Rôle de la signalisation Wnt non-canonique dans l’étiologie de l’ostéoarthrose chez l’humain

Les études cliniques et in vitro suggèrent que la sclérose de l’os sous-chondral due aux ostéoblastes (Ob) anormaux est impliquée dans la progression de l’ostéoarthrose (OA). Les Ob OA humains isolés à partir d’os sous-chondral sclérosé montrent un phénotype altéré, un niveau réduit de signalisation Wnt/β-caténine canonique et une minéralisation in vitro réduite. Il existe également deux voies non-canoniques, Wnt/PKC et Wnt/PCP qui ont étés décrites dans la littérature. Cependant, il n’existe aucune étude qui traite de ces deux voies dans les Ob OA. Ces voies sont activées après qu’un ligand Wnt non-canonique tel que Wnt-5a se lie à un récepteur Wnt couplé à des corécepteurs de la voie non-canonique. Ceci enclenche, respectivement pour la voie Wnt/PKC-Ca2+ et Wnt/PCP, la phosphorylation de PKC (p-PKC) et la phosphorylation de JNK (p-JNK) et agit sur les cibles en aval. Nous avons voulu déterminer s’il était possible de constater des altérations dans les voies Wnt non-canoniques dans les Ob OA. Nous avons préparé des cultures primaires d’ostéoblastes sous-chondral humains à partir de plateaux tibiaux de patients OA subissant une arthroplastie totale du genou, ainsi qu’à partir de plateaux tibiaux recueillis à l’autopsie de patients « normaux ». L’expression des gènes impliqués dans les voies Wnt/PKC et Wnt/PCP a été évaluée par RT-qPCR et la production par Western Blot des protéines, ainsi que celle de p-PKC et p-JNK et que l’activité des facteurs NFAT et AP-1 utilisés par ces deux voies. L’activité phosphatase alcaline (ALPase) et la quantité d’ostéocalcine (OC) ont étés évaluées respectivement à l’aide d’hydrolyse de substrat et d’ELISA. Le niveau de minéralisation a été évalué par la coloration au rouge Alizarine. Nos résultats montrent que l’expression et la production de Wnt-5a étaient augmentées dans les Ob OA comparées aux Ob N et LGR5 était significativement plus élevée. De plus, l’expression de LGR5 est directement régulée via la stimulation ou la diminution de Wnt-5a, à la fois au niveau de l’ARNm et des protéines. Par ailleurs, Wnt-5a a stimulé la phosphorylation de JNK et de PKC ainsi que l’activité NFAT et AP-1. Les niveaux de minéralisation ainsi que d’activité ALPase et de sécrétion d’OC ont aussi été affectés par les changements du niveau de Wnt-5a. Ces résultats suggèrent que Wnt-5a, qui est augmentée dans les OA Ob, peut stimuler les voies Wnt non-canoniques et affecter le phénotype et la minéralisation des OA Ob humains.

Design and performance of monolithic integrated electro-absorption modulated distributed feedback laser - art. no. 67820Y

High performance InGaAsP/InGaAsP strained compensated multiple-quantum-well (MQW) electroabsorption modulators (EAM) monolithically integrated with a DFB laser diode have been designed and realized by ultra low metal-organic vapor phase epitaxy (MOVPE) based on a novel butt joint scheme. The optimization thickness of upper SCH layer for DFB and EAM was obtained of the proposed MQW structure of the EAM through numerical simulation and experiment. The device containing 250(mu m) DFB and 170(mu m) EAM shows good material quality and exhibits a threshold current of 17mA, an extinction ratio of higher than 30 dB and a very high modulation efficiency (12dB/V) from 0V to 1V. By adopting a high-mesa ridge waveguide and buried polyimide, the capacitance of the modulator is reduced to about 0.30 pF corresponding to a 3dB bandwidth more than 20GHz.

