Translating the combination of gene therapy and tissue engineering for treating recessive dystrophic epidermolysis bullosa.

The combination of gene therapy and tissue engineering is one of the most promising strategies for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). RDEB is a rare genetic disease characterised by mutations in the COL7A1 gene, encoding type VII collagen (COLVII), which forms anchoring fibrils at the dermal-epidermal junction of the skin. This disease causes severe blistering and only palliative treatments are offered. In this study, the base of a strategy combining gene therapy and a tissue-engineered skin substitute (TES), which would be suitable for the permanent closure of skin wounds, was set-up. As a high transduction efficiency into fibroblasts and/or keratinocytes seems to be a prerequisite for a robust and sustained correction of RDEB, different envelope pseudotyped retroviral vectors and the transduction enhancer EF-C were tested. When green fluorescent protein (GFP) was used as a reporter gene to evaluate the retroviral-mediated gene transfer, the fibroblast infection efficiency was 30 % higher with the Ampho pseudotyped vector as compared with the other pseudotypes. At least a 3.1-fold and a 1.3-fold increased transduction were obtained in fibroblasts and keratinocytes, respectively, with EF-C as compared with polybrene. A continuous and intense deposit of haemagglutinin (HA)-COLVII was observed at the dermal-epidermal junction of self-assembled TESs made of cells transduced with a HA-tagged COL7A1 vector. Furthermore, HA-tagged basal epidermal cells expressing keratin 19 were observed in TESs, suggesting stem cell transduction. This approach could be a valuable therapeutic option to further develop, in order to improve the long-term life quality of RDEB patients.

Segmented silicon MZM for PAM-8 transmissions at 114 Gb/s with binary signaling.

We experimentally demonstrate PAM-8 generation from binary electrical signals driving a silicon multi-electrode Mach-Zehnder modulator acting as an optical digital-to-analog converter. Measured BER in back-to-back configuration is used to evaluate signal quality. We demonstrate 38 GBd PAM-8 transmission below the forward error correction (FEC) threshold using minimum mean square error (MMSE) equalization. The results show that modulators with segmented phase shifters can be advantageously used to eliminate the need for high bandwidth electronic digital-to-analog converters in the generation of multilevel signals. These modulators, that can be designed and fabricated with standard CMOS compatible tools and processes, are of high interest for short range high-speed data links.

Dual phase-shift Bragg grating silicon photonic modulator operating up to 60 Gb/s.

We demonstrate PAM-4 and OOK operation of a novel silicon photonic modulator. The modulator design is based on two phase-shifts in a Bragg Grating structure driven in a push pull configuration. Back-to-back PAM-4 modulation is demonstrated below the FEC threshold at up to 60 Gb/s. OOK modulation is also shown up to 55 Gb/s with MMSE equalization and up to 50 Gb/s without equalization. Eye diagrams and BER curves at different bit rates are provided for both PAM-4 and OOK modulations. To our knowledge, this structure is the fastest silicon photonic modulator based on Bragg gratings, reaching modulation speed comparable to the fastest Mach-Zehnder modulators and micro-ring modulators.

Characterization of OAM fibers using fiber Bragg gratings.

The reflectogram of a fiber grating is used to characterize vector modes of an optical fiber supporting orbital angular momentum states. All modes, with a minimal effective index separation around 10(-4), are simultaneously measured. OAM states are reflected by the FBG, along with a charge inversion, at the center wavelength of the Bragg reflection peak of the corresponding fiber vector mode.

Few-mode fiber with inverse-parabolic graded-index profile for transmission of OAM-carrying modes.

A novel type of few-mode fiber, characterized by an inverse-parabolic graded-index profile, is proposed for the robust transmission of cylindrical vector modes as well as modes carrying quantized orbital angular momentum (OAM). Large effective index separations between vector modes (>2.1 × 10(-4)) are numerically calculated and experimentally confirmed in this fiber over the whole C-band, enabling transmission of OAM(+/-1,1) modes for distances up to 1.1 km. Simple design rules are provided for the optimization of the fiber parameters.

