A technique suitable for diffusion tensor imaging (DTI) at high field strengths is presented in this work. The method is based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) k-space trajectory using EPI as the signal readout module, and hence is dubbed PROPELLER EPI. The implementation of PROPELLER EPI included a series of correction schemes to reduce possible errors associated with the intrinsically higher sensitivity of EPI to off-resonance effects. Experimental results on a 3.0 Tesla MR system showed that the PROPELLER EPI images exhibit substantially reduced geometric distortions compared with single-shot EPI, at a much lower RF specific absorption rate (SAR) than the original version of the PROPELLER fast spin-echo (FSE) technique. For DTI, the self-navigated phase-correction capability of the PROPELLER EPI sequence was shown to be effective for in vivo imaging. A higher signal-to-noise ratio (SNR) compared to single-shot EPI at an identical total scan time was achieved, which is advantageous for routine DTI applications in clinical practice.

Cs0.33WO3 nanoparticles have been prepared successfully by a stirred bead milling process. By grinding micro-sized coarse powder with grinding beads of 50 μm in diameter, the mean hydrodynamic diameter of Cs0.33WO3 powder could be reduced to about 50 nm in 3 h, and a stable aqueous dispersion could be obtained at pH 8 via electrostatic repulsion mechanism. After grinding, the resulting Cs0.33WO3 nanoparticles retained the hexagonal structure and had no significant contaminants from grinding beads. Furthermore, they exhibited a strong characteristic absorption and an excellent photothermal conversion property in the near-infrared (NIR) region, owing to the free electrons or polarons. Also, the NIR absorption and photothermal conversion property became more significant with decreasing particle size or increasing particle concentration. When the concentration of Cs0.33WO3 nanoparticles was 0.08 wt.%, the solution temperature had a significant increase of above 30°C in 10 min under NIR irradiation (808 nm, 2.47 W/cm2). In addition, they had a photothermal conversion efficiency of about 73% and possessed excellent photothermal stability. Such an effective NIR absorption and photothermal conversion nanomaterial not only was useful in the NIR shielding, but also might find great potential in biomedical application.

Abstract

Social anxiety was compared between online and real-life interaction in a sample of 2,348 college students. Severity of social anxiety in both real-life and online interaction was tested for associations with depression, Internet addiction, Internet activity type (gaming versus chatting), and scores on Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) scales. The results showed that social anxiety was lower when interacting online than when interacting offline. Depression, Internet addiction, and high BIS and BAS scores were associated with high social anxiety. The social anxiety decreased more in online interaction among subjects with high social anxiety, depression, BIS, and BAS. This result suggests that the Internet has good potential as an alternative medium for delivering interventions for social anxiety. Further, the effect of BIS on social anxiety is decreased in online interaction. More attention should be paid for BIS when the treatment for social anxiety is delivered online.

Crossing over between homologous chromosomes occurs during the prophase of meiosis I and is critical for chromosome segregation. In baker’s yeast, two heterodimeric complexes, Msh4-Msh5 and Mlh1-Mlh3, act in meiosis to promote interference-dependent crossing over. Mlh1-Mlh3 also plays a role in DNA mismatch repair (MMR) by interacting with Msh2-Msh3 to repair insertion and deletion mutations. Mlh3 contains an ATP-binding domain that is highly conserved among MLH proteins. To explore roles for Mlh3 in meiosis and MMR, we performed a structure−function analysis of eight mlh3 ATPase mutants. In contrast to previous work, our data suggest that ATP hydrolysis by both Mlh1 and Mlh3 is important for both meiotic and MMR functions. In meiotic assays, these mutants showed a roughly linear relationship between spore viability and genetic map distance. To further understand the relationship between crossing over and meiotic viability, we analyzed crossing over on four chromosomes of varying lengths in mlh3Δ mms4Δ strains and observed strong decreases (6- to 17-fold) in crossing over in all intervals. Curiously, mlh3Δ mms4Δ double mutants displayed spore viability levels that were greater than observed in mms4Δ strains that show modest defects in crossing over. The viability in double mutants also appeared greater than would be expected for strains that show such severe defects in crossing over. Together, these observations provide insights for how Mlh1-Mlh3 acts in crossover resolution and MMR and for how chromosome segregation in Meiosis I can occur in the absence of crossing over.

