A diet rich in omega-3 fatty acids enhances expression of soluble epoxide hydrolase in murine brain.

Several studies suggest that intake of omega-3 polyunsaturated fatty acids (n3-PUFA) beneficially influences cognitive function. However, effects on the adult brain are not clear. Little is known about the impact of dietary intervention on the fatty acid profile in adult brain, the modulation in the expression of enzymes involved in fatty acid biosynthesis and metabolism as well as changes in resulting oxylipins. These questions were addressed in the present study in two independent n3-PUFA feeding experiments in mice. Supplementation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA, 1% each in the diet) for 30days to adult NMRI and C57BL/6 mice led to a distinct shift in the brain PUFA pattern. While n3-PUFAs EPA, n3 docosapentaenoic acid and DHA were elevated, many n6-PUFAs were significantly decreased (except, e.g. C20:3 n6 which was increased). This shift in PUFAs was accompanied by immense differences in concentrations of oxidative metabolites derived from enzymatic conversion of PUFAs, esp. arachidonic acid whose products were uniformly decreased, and a modulation in the activity and expression pattern of delta-5 and delta-6 desaturases. In both mouse strains a remarkable increase in the soluble epoxide hydrolase (sEH) activity (decreased epoxy-FA concentrations and epoxy-FA to dihydroxy-FA-ratios) as well as sEH expression was observed. Taking the high biological activity of epoxy-FA, e.g. on blood flow and nociceptive signaling into account, this finding might be of relevance for the effects of n3-PUFAs in neurodegenerative diseases. On any account, our study suggests a new distinct regulation of brain PUFA and oxylipin pattern by supplementation of n3-PUFAs to adult rodents.

Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro.

Free fatty acids (FFA), hyperglycemia, and inflammatory cytokines are major mediators of ß-cell toxicity in type 2 diabetes mellitus, impairing mitochondrial metabolism. Glutaredoxin 5 (Glrx5) is a mitochondrial protein involved in the assembly of iron-sulfur clusters required for complexes of the respiratory chain. We have provided evidence that islet cells are deprived of Glrx5, correlating with impaired insulin secretion during diabetes in genetically obese mice. In this study, we induced diabesity in C57BL/6J mice in vivo by feeding the mice a high-fat diet (HFD) and modelled the diabetic metabolism in MIN6 cells through exposure to FFA, glucose, or inflammatory cytokines in vitro. qRT-PCR, ELISA, immunohisto-/cytochemistry, bioluminescence, and respirometry were employed to study Glrx5, insulin secretion, and mitochondrial biomarkers. The HFD induced a depletion of islet Glrx5 concomitant with an obese phenotype, elevated FFA in serum and reactive oxygen species in islets, and impaired glucose tolerance. Exposure of MIN6 cells to FFA led to a loss of Glrx5 in vitro. The FFA-induced depletion of Glrx5 coincided with significantly altered mitochondrial biomarkers. In summary, we provide evidence that Glrx5 is regulated by FFA in type 2 diabetes mellitus and is linked to mitochondrial dysfunction and blunted insulin secretion.

Correlation of Early Nutritional Supply and Development of Bronchopulmonary Dysplasia in Preterm Infants <1,000 g.

Background: Bronchopulmonary dysplasia (BPD) has multifactorial origins and is characterized by distorted physiological lung development. The impact of nutrition on the incidence of BPD is less studied so far. Methods: A retrospective single center analysis was performed on n = 207 preterm infants <1,000 g and <32 weeks of gestation without severe gastrointestinal complications to assess the impact of variations in nutritional supply during the first 2 weeks of life on the pulmonary outcome. Infants were grouped into no/mild and moderate/severe BPD to separate minor and major limitations in lung function. Results: After risk adjustment for gestational age, birth weight, sex, multiples, and antenatal steroids, a reduced total caloric intake and carbohydrate supply as the dominant energy source during the first 2 weeks of life prevailed statistically significant in infants developing moderate/severe BPD (p < 0.05). Enteral nutritional supply was increased at a slower rate with prolonged need for parenteral nutrition in the moderate/severe BPD group while breast milk provision and objective criteria of feeding intolerance were equally distributed in both groups. Conclusion: Early high caloric intake is correlated with a better pulmonary outcome in preterm infants <1,000 g. Our results are in line with the known strong impact of nutrient supply on somatic growth and psychomotor development. Our data encourage paying special attention to further decipher the ideal nutritional requirements for unrestricted lung development and promoting progressive enteral nutrition in the absence of objective criteria of feeding intolerance.