264 W output power at 1585 nm in Er-Yb codoped fiber laser using in-band pumping.

We demonstrate a high-power cladding-pumped Er-Yb codoped fiber laser with 74% efficiency. A pump-limited output power of 264 W is obtained using in-band pumping at 1535 nm. We compare the efficiency of 1480 and 1535 nm pumping through numerical simulations and experimental measurements.

Towards REPO4 nanocrystal-doped optical fibers for distributed sensing applications.

Rayleigh scattering enhanced nanoparticle-doped optical fibers, for distributed sensing applications, is a new technology that offers unique advantages to optical fiber community. However, the existing fabrication technology, based on in situ grown alkaline earth nanoparticles, is restricted to few compositions and exhibit a great dependence on many experimental conditions. Moreover, there is still several uncertainties about the effect of drawing process on the nanoparticle characteristics and its influence on the scattering enhancement and the induced optical loss. In this work, we shed light on all these issues that prevent the progress in the field and demonstrate the suitability of doping optical fibers with YPO4 nanocrystals for developing tunable Rayleigh scattering enhanced nanoparticle-doped optical fibers. An exhaustive 3D microstructural study reveals that their features are closely linked to the fiber drawing process, which allow the size and shape engineering at the nanoscale. In particular, the YPO4 nanocrystals preserve their features to a large extent when the optical fibers are drawn below 1950 °C, which allows obtaining homogeneous nanocrystal features and optical performance. Fabricated fibers exhibit a tunable enhanced backscattering in the range of 15.3-54.3 dB, with respect to a SMF-28 fiber, and two-way optical losses in the range 0.3-160.7 dB/m, revealed by Optical Backscatter Reflectometry (OBR) measurements. This allows sensing lengths from 0.3 m up to more than 58 m. The present work suggests a bright future of YPO4 nanocrystals for distributed sensing field and open a new gate towards the incorporation of other rare-earth orthophosphate (REPO4) nanocrystals with pre-defined characteristics that will overcome the limitations of the current in situ grown alkaline earth-based technology.

UV-induced modification of stress distribution in optical fibers and its contribution to Bragg grating birefringence.

This paper discusses the importance of stress-induced contributions to the photo-induced birefringence observed in fiber Bragg gratings. Optical tomography measurements are performed in exposed and unexposed fibers to extract the stress profiles induced by UV-writing of fiber Bragg gratings for various exposure levels. A photoelastic analysis and a high-order isoparametric finite elements method are then used to calculate the birefringence caused by stress profile modifications. The results are compared to the birefringence directly measured by spectral analysis of a chirped fiber grating with multiple phase-shifts. We can therefore estimate the fraction of the photo-induced birefringence due to stress-induced anisotropy following UV exposure.

Optical multicarrier generator for radio-over-fiber systems.

We propose an optical multicarrier generation method for radio-over-fiber (ROF) systems. The multicarrier generator is composed of a phase-modulated laser and two chirped fiber Bragg gratings used as flattening filters. The chirped gratings are spectrally tailored to equalize the intrinsically uneven envelope of the phase-modulated laser spectrum. A flattened multicarrier spectrum with 7 carriers at a frequency spacing of 12.5 GHz is demonstrated with less than 2 dB peak-to-peak variations and 40 dB optical signal-to-noise ratio (OSNR). We evaluate the quality of the multicarrier generator by using it as an externally modulated source for 802.11 compliant signals. We performed error vector magnitude (EVM) measurements on each of the filtered carrier and found an average value of 32.8 dB compared to 36.2 dB for a tunable laser source. The results show that the multicarrier source could be used for error free transmission.

High-resolution x-ray study of nematic-smectic-A and smectic-A-reentrant-nematic transitions in liquid-crystal-aerosil gels.

We have studied the effects of quenched random disorder created by dispersed aerosil nanoparticle gels on the nematic to smectic- A (N- SmA ) and smectic- A to reentrant nematic ( SmA -RN) phase transitions of thermotropic liquid-crystal mixtures of hexyloxycyanobiphenyl (6OCB) and octyloxycyanobiphenyl (8OCB). These effects are probed using high-resolution synchrotron x-ray diffraction techniques. We find that the reentrant characteristics of the system are largely unchanged by the presence of the aerosil gel network. By comparing measurements of the smectic static structure amplitude for this 8OCB- 6OCB+aerosil system with those for butyloxybenzilidene-octylaniline (4O.8)+aerosil gels, we find that the short-range smectic order in the smectic- A phase is significantly weaker in the reentrant system. This result is consistent with the behavior seen in pure 8OCB-6OCB mixtures. The strength of the smectic ordering decreases progressively as the 6OCB concentration is increased. Detailed line shape analysis shows that the high- and low-temperature nematic phases (N and RN) are similar to each other.

