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In this study, we explore the evolution of martensitic structures during deformation and their correlation with solution temperature in a metastable β-type Ti–10V–2Fe–3Al alloy. After a solution treatment at 760 °C, microstructures consist of equiaxed β grains and primary α particles. Increasing the solution temperature to 780 °C minimally affects equiaxed β grain size (~4.1–4.7 μm) but significantly reduces the α phase volume fraction. The α particles become scarce and completely absent following solution treatments at 800 and 820 °C, where the β grain size grows to ~109.1 and ~151.3 μm, respectively. Thermally-induced martensite (TIM) α″ laths are formed in specimens solution-treated at 770 °C or higher, predominantly populating the β grains of the specific specimens solution-treated at 800 and 820 °C. All solution-treated specimens exhibit a double yielding phenomenon. For specimens solution-treated at 760–780 °C, this results primarily from the stress-induced martensitic transformation (SIMT) process, while for those solution-treated at 800 and 820 °C, it mainly arises from the martensite reorientation (MR) process. The triggering stress for the SIMT/MR process increases with increasing solution temperature. In early deformation stages, TIM α″ laths initially undergo the MR process, transforming into a favored α″ variant, and the SIMT process can occur concurrently. As deformation progresses, the α″ phase changes orientation continuously through deformation twinning, transforming into the favored α″ variant dictated by the evolving stress conditions. This study provides insights into martensitic structure evolution and its influence on mechanical properties in metastable β titanium alloys. [ABSTRACT FROM AUTHOR]

A proportional-integral-derivative-based (PID based) sliding mode control (SMC) was applied to the linear stage driven by a constraint-tuning modified-mode (CTMM) ultrasonic actuator. Based upon the driving variation of voltage amplitude and the preload on the CTMM ultrasonic actuator, nonlinear phenomena, such as frequencies shifting in electromechanical resonance and the dead zone in moving response, could be suppressed almost completely by the PID based SMC controller with output biases. Using system identification technique, an approximate second-order model of the linear stage could be obtained for the equivalent control term of the PID based SMC controller. Through an estimated model error, the design of the switching control term was used to compensate for the shifting property of resonant frequencies under electromechanical coupling. A target-command-shaping function matched the responding speed of the system during tracking experiments. Experimental results demonstrate that the SMC controller has the capacity for noise rejection to control the slider's position in bilateral tracking motions. Its resolution is sufficient to approach micrometer-level accuracy. [ABSTRACT FROM AUTHOR]

Separation from parents is a key aspect of adolescent development and has been linked to a variety of important mental and behavioral health outcomes. Separation-individuation measures were developed in the United States and have been used in Asian contexts. However, no cross-cultural studies have demonstrated that measures of separation-individuation tap the same domains across Asian and American adolescents. This article describes two studies conducted to develop and initially validate a scale for measuring adolescent separation-individuation. Study 1 (n = 300) developed a Brief Measure of Separation-Individuation (BMSI) using Confirmatory Factor Analysis and Item Response Theory. The result was a 32-item BMSI that provided comparable test information to the original 148-item measure. Study 2 examined the BMSI for measurement invariance and convergent validity across U.S. and Taiwanese samples (ns = 231 and 323). Findings suggest that functional independence, attitudinal independence, and emotional independence may be culturally invariant separation-individuation constructs. However, conflictual independence seems to be more culturally dependent in that its items were only partially scalar invariant and it was only loosely related to the other separation-individuation factors. Findings are consistent with previous research that recommended against using total scores for the PSI (i.e., scoring a single separation-individuation dimension). This study suggests the BMSI holds promise as a brief measure of separation-individuation that can be used in cross-cultural research. [ABSTRACT FROM AUTHOR]

The cancellation of birefringence in the distributed Bragg reflector based on 90° rotation offset method is demonstrated. It is found that the birefringence, which causes the peak bifurcation has been eliminated and a single peak is produced at each resonance in the output spectrum. This modification is an economic solution for eliminating the birefringence of the optical fibre devices. [ABSTRACT FROM AUTHOR]

Cold-worked alloys exhibit high strength, but suffer from limited ductility. In contrast, Ti-based gum metal was reported to exhibit high strength combined with good ductility upon severe pre-straining. Motivated by this anomaly, we systematically studied the evolution of gum metal microstructure during severe cold working (swaging and rolling) and the resulting deformation and damage micro-mechanical mechanisms during follow-up tensile deformation. To this end, various experimental in situ and post-mortem methodologies are employed, including scanning electron microscopy imaging, high-resolution electron backscatter diffraction mapping and transmission electron microscopy. These observations reveal that intense grain refinement takes place through dislocation plasticity-dominated deformation banding upon cold working. The observed enhancement in crack blunting and failure resistance which prolongs the post-necking ductility of gum metal during follow-up tensile straining can be attributed to the deformation-induced development of local heterogeneities in texture and grain size. [ABSTRACT FROM AUTHOR]

Mutant Kras (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is observed in more than 20% of non-small-cell lung cancers; however, no effective Kras target therapy is available at present. The Kras DNA vaccine may represent as a novel immunotherapeutic agent in lung cancer. In this study, we investigated the antitumor efficacy of the Kras DNA vaccine in a genetically engineered inducible mouse lung tumor model driven by KrasG12D. Lung tumors were induced by doxycycline, and the therapeutic effects of Kras DNA vaccine were evaluated with delivery of KrasG12D plasmids. Mutant KrasG12D DNA vaccine significantly decreased the tumor nodules. A dominant-negative mutant KrasG12DN17, devoid of oncogenic activity, achieved similar therapeutic effects. The T-helper 1 immune response was enhanced in mice treated with Kras DNA vaccine. Splenocytes from mice receiving Kras DNA vaccine presented an antigen-specific response by treatment with peptides of Kras but not Hras or OVA. The number of tumor-infiltrating CD8+ T cells increased after Kras vaccination. In contrast, Kras DNA vaccine was not effective in the lung tumor in transgenic mice, which was induced by mutant L858R epidermal growth factor receptor. Overall, these results indicate that Kras DNA vaccine produces an effective antitumor response in transgenic mice, and may be useful in treating lung cancer-carrying Ras mutation. [ABSTRACT FROM AUTHOR]