Objective

To evaluate a biochip system in determining isoniazid and rifampicin resistances of Mycobacterium tuberculosis in sputum samples in a Chinese population.

Methods

We assembled 907 sputum smeared positive specimens of tuberculosis patients in total. Each sample would be separated into two parts for culture and biochip assay simultaneously. And those cultured positive and having full drug resistance results would be used as reference. The McNemar χ2 test was adopted for evaluating the paired 2×2 table.

Results

Compared with drug sensitivity test, the agreement rates of the two methods in detecting rifampicin and isoniazid resistances were 93.37% and 94.49%, respectively. The sensitivity and specificity of biochip in detecting isoniazid were 74.31% and 96.92%, respectively. Meanwhile, the sensitivity and specificity for rifampicin were 79.76% and 96.53%, respectively. For multi-drug resistance, the sensitivity and specificity were 64.62% and 97.75%, respectively.

Conclusions

The biochip system is a rapid and accurate method for drug resistant tuberculosis diagnosis using sputum samples directly, especially for rifampicin resistance detection.

How to design highly reputable and hot-selling products is an essential issue in product design. Whether consumers choose a product depends largely on their perception of the product image. A consumer-oriented design approach presented in this paper helps product designers incorporate consumers' perceptions of product forms in the design process. The consumer-oriented design approach uses quantification theory type I, grey prediction (the linear modeling technique), and neural networks (the nonlinear modeling technique) to determine the optimal form combination of product design for matching a given product image. An experimental study based on the concept of Kansei Engineering is conducted to collect numerical data for examining the relationship between consumers' perception of product image and product form elements of personal digital assistants (PDAs). The result of performance comparison shows that the QTTI model is good enough to help product designers determine the optimal form combination of product design. Although the PDA form design is used as a case study, the approach is applicable to other consumer products with various design elements and product images. The approach provides an effective mechanism for facilitating the consumer-oriented product design process.

Biofilms are microbial communities growing on surfaces, and are ubiquitous in nature, in bioreactors, and in human infection. Coupling between physical, chemical, and biological processes is known to regulate the development of biofilms; however, current experimental systems do not provide sufficient control of environmental conditions to enable detailed investigations of these complex interactions. We developed a novel planar flow cell that supports biofilm growth under complex two-dimensional fluid flow conditions. This device provides precise control of flow conditions and can be used to create well-defined physical and chemical gradients that significantly affect biofilm heterogeneity. Moreover, the top and bottom of the flow chamber are transparent, so biofilm growth and flow conditions are fully observable using non-invasive confocal microscopy and high-resolution video imaging. To demonstrate the capability of the device, we observed the growth of Pseudomonas aeruginosa biofilms under imposed flow gradients. We found a positive relationship between patterns of fluid velocity and biofilm biomass because of faster microbial growth under conditions of greater local nutrient influx, but this relationship eventually reversed because high hydrodynamic shear leads to the detachment of cells from the surface. These results reveal that flow gradients play a critical role in the development of biofilm communities. By providing new capability for observing biofilm growth, solute and particle transport, and net chemical transformations under user-specified environmental gradients, this new planar flow cell system has broad utility for studies of environmental biotechnology and basic biofilm microbiology, as well as applications in bioreactor design, environmental engineering, biogeochemistry, geomicrobiology, and biomedical research.

Background

The CXC chemokine ligand 12 (CXCL12)/stromal cell-derived factor-1 (SDF-1) and CXC receptor 4 (CXCR4) axis is involved in human colorectal cancer (CRC) carcinogenesis and can promote the progression of CRC. Interaction between CRC cells and endothelium is a key event in tumor progression. The aim of this study was to investigate the effect of SDF-1 on the adhesion of CRC cells.

