Pax9 and Jagged1 act downstream of Gli3 in vertabrate limb development

From early in limb development the transcription factor Gli3 acts to define boundaries of gene expression along the anterior-posterior (AP) axis, establishing asymmetric patterns required to provide positional information. As limb development proceeds, posterior mesenchyme expression of Sonic hedgehog (Shh) regulates Gli3 transcription and post-translational processing to specify digit number and identity. The molecular cascades dependent on Gli3 at later stages of limb development, which link early patterning events with final digit morphogenesis, remain poorly characterised. By analysing the transcriptional consequences of loss of Gli3 in the anterior margin of the E11.5 and E12.5 limb bud in the polydactylous mouse mutant extra-toes (Gli3(Xt/Xt)), we have identified a number of known and novel transcripts dependent on Gli3 in the limb. In particular, we demonstrated that the genes encoding the paired box transcription factor Pax9, the Notch ligand Jagged1 and the cell surface receptor Cdo are dependent on Gli3 for correct expression in the anterior limb mesenchyme. Analysis of expression in compound Shh;Gli3 mutant mouse embryos and in both in vitro and in vivo Shh signaling assays, further defined the importance of Shh regulated processing of Gli3 in controlling gene expression. In particular Pax9 regulation by Shh and Gli3 was shown to be context dependent, with major differences between the limb and somite revealed by Shh bead implantation experiments in the chick. Jagged1 was shown to be induced by Shh in the chick limb and in a C3H10T1/2 cell based signaling assay, with Shh;Gli3 mutant analysis indicating that expression is dependent on Gli3 derepression. Our data have also revealed that perturbation of early patterning events within the Gli3(Xt/Xt), limb culminates in a specific delay of anterior chondrogenesis which is subsequently realised as extra digits. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

NOVAS CONFIGURAÇÕES DAS FAMÍLIAS CONTEMPORÂNEAS: RUPTURAS E/OU CONTINUIDADES NOS DISCURSOS E PRÁTICAS DE METODISTAS E LUTERANOS ACERCA DO DIVÓRCIO E NOVOS CASAMENTOS

Na contemporaneidade, a família tradicional (pai, mãe, filhos) passou por mudanças de paradigmas, gerando novas configurações familiares, mais flexíveis e plurais. Nas novas configurações, o elemento de constituição não é só a partir dos laços de parentesco de nature-za biológica e civil, mas, principalmente, o da afetividade. Nesta dissertação, analisamos as rupturas e/ou continuidades dos discursos institucionais religiosos no protestantismo histórico, mais especificamente nas Igrejas Metodista e Luterana, acerca dos divórcios e novos casa-mentos. O objetivo da pesquisa foi o de identificar em que medida o posicionamento institu-cional religioso e a prática das comunidades de fé são coerentes e/ou dissonantes em relação às transformações experimentadas pela instituição família na contemporaneidade. Os docu-mentos utilizados para as análises foram: pastorais, jornais oficiais, atas, e demais documentos que foram pesquisados nos acervos da biblioteca da UMESP e no Portal Luteranos. A pesqui-sa de campo foi realizada através da aplicação de questionários e entrevistas aos sujeitos reli-giosos no município de Ferraz de Vasconcelos, nas Igrejas Metodista e Luterana. Através da análise documental e da pesquisa de campo, buscamos identificar o impacto que as novas con-figurações familiares causaram sobre o discurso institucional e sobre a prática eclesial.

RESILIÊNCIA EM IDOSOS QUE MEDITAM

Resiliência é definida como a capacidade das pessoas em enfrentar, vencer e serem fortalecidos ou transformados por experiências adversas. Estudos têm mostrado que pessoas resilientes adoecem menos e possuem melhor desempenho no trabalho, nas relações familiares e na vida, além da resiliência poder ser desenvolvida desde a infância até a velhice. Por sua vez, a meditação tem mostrado ser um recurso útil para a melhoria da saúde em geral, incluindo a qualidade de vida daqueles que a praticam por proporcionar maiores níveis de bem estar, melhoria nos relacionamentos interpessoais e redução de estresse. Parece que a meditação, assim como a resiliência, pode contribuir para melhores níveis de saúde da população. O objetivo deste estudo foi verificar os níveis de resiliência em idosos que meditam. Participaram 60 pessoas, sendo 78% mulheres, com idade média de 69 anos, 82% aposentados, 65% praticantes de meditação, 42% com baixa escolaridade e 60% católicos. O instrumento utilizado foi um questionário auto-aplicável, composto pela Escala de Avaliação de Resiliência (EAR) em sua forma reduzida e um questionário para coletar dados sociodemográficos dos participantes. Análise de variância revelou não haver diferença nos níveis de resiliência entre o grupo que medita uma vez ao dia e aquele que o faz mais do que uma vez ao dia. Médias fatoriais e desvios-padrão revelaram que os participantes possuem capacidade levemente acima da média de adaptarem-se positivamente diante das dificuldades da vida, persistindo para superar crises e adversidades, poucas vezes se resignando, embora algumas vezes não se julguem competentes para enfrentá-las. Para defrontarem as dificuldades da vida, contam com as crenças de que podem confiar no apoio de um ente ou algo superior e acreditam que podem aprender e melhorar com as adversidades.

Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity

Tuberculosis (TB) is an escalating global health problem and improved vaccines against TB are urgently needed. HLA-E restricted responses may be of interest for vaccine development since HLA-E displays very limited polymorphism (only 2 coding variants exist), and is not down-regulated by HIV-infection. The peptides from Mycobacterium tuberculosis (Mtb) potentially presented by HLA-E molecules, however, are unknown. Here we describe human T-cell responses to Mtb-derived peptides containing predicted HLA-E binding motifs and binding-affinity for HLA-E. We observed CD8(+) T-cell proliferation to the majority of the 69 peptides tested in Mtb responsive adults as well as in BCG-vaccinated infants. CD8(+) T-cells were cytotoxic against target-cells transfected with HLA-E only in the presence of specific peptide. These T cells were also able to lyse M. bovis BCG infected, but not control monocytes, suggesting recognition of antigens during mycobacterial infection. In addition, peptide induced CD8(+) T-cells also displayed regulatory activity, since they inhibited T-cell proliferation. This regulatory activity was cell contact-dependent, and at least partly dependent on membrane-bound TGF-beta. Our results significantly increase our understanding of the human immune response to Mtb by identification of CD8(+) T-cell responses to novel HLA-E binding peptides of Mtb, which have cytotoxic as well as immunoregulatory activity.

Design and implementation of graphical user interfaces for complex simulations

The development of increasingly powerful computers, which has enabled the use of windowing software, has also opened the way for the computer study, via simulation, of very complex physical systems. In this study, the main issues related to the implementation of interactive simulations of complex systems are identified and discussed. Most existing simulators are closed in the sense that there is no access to the source code and, even if it were available, adaptation to interaction with other systems would require extensive code re-writing. This work aims to increase the flexibility of such software by developing a set of object-oriented simulation classes, which can be extended, by subclassing, at any level, i.e., at the problem domain, presentation or interaction levels. A strategy, which involves the use of an object-oriented framework, concurrent execution of several simulation modules, use of a networked windowing system and the re-use of existing software written in procedural languages, is proposed. A prototype tool which combines these techniques has been implemented and is presented. It allows the on-line definition of the configuration of the physical system and generates the appropriate graphical user interface. Simulation routines have been developed for the chemical recovery cycle of a paper pulp mill. The application, by creation of new classes, of the prototype to the interactive simulation of this physical system is described. Besides providing visual feedback, the resulting graphical user interface greatly simplifies the interaction with this set of simulation modules. This study shows that considerable benefits can be obtained by application of computer science concepts to the engineering domain, by helping domain experts to tailor interactive tools to suit their needs.

Unrepeatered field transmission of 2 Tbit/s multi-banded coherent WDM over 124 km of installed SMF

In this paper we report field transmission of a 2Tbit/s multi-banded Coherent WDM signal over BT Ireland's installed SMF, using EDFA amplification only, with mixed Ethernet (with FEC) and PRBS payloads. To the best of our knowledge, the results obtained represent the highest total capacity transmitted over installed SMF with orthogonal subcarriers. BERs below 10(-5) and no frame-loss were recorded for all 49 subcarriers. Extended BER measurements over several hours showed fluctuations that can be attributed to PMD and to dynamic effects associated with clock instabilities.

PMD tolerance of 288 Gbit/s Coherent WDM and transmission over unrepeatered 124 km of field-installed single mode optical fiber

Low-cost, high-capacity optical transmission systems are required for metropolitan area networks. Direct-detected multi-carrier systems are attractive candidates, but polarization mode dispersion (PMD) is one of the major impairments that limits their performance. In this paper, we report the first experimental analysis of the PMD tolerance of a 288Gbit/s NRZ-OOK Coherent Wavelength Division Multiplexing system. The results show that this impairment is determined primarily by the subcarrier baud rate. We confirm the robustness of the system to PMD by demonstrating error-free performance over an unrepeatered 124km field-installed single-mode fiber with a negligible penalty of 0.3dB compared to the back-to-back measurements. (C) 2010 Optical Society of America

Impact of Raman amplification on a 2 Tb/s coherent WDM system

The impact of hybrid erbium-doped fiber amplifier (EDFA)/Raman amplification on a spectrally efficient coherent-wavelength-division-multiplexed (CoWDM) optical communication system is experimentally studied and modeled. Simulations suggested that 23-dB Raman gain over an unrepeatered span of 124 km single-mode fiber would allow a decrease of the mean input power of ~6 dB for a fixed bit-error rate (BER). Experimentally we demonstrated 1.2-dB Q-factor improvement for a 2-Tb/s seven-band CoWDM with backward Raman amplification. The system delivered an optical signal-to-noise ratio of 35 dB at the output of the receiver preamplifier providing a worst-case BER of 2 × 10 -6 over 49 subcarriers at 42.8 Gbaud, leaving a system margin (in terms of Q -factor) of ~4 dB from the forward-error correction threshold.