Background: A histamine-2 receptor antagonist (H2RA) is one of the common gastroprotective co-therapies used with non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention or treatment of peptic ulcers (PUs). To date, no study has directly compared the prophylactic effectiveness between high-dose and low-dose H2RA.Objective: Our objective was to compare the effectiveness of high-dose versus low-dose H2RAs in the primary prophylaxis of PUs among short-term NSAID users.Methods: A retrospective cohort study was conducted using the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. Patients aged 18 years or above who received a single prescription of oral NSAID with oral H2RA were identified within the study period (1 January 2009-31 December 2012). Patients with a history of or risk factors for PU in the corresponding 2 years prior to the index date (of the first NSAID prescription) were excluded. Log binomial regression analysis was used to calculate the relative risk of PU among NSAID users with high-dose H2RA versus low-dose H2RA exposure.Results: Among the NSAID cohort (n = 102,042), 77,509 (76 %) were on low-dose H2RA and 24,533 (24 %) were on high-dose H2RA. Of the total 69 PU cases identified during the drug exposure period, 64 (0.08 %) received low-dose-H2RA and five (0.02 %) received high-dose H2RA. The overall absolute risk of PUs for NSAID users whilst on H2RA was approximately 1 per 1,479 patients. The adjusted relative risk for NSAID users receiving high-dose H2RA versus low-dose H2RA was 0.32 (95 % confidence interval [CI] 0.13-0.79). Patients aged ≥65 years, receiving a longer duration of treatment, or with concomitant use of antiplatelet agents were found to be at higher risk of PU.Conclusion: High-dose H2RA showed greater effectiveness than low-dose H2RA in the primary prophylaxis of NSAID-associated PUs in short-term new users. [ABSTRACT FROM AUTHOR]

EGFR overexpression and chromosome 3p deletion are two frequent events in head and neck cancers. We previously mapped the smallest region of recurrent copy-number loss at 3p12.2-p14.1. LRIG1, a negative regulator of EGFR, was found at 3p14, and its copy-number loss correlated with poor clinical outcome. Inducible expression of LRIG1 in head and neck cancer TW01 cells, a line with low LRIG1 levels, suppressed cell proliferation in vitro and tumor growth in vivo. Gene expression profiling, quantitative RT-PCR, chromatin immunoprecipitation, and western blot analysis demonstrated that LRIG1 modulated extracellular matrix (ECM) remodeling and EGFR-MAPK-SPHK1 transduction pathway by suppressing expression of EGFR ligands/activators, MMPs and SPHK1. In addition, LRIG1 induction triggered cell morphology changes and integrin inactivation, which coupled with reduced SNAI2 expression. By contrast, knockdown of endogenous LRIG1 in TW06 cells, a line with normal LRIG1 levels, significantly enhanced cell proliferation, migration and invasiveness. Such tumor-promoting effects could be abolished by specific MAPK or SPHK1 inhibitors. Our data suggest LRIG1 as a tumor suppressor for head and neck cancers; LRIG1 downregulation in cancer cells enhances EGFR-MAPK-SPHK1 signaling and ECM remodeling activity, leading to malignant phenotypes of head and neck cancers. [ABSTRACT FROM AUTHOR]

Cellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of caspase-8 and is required for macrophage survival. Recent studies have revealed a selective role of caspase-8 in noncanonical IL-1β production that is independent of caspase-1 or inflammasome. Here we demonstrated that c-FLIPL is an unexpected contributor to canonical inflammasome activation for the generation of caspase-1 and active IL-1β. Hemizygotic deletion of c-FLIP impaired ATP- and monosodium uric acid (MSU)-induced IL-1β production in macrophages primed through Toll-like receptors (TLRs). Decreased IL-1β expression was attributed to a reduced activation of caspase-1 in c-FLIP hemizygotic cells. In contrast, the production of TNF-α was not affected by downregulation in c-FLIP. c-FLIPL interacted with NLRP3 or procaspase-1. c-FLIP is required for the full NLRP3 inflammasome assembly and NLRP3 mitochondrial localization, and c-FLIP is associated with NLRP3 inflammasome. c-FLIP downregulation also reduced AIM2 inflammasome activation. In contrast, c-FLIP inhibited SMAC mimetic-, FasL-, or Dectin-1-induced IL-1β generation that is caspase-8-mediated. Our results demonstrate a prominent role of c-FLIPL in the optimal activation of the NLRP3 and AIM2 inflammasomes, and suggest that c-FLIP could be a valid target for treatment of inflammatory diseases caused by over-activation of inflammasomes. [ABSTRACT FROM AUTHOR]

Since most current seismic capacity evaluations of reinforced concrete (RC) frame structures are implemented by either static pushover analysis (PA) or dynamic time history analysis, with diverse settings of the plastic hinges (PHs) on such main structural components as columns, beams and walls, the complex behavior of shear failure at beam-column joints (BCJs) during major earthquakes is commonly neglected. This study proposes new nonlinear PA procedures that consider shear failure at BCJs and seek to assess the actual damage to RC structures. Based on the specifications of FEMA-356, a simplified joint model composed of two nonlinear cross struts placed diagonally over the location of the plastic hinge is established, allowing a sophisticated PA to be performed. To verify the validity of this method, the analytical results for the capacity curves and the failure mechanism derived from three different full-size RC frames are compared with the experimental measurements. By considering shear failure at BCJs, the proposed nonlinear analytical procedures can be used to estimate the structural behavior of RC frames, including seismic capacity and the progressive failure sequence of joints, in a precise and effective manner. [ABSTRACT FROM AUTHOR]