Methods

Human CRC DLD-1 cells were used to study the effect of SDF-1 on intercellular adhesion molecule-1 (ICAM-1) expression and cell adhesion to endothelium.

Results

SDF-1 treatment induced adhesion of DLD-1 cells to the endothelium and increased the expression level of the ICAM-1. Inhibition of ICAM-1 by small interfering RNA (siRNA) and neutralizing antibody inhibited SDF-1-induced cell adhesion. By using specific inhibitors and short hairpin RNA (shRNA), we demonstrated that the activation of ERK, JNK and p38 pathways is critical for SDF-1-induced ICAM-1 expression and cell adhesion. Promoter activity and transcription factor ELISA assays showed that SDF-1 increased Sp1-, C/EBP-β- and NF-κB-DNA binding activities in DLD-1 cells. Inhibition of Sp1, C/EBP-β and NF-κB activations by specific siRNA blocked the SDF-1-induced ICAM-1 promoter activity and expression. The effect of SDF-1 on cell adhesion was mediated by the CXCR4.

Conclusion

Our findings support the hypothesis that ICAM-1 up-regulation stimulated by SDF-1 may play an active role in CRC cell adhesion.

The signaling by p120 catenin via its downstream effector RhoA is essential for filopodial growth and synaptic vesicle clustering along spinal axons and contributes to the formation of the neuromuscular junction.

At the developing neuromuscular junction (NMJ), physical contact between motor axons and muscle cells initiates presynaptic and postsynaptic differentiation. Using Xenopus nerve–muscle cocultures, we previously showed that innervating axons induced muscle filopodia (myopodia), which facilitated interactions between the synaptic partners and promoted NMJ formation. The myopodia were generated by nerve-released signals through muscle p120 catenin (p120ctn), a protein of the cadherin complex that modulates the activity of Rho GTPases. Because axons also extend filopodia that mediate early nerve–muscle interactions, here we test p120ctn's function in the assembly of these presynaptic processes. Overexpression of wild-type p120ctn in Xenopus spinal neurons leads to an increase in filopodial growth and synaptic vesicle (SV) clustering along axons, whereas the development of these specializations is inhibited following the expression of a p120ctn mutant lacking sequences important for regulating Rho GTPases. The p120ctn mutant also inhibits the induction of axonal filopodia and SV clusters by basic fibroblast growth factor, a muscle-derived molecule that triggers presynaptic differentiation. Of importance, introduction of the p120ctn mutant into neurons hinders NMJ formation, which is observed as a reduction in the accumulation of acetylcholine receptors at innervation sites in muscle. Our results suggest that p120ctn signaling in motor neurons promotes nerve–muscle interaction and NMJ assembly.

Lung cancer is one of the leading causes of cancer death in worldwide and required for novel therapeutic strategy. Our previous research demonstrated that the crude acetone extract of Bupleurum scorzonerifolium (BS-AE) and its component isochaihulactone induce antiproliferative and apoptotic effects on the lung adenocarcinoma cell line. Structural analysis has identified isochaihulactone as a lignan, with a chiral center and two racemic forms (Z-isochaihulactone and E-isochaihulactone). In this study, Z-isochaihulactone displayed significantly higher tumor cytotoxicity than E-isochaihulactone in A549 cells. The notch signaling pathway plays a pivotal role in determination of cell fate during development, while in lung cancer, it might have oncogenic or tumor-suppressive controversial functions. We showed that Z-isochaihulactone induced morphological changes in the A549 cells, inhibited cell growth, and arrested the cell cycle at the G2/M phase. It also induced upregulation of the active form of Notch1 (notch intracellular domain, NICD), which further induced p21 and c-Myc expression in time- and dose-dependent manners. Administrations of Z-isochaihulactone in nude mice can significantly inhibit tumor growth due to enhancement of NICD expression confirmed by immunohistochemical analysis. Taken together, our results supported that Z-isochaihulactone can efficiently inhibit tumorigenicity and be a potential compound for therapy.

Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function.

