Delamination of ceramic top coat accelerated by CMAS in an EB-PVD thermal barrier coating specimen

Application of thermal barrier coatings (TBCs) which provides thermal insulation to the underlying Nickel-based superalloy substrate has been key technologies in advanced gas turbines. More recently, it has been recognized that the TBCs can be damaged by calcium–magnesium–alumino-silicates (CMAS) resulting from siliceous minerals (dust, sand, ash) containing the intake air and from unclean fuels such as a syngas and biomass gas. In this work basic mechanisms and mechanics as well as the kinetics, were explored, via a model CMAS, by specifying a TBC specimen which consisted of a Ni-base superalloy, MCrAlY bond coat and YSZ top coat fabricated by electron beam physical vapor deposition (EB-PVD) process. It was demonstrated that the penetration and the resultant phase transformation of the YSZ with the CMAS were basic mechanisms(Fig.1(a)). It was a particular finding that the thickness of thermal grown oxide was significantly accelerated by CMAS at the top/bond coat interface, resulting in a predominant delamination of top coat(Fig.1(b)). The behavior was discussed, in comparison with that in the TBC specimen fabricated by an air plasma spraying process(Fig.1(c)). Please click Additional Files below to see the full abstract

Reassessing the Role of APOBEC3G in Human Immunodeficiency Virus Type 1 Infection of Quiescent CD4+ T-Cells

HIV-1 is restricted for infection of primary quiescent T-cells. After viral entry, reverse transcription is initiated but is not completed. Various hypotheses have been proposed for this cellular restriction including insufficient nucleotide pools and cellular factors, but none have been confirmed as the primary mechanism for restriction. A recent study by Chiu et al. implicates APOBEC3G, an anti-retroviral cytidine deaminase, as the cellular restriction factor. Here, we attempted to confirm these findings using the same strategy as reported by Chiu et al. of siRNA targeting knock-down of APOBEC3G expression. In contrast to the published study, our results do not support a role for APOBEC3G in restriction of HIV-1 in quiescent CD4+ T-cells. In our study, we tested the same siRNA as reported by Chiu et al. as well as two additional siRNAs targeting APOBEC3G, one of which showed 2-fold greater knock-down of APOBEC3G mRNA. However, none of the three siRNAs tested had a discernable effect on enhancing infection by HIV-1 in quiescent CD4+ T-cells. Therefore, we conclude that the primary mechanism of HIV-1 restriction in quiescent CD4+ T-cells remains to be elucidated

A New Experimental Approach to Evaluate Plasma-induced Damage in Microcantilever

Plasma  etching,  during  micro-fabrication  processing  is  indispensable  for  fabricating  MEMS  structures.  During  the plasma  processes,  two  major matters,  charged  ions  and  vacuum–ultraviolet  (VUV)  irradiation  damage,  take  charge  of reliability  degradation.  The  charged  ions  induce  unwanted  sidewall  etching,  generally  called  as  “notching”,  which causes  degradation  in  brittle  strength.  Furthermore,  the  VUV  irradiation  gives  rise  to  crystal  defects  on  the  etching surface.  To  overcome  the  problem,  neutral  beam  etching  (NBE),  which  use  neutral  particles  without  the  VUV irradiation,  has  been  developed.  In  order  to  evaluate  the  effect  of  the  NBE  quantitatively,  we  measured  the  resonance property of a micro-cantilever before and after NBE treatment. The thickness of damage layer (δ) times the imaginary part  of  the  complex  Young's  modulus  (Eds)  were  then  compared,  which  is  a  parameter  of  surface  damage.  Although plasma processes  make the initial surface of cantilevers damaged during their fabrication, the removal of that damage by NBE was confirmed as the reduction in δEds. NBE will realize a damage-free surface for microstructures

First-principles study on the intermediate compounds of LiBH4_4

We report the results of the first-principles calculation on the intermediate compounds of LiBH$_4$. The stability of LiB$_3$H$_8$ and Li$_2$B$_n$H$_n (n=5-12)$ has been examined with the ultrasoft pseudopotential method based on the density functional theory. Theoretical prediction has suggested that monoclinic Li$_2$B$_{12}$H$_{12}$ is the most stable among the candidate materials. We propose the following hydriding/dehydriding process of LiBH$_4$ via this intermediate compound : LiBH$_4 \leftrightarrow {1/12}$Li$_{2}$B$_{12}$H$_{12} + {5/6}$ LiH $+ {13/12}$H$_2 \leftrightarrow$LiH $+$ B $+ {3/2}$H$_2$. The hydrogen content and enthalpy of the first reaction are estimated to be 10 mass% and 56 kJ/mol H$_2$, respectively, and those of the second reaction are 4 mass% and 125 kJ/mol H$_2$. They are in good agreement with experimental results of the thermal desorption spectra of LiBH$_4$. Our calculation has predicted that the bending modes for the $\Gamma$-phonon frequencies of monoclinic Li$_2$B$_{12}$H$_{12}$ are lower than that of LiBH$_4$, while stretching modes are higher. These results are very useful for the experimental search and identification of possible intermediate compounds.Comment: 7 pages, 5 figures, submitted to PR