Histone deacetylase (HDAC) inhibitors are used in treating certain human malignancies. Our laboratories demonstrated their capability in enhancing antitumor effect of DNA vaccine driven by an RNA polymerase II (RNA pol II) promoter. However, it is unknown whether HDAC inhibitors enhance the therapeutic short hairpin RNA (shRNA) expressed by an RNA polymerase III (RNA pol III) promoter. We investigated whether HDAC inhibitors augmented antitumor effect of indoleamine 2,3 dioxygenase (IDO) shRNA. HDAC inhibitor OSU-HDAC42 and suberoylanilide hydroxamic acid enhanced RNA pol Ill-driven U6 and H1 promoter activity in three different cell types in vitro: 293, NIH3T3 and dendritic cell line DC2.4. Subcutaneous injection of OSU-HDAC42 enhanced U6 and H1 promoter activity on abdominal skin of mice in vivo. Combination of IDO shRNA and OSU-HDAC42 increased antitumor effect of IDO shRNA in MBT-2 murine bladder tumor model. IDO shRNA induced tumor-infiltrating CD8+ and CD4+ T cells, whereas OSU-HDAC42 treatment induced tumor-infiltrating CD4+ T cells. Combination of OSU-HDAC42 and IDO shRNA further induced tumor-infiltrating natural killer cells and enhanced interferon-y in lymphocytes, but suppressed interleukin (IL)-4 expression of lymphocytes. In addition, OSU-HDAC42 treatment did not alter mRNA expression of IL-12 and tumor necrosis factor-a. In conclusion, HDAC inhibitor OSU-HDAC42 may serve as adjuvant of the therapeutic shRNA expressed by an RNA pol III promoter. [ABSTRACT FROM AUTHOR]

(LaGd)SrMnO manganite perovskite nanorods were synthesized by sonication-assisted coprecipitation. Lower sintering temperatures were required for all the samples to crystallize. The fully crystallize samples of (LaGd)SrMnO and (LaGd)SrMnO show the formation of nanorods upon their synthesis with an average length and width of 160 nm and 20 nm, respectively. The structural, electrical, and magnetic transport properties were investigated. [ABSTRACT FROM AUTHOR]

To develop and validate prediction rules to identify the risk of methicillin-resistant Staphylococcus aureus (MRSA) infection among community patients who have healthcare-associated (HA) exposure and S. aureus bacteremia. A total of 1,166 adults with community-onset S. aureus bacteremia were retrospectively enrolled. The background prevalence of community MRSA infection was extrapolated from 392 community-associated S. aureus bacteremia (CA-SAB) patients without HA exposure. Complete and clinical risk scores were derived and tested using data from 774 healthcare-associated S. aureus bacteremia (HA-SAB) patients. The risk scores were modeled with and without incorporating previous microbiological data as a model predictor and stratified patients to low-, intermediate-, and high-risk groups for MRSA infection. The clinical risk score included five independent predictors and the complete risk score included six independent predictors. The clinical and complete risk scores stratified 32.7 % and 42.0 % of HA-SAB patients to the low-risk group for MRSA infection respectively. The prevalence of MRSA infection in score-stratified low-risk groups ranged from 16.3 % to 23.3 %, comparable to that of CA-SAB patients (13.8 %). Simple decision rules allow physicians to stratify the risk of MRSA infection when treating community patients with prior HA exposure and possible S. aureus infection. [ABSTRACT FROM AUTHOR]

Molecular dynamics (MD) simulations of nanometric-cutting copper are conducted to study the critical rake angle during the cutting process. A new approach based on the maximum displacement of atoms in cutting direction is proposed to estimate the chip formation in MD simulation. It is found that the minimum rake angle for chip formation is −65-(−70) and the subsurface deformations of copper are mostly the dislocation and stacking faults. Three-dimensional simulation results show that the effective rake angle of stagnation region is constant with the same depth of cut. According to the limited depth of cut of copper can be achieved, the available minimum tool edge radius is suggested to be not less than 10 nm. [ABSTRACT FROM AUTHOR]

Apoptosis has a vital role in maintaining tissue homeostasis, and dysregulation of the apoptotic pathway is now widely recognized as a key step in tumourigenesis. Increasingly, evidence has demonstrated that microRNA (miRNA) can exert various biological functions in tumours by targeting oncogenes or tumour suppressors. Nevertheless, the role of miRNA in apoptosis remains unclear. Here we show that ectopical expression of miR-148a can induce apoptosis in colorectal cancer cells. In addition, MYB can inhibit miR-148a by directly acting on the transcription factor binding site in miR-148a gene and miR-148a can posttranscriptionally silence Bcl-2. Subsequently, the intrinsic apoptosis pathway is activated by releasing cytochrome c, cleaving caspase 9, caspase 3 and PARP, which eventually induce cancer-cell apoptosis. These findings are part of a hitherto undocumented apoptotic regulatory pathway in which a pleiotropic transcription factor controls the expression of a miRNA and the miRNA inhibits the target, leading to activation of an intrinsic mitochondrial pathway and tumour apoptosis. [ABSTRACT FROM AUTHOR]

