Designing a stronger interface through graded structures in amorphous/nanocrystalline ZrCu/Cu multilayered films.

Many multilayered nano-structures appear to fail due to brittle matter along the interfaces. In order to toughen them, in this study, the microstructure and interface strength of multilayered thin films consisting of amorphous ZrCu and nanocrystalline Cu (with sharp or graded interfaces) are examined and analyzed. The interface possesses a gradient nature in terms of composition, nanocrystalline phase size and volume fraction. The bending results extracted from the nano-scaled cantilever bending samples demonstrate that multilayered films with graded interfaces would have a much higher interface bending strength/strain/modulus, and an overall improvement upgrade of more than 50%. The simple graded interface design of multilayered thin films with improved mechanical properties can offer much more promising performance in structural and functional applications for MEMS or optical coating.

Occurrence and distribution of Naegleria species from thermal spring environments in Taiwan.

UNLABELLED: Naegleria spp. is a free-living amoeba that can be found in the natural environment. A number of Naegleria spp. can cause fatal infections in the central nervous system in humans and animals, and the most important source of infection is through direct water contact. In this study, water samples from various thermal springs were taken from four thermal spring areas. Naegleria spp. was detected via culture confirmation and molecular taxonomic identification. Among the 60 samples obtained, Naegleria spp. was identified in 26 (43·3%) samples. The identified species included Naegleria australiensis, Naegleria gruberi, Naegleria lovaniensis and Naegleria mexicana. The presence of living Naegleria spp. was significantly associated with elevated pH value in the water sample. SIGNIFICANCE AND IMPACT OF STUDY: In this study, we examined the presence of living Naegleria spp. in thermal spring waters in south-eastern Taiwan. Naegleria spp. was isolated and culture-confirmed from thermal spring water. Naegleria fowleri was not found in all water samples, and Naegleria australiensis was the most common Naegleria genotype.

A numerical scheme for the ground state of rotating spin-1 Bose-Einstein condensates.

We study the existence of nontrivial solution branches of three-coupled Gross-Pitaevskii equations (CGPEs), which are used as the mathematical model for rotating spin-1 Bose-Einstein condensates (BEC). The Lyapunov-Schmidt reduction is exploited to test the branching of nontrivial solution curves from the trivial one in some neighborhoods of bifurcation points. A multilevel continuation method is proposed for computing the ground state solution of rotating spin-1 BEC. By properly choosing the constraint conditions associated with the components of the parameter variable, the proposed algorithm can effectively compute the ground states of spin-1 [Formula: see text] and [Formula: see text] under rapid rotation. Extensive numerical results demonstrate the efficiency of the proposed algorithm. In particular, the affect of the magnetization on the CGPEs is investigated.

Prediction of conversion from clinically isolated syndrome to clinically definite multiple sclerosis according to baseline MRI findings: comparison of revised McDonald criteria and Swanton modified criteria.

BACKGROUND: The International Panel on the Diagnosis of Multiple Sclerosis first incorporated abnormalities demonstrated by brain and spinal cord MRI into the diagnostic criteria (McDonald criteria) for multiple sclerosis (MS), which were later revised in 2005. In 2006, Swanton and colleagues modified the MRI criteria to simplify and speed the diagnosis. OBJECTIVE: The purpose of this study was to compare the ability of two sets of criteria (the revised McDonald MRI criteria and Swanton's modified criteria) to predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) from baseline MRI findings. METHODS: Sixty-four patients presenting with CIS suggestive of multiple sclerosis were recruited from 2001 to 2006 and followed up for at least 2 years. Their baseline brain and spinal cord MRI studies were retrospectively evaluated. The patients who developed CDMS during follow-up were treated as positive cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the two MRI dissemination-in-space criteria were calculated. RESULTS: Thirty patients (46.9%) converted to CDMS. The sensitivity specificity, PPV, NPV and accuracy (%) of the revised McDonald criteria were 53, 100, 100, 71 and 78, respectively, while those for Swanton's modified criteria were 60, 100, 100, 74 and 81. CONCLUSIONS: In conclusion, Swanton's modified criteria are more sensitive and accurate (but not significantly so). However, Swanton's criteria are simpler to use and have equally high specificity and PPV.

CD56+ B-cell Neurolymphomatosis in a Cat.

A 16-year-old male Russian blue cat was presented with acute onset of paraparesis of the forelimbs that progressed to tetraparesis. Neurological examination revealed non-ambulatory tetraparesis with decreased postural reactions in all four limbs. Magnetic resonance imaging revealed multifocal nerve root swelling on the right at C6/C7 and C7/T1, while ultrasonography demonstrated swelling of the right brachial plexus. To understand the cause of the nerve swelling, the right musculocutaneous nerve arising from the brachial plexus and the pectoralis muscle were biopsied. Histologically, there was evidence of neurolymphomatosis (neurotropic lymphoma) with Wallerian degeneration and denervation atrophy of myofibres. The neoplastic lymphoid cells expressed CD79a, CD20 and CD56. Based on these findings, a diagnosis of B-cell neurolymphomatosis was made. Expression of CD56, synonymous with neural cell adhesion molecule, is rare in B-cell lymphomas and has not been reported in feline B-cell lymphomas or feline neurolymphomatosis. CD56 expression was suspected to have played an important role in neurotropism of the neoplastic cells in this case.

Analyses of layer-thickness effects in bilayered dental ceramics subjected to thermal stresses and ring-on-ring tests.

OBJECTIVES: The purpose of this study was to analyze the stress distribution through the thickness of bilayered dental ceramics subjected to both thermal stresses and ring-on-ring tests and to systematically examine how the individual layer thickness influences this stress distribution and the failure origin. METHODS: Ring-on-ring tests were performed on In-Ceram Alumina/Vitadur Alpha porcelain bilayered disks with porcelain in the tensile side, and In-Ceram Alumina to porcelain layer thickness ratios of 1:2, 1:1, and 2:1 were used to characterize whether failure originated at the surface or the interface. Based on (1) the thermomechanical properties and thickness of each layer, (2) the difference between the test temperature and the glass transition temperature, and (3) the ring-on-ring loading configuration, the stress distribution through the thickness of the bilayer was calculated using closed-form solutions. Finite element analyses were also performed to verify the analytical results. RESULTS: The calculated stress distributions showed that the location of maximum tension during testing shifted from the porcelain surface to the In-Ceram Alumina/porcelain interface when the relative layer thickness ratio changed from 1:2 to 1:1 and to 2:1. This trend is in agreement with the experimental observations of the failure origins. SIGNIFICANCE: For bilayered dental ceramics subjected to ring-on-ring tests, the location of maximum tension can shift from the surface to the interface depending upon the layer thickness ratio. The closed-form solutions for bilayers subjected to both thermal stresses and ring-on-ring tests allow the biaxial strength of the bilayer to be evaluated.

Endovascular procedures for cerebrovenous disorders.

Cerebral venous anomalies may have a variety of clinical consequences. MR or CT venogram can assist the imaging diagnosis; yet, cerebral angiogram may be required to confirm or establish the correct diagnosis. Venous anomalies predisposing venous hypertension may be categorized into three major entities such as congenital variations, outflow obstruction, and increased blood flow. The degree of clinical presentations of venous hypertension depends upon the chronicity or acuteness. Venous hypertension may lead to venous congestion with edema, hemorrhage and encephalopathy. Endovascular therapeutic procedures may be employed to relieve venous congestion either from reducing blood flow or relieving obstruction. Those endovascular treatment options include embolization, thrombolysis and angioplastic stentings.

Turbulence in a matter-wave supersolid.

