Intermetallic: A Pseudoelement for Catalysis.

A clear correlation between electronic structure and CO2 selectivity for steam reforming of methanol (SRM) was obtained with PdZn, PtZn, NiZn, and PdCd intermetallics on the basis of experiments and calculations. In order to rule out the effects of oxide supports, the intermetallic powders were simply prepared by alloying in an arc furnace followed by crushing in a mortar. PdZn and PdCd exhibit valence electronic densities of states similar to that of Cu and significant chemical shifts (larger than 1 eV) of Pd 3d states with respect to pure Pd, as verified by high-resolution hard X-ray photoelectron spectroscopy (HXPS) measurements and density functional theory (DFT) calculations. Consequently, they show the similar high selectivity of CO2 for the SRM reaction. However, this is not the case for PtZn and NiZn because of the slight differences in their valence electronic structures from that of PdZn. The interval between the Fermi level and the top of the d band is closely related to the selectivity of CO2 for the SRM: the larger the interval is, the higher is the selectivity of CO2. According to DFT calculations for bulk PdZn performed by Chen et al. ( Phys. Rev. B 2003 , 68 , 075417 ), the (111) and (100) surfaces exposing Zn and Pd in an equimolar ratio are more stable than the (001) or (110) surfaces terminated by alternative Zn or Pd layers. First-principles slab calculations for PdZn, PtZn, and NiZn show that bond breaking on the surface leads to a reduction in the d bandwidth but that the d band for stable (111) or (100) surfaces remains essentially unchanged from that of the bulk. It is intriguing that PdZn and PdCd do not contain Cu but show similar valence electronic structure and catalytic selectivity, and hence, a concept is proposed where PdZn and PdCd are regarded as pseudoelements of Cu. The basis of this concept is like electronic structure, like catalysis, which has been demonstrated by experiments and calculations. This is a logical way to enable us to look for new catalysts in which precious metals are partially or completely replaced by base metals. We do not expect that this concept can be applied to all catalytic reactions, but this approach is one of most promising ways to derive a better understanding of the origin of catalytic mechanisms and eventually allow us to design useful catalysts intentionally in the future. This Account reviews the authors' published works on this topic.

Randomized clinical trial of adjuvant chemotherapy with S-1 versus gemcitabine after pancreatic cancer resection.

BACKGROUND: Randomized studies of adjuvant chemotherapy using gemcitabine suggest a survival benefit after resection of pancreatic cancer. S-1 has also been shown to prolong survival in patients with unresectable pancreatic cancer. This study compared the effects of adjuvant chemotherapy with S-1 or gemcitabine after resection of pancreatic cancer in a randomized trial. METHODS: Patients who had undergone resection of pancreatic cancer were registered in this randomized clinical trial. The primary endpoint was disease-free survival (DFS). Expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) mRNAs in cancer tissues were measured as indicators of fluoropyrimidine sensitivity. RESULTS: Of 57 patients registered, 29 were allocated to the S-1 group and 28 to gemcitabine. DFS tended to be better with S-1 (median 14·6 (90 per cent c.i. 8·8 to 28·4) months versus 10·5 (7·0 to 28·4) months in the gemcitabine group; P = 0·188), with a similar pattern for overall survival: 21·5 (95 per cent c.i. 14·4 to 42·3) and 18·0 (13·3 to 42·8) months respectively (P = 0·293). When patients were divided into subgroups based on high or low DPD and TS expression, those with a DPD level below the median of 0·88 or a TS level of at least 2·00 had a significant prolongation of DFS after S-1 treatment compared with gemcitabine (P = 0·008 and P = 0·035 respectively). CONCLUSION: Overall, S-1 did not improve DFS compared with gemcitabine after pancreatic cancer resection, but there seemed to be a DFS advantage in patients with low expression of DPD or high expression of TS. Reference number: UMIN000009118 (http://www.umin.ac.jp/ctr/).

Construction of novel immune-related signature for prediction of pathological complete response to neoadjuvant chemotherapy in human breast cancer.