BRCA1, a well-known tumor suppressor with multiple interacting partners, is predicted to have diverse biological functions. However, so far its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low-penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate-risk variant, and found that it does not impair DNA damage repair but abrogates the repression of microRNA-155 (miR-155), a bona fide oncomir. Mechanistically, we found that BRCA1 epigenetically represses miR-155 expression via its association with HDAC2, which deacetylates histones H2A and H3 on the miR-155 promoter. We show that overexpression of miR-155 accelerates but the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Our findings demonstrate a new mode of tumor suppression by BRCA1 and suggest that miR-155 is a potential therapeutic target for BRCA1-deficient tumors. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to validate the Multinational Association for Supportive Care in Cancer (MASCC) risk index, and compare it with the Talcott model and artificial neural network (ANN) in predicting the outcome of febrile neutropenia in a Chinese population.Methods: We prospectively enrolled adult cancer patients who developed febrile neutropenia after chemotherapy and risk classified them according to MASCC score and Talcott model. ANN models were constructed and temporally validated in prospectively collected cohorts.Results: From October 2005 to February 2008, 227 consecutive patients were enrolled. Serious medical complications occurred in 22% of patients and 4% died. The positive predictive value of low risk prediction was 86% (95% CI = 81-90%) for MASCC score ≥ 21, 84% (79-89%) for Talcott model, and 85% (78-93%) for the best ANN model. The sensitivity, specificity, negative predictive value, and misclassification rate were 81%, 60%, 52%, and 24%, respectively, for MASCC score ≥ 21; and 50%, 72%, 33%, and 44%, respectively, for Talcott model; and 84%, 60%, 58%, and 22%, respectively, for ANN model. The area under the receiver-operating characteristic curve was 0.808 (95% CI = 0.717-0.899) for MASCC, 0.573 (0.455-0.691) for Talcott, and 0.737 (0.633-0.841) for ANN model. In the low risk group identified by MASCC score ≥ 21 (70% of all patients), 12.5% developed complications and 1.9% died, compared with 43.3%, and 9.0%, respectively, in the high risk group (p < 0.0001).Conclusions: The MASCC risk index is prospectively validated in a Chinese population. It demonstrates a better overall performance than the Talcott model and is equivalent to ANN model. [ABSTRACT FROM AUTHOR]

We propose a novel breakup model to simulate the catastrophic breakup regime in a supersonic cross flow. A developed model has been extended from an existing Kelvin-Helmholtz/Rayleigh-Taylor (K-H/R-T) hybrid model. A new mass reduction rate equation, which has critical effects on overall spray structure, is successfully adopted, and the breakup length, which is an important parameter in existing model, is replaced by the breakup initiation time. Measured data from the supersonic wind tunnel with a dimension of 762×152×127 mm was employed to validate the newly developed breakup model. A nonaerated injector with an orifice diameter of 0.5 mm is used to inject water into a supersonic flow prescribed by the momentum flux ratio of the liquid jet to free stream air, q. The conservation-element and solution-element (CE/SE) method, a novel numerical framework for the general conservation law, is applied to simulate the supersonic compressible flow. The spray penetration height and average droplet size along with a spray penetration axis are quantitatively compared with data. The shock train flow structures induced by the presence of a liquid jet are further discussed. [ABSTRACT FROM AUTHOR]

The article looks at a study in which a novel technique to quantify the signal-to-noise ratio (SNR) of magnetic resonance images is developed. Topics covered include representation of signal and noise components on a plot of the autocorrelation function, SNR estimation method using a single image, and a table that shows parameters derived from the noisy images.

BiFeO(BFO) thin films of about 200 nm in thickness have been successfully grown on oxide bottom electrode, LaNiO(LNO), via pulsed laser ablation. X-ray diffraction spectrum of the as-deposited BFO film reveals a (100) preferred textured structure. The morphology of the BFO film is found to be strongly dependent on oxygen partial pressure in laser ablation. A saturated hysteresis loop with remanent polarization of 42 μC/cm and coercive field of 100 kV/cm is obtained at the film deposition at 50 mTorr. The dielectric properties have also been obtained based on the influence of the oxygen pressure. [ABSTRACT FROM AUTHOR]

Ezrin links cortical actin filaments with the cell membrane, and has a critical role in many membrane-initiated events. Fas is directly associated with ezrin, but conflicting results have been reported for the involvement of ezrin in Fas-induced cell death. In this study we show that ezrin was associated with Fas in T cells before stimulation and was released shortly after Fas ligand (FasL) engagement. The knockdown of ezrin moderately increased Fas-triggered or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-triggered cell death in normal T lymphocytes and in H9 cells, but had no effect on death receptor-induced apoptosis in type II cells, such as Jurkat and CEM. Expression of a dominant-negative form of ezrin also led to an increased Fas-induced apoptosis in H9 cells. Ezrin deficiency did not affect the internalization of Fas after Fas ligation. Instead, an enhanced formation of death-inducing signaling complex (DISC) was observed in H9 cells with ezrin knockdown, leading to accelerated caspase-8 activation. Together, our results suggest that ezrin has a negative role in the recruitment of Fas into signaling complexes in type I T cells. Loss of ezrin likely removes the constraint imposed by ezrin and facilitates the assembly of death receptor complex in T cells. [ABSTRACT FROM AUTHOR]

The cytomegalovirus (CMV) promoter is considered to be one of the strongest promoters for driving the in vivo expression of genes encoded by DNA vaccines. However, the efficacy of DNA vaccines has so far been disappointing (particularly in humans), and this might be explained in part by histone deacetylase (HDAC)-mediated chromatin condensation. Hence, we sought to investigate whether increasing the expression of DNA vaccine antigens with the HDAC inhibitor OSU-HDAC42 would enhance the efficacy of DNA vaccines in vivo. A luciferase assay was used to determine the effects of OSU-HDAC42 on CMV promoter-driven DNA plasmids in vitro and in vivo. Three HDAC inhibitors were able to activate expression from the CMV promoter in NIH3T3 cells and MBT-2 bladder cancer cells. The expression of luciferase was significantly enhanced by co-administration of pCMV-luciferase and OSU-HDAC42 in mice. To explore whether OSU-HDAC42 could enhance the specific antitumor activity of a neu DNA vaccine driven by the CMV promoter, we evaluated therapeutic effects and immune responses in a mouse tumor natively overexpressing HER2/neu. Mice receiving OSU-HDAC42 in combination with the CMV-promoter neu DNA vaccine exhibited stronger antitumor effects than mice given the DNA vaccine only. In addition, a correlation between the antitumor effects and the specific cellular immune responses was observed in the mice receiving the DNA vaccine and OSU-HDAC42. [ABSTRACT FROM AUTHOR]