Quantum turbulence associated with wave and vortex dynamics is numerically investigated for a two-dimensional trapped atomic Rydberg-dressed Bose-Einstein condensate (BEC). When the coupling constant of the soft-core interaction is over a critical value, the superfluid (SF) system can transition into a hexagonal supersolid (SS) state. Based on the Gross-Pitaevskii equation approach, we have discovered a new characteristic k-13/3 scaling law for wave turbulence in the SS state, that coexists with the waveaction k-1/3 and energy k-1 cascades commonly existing in a SF BEC. The new k-13/3 scaling law implies that the SS system exhibits a negative, minus-one power energy dispersion (E ~ k-1) at the wavevector consistent with the radius of the SS droplet. For vortex turbulence, in addition to the presence of the Kolmogorov energy k-5/3 and Saffman enstrophy k-4 cascades, it is found that large amount of independent vortices and antivortices pinned to the interior of the oscillating SS results in a strong k-1 scaling at the wavevector consistent with the SS lattice constant.

PBPK Modeling of the Effect of Reduced Kidney Function on the Pharmacokinetics of Drugs Excreted Renally by Organic Anion Transporters.

Altered pharmacokinetics (PK) in subjects with chronic kidney disease (CKD) may lead to dosing adjustment of certain drugs in subjects with CKD. It can be valuable to quantitatively predict PK in CKD for the management of drug dosing in these subjects. We developed physiologically based pharmacokinetic (PBPK) models of seven renally eliminated drugs: adefovir, avibactam, entecavir, famotidine, ganciclovir, oseltamivir carboxylate, and sitagliptin. These drugs are all substrates of renal organic anion transporters (OATs). Drug models verified using PK data from healthy subjects (HS) were coupled with physiological models representing CKD that incorporated prior knowledge of effects of CKD on hepatic and renal elimination. The models reasonably described clinically observed PK changes in subjects with CKD (compared to subjects with normal renal function), with predicted AUC changes within 50% of the observed changes. PBPK models can be used to prospectively predict PK of renally eliminated OAT substrates in subjects with CKD.

Diffuse-type Gastric Mucinous and Signet Ring Cell Adenocarcinoma in a Captive California King Snake (Lampropeltis getula californiae).

An adult female California king snake (Lampropeltis getula californiae) housed in Taipei Zoo was presented with a 2-week history of anorexia, fatigue and abdominal swelling. Exploratory laparotomy revealed a gastric mass with two circular perforations and multiple mottled white to beige protuberances along the mucosal surface. Histologically, the gastric mass showed an invasive, transmural growth of epithelial cells arranged in nests, lobules, acini and sheets in the mucosa and submucosa that progressively transformed into signet ring cells in the muscularis externa and subserosa. All of the neoplastic cells expressed pan-cytokeratin immunohistochemically. Based on the World Health Organization histological criteria, a diagnosis of diffuse-type gastric mucinous and signet ring cell adenocarcinoma was made.

Different intestinal tropism of the G2b Taiwan porcine epidemic diarrhea virus-Pintung 52 strain in conventional 7-day-old piglets.

The group 2b (G2b) porcine epidemic diarrhea virus (PEDV) that emerged in 2013 has since caused devastating diseases and economic loss. The full-length genome of the G2b Taiwan PEDV-Pintung 52 (PEDV-PT) strain and its intestinal tropism by evaluating the pathological changes in the original PEDV-PT infected field piglet and orally inoculation of either 10, 103, or 105 50% tissue culture infective dose/mL (TCID50/mL) of the plaque-purified PEDV-PT-Passage 5 (P5) in 7-day-old conventional piglets were analyzed. Phylogenetic analysis of the full-length genome indicated that the G2b Taiwan PEDV-PT strain was closely related to the North American G2b PEDV strains. Some pathological features of the G2b Taiwan PEDV-PT infection, including the absence of lesions and antigen signal in the crypt epithelial cells of the jejunum and ileum and in the villus enterocytes of the duodenum and colon, were different from those of infections by the North American G2b PEDV strains. This difference in the intestinal tropism of the G2b Taiwan PEDV-PT strain highlights the importance of studying the pathogenicities of different PEDV variants. Moreover, similar distributions of PEDV antigens and lesions in the G2b Taiwan PEDV-PT infected field piglet and its plaque-purified isolate, PEDV-PT-P5, inoculated piglets indicating that the plaque-purified PEDV-PT-P5 viral stock could facilitate the preclinical evaluation of vaccines and other interventions aimed at preventing the G2b PEDV infection.

