Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized,placebo-controlled P MRS study

Randomized, placebo-controlled single blinded study was carried out to evaluate the effect of oral creatine supplementation on cellular energetics, manual muscle test (MMT) score and functional status in steroid-naive, ambulatory boys suffering with Duchenne muscular dystrophy (DMD; n=33). Eighteen patients received creatine monohydrate (Cr; 5 g/day for 8 weeks), while 15 received placebo (500 mg of vitamin C). Phosphorus metabolite ratios were determined from the right calf muscle of patients using phosphorus magnetic resonance spectroscopy (³¹P MRS) both prior to (baseline) and after supplementation of Cr or placebo. In addition, metabolite ratios were determined in normal calf muscle of age and sex matched controls (n=8). Significant differences in several metabolite ratios were observed between controls and DMD patients indicating a lower energy state in these patients. Analysis using analysis of covariance adjusted for age and stature showed that the mean phosphocreatine (PCr)/inorganic phosphate (Pi) ratio in patients treated with Cr (4.7; 95% CI; 3.9–5.6) was significantly higher (P=.03) compared to the placebo group (3.3; 95% CI; 2.5–4.2). The mean percentage increase in PCr/Pi ratio was also more in patients <7 years of age compared to older patients after Cr supplementation indicating variation in therapeutic effect with the age. In the placebo group, significant reduction in PCr/Pi (P=.0009), PCr/t-ATP (P=.05) and an increase in phosphodiester (PDE)/PCr ratios was observed after supplementation. Further, in the placebo group, patients <7 years showed reduction of PCr/t-ATP and Pi/t-ATP compared to older patients (>7 years), after supplementation. These results imply that the significant difference observed in PCr/Pi ratio between the Cr and the placebo groups after supplementation may be attributed to a decrease of PCr in the placebo group and an increase in PCr in the Cr group. Changes in MMT score between the two groups was significant (P=.04); however, no change in functional scale (P=.19) was observed. Parents reported subjective improvement on Cr supplementation versus worsening in placebo (P=.02). Our results indicated that Cr was well tolerated and oral Cr significantly improved the muscle PCr/Pi ratio and preserved the muscle strength in short term. However, this study provides no evidence that creatine will prove beneficial after long-term treatment, or have any positive effect on patient lifespan.     

Third-order nonlinear optical response in transparent solids using ultrashort laser pulses

The third-order optical nonlinearity, χ ⁽³⁾, is measured in transparent glasses (BK7 and fused silica) and crystals (BaF₂ and quartz) using 36-fs, 800-nm laser pulses and the optical Kerr gate (OKE) technique; values are found to lie in the range 1.3–1.7×10^-14 esu, in accordance with theoretical estimates. We probe the purely electronic response to the incident ultrashort laser pulse in fused silica and BK7 glass. In BaF₂ and quartz, apart from the electronic response we also observe contribution from the nuclear response to the incident ultrashort pulses. We observe oscillatory modulations that persist for ～400 fs. The response of the media (glasses and crystals) to ultrashort pulses is also measured using two-beam self-diffraction; the diffraction efficiency in the first-order grating is measured to be in the range of 0.06–0.13 %. Third harmonic generation due to self-phase matching in the transient grating geometry is measured as a function of temporal delay between the two incident ultrashort pulses, yielding the autocorrelation signal.     

Metabolism of the colonic mucosa in patients with inflammatory bowel diseases: an in vitro proton magnetic resonance spectroscopy study

Metabolism of the colonic mucosa of patients with ulcerative colitis (UC; n=31) and Crohn's disease (CD; n=26) and normal mucosa (control, n=26) was investigated using in vitro high-resolution proton magnetic resonance spectroscopy. Of the 31 UC patients, 20 were in the active phase and 11 were in the remission phase of the disease. Out of 26 CD patients, 20 were in the active phase, while 6 were in the remission phase of the disease. Twenty-nine metabolites were assigned unambiguously in the perchloric acid extract of colonic mucosa. In the active phase of UC and CD, significantly lower (P相似文献   

Simulation-driven formulation of transportation fuel surrogates

An alternative way to formulate transportation fuel surrogates using model predictions of gas-phase combustion targets is explored and compared to conventional approaches. Given a selection of individual fuel components, a multi-component chemical mechanism describing their oxidation kinetics, and a database of experimental measurements for key combustion quantities such as ignition delay times and laminar burning velocities, the optimal fractional amount of each fuel is determined as the one yielding the smallest error between experiments and model predictions. Using a previously studied three-component jet fuel surrogate containing n-dodecane, methyl-cyclohexane, and m-xylene as a case study, this article investigates in a systematic manner how the surrogate composition affects model predictions for ignition delay time and laminar burning velocities over a wide range of temperature, pressure and stoichiometry conditions, and compares the results to existing surrogate formulation techniques, providing new insights on how to define surrogates for simulation purposes. Finally, an optimisation algorithm is described to accelerate the identification of optimal surrogate compositions in this context.     