Metastasis is the most significant process affecting the clinical management of cancer patients and occurs in multiple sequential steps. However, the molecular pathways underlying each step still remain obscure. Recent research has shown that there is a microRNA (miRNA) network that functions as a regulator of tumor metastasis. In this paper, we review the role of miRNAs in tumor metastasis, including control of epithelial–mesenchymal transition, regulation of metastasis-associated genes and epigenetic alterations. More information on miRNAs will promote a better understanding of the molecular mechanism of metastasis. [ABSTRACT FROM AUTHOR]

Vitamin D exhibits immunomodulatory and antiproliferative effects through vitamin D receptor (VDR) in chronic infections and cancers. We genotyped the BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) polymorphisms of VDR gene in 250 Taiwanese chronic hepatitis B virus (HBV) carriers who were categorized into six phenotypes. After adjustment for age and sex, the frequencies of the VDR B/b, B/a, B/T, B/a/T in patients with hepatitis flare(s) were lower than those without (7 vs 20%, P=0.009; 1 vs 9%, P=0.004; 3 vs 10%, P=0.007; 1 vs 9%, P=0.005, respectively); in contrast, T/t, A/T, A/t, b/A/t were higher in flare(s) (8 vs 3%, P=0.003; 49 vs 34%, P=0.027; 2 vs 1%, P=0.004; 0.5 vs 0%, P=0.001, respectively). In addition, B/b, B/B, T/t, b/A, B/a, B/A, B/T, B/t, A/t, b/A/T, B/a/T, B/A/T, B/A/t, b/A/t were higher in patients positive for HBeAg. The distribution of VDR genotypes was comparable between patients with and without hepatocellular carcinoma (HCC). VDR gene polymorphisms are associated with distinct clinical phenotypes in Taiwanese HBV carriers but not with HCC development. [ABSTRACT FROM AUTHOR]

Background: Tumour necrosis factor (TNF) is capable of activating the cell death pathway, and has been implicated in killing transformed cells. However, TNF also activates survival signals, including NF-kappaB activation and the subsequent expression of anti-apoptotic genes, leading to protection against TNF toxicity.Methods: In this study, we show that, although untransformed mouse embryonic fibroblasts (MEFs) were resistant to TNF killing, E1A/Ras-transformed MEFs were susceptible to extensive apoptosis induced by TNF. The key factors for determining TNF sensitivity were explored by comparing wild-type and E1A/Ras-transformed MEFs.Results: TNF signalling to NF-kappaB and to its target genes such as IkappaBalpha seemed to be mostly intact in E1A/Ras-transformed cells. Instead, the induction of A20 was completely abolished in E1A/Ras-transformed MEFs, although A20 is known to be NF-kappaB dependent. Reintroduction of A20 into E1A/Ras-transformed MEFs rescued these cells from TNF-induced death and reduced the formation of the FADD/caspase-8 complex. This impaired A20 induction in E1A/Ras MEFs was not because of the stabilisation of p53 or a defective TNF-induced p38 and Jun N-terminal kinase (JNK) signalling. Consistently, we found a reduced A20 promoter activity but normal NF-kappaB activity in TNF-treated E1A/Ras MEFs. However, Bcl-3 seemed to have a role in the transactivation of the A20 promoter in E1A/Ras cells.Conclusions: Our results suggest that specific inhibition of certain survival factors, such as A20, may determine the sensitivity to TNF-induced apoptosis in transformed cells such as E1A/Ras MEFs. [ABSTRACT FROM AUTHOR]

Nanostructured α-MnO2 thin films with different morphologies are grown on the platinum substrates by a facile solution method without any assistance of template or surfactant. Microstructural characterization reveals that morphology evolution from dandelion-like spheres to nanoflakes of the as-grown MnO2 is controlled by synthesis temperature. The capacitive behavior of the MnO2 thin films with different morphologies are studied by cyclic voltammetry. The α-MnO2 thin films composed of dandelion-like spheres exhibit high specific capacitance, good rate capability, and excellent long-term cycling stability. [ABSTRACT FROM AUTHOR]

A piezoelectric atomization device achieves fuel pressure modulation through vibration of a piezoelectric pressure modulator. As a consequence, the fast alternating and slow moving streams collide with each other and further break up the fuel drop. In this paper, an experimental investigation was carried out to study the fluid dynamic characteristics of the spray atomization process of automotive port fuel injectors with a piezoelectric pressure modulator. The investigation mainly focuses on: (a) the coupling characteristics between the piezoelectric stack and the hydraulic as well as the transfer characteristics of pressure modulation from the piezoelectric modulator to the point above the orifice; (b) the time history of the pressure dynamic response at the point above the orifice under a typical modulation frequency, which reflects the variation of pressure modulation while the fuel injector is working; and (c) the time-variation characteristics related to mechanical structure and fluid dynamics. The experimental results expose some important dynamic characteristics of pressure modulation, which will be very significant and lead us to greatly improve the fuel injection system, optimize the control parameters and implement spray atomization with a high quality performance in the near future. [ABSTRACT FROM AUTHOR]