BACKGROUND: The aim of this study was to construct a novel prediction model for the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) using immune-related gene expression data. PATIENTS AND METHODS: DNA microarray data were used to perform a gene expression analysis of tumor samples obtained before NAC from 117 primary breast cancer patients. The samples were randomly divided into the training (n = 58) and the internal validation (n = 59) sets that were used to construct the prediction model for pCR. The model was further validated using an external validation set consisting of 901 patients treated with NAC from six public datasets. RESULTS: The training set was used to construct an immune-related 23-gene signature for NAC (IRSN-23) that is capable of classifying the patients as either genomically predicted responders (Gp-R) or non-responders (Gp-NR). IRSN-23 was first validated using an internal validation set, and the results showed that the pCR rate for Gp-R was significantly higher than that obtained for Gp-NR (38 versus 0%, P = 1.04E-04). The model was then tested using an external validation set, and this analysis showed that the pCR rate for Gp-R was also significantly higher (40 versus 11%, P = 4.98E-23). IRSN-23 predicted pCR regardless of the intrinsic subtypes (PAM50) and chemotherapeutic regimens, and a multivariate analysis showed that IRSN-23 was the most important predictor of pCR (odds ratio = 4.6; 95% confidence interval = 2.7-7.7; P = 8.25E-09). CONCLUSION: The novel prediction model (IRSN-23) constructed with immune-related genes can predict pCR independently of the intrinsic subtypes and chemotherapeutic regimens.

Crystalline and quasicrystalline allotropes of Pb formed on the fivefold surface of icosahedral Ag-In-Yb.

Crystalline and quasicrystalline allotropes of Pb are formed by evaporation on the fivefold surface of the icosahedral (i) Ag-In-Yb quasicrystal under ultra-high vacuum. Lead grows in three dimensional quasicrystalline order and subsequently forms fivefold-twinned islands with the fcc(111) surface orientation atop of the quasicrystalline Pb. The islands exhibit specific heights (magic heights), possibly due to the confinement of electrons in the islands. We also study the adsorption behavior of C60 on the two allotropes of Pb. Scanning tunneling microcopy reveals that a high corrugation of the quasicrystalline Pb limits the diffusion of the C60 molecules and thus produces a disordered film, similar to adsorption behavior of the same molecules on the clean substrate surface. However, the sticking coefficient of C60 molecules atop the Pb islands approaches zero, regardless of the overall C60 coverage.

Stimulation of adult resident cardiac progenitor cells by durable myocardial expression of thymosin beta 4 with ultrasound-targeted microbubble delivery.

It has been proposed that thymosin beta 4 (TB4)-protein delivery stimulates differentiation of resident adult WT1-positive cardiac progenitor cells, but with very low efficiency. We determined whether gene therapy with human TB4 stimulates proliferation of resident adult cardiac progenitor cells in normal rat heart. Ultrasound-targeted microbubble destruction (UTMD) was used to deliver the human TB4 gene under a piggybac transposon plasmid to normal rat heart. The rat hearts were assayed by quantitative reverse transcription-PCR and immunohistology with a confocal microscope at 1, 2, 3, 4 and 12 weeks after UTMD. Exogenous TB4 stimulation resulted in the presence of WT1-positive cardiac progenitor cells from epicardium to endocardium. TB4 stimulated angiogenesis and arteriogenesis. One month after TB4 gene therapy by UTMD, the percentage of NKX2.5-positive cardiomyocytes was 5.5±1.0% and NKX2.5 mRNA was 24-fold higher than in the control groups (P<0.001). Similar results were found for ISL-1, BrDu, Ki-67, PHH3 and aurora B (P<0.001). Cardiac-specific delivery of exogenous human TB4 gene efficiently stimulates proliferation and differentiation of resident WT1-positive adult cardiac progenitor cells into three intact cardiac cell lineages-vascular endothelial cells, coronary artery smooth muscle cells and cardiac muscle cells in normal adult rat heart.

Vildagliptin preserves the mass and function of pancreatic ß cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes.

AIM: We investigated the molecular mechanisms by which vildagliptin preserved pancreatic ß cell mass and function. METHODS: Morphological, biochemical and gene expression profiles of the pancreatic islets were investigated in male KK-A(y) -TaJcl(KK-A(y) ) and C57BL/6JJcl (B6) mice aged 8 weeks which received either vildagliptin or a vehicle for 4 weeks. RESULTS: Body weight, food intake, fasting blood glucose, plasma insulin and active glucagon-like peptide-1 were unchanged with vildagliptin treatment in both mice. In KK-A(y) mice treated with vildagliptin, increased plasma triglyceride (TG) level and islet TG content were decreased, insulin sensitivity significantly improved, and the glucose tolerance ameliorated with increases in plasma insulin levels. Furthermore, vildagliptin increased glucose-stimulated insulin secretion, islet insulin content and pancreatic ß cell mass in both strains. By vildagliptin, the expression of genes involved in cell differentiation/proliferation was upregulated in both strains, those related to apoptosis, endoplasmic reticulum stress and lipid synthesis was decreased and those related to anti-apoptosis and anti-oxidative stress was upregulated, in KK-A(y) mice. The morphological results were consistent with the gene expression profiles. CONCLUSION: Vildagliptin increases ß cell mass by not only directly affecting cell kinetics but also by indirectly reducing cell apoptosis, oxidative stress and endoplasmic reticulum stress in diabetic mice.