The lipoxygenase inhibitor, baicalein, modulates cell adhesion and migration by up-regulation of integrins and vinculin in rat heart endothelial cells.

BACKGROUND AND PURPOSE: Endothelial cell proliferation, migration and adhesion are necessary for the formation of new blood vessels. We reported previously that baicalein strongly inhibited proliferation of rat heart endothelial cells and here we assess effects on migration and adhesion of these cells. EXPERIMENTAL APPROACH: Effects of baicalein on endothelial migration and adhesion were determined by in vitro wound assays and in modified Boyden chambers. Protein expression and subcellular distribution in rat heart endothelial cells were analysed by immunoblots and immunofluorescence staining. RESULTS: Pretreatment with baicalein for 48 h resulted in a concentration-dependent inhibition of endothelial migration, with an IC(50) of approximately 20 microM. Adhesion assays revealed that baicalein stimulated endothelial cell adhesion to fibronectin and vitronectin, effects blocked by the synthetic peptide Arg-Gly-Asp (RGD). Moreover, treatment with a blocking antibody against integrin alpha5beta1 drastically attenuated baicalein-mediated endothelial adhesion to fibronectin, but not to vitronectin. Furthermore, baicalein-mediated anti-migration effect and adhesion promotion could be partially reversed by the addition of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). Western blot analysis indicated that baicalein increased expression levels of integrin-alpha5beta1, -alphavbeta3 and vinculin proteins. Immunofluorescence staining showed that baicalein induced a marked reorganization of actin stress fibres and the recruitment of vinculin and integrins to focal adhesion plaques, with consequently increased formation of focal adhesion contacts. CONCLUSIONS AND IMPLICATIONS: Baicalein markedly inhibited the migration and enhanced the adhesion of rat heart endothelial cells, possibly by up-regulation of the integrins (alpha5beta1 and alphavbeta3) and vinculin and by promotion of actin reorganization and focal adhesion contact formation.

Diffusion-tensor MR imaging for evaluation of the efficacy of hyperbaric oxygen therapy in patients with delayed neuropsychiatric syndrome caused by carbon monoxide inhalation.

The purpose of this study is to assess the efficacy of hyperbaric oxygen therapy (HBOT) in patients with delayed neuropsychiatric syndrome (DNS) caused by carbon monoxide (CO) inhalation using diffusion tensor magnetic resonance (MR) imaging and neuropsychological test. Conventional and diffusion tensor brain MR imaging exams were performed in six patients with DNS immediately before and 3 months after the HBOT to obtain fractional anisotropy (FA) values. Six age- and sex-matched normal control subjects also received MR exams for comparison. Mini-Mental State Examination (MMSE) was also performed in patients immediately before and 3 months after the HBOT. A significantly higher mean FA value was found in control subjects as compared with the patients both before and 3 months after the HBOT (P < 0.001). The mean FA value 3 months after the HBOT was also significantly higher than that before the HBOT in the patient group (P < 0.001). All of the patients regained full scores in the MMSE 3 months after the HBOT. Diffusion tensor MR imaging can be a quantitative method for the assessment of the white matter change and monitor the treatment response in patients of CO-induced DNS with a good clinical correlation. HBO may be an effective therapy for DNS.

Reperfusion liver injury-induced superoxide dismutase and catalase expressions and the protective effects of N-acetyl cysteine.

AIM: Reperfusion of the ischemic liver results in the generation of oxygen radicals. In this study, we analyzed if the mRNA and protein expressions of superoxide dismutase (SOD) and catalase increased after ischemia (I) and reperfusion (R) of the rat liver. MATERIALS AND METHODS: Ischemia was induced by clamping off the common hepatic artery and portal vein of rats for 40 minutes, which were then reperfused for 90 minutes. Blood samples collected prior to I and after R were analyzed for hydroxyl radical (.OH), nitric oxide (NO), and alanine transferase (ALT). Liver tissues were used to analyze the SOD and catalase mRNA and protein expressions by real-time polymerase chain reaction and Western blot. RESULTS: The results showed that this protocol resulted in elevation of the blood ALT, NO, and .OH levels (P<.001). mRNA (P<.01) and protein expressions (P<.05) of SOD and catalase were all increased. Pretreatment with antioxidant, N-acetyl cysteine, attenuated the liver injury. CONCLUSION: These results indicate that reperfusion of the ischemic liver induced antioxidant enzymes expressions so that oxygen radicals are scavenged. Oxygen radical scavenger could further attenuate the I/R-induced liver injury.

Appraisal of formulas for stresses in bilayered dental ceramics subjected to biaxial moment loading.

OBJECTIVES: The purpose of this study was to compare three existing sets of formulas predicting stresses in a thin circular plate subjected to biaxial moment loading, such that limitations for each set of formulas could be understood. These formulas include American Society for Testing and Materials (ASTM) formulas for monolayered plates, Roark's formulas for bilayered plates, and Hsueh et al.'s formulas for multilayered plates. METHODS: The three sets of formulas were summarized and appraised. Biaxial moment loading is generally achieved using biaxial flexure tests, and the plate is placed on a support ring and loaded in the central region. While both ASTM and Hsueh et al.'s formulas predict stresses through the thickness of the plate, Roark's formulas predict stresses only on the top and the bottom surfaces of the plate. Also, a simply supported plate at its edge is considered in Roark's formulas. We modified Roark's formulas to include the overhang region of the plate to more closely simulate the actual loading configuration. Then, the accuracy of formulas was examined by comparing with finite element results of monolayered and bilayered plates subjected to ring-on-ring loading. RESULTS: Monolayer is a special case of bilayer, and both monolayer and bilayer are special cases of multilayer. For monolayered plates, ASTM and Hsueh et al.'s formulas are identical, and both are in excellent agreement with finite element results. For bilayered plates, Hsueh et al.'s formulas are in excellent agreement with finite element results. For both monolayered and bilayered plates, Roark's formulas deviate from finite element results while the modified Roark's formulas are accurate. CONCLUSIONS: Roark's formulas for evaluating the biaxial strength of bilayered dental ceramics will result in errors in predicted stresses which depend on the size of the overhang region of the plate in the actual loading configuration. Also, Roark's formulas are limited to predicting stresses on the top and the bottom surfaces of the plate. On the other hand, Hsueh et al.'s formulas are for multilayered plates and predict stresses through the plate thickness.

Novel activated alumina-supported iron oxide-composite as a heterogeneous catalyst for photooxidative degradation of reactive black 5.

A novel activated alumina-supported iron oxide-composite (denoted as FeAA-500) was prepared by so-called fluidized-bed reactor (FBR) crystallization. X-ray powder diffraction (XRD), N2 adsorption/desorption, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) were used to characterize the FeAA-500. The photo-catalytic activity of the FeAA-500 was evaluated in the photooxidative degradation of 0.1 mM azo-dye reactive black 5 (RB5) in the presence of H2O2 and UVA light (lambda = 365 nm) in a solution with a pH of 2.5. Complete decolorization of the model pollutant RB5 was achieved; the total organic carbon (TOC) removal ratio was 95%, and a trace amount of leached ferric ion was detected following 75 min of reaction when 2.0 g/L FeAA-500 was used as a catalyst. FeAA-500 has high photo-catalytic activity; it is therefore a promising heterogeneous photocatalysis of the degradation of organic compounds.

Photooxidation of azo dye reactive black 5 using a novel supported iron oxide: heterogeneous and homogeneous approach.

Photooxidation of azo dye Reactive Black 5 (RB5) by H202 was performed with a novel supported iron oxide in a batch reactor in the range of pH 2.5-6.0. The iron oxide was prepared through a fluidized-bed reactor (FBR) and much cheaper than the Nafion-based catalysts. Experimental results indicate that the iron oxide can significantly accelerate the degradation of RB5 under the irradiation of UVA light (wavelength = 365 nm). An advantage of the catalyst is its long-term stability, which was confirmed through using the catalyst for multiple runs in the degradation of RB5. In addition, this study focused mainly on determining the proportions of homogeneous catalysis and heterogeneous catalysis in the batch reactor. Conclusively, although heterogeneous catalysis contributes primarily to the oxidation of RB5 during pH 4.5-6.0, the homogeneous catalysis is of increasing importance below pH 4.0 because of the Fe ions leaching from the catalyst to solution.

Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.

Transporter-mediated drug-drug interactions (DDIs) are a major cause of drug toxicities. Using published genome-wide association studies (GWAS) of the human metabolome, we identified 20 metabolites associated with genetic variants in organic anion transporter, OATP1B1 (P < 5 × 10-8 ). Of these, 12 metabolites were significantly higher in plasma samples from volunteers dosed with the OATP1B1 inhibitor, cyclosporine (CSA) vs. placebo (q-value < 0.2). Conjugated bile acids and fatty acid dicarboxylates were among the metabolites discovered using both GWAS and CSA administration. In vitro studies confirmed tetradecanedioate (TDA) and hexadecanedioate (HDA) were novel substrates of OATP1B1 as well as OAT1 and OAT3. This study highlights the use of multiple datasets for the discovery of endogenous metabolites that represent potential in vivo biomarkers for transporter-mediated DDIs. Future studies are needed to determine whether these metabolites can serve as qualified biomarkers for organic anion transporters. Quantitative relationships between metabolite levels and modulation of transporters should be established.

UCN-01 suppresses thymidylate synthase gene expression and enhances 5-fluorouracil-induced apoptosis in a sequence-dependent manner.

UCN-01, a protein kinase C/cyclin-dependent kinase inhibitor, suppressed thymidylate synthase (TS) protein expression in a dose-dependent manner with near complete suppression at 1 microM after a 24-h exposure in human gastric cancer cell line SK-GT5. Other protein kinase C/cyclin-dependent kinase inhibitors, including flavopiridol and safingol, had a similar effect on TS protein expression, but to a lesser degree. Moreover, UCN-01 repressed the induction of TS after 5-fluorouracil (FU) exposure by 90-95% and significantly enhanced the induction of apoptosis by FU from 4-8% with either FU or UCN-01 alone to 46+/-1% (P < 0.005 versus either single drug, reverse sequence, or the combination) when UCN-01 was given after FU. The effect of UCN-01 on TS was associated with a dose-dependent suppression of the E2F-1 protein, a transcriptional activator of TS. Northern blot analysis revealed that TS mRNA levels decreased gradually as the concentration of UCN-01 increased, but that E2F-1 mRNA levels remained relatively unchanged. UCN-01 may provide a novel way to enhance cellular sensitivity toward FU by means of suppressing TS expression mediated mainly by down-regulation of E2F-1.

UCN-01 suppresses E2F-1 mediated by ubiquitin-proteasome-dependent degradation.

E2F-1 regulates the transcription of genes required for DNA synthesis. Previously, we have reported that UCN-01 suppresses E2F-1 protein expression without any noticeable effect on its mRNA level in gastric cancer cell line SK-GT5 (Clin. Cancer Res., 4: 2201-2206, 1998). In this study, we investigated the mechanism responsible for the suppression of E2F-1 expression by UCN-01 in SK-GT5 cells. After 24-h exposure to 1 microM UCN-01, E2F-1 protein expression was decreased by >99%. The suppressive effect of UCN-01 could be reversed by ubiquitin-dependent proteasome inhibitors such as calpain inhibitor I and lactacystin. Transfection experiments using expression plasmids encoding full-length E2F-1 or truncated E2F-1 with deletion of the COOH-terminal region (which is required for eliciting ubiquitination and protein degradation) revealed that the expression of truncated E2F-1 was not affected by UCN-01. Other cell-cycle-related and ubiquitin-proteasome-regulated proteins such as p21, p27, and cyclin B1 were not repressed by UCN-01 in E2F-1-overexpressing cells. In vitro-translated, full-length E2F-1 degraded more rapidly upon incubation with extracts from UCN-01-treated cells when compared with truncated E2F-1. Taken together, these data indicate that UCN-01 suppresses E2F-1 protein expression mediated by the ubiquitin-proteasome pathway in a specific manner.