Activation of JNK Signaling Mediates Amyloid-ß-Dependent Cell Death

Alzheimer's disease (AD) is an age related progressive neurodegenerative disorder. One of the reasons for Alzheimer's neuropathology is the generation of large aggregates of Aß42 that are toxic in nature and induce oxidative stress, aberrant signaling and many other cellular alterations that trigger neuronal cell death. However, the exact mechanisms leading to cell death are not clearly understood.We employed a Drosophila eye model of AD to study how Aß42 causes cell death. Misexpression of higher levels of Aß42 in the differentiating photoreceptors of fly retina rapidly induced aberrant cellular phenotypes and cell death. We found that blocking caspase-dependent cell death initially blocked cell death but did not lead to a significant rescue in the adult eye. However, blocking the levels of c-Jun NH(2)-terminal kinase (JNK) signaling pathway significantly rescued the neurodegeneration phenotype of Aß42 misexpression both in eye imaginal disc as well as the adult eye. Misexpression of Aß42 induced transcriptional upregulation of puckered (puc), a downstream target and functional read out of JNK signaling. Moreover, a three-fold increase in phospho-Jun (activated Jun) protein levels was seen in Aß42 retina as compared to the wild-type retina. When we blocked both caspases and JNK signaling simultaneously in the fly retina, the rescue of the neurodegenerative phenotype is comparable to that caused by blocking JNK signaling pathway alone.Our data suggests that (i) accumulation of Aß42 plaques induces JNK signaling in neurons and (ii) induction of JNK contributes to Aß42 mediated cell death. Therefore, inappropriate JNK activation may indeed be relevant to the AD neuropathology, thus making JNK a key target for AD therapies

Antifriction and Antiwear Properties of an Ionic Liquid with Fluorine-Containing Anion Used as Lubricant Additive.

Tribological behavior of trihexyltetradecylphosphonium bis(trifluoromethylsulfonyl) imide [P66614][NTf2] ionic liquid (IL) used as additive in a diester oil at concentrations of 0.25, 0.5 and 1 wt% was studied in this research. The IL solubility in the base oil was measured using the inductively coupled plasma mass spectrometry (ICP-MS) technique, and corrosion analysis was done at room temperature at relative humidity of 49–77%. Tribological tests were conducted for 30 min at room temperature, 15 Hz frequency, 4 mm of stroke length, a load of 80 N (corresponding to 2 GPa of maximum contact pressure) and relative humidity of 35–53%. Friction coefficient was recorded during tests, and the wear scar was measured by confocal microscopy. Worn surface was also analyzed by SEM, EDS and XPS. Results showed that a saturated solution of [P66614][NTf2] in the base oil contains about 30 wt% of IL and corrosion activity for the highest concentration of IL (1 wt%) was not found after a 20-day test. Although the base oil and the mixtures had similar friction behavior, only the 1 wt% sample exhibited slightly lower wear volume than the base oil. SEM images exhibited similar wear track width (707–796 µm) and wear mechanism (adhesive) for all samples tested. In addition, the EDS spectra only showed the elements present in the steel. Finally, the XPS measurements could not detect differences regarding iron chemical state among the samples, which is consistent with the tribological behavior obtained

Structural and mechanical properties of TiC/Ti and TiC/B4C multilayers deposited by pulsed laser deposition

Multilayers of TiC/Ti and TiC/B4C have been deposited by pulsed laser deposition. Ti, B4C, and TiC targets were used to deposit multilayer films onto 440C steel and silicon substrates at 40 degreesC. The structural, compositional, and mechanical properties of the multilayers were examined by x-ray diffraction, x-ray photoelectron spectroscopy, transmission electron microscopy, and nanoindentation techniques. Tribological properties were also evaluated using a pin-on-disc friction and wear test. The TiC/Ti films were found to have a crystalline structure, and both (200)TiC/(100)Ti and (111)TiC/(101)Ti orientation relationships were found in these films. In the TiC/B4C films, only the sample with the largest bilayer thickness (25 nm) had significant crystallinity and only the TiC layer was crystalline. X-ray photoelectron spectroscopy depth profiles confirmed the presence of composition modulations in these films. Nanoindentation tests of the TiC/Ti multilayers showed hardness levels exceeding that predicted by the rule-of-mixtures. The TiC/B4C multilayers showed increasing hardness with decreasing bilayer thickness but reached only 221 GPa. The pin-on-disc tests gave friction values ranging from 0.3 to 0.9 for both sets of films. These results were correlated with the degree of crystallinity and grain structure of the films

