Tuning the Internal Energy of Ions Produced by Atmospheric and High-Pressure Electrospray by Modulating the Gas Throughput into the First Vacuum Stage.

In a high-pressure environment, electrospray ionization (ESI) can be achieved without discharge between the emitter and the counter electrode, thus enabling the generation of gas-phase ions from liquid with high surface tension, such as pure water, which requires a high onset voltage for stable ESI. In this study, the ion dissociation during the transferring of ions/charged droplets from a superatmospheric pressure environment to vacuum has been systematically investigated using benzyl ammonium thermometer ions. The ion source pressure did not affect the internal energy distribution of ions, whereas the gas throughput into the first vacuum stage clearly influences the internal energy distribution of the ions. The increase in the gas throughput increased the density of molecules/atoms presented in ion transfer/focusing electrodes located in the first vacuum stage. As a result, the mean free path of ions in the first vacuum stage decreases, and the energy of ions decreases by decreasing the kinetic energy involved in each collision between ions and residue gas. The gas throughput into the first vacuum stage is found to describe the internal energy distribution of ions associated with the local conditions more quantitatively instead of using the measured pressure of the vacuum stage, which is different from the effective local pressure. This study also demonstrated the controlled dissociation of ions using the ion transfer settings of the instrument in combination with ion inlet tubes of different sizes.

Global Diversification of Anelosimus Spiders Driven by Long-Distance Overwater Dispersal and Neogene Climate Oscillations.

Vicariance and dispersal events, combined with intricate global climatic history, have left an imprint on the spatiotemporal distribution and diversity of many organisms. Anelosimus cobweb spiders (Theridiidae), are organisms ranging in behavior from solitary to highly social, with a cosmopolitan distribution in temperate to tropical areas. Their evolutionary history and the discontinuous distribution of species richness suggest that 1) long-distance overwater dispersal and 2) climate change during the Neogene (23-2.6 Ma), may be major factors in explaining their distribution and diversification. Here, we test these hypotheses, and explicitly test if global Miocene/Pliocene climatic cooling in the last 8 Ma affected Anelosimus radiation in parallel in South America and Madagascar. To do so, we investigate the phylogeny and spatiotemporal biogeography of Anelosimus through a culmination of a 20-year comprehensive global sampling at the species level (69 species, including 84% of the known 75 species worldwide, represented by 268 individuals) using nucleotide data from seven loci (5.5 kb). Our results strongly support the monophyly of Anelosimus with an Oligocene ($\sim $30 Ma) South American origin. Major clades on other continents originate via multiple, long-distance dispersal events, of solitary or subsocial-but not social-lineages, from the Americas. These intercontinental dispersals were to Africa, Madagascar (twice), and SE Asia/Australasia. The early diversification of Anelosimus spiders coincides with a sudden thermal increase in the late Oligocene ($\sim $27-25 Ma), though no causal connection can be made. Our results, however, strongly support the hypothesis that global Neogene climatic cooling in the last 8 Ma drove Anelosimus radiation in parallel in South America and Madagascar, offering a rare empirical evidence for diversification of a socially diverse group driven by an interplay between long-distance dispersal and global Neogene climatic changes. [Cobweb spiders; diversification; global biogeography; long-distance dispersal; molecular phylogenetics; neogene climate changes; sociality; vicariance.].

Accurate and stable equal-pressure measurements of water vapor transmission rate reaching the 10-6 g m-2 day-1 range.

The water vapor transmission rate (WVTR) of a gas barrier coating is a critically important parameter for flexible organic device packaging, but its accurate measurement without mechanical stress to ultrathin films has been a significant challenge in instrumental analysis. At the current stage, no reliable results have been reported in the range of 10-6 g m-2 day-1 that is required for organic light emitting diodes (OLEDs). In this article, we describe a solution for this difficult, but important measurement, involving enhanced sensitivity by a cold trap, stabilized temperature system, pumped sealing and calibration by a standard conductance element.

[Do practices of learning activities improve the cognitive functioning of healthy elderly adults? From the viewpoint of a transfer effect].

The present study examined influences of reading aloud and performing simple calculation on the cognitive functioning of healthy elderly adults, based on the findings that these tasks activated the prefrontal lobe. The elderly adults' memory and inhibitory functions were assesed by Short-Term memory, CST, Stroop, and SRC tasks, before and after intervention for 18 months. The study found that the learning group had significant improvement from the pre- to the post-test for the short-term memory, STM, CST, and Stroop tasks. On the other hand, there was significant decline over the 18 months in the control group which was given only the assessment tasks. These results are discussed in terms of the effectiveness of cognitive training.