Towards a practical implementation of coherent WDM:analytical, numerical, and experimental studies

Future optical networks will require the implementation of very high capacity (and therefore spectral efficient) technologies. Multi-carrier systems, such as Orthogonal Frequency Division Multiplexing (OFDM) and Coherent WDM (CoWDM), are promising candidates. In this paper, we present analytical, numerical, and experimental investigations of the impact of the relative phases between optical subcarriers of CoWDM systems, as well as the effect that the number of independently modulated subcarriers can have on the performance. We numerically demonstrate a five-subcarrier and three-subcarrier 10-GBd CoWDM system with direct detected amplitude shift keying (ASK) and differentially/coherently detected (D) phase shift keying (PSK). The simulation results are compared with experimental measurements of a 32-Gbit/s DPSK CoWDM system in two configurations. The first configuration was a practical 3-modulator array where all three subcarriers were independently modulated, the second configuration being a traditional 2-modulator odd/even configuration, where only odd and even subcarriers were independently modulated. Simulation and experimental results both indicate that the independent modulation implementation has a greater dependency on the relative phases between subcarriers, with a stronger penalty for the center subcarrier than the odd/even modulation scheme.

Comparison of frequency symmetric signal generation from a BPSK input using fiber and semiconductor-based nonlinear elements

This letter compares two nonlinear media for simultaneous carrier recovery and generation of frequency symmetric signals from a 42.7-Gb/s nonreturn-to-zero binary phase-shift-keyed input by exploiting four-wave mixing in a semiconductor optical amplifier and a highly nonlinear optical fiber for use in a phase-sensitive amplifier.

DPSK signal regeneration with a dual-pump nondegenerate phase-sensitive amplifier

We demonstrate, for the first time to our knowledge, regeneration of a 42.66-Gb/s differential phase-shift keyed signal using a dual-pump nondegenerate four-wave-mixing-based fiber-optic parametric amplifier. The regenerative performance of the subsystem is characterized in terms of bit-error rate against narrowband and wideband introduced noise. While a strong receiver sensitivity improvement, up to 20 dB, is noticed against narrowband noise, against quasi-random (wideband) noise we observe a regeneration of 2.7 dB.

Demonstration of CoWDM using DPSK modulator array with injection-locked lasers

A practical implementation of coherent wavelength division multiplexing (CoWDM) is demonstrated for the first time using injection-locked lasers and a DPSK modulator array. For a 31.99 Gbit/s system (three subcarriers at 10.664 Gbit/s) the null-to-null spectral bandwidth was only 42.656 GHz and the average receiver sensitivity measured was -33.5 dBm when all subcarrier phases were optimised.

Integration of a 3D hydrogel matrix within a hollow core photonic crystal fibre for DNA probe immobilization

In this paper, we demonstrate the integration of a 3D hydrogel matrix within a hollow core photonic crystal fibre (HC-PCF). In addition, we also show the fluorescence of Cy5-labelled DNA molecules immobilized within the hydrogel formed in two different types of HC-PCF. The 3D hydrogel matrix is designed to bind with the amino groups of biomolecules using an appropriate cross-linker, providing higher sensitivity and selectivity than the standard 2D coverage, enabling a greater number of probe molecules to be available per unit area. The HC-PCFs, on the other hand, can be designed to maximize the capture of fluorescence to improve sensitivity and provide longer interaction lengths. This could enable the development of fibre-based point-of-care and remote systems, where the enhanced sensitivity would relax the constraints placed on sources and detectors. In this paper, we will discuss the formation of such polyethylene glycol diacrylate (PEGDA) hydrogels within a HC-PCF, including their optical properties such as light propagation and auto-fluorescence.

First demonstration of 2μm data transmission in a low-loss hollow core photonic Bandgap fiber

The first demonstration of a hollow core photonic bandgap fiber suitable for high-rate data transmission at 2µm is presented. Using a custom built Thulium doped fiber amplifier, error-free 8Gbit/s transmission in an optically amplified data channel at 2008nm is reported for the first time.

Nonlinear pulse distortion in few-mode fiber

Nonlinear pulse propagation in a few mode fiber is experimentally investigated, by measuring temporal and phase responses of the output pulses by use of a frequency discriminator technique, showing that self-phase modulation, dispersion and linear mode-coupling are the dominant effects.