Missense mutations in the human presenilin-1 (PS1) gene, which is found on chromosome 14, cause early-onset familial Alzheimer's disease (FAD). FAD-linked PS1 variants alter proteolytic processing of ...the amyloid precursor protein and cause an increase in vulnerability to apoptosis induced by various cell stresses. However, the mechanisms responsible for these phenomena are not clear. Here we report that mutations in PS1 affect the unfolded-protein response (UPR), which responds to the increased amount of unfolded proteins that accumulate in the endoplasmic reticulum (ER) under conditions that cause ER stress. PS1 mutations also lead to decreased expression of GRP78/Bip, a molecular chaperone, present in the ER, that can enable protein folding. Interestingly, GRP78 levels are reduced in the brains of Alzheimer's disease patients. The downregulation of UPR signalling by PS1 mutations is caused by disturbed function of IRE1, which is the proximal sensor of conditions in the ER lumen. Overexpression of GRP78 in neuroblastoma cells bearing PS1 mutants almost completely restores resistance to ER stress to the level of cells expressing wild-type PS1. These results show that mutations in PS1 may increase vulnerability to ER stress by altering the UPR signalling pathway.
To improve the tap density of TiO sub(2)(B) as a high potential negative electrode for lithium-ion batteries, the particle size and the shape of the TiO sub(2)(B) were controlled by a new synthetic ...method using large-size Nb-doped rutile TiO sub(2) as a starting material. The Nb-doped TiO sub(2)(B) particles, Ti sub(0.93)Nb sub(0.07)O sub(2)(B) and Ti sub(0.90)Nb sub(0.10)O sub(2)(B), were much smaller (diameter: ca. 100 nm, length: ca. 800 nm) than the conventional TiO sub(2)(B) prepared using fine anatase TiO sub(2) particles as a starting material, and were agglomerated to form secondary particles with a diameter of 3-30 mu m. The tap densities of Ti sub(0.93)Nb sub(0.07)O sub(2)(B) and Ti sub(0.90)Nb sub(0.10)O sub(2)(B) were successibly high (0.77 and 0.66 g cm super(-3), respectively), which were ca. 2-fold higher than that of the conventional TiO sub(2)(B) (0.30 g cm super(-3)). As a result, the discharge capacity per electrode volume was significantly improved for both Nb-doped samples without sacrificing the cycleability. Non-doped TiO sub(2)(B) was prepared from large-size rutile TiO sub(2) by a similar method, but it deteriorated upon cycling, accompanied by the formation of the anatase phase. It was shown that Nb-doping not only improves the discharge capacity per electrode volume, but also effectively stabilizes the TiO sub(2)(B) crystal structure of the small particles.
The aim of this study was to evaluate the 24-hour intraocular pressure (IOP)-control effect of the tafluprost/timolol fixed combination (TAF/TIM-FC) in patients with primary open-angle glaucoma after ...they switched from the concomitant use of tafluprost and timolol gel-forming solution.
Twenty patients with primary open-angle glaucoma (12 male and 8 female; mean ± SD age, 57.0±7.1 years) were included in this study. The patients were treated for 8 weeks with the concomitant administration of tafluprost and timolol gel-forming solution (evening dosing). At the end of this period, the patients underwent 24-hour IOP monitoring (measured at 21:00, 01:00, 05:00, 09:00, 13:00 and 17:00). IOP was measured with Goldmann applanation tonometer (GAT) and Icare PRO at sitting position at all timepoints and additionally, at supine position with Icare PRO tonometer at 01:00 and 05:00. The patients were then all switched to TAF/TIM-FC treatment (evening dosing). After 8 weeks, the 24-hour IOP monitoring was repeated.
Nineteen patients completed the study. The mean 24-hour IOPs in the concomitant and TAF/TIM-FC phases were 13.8±2.7 vs 13.3±2.8 mmHg (
=0.0033) with the GAT in the sitting position and 13.96±2.56 vs 13.48±2.56 mmHg (
=0.0120) with the Icare PRO in habitual positions. In comparison with the concomitant phase, significantly lower IOP was observed for the TAF/TIM-FC phase at 21:00 and 01:00 with the GAT and at 01:00 with the Icare PRO. In addition, the maximum IOP and fluctuations in IOP in habitual positions were lower for the TAF/TIM-FC phase than for the concomitant phase.
