Modified hippocampal long-term potentiation in PKC gamma-mutant mice

Calcium-phospholipid-dependent protein kinase (PKC) has long been suggested to play an important role in modulating synaptic efficacy. We have created a strain of mice that lacks the gamma subtype of PKC to evaluate the significance of this brain-specific PKC isozyme in synaptic plasticity. Mutant mice are viable, develop normally, and have synaptic transmission that is indistinguishable from wild-type mice. Long-term potentiation (LTP), however, is greatly diminished in mutant animals, while two other forms of synaptic plasticity, long-term depression and paired-pulse facilitation, are normal. Surprisingly, when tetanus to evoke LTP was preceded by a low frequency stimulation, mutant animals displayed apparently normal LTP. We propose that PKC gamma is not part of the molecular machinery that produces LTP but is a key regulatory component.     

NUCLEAR MAGNETIC RESONANCE STUDIES OF ASPHALTENES AND COALS. A NEW APPROACH TO OBTAINING ASPHALTENE STRUCTURAL PARAMETERS WITH DIPOLAR DEPHASING

Apparent carbon aromaticities, fa, of some asphaltenes have been measured by n.m.r. in solution and compared with those obtained by the CP/MAS technique on solid samples. The aromaticities were also measured for several Alberta plains coals. From the 1H solution spectra and 13C solid nmr spectra of asphaltenes, some of their skeletal features, not obtainable from solution spectra only, have been suggested.     

A method for locating fault section by using sequential information at substations

This paper presents a new real-time method for locating fault section at substations. When a fault occurs, considerable information resulting from protective relay operation and circuit-breaker operation is recorded. Using this information an attempt is made to locate the fault section, especially by considering the sequential relationship of the information and by dividing fault areas. Primarily, in this method, the fault area is divided into several sections based on protection area and operation time of protective relays. Next, expecting subsequent operation of backup relays, the “waiting time” for reasoning is given to each divided section. After a lapse of “waiting time,” all the suspected fault sections are extracted and given priority based on the empirical knowledge of experts. A prototype of the expert system was developed for fault section location, which was applied to various complicated fault cases. The effectiveness of the method was proved even in case of multiple faults and no-operation of protective relays the circuit breakers.     

Reduction of the off-state current of polysilicon thin-filmtransistors by means of a polysilicon buffer layer

The off state current for polysilicon thin-film transistors for pixels in LCDs has been successfully reduced by introducing a polysilicon buffer layer between a polysilicon active layer fabricated by solid-phase-crystallisation (SPC) and a fused quartz substrate. Off-slate current of less than 1 pA under V_gs=-25 V at V_ds=3 V was obtained for n-channel single-gate coplanar transistors using the buffer layer (400 Å)     

Characteristics and classification of high-current fault arcs on distribution systems

When a fault occurs on transmission or distribution systems due to lightning or overvoltage, often an arc discharge occurs at the fault point. The arc discharge, which is caused by a fault current, has a high current, high temperature, strong light emission, etc., thus it sometimes causes heavy damages to electric power equipment. The arc discharge is influenced by the conditions around the arcs, i.e., gas, insulation materials, gap length, weather, etc. Also, the arc voltage along the arc column indicates the characteristics of the arc. If the voltage waveforms of the arcs caused by the fault on transmission or distribution systems are classified, it is possible to find the location and the equipment where the fault occurred. In this paper, the arc voltage data in 6-kV class XLPE cables and 6-kV class overhead lines are analyzed and an artificial neural network method is applied to classify the arc voltage waveforms. The results obtained from the six artificial neural networks developed show that the artificial neural network method is effective for classification of arc voltage waveforms if adequate input parameters are selected.     

MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.     

Water structure and improved mechanical properties of phospholipid polymer hydrogel with phosphorylcholine centered intermolecular cross-linker

We investigated the water structure and the mechanical properties of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer hydrogels cross-linked with a novel hydrophilic 2-(methacryloyloxy)ethyl-[N-(2-methacryloyloxy)ethyl]phosphorylcholine (MMPC) for soft contact lenses (SCL) applications and commercial methacrylic cross-linkers were in addition used for comparison with MMPC. Water structure in hydrogels, which influences the protein adsorption by dehydration was determined by differential scanning calorimetry. MMPC increased the freezing water content of the MPC polymer hydrogel compared with hydrophilic N,N′-methylenebisacrylamide (BIS) at the same water content. MMPC also improved fracture strength of the MPC polymer hydrogel to 120 kPa in tensile, which was considerably higher than that hydrogel cross-linked with BIS. It is suggested that MMPC shows higher cross-linking reactivity with MPC than BIS. We concluded that the MMPC increase both the free water content and the tensile properties. The MPC polymer hydrogel cross-linked with MMPC can be a useful SCL biomaterial.     