This study investigates an effective method for manufacturing electrical discharge machining (EDM) electrodes using the rapid prototyping (RP) system based on electroless plating (nickel plating) and electroforming (copper). This method was shown to finish the development of die-sinking electrical discharge machining (EDM) electrodes, shorten the electrode manufacturing process, decrease the manufacturing duration as well as the cost of electrodes. The electrode prototype was drawn with Pro/E 3D CAD, and the CAD model was then transformed into the stereo lithography (STL) file format. A Zcorp 402 3DP rapid prototyping machine was adopted to make a gypsum powder electrode prototype with a complex appearance. The gypsum material is sealed by resin permeation, enhancing its water-resistance and strength. Electroless plating was then performed to introduce electric conductivity onto the gypsum electrode surface, followed by copper electroforming of the thickness about 1 mm to obtain the EDM electrode. Furthermore, die-sinking electric discharge machining was performed. Test results indicate that no crack was found on the electrode and that the electrical discharge machining effects are promising. [ABSTRACT FROM AUTHOR]

Promyelocytic leukemia (PML) protein is a tumor suppressor with complicated action mechanisms not yet fully understood. In this study, we found that the nuclear factor of activated T cell (NFAT) is an unexpected partner of PML: PML specifically enhanced the transcription activation of NFAT. In PML-null mouse embryonic fibroblasts, no transcription activity of NFAT could be detected. There was a selective requirement of PML isoform in NFAT activation: PML-I and PML-VI, but not PML-IV, increased NFAT transactivation. PML specifically promoted the expression of many, but not all, NFAT-targeted genes. We found a specific binding of PML to NFATc. The interaction of PML with NFATc in vivo was further confirmed by chromatin immunoprecipitation and DNA affinity precipitation assay analysis. The unexpected coupling of PML with NFAT reveals a novel mechanism underlying the diverse physiological functions of PML.Oncogene (2008) 27, 3821–3830; doi:10.1038/onc.2008.2; published online 4 February 2008 [ABSTRACT FROM AUTHOR]

Neuropsychiatric behaviours in Alzheimer’s disease (AD) patients have been associated with neocortical alterations of presynaptic cholinergic and muscarinic M2 receptor markers. In contrast, it is unclear whether non-M2 muscarinic receptors have a role to play in AD behavioural symptoms. To correlate the alterations of neocortical postsynaptic muscarinic receptors with clinical features of AD. [3H]4-DAMP were used in binding assays with lysates of Chinese hamster ovary (CHO) cells stably transfected with M1–M5 receptors. [3H]4-DAMP was further used to measure muscarinic receptors in the postmortem orbitofrontal cortex of aged controls and AD patients longitudinally assessed for cognitive decline and behavioural symptoms. [3H]4-DAMP binds to human postmortem brain homogenates and M1-, M3-, M4- and M5-transfected CHO lysates with subnanomolar affinity. Compared to the controls, the [3H]4-DAMP binding density is reduced only in AD patients with significant psychotic symptoms. The association between reduced [3H]4-DAMP binding and psychosis is independent of the effects of dementia severity or neurofibrillary tangle burden. This study suggests that the loss of non-M2 muscarinic receptors in the orbitofrontal cortex may be a neurochemical substrate of psychosis in AD and provides a rationale for further development of muscarinic receptor ligands in AD pharmacotherapy. [ABSTRACT FROM AUTHOR]

Pb(Zr0.52Ti0.48)O3 (PZT)/LaNiO3 (LNO) thin films with highly (100) out of plane orientation were produced on SiO2/Si(100) and alkaline earth aluminosilicate glass substrates by pulsed laser deposition (PLD). Orientations of both PZT and LNO films were evaluated using X-ray diffraction. The pure (100)-oriented PZT/LNO films were obtained under optimized deposition conditions. Time of flight-secondary ion mass spectrometry analysis showed that LNO could effectively block interdiffusion between the PZT films and the substrates. Fairly smooth surfaces of the PZT films with roughness of about 4 nm were observed using an atomic force microscope. Cross sectional examination revealed that the films grew in columnar grains. The PZT films grown on both SiO2/Si and glass substrates demonstrated very good ferroelectric characteristic at room temperature with remnant polarization of up to 26 μC/cm2. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the antioxidant activities of a cultured medicinal fungus— Armillariella mellea (Vahl. ex Fr.) Karst. ( AM). Three antioxidant assay systems, namely cytochrome c, xanthine oxidase inhibition, and FeCl2-ascorbic acid stimulated lipid peroxidation in rat tissue homogenate tests, were used. Total flavonoid and phenol contents of AM extracts were also analyzed. Results showed that both aqueous (AM-H2O) and ethanolic (AM-EtOH) extracts of solid state cultured AM showed antioxidant activities in a concentration-dependent manner. At concentrations 1–100 μg/ml, the free radical scavenging activity was 73.7–92.1% for AM-H2O, and 60.0–90.8% for AM-EtOH. These extracts also showed an inhibitory effect on xanthine oxidase activity, but with a lesser potency (IC50 is 9.17 μg/ml for AM-H2O and 7.48 μg/ml for AM-EtOH). In general, AM-H2O showed a stronger antilipid peroxidation activity on different rat’s tissues than AM-EtOH. However, both AM extracts displayed a weak inhibitory effect on lipid peroxidation in plasma. Interestingly, the antilipid peroxidation activity of AM-H2O (IC50–6.66 μg/ml) in brain homogenate was as good as IC50–5.42 μg/ml. AM-H2O (80.0 mg/g) possessed a significantly higher concentration of total flavonoids than AM-EtOH (30.0 mg/g), whereas no difference was noted in the total phenol content between these two extracts. These results conclude that AM extracts possess potent free radical scavenging and antilipid peroxidation activities, especially the AM-H2O in the brain homogenate. [ABSTRACT FROM AUTHOR]