High-resolution x-ray scattering study of the effect of quenched random disorder on the nematic-smectic-A transition.

Using high-resolution x-ray scattering, the effect of quenched random disorder (QRD) on the second-order nematic-smectic-A (N-SmA) phase transition in butyloxybenzilidene-octylaniline (4O.8) has been studied. 4O.8 is a nonpolar liquid crystal (LC) with a monomeric smectic-A phase. The QRD is created by aerosil nanoparticles which gelate to form a three-dimensional network, confining the LC. The QRD caused by the aerosil gel generates quenched random fields acting on both the nematic and smectic-A order parameters. This results in the destruction of the quasi-long-range order of the smectic-A phase. The x-ray scattering data are modeled with a structure factor composed of two terms, one thermal and one static, corresponding to the connected and disconnected susceptibilities, respectively. Unlike previous studies, the two parts of the structure factor are decoupled by allowing different thermal and static correlation lengths. Our fitting procedure involves temperature-dependent and temperature-independent (global) variables. The amplitude and the parallel correlation length for the thermal part of the line-shape show critical-like behavior both above and below the transition temperature. Detailed analysis reveals that the thermal correlation length does not truly diverge at the phase transition. This effect is discussed on the basis of a cutoff for the divergence caused by the random fields generated by the aerosil network confining the liquid crystal. The intensity of the static term in the line-shape behaves like the order parameter squared at a conventional second-order phase transition. The effective order parameter critical exponent shows an evolution with increasing aerosil gel density ranging from the Gaussian tricritical value to the 3D- XY value. The results of a pseudocritical scaling analysis are compared to an analysis of 4O.8+aerosil heat capacity data and discussed using a phenomenological correlation between the nematic range of pure liquid crystals and the aerosil mass density, rho{s}.

Effects of disorder on a smectic--nematic phase transition.

Using x-ray scattering, we have studied the nematic to smectic- phase transition of the liquid crystal butyloxybenzilidene-octylaniline confined in an aerosil network. We find that the disorder introduced by the aerosil network destroys the long-range nature of the phase transition, and that the transition becomes similar to that observed in a finite-size system, with finite low-temperature correlation lengths of the ordered moments and a power-law behavior of the order parameter with respect to the reduced temperature observable in a limited temperature range. We also show evidence for a systematic evolution of the effective order parameter critical exponent beta with increasing disorder.

Molecular cloning of the Drosophila homologue of the rat ribosomal protein L11 gene.

We report the isolation of the Drosophila melanogaster homologue of the rat ribosomal protein L11 gene. The gene is present in the Drosophila genome at polytene chromosome location 56D, on the right arm of the second chromosome. The Drosophila DL11 gene appears to encode two messages of 0.8 and 0.9 kb which are expressed throughout development with variations in their relative abundance. DL11 codes for a predicted protein of 184 amino acids with a molecular mass of 21.1 kDa.

The Drosophila melanogaster homolog of the mammalian MAPK-activated protein kinase-2 (MAPKAPK-2) lacks a proline-rich N-terminus.

Recently, a mammalian kinase cascade was discovered that is triggered by stress and heat shock, and leads to the stimulation of mitogen-activated protein kinase (MAPK)-activated protein kinase-2 (MAPKAPK-2). Surprisingly, this process turns out to be independent of the classical MAPK. The stress-induced activation of MAPKAPK-2, in turn, results in the phosphorylation of small heat-shock proteins (Hsp). We have isolated a Drosophila melanogaster (Dm) cDNA encoding a polypeptide that has extensive sequence similarity to the mammalian MAPKAPK-2. As in mammalian MAPKAPK-2, the Dm MAPKAPK-2 possesses a MAPK phosphorylation site and a nuclear targeting sequence located C-terminal to the catalytic domain. However, in contrast to its mammalian counterpart, it lacks the Pro-rich N-terminal region proposed to form Src-homology domain 3 (SH3) binding domains. A 2.4-kb MAPKAPK-2 message is expressed throughout development, while two shorter transcripts of 2.3 and 1.8 kb appear to be specifically expressed in the germline. The 1.8-kb transcript results from the usage of an atypical germline-specific polyadenylation signal (AATATA) located early within the 3' untranslated region. Dm MAPKAPK-2 is located at cytological position 5D in the Dm genome.