Mechanical and tribological properties of sub- and superstoichiometric Ti-C and Ti-Si-C films deposited by magnetron sputtering-pulsed laser deposition

The magnetron sputtering-pulsed laser deposition (MSPLD) method has been used to deposit Ti-C and Ti-Si-C films with both sub- and superstoichiometric levels of carbon. The structure and composition of the films were analyzed by transmission electron microscopy, x-ray diffraction, and x-ray photoelectron spectroscopy. The mechanical properties were determined by nanoindentation and the tribological properties by pin-on-disk testing. Films deposited with sub- and near stoichiometric levels of carbon had good crystallinity and strong (111) texture. However, films deposited under similar conditions but with a substrate bias resulted in superstoichiometric carbon levels and nanocrystalline or near-amorphous structures. The hardness of these superstoichiometric films was generally lower than the substoichiometric films, but they also exhibited significantly better wear life. The laser power used in the MSPLD process was also found to influence hardness, where increased laser power led to higher hardness levels. Using these results, an effort was made to deposit a film with optimal mechanical and tribological properties by depositing a Ti4Si-C film with -150 V bias, maximum laser power (700 mJ/pulse) at a temperature of 400degreesC. This film contained 55% carbon, had a hardness of 28 GPa, and ran for greater than 106 cycles on the pin-on-disk test. (C) 2003 American Vacuum Society

Composite coatings incorporating solid lubricant phases

The concept of incorporating a solid lubricant, silver (Ag), within a hard carbide film for vacuum tribology applications is investigated in this paper. SiC/Ag and HfC/Ag films were deposited by magnetron cosputtering at 200 degreesC onto Si and 440C steel substrates. The composition, phase structure, and morphology in these films was examined using x-ray diffraction, scanning electron microscopy, and x-ray photoelectron spectroscopy. The microstructural analysis showed that Ag was incorporated both within and on the surface of the films. There was a strong tendency for Ag to segregate to the film surface. Vacuum tribology tests were conducted using a ball-on-disk test in a vacuum of 1.33 muPa with a 1 N load for 10 000 cycles. For both the SiC/Ag and HfC/Ag films, the average friction coefficients were reduced when sufficient Ag was present. These tests show that carbide-Ag composite films hold promise for vacuum tribology applications

Structure and mechanical properties of Ti-Si-C coatings deposited by magnetron sputtering

Nanostructured coatings consisting of mixed carbide phases can provide a potential means to developing superhard coatings. Heterogeneous nanostructured coatings can be obtained by either deposition of multilayer structures or by depositing film compositions that undergo a natural phase separation due to thermodynamic immiscibility. In the present work, we have taken the latter approach, and deposited films by radio frequency cosputtering from dual carbide targets. We have examined a number of ternary carbide systems, and here we report the results obtained on Ti-Si-C films with a nominal (Ti1-xSix)C stoichiometry and with x less than or equal to0.31. It was found that the nanoindentation hardness increased with Si content, and the maximum hardness achieved was nearly twice that of sputter-deposited TiC. We further analyzed these films using high-resolution transmission electron microscopy (TEM), x-ray photoelectron spectroscopy (XPS), and x-ray diffraction. Since cubic SiC has an x-ray pattern almost identical to that of TiC, the extent of phase separation could not be determined by that method. However, XRD did demonstrate a general disordering of the films with increasing SiC content. In addition, a mottled structure was observed in high-resolution TEM images of the Si-containing films, confirming microstructural effects due to the Si additions. (C) 2001 American Vacuum Society

Structural and mechanical properties of TiC and Ti-Si-C films deposited by pulsed laser deposition

TiC and Ti-Si-C films have been deposited by pulsed laser deposition at substrate temperatures ranging from room temperature to 600 degreesC onto (111) silicon wafers and 440C stainless steel substrates. X-ray diffraction, x-ray photoelectron spectroscopy, and electron microscopy were employed for structural and compositional evaluation of the films, and nano-indentation hardness testing and pin-on-disk wear tests were used to evaluate the mechanical and tribological properties. All the TiC films were highly crystalline except the one deposited at room temperature, whereas for the Ti-Si-C films the degree of crystallinity increased with temperature, ranging from amorphous for the room temperature deposit to about 50% crystalline at 600 degreesC. The hardness of the TiC films was relatively constant with deposition temperature at about 25 GPa, whereas the hardness of the Ti-Si-C films increased with deposition temperature from 11 to 33 GPa. The temperature dependence of the hardness is attributed to the degree of crystallinity and the extent of phase separation in the Ti-Si-C films. The wear test data showed good results for all films up to the tested limit of 10 000 cycles at 1 N load. (C) 2001 American Vacuum Society

Magnetron sputter deposition of WC-Ag and TiC-Ag coatings and their frictional properties in vacuum environments

Thin films of WC-Ag and TiC-Ag were deposited by magnetron sputtering for the purpose of analyzing their tribological properties in vacuum. X-ray diffraction was used to determine structural properties, and energy dispersive X-ray analysis was used to determine the relative atomic content of silver in the films. Pin on disk friction tests were performed to obtain the coefficient of friction in vacuum. The deposited films showed a structure containing separate carbide/silver phases, as was desired for providing both high wear resistance and low friction. The tribological test results show a significant decrease in the friction coefficient for both TiC-Ag and WC-Ag, to a minimum value of 0.2, with increasing silver content. (C) 2002 Acta Materialia Inc. Published by Elsevier Science Ltd. All rights reserved

Microstructure and vacuum tribology of TiC-Ag composite coatings deposited by magnetron sputtering-pulsed laser deposition

Composite titanium carbide-silver films have been co-deposited by magnetron sputtering-pulsed laser deposition (MSPLD) to study their friction and wear properties in vacuum. The films deposited were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS), The silver content in the films ranged from 6 to 46 at.%. Structural characterization of the films revealed that Ag had a nano-crystalline structure when dispersed in the film, but larger crystallites of Ag (similar to50-200 nm) also formed on the surface. Films with higher Ag contents showed evidence of higher diffusion rates, leading to a coarser structure and greater surface coverage. Pin-on-disk friction tests were performed under vacuum to observe the friction and wear behavior of these films. Friction was lower with higher Ag content, but wear was higher; the optimal Ag concentration was found to be 15%. SEM images from the surface of the films and wear tracks were obtained to understand the morphology of this type of composite ceramic coating, and revealed Ag layers in the wear track elongated in the direction of wear. Based on these results, the significance of silver as a friction-reducing agent in vacuum environments was demonstrated. (C) 2002 Elsevier Science B.V. All rights reserved

Pulsed laser-ablated MoS2-Al films: friction and wear in humid conditions

The application of MoS2 as a solid lubricant in dry conditions is well established, but the presence of humidity degrades the tribological behavior of MoS2 films. There has been much progress toward increasing the efficiency of MoS2 films in humid environments by using various additives. In our work, aluminum is evaluated as an additive because of its affinity for O-2 and (OH) compared to Mo and its potential to modify transfer film formation. The MoS2 films examined here were deposited on 440C steel substrates by laser ablation along with simultaneous magnetron sputtering of Al. The friction and wear studies were made on a ball on disc tribometer. Films containing Al outperformed pure MoS2. Under optimal conditions, 1-2-mum-thick films with similar to 8% aluminum had a wear life of 150 to 250 K cycles in 25% humidity. Micro-Raman and X-ray photoelectron spectroscopy (XPS) were used to analyze chemistry and scanning electron microscopy (SEM) was used to study the morphology and film cross-section. Nanoindentation showed that Al addition did not increase film hardness. The role of aluminum in increasing the wear life of laser-ablated MoS2 films in humid conditions is discussed. The mechanism controlling the increased wear life is partially explained by showing that Al is gradually turned into alumina, creating an adhesive and lubricating mix of wear debris under tribostress in humid surroundings. (C) 2004 Elsevier B.V. All rights reserved