Background

RNA interference (RNAi) is commonly applied in genome-scale gene functional screens. However, a one-on-one RNAi analysis that targets each gene is cost-ineffective and laborious. Previous studies have indicated that siRNAs can also affect RNAs that are near-perfectly complementary, and this phenomenon has been termed an off-target effect. This phenomenon implies that it is possible to silence several genes simultaneously with a carefully designed siRNA.

Results

We propose a strategy that is combined with a heuristic algorithm to design suitable siRNAs that can target multiple genes and a group testing method that would reduce the number of required RNAi experiments in a large-scale RNAi analysis. To verify the efficacy of our strategy, we used the Orchid expressed sequence tag data as a case study to screen the putative transcription factors that are involved in plant disease responses. According to our computation, 94 qualified siRNAs were sufficient to examine all of the predicated 229 transcription factors. In addition, among the 94 computer-designed siRNAs, an siRNA that targets both TF15 (a previously identified transcription factor that is involved in the plant disease-response pathway) and TF21 was introduced into orchids. The experimental results showed that this siRNA can simultaneously silence TF15 and TF21, and application of our strategy successfully confirmed that TF15 is involved in plant defense responses. Interestingly, our second-round analysis, which used an siRNA specific to TF21, indicated that TF21 is a previously unidentified transcription factor that is related to plant defense responses.

Conclusions

Our computational results showed that it is possible to screen all genes with fewer experiments than would be required for the traditional one-on-one RNAi screening. We also verified that our strategy is capable of identifying genes that are involved in a specific phenotype.

Introduction

Patients who require prolonged mechanical ventilation (PMV) are increasing and producing financial burdens worldwide. This study determines the cost per QALY (quality-adjusted life year), out-of-pocket expenses, and lifetime costs for PMV patients stratified by underlying diseases and cognition levels.

Methods

A nationwide sample of 50,481 patients with continual mechanical ventilation for more than 21 days was collected during 1997–2007. After stratifying the patients according to specific diagnoses, a latent class analysis (LCA) was performed to categorise PMV patients with multiple co-morbidities into several homogeneous groups. The survival functions were estimated for individual groups using the Kaplan-Meier method and extrapolated to 300 months through a semi-parametric method. The survival functions were adjusted using an EQ-5D utility value derived from a convenience sample of 142 PMV patients to estimate quality-adjusted life expectancies (QALE). Another convenience sample of 165 patients was used to estimate the out-of-pocket expenses. The lifetime expenditures paid by the single-payer National Health Insurance (NHI) system and patients' families were estimated by multiplying average monthly expenditures by the survival probabilities and summing the values over lifetime.

Results

PMV therapy costs more than 100,000 U.S. dollars (USD) per QALY for all patients with poor cognition. For patients with partial cognition, PMV therapy costs less than 56,000 USD per QALY for those with liver cirrhosis, intracranial or spinal cord injuries, and 57,000–69,000 USD for patients with multiple co-morbidities under age of 65. The average lifetime cost of PMV was usually below 56,000 USD. The out-of-pocket expenses were often more than one-third of the total cost of treatment.

Conclusions

PMV treatment for patients with poor cognition would cost more than 5 times Taiwan's GDP (gross domestic products), or less cost-effective. The out-of-pocket expenses for PMV provision should also be considered in policy decision.

OBJECTIVE

To investigate whether circulating levels of fibroblast growth factor 21 (FGF21), which previously has been shown to be elevated in obesity, could predict the development of type 2 diabetes in a 5.4-year, population-based, prospective study.

RESEARCH DESIGN AND METHODS

Baseline plasma FGF21 levels were measured using an enzyme-linked immunosorbent assay in 1,900 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). The prospective association of FGF21 with diabetes development over 5.4 years was analyzed using multiple logistic regression.

RESULTS

At baseline, plasma levels of FGF21 increased progressively with worsening dysglycemia from normal glucose tolerance, through prediabetes, to diabetes (global trend, P < 0.001). Of 1,292 subjects without diabetes at baseline, a high baseline FGF21 level was a strong independent predictor for diabetes development (odds ratio 1.792; P < 0.01), together with waist circumference and fasting plasma glucose levels.