Form birefringence in UV-exposed photosensitive fibers computed using a higher order finite element method.

The effective index change and form birefringence are calculated in UV-exposed fibers using a high-order vectorial finite element method. The birefringence is compared in optical fibers with and without photosensitive inner cladding.

Subtle neuropsychological deficits in patients with good recovery after closed head injury.

This study demonstrates residual mental deficits in patients who have apparently recovered after closed head injury. Twenty closed head injury patients were compared to 20 normal control subjects matched for age, sex, handedness, education, language, and IQ. All received a series of neuropsychological tests. Discriminant function analysis significantly differentiated the two groups. Correct classification of individuals as having suffered a head injury or not was 85%. The head injury patients did have primary impairment on tests of divided attention. Litigation was not a factor. We propose that this impairment of information processing reflects residual brain damage secondary to the closed head injury.

Context and the allocation of resources in word recognition.

Three experiments are reported that investigate the effects of context on the use of limited processing resources in word recognition. On each trial in all of the experiments, the subjects were presented with an incomplete sentence followed by a target display containing a word and two digits. In all cases, accuracy at reporting the word was affected by context, as expected. The effect of context on processing resources was examined by considering the accuracy of reports of the digits in cases in which the word did or did not fit the context. Accuracy of digit report was greater for digits surrounding words in related context, but only when the subjects were required to report the word before reporting the digits. There was no effect of word context on the digit report when subjects had to report the digits first. There was likewise no effect on accuracy of digit report when subjects were required to report only the word or only the digits, even when the cue was presented 250 msec after the target display was replaced by a patterned mask. The results suggest that the effect of context on the resources consumed in word recognition is restricted to aspects of processing that can be delayed until the subject is required to select an overt response, and a simple interpretation of the results may be given in terms of a slight modification of Morton's model of the interaction of stimulus information and context.

What some effects might not be: the time to verify membership in "well-defined" categories.

Armstrong, Gleitman, and Gleitman (1983) reported shorter categorization times for members of well-defined categories judged more typical. They concluded that these effects could not originate in a graded, similarity-based category representation and consequently that the typicality effects obtained with natural categories might not be indicative of such a structure either. In this article, we re-examine this conclusion, focusing first on the performance obtained with well-defined categories of different sizes. Only the larger categories used showed variations in typicality ratings and produced typicality effects on categorization times. However, multiple regression analyses showed the effects on categorization times to be better explained by a measure of associative strength, called category dominance. The range of various predictor variables was equated in a follow-up experiment involving large, natural, and well-defined categories. Results obtained with well-defined categories showed pronounced dominance effects when typicality was controlled, but no reliable typicality effect when category dominance and instance familiarity were controlled. Results were opposite for natural categories. By showing that well-defined categories fail to produce unbiased typicality effects, our results bring added support to the hypothesis that the effects obtained with natural categories originate in a graded, similarity-based category structure.

The neuropsychology of paramedian thalamic infarction.

A longitudinal study of three patients with CT-scan documented paramedian thalamic infarctions (bilateral, primarily right, unilateral left) is reported and the neuropsychology of human paramedian thalamic infarction is reviewed. The neuropsychological deficits following these selected lesions, the nature of the clinical memory disorder, and the neuroanatomy of memory are discussed. The significance of cortical/subcortical relationship in explaining observed behavioral changes is emphasized. Brain damage with maximum involvement in the dorsomedial nuclei and mamillothalamic tracts appears to cause primarily a memory disorder and frontal-limbic behavioral changes, the severity and profile of deficits depending on lesion extent and location. Both anterograde and remote memory loss may be present. Asymmetry in memory at the level of the thalamus was observed, following the left-verbal, right-nonverbal dichotomy.