NMR analysis of 13C-labelling patterns showed that the Embden–Meyerhof (EM) pathway is the main route for glycolysis in the extreme thermophile Caldicellulosiruptor saccharolyticus. Glucose fermentation via the EM pathway to acetate results in a theoretical yield of 4 mol of hydrogen and 2 mol of acetate per mole of glucose. Previously, approximately 70% of the theoretical maximum hydrogen yield has been reached in batch fermentations. In this study, hydrogen and acetate yields have been determined at different dilution rates during continuous cultivation. The yields were dependent on the growth rate. The highest hydrogen yields of 82 to 90% of theoretical maximum (3.3 to 3.6 mol H2 per mol glucose) were obtained at low growth rates when a relatively larger part of the consumed glucose is used for maintenance. The hydrogen productivity showed the opposite effect. Both the specific and the volumetric hydrogen production rates were highest at the higher growth rates, reaching values of respectively 30 mmol g−1 h−1 and 20 mmol l−1 h−1. An industrial process for biohydrogen production will require a bioreactor design, which enables an optimal mix of high productivity and high yield. [ABSTRACT FROM AUTHOR]

When the motion of a particle is constrained on the two-dimensional surface, excess terms exist in usual kinetic energy 1/(2μ) ∑ p i 2 with hermitian form of Cartesian momentum p i ( i = 1,2,3), and the operator ordering should be taken into account in the kinetic energy which turns out to be 1/(2μ) ∑ (1/ f i ) p i f i p i where the functions f i are dummy factors in classical mechanics and nontrivial in quantum mechanics. In this article, the explicit forms of the dummy functions f i for quantum motion on some 2D surfaces of revolution of spherical topology are given. [ABSTRACT FROM AUTHOR]

Overproduction of reactive oxygen species is one of the major causes of cell death in ischemic–reperfusion (I/R) injury. In I/R animal models, electron microscopy (EM) has shown mixed apoptotic and necrotic characteristics in the same cardiomyocyte. The present study shows that H2O2 activates both apoptotic and necrotic machineries in the same myocyte and that the ultrastructure seen using EM is very similar to that in I/R animal studies. The apoptotic component is caused by the activation of clotrimazole-sensitive, NAD+/ADP ribose/poly(ADP-ribose) polymerase (PARP)-dependent transient receptor potential M2 (TRPM2) channels, which induces mitochondrial [Na+]m (and [Ca2+]m) overload, resulting in mitochondrial membrane disruption, cytochrome c release, and caspase 3-dependent chromatin condensation/fragmentation. The necrotic component is caspase 3-independent and is caused by PARP-induced [ATP]i/NAD+ depletion, resulting in membrane permeabilization. Inhibition of either TRPM2 or PARP activity only partially inhibits cell death, while inhibition of both completely prevents the ultrastructural changes and myocyte death.Cell Death and Differentiation (2006) 13, 1815–1826. doi:10.1038/sj.cdd.4401813; published online 18 November 2005 [ABSTRACT FROM AUTHOR]

Thermal and dynamic mechanical properties of carbon dioxide and propylene oxide alternative copolymer, poly(propylene carbonate) (PPC), and the end-capped PPC with maleic anhydride were investigated by means of TG and DMA. A master curve of the storage modulus vs. frequency can be deduced from the isochronal curves. Physical parameters of both plain and MA end-capped PPC were discussed. The results showed that for maleic anhydride (MA) end-capping PPC, an improvement of its thermal stability and mechanical properties accompanied with some modifications of the viscoelastic behavior were obtained. [ABSTRACT FROM AUTHOR]

In a case-control study in a veterans hospital in Taiwan, we compared 237 histology-confirmed prostate carcinoma cases with 481 controls, frequency matched by age, for their consumption of vegetarian food, namely soybean products, rice, wheat protein and other vegetables. The multivariable logistic regression analysis showed a significant association with such food (odds ratio (OR)=0.67, 95% confidence interval (CI)=0.47, 0.94). This beneficial effect presented for men with body mass index (BMI) < or =25 kg m(-2) (OR=0.50, 95% CI=0.32, 0.76) but not for men with greater BMI. The OR of prostate carcinoma for men with BMI < or =25 kg m(-2) was 1.74 (95% CI=1.21, 2.51), compared with men with higher BMI (>25 kg m(-2)). Other significant risk factors associated with the disease included higher income (OR=2.40, 95% CI=1.07, 5.42), physical activity (OR=1.75, 95% CI=1.08, 2.83), being married (OR=2.49, 95% CI=1.40, 4.43) and coffee consumption (OR=1.88, 95% CI=1.07, 3.30). Stratified analysis also showed that the consumption of fish/shellfish had an adverse association for men with higher BMI. This study suggests that the intake of the low fat local vegetarian food has a protective effect against prostate carcinoma for thin men in this study population. [ABSTRACT FROM AUTHOR]

There is an increasing interest in lead-zirconate-titanate (PZT) based ferroelectric thin film and devices in recent years. Pulsed laser deposition (PLD) technique has been demonstrated to be a versatile and successful tool for the deposition of epitaxial multi-component metal oxide films and heterostructures. This review presents a reasonable understanding of the relationship between PLD processing and composition, crystal structure and orientation of PZT ferroelectric thin films, and heterostructures. Processing-related issues from PLD of PZT thin films and material-integration strategies developed to fabrication of highly oriented or epitaxial PZT thin film based capacitors with excellent ferroelectric properties are discussed in detail. [ABSTRACT FROM AUTHOR]