TAF/TIM-FC showed a stable 24-hour IOP-lowering effect and was equally or more effective than the concomitant use of tafluprost and timolol gel, both when sitting and when in habitual positions.
We have developed a novel recovery system of palladium (Pd) from wastes such as spent catalysts or scraps, using tannin gel particles synthesized from condensed-tannin molecules. The Pd(II) ionic ...species are reduced to metallic Pd(0) on the network of the tannin gel: a two-electron transfer from the tannin gel to Pd(II). The kinetic study of the electron transfer was performed with a multiple reaction model containing an intermediate step (formation of a ligand-substituted Pd(II)–tannin inner sphere complex), resulting in a better fit with the experimental results than with the single reaction model (outer sphere redox reaction), which means that the inner sphere redox mechanism is an appropriate reaction model for the Pd(II) adsorption process. Because the intermediate is included in the adsorption amount, the adsorption process can be divided into two steps: fast adsorption by the ligand substitution at the initial stage and slow adsorption by the subsequent redox reaction after the ligand substitution reaches an equilibrium state, with different adsorption rates between the Pd(II) ionic species
(
PdCl
+
>
PdCl
2
>
PdCl
3
-
,
PdCl
4
2
-
)
.
To evaluate the effects of vitreomacular and cataract surgery on retinal oximetry in vitreomacular disease.
Thirty-eight eyes with epiretinal membrane (ERM) and 15 with idiopathic macular hole (MH) ...underwent 25 gauge pars plana vitrectomy combined with cataract surgery and intraocular lens implantation. Retinal oximetry was performed using the Oxymap T1 before, 1 month, and 6 months after surgery. Oxymap T1 simultaneously captures monochrome images of the fundus at two different wavelengths of light. Built-in Oxymap Analyzer software measures the oxygen saturation and vessel diameter.
Mean arterial oxygen saturation significantly increased from 96.8%±6.2% to 100.2%±5.8% at 1 month and to 99.6%±5.8% at 6 months after surgery (
<0.01). Mean venous oxygen saturation also significantly increased from 54.6%±7.5% to 61.2%±6.4% at 1 month and to 62.6%±5.9% at 6 months after surgery (
<0.01). Mean arteriovenous (A-V) difference decreased from 42.2%±6.6% to 39.0%±7.8% at 1 month and to 37.0%±6.9% at 6 months after surgery (
<0.01). The ERM and MH groups showed similar changes in retinal oxygen saturation. However, there were no significant changes in the caliber of major retinal vessels after surgery (from 125.2±15.2 μm to 124.0±15.4 μm in artery, from 168.7±14.6 μm to 169.8±14.6 μm in vein).
Oxymap T1 was able to measure the increase in oxygen saturation in retinal arteries and veins, which led to a decrease in the A-V difference in oxygen saturation after vitrectomy combined with cataract surgery.
Net activity of tissue-nonspecific alkaline phosphatase (TNAP) and acid phosphatase (ACP) remains to be determined since enzyme histochemistry has adopted biochemically determined optimal pH, which ...is not likely to represent local pH in vivo. The present study aimed to evaluate TNAP and ACP activities associated with bone cells at physiological pH. At the physiological pH of tissue fluid, intense phosphatase reactions were demonstrable in osteoblasts and osteoclasts as well as the bone matrix associated with osteoclasts. In fresh-frozen and freeze-substituted specimens, intense phosphatase reactions appeared at both alkaline and neutral pH along the entire surface of osteoblasts including the osteoidal surface, where TNAP was shown to be absent by immunohistochemistry. Combined specificity tests suggested that TNAP and ACP in bone cells can serve as phosphohydrolases at pH 7.3 and that reactions along the osteoidal surface of osteoblasts differ from that of TNAP and represent novel enzyme.
The fabrication and the characteristics of the laterally coupled GaInAsP-InP quantum-well ridge waveguide distributed-feedback (DFB) lasers are presented. The electron beam (EB) lithography and the ...wet and dry hybrid etching technique have been used to fabricate the deep grating structures for the DFB lasers on and beside the sidewalls of the narrow ridge waveguide. The threshold current was 18.5 mA at 20/spl deg/C, and the sidemode suppression ratios (SMSRs) were ensured to be more than 40 dB for as-cleaved devices with various cavity lengths. The continuous-wave output powers of over 15 mW/facet have been observed, while transverse and longitudinal modes have remained in single mode at this output level.
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