NMR-Guided Repositioning of Non-Steroidal Anti-Inflammatory Drugs into Tight Junction Modulators

Bioavailability is a major bottleneck in the clinical application of medium molecular weight therapeutics, including protein and peptide drugs. Paracellular transport of these molecules is hampered by intercellular tight junction (TJ) complexes. Therefore, safe chemical regulators for TJ loosening are desired. Here, we showed a potential application of select non-steroidal anti-inflammatory drugs (NSAIDs) as TJ modulators. Based on our previous observation that diclofenac and flufenamic acid directly bound various PDZ domains with a broad specificity, we applied solution nuclear magnetic resonance techniques to examine the interaction of other NSAIDs and the first PDZ domain (PDZ1) of zonula occludens (ZO)-1, ZO-1(PDZ1). Inhibition of ZO-1(PDZ1) is expected to provide loosening of the epithelial barrier function because the domain plays a crucial role in maintaining TJ integrity. Accordingly, diclofenac and indomethacin were found to decrease the subcellular localization of claudin (CLD)-2 but not occludin and ZO-1 at the apicolateral intercellular compartment of Madin–Darby canine kidney (MDCK) II cells. These NSAIDs exhibited 125–155% improved paracellular efflux of fluorescein isothiocyanate insulin for the Caco-2 cell monolayer. We propose that these NSAIDs can be repurposed as drug absorption enhancers for peptide drugs.     

Comparison of soyasaponin and isoflavone contents between genetically modified (GM) and non-GM soybeans

Soyasaponins and isoflavones are main secondary metabolites in soybeans. In this report we compared the content of secondary metabolites between genetically modified (GM) and non-GM soybeans. Six cultivars/lines of GM and six cultivars/lines of non-GM soybeans were extracted with methanol. Each extract was partitioned with aqueous methanol and hexane and the aqueous methanol fraction was partially purified by HP-20 and LH-20 column chromatography to afford crude soyasaponin and isoflavone fractions. The main A-type soyasaponin, acetylsoyasaponin A1 (AcA1), and the main B-type soyasaponins, soyasaponins I and II (I and II), in the crude fractions were identified by LC/MS analyses with authentic samples. The main isoflavones, daidzin, genistin, daidzein and genistein (DI, GI, DE and GE), in the crude fractions were identified by LC photo-diode array analyses with authentic samples. The contents of AcA1, I and II in the crude soyasaponin fractions and those of DI, GI, DE and GE in the crude isoflavone fractions were analyzed by reversed-phase HPLC. The average contents (mg/100 g) of AcA1, I, II and total of B-type soyasaponins in GM soybeans were 36.4 +/- 24.2, 51.2 +/- 11.8, 26.4 +/- 7.6 and 77.7 +/- 18.5, respectively, and those in non-GM ones were 22.3 +/- 14.7, 46.3 +/- 17.8, 19.8 +/- 9.1 and 65.9 +/- 26.9, respectively. The average contents (mg/100 g) of DI, GI, DE, GE and total isoflavones in GM soybeans were 93.1 +/- 15.5, 121.8 +/- 19.4, 0.073 +/- 0.178, 0.320 +/- 0.082 and 215.3 +/- 33.3, respectively, and those in non-GM ones were 78.8 +/- 34.6, 106.7 +/- 28.3, 2.206 +/- 4.468, 0.822 +/- 0.754 and 188.5 +/- 26.7, respectively. There were no statistically significant differences in soyasaponin and isoflavone contents between GM and non-GM soybeans. Therefore, it was estimated that the GM soybeans are equivalent to the non-GM ones in terms of the composition of the main secondary metabolites.     

Finite element analysis of a polymer composite subjected to a sliding steel asperity Part I Normal fibre orientation

FE micro-models have been developed in order to determine contact, stress and strain conditions produced by a steel asperity sliding on the surface of a normally oriented fibre-reinforced polymer composite. A displacement coupling technique was introduced to model a micro-environment as part of a macro-environment and to get more realistic simulation results about the failure conditions in the composite structure, in comparison to the so far widely applied anisotropic analytical or numerical macro-models. On the basis of the results, conclusions may be drawn for the possible wear mechanisms of the fibre-reinforced polymer composite. Stress results in the vicinity of the fibers in the contact area show high shear loading of the matrix leading to the formation of stretched-out matrix wear debris. In addition, high repeated compression-tension stresses at the fibre/matrix interface near the surface can lead to fibre debonding phenomena. Considering the fibre ends in the contact region, high compression stresses at their rear edges can produce fibre cracking features. To study the wear mechanisms experimentally, a single asperity scratch test was also performed showing shear failure events of the polymer matrix, fibre/matrix debonding and fibre cracking effects, as expected from the modelling studies.