The human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes.

AIMS/HYPOTHESIS: We investigated the molecular mechanism by which the human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells in diabetic db/db mice. METHODS: Male db/db and m/m mice aged 10 weeks received liraglutide or vehicle for 2 days or 2 weeks. In addition to morphological and biochemical analysis of pancreatic islets, gene expression profiles in the islet core area were investigated by laser capture microdissection and real-time RT-PCR. RESULTS: Liraglutide treatment for 2 weeks improved metabolic variables and insulin sensitivity in db/db mice. Liraglutide also increased glucose-stimulated insulin secretion (GSIS) and islet insulin content in both mouse strains and reduced triacylglycerol content in db/db mice. Expression of genes involved in cell differentiation and proliferation in both mouse strains was regulated by liraglutide, which, in db/db mice, downregulated genes involved in pro-apoptosis, endoplasmic reticulum (ER) stress and lipid synthesis, and upregulated genes related to anti-apoptosis and anti-oxidative stress. In the 2 day experiment, liraglutide slightly improved metabolic variables in db/db mice, but GSIS, insulin and triacylglycerol content were not affected. In db/db mice, liraglutide increased gene expression associated with cell differentiation, proliferation and anti-apoptosis, and suppressed gene expression involved in pro-apoptosis; it had no effect on genes related to oxidative stress or ER stress. Morphometric results for cell proliferation, cell apoptosis and oxidative stress in db/db mice islets were consistent with the results of the gene expression analysis. CONCLUSIONS/INTERPRETATION: Liraglutide increases beta cell mass not only by directly regulating cell kinetics, but also by suppressing oxidative and ER stress, secondary to amelioration of glucolipotoxicity.

Duration of hepatic vascular inflow clamping and survival after liver resection for hepatocellular carcinoma.

BACKGROUND: The aim of this study was to evaluate the influence of the duration of hepatic vascular inflow clamping (Pringle time) on the survival of patients with any type of liver background (not only cirrhosis) undergoing liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent liver resection between April 2000 and December 2008 for HCC using the Pringle manoeuvre were identified retrospectively from an institutional database and divided into two groups: group 1 had a Pringle time of 60 min or less, and group 2 a Pringle time of more than 60 min. Univariable and multivariable analyses were performed to identify predictors of postoperative survival. Kaplan-Meier analysis was used to compare overall survival between the groups. RESULTS: A total of 357 patients were enrolled; 242 patients had a Pringle time of 60 min or less (group 1), and 115 patients had a Pringle time of more than 60 min (group 2). Patients in group 2 had a shorter overall survival than those in group 1 (P = 0·010). Univariable analyses showed that type of HCC (primary versus recurrent), maximum tumour diameter, hepatic venous infiltration, platelet count, serum protein induced by vitamin K absence or antagonist II level, blood loss (700 ml or less versus more than 700 ml), duration of operation (300 min or less versus more than 300 min) and Pringle time (60 min or less versus more than 60 min) were predictive of postoperative survival. Multivariable analysis indicated that only Pringle time was associated with postoperative survival (odds ratio 1·83, 95 per cent confidence interval 1·08 to 3·10; P = 0·024). CONCLUSION: Longer Pringle time is an important predictor of shorter postoperative survival in patients undergoing liver resection for HCC.

In vivo non-viral gene delivery of human vascular endothelial growth factor improves revascularisation and restoration of euglycaemia after human islet transplantation into mouse liver.