Offset quantum-well method for tunable distributed Bragg reflector lasers and electro-absorption modulated distributed feedback lasers

A two-section offset quantum-well structure tunable laser with a tuning range of 7 nm was fabricated using offset quantum-well inethod. The distributed Bragg reflector （DBR） was realized just by selectively wet etching the multiquantum-well （MQW） layer above the quaternary lower waveguide. A threshold current of 32 mA and an output power of 9 mW at 100 mA were achieved. Furthermore, with this offset structure method, a distributed feedback （DFB） laser was integrated with an electro-absorption modulator （EAM）, which was capable of producing 20 dB of optical extinction.

Perpendicularly self-oriented and shape-controlled L1(0)-FePt nanorods directly synthesized by a temperature-modulated process

The synthesis and self-assembly of tetragonal phase-containing L1(0)-Fe(55)Pt(45) nanorods with high coercive field is described. The experimental procedure resulted in a tetragonal/cubic phase ratio close to 1:1 for the as-synthesized nanoparticles. Using different surfactant/solvent proportions in the process allowed control of particle morphology from nanospheres to nanowires. Monodisperse nanorods with lengths of 60 +/- 5 nm and diameters of 2-3 nm were self-assembled in a perpendicular oriented array onto a substrate surface using hexadecylamine as organic spacer. Magnetic alignment and properties assigned, respectively, to the shape anisotropy and the tetragonal phase suggest that the self-assembled materials are a strong candidate to solve the problem of random magnetic alignment observed in FePt nanospheres leading to applications in ultrahigh magnetic recording (UHMR) systems capable of achieving a performance of the order of terabits/in(2).

Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins

The immunosuppressant rapamycin inhibits Tor1p and Tor2p (target of rapamycin proteins), ultimately resulting in cellular responses characteristic of nutrient deprivation through a mechanism involving translational arrest. We measured the immediate transcriptional response of yeast grown in rich media and treated with rapamycin to investigate the direct effects of Tor proteins on nutrient-sensitive signaling pathways. The results suggest that Tor proteins directly modulate the glucose activation and nitrogen discrimination pathways and the pathways that respond to the diauxic shift (including glycolysis and the citric acid cycle). Tor proteins do not directly modulate the general amino acid control, nitrogen starvation, or sporulation (in diploid cells) pathways. Poor nitrogen quality activates the nitrogen discrimination pathway, which is controlled by the complex of the transcriptional repressor Ure2p and activator Gln3p. Inhibiting Tor proteins with rapamycin increases the electrophoretic mobility of Ure2p. The work presented here illustrates the coordinated use of genome-based and biochemical approaches to delineate a cellular pathway modulated by the protein target of a small molecule.

A new framework for force feedback teleoperation of robotic vehicles based on optical flow

This paper proposes the use of optical flow from a moving robot to provide force feedback to an operator's joystick to facilitate collision free teleoperation. Optic flow is measured by wide angle cameras on board the vehicle and used to generate a virtual environmental force that is reflected to the user through the joystick, as well as feeding back into the control of the vehicle. The coupling between optical flow (velocity) and force is modelled as an impedance - in this case an optical impedance. We show that the proposed control is dissipative and prevents the vehicle colliding with the environment as well as providing the operator with a natural feel for the remote environment. The paper focuses on applications to aerial robotics vehicles, however, the ideas apply directly to other force actuated vehicles such as submersibles or space vehicles, and the authors believe the approach has potential for control of terrestrial vehicles and even teleoperation of manipulators. Experimental results are provided for a simulated aerial robot in a virtual environment controlled by a haptic joystick.

Oestrogen-modulated gene expression in the human endometrium

To identify key regulatory mechanisms in the growth and development of the human endometrium, microarray analysis was performed on uncultured human endometrium collected during menstruation (M) and the late-proliferative (LATE-P)-phase of the menstrual cycle, as well as after 24 h incubation in the presence of oestradiol (17beta-E2). We demonstrate the expression of novel gene transcripts in the human endometrium. i.e. mucin-9, novel oestrogen-responsive gene transcripts, i.e. gelsolin and flotillin-1, and genes known to be expressed in human endometrium but not yet shown to be oestrogen responsive, i.e. connexin-37 and TFF1/pS2. Genes reported to be expressed during the implantation window and implicated in progesterone action, i.e. secretoglobin family 2A, member 2 (mammaglobin) and homeobox-containing proteins, were up-regulated in uncultured LATE-P-phase endometrium compared to M-phase endometrium. Some gene transcripts are regulated directly by 17beta-E2 alone, others are influenced by the in vivo environment as well. These observations emphasise that the regulation of endometrium maturation by oestrogen entails more then just stimulation of cell proliferation.

Dynamics of free-running, pump-modulated and coupled semiconductor and solid-state lasers

The output of a laser is a high frequency propagating electromagnetic field with superior coherence and brightness compared to that emitted by thermal sources. A multitude of different types of lasers exist, which also translates into large differences in the properties of their output. Moreover, the characteristics of the electromagnetic field emitted by a laser can be influenced from the outside, e.g., by injecting an external optical field or by optical feedback. In the case of free-running solitary class-B lasers, such as semiconductor and Nd:YVO4 solid-state lasers, the phase space is two-dimensional, the dynamical variables being the population inversion and the amplitude of the electromagnetic field. The two-dimensional structure of the phase space means that no complex dynamics can be found. If a class-B laser is perturbed from its steady state, then the steady state is restored after a short transient. However, as discussed in part (i) of this Thesis, the static properties of class-B lasers, as well as their artificially or noise induced dynamics around the steady state, can be experimentally studied in order to gain insight on laser behaviour, and to determine model parameters that are not known ab initio. In this Thesis particular attention is given to the linewidth enhancement factor, which describes the coupling between the gain and the refractive index in the active material. A highly desirable attribute of an oscillator is stability, both in frequency and amplitude. Nowadays, however, instabilities in coupled lasers have become an active area of research motivated not only by the interesting complex nonlinear dynamics but also by potential applications. In part (ii) of this Thesis the complex dynamics of unidirectionally coupled, i.e., optically injected, class-B lasers is investigated. An injected optical field increases the dimensionality of the phase space to three by turning the phase of the electromagnetic field into an important variable. This has a radical effect on laser behaviour, since very complex dynamics, including chaos, can be found in a nonlinear system with three degrees of freedom. The output of the injected laser can be controlled in experiments by varying the injection rate and the frequency of the injected light. In this Thesis the dynamics of unidirectionally coupled semiconductor and Nd:YVO4 solid-state lasers is studied numerically and experimentally.

High sensitivity detection of radio-frequency modulated magnetic moment in semiconductors

An experimental setup has been realized to measure weak magnetic moments which can be modulated at radio frequencies (similar to 1-5 MHz). Using an optimized radio-frequency (RF) pickup coil and lock-in amplifier, an experimental sensitivity of 10(-15) Am(2) corresponding to 10(-18) emu has been demonstrated with a 1 s time constant. The detection limit at room temperature is 9.3 x 10(-16) Am(2)/root Hz limited by Johnson noise of the coil. The setup has been used to directly measure the magnetic moment due to a small number (similar to 7 x 10(8)) of spin polarized electrons generated by polarization modulated optical radiation in GaAs and Ge. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3654229]

Plant reproductive traits mediate tritrophic feedback effects within an obligate brood-site pollination mutualism

Plants, herbivores and parasitoids affect each other directly and indirectly; however, feedback effects mediated by host plant traits have rarely been demonstrated in these tritrophic interactions. Brood-site pollination mutualisms (e.g. those involving figs and fig wasps) represent specialised tritrophic communities where the progeny of mutualistic pollinators and of non-mutualistic gallers (both herbivores) together with that of their parasitoids develop within enclosed inflorescences called syconia (hence termed brood-sites or microcosms). Plant reproductive phenology (which affects temporal brood-site availability) and inflorescence size (representing brood-site size) are plant traits that could affect reproductive resources, and hence relationships between trees, pollinators and non-pollinating wasps. Analysing wasp and seed contents of syconia, we examined direct, indirect, trophic and non-trophic relationships within the interaction web of the fig-fig wasp community of Ficus racemosa in the context of brood site size and availability. We demonstrate that in addition to direct resource competition and predator-prey (host-parasitoid) interactions, these communities display exploitative or apparent competition and trait-mediated indirect interactions. Inflorescence size and plant reproductive phenology impacted plant-herbivore and plant-parasitoid associations. These plant traits also influenced herbivore-herbivore and herbivore-parasitoid relationships via indirect effects. Most importantly, we found a reciprocal effect between within-tree reproductive asynchrony and fig wasp progeny abundances per syconium that drives a positive feedback cycle within the system. The impact of a multitrophic feedback cycle within a community built around a mutualistic core highlights the need for a holistic view of plant-herbivore-parasitoid interactions in the community ecology of mutualisms.

