensitive and highly asymmetric 113 reflection revealed that the reactive ion etched samples etched displayed less diffusely scattered intensity than unetched samples, indicating a higher level of structural perfection. Increasing the reaction ion etch bias voltage was found to result in decreased diffuse scattering initially, until an apparent threshold voltage was reached, after which no further structural improvement was observed. Furthermore, we have shown that this reduction in process‐induced surfacestructural damage is not due merely to the removal of residual chemical‐mechanical polishing damage
Tumor-suppressor activity of RRIG1 in breast cancer
<p>Abstract</p> <p>Background</p> <p>Retinoid receptor-induced gene-1 (RRIG1) is a novel gene that has been lost in several types of human cancers. The aim of this study was to determine whether RRIG1 plays a role in breast cancer, such as in the suppression of breast cancer cell growth and invasion.</p> <p>Methods</p> <p>Immunohistochemistry was used to detect RRIG1 expression in breast tissue specimens. Gene transfection was used to restore or knock down RRIG1 expression in breast cancer cell lines for analysis of cell viability, colony formation, and migration/invasion potential. Reverse-transcription polymerase chain reaction and western blot assays were used to detect the changes in gene expression. The RhoA activation assay was used to assess RRIG1-induced inhibition of RhoA activity.</p> <p>Results</p> <p>The immunohistochemical data showed that <it>RRIG1 </it>expression was reduced in breast cancer tissues compared with normal and atypical hyperplastic breast tissues. <it>RRIG1 </it>expression was inversely correlated with lymph node metastasis of breast cancer but was not associated with the status of hormone receptors, such as estrogen receptor, progesterone receptor, or HER2. Furthermore, restoration of <it>RRIG1 </it>expression inhibited proliferation, colony formation, migration, and invasion of breast cancer cells. Expression of RRIG1 also reduced phosphorylated Erk1/2 and Akt levels; c-Jun, MMP9, and Akt expressions; and RhoA activity. In contrast, knockdown of RRIG1 expression promoted breast cancer cell proliferation, colony formation, migration, and invasion potential.</p> <p>Conclusion</p> <p>The data from the current study indicated that <it>RRIG1 </it>expression was reduced or lost in breast cancer and that restoration of RRIG1 expression suppressed breast cancer cell growth and invasion capacity. Future studies will determine the underlying molecular mechanisms and define RRIG1 as a tumor-suppressor gene in breast cancer.</p
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Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.
[This corrects the article DOI: 10.1186/s13054-016-1208-6.]
Wafer-Bonded Active/Passive Vertically Coupled Microring Lasers
We summarize the results of a European Project entitled WAPITI (Waferbonding and Active Passive Integration Technology and Implementation) dealing with the fabrication and investigation of active/passive vertically coupled ring resonators, wafer bonded on GaAs, and based on full wafer technology. The concept allows for the integration of an active ring laser vertically coupled to a transparent bus waveguide. All necessary layers are grown in a single epitaxial run so that the critical coupling gap can be precisely controlled with the high degree of accuracy of epitaxial growth. One key challenge of the project was to establish a reliable wafer bonding technique using BCB as an intermediate layer. In intensive tests we investigated and quantified the effect of unavoidable shrinkage of the BCB on the overall device performance. Results on cw-operation, low threshold currents of about 8 mA, high side-mode suppression ratios in the range of 40 dB and large signal modulation bandwidths of up to 5 GHz for a radius of 40 μm shows the viability of the integration process
Log-moment estimators of the Nakagami-lognormal distribution
[EN] In this paper, estimators of the Nakagami-lognormal (NL) distribution based on the method of log-moments have
been derived and thoroughly analyzed. Unlike maximum likelihood (ML) estimators, the log-moment estimators of
the NL distribution are obtained using straightforward equations with a unique solution. Also, their performance has
been evaluated using the sample mean, confidence regions and normalized mean square error (NMSE). The NL
distribution has been extensively used to model composite small-scale fading and shadowing in wireless
communication channels. This distribution is of interest in scenarios where the small-scale fading and the shadowing
processes cannot be easily separated such as the vehicular environment.This work has been funded in part by the Programa de Estancias de Movilidad de Profesores e Investigadores en Centros Extranjeros de Ensenanza Superior e Investigacion of the Ministerio de Educacion, Cultura y Deporte, Spain, PR2015-00151 and by the Ministerio de Economia, Industria y Competitividad of the Spanish Government under the national project TEC2017-86779-C2-2-R, through the Agencia Estatal de Investigacion (AEI) and the Fondo Europeo de Desarrollo Regional (FEDER).Reig, J.; Brennan, C.; Rodrigo Peñarrocha, VM.; Rubio Arjona, L. (2019). Log-moment estimators of the Nakagami-lognormal distribution. EURASIP Journal on Wireless Communications and Networking. 1-10. https://doi.org/10.1186/s13638-018-1328-6S110J. M. Ho, G. L. Stüber, in Co-channel interference of microcellular systems on shadowed Nakagami fading channels. Proc. 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A simple importance sampling technique for orthogonal space-time block codes on Nakagami fading channels
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