The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues

Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, leading to reduced expression of frataxin protein. Evidence suggests that the mutation may induce epigenetic changes and heterochromatin formation, thereby impeding gene transcription. In particular, studies using FRDA patient blood and lymphoblastoid cell lines have detected increased DNA methylation of specific CpG sites upstream of the GAA repeat and histone modifications in regions flanking the GAA repeat. In this report we show that such epigenetic changes are also present in FRDA patient brain, cerebellum and heart tissues, the primary affected systems of the disorder. Bisulfite sequence analysis of the FXN flanking GAA regions reveals a shift in the FRDA DNA methylation profile, with upstream CpG sites becoming consistently hypermethylated and downstream CpG sites becoming consistently hypomethylated. We also identify differential DNA methylation at three specific CpG sites within the FXN promoter and one CpG site within exon 1. Furthermore, we show by chromatin immunoprecipitation (ChIP) analysis that there is overall decreased histone H3K9 acetylation together with increased H3K9 methylation of FRDA brain tissue. Further studies of brain, cerebellum and heart tissues from our GAA repeat expansion-containing FRDA YAC transgenic mice reveal comparable epigenetic changes to those detected in FRDA patient tissue. We have thus developed a mouse model that will be a valuable resource for future therapeutic studies targeting epigenetic modifications of the FXN gene to increase frataxin expression

Design of a compact SOI polarization rotator for mid-IR application

Design of a compact polarization rotator (PR) exploiting power coupling through phase matching between the TM mode of a strip waveguide (WG) and TE mode of a vertical slot WG is presented. Optimized cross sectional dimensions of the coupler have been achieved to use this device as a compact PR at 3 μm wavelength with device length of just 2 mm. We also investigate the device performance at the operating wavelength (λ) = 1.55 μm

Design and Performance Study of a Compact SOI Polarization Rotator at 1.55 mu m

We numerically design a compact silicon (Si) based polarization rotator (PR) by exploiting power coupling through phase matching between the TM mode of a Si strip waveguide (WG) and TE mode of a Si-air vertical slot WG. In such structures, the coupling occurs due to horizontal structural asymmetries and extremely high modal hybridness due to high refractive index contrast of Si-on-insulator (SOI) structure. Design parameters of the coupler have been optimized to achieve a compact PR of ~135 μm length at the telecommunication wavelength of 1.55 μm. Maximum power coupling efficiency Cm, which is studied by examining the transmittance of light, is achieved as high as 80% for both polarization conversions. Fabrication tolerances and the band width of operation of the designed PR have also been studied

Response Functions to Critical Shocks in Social Sciences: An Empirical and Numerical Study

We show that, provided one focuses on properly selected episodes, one can apply to the social sciences the same observational strategy that has proved successful in natural sciences such as astrophysics or geodynamics. For instance, in order to probe the cohesion of a policy, one can, in different countries, study the reactions to some huge and sudden exogenous shocks, which we call Dirac shocks. This approach naturally leads to the notion of structural (as opposed or complementary to temporal) forecast. Although structural predictions are by far the most common way to test theories in the natural sciences, they have been much less used in the social sciences. The Dirac shock approach opens the way to testing structural predictions in the social sciences. The examples reported here suggest that critical events are able to reveal pre-existing ``cracks'' because they probe the social cohesion which is an indicator and predictor of future evolution of the system, and in some cases foreshadows a bifurcation. We complement our empirical work with numerical simulations of the response function (``damage spreading'') to Dirac shocks in the Sznajd model of consensus build-up. We quantify the slow relaxation of the difference between perturbed and unperturbed systems, the conditions under which the consensus is modified by the shock and the large variability from one realization to another

Possible manifestation of spin fluctuations in the temperature behavior of resistivity in Sm_{1.85}Ce_{0.15}CuO_4 thin films

A pronounced step-like (kink) behavior in the temperature dependence of resistivity $\rho (T)$ is observed in the optimally-doped $Sm_{1.85}Ce_{0.15}CuO_4$ thin films around $T_{sf}=87K$ and attributed to manifestation of strong spin fluctuations induced by $Sm^{3+}$ moments with the energy $\hbar \omega_{sf}=k_BT_{sf}\simeq 7meV$. In addition to fluctuation induced contribution $\rho_{sf}(T)$ due to thermal broadening effects (of the width $\omega_{sf}$), the experimental data are found to be well fitted accounting for residual (zero-temperature) $\rho_{res}$, electron-phonon $\rho _{e-ph}(T)=AT$ and electron-electron $\rho_{e-e}(T)=BT^2$ contributions. The best fits produced $\omega_p=2.1meV$, $\tau_0^{-1}=9.5\times 10^{-14}s^{-1}$, $\lambda =1.2$, and $E_F=0.2eV$ for estimates of the plasmon frequency, the impurity scattering rate, electron-phonon coupling constant, and the Fermi energy, respectively.Comment: 6 pages (REVTEX4), 2 EPS figures; accepted for publication in JETP Letter

Design of a Polymer-Based Hollow-Core Bandgap Fiber for Low-Loss Terahertz Transmission

We use numerical simulations to design a hollowcore microstructured polymer optical fiber (HC-mPOF) suitable for broadband, terahertz (THz) pulse transmission with relatively low losses and small dispersion. The HC-mPOF consists of a central large air-core surrounded by periodically arranged wavelength-scale circular air holes in a hexagonal pattern, embedded in a uniform Teflon matrix. The THz guidance in this fiber is achieved by exploiting the photonic bandgap (PBG) effect. In our low index contrast Teflon-air (1.44:1) hexagonal periodic lattice, the PBG appears only for a certain range of non-zero values of the longitudinal wavevector. We have achieved PBG over a broad spectral range (bandwidth ~400 GHz) ranging from 1.65 to 2.05 THz in the proposed HC-mPOF. The achievable loss coefficient in our designed HC-mPOF is <;4 m-1 and the group velocity dispersion parameter is <;±5 ps/THz·cm over a 300-GHz bandwidth (1.65~1.95 THz)

An efficient polarization converter for Mid-IR wavelength

Design of a silicon-based polarization converter through phase matched power coupling between TE and TM modes is presented. Conversion efficiency up to 90% is feasible at 3 μm wavelength with device length of 536 μm

A pervasive approach to a real-time intelligent decision support system in intensive medicine

The decision on the most appropriate procedure to provide to the patients the best healthcare possible is a critical and complex task in Intensive Care Units (ICU). Clinical Decision Support Systems (CDSS) should deal with huge amounts of data and online monitoring, analyzing numerous parameters and providing outputs in a short real-time. Although the advances attained in this area of knowledge new challenges should be taken into account in future CDSS developments, principally in ICUs environments. The next generation of CDSS will be pervasive and ubiquitous providing the doctors with the appropriate services and information in order to support decisions regardless the time or the local where they are. Consequently new requirements arise namely the privacy of data and the security in data access. This paper will present a pervasive perspective of the decision making process in the context of INTCare system, an intelligent decision support system for intensive medicine. Three scenarios are explored using data mining models continuously assessed and optimized. Some preliminary results are depicted and discussed.Fundação para a Ciência e a Tecnologia (FCT