Motor inhibition in aging: impacts of response type and auditory stimulus.

The authors examined the effects of response types and the presentation of auditory stimulus on motor inhibition. Continuous responding tasks were conducted with 27 younger adults and 39 older adults. The results indicated the following: (a) response type significantly affected error rates in older adults, (b) the presentation of an auditory stimulus facilitated responses and decreased reaction times in both younger and older adults, (c) the presentation of an auditory stimulus also increased error rates in older adults, and (d) the effect of response type on error rate remained in experiments conducted under different conditions in older adults. This suggests that in older adults, movement and the associated nervous excitation have significant effects on motor inhibition.

Capacitance distribution of Ni-Nb-Zr-H glassy alloys.

Capacitance distribution of {(Ni(0.6)Nb(0.4)(1-x)Zrx}(100-y)-Hy (x = 0.30, 0.35, 0.40, 0.45 and 0.50, 0 < or = y < or = 20) glassy alloy ribbons was carried out by ac impedance analysis at frequency of 1 kHz, in terms of a distributed constant equivalent circuit. The capacitance can be represented by oblique contour lines. The highest capacitance (1-11 microF) could be found near the point when x = 0.40, y = 10, which is a composition occurring room-temperature Coulomb oscillation, while capacitance of the composition (x = 0.35, y = 4) occurring ballistic transport was around 0.8 microF. The capacitance difference would be explained by an effect of hydrogen localization derived from morphology of distorted Zr-centered icosahedral Zr5Ni5Nb3 clusters and ideal Ni-centered clusters. The electrocapillarity equation showed that the specific capacitance between two electrodes increases parabolic with decreasing the distance, as a polarized glutinous liquid.

Superconductivity of Ni-Nb-Zr-H glassy alloys with nanoclusters.

We investigated the hydrogen effect on superconductivity in the (Ni0.36Nb0.24Zr0.40)(100-x)H(x)(0 < or = x < or = 6.4) glassy alloys with nanoclusters, as a function of temperature. The resistivity of these alloys started to drop from onset temperature of around 9.5 K. The (Ni0.36Nb0.24Zr0.40)98.6H1.6 showed zero resistance at 2.1 K. However, the application of a magnetic field > 4.6 T arrested the drop of resistivity, showing the existence of superconductivity of type II. The maximum onset temperature of 11.3 K was observed at 4.4 at% H. The superconducting behavior of the glassy alloys would be associated with electron pair transport along zigzag paths, which link the shortened atomic -Ni-Ni-Ni- array in the Zr5Ni5Nb3 clusters, and tunneling among the clusters.

Reversible haptotropic shift in zirconocene-hexapentaene complexes.

Low-valent zirconocene species reacted with 1,1,6,6-tetraalkyl-1,2,3,4,5-hexapentaenes to form both 1-zirconacyclopent-3-ynes and eta2-pi-coordinated complexes according to the alkyl groups (R) and the existence of the neutral ligand (L). Haptotropic interconvertion between these two complexes was observed. It was proposed that double insertion of isocyanide into the Zr-C bond of 1-zirconacyclopent-3-ynes takes place via the isocyanide adduct of the eta2-pi-complex as an intermediate.

Ribonucleotide reductase small subunit p53R2 promotes oral cancer invasion via the E-cadherin/beta-catenin pathway.

The p53-inducible p53R2 gene has been isolated and shown to play a crucial role in DNA repair and synthesis after DNA damage. Moreover, the expression and activity of p53R2 has been reported to be associated with the anticancer agent resistance of human cancer cells. Previously, we reported that the presence of p53R2 expression was a predictive factor for regional lymph node metastasis in oral squamous cell carcinoma; however, the mechanism of cancer metastasis by p53R2 expression is still unclear. In the present study, we analyzed the correlation of p53R2 expression with cancer invasion in vitro. Three human oral cancer cell lines (SAS, HSC-3 and Ca9-22) were cultured, and the invasive potential of these cancer cells was evaluated using Matrigel invasion assay. To investigate the effect of p53R2 on cancer invasion, the down-regulation of p53R2 was examined by small interfering RNA (siRNA). Moreover, we examined the intracellular localization of cell adhesion molecules (E-cadherin and beta-catenin) in subcellular extractions of cancer cells by immunoblotting. The proteolytic activity of matrix metalloproteinases (MMPs) was assessed by gelatin zymography. Down-regulation of p53R2 significantly enhanced the invasion potential (p<0.01), and enhanced nuclear translocation of beta-catenin with loss of total cellular E-cadherin expression in p53 mutant cancer cells, but not in p53 wild-type cancer cells. These changes in the invasion index by p53R2 siRNA transfection were not accompanied by alterations in MMP activity and expression. These results suggested that the expression of p53R2 could be associated with the invasion of cancer cells, and indicated that p53R2 might promote cancer invasion via the E-cadherin/beta-catenin pathway without the alteration of MMP activity.

Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-kappaB and Akt pathways.

Berberine, an isoquinoline alkaloid isolated from several medicinal plants, has been reported to possess anti-bacterial, anti-inflammatory and antitumor properties. Although berberine also inhibits osteoclastogenesis and bone resorption, the molecular machinery for its inhibitory effects remains unknown. This study focused on the suppressive effects of berberine on receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-induced osteoclastogenesis and survival. Berberine inhibited RANKL-mediated osteoclast formation and survival while having no cytotoxic effects on bone marrow macrophages or osteoblastic cells. Berberine attenuated RANKL-induced activation of NF-kappaB through inhibiting phosphorylation at the activation loop of IkappaBalpha kinase beta, phosphorylation and degradation of IkappaBalpha, and NF-kappaB p65 nuclear translocation. RANKL-induced Akt phosphorylation was strongly inhibited by berberine; however, neither monocyte/macrophage-colony stimulating factor (M-CSF)-induced nor insulin-induced Akt activation was inhibited by the drug. Under M-CSF- and RANKL-deprived condition, berberine increased the active form of caspase-3 in osteoclasts. By contrast, berberine did not potentiate the activation of caspase-3 in M-CSF-deprived bone marrow macrophages. These findings indicate that berberine inhibits osteoclast formation and survival through suppression of NF-kappaB and Akt activation and that both pathways in the osteoclast lineage are highly sensitive to berberine treatment.

Chordal "translocation" for functional mitral regurgitation with severe valve tenting: an effort to preserve left ventricular structure and function.

OBJECTIVE: The chordal cutting method is performed for mitral valve tenting in functional mitral regurgitation, such as ischemic mitral regurgitation. However, the method may interfere with the mitral valvular-ventricular continuity. To maintain the continuity and the natural force direction between the papillary muscles and the mitral annulus after chordal cutting, we developed "translocation" of the secondary chordae tendineae. METHODS: Six mongrel dogs had sonomicrometry crystal markers implanted in the left ventricle, mitral annulus, and papillary muscle tips. After the secondary chordae tendineae of the anterior mitral leaflet from each papillary muscle were resected, each papillary muscle tip was connected to the mid-anterior mitral annulus with 4-0 polypropylene sutures, and then the sutures were taken out of the left atrium to control the chordal tension. The condition under which the artificial chordae were released was defined as "redundant." The chordal tension of 15 g of weight was defined as "taut," whereas the tension for 2-mm chordal shortening after "taut" was defined as "tight." After the dogs were weaned from cardiopulmonary bypass, hemodynamic and 3-dimensional data were acquired under the condition of "redundant," and then "taut," "tight," and "redundant." RESULTS: End-systolic elastance increased from 1.81 +/- 0.24 mm Hg/mL to 2.69 +/- 0.89 mm Hg/mL (P = .015) between "redundant" and "taut," and this was maintained between "taut" and "tight." However, preload recruitable stroke work increased from 41.3 +/- 12.0 mm Hg to 58.1 +/- 19.7 mm Hg (P = .005) between "redundant" and "taut," and was reduced to 51.7 +/- 22.9 mm Hg (P = .037) between "taut" and "tight." CONCLUSION: "Translocation" of the secondary chordae tendineae after chordal cutting improved left ventricular systolic function compared with simple chordal cutting.

Pepstatin A, an aspartic proteinase inhibitor, suppresses RANKL-induced osteoclast differentiation.

Pepstatin A is well known to be an inhibitor of aspartic proteinases such as pepsin, cathepsins D and E. Except for its role as a proteinase inhibitor, however, the pharmacological action of pepstatin A upon cells remain unclear. In this study, we found that pepstatin A suppressed receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast differentiation. Pepstatin A suppressed the formation of multinuclear osteoclasts dose-dependently. This inhibition of the formation only affected osteoclast cells, i.e., not osteoblast-like cells. Furthermore, pepstatin A also suppressed differentiation from pre-osteoclast cells to mononuclear osteoclast cells dose-dependently. This inhibition seems to be independent of the activities of proteinases such as cathepsin D, because the formation of osteoclasts was not suppressed with the concentration that inhibited the activity of cathepsin D. Cell signaling analysis indicated that the phosphorylation of ERK was inhibited in pepstatin A-treated cells, while the phosphorylation of IkappaB and Akt showed almost no change. Furthermore, pepstatin A decreased the expression of nuclear factor of activated T cells c1 (NFATc1). These results suggest that pepstatin A suppresses the differentiation of osteoclasts through the blockade of ERK signaling and the inhibition of NFATc1 expression.