CONCLUSIONS

Plasma FGF21 levels were significantly increased in subjects with prediabetes and diabetes and predicted the development of diabetes in humans.

Bacteriophage P1 has a contractile tail that targets the conserved lipopolysaccharide on the outer membrane surface of the host for initial adsorption. The mechanism by which P1 DNA enters the host cell is not well understood, mainly because the transient molecular interactions between bacteriophage and bacteria have been difficult to study by conventional approaches. Here, we engineered tiny E. coli host cells so that the initial stages of P1-host interactions could be captured in unprecedented detail by cryo-electron tomography. Analysis of three-dimensional reconstructions of frozen-hydrated specimens revealed three predominant configurations: an extended tail stage with DNA present in the phage head, a contracted tail stage with DNA, and a contracted tail stage without DNA. Comparative analysis of various conformations indicated that there is uniform penetration of the inner tail tube into the E. coli periplasm and a significant movement of the baseplate away from the outer membrane during tail contraction.

Nuclear morphology and structure as visualized from histopathology microscopy images can yield important diagnostic clues in some benign and malignant tissue lesions. Precise quantitative information about nuclear structure and morphology, however, is currently not available for many diagnostic challenges. This is due, in part, to the lack of methods to quantify these differences from image data. We describe a method to characterize and contrast the distribution of nuclear structure in different tissue classes (normal, benign, cancer, etc.). The approach is based on quantifying chromatin morphology in different groups of cells using the optimal transportation (Kantorovich-Wasserstein) metric in combination with the Fisher discriminant analysis and multidimensional scaling techniques. We show that the optimal transportation metric is able to measure relevant biological information as it enables automatic determination of the class (e.g. normal vs. cancer) of a set of nuclei. We show that the classification accuracies obtained using this metric are, on average, as good or better than those obtained utilizing a set of previously described numerical features. We apply our methods to two diagnostic challenges for surgical pathology: one in the liver and one in the thyroid. Results automatically computed using this technique show potentially biologically relevant differences in nuclear structure in liver and thyroid cancers.

Nephrin, an important structural and signal molecule of podocyte slit-diaphragm (SD), has been suggested to contribute to the angiotensin II (Ang II)-induced podocyte injury. Caveolin-1 has been demonstrated to play a crucial role in signaling transduction. In the present study, we evaluated the role of caveolin-1 in Ang II-induced nephrin phosphorylation in podocytes. Wistar rats-receiving either Ang II (400 ng/kg/min) or normal saline (via subcutaneous osmotic mini-pumps, control) were administered either vehicle or telmisartan (3 mg/kg/min) for 14 or 28 days. Blood pressure, 24-hour urinary albumin and serum biochemical profile were measured at the end of the experimental period. Renal histomorphology was evaluated through light and electron microscopy. In vitro, cultured murine podocytes were exposed to Ang II (10−6 M) pretreated with or without losartan (10−5 M) for variable time periods. Nephrin and caveolin-1 expression and their phosphorylation were analyzed by Western-blotting and immunofluorescence. Caveolar membrane fractions were isolated by sucrose density gradient centrifugation, and then the distribution and interactions between Ang II type 1 receptor (AT1), nephrin, C-terminal Src kinase (Csk) and caveolin-1 were evaluated using Western-blotting and co-immunoprecipitation. Podocyte apoptosis was evaluated by cell nucleus staining with Hoechst-33342.

Ang II-receiving rats displayed diminished phosphorylation of nephrin but enhanced glomerular/podocyte injury and proteinuria when compared to control rats. Under control conditions, podocyte displayed expression of caveolin-1 in abundance but only a low level of phospho moiety. Nonetheless, Ang II stimulated caveolin-1 phosphorylation without any change in total protein expression. Nephrin and caveolin-1 were co-localized in caveolae fractions. AT1 receptors and Csk were moved to caveolae fractions and had an interaction with caveolin-1 after the stimulation with Ang II. Transfection of caveolin-1 plasmid (pEGFPC3-cav-1) significantly increased Ang II-induced nephrin dephosphorylation and podocyte apoptosis. Furthermore, knockdown of caveolin-1 expression (using siRNA) inhibited nephrin dephosphorylation and prevented Ang II-induced podocyte apoptosis. These findings indicate that Ang II induces nephrin dephosphorylation and podocyte injury through a caveolin-1-dependent mechanism.

