269 research outputs found
Josephson current in s-wave superconductor / Sr_2RuO_4 junctions
The Josephson current between an s-wave and a spin-triplet superconductor
SrRuO (SRO) is studied theoretically. In spin-singlet / spin-triplet
superconductor junctions, there is no Josephson current proportional to in the absence of the spin-flip scattering near junction interfaces,
where is a phase-difference across junctions. Thus a dominant term of
the Josephson current is proportional to . The spin-orbit
scattering at the interfaces gives rise to the Josephson current proportional
to , which is a direct consequence of the chiral paring symmetry in
SRO
Inhibition of Phosphodiesterase-4 (PDE4) activity triggers luminal apoptosis and AKT dephosphorylation in a 3-D colonic-crypt model
BACKGROUND: We previously established a three-dimensional (3-D) colonic crypt model using HKe3 cells which are human colorectal cancer (CRC) HCT116 cells with a disruption in oncogenic KRAS, and revealed the crucial roles of oncogenic KRAS both in inhibition of apoptosis and in disruption of cell polarity; however, the molecular mechanism of KRAS-induced these 3-D specific biological changes remains to be elucidated. RESULTS: Among the genes that were upregulated by oncogenic KRAS in this model, we focused on the phosphodiesterase 4B (PDE4B) of which expression levels were found to be higher in clinical tumor samples from CRC patients in comparison to those from healthy control in the public datasets of gene expression analysis. PDE4B2 was specifically overexpressed among other PDE4 isoforms, and re-expression of oncogenic KRAS in HKe3 cells resulted in PDE4B overexpression. Furthermore, the inhibition of PDE4 catalytic activity using rolipram reverted the disorganization of HCT116 cells into the normal physiologic state of the epithelial cell polarity by inducing the apical assembly of ZO-1 (a tight junction marker) and E-cadherin (an adherens junction marker) and by increasing the activity of caspase-3 (an apoptosis marker) in luminal cavities. Notably, rolipram reduced the AKT phosphorylation, which is known to be associated with the disruption of luminal cavity formation and CRC development. Similar results were also obtained using PDE4B2-shRNAs. In addition, increased expression of PDE4B mRNA was found to be correlated with relapsed CRC in a public datasets of gene expression analysis. CONCLUSIONS: These results collectively suggested that PDE4B is upregulated by oncogenic KRAS, and also that the inhibition of PDE4 catalytic activity can induce both epithelial cell polarity and luminal apoptosis in CRC, thus highlighting the utility of our 3-D culture (3 DC) model for the KRAS-induced development of CRC in 3-D microenvironment. Indeed, using this model, we found that PDE4B is a promising candidate for a therapeutic target as well as prognostic molecular marker in CRC. Further elucidation of the signaling network of PDE4B2 in 3 DC would provide a better understanding of CRC in vivo
Exploring Flavor Structure of Supersymmetry Breaking at B factories
We investigate quark flavor signals in three different supersymmetric models,
the minimal supergravity, the SU(5) SUSY GUT with right handed neutrinos, and
the minimal supersymmetric standard model with U(2) flavor symmetry, in order
to study physics potential of the present and future factories. We evaluate
CP asymmetries in various B decay modes, , ,
and . The allowed regions of the CP asymmetry in
and are different for the three models so that
precise determinations of these observables in near future experiments are
useful to distinguish the three models. We also investigate possible deviations
from the standard model predictions of CP asymmetries in other B decay modes.
In particular, a large deviation is possible for the U(2) model. The
consistency check of the unitarity triangle including , and so on, at future high
luminosity factories and hadronic experiments is therefore
important to distinguish flavor structures of different supersymmetric models.Comment: revtex4, 31 pages, 7 figure
Magnetohydrodynamic stability at the edge region in H-mode plasmas with long edge-localized-mode-free phases in the large helical device
Clear suppression of magnetic fluctuations associated with resistive interchange modes (RICs) is observed during long edge-localized-mode (ELM)-free phases of the H-mode plasma in an outward-shifted configuration of the Large Helical Decice, in which a steep pressure gradient is generated at the plasma edge in the magnetic hill. The ELM-free H-phase is interrupted by large amplitude ELMs which are thought to be induced through nonlinear evolution of the RICs having m = 1/n = 1 dominant component (m: poloidal mode number, n: toroidal one). The m = 1/n = 1 RIC amplitude is enhanced about 10 times compared with the H-phase level during each ELM. In most of the H-mode shots, the final ELM-free phase returns to L-phase by a large amplitude ELM. In the L-phase, the RIC amplitude is enhanced by a factor of ~3 compared with that in the H-phase, although the edge pressure gradient is reduced considerably. Linear resistive magnetohydrodynamic stability analysis is attempted using experimentally obtained equilibrium profiles. From the numerical analysis, the distance between the location of the steepest pressure gradient and the main mode resonance surface, i.e. the rotational transform ι = 1, is found to be important for a large growth of the m = 1/n = 1 RIC in the H-phase
Structure of Protein Interaction Networks and Their Implications on Drug Design
Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly optimized tolerance (HOT) networks that are similar to the router-level topology of the Internet. This is different from claims that such networks are scale-free and configured through simple preferential-attachment processes. Further analysis revealed that there are extensive interconnections among middle-degree nodes that form the backbone of the networks. Degree distributions of essential genes, synthetic lethal genes, synthetic sick genes, and human drug-target genes indicate that there are advantageous drug targets among nodes with middle- to low-degree nodes. Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects
A Single Nucleotide Polymorphism within the Novel Sex-Linked Testis-Specific Retrotransposed PGAM4 Gene Influences Human Male Fertility
The development of novel fertilization treatments, including in vitro fertilization and intracytoplasmic injection, has made pregnancy possible regardless of the level of activity of the spermatozoa; however, the etiology of male-factor infertility is poorly understood. Multiple studies, primarily through the use of transgenic animals, have contributed to a list of candidate genes that may affect male infertility in humans. We examined single nucleotide polymorphisms (SNPs) as a cause of male infertility in an analysis of spermatogenesis-specific genes.We carried out the prevalence of SNPs in the coding region of phosphoglycerate mutase 4 (PGAM4) on the X chromosome by the direct sequencing of PCR-amplified DNA from male patients. Using RT-PCR and western blot analyses, we identified that PGAM4 is a functional retrogene that is expressed predominantly in the testes and is associated with male infertility. PGAM4 is expressed in post-meiotic stages, including spermatids and spermatozoa in the testes, and the principal piece of the flagellum and acrosome in ejaculated spermatozoa. A case-control study revealed that 4.5% of infertile patients carry the G75C polymorphism, which causes an amino acid substitution in the encoded protein. Furthermore, an assay for enzymatic activity demonstrated that this polymorphism decreases the enzyme's activity both in vitro and in vivo.These results suggest that PGAM4, an X-linked retrogene, is a fundamental gene in human male reproduction and may escape meiotic sex chromosome inactivation. These findings provide fresh insight into elucidating the mechanisms of male infertility
Tunneling Spectra of Skutterudite PrOs_4Sb_{12}
The tunnel conductance in normal-metal / insulator / PrOsSb
junctions is theoretically studied, where skutterudite PrOsSb is
considered to be an unconventional superconductor. The conductance are
calculated for several pair potentials which have been proposed in recent
works. The results show that the conductance is sensitive to the relation
between the direction of electric currents and the position of point nodes. We
also show that the conductance spectra often deviate from the shape of the bulk
density of states and that the sub gap spectra have peak structures in the case
of the spin-triplet pair potentials. The results indicate that the tunnel
conductance is a useful tool to obtain an information of the pairing symmetry.Comment: 9 page
Exploring flavor structure of supersymmetry breaking from rare B decays and unitarity triangle
We study effects of supersymmetric particles in various rare B decay
processes as well as in the unitarity triangle analysis. We consider three
different supersymmetric models, the minimal supergravity, SU(5) SUSY GUT with
right-handed neutrinos, and the minimal supersymmetric standard model with U(2)
flavor symmetry. In the SU(5) SUSY GUT with right-handed neutrinos, we consider
two cases of the mass matrix of the right-handed neutrinos. We calculate direct
and mixing-induced CP asymmetries in the b to s gamma decay and CP asymmetry in
B_d to phi K_S as well as the B_s--anti-B_s mixing amplitude for the unitarity
triangle analysis in these models. We show that large deviations are possible
for the SU(5) SUSY GUT and the U(2) model. The pattern and correlations of
deviations from the standard model will be useful to discriminate the different
SUSY models in future B experiments.Comment: revtex4, 36 pages, 10 figure
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