First experimental demonstration of low-cost VCSEL-intensity modulated end-to-end real-time optical OFDM signal transmission at 11.25Gb/s over 25km SSMFs

Low-cost, narrow modulation bandwidth, un-cooled VCSELs can be utilized to directly modulate 64-QAM-encoded 11.25Gb/s signals for end-to-end real-time optical OFDM transmission over 25km SSMF IMDD systems with excellent performance robustness. © 2011 Optical Society of America.

10 Gbit s(-1) electroabsorption-modulated laser light-source module using selective area MOVPE

A distributed-feedback (DFB) laser and a high-speed electroabsorption (EA) modulator are integrated, on the basis of the selective area MOVPE growth (SAG) technique and the ridge waveguide structure, for a 10 Gbit s(-1) optical transmission system. The integrated DFB laser/EA modulator device is packaged in a compact module with a 20% optical coupling efficiency to the single-mode fibre. The typical threshold current is 15 mA, and the side-mode suppression ratio is over 40 dB with the single-mode operation at 1550 nm. The module exhibits 1.2 mW fibre output power at a laser gain current of 70 mA and a modulator bias voltage of 0 V. The 3 dB bandwidth is 12 GHz. A dynamic extinction ratio of over 10 dB has been successfully achieved under 10 Gbit s(-1) non-return to zero (NRZ) operation, and a clearly open eye diagram is obtained.

A 10-GHz bandwidth electroabsorption modulated laser by ultra-low-pressure selective area growth

A novel integration technique has been developed using band-gap energy control of InGaAsP/InGaAsP multi-quantum-well (MQW) structures during simultaneous ultra-low-pressure (22 mbar) selective-area-growth (SAG) process in metal-organic chemical vapour deposition. A fundamental study of the controllability of band gap energy by the SAG method is performed. A large band-gap photoluminescence wavelength shift of 83nm is obtained with a small mask width variation (0-30 mu m). The method is then applied to fabricate an MQW distributed-feedback laser monolithically integrated with an electroabsorption modulator. The experimental results exhibit superior device characteristics with low threshold of 19 mA, over 24 dB extinction ratio when coupled into a single mode fibre. More than 10GHz modulation bandwidth is also achieved, which demonstrates that the ultra-low-pressure SAG technique is a promising approach for high-speed transmission photonic integrated circuits.

Electroabsorption-Modulated DFB laser Integrated.With dual-core spot-size converters

A 1.55-mu m single shallow ridge electroabsorptionmodulated distributed feedback laser that is monolithically integrated with a buried-ridge-stripe dual-core spot-size converter (SSC) at the input and output ports was fabricated by combining selective area growth, quantum-well intermixing, and dual-core integration techniques simultaneously. These devices exhibit a threshold current of 34 mA, a side mode suppression ratio of 38.0 dB, a 3-dB modulation bandwidth of 11.0 GHz, and a modulator extinction ratio of 25.0 dB dc. The output beam divergence angles of the SSC in the horizontal and vertical directions are as small as 7.3 degrees x 18 degrees, respectively, resulting in 3.2-dB coupling loss with a cleaved single-mode optical fiber.

Quantum coherence control of solid-state charge qubit by means of a suboptimal feedback algorithm

The quantum coherence control of a solid-state charge qubit is studied by using a suboptimal continuous feedback algorithm within the Bayesian feedback scheme. For the coherent Rabi oscillation, the present algorithm suggests a simple bang-bang control protocol, in which the control parameter is modulated between two values. For the coherence protection of the idle state, the present approach is applicable to arbitrary states, including those lying on the equator of the Bloch sphere which are out of control in the previous Markovian feedback scheme.