Fucose as a Cleavage Product of 2'Fucosyllactose Does Not Cross the Blood-Brain Barrier in Mice.

SCOPE: To further examine the role of the human milk oligosaccharide 2'fucosyllactose (2´FL) and fucose (Fuc) in cognition. Using 13 C-labeled 2'FL,thestudy previously showed in mice that 13 C-enrichment of the brain is not caused by 13 C1 -2´FL itself, but rather by microbial metabolites. Here, the study applies 13 C1 -Fuc in the same mouse model to investigate its uptake into the brain. METHODS AND RESULTS: Mice received 13 C1 -Fuc via oral gavage (2 mmol 13 C1 -Fuc/kg-1 body weight) or intravenously (0.4 mmol/kg-1 body weight). 13 C-enrichment is measured in organs, including various brain regions, biological fluids and excrements. By EA-IRMS, the study observes an early rise of 13 C-enrichment in plasma, 30 min after oral dosing. However, 13 C-enrichment in the brain does not occur until 3-5 h post-dosing, when the 13 C-Fuc bolus has already reached the lower gut. Therefore, the researcher assume that 13 C-Fuc is absorbed in the upper small intestine but cannot cross the blood-brain barrier which is also observed after intravenous application of 13 C1 -Fuc. CONCLUSIONS: Late 13 C-enrichment in the rodent brain may be derived from 13 C1 -Fuc metabolites derived from bacterial fermentation. The precise role that Fuc or 2´FL metabolites might play in gut-brain communication needs to be investigated in further studies.

Optical phase conjugation of picosecond pulses at 1.06 mum in Sn(2)P(2)S(6):Te for wavefront correction in high-power Nd-doped amplifier systems.

We report, for the first time to our knowledge, on picosecondpulse optical phase conjugation using photorefractive Sn(2)P(2)S(6) crystals. For 7.2-ps pulses at 1.06 mum, we have achieved phase-conjugate reflectivities of up to 45% with very fast build-up times, about 15 ms at an intensity of 23 W/cm(2) using Te-doped Sn(2)P(2)S(6). We furthermore demonstrate aberration-free 5 W optical output of 8-ps pulses at 1.06 mum from a side pumped Nd:YVO(4) amplifier using the Sn(2)P(2)S(6)-based phase-conjugate feedback.

Fast dynamic waveguides and waveguide arrays in photorefractive Sn(2)P(2)S(6) induced by visible light.

We report on dynamic waveguides and waveguide arrays induced beneath the surface of electro-optic Sn(2)P(2)S(6) crystals by visible light at 514 nm. The waveguide structures are generated by interband photoexcitation and drift or diffusion charge transport mechanism. These structures are probed nondestructively in the transverse direction with a beam at a longer wavelength. We measured the fastest formation of light induced waveguides in the visible up to now. The recording times are below 200 mus for intensities above 0.1 W/cm2. By interfering two light beams, dynamic waveguide arrays are generated with waveguide spacings of 7 microm. If an electric field is applied to the crystal, these arrays can be spatially shifted by 1.5 mum for an applied field of E(0) = 1 kV/cm.

Photonic crystal structures in ion-sliced lithium niobate thin films.

We report on the first realization of photonic crystal structures in 600-nm thick ion-sliced, single-crystalline lithium niobate thin films bonded on a lithium niobate substrate using adhesive polymer benzocyclobutene (BCB). Focused ion beam (FIB) milling is used for fast prototyping of photonic crystal structures with regular cylindrical holes. Unwanted redeposition effects leading to conically shaped holes in lithium niobate are minimized due to the soft BCB layer underneath. A high refractive index contrast of 0.65 between the lithium niobate thin film and the BCB underlayer enables strong light confinement in the vertical direction. For TE polarized light a triangular photonic crystal lattice of air holes with a diameter of 240 nm and a separation of 500 nm has a photonic bandgap in the wavelength range from 1390 to 1500 nm. Experimentally measured transmission spectra show a spectral power dip for the GK direction of the reci ocal lattice with an extinction ratio of up to 15 dB. This is in good agreement with numerical simulations based on the three-dimensional plane wave expansion (PWE) and the finite-difference time-domain (FDTD) method.

