Expression of polyglutamine-expanded Huntingtin activates the SEK1-JNK pathway and induces apoptosis in a hippocampal neuronal cell line

Huntington's disease is one of a growing number of hereditary neurodegenerative disorders caused by expansion of a polyglutamine stretch at the NH2 terminus of huntingtin. To explore whether polyglutamine-expanded huntingtin induces neuronal toxicity, I examined the expression of the full-length of huntingtin with 16, 48, or 89 polyglutamine repeats in a rat hippocampal neuronal cell (HN33). Expression of mutated huntingtin with 48 or 89 polyglutamine repeats stimulated c-Jun amino-terminal kinases (JNKs) activity and induced apoptotic cell death in HN33 cells while expression of normal huntingtin with 16 polyglutamine repeats had no toxic effect. The JNK activation precedes apoptotic cell death and co-expression of a dominant negative mutant form of stress-signaling kinase (SEK1) nearly completely blocked activation of JNKs and neuronal apoptosis mediated by mutated huntingtin. Taken together, my studies demonstrate that expression of polyglutamine-expanded huntingtin induces neuronal apoptosis via activation of the SEK1-JNK pathway.     

Energy function analysis of dynamic programming neural networks

All analytical examination of the energy function associated with a dynamic programming neural network is presented. The analysis is carried out in two steps. First, the locations and numbers of the minimum states for different components of the energy function are investigated in the extreme cases. A clearer insight into the energy function can be gained through the minimum states of different components. Secondly, the locations of the minimum states of the energy function using different parameter values are derived. It is shown that the minimum states can reside in regions which are regarded as valid solutions with certain conditions. Examples and simulation results are given to justify the validity of the theories developed.     

Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy

From April 1990 to December 1993, 140 patients were recruited to a randomized study to evaluate transcatheter hepatic arterial chemoembolization (TACE) as an adjuvant therapy for primary liver carcinoma after hepatectomy. This study investigated the principle, techniques and results of TACE. The results showed that the intrahepatic recurrence rate was 48.9% in the patients who underwent radical resection only, but only 21.3% in the patients who also underwent TACE 3-4 weeks after hepatectomy (P < 0.01). The 1-, 2-, 3-, and 4-year survival rates were 72.3%, 52.7%, 35.1%, and 35.1% respectively for the patients who underwent radical resection only, and were 97.9%, 85.5%, 69.5%, and 56.9% for the patients who also underwent TACE 3-4 weeks after radical resection (P < 0.001). The 1-, 2-, 3-, and 4-year survival rates were 38.9%, 0%, 0%, and 0% for the patients who underwent palliative resection only, and were 68.3%, 32.3%, 21.5%, and 21.5% respectively for the patients undergoing TACE 3-4 weeks after palliative hepatectomy (P < 0.001).     

A new simplified threshold-voltage model for n-MOSFETs with nonuniformly doped substrate and its application to MOSFET's miniaturization

The formulation, verification, and application of a new simplified 2-D threshold voltage model for n-MOSFETs with nonuniformly doped substrate profile are provided, in which the averaged normal field at the Si/SiO/sub 2/ interface in the active channel is quoted from a simplified solution of two-dimensional Poisson equation using the Green function technique. Starting with the expression of this average normal field, a simple threshold-voltage model for short-channel n-MOSFETs with nonuniformly doped substrate profile is explicitly expressed in terms of device structures and terminal voltages by considering parabolic source-drain boundary potentials. Moreover, the effects of the junction depth on the threshold voltage are examined in detail. It is shown that the DIBL effect cannot be completely eliminated by simply increasing the substrate doping concentration. Comparisons among developed model, 2-D numerical analysis, and experimental data have been made and the accuracy of the developed analytical model has been verified. In addition, a direct extension of our model to the case of uniformly doped substrates leads to a new constraint equation for device miniaturization.<>     

Effect of lanthanide ions on the phase behavior of dipalmitoylphosphatidylcholine multilamellar liposomes

The effect of lanthanide ions (Ln3+) and their coordination compounds of diethylenetriamine pentaacetic acid (DTPA) on the phase behavior of dipalmitoylphosphatidylcholine (DPPC) multi-lamellar liposomes has been studied by differential scanning calorimetry (DSC), Raman spectroscopy, and freeze-fracture electron microscopic techniques. The displacement of Ca2+ binding on DPPC liposomes by lanthanide ions was also studied. The results show that the binding degree of four kinds of chloride salts with DPPC liposomes is: YbCl3 > GdCl3 > LaCl3 > CaCl2. Lanthanide ions increase the phase transition temperature of DPPC liposomes and decrease the membrane fluidity. Freeze-fracture electron microscopic results show that La3+ enhances the order of DPPC membrane. The effect of coordination compounds of lanthanides with DTPA on the phase behavior of DPPC liposomes is smaller than that of their chlorides. La3+, Gd3+, and Yb3+, can displace Ca2+ binding on DPPC liposomes, but there coordination compounds of DTPA can hardly displace Ca2+. Raman spectroscopic results show that a very slight effect in lateral packing order of DPPC liposomes was observed at various concentrations of lanthanides.