A distribution centre (DC) is usually supplied by manufacturing factories and in turn it supplies the consumers. To reduce transportation costs and enhance operation efficiency, selecting a suitable DC location has become a very important issue for both manufacturing and distribution industries. Recently, Chen [1] proposed a fuzzy MCDM (multiple criteria decision-making) approach to selecting the location of a distribution centre. Despite its merits, two limitations were found in his works, i.e. follows: (1) the final fuzzy evaluation value P i was treated as a triangular fuzzy number. This is not correct because it may not produce a triangular shape and (2) the difference of two final fuzzy evaluation values, i.e. P i− P j, was regarded as a triangular fuzzy number. This is also incorrect. Obviously, P i− P j may not produce triangular shape because P i and P j may not be triangular fuzzy numbers. To resolve the above limitations and enhance the applicability of the fuzzy MCDM to the DC location selection problem, an improved fuzzy MCDM approach is proposed. In this work, the membership functions of P i and P i− P j are developed to construct an improved fuzzy preference relation, which is further employed with the Chen ranking procedure to complete the proposed method. Finally, a numerical example demonstrates the feasibility of the proposed method. [ABSTRACT FROM AUTHOR]

The study measures the concentrations of zinc (Zn), copper (Cu), lead (Pb) and chromium (Cr) in the bodies of two most abundant microgastropod species, Sermyla riqueti and Stenothyra devalis, from sediments. Sediment samples were collected from three ecological monitoring sites defined by the Agriculture, Fisheries and Conservation Department in Hong Kong, China on the Mai Po Inner Deep Bay mudflat from November 2001 to May 2003. The research provides indication on the potential environmental health of heavy metals in the higher trophic levels, particularly in birds in the Mai Po Inner Deep Bay Ramsar site.

Rationale: Previous studies have demonstrated reductions of serotonin 5-HT2A receptors in the neocortex of Alzheimer's disease (AD) patients. However, it is unclear whether such losses play a role in the cognitive decline of AD. Objectives: To correlate neocortical 5-HT2A receptor alterations with cognitive decline in AD. Methods: Post-mortem frontal and temporal cortical 5-HT2A receptors were measured by [³H] ketanserin binding in aged controls as well as in a cohort of AD patients who had been longitudinally assessed for cognitive decline and behavioral symptoms. Results: 5-HT2A receptor densities in both regions were reduced in severely demented AD patients compared to age-matched controls. In the temporal cortex, this reduction also correlated with the rate of decline of Mini-Mental State Examination (MMSE) scores. The association between 5-HT2A receptor loss and cognitive decline was independent of the effects of choline acetyltrans-ferase (ChAT) activity and presence of behavioral symptoms. Conclusions: Ourdata suggest that loss of neocortical 5-HT2A receptors may predict for faster cognitive decline in AD, and point to serotomimetics as potentially useful adjuvants to cholinergic replacement therapies. [ABSTRACT FROM AUTHOR]

Blends of poly(ether-sulfone) (PES) and poly(phenylene sulfide) (PPS) with various compositions were prepared using an internal mixer at 290°C and 50 rpm for 10 min. The thermal and dynamic mechanical properties of PES/PPS blends have been investigated by means of DSC and DMA. The blends showed two glass transition temperatures corresponding to PPS-rich and PES-rich phases. Both of them decreased obviously for the blends with PES matrix. On the other hand, Tg of PPS and PES phase decreased a little when PPS is the continuous phase. In the blends quenched from molten state the cold crystallization temperature of PPS was detected in the blends of PES/PPS with mass ratio 50/50 and 60/40. The melting point, crystallization temperature and the crystallinity of blended PPS were nearly unaffected when the mass ratio of PES was less than 60%, however, when the amount of PES is over 60% in the blends, the crystallization of PPS chains was hindered. The thermal and the dynamic mechanical properties of the PPS/PES blends were mainly controlled by the continued phase. [ABSTRACT FROM AUTHOR]

Cellular FLICE-inhibitory protein (c-FLIP) inhibits death receptor-mediated apoptosis by specific interaction with FADD and procaspase-8, and may thus interfere with activation events mediated by FADD and caspase-8. Recent studies, however, suggest that c-FLIP also transmits activation signals. The role of c-FLIP on T-cell activation was examined here using several transgenic mice with variable c-FLIP expression. In all c-FLIP-transgenic mice, Fas-mediated apoptosis and in vitro activation-induced T-cell death were suppressed, and T-cell proliferation and IL-2 production were inhibited. c-FLIP transgene also promoted in vivo thymocyte death. Higher c-FLIP transgene expression was correlated with a more profound suppression of T-cell activation and a prominent disturbance in mature thymocyte development. There was no evidence of increased activation and proliferation in all c-FLIP-transgenic T cells examined. Instead, suppression of T-cell activation in c-FLIP-transgenic T cells could be a combinatory effect of FADD/caspase-8-dependent signals and c-FLIP-specific activities.Cell Death and Differentiation (2004) 11, 69-79. doi:10.1038/sj.cdd.4401316 Published online 29 August 2003 [ABSTRACT FROM AUTHOR]

Unlike mode I, mode II fracture toughness (KIIC) testing is still some way from standardization. In the present study, a specimen is proposed for KIIC testing. The specimen is an adaptation of Richard's (1981) specimen, with the exception that the ligament is extended. Based on numerical analysis, the suitability of the proposed specimen has been assessed by comparing it against the two commonly-used mode II specimens of Banks-Sills and Arcan (1986), and Richard (1981), respectively. In comparison, the proposed specimen has been found to be more compact, and to have a significantly lower intensity of normal stress ahead of the crack tip. As a result, it may be inferred that the proposed specimen would be more suitable for KIIC testing. The modes I and II K-calibration formulae of the proposed specimen have also been deduced. [ABSTRACT FROM AUTHOR]