A terahertz time-domain spectrometer for simultaneous transmission and reflection measurements at normal incidence.

We present a versatile terahertz time-domain spectrometer which allows reflection measurements at normal incidence and double pass transmission measurements in a single experimental setup. Two different modes for transmission measurements are demonstrated for precise measurements of transparent high or low refractive index materials, respectively. The refractive indices and absorption coefficients of cesium iodide, potassium bromide, sodium chloride, polytetrafluoroethylene (PTFE, Teflon), and silicon have been measured in the frequency range between 1.4 and 4.7 THz. The parameters of the Lorentz oscillator functions describing the phonon polariton dispersions of CsI and KBr have been determined.

Influence of phenolic hydroxyl groups on second-order optical nonlinearity at an example of 2,4- and 3,4-dihydroxyl hydrazone isomorphic crystals.

We investigate the crystal structure and physical properties of 2,4- and 3,4-dihydroxybenzaldehyde-4-nitrophenylhydrazone (DHNPH) isomer crystals to understand the relation between molecular ordering with noncovalent interactions based on phenolic OH groups. The microscopic and macroscopic optical nonlinearities of 2,4- and 3,4-DHNPH crystals are investigated experimentally and theoretically by using density functional theory calculations. Although the two isomer crystals possess a very similar molecular orientation based on a similar supramolecular synthon, 2,4-DHNPH exhibits a 1.7 times larger powder second harmonic generation efficiency than 3,4-DHNPH, which is attributed to their different intermolecular interactions involving phenolic OH groups. We show that the microscopic nonlinearity of the DHNPH molecules is particularly sensitive to variations in phenolic OH characteristics such as the orientation and intermolecular interactions.

Metabolic Fate and Distribution of 2´-Fucosyllactose: Direct Influence on Gut Microbial Activity but not on Brain.

SCOPE: 2´-Fucosyllactose (2´FL) is an abundant oligosaccharide in human milk. It is hypothesized that its brain enrichment is associated with improved learning. Accumulation of 2´FL in organs, biological fluids, and feces is assessed in wild-type and germ-free mice. METHODS AND RESULTS: 13 C-labelled 2´FL is applied to NMRI wild-type mice intravenously (0.2 g kg-1 ) or orally (1 g kg-1 ), while controls receive saline. Biological samples are collected (0.5-15 h) and 13 C-enrichment is measured by elemental analysis isotope ratio mass spectrometry (EA-IRMS). After oral application, 2´FL is primarily eliminated in the feces. 13 C-enrichment in organs including the brain follows the same pattern as in plasma with a maximum peak after 5 h. However, 13 C-enrichment is only detected when the 13 C-2´FL bolus reaches the colon. In contrast, in germ-free mice, the 13 C-bolus remains in the intestinal content and is expelled via the feces. Furthermore, intravenously applied 13 C-2´FL is eliminated via urine; no 13 C-enrichment of organs is observed, suggesting that intact 2´FL is not retained. CONCLUSIONS: 13 C-enrichment in brain and other organs after oral application of 13 C-2´FL in wild-type mice indicates cleaved fucose or other gut microbial 2´FL metabolites may be incorporated, as opposed to intact 2´FL.

Double phase conjugate mirror using Sn2P2S6 for injection locking of a laser diode bar.

We demonstrate double phase-conjugation in pure and Te-doped Sn(2)P(2)S(6), a semiconducting ferroelectric material, at the wavelength of 685 nm. We observe a phase conjugate reflectivity of more than 800% at an intensity ratio of the pump beams of 44 for Te-doped Sn(2)P(2)S(6). Using a laser diode bar emitting at 685 nm, we demonstrate double phase conjugation of three independent emitters of the laser diode bar with a single mode master laser. By adjusting the center wavelength of the master laser to the center wavelength of an emitter with an accuracy of less than 0.1 nm, locking of any emitter of the laser diode bar is demonstrated. We improve the spectral width of the emitter from 0.5 nm to below 2.5 x 10(-4) nm.

Optical microring resonators in fluorineimplanted lithium niobate.

