The Role of Sphingosine Kinase 2 in Alcoholic Liver Disease

Alcoholic liver disease (ALD) is one of the most common liver diseases worldwide characterized by the accumulation of lipids within the liver, inflammation and the possibility of progressing to cirrhosis and liver failure. More importantly, there are currently no effective treatments for ALD and liver transplantation remains the only therapeutic option for end-stage liver disease. Previous studies have shown that ALD is a result of a combination of endoplasmic reticulum (ER) stress, lipid metabolism dysregulation and inflammation. It has been previously reported that alcohol disrupts gut microbiota homeostasis and causes increased endotoxins that contribute to the pathology of ALD. However, the detailed mechanism(s) underlying ALD and disease progression is poorly understood. We have discovered that sphingosine kinase 2 (SphK2) deficient (SphK2-/-) mice on an alcohol diet exhibit increased steatosis and inflammation compared to wild type mice. Sphingosine 1-phosphate receptor 2 (S1PR2) and SphK2 have been previously shown to play a key role in nutrient metabolism and signaling. However, their roles in alcohol-induced liver injury have not been characterized. The overall objective of this study is to determine the molecular mechanism(s) by which disruption of S1PR2-mediated SphK2 signaling contributes to ALD. The effects of alcohol on mouse primary hepatocytes and cultured RAW264.7 macrophages were examined. The acute on chronic alcohol mouse model from NIAAA that recapitulates the drinking pattern of human ALD patients was used to study the effects of SphK2 deficiency in ALD. In addition, 60-day chronic alcohol mouse model was used to determine whether a more severe form of ALD was present in SphK2-/- mice. The results indicated that SphK2-/- mice on an alcohol diet exhibited an increased amount of hepatic steatosis compared to wild type mice. Genes regulating lipid metabolism were also dysregulated in SphK2-/- mice. SphK2-/- mice also had increased inflammation and liver injury as shown by an upregulation of inflammatory markers and increased levels of liver enzymes. Moreover, SphK2 protein expression levels were downregulated in the human livers of alcoholic cirrhotic and hepatocellular carcinoma (HCC) patients. These findings contribute to a greater understanding of the pathophysiology of ALD and could provide information on the development of novel therapeutics against ALD

High-power 1.3 µm superluminescent diode

Superluminescent diodes with high output power (10 mW at 175 mA), wide spectral width (28 nm), low spectral modulation depth (<15%), wide frequency modulation bandwidth (570 MHz), and high single-mode fiber coupling efficiency (40%) are reported. The structure is based on a buried crescent laser structure with an antireflection coating and a "short-circuit" absorber to suppress lasing

Long time Solutions for a Burgers-Hilbert Equation via a Modified Energy Method

We consider an initial value problem for a quadratically nonlinear inviscid Burgers-Hilbert equation that models the motion of vorticity discontinuities. We use a modified energy method to prove the existence of small, smooth solutions over cubically nonlinear time-scales

Unconditionally secure key distillation from multi-photons

In this paper, we prove that the unconditionally secure key can be surprisingly extracted from {\it multi}-photon emission part in the photon polarization-based QKD. One example is shown by explicitly proving that one can indeed generate an unconditionally secure key from Alice's two-photon emission part in ``Quantum cryptography protocols robust against photon number splitting attacks for weak laser pulses implementations'' proposed by V. Scarani {\it et al.,} in Phys. Rev. Lett. {\bf 92}, 057901 (2004), which is called SARG04. This protocol uses the same four states as in BB84 and differs only in the classical post-processing protocol. It is, thus, interesting to see how the classical post-processing of quantum key distribution might qualitatively change its security. We also show that one can generate an unconditionally secure key from the single to the four-photon part in a generalized SARG04 that uses six states. Finally, we also compare the bit error rate threshold of these protocols with the one in BB84 and the original six-state protocol assuming a depolarizing channel.Comment: The title has changed again. We considerably improved our presentation, and furthermore we proposed & analyzed a security of a modified SARG04 protocol, which uses six state

Neuroprotection and acidosis induced by cortical spreading depression

We read with interest the article “Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5” published in Neuropsychiatr Dis Treat by Viggiano et al.1 The authors showed that cerebral spreading depression (CSD) triggered uncoupling protein-5 (UCP-5),1 which had been reported to exert a long-term effect upon neuron protection.2 The result is another piece in CSD literature on modifying gene expressions to provide neuroprotection to subsequent ischemic episodes.3,

What could be learnt from Positronium for Quarkonium?

In order to fulfill Low's theorem requirements, a new lowest order basis for bound state decay computations is proposed, in which the binding energy is treated non-perturbatively. The properties of the method are sketched by reviewing standard positronium decay processes. Then, it is shown how applying the method to quarkonia sheds new light on some longstanding puzzles.Comment: 12 pages, 10 figures. Talk given at the ETH Workshop on Positronium Physics, May 30-31, 2003, Zurich, Switzerlan

A Field Test Study on Instrumented Soil Nail Installed in Cut Slope

Soil nailing is a technique routinely used in Hong Kong whereby closely spaced steel bars are installed into a slope so that its stability conditions can be improved. A full-scale field test has been carried out by The Department of Civil Engineering of The University of Hong Kong to study the development of passive load along the full length of soil nails when subjected to induced rise in groundwater table. The cut slope was formed to a very steep angle of 55° and 10 m high in completely decomposed volcanic material. Grouted curtain was also formed behind, at the bottom and on both ends of the slope in order to form an impermeable barrier that would allow groundwater table to increase artificially by injecting water into slotted PVC pipes. Nine number of soil nails (in regular 2 m c/c spacing of 3 rows and 3 columns) of 6 m long high yield steel bar were installed at 15° from horizontal into the formed cut slope. Instrumentation included strain gauges along the nails, inclinometers, piezometers, and settlement prisms. This paper describes the method of construction and the load developed along the soil nails when the groundwater table was raised to the ground surface. It was found that the measured passive load along the soil nail was smaller than the commonly assumed design parameters, an indication that substantial savings can be achieved if mobilization of shearing resistance along the full length of the soil nail was considered in routine design. Finite element analysis has also been carried out to compare the measured load with the simulated load and the stability factor is compared with the factor of safety at each stage of loading