Lyman Alpha Emitters in the Hierarchically Clustering Galaxy Formation

We present a new theoretical model for the luminosity functions (LFs) of Lyman alpha (Lya) emitting galaxies in the framework of hierarchical galaxy formation. We extend a semi-analytic model of galaxy formation that reproduces a number of observations for local and high-z galaxies, without changing the original model parameters but introducing a physically-motivated modelling to describe the escape fraction of Lya photons from host galaxies (f_esc). Though a previous study using a hierarchical clustering model simply assumed a constant and universal value of f_esc, we incorporate two new effects on f_esc: extinction by interstellar dust and galaxy-scale outflow induced as a star formation feedback. It is found that the new model nicely reproduces all the observed Lya LFs of the Lya emitters (LAEs) at different redshifts in z ~ 3-6. Especially, the rather surprisingly small evolution of the observed LAE Lya LFs compared with the dark halo mass function is naturally reproduced. Our model predicts that galaxies with strong outflows and f_esc ~ 1 are dominant in the observed LFs. This is also consistent with available observations, while the simple universal f_esc model requires f_esc << 1 not to overproduce the brightest LAEs. On the other hand, we found that our model significantly overpredicts LAEs at z > 6, and absorption of Lya photons by neutral hydrogen in intergalactic medium (IGM) is a reasonable interpretation for the discrepancy. This indicates that the IGM neutral fraction x_HI rapidly evolves from x_HI << 1 at z < 6 to a value of order unity at z ~ 6-7, which is broadly consistent with other observational constraints on the reionization history.Comment: 14 pages, 7 figures, 1 table; accepted to ApJ; the html abstract is replaced to match the accepted version, the .ps and .pdf files are strictly identical between the 2nd and the 3rd version

Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates

RNAi is a powerful method for suppressing gene expression that has tremendous potential for therapeutic applications. However, because endogenous RNAi plays a role in normal cellular functions, delivery and expression of siRNAs must be balanced with safety. Here we report successful stable expression in primates of siRNAs directed to chemokine (c-c motif) receptor 5 (CCR5) introduced through CD34+ hematopoietic stem/progenitor cell transplant. After hematopoietic reconstitution, to date 14 months after transplant, we observe stably marked lymphocytes expressing siRNAs and consistent down-regulation of chemokine (c-c motif) receptor 5 expression. The marked cells are less susceptible to simian immunodeficiency virus infection ex vivo. These studies provide a successful demonstration that siRNAs can be used together with hematopoietic stem cell transplant to stably modulate gene expression in primates and potentially treat blood diseases such as HIV-1

Efficient derivation of chimeric-antigen receptor-modified TSCM cells

Chimeric-antigen receptor (CAR) T-cell immunotherapy employs autologous-T cells modified with an antigen-specific CAR. Current CAR-T manufacturing processes tend to yield products dominated by effector T cells and relatively small proportions of long-lived memory T cells. Those few cells are a so-called stem cell memory T (TSCM) subset, which express naïve T-cell markers and are capable of self-renewal and oligopotent differentiation into effector phenotypes. Increasing the proportion of this subset may lead to more effective therapies by improving CAR-T persistence; however, there is currently no standardized protocol for the effective generation of CAR-TSCM cells. Here we present a simplified protocol enabling efficient derivation of gene-modified TSCM cells: Stimulation of naïve CD8+ T cells with only soluble anti-CD3 antibody and culture with IL-7 and IL-15 was sufficient for derivation of CD8+ T cells harboring TSCM phenotypes and oligopotent capabilities. These in-vitro expanded TSCM cells were engineered with CARs targeting the HIV-1 envelope protein as well as the CD19 molecule and demonstrated effector activity both in vitro and in a xenograft mouse model. This simple protocol for the derivation of CAR-TSCM cells may facilitate improved adoptive immunotherapy

Impact of cystic fibrosis transmembrane conductance regulator gene mutation on the occurrence of chronic pancreatitis in Japanese patients