Experimental and computational investigation of extinction and autoignition of propane and n-heptane in nonpremixed flows

An experimental and computational investigation is carried out to characterize the influence of reactants on critical conditions for extinction and for autoignition of propane and n-heptane in nonpremixed counterflow configurations. Propane or vaporized n-heptane mixed with nitrogen is transported in one stream while the other stream is made up of air mixed with nitrogen. Measurements of the oxidizer stream temperature needed for autoignition are made at fixed values of the strain rate, either with the fuel mass fraction varied at a fixed oxygen mass fraction or with the oxygen mass fraction varied at a fixed fuel mass fraction. Extinction strain rates for propane are measured as a function of the oxygen mass fraction with room-temperature feed streams and the fuel mass fraction fixed and for n-heptane as a function of the fuel mass fraction with the oxygen mass fraction and feed-stream temperatures fixed. Predictions of critical conditions for extinction and autoignition are made employing detailed kinetic mechanisms. Predictions of critical conditions for extinction are in reasonable agreement with measurements, but there are significant discrepancies for autoignition. Measurements show that increasing the mass fraction of either fuel or oxygen increases the overall reactivity thereby reducing the autoignition temperature. The kinetic models predict the increase in reactivity of the mixing layer with increasing mass fraction of fuel but predict very little change in reactivity of the mixing layer with increasing mass fraction of oxygen, thus failing to predict the influence of oxygen on autoignition. It is concluded that there may exist kinetic pathways responsible for this disagreement that are yet to be discovered, and paths that fail to explain the results are identified.     

Al2O3(1120) surface as a template for the ordered growth of Ni and Co nanoclusters

The morphology and thermal stability of Ni and Co nanoclusters grown by physical vapour deposition on a reconstructed (1120) surface of α-Al(2)O(3) is investigated using non-contact atomic force microscopy (NC-AFM). NC-AFM images reveal that the clean α-Al(2)O(3)(1120) substrate adopts a characteristic (12 × 4) reconstruction when prepared in vacuum at high temperature. Subsequent deposition of Ni and Co onto this substrate at room temperature facilitates the growth of well-ordered metal nanocluster arrays with a preferred inter-cluster distance determined by the (12 × 4) periodicity of the substrate surface. The order in the cluster arrangement remains intact even upon annealing the system to temperatures up to 500 °C indicating a high resistance against sintering. The reconstructed α-Al(2)O(3)(1120) surface can, therefore, serve as an appropriate insulating template for studies of size-dependent magnetic or catalytic effects in a well-defined ensemble of metallic nanoclusters.     

Dibutyl 2-(trifluoromethyl)cyclopropylboronate as a useful (trifluoromethyl)cyclopropyl donor: application to antagonists of TRPV1

Dibutyl-2-(trifluoromethyl)cyclopropylboronate 2, available in one step from commercially available reagents, serves as a useful (trifluoromethyl)cyclopropylating reagent by participating in a palladium-catalyzed Suzuki coupling. The use of boronate ester 2 in medicinal chemistry was exemplified by preparation of TRPV1 receptor antagonists.     

Effect of group velocity dispersion on supercontinuum generation and filamentation in transparent solids

We experimentally investigate the spectral extent and spectral profile of the supercontinuum (SC) generated in transparent solids: barium fluoride, calcium fluoride, and fused silica upon irradiation by intense femtosecond-long pulses of 800, 1,380, and 2,200 nm light. These wavelengths correspond to the normal and anomalous group velocity dispersion (GVD) regimes in fused silica calcium fluoride and barium fluoride. We observe an isolated (anti-Stokes) wing on the blue side most prominently in fused silica but also in CaF₂. The SC conversion efficiency is measured for the long wavelengths used in our experiments. We also present results on filamentation in BaF₂ in the anomalous GVD regime, including visualization of focusing–refocusing events within the crystal; the size of a single filament is also determined. The 15-photon absorption cross section in BaF₂ is deduced to be 6.5 × 10^?190 cm³⁰ W^?15 s^?1.