AIMS/HYPOTHESIS: Delivery of the gene for human vascular endothelial growth factor (VEGF, also known as VEGFA) to both the transplanted islets and the surrounding tissue may promote islet revascularisation and survival. We previously showed the effective delivery of VEGF gene to rat myocardium by an ultrasound-mediated gene-transfer method named ultrasound-targeted microbubble destruction (UTMD). Here we examined the effect of non-viral VEGF delivery using UTMD on transplanted islets in vivo. METHODS: A marginal number of human islets were transplanted into livers of mice which were a model for diabetes. Then, non-viral plasmid vectors encoding VEGF (VEGF group, n = 11) or the gene for green fluorescent protein (GFP) (GFP group, n = 7) were introduced into the host liver by UTMD. Transplantation without gene delivery was performed as a control (no-UTMD group, n = 8). Blood glucose, serum human insulin, C-peptide levels and the revascularisation in graft islets were evaluated. RESULTS: Restoration of euglycaemia occurred in 13% in the no-UTMD group and 14% in the GFP group, whereas 73% mice in the VEGF group became euglycaemic at day 30 (p < 0.05 in no-UTMD vs VEGF). Serum human insulin and C-peptide were significantly higher in the VEGF group at day 32 (insulin: no-UTMD, 17 +/- 8; GFP, 37 +/- 17; VEGF, 109 +/- 26 pmol/l, respectively, p < 0.05; C-peptide: no-UTMD, 68 +/- 38; GFP, 115 +/- 58; VEGF, 791 +/- 230 pmol/l, respectively, p < 0.05). Vessel density in graft islets was significantly higher in the VEGF group (no-UTMD, 169 +/- 36; GFP, 227 +/- 39; VEGF, 649 +/- 51 counts/mm(2), respectively, p < 0.05). CONCLUSIONS/INTERPRETATION: Delivery of VEGF gene to host liver using UTMD promoted islet revascularisation after islet transplantation and improved the restoration of euglycaemia.

Regeneration of pancreatic islets in vivo by ultrasound-targeted gene therapy.

This study uses a novel approach to gene therapy in which plasmid DNA is targeted to the pancreas in vivo using ultrasound-targeted microbubble destruction (UTMD) to achieve islet regeneration. Intravenous microbubbles carrying plasmids are destroyed within the pancreatic microcirculation by ultrasound, achieving local gene expression that is further targeted to ß-cells by a modified rat insulin promoter (RIP3.1). A series of genes implicated in endocrine development were delivered to rats 2 days after streptozotocin-induced diabetes. The genes, PAX4, Nkx2.2, Nkx6.1, Ngn3 and Mafa, produced α-cell hyperplasia, but no significant improvement in ß-cell mass or blood glucose level 30 days after UTMD. In contrast, RIP3.1-NeuroD1 promoted islet regeneration from surviving ß-cells, with normalization of glucose, insulin and C-peptide levels at 30 days. In a longer-term experiment, four of six rats had a return of diabetes at 90 days, accompanied by ß-cell apoptosis on Tunel staining. Pretreatment with the JNK inhibitor SP600125 successfully blocked ß-cell apoptosis and resulted in restoration of ß-cell mass and normalization of blood glucose level for up to 90 days. This technique allows in vivo islet regeneration, restoration of ß-cell mass and normalization of blood sugar, insulin and C-peptide in rats without viruses.

Isotype-specific selection of high affinity memory B cells in nasal-associated lymphoid tissue.

Mucosal immunoglobulin (Ig)A dominance has been proposed to be associated with preferential class switch recombination (CSR) to the IgA heavy chain constant region, Calpha. Here, we report that B cell activation in nasal-associated lymphoid tissue (NALT) upon stimulation with the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken gamma globulin caused an anti-NP memory response dominated by high affinity IgA antibodies. In the response, however, NP-specific IgG(+) B cells expanded and sustained their number as a major population in germinal centers (GCs), supporting the view that CSR to IgG heavy chain constant region, Cgamma, operated efficiently in NALT. Both IgG(+) and IgA(+) GC B cells accumulated somatic mutations, indicative of affinity maturation to a similar extent, suggesting that both types of cell were equally selected by antigen. Despite the selection in GCs, high affinity NP-specific B cells were barely detected in the IgG memory compartment, whereas such cells dominated the IgA memory compartment. Taken together with the analysis of the V(H) gene clonotype in GC and memory B cells, we propose that NALT is equipped with a unique machinery providing IgA-specific enrichment of high affinity cells into the memory compartment, facilitating immunity with high affinity and noninflammatory secretory antibodies.

Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice.

The role of apoptosis in affinity maturation was investigated by determining the affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific antibody-forming cells (AFCs) and serum antibody in transgenic mice that overexpress a suppressor of apoptosis, Bcl-xL, in the B cell compartment. Although transgenic animals briefly expressed higher numbers of splenic AFCs after immunization, the bcl-xL transgene did not increase the number or size of germinal centers (GCs), alter the levels of serum antibody, or change the frequency of NP-specific, long-lived AFCs. Nonetheless, the bcl-xL transgene product, in addition to endogenous Bcl-xL, reduced apoptosis in GC B cells and resulted in the expansion of B lymphocytes bearing VDJ rearrangements that are usually rare in primary anti-NP responses. Long-lived AFCs bearing these noncanonical rearrangements were frequent in the bone marrow and secreted immunoglobulin G(1) antibodies with low affinity for NP. The abundance of noncanonical cells lowered the average affinity of long-lived AFCs and serum antibody, demonstrating that Bcl-xL and apoptosis influence clonal selection/maintenance for affinity maturation.

Amyloid-beta causes memory impairment by disturbing the JAK2/STAT3 axis in hippocampal neurons.

Elevation of intracranial soluble amyloid-beta (Abeta) levels has been implicated in the pathogenesis of Alzheimer's disease (AD). Intracellular events in neurons, which lead to memory loss in AD, however, remain elusive. Humanin (HN) is a short neuroprotective peptide abolishing Abeta neurotoxicity. Recently, we found that HN derivatives activate the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling axis. We here report that an HN derivative named colivelin completely restored cognitive function in an AD model (Tg2576) by activating the JAK2/STAT3 axis. In accordance, immunofluorescence staining using a specific antibody against phospho- (p-) STAT3 revealed that p-STAT3 levels in hippocampal neurons age-dependently decreased in both AD model mice and AD patients. Intracerebroventricular administration of Abeta1-42 downregulated p-STAT3 whereas passive immunization with anti-Abeta antibody conversely restored hippocampal p-STAT3 levels in Tg2576 mice, paralleling the decrease in the brain Abeta burden. Abeta1-42 consistently modulated p-STAT3 levels in primary neurons. Pharmacological inhibition of the JAK2/STAT3 axis not only induced significant loss of spatial working memory by downregulating an acetylcholine-producing enzyme choline acetyltransferase but also desensitized the M(1)-type muscarinic acetylcholine receptor. Thus, we propose a novel theory accounting for memory impairment related to AD: Abeta-dependent inactivation of the JAK2/STAT3 axis causes memory loss through cholinergic dysfunction. Our findings provide not only a novel pathological hallmark in AD but also a novel target in AD therapy.

Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly.

Disrupted-in-schizophrenia-1 (DISC1) is one of major susceptibility factors for a wide range of mental illnesses, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions. DISC1 is located in several subcellular domains, such as the centrosome and the nucleus, and interacts with various proteins, including NudE-like (NUDEL/NDEL1) and activating transcription factor 4 (ATF4)/CREB2. Nevertheless, a role for DISC1 in vivo remains to be elucidated. Therefore, we have generated a Drosophila model for examining normal functions of DISC1 in living organisms. DISC1 transgenic flies with preferential accumulation of exogenous human DISC1 in the nucleus display disturbance in sleep homeostasis, which has been reportedly associated with CREB signaling/CRE-mediated gene transcription. Thus, in mammalian cells, we characterized nuclear DISC1, and identified a subset of nuclear DISC1 that colocalizes with the promyelocytic leukemia (PML) bodies, a nuclear compartment for gene transcription. Furthermore, we identified three functional cis-elements that regulate the nuclear localization of DISC1. We also report that DISC1 interacts with ATF4/CREB2 and a corepressor N-CoR, modulating CRE-mediated gene transcription.

V(D)J recombinase activity in a subset of germinal center B lymphocytes.

Reexpression of the V(D)J recombinase-activating genes RAG1 and RAG2 in germinal center B cells creates the potential for immunoglobulin gene rearrangement and the generation of new antigen receptor specificities. Intermediate products of V(D)J recombination are abundant in a subset of germinal center B cells, demonstrating that the kappa immunoglobulin light-chain locus becomes a substrate for renewed V(D)J recombinase activity. This recombinationally active cell compartment contains many heavy-chain VDJ rearrangements that encode low-affinity or nonfunctional antibody. In germinal centers, secondary V(D)J recombination may be induced by diminished binding to antigen ligands, thereby limiting abrupt changes in receptor specificity to B cells that are usually eliminated from the germinal center reaction. This restriction preserves efficient antigen-driven selection in germinal centers while allowing for saltations in the somatic evolution of B cells.