金沢大学医薬保健研究域医学系DNA analyses of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in japanese patients with idiopathic chronic pancreatitis (ICP) were performed to determine the relationship between the CFTR mutation and ICP. The study included patients with alcoholic pancreatitis (n = 20), patients with ICP (n = 20) and healthy volunteers (controls; n = 110). The poly-T region in intron 8 of the CFTR gene was analysed by direct sequencing. The CFTR coding region was screened using single-strand conformational polymorphism and direct sequencing. In the controls, frequencies of the 5T genotype and 5T allele were 4.5% and 3.6%, respectively. The frequency of the 5T genotype was significantly higher in the ICP group (20%) versus controls, but was not significantly different in alcolohol chronic pacreatitis patients (5%). Thus, the CFIR gene mutation, especially the 5T genotype, appears to have some relationship to ICP prevalence in japanese patients independent of cystic fibrosis. Copyright © 2009 Field House Publishing LLP

Geochemical characteristics of back-arc basin lower crust and upper mantle at final spreading stage of Shikoku Basin: an example of Mado Megamullion

AbstractThis paper explores the evolutional process of back-arc basin (BAB) magma system at final spreading stage of extinct BAB, Shikoku Basin (Philippine Sea) and assesses its tectonic evolution using a newly discovered oceanic core complex, the Mado Megamullion. Bulk and in-situ chemical compositions together with in-situ Pb isotope composition of dolerite, oxide gabbro, gabbro, olivine gabbro, dunite, and peridotite are presented. Compositional ranges and trends of the igneous and peridotitic rocks from the Mado Megamullion are similar to those from the slow- to ultraslow-spreading mid-ocean ridges (MOR). Since the timing of the Mado Megamullion exhumation corresponds to the very end of the Shikoku Basin opening, the magma supply was subdued and highly episodic, leading to extreme magma differentiation to form ferrobasaltic, hydrous magmas. In-situ Pb isotope composition of magmatic brown amphibole in the oxide gabbro is identical to that of depleted source mantle for mid-ocean ridge basalt (MORB). In the context of hydrous BAB magma genesis, the magmatic water was derived solely from the MORB source mantle. The distance from the back-arc spreading center to the arc front increased away through maturing of the Shikoku Basin to cause MORB-like magmatism. After the exhumation of Mado Megamullion along detachment faults, dolerite dikes intruded as a post-spreading magmatism. The final magmatism along with post-spreading Kinan Seamount Chain volcanism were introduced around the extinct back-arc spreading center after the opening of Shikoku Basin by residual mantle upwelling

Nitric oxide activates ATP-sensitive potassium channels in mammalian sensory neurons: action by direct S-nitrosylation

<p>Abstract</p> <p>Background</p> <p>ATP-sensitive potassium (K_ATP) channels in neurons regulate excitability, neurotransmitter release and mediate protection from cell-death. Furthermore, activation of K_ATPchannels is suppressed in DRG neurons after painful-like nerve injury. NO-dependent mechanisms modulate both K_ATPchannels and participate in the pathophysiology and pharmacology of neuropathic pain. Therefore, we investigated NO modulation of K_ATPchannels in control and axotomized DRG neurons.</p> <p>Results</p> <p>Cell-attached and cell-free recordings of K_ATPcurrents in large DRG neurons from control rats (sham surgery, SS) revealed activation of K_ATPchannels by NO exogenously released by the NO donor SNAP, through decreased sensitivity to [ATP]i.</p> <p>This NO-induced K_ATPchannel activation was not altered in ganglia from animals that demonstrated sustained hyperalgesia-type response to nociceptive stimulation following spinal nerve ligation. However, baseline opening of K_ATPchannels and their activation induced by metabolic inhibition was suppressed by axotomy. Failure to block the NO-mediated amplification of K_ATPcurrents with specific inhibitors of sGC and PKG indicated that the classical sGC/cGMP/PKG signaling pathway was not involved in the activation by SNAP. NO-induced activation of K_ATPchannels remained intact in cell-free patches, was reversed by DTT, a thiol-reducing agent, and prevented by NEM, a thiol-alkylating agent. Other findings indicated that the mechanisms by which NO activates K_ATPchannels involve direct S-nitrosylation of cysteine residues in the SUR1 subunit. Specifically, current through recombinant wild-type SUR1/Kir6.2 channels expressed in COS7 cells was activated by NO, but channels formed only from truncated isoform Kir6.2 subunits without SUR1 subunits were insensitive to NO. Further, mutagenesis of SUR1 indicated that NO-induced K_ATPchannel activation involves interaction of NO with residues in the NBD1 of the SUR1 subunit.</p> <p>Conclusion</p> <p>NO activates K_ATPchannels in large DRG neurons via direct S-nitrosylation of cysteine residues in the SUR1 subunit. The capacity of NO to activate K_ATPchannels via this mechanism remains intact even after spinal nerve ligation, thus providing opportunities for selective pharmacological enhancement of K_ATPcurrent even after decrease of this current by painful-like nerve injury.</p