We report on the production and characterisation of optical microring resonators and optical channel waveguides by using fluorine-ion implantation and planar structuring in lithium niobate. We demonstrate the production of single-mode planar waveguides by low fluence fluorine-ion implantation (?? = 2.5 x10(14) ions/cm(2)) into lithium niobate wafers. The waveguides are strongly confined by the amorphous 2-microm wide optical barrier induced by the implantation process. A refractive index contrast of Deltan(o) = 0.17 at the telecom wavelength lambda = 1.5 microm has been determined between the waveguide and the barrier. Planar structuring with ridge height of up to 1.2 microm has been achieved by laser lithography masking and Ar(+) sputtering. For TE waves, the channel waveguides exhibit propagation losses lower than 8 dB/cm. First ring resonators with 80-microm radius have been fabricated by planar structuring in fluorine-ion implanted lithium niobate. The measured resonance curves show an extinction ratio of 14 dB, a free spectral range of 2.0 nm and a finesse of 4.

Electro-optic and nonlinear optical properties of ion implanted waveguides in organic crystals.

We report on the electro-optic and nonlinear optical properties of waveguides produced by low fluence (Phi = 1.25x10(14) ions/cm(2)) H+ ion implantation in the organic nonlinear optic crystal 4-N,N-dimethylamino-4'-N'-methyl-stilbazolium tosylate (DAST). The profile of the nonlinear optical susceptibility has been determined by measuring the reflected second-harmonic generation efficiency from a wedged-polished sample at a fundamental wavelength of lambda(omega) = 1176nm. In the waveguide core region the nonlinear optical susceptibility is shown to be preserved to more than 90% of its bulk value. A model which relates the molecular changes to the measured macroscopic alteration of the refractive index and the nonlinear coefficient has been introduced to quantify the fraction of molecules modified by ion implantation. Furthermore, a first electro-optic modulation in ion implanted DAST waveguides has been demonstrated.

Electro-optic single-crystalline organic waveguides and nanowires grown from the melt.

Organic nonlinear optical materials have proven to possess high and extremely fast nonlinearities compared to conventional inorganic crystals, allowing for sub-1-V driving voltages and modulation bandwidths of over 100 GHz. Compared to more widely studied poled electro-optic polymers, organic electro-optic crystals exhibit orders of magnitude better thermal and photochemical stability. The lack of available structuring techniques for organic crystals has been the major drawback for exploring their potential for photonic structures. Here we present a new approach to fabricate high-quality electro-optic single crystal waveguides and nanowires of configurationally locked polyene DAT2 (2-(3-(2-(4-dimethylaminophenyl)vinyl)-5,5-dimethylcyclohex-2-enylidene)malononitrile). The high-index-contrast waveguides (delta(n) = 0.54 +/- 0.04) are grown from the melt between two anodically bonded borosilicate glass wafers, which are structured and equipped with electrodes prior to bonding. Electro-optic phase modulation is demonstrated for the first time in the non-centrosymmetric DAT2 single crystalline channel waveguides at a wavelength of 1.55 microm. We also show that this technique in combination with DAT2 material allows for the fabrication of single-crystalline nanostructures inside large-area devices with crystal thicknesses below 30 nm and lengths of above 7 mm.

Light deflection and modulation through dynamic evolution of photoinduced waveguides.

Light induced waveguides produced by lateral illumination of a hotorefractive crystal show a complex dynamic evolution upon removal of the sustaining applied electric field. Using this effect, deflection and modulation of the guided light is realized by taking advantage of the screening and counter-screening of the space charge distribution. The spot separation upon deflection can exceed 10 times the original waveguide width. Numerical simulations of the refractive index evolution and beam propagation show a good agreement with the observations.

Fabrication and phase modulation in organic single-crystalline configurationally locked, phenolic polyene OH1 waveguides.

A novel and promising technique for the fabrication of electro-optically active single crystalline organic waveguides from 2-{3-(4-hydroxystyryl)-5,5-dimethylcyclohex-2-enylidene}malononitrile (OH1) is presented. OH1 is an interesting material for photonic applications due to the large electro-optic coefficients (r333 = 109+/-4 pm/V at 632.8 nm) combined with a relatively high crystal symmetry (orthorhombic with point group mm2). Due to the very favorable growth characteristics, large-area (> 150 mm(2)) single crystalline thin films with very good optical quality and thickness between 0.05-10 microm have been grown on amorphous glass substrates. We have developed and optimized optical lithography and reactive ion etching processes for the fabrication of wire optical waveguides with dimensions of w x h = 3.4 x 3.5 microm(2) and above. The technique is capable of producing low loss integrated optical waveguides having propagation losses of 2 dB/cm with a high refractive index contrast between core-cladding and core-substrate of delta n = 1.23 and 0.72, respectively at 980 nm. Electro-optic phase modulation in these waveguides has been demonstrated at 632.8 nm and 852 nm. Calculations show that with an optimized electrode configuration the half-wave voltage x length product V(pi) x L can be reduced from 8.4 Vcm, as obtained in our device, to 0.3 Vcm in the optimized case. This allows for the fabrication of sub-1 V half-wave voltage, organic electro-optic modulators with highly stable chromophore orientation.

