Dielectric responses of the layered cobalt oxysulfide Sr_2Cu_2CoO_2S_2 with CoO_2 square-planes

We have studied the dielectric responses of the layered cobalt oxysulfide Sr$_2$Cu$_2$CoO$_2$S$_2$ with the CoO$_2$ square-planes. With decreasing temperature below the N\'eel temperature, the resistivity increases like a semiconductor, and the thermopower decreases like a metal. The dielectric constant is highly dependent on temperature, and the dielectric relaxation is systematically changed with temperature, which is strongly correlated to the magnetic states. These behaviors suggest that carriers distributed homogeneously in the paramagnetic state at high temperatures are expelled from the antiferromagnetically ordered spin domain below the N\'eel temperature.Comment: 3 pages, 4 eps figures, to be published in J. Appl. Phy

Stability of Simple Periodic Orbits and Chaos in a Fermi -- Pasta -- Ulam Lattice

We investigate the connection between local and global dynamics in the Fermi -- Pasta -- Ulam (FPU) $\beta$ -- model from the point of view of stability of its simplest periodic orbits (SPOs). In particular, we show that there is a relatively high $q$ mode $(q=2(N+1)/{3})$ of the linear lattice, having one particle fixed every two oppositely moving ones (called SPO2 here), which can be exactly continued to the nonlinear case for $N=5+3m, m=0,1,2,...$ and whose first destabilization, $E_{2u}$, as the energy (or $\beta$) increases for {\it any} fixed $N$, practically {\it coincides} with the onset of a ``weak'' form of chaos preceding the break down of FPU recurrences, as predicted recently in a similar study of the continuation of a very low ($q=3$) mode of the corresponding linear chain. This energy threshold per particle behaves like $\frac{E_{2u}}{N}\propto N^{-2}$. We also follow exactly the properties of another SPO (with $q=(N+1)/{2}$) in which fixed and moving particles are interchanged (called SPO1 here) and which destabilizes at higher energies than SPO2, since $\frac{E_{1u}}{N}\propto N^{-1}$. We find that, immediately after their first destabilization, these SPOs have different (positive) Lyapunov spectra in their vicinity. However, as the energy increases further (at fixed $N$), these spectra converge to {\it the same} exponentially decreasing function, thus providing strong evidence that the chaotic regions around SPO1 and SPO2 have ``merged'' and large scale chaos has spread throughout the lattice.Comment: Physical Review E, 18 pages, 6 figure

Low expression of gamma-glutamyl hydrolase mRNA in primary colorectal cancer with the CpG island methylator phenotype

Division of Translational and Clinical Oncolog

Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients

Objectives Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000–3000 years. Methods Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype. Results In addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10–8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients’ gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout. Conclusions Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia

Effects of small interfering RNA targeting thymidylate synthase on survival of ACC3 cells from salivary adenoid cystic carcinoma

<p>Abstract</p> <p>Background</p> <p>Thymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer and high expression of TS has been associated with poor prognosis or refractory disease in several cancers including colorectal and head and neck cancer. Although TS is known to regulate cell cycles and transcription factors, its potency as a therapeutic target has not been fully explored in adenoid cystic carcinoma (ACC).</p> <p>Methods</p> <p>An ACC cell line (ACC3) was transfected with siRNA targeting the TS gene and inhibition of cell growth and induction of apoptosis-associated molecules were evaluated <it>in vitro</it>. In addition, the <it>in vivo </it>effect of TS siRNA on tumor progression was assessed using a xenograft model.</p> <p>Results</p> <p>Our results demonstrated that ACC3 cells showed significantly higher TS expression than non-cancer cell lines and the induction of TS siRNA led to inhibition of cell proliferation. The effect was associated with an increase in p53, p21, and active caspase-3 and S-phase accumulation. We also found up-regulation of spermidine/spermine N1-acetyltransferase (SSAT), a polyamine metabolic enzyme. Furthermore, treatment with TS siRNA delivered by atelocollagen showed a significant cytostatic effect through the induction of apoptosis in a xenograft model.</p> <p>Conclusion</p> <p>TS may be an important therapeutic target and siRNA targeting TS may be of potential therapeutic value in ACC.</p

Using Expression and Genotype to Predict Drug Response in Yeast

Personalized, or genomic, medicine entails tailoring pharmacological therapies according to individual genetic variation at genomic loci encoding proteins in drug-response pathways. It has been previously shown that steady-state mRNA expression can be used to predict the drug response (i.e., sensitivity or resistance) of non-genotyped mammalian cancer cell lines to chemotherapeutic agents. In a real-world setting, clinicians would have access to both steady-state expression levels of patient tissue(s) and a patient's genotypic profile, and yet the predictive power of transcripts versus markers is not well understood. We have previously shown that a collection of genotyped and expression-profiled yeast strains can provide a model for personalized medicine. Here we compare the predictive power of 6,229 steady-state mRNA transcript levels and 2,894 genotyped markers using a pattern recognition algorithm. We were able to predict with over 70% accuracy the drug sensitivity of 104 individual genotyped yeast strains derived from a cross between a laboratory strain and a wild isolate. We observe that, independently of drug mechanism of action, both transcripts and markers can accurately predict drug response. Marker-based prediction is usually more accurate than transcript-based prediction, likely reflecting the genetic determination of gene expression in this cross

Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer

Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. manifested a reversed pattern.We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment