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Doxorubicin (DOX) is a widely used antitumor drug that causes severe neurotoxicity in patients. Diallyl trisulfide (DATS) is an organosulfur compound with established potent antioxidant and anti-inflammatory properties. Herein, we investigated the neuroprotective efficacy of DATS in preventing DOX-induced neurotoxicity in a rat model. Specifically, DATS (40 mg/kg) was administered to rats 24 h after DOX treatment, once a week for 8 weeks. Our results showed that DATS treatment led to a decrease in plasma levels of tumor necrosis factor-alpha (TNF-α) induced by DOX. DATS restored cerebral cortex and hippocampus histopathological architecture and neuronal loss. Immunohistochemical staining indicated that DATS decreased the expression of glial fibrillar acidic protein (GFAP) in DOX treated rats. Components of stress-related inflammatory proteins (TNF-α, phospho nuclear factor kappa B (NF-κB), inducible nitricoxide synthase (iNOS) and cyclooxygenase-2 (COX-2)) were all significantly increased in the DOX group, in comparison with the control group, whereas they were decreased after DATS treatment. In addition, the mRNA of antioxidant enzymes (superoxide dismutase 2 (SOD2), catalase, glutathione peroxidase 1, 4 (GPx1 and GPx4)) and antioxidant proteins (heme oxygenase-1 (HO-1), superoxide dismutase 1, 2 (SOD1 and SOD2), Γ-glutamylcysteine synthase (Γ-GCSc)) were markedly increased in DOX group compared with the control group, which were significantly attenuated by DATS treatment. The upregulation of antioxidants enzymes in DOX group was probably a compensatory effect against elevated oxidative stress induced by DOX. DATS treatment could ameliorate this oxidative stress in brain. Our results suggested that DATS has potential clinical applications in the prevention of DOX-induced neurotoxicity by ameliorating inflammatory insults and oxidative stress.

We report on CdSe@ZnS light-emitting diodes (QLEDs) showing both high efficiency and long operational lifetime by introducing thermally cross-linkable 2,7-disubstituted fluorene-based triaryldiamine (VB-FNPD) as the hole transporting layer and 1,4,5,8,9,11-hexaazatriphenylene hexacarbonitrile (HAT-CN) as the hole injection layer. The green QLEDs achieved a maximum external quantum efficiency (EQE) of 8.0% and power efficiency (PE) of 32.1 lm W−1 with low efficiency roll-offs. More importantly, the corresponding QLED demonstrated a long lifespan in operation by simple encapsulation without desiccation. Under the initial luminance of 2000 cd m−2 and a continuous flow of constant current, the device still held luminance of 1000 cd m−2 after 50 h operation. The overall decay profile was fitted by two single exponential components, with time constants of 17.2 and ∼104 h, which is superior to that using the conventional polymer as the hole transporting layer. The thermally polymerizable hole transporting materials therefore offer an effective approach to realize both good efficiency and long-term stability in QLED.

Continuous scaling down NAND flash memory toward below 1Xnm node generation will result in serious floating gate (FG) poly depletion and significantly impact the cell reliability performance. In this study, the FG implantation before inter-poly-dielectric deposition was proposed. We have successfully explored the methods to minimize the FG implanted damage issue and hence the void-free control gate (CG) can be achieved after the CG poly-Si fill-in. After optimizing the FG implanted processes, the cell reliabilities on 1Xnm NAND flash device were verified. The FG poly depletion can be effectively reduced by the additional FG dopant, which results in the significant improvement on the natural threshold-voltage (Vt) distribution width, the program noise, and the program/erase Vt degradation. Moreover, there is no degradation on non-cycle data retention when adding the FG implantation, which suggests no extra FG dopant penetrated into tunnel oxide as the trap sites to enhance the trap-assisted tunneling leakage under high temperature baking.

Hepatitis B virus (HBV) pre-S deletion was associated with chronic hepatitis (CH) and liver cirrhosis (LC); however, the type of pre-S deletion associated with these conditions and the mechanism of the generation of pre-S deletion remain unknown. Here, pre-S sequences from asymptomatic carriers (ASCs) and carriers with CH or LC were analyzed. The results indicated that deletion in the S promoter and the C-terminal half of the pre-S1 region was more frequent in CH and LC patients than in ASCs. RNA splicing analysis revealed that one type of pre-S1 deletion mutant, termed spPS1, was derived from splicing. This variant was associated with CH (12.7% vs. 1.8%, P = 0.06) and LC (14.5% vs. 1.8%, P = 0.032) when compared with ASC. In conclusion, spPS1, a putative splice variant; S promoter deletion mutant; and deletion in the C-terminal half of the pre-S1 region were closely associated with CH and LC development.

In the development of semiconductor packaging technology from planar to three-dimensional vertical integration, chip interconnection density has increased, and the distance of signal transmission has dropped to improve overall device performance. In this research, an architecture composed of through‑silicon via (TSV) and solder microbump (μbump) is utilized to assemble an ultra thin-type chip into a three-dimensional integrated circuit (3D-IC) package. To explore the influence of residual thermomechanical residual stress induced during the manufacture of the 3D-IC package on the subsequent reliability of the thermal cycling test (TCT), this study establishes a nonlinear simulation methodology for investigating the coupling effect of the manufacturing process and the TCT. The plastic and creep behaviors of the solder μbump are considered in the finite element modeling. The concerned geometric dimensions and underfill materials are also parametrically analyzed. Furthermore, the inelastic strain accumulated in the crucial SnAg solder μbump is examined. Results indicate that the residual strain in the manufacturing process causes an obvious packaging warpage and converges at the subsequent TCT stage. The creep of the solder μbump increases up to 50% in thermal cycling, thereby highlighting the importance of considering the creep model. Moreover, the parameterization of chip thickness can minimize the inelastic strain increment of the solder μbump, and the low Young's modulus of the underfill materials exerts a significant effect on the warpage of the packaging module and the stress compliance of the μbumps.

To resolve and simplify the critical assembly issue regarding the interposer of 3D integrated circuits (3D-ICs), a prototype of an embedded interposer carrier (EIC) is developed and demonstrated. However, the serious warping induced during the laminating process of multi-stacked organic films needs to be resolved to achieve good co-planarity of the EIC assembled by either dies or a printed circuit board. Hence, a unique design with an additional ring-type stiff frame is proposed and introduced into EIC fabrication. Through process-based simulation combined with the full factor design approach, a restraint for the warping of EIC lower than 14.24µm is estimated; a steel-made ring-type frame combined with suitable conjugations of laminated materials is considered. Analytic results reveal that laminated layers having high elastic modulus and a small coefficient of thermal expansion are useful in moderating EIC warping. Consequently, the assembly reliability of 3D-ICs through EIC technology is expected to increase significantly. Display Omitted An embedded interposer carrier (EIC) is developed and demonstrated.Warpage issue of EIC is addressed by proposed ring-type framework.The warp of EIC is estimated and validated by simulations and experimental inspection.A steel-made ring-type frame with suitable conjugations of laminations is preferred.A significant reduction in warping lower by 14.24µm for EIC can be achieved.

This study presents a process for wafer handling and robust assembly, which is a novel pre-molding technology applied to assembled stacked modules prior to chip thinning. These steps aim to overcome severe challenges of achieving extra-thin thickness as low as 10µm for chip stacking in 3D-IC module, such as mechanical damage that appears during chip grinding. A packaging vehicle is fabricated to demonstrate the feasibility of the proposed approach. Analysis results show that underfill flexibility can relieve expansion of the produced stress to establish a 3D simulation model. The top layer of the outermost microjoint has the most serious reliability concern under a load of temperature change. Moreover, failure estimation and mechanical reliability are also performed via 3D nonlinear finite element analysis. Display Omitted This study presents a process for wafer handling and robust assembly for thin chip stacking.A pre-molding technology is used to achieve extra-thin chip thickness down to 10µm.Testing vehicle is fabricated to demonstrate the possibility of proposed approach.A simulation methodology is adopted to find the stress-induced failure of vehicles.Effects of underfill flexibility and die thickness of proposed framework are considered.

Three-dimensional integrated circuit (3D-IC) packaging has attracted considerable research interest because it allows the integration of heterogeneous functions among stacked chips. The thermal mismatch stresses induced by thermal cycling loads in the interconnects that are composed of a through silicon via (TSV) and microbumps are a serious concern, and thus, a thinner stacked die is required. To shrink the foregoing thickness to less than 10 μm, a novel assembly approach involving the use of pre-stuffed molding material at the wafer-level grinding process is proposed in this study. The assembly results are performed by using a chip-on-wafer module. In addition, the parametric estimation of the induced stress/strain resulting from the geometries of fine-pitch TSVs under temperature cycling loads is also performed by using non-linear finite element analysis. In thick silicon chips, the capability of a stress-release mechanism for the TSV and microbumps depends on the adoption of underfill material and the proper selection of its elastic modulus. By contrast, the non-linear stress/strain at all the interconnects of a 3D-IC package with extremely thin stacked chips decreases due to the excellent flexibility provided by the silicon chip. The results of this study are valuable to the configuration design and demonstrate the feasibility of 3D-IC packages with thin stacked chips assembled through the proposed assembly approach.

Sequential and transient electrocatalysis of d- glucose oxidation reactions (GORs) were studied using core-shell Pd@Pt particles with octahedral (Pd@PtOct, 76.2 nm), rhombic dodecahedral (Pd@PtRD, 79.3 nm), and nanocubic (Pd@PtNC, 62.7 nm) geometries to determine the reaction mechanism. The resulting currents and in situ frequency changes, measured using an electrochemical quartz crystal microbalance, clearly revealed that the molar ratios of electron to d- glucose mass were 1.24 and 1.22 for the sequential catalysis of the glucose oxidation by Pd@PtOct and Pd@PtNC, respectively; however, a higher ratio of 2.22 was observed for Pd@PtRD. The GORs catalyzed by Pd@PtOct and Pd@PtNC occurred via a one-electron pathway to produce gluconate, whereas the GOR catalyzed by Pd@PtRD occurred via a two-electron mechanism to generate δ-gluconolactone. A comparison based on the same electrochemical surface areas suggested that Pd@PtOct and Pd@PtRD have slightly higher activities than that of Pd@PtNC. The amperometric curves of transient catalysis at −0.05 V vs. Ag/AgCl revealed that the oxidative current density of the tested catalysts after 200 s follow the order of Pd@PtOct > Pd@PtNC > Pd@PtRD.

More than 20% of chronic hepatitis C (CHC) patients receiving interferon-alpha (IFN-α)-based anti-hepatitis C virus (HCV) therapy experienced significant depression, which was relieved by treatment with fluoxetine. However, whether and how fluoxetine affected directly the anti-HCV therapy remained unclear. Here, we demonstrated that fluoxetine inhibited HCV infection and blocked the production of reactive oxygen species (ROS) and lipid accumulation in Huh7.5 cells. Fluoxetine facilitated the IFN-α-mediated antiviral actions via activations of signal transducer and activator of transcription (STAT)-1 and c-Jun amino-terminal kinases (JNK). Alternatively, fluoxetine elevated peroxisome proliferator-activated receptor (PPAR) response element activity under HCV infection. The inhibitory effects of fluoxetine on HCV infection and lipid accumulation, but not production of ROS, were partially reversed by the PPAR-β, -γ, and JNK antagonists. Furthermore, fluoxetine intervention to the IFN-α-2b regimen facilitated to reduce HCV titer and alanine transaminase level for CHC patients. Therefore, fluoxetine intervention to the IFN-α-2b regimen improved the efficacy of anti-HCV treatment, which might be related to blockades of ROS generation and lipid accumulation and activation of host antiviral JNK/STAT-1 and PPARβ/γ signals.

The one-pot synthesis of Pd/Cu concave nanocubes (CNCs) with (510) facets as oxygen reduction reaction catalysts has been successfully demonstrated in this work. Based on the same loading weight of metal catalyst and supported by rotating ring-disk electrode measurements, our results showed that the CNC catalysts of small electrochemical surface area (8.57 m2 g−1) had fast kinetics in the mixed-controlled region for 0.1 M NaOH solutions. Also, at 0.9 V versus reversible hydrogen electrode, the specific activity was 0.422 mA cm−2. This is 1.7 times higher than that of commercial Pt/C catalysts (0.248 mA cm−2) with high electrochemical surface area (29.73 m2 g−1).

Skin injuries, congenital lesions, melasma, Addison's disease and many pigment abnormalities prompt us to search for an effective whitening agent. Ideal whitening agent is a natural compound that can inhibit melanogenesis and has no cytotoxic effects. In a previous study, we have developed an optimum method for the production and characterization of ectoine from a halophilic bacterium isolated from a salt environment in Taiwan was identified as Marinococcus sp. In the present study, we screened the whitening properties of the biosynthesized ectoine using mouse and human melanoma cell lines, B16-F0 and A2058. Here, we examined the cell viabilities of melanoma cells after ectoine treatment at various concentrations up to 500 μM. Also, we addressed the melanin synthesis of melanoma cells after treatment with ectoine. The inhibitory effects of ectoine on tyrosinase activity were assessed in both mushroom tyrosinase and cellular tyrosinase. Furthermore, we investigated the type of inhibition of mushroom tyrosinase using Lineweaver–Burk enzyme kinetic. The melanogenesis-related gene expression (tyrosinase, TRP1, TRP2 and MITF) and their protein secretion were determined by the assays of quantitative real-time PCR and western blots, respectively. Our results demonstrated that ectoine is a safe and effective whitening agent, inhibited melanin synthesis, reduced both mushroom tyrosinase and cellular tyrosinase, and had various inhibitory effects on the expressions of melanogenesis-related genes and secretion of proteins in mouse and human melanoma cell lines. Thus, we suggest that ectoine can serve as a useful and safe new agent in cosmetic and clinical applications.

Myositis ossificans circumscripta is a benign, self-limiting, ossifying soft-tissue mass that typically occurs in skeletal muscle of the extremities after trauma. Occurrence in the psoas muscle is rare with no reports of this condition presenting as femoral neuropathy. A 54-year-old woman visited our hospital because of progressive left leg pain and weakness, which she had experienced for 2 years. Physical examination indicated left femoral neuropathy, and a 6 cm × 5 cm mass was palpable in the left groin. Plain radiographs showed an irregular calcification over the left hip. Computed tomography of the pelvis showed a fusiform mass within the left psoas muscle. A modified ilioinguinal approach was used to excise the mass, and histologic examination confirmed the diagnosis. After surgery, the patient's symptoms resolved and there was no recurrence at 4 years' follow-up. Excision may be considered when a patient has a large, painful mass with neuropathy and significant functional impairment after conservative treatment.

Osteosarcoma is characterized by a high malignant and metastatic potential. Interleukin-6 (IL-6) is a multifunctional cytokine that is associated with the disease status and outcomes of cancers. However, the effect of IL-6 on migration activity in human osteosarcoma cells is mostly unknown. Here we found that IL-6 increased the migration and expression of intercellular adhesion molecule-1 (ICAM-1) in human osteosarcoma cells. Transfection of cells with ICAM-1 siRNA reduced IL-6-mediated cell migration. We also found that expression of IL-6 was significantly greater in human osteosarcoma tissues than in normal bone. The integrin-linked kinase (ILK)/Akt/AP-1 pathway was activated after IL-6 treatment, and IL-6-induced expression of ICAM-1 and migration activity was inhibited by the specific inhibitor and siRNA of ILK, Akt, and AP-1 cascades. In addition, over-expression of IL-6 shRNA inhibited the migratory ability and ICAM-1 expression in osteosarcoma cells. Taken together, these results indicate that IL-6 and IL-6 receptor interaction occurs through ILK and Akt, which in turn activates AP-1, resulting in the activations of ICAM-1 and contributing the migration of human osteosarcoma cells.

Epigenetic inactivation of tumor-suppressor genes, often in association with aberrant DNA methylation of CpG islands in the promoter region of these genes, is a key factor in tumorigenesis. CCAAT/enhancer binding protein alpha (CEBPA) methylation is a favorable prognostic biomarker for acute myeloid leukemia; however, rather than the complete methylation observed in inherited disorders, CEBPA methylation is heterogeneous. In this study, we established an algorithm called the “methylation index,” deduced from high-resolution melting profiles, which includes Tm shifting (ΔTm) and Tm width ratio (fold of width), to evaluate the heterogeneous methylation status. The methylation index was highly correlated with the exact methylation levels detected by using the MassARRAY method (R2 = 0.80; P < 0.001). Within-run reproducibility for the methylation index was 0.9% as the coefficient of variation, and between-run reproducibility was 2.6%. It was determined that with a cutoff methylation index of 1.412, the best measures of sensitivity and specificity could be obtained (97.14% and 95.89%, respectively) to discern low or high CEBPA methylation status. This novel algorithm for calculation of the methylation index from high-resolution melting profiles for CEBPA methylation is compatible with measurement of the methylation level as assayed using MassARRAY and could be a simple and efficient screening method for determination of CEBPA methylation status in acute myeloid leukemia.

Background Our previous studies revealed that cardioplegia-induced cardiac arrest under cardiopulmonary bypass (CPB) decreased cardiomyocytic nitric oxide and increased apoptosis. We hypothesized that pretreatment with bradykinin (BK) would improve the profile of anti-apoptotic proteins and inhibit cardiomyocytic apoptosis. Materials and Methods New Zealand white rabbits received total CPB. Rabbits were weaned from CPB and reperfused for 4 h. Blood was sampled at various time points. Bradykinin and/or nitric oxide synthase (NOS) inhibitors or BK-receptor antagonists were infused systemically 30 min before beginning of CPB, and continued throughout the procedure. The ascending aorta was cross-clamped for 60 min while cold crystalloid cardioplegic solution was intermittently infused into the aortic root. The hearts were harvested and studied for evidence of apoptosis and ischemia/reperfusion induced inflammation-related cytokine production by cardiomyocytes. Results Our results revealed that bradykinin supplementation during cardioplegia could prevent I/R-induced inflammatory and apoptotic effects, which could be reversed with a NOS inhibitor. BK antagonists and NOS inhibitors worsened the inflammatory and apoptotic responses of cardiomyocytes, which could be reversed with an exogenous NO donor. Conclusions Restoring the NO concentration after cardioplegia-induced cardiac arrest (CCA) under CPB with bradykinin could modulate (1) the nuclear translocation of NF-κB, (2) the plasma levels of inflammation-related cytokines, (3) the Bcl-2/Bax ratio, and (4) the occurrence of apoptosis. Exogenous bradykinin administration was associated with the myocardial apoptotic response by inhibition of NF-κB translocation, inflammatory cytokine production, Akt activation, and elevation of the Bcl-2/Bax ratio via a NO-mediated pathway.

Cationic antimicrobial peptides/proteins (AMPs) are important components of the host innate defense mechanisms against invading microorganisms. Here we demonstrate that OprI (outer membrane protein I) of Pseudomonas aeruginosa is responsible for its susceptibility to human ribonuclease 7 (hRNase 7) and alpha-helical cationic AMPs, instead of surface lipopolysaccharide, which is the initial binding site of cationic AMPs. The antimicrobial activities of hRNase 7 and alpha-helical cationic AMPs against P. aeruginosa were inhibited by the addition of exogenous OprI or anti-OprI antibody. On modification and internalization of OprI by hRNase 7 into cytosol, the bacterial membrane became permeable to metabolites. The lipoprotein was predicted to consist of an extended loop at the N terminus for hRNase 7/lipopolysaccharide binding, a trimeric alpha-helix, and a lysine residue at the C terminus for cell wall anchoring. Our findings highlight a novel mechanism of antimicrobial activity and document a previously unexplored target of alpha-helical cationic AMPs, which may be used for screening drugs to treat antibiotic-resistant bacterial infection.

Background NF-κB and AP-1 play important roles in regulation of inflammatory responses that lead to cardiomyocytic injury following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion. It has been reported that heme oxygenase-1 (HO-1) can block those responses. Our aim was to determine whether HO-1 activation could decrease myocardial ischemia-reperfusion injury with cardioplegia during CPB and attenuate apoptosis of cardiomyocytes. Materials and Methods Rabbits (10 in each group) were randomized to receive either bypass only (Group 1), CPB plus intravenous normal saline (Group 2), hemin (HO-1 inducer; Group 3), SnPP (HO-1 inhibitor; Group 4), or hemin + SnPP (Group 5) 2 d before CPB. In all groups except Group 1, cold (4°C) antegrade intermittent crystalloid cardioplegia was delivered every 20 min for a total of 60 min of cardiac arrest, after CPB was established. Rabbits were weaned from CPB and reperfused for 4 h. Blood was sampled at various time points. The reperfused hearts were harvested for Western blotting and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) experiments. Results The postoperative elevation of serum levels of IL-10, IL-6, and TNF-α were significantly decreased in Group 3, but HO-1 inhibitor abolished this effect (Group 4). Moreover in Group 3, the number of apoptotic cardiomyocytes, level of apoptosis-related activated fragments of caspase-3 and Akt, and level of nuclear NF-κB and AP-1 translocation were significantly decreased. Conclusions HO-1 activation can dampen the surge of inflammation-related cytokines during CPB and decrease the occurrence of cardiomyocytic apoptosis via inhibition of NF-κB and AP-1 translocation.

A flip chip package was assembled by using 6-layer laminated polyimide coreless substrate, eutectic Sn37Pb solder bump, two kinds of underfill materials and Sn3.0Ag0.5Cu solder balls. Regarding to the yield, the peripheral solder joints were often found not to connect with the substrate due to the warpage at high temperature, modification of reflow profile was benefit to improve this issue. All the samples passed the moisture sensitive level test with a peak temperature of 260 °C and no delamination at the interface of underfill and substrate was found. In order to know the reliability of coreless flip chip package, five test items including temperature cycle test (TCT), thermal shock test (TST), highly accelerated stress test (HAST), high temperature storage test (HTST) and thermal humidity storage test (THST) were done. Both of the two underfill materials could make the samples pass the HTST and THST, however, in the case of TCT, TST and HAST, the reliability of coreless flip chip package was dominated by underfill material. A higher Young’s modules of underfill, the more die crack failures were found. Choosing a correct underfill material was the key factor for volume production of coreless flip chip package.

Death-associated protein kinase (DAPK) is a calmodulin-regulated serine/threonine kinase and elicits tumor suppression function through inhibiting cell adhesion/migration and promoting apoptosis. Despite these biological functions, the signaling mechanisms through which DAPK is regulated remain largely elusive. Here, we show that the leukocyte common antigen-related (LAR) tyrosine phosphatase dephosphorylates DAPK at pY491/492 to stimulate the catalytic, proapoptotic, and antiadhesion/antimigration activities of DAPK. Conversely, Src phosphorylates DAPK at Y491/492, which induces DAPK intra-/intermolecular interaction and inactivation. Upon EGF stimulation, a rapid Src activation leads to subsequent LAR downregulation, and these two events act in synergism to inactivate DAPK, thereby facilitating tumor cell migration and invasion toward EGF. Finally, DAPK Y491/492 hyperphosphorylation is found in human cancers in which Src activity is aberrantly elevated. These results identify LAR and Src as a DAPK regulator through their reciprocal modification of DAPK Y491/492 residues and establish a functional link of this DAPK-regulatory circuit to tumor progression.

In this study, we employed a thermodynamic method to obtain information on the second virial coefficient of the interactions between liposomes, and we also determined the stabilities of dipalmitoyl-L-alpha-phosphatidylglycerol (DPPG)- and dipalmitoyl-L-alpha-phosphatidylcholine (DPPC)-liposomes. In this study, an interaction model based on a hard-sphere interaction potential assumption was employed, and we used high-sensitivity isothermal titration nanocalorimetry (ITC) to measure the dilution heat of liposomal suspensions. Information on the second virial coefficient of interactions between liposomes can be derived from the number density of the liposomal suspension. Additionally, we qualitatively demonstrated the repulsive forces of DPPG- and DPPC-liposomes systems. In this work, both the b2 and b2/B0 levels of DPPG-liposome were greater and had better physical stability than those of DPPC-liposome. # 2007 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

Phylogeny reconstruction is too complex a combinatorial problem for an exhaustive search, because the number of possible solutions increases exponentially with the number of taxa involved. In this paper, we adopt the parsimony principle and design a tabu search algorithm for finding a most parsimonious phylogeny tree. A special array structure is employed to represent the topology of trees and to generate the neighboring trees. We test the proposed tabu search algorithm on randomly selected data sets obtained from nuclear ribosomal DNA sequence data. The experiments show that our algorithm explores fewer trees to reach the optimal one than the commonly used program “dnapenny” (branch-and-bound based) while it generates much more accurate results than the default options of the program “dnapars” (heuristic search based). The percentage of search space needed to find the best solution for our algorithm decreased rapidly as the number of taxa increased. For a 20-taxon phylogeny problem, it needs on average to examine only 3.92 × 10 −15 % of the sample space.

Sea shells are composed of calcium carbonate crystals interleaved with layers of viscoelastic proteins, having dense, tailored structures that yield excellent mechanical properties. Shells such as conch (Strombus gigas), giant clam (Tridacna gigas), and red abalone (Haliotis rufescens) have hierarchical architectures that differ depending on growth requirements and shell formation of the particular mollusk. Mechanical tests have been carried out on these shells for a comparison of strength with respect to the microstructural architecture and sample orientation. The mechanical response is found to vary significantly from specimen to specimen and requires the application of Weibull statistics in order to be quantitatively evaluated. The complex micro-laminate structure of these biocomposite materials is characterized and related to their mechanical properties. The red abalone has the highest compressive (233–540 MPa) and flexure strengths of the three shells. The giant clam has the lowest strength (87–123 MPa) and the conch has an intermediate value (166–218 MPa) in compression. The high compressive strength observed in the abalone is attributed to an optimization of microstructural architecture in the form of 2-D laminates, enhancing the fracture toughness of this shell material and enabling higher stresses to develop before fracture. D 2005 Elsevier B.V. All rights reserved.

Background. Following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion, proinflammatory cytokines are activated and cause cardiomyocytic injury. Nuclear factor (NF)-B is involved in regulating inflammatory signal transduction. Curcumin inhibits NF-B activation and blocks the inflammatory responses. We studied whether curcumin could decrease myocardial ischemia/reperfusion injury with cardioplegia during CPB and attenuate the appearance of apoptosis of cardiomyocytes. Materials and methods. Rabbits received normal saline (group 1) or curcumin (70 M/kg, group 2; 100 M/kg, group 3) injection 2 h before CPB. Total CPB was initiated and cold (4°C) antegrade intermittent crystalloid cardioplegia was delivered every 20 min for 60 min of cardiac arrest. Rabbits were weaned from CPB and reperfused for 4 h. Blood was sampled at various time points and then the reperfused hearts were harvested. Results. Postoperative elevation of plasma levels of interleukin (IL)-8 (14.5, 0.9, 2.9 times over baseline in groups 1‐3, respectively, P < 0.05), IL-10 (201.1, 6.0, 14.9 times over baseline in groups 1‐3, respectively, P < 0.05), TNF- (9.4, 3.1, 3.9 times over baseline in groups 1‐3, respectively, P < 0.05), and cardiac troponin I (141.2, 14.9, 15.0 times over baseline) significantly decreased in the curcumin groups. Appearance of apoptotic cardiomyocytes significantly decreased in the curcumin groups (5.69 1.64, 1.51 0.41, 2.43 0.49 per 1000 nuclei in groups 1‐3, respectively, P < 0.01). The activation of neutrophil in the myocardium, which was measured using myocardial myloperoxidase activity assay, was significantly attenuated in the curcumin group. There was a significant increase in apoptosis-related cleavage fragments of caspase-3 and poly-ADP-ribose polymerase in group 1 compared to the other groups. Conclusions. Curcumin, an inhibitor of NF-B, ameliorated the surge of pro-inflammatory cytokines during CPB and decreased the occurrence of cardiomyocytic apoptosis after global cardiac ischemia/reperfusion

In this paper, the p-type Si/SiGe metal-oxide-semiconductor field-effect transistor (PMOSFET) utilizing a strain-graded-Si 1− x Ge x well, has been successfully fabricated by ultra-high-vacuum chemical vapor deposition (UHVCVD). Due to the inverse grading Ge composition in conjunction with higher valence-band discontinuity at Si 0.7 Ge 0.3 /Si-buffer interface, most of carriers are populated at the bottom of SiGe-conducting channel, which undergo higher mobility. It is found that by grading Ge fraction in the channel, the devices exhibit the excellent property not only of higher mobility but also enhancement in extrinsic transconductance and linear operation range over a wider dynamic range than those of devices with uniform Ge profile for the same integrated Ge dose in SiGe conducting well.