Reading aloud and arithmetic calculation improve frontal function of people with dementia.

BACKGROUND: Recent findings of neuroimaging studies indicate that reading aloud and arithmetic calculation activate bilateral dorsolateral prefrontal cortex of humans. The purpose of this study was to measure the effect of reading aloud and arithmetic calculation, by elderly people who were clinically diagnosed with dementia Alzheimer type, on their brain functions and activities of daily living. METHODS: Sixteen experimental and 16 age- and Mini-Mental State Examination score-matched control subjects participated. The participants in the experimental group were asked to perform a training program using learning tasks in reading and arithmetic for 2-6 days a week. The function of the frontal cortex of the subjects was assessed by FAB at bedside (Frontal Assessment Battery). RESULTS: After 6 months of training, the FAB score of the experimental group showed a statistically significant improvement. The FAB score of the control group decreased slightly over the 6-month period, and the difference between the scores of the experimental and control groups was statistically significant. We also observed the restoration of communication and independence in the experimental group. CONCLUSION: Our results indicate that learning tasks of reading aloud and arithmetic calculation can be used for cognitive rehabilitation of dementia patients.

A functional MRI study of simple arithmetic--a comparison between children and adults.

The purpose of this study was to examine brain areas involved in simple arithmetic, and to compare these areas between adults and children. Eight children (four girls and four boys; age, 9-14 years) and eight adults (four women and four men; age, 40-49 years) were subjected to this study. Functional magnetic resonance imaging (fMRI) was performed during mental calculation of addition, subtraction, and multiplication of single digits. In each group, the left middle frontal, bilateral inferior temporal and bilateral lateral occipital cortices were activated during each task. The adult group showed activation of the right frontal cortex during addition and multiplication tasks, but the children group did not. Activation of the intraparietal cortex was observed in the adult group during each task. Although, activation patterns were slightly different among tasks, as well as between groups, only a small number of areas showed statistically significant differences. The results indicate that cortical networks involved in simple arithmetic are similar among arithmetic operations, and may not show significant changes in the structure during the second decade of life.

Plasma separator Plasmaflo OP.

In recent years, polyethylene and polysulfone membranes have been used for plasma separation in Japan. The polyethylene membrane, manufactured by melt spinning method, has a sponge-like symmetric structure. The plasma separator Plasmaflo OP (Asahi Medical, Tokyo, Japan) with a polyethylene membrane shows excellent performance and safety for plasma separation. More than 20 indications for therapeutic plasmapheresis are reimbursed in Japan. Future development is expected in new membrane designs for new indications or advanced plasmapheresis methodologies.

Production of ubiquinone-10 using bacteria.

Among the bacterial strains known to contain ubiquinone-10, three strains, Agrobacterium tumefaciens KY-3085 (ATCC4452), Paracoccus denitrificans KY-3940 (ATCC19367) and Rhodobacter sphaeroides KY-4113 (FERM-P4675), were selected as excellent producers of this ubiquinone. The ubiquinone-10 production by the Agrobacterium and Rhodobacter strains was affected by aeration. An ethionine-resistant mutant (M-37) derived from A. tumefaciens KY-3085 promoted increased production of ubiquinone-10 (20% higher than the parent). Another Agrobacterium mutant (AU-55), which was induced by the successive addition of four genetic markers, showed a tolerance to the suppression of ubiquinone-10 production caused by aeration, and the fermentation time for production was remarkably shortened. The amount of ubiquinone-10 produced by this Agrobacterium mutant reached 180 mg/l in a 58 h culture. A green mutant (carotenoid-deficient mutant, Co-22-11) derived from R. sphaeroides KY-4113 produced 350 mg/l of ubiquinone-10 under culturing conditions with a limited supply of air, the ubiquinone-10 content being 8.7 mg/g-dry cell. In this case, the amount and content corresponded to 2.8 and 3.6 times larger than those given by the wild-type strain, respectively. A multiple-layer structure of cell membrane was observed in the highly ubiquinone-10 accumulating cell of the green mutant by electron microscopy. The amount of ubiquinone-10 produced by P. denitrificans was much lower than those of the other two strains.