Stroke power consistency and 2000 m rowing performance in varsity rowers.

We studied the relationship between stroke power consistency and 2000 m rowing time besides determining maximal oxygen uptake (VO(2max)) and leg extension power. The subjects (n=16, male varsity rowers) carried out an incremental test to volitional exhaustion on a rowing ergometer, and the VO(2) at each stage was determined. The stroke power consistency was assessed by the coefficient of variation of power (CVP(high)) at the highest workload at which each subject could maintain power. Besides the incremental test, 2000 m all-out rowing was performed on the ergometer and leg extension power was measured. Stepwise multiple regression analysis indicated that the 2000 m rowing time could be predicted by VO(2max), leg extension power and CVP(high) in order of strength of standardized partial correlation coefficients as explanatory variables. The CVP(high) correlated with the residual of the regression between 2000 m rowing time and VO(2max). The findings suggest that the stroke power consistency contributes to maintenance of the power during ergometer rowing.

Pharmacokinetics and milk distribution characteristics of orbifloxacin following intravenous and intramuscular injection in lactating ewes.

The purpose of the current investigation is to elucidate the pharmacokinetic profiles of orbifloxacin (OBFX) in lactating ewes (n = 6) following intravenous (i.v.) and intramuscular (i.m.) administrations of 2.5 mg/kg W. In a crossover study, frequent blood, milk, and urine samples were drawn for up to 48 h after the end of administration, and were then assayed to determine their respective drug concentrations through microbiological assay using Klebsiella pneumoniae as the test micro-organism. Plasma pharmacokinetic parameters were derived from plasma concentration-time data using a compartmental and noncompartmental analysis, and validated a relatively rapid elimination from the blood compartment, with a slope of the terminal phase of 0.21 +/- 0.02 and 0.19 +/- 0.06 per hour and a half-life of 3.16 +/- 0.43 and 3.84 +/- 0.59 h, for i.v. and i.m. dosing, respectively. OBFX was widely distributed with a volume of distribution V((d(ss))) of 1.31 +/- 0.12 L/kg, as suggested by the low percentage of protein binding (22.5%). The systemic body clearance (Cl(B)) was 0.32 +/- 0.12 L/h x kg. Following i.m. administration, the maximum plasma concentration (C(max)) of 1.53 +/- 0.34 microg/mL was reached at t(max) 1.25 +/- 0.21 h. The drug was completely absorbed after i.m. administration, with a bioavailability of 114.63 +/- 11.39%. The kinetic milk AUC(milk)/AUC(plasma) ratio indicated a wide penetration of orbifloxacin from the bloodstream to the mammary gland. OBFX urine concentrations were higher than the concurrent plasma concentrations, and were detected up to 30 h postinjection by both routes. Taken together, these findings indicate that systemic administration of orbifloxacin could be efficacious against susceptible mammary and urinary pathogens in lactating ewes.

Epidemiological study of acute encephalitis in Tottori Prefecture, Japan.

BACKGROUND AND PURPOSE: To conduct an epidemiological survey of acute encephalitis focusing on non-herpetic acute limbic encephalitis (NHALE) in Tottori Prefecture, western area of Japan. METHODS: A questionnaire survey on the annual number of patients aged 16 years or more with acute encephalitis from 2001 to 2005 was undertaken in 2006. RESULTS: During the study period, 49 patients were diagnosed with acute encephalitis. The subtype of acute encephalitis was as follows: 10 patients with herpes simplex encephalitis (HSE), 12 patients with NHALE, 4 patients with paraneoplastic encephalitis, 2 patients with encephalitis associated with collagen disease, one patient with viral encephalitis other than HSE, 20 patients with encephalitis with unknown causes. The service-based incidence rate of acute encephalitis was 19.0 per million person-years. The incidence rate of NHALE subtype was 4.7 per million person-years. CONCLUSIONS: Our epidemiological survey indicated an estimated 550 patients would develop NHALE per year in Japan, suggesting that NHALE may not be a rare disorder.

Optimal design of a tuned liquid damper using a magnetic fluid with one electromagnet.

Characteristics of a tuned magnetic fluid damper are examined. The optimal depth of a magnetic fluid in a cylindrical container is calculated using a linear analysis of a magnetic fluid sloshing. In order to avoid swirling in lower depth fluids, several experiments using greater fluid depths are carried out and a good damping range is obtained.