Electro-optic Charon polymeric microring modulators.

We propose and demonstrate a new type of electro-optic polymeric microring resonators, where the shape of the transmission spectrum is controlled by losses and phase shifts induced at the asymmetric directional coupler between the cavity and the bus waveguide. The theoretical analysis of such Charon microresonators shows, depending on the coupler design, three different transmission characteristics: normal Lorentzian dips, asymmetric Fano resonances, and Lorentzian peaks. The combination of the active azo-stilbene based polyimide SANDM2 surrounded by the hybrid polymer Ormocomp allowed the first experimental demonstration of electro-optic modulation in Charon microresonators. The low-loss modulators (down to 0.6 dB per round trip), with a radius of 50 microm, were produced by micro-embossing and exhibit either highly asymmetric and steep Fano resonances with large 43-GHz modulation bandwidth or strong resonances with 11-dB extinction ratio. We show that Charon microresonators can lead to 1-V half wave voltage all-polymer micrometer-scale devices with larger tolerances to coupler fabrication limitations and wider modulation bandwidths than classical ring resonators.

A hydrogen-bonded organic nonlinear optical crystal for high-efficiency terahertz generation and detection.

Broadband THz pulses have been generated in 2-[3-(4- hydroxystyryl)-5,5-dimethylcyclohex-2-enylidene]malononitrile (OH1) by optical rectification of sub-picosecond laser pulses. We show that OH1 crystals allow velocity-matched generation and detection of THz frequencies in the whole range between 0.3 and 2.5 THz for a pump laser wavelength range from 1200 to 1460 nm. OH1 crystals show a higher figure of merit for THz generation and detection in the optimized range compared to the benchmark inorganic semiconductor crystals ZnTe and GaAs and the organic ionic salt crystal 4-N,N-dimethylamino-4'-N'-methyl stilbazolium tosylate (DAST). The material shows a low THz absorption coefficient alpha3 in the range between 0.3 and 2.5 THz, reaching values lower than 0.2mm(-1) between 0.7 and 1.0 THz. This is similar as in ZnTe and GaAs, but much lower than in DAST in the respective optimum frequency range. A peak THz electric field of 100 kV/cm and a photon conversion efficiency of 11 percent have been achieved at a pump pulse energy of 45 microJ.

Electro-optic phase modulation in ridge waveguides of epitaxial K(0.95)Na(0.05)Ta(0.71)Nb(0.29)O(3) thin films.

Electro-optic modulation at lambda=1.5 mum has been demonstrated for the first time to the best of our knowledge in a ridge waveguide phase modulator produced in cubic potassium sodium tantalate niobate thin films epitaxially grown on potassium tantalate substrates exploiting the large quadratic electro-optic Kerr coefficient of R11 = 8.2x10(-17) m(2)/V(2). The relative permittivity, Kerr coefficient, and refractive index have been evaluated for the thin film crystal and are compared to the values measured in bulk crystals. The half-wave voltage times length figure of merit of the modulator has been measured to be Vpil=38 Vcm at room temperature.

Direct electron beam writing of channel waveguides in nonlinear optical organic crystals.

We report on optical channel waveguiding in an organic crystalline waveguide produced by direct electron beam patterning. The refractive index profile as a function of the applied electron fluence has been determined by a reflection scan method in the nonlinear optical organic crystal 4-N, N-dimethylamino-4'-N'-methyl-stilbazolium tosylate (DAST). A maximal refractive index reduction of Deltan1 = -0.3 at a probing wave-length of 633 nm has been measured for an electron fluence of 2.6mC/cm(2). Furthermore, a new concept of direct channel waveguide patterning in bulk crystals is presented and waveguiding has been demonstrated in the produced structures by end-fire coupling. Mach-Zehnder modulators have been successfully realized and a first electro-optic modulation at a wavelength of lambda= 1.55mum has been demonstrated therein.