The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This prospective study assessed the efficacy and safety of HBOT as adjuvant treatment on 46 acute ischemic stroke in patients who did not receive thrombolytic therapy. The HBOT group (n = 16) received conventional medical treatment with 10 sessions of adjunctive HBOT within 3–5 days after stroke onset, while the control group (n = 30) received the same treatment but without HBOT. Early (around two weeks after onset) and late (one month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. The baseline clinical characteristics were similar in both groups. Both early and late outcomes of the HBOT group showed significant difference (P ≤ 0.001). In the control group, there was only significant difference in early outcome (P = 0.004). For early efficacy, there was no difference when comparing changes of NIHSS scores between the two groups (P = 0.140) but there was statistically significant difference when comparing changes of NIHSS scores at one month (P ≤ 0.001). The HBOT used in this study may be effective for patients with acute ischemic stroke and is a safe and harmless adjunctive treatment.

In this study, a novel redox-responsive hyperbranched poly(amido amine) (named PCD) was synthesized and used as a cationic polymer to form a ternary complex with small interfering RNA (siRNA) and hyaluronic acid (HA) for siRNA delivery. Here, it is hypothesized that different mixing orders result in different assembly structures, which may affect the siRNA delivery efficiency. To investigate the effects of mixing orders on siRNA delivery efficiency in two human breast cancer cell lines, three ternary complexes with different mixing orders of siRNA/PCD/HA were prepared and characterized: mixing order I (initially prepared siRNA/PCD binary complex further coated by negatively charged HA), mixing order II ( initially prepared HA/PCD binary complex further incubated with siRNA), and mixing order III ( initially prepared siRNA/HA mixture further electrostatically compacted by positively charged PCD). With an optimized siRNA/PCD/HA charge ratio of 1/20/16, the particle sizes and zeta potentials of these ternary complexes were 124.8 nm and 27.3 mV (mixing order I), 147.5 nm and 29.9 mV (mixing order II), and 128.8 nm and 19.4 mV (mixing order III). Also, the effects on stability, cellular uptake, and gene silencing efficiency of siRNA formulated in ternary complexes with different mixing orders were investigated. The results showed that mixing orders I and III displayed better siRNA transfection and protection than mixing order II in human breast cancer MCF-7 and MDA-MB-231 cells. More interesting, at the siRNA/PCD/HA charge ratio of 1/20/16, the gene silencing effects on vascular endothelial growth factor expression in MDA-MB- 231 cells were as follows: mixing order III > mixing order I > mixing order II. Based on these results, a likely explanation for the difference in functionality dependent on mixing orders is the formation of different assembly structures. These results may help future optimization of siRNA ternary complexes for achieving better delivery efficiencies, especially for target-specific siRNA delivery to cells with HA receptor overexpression.

Background

Mycobacteria can be quickly and simply identified by PCR restriction-enzyme analysis (PRA), but misidentification can occur because of similarities in band sizes that are critical for discriminating among species. Capillary electrophoresis can provide computer-aided band discrimination. The aim of this research was to develop an algorithm for identifying mycobacteria by combined rpoB duplex PRA (DPRA) and hsp65 PRA with capillary electrophoresis.

Results

Three hundred and seventy-six acid-fast bacillus smear-positive BACTEC cultures, including 200 Mycobacterium tuberculosis complexes (MTC) and 176 non-tuberculous mycobacteria (NTM) were analyzed. With combined hsp65 and rpoB DPRA, the accuracy rate was 100% (200 isolates) for the MTC and 91.4% (161 isolates) for the NTM. Among the discordant results (8.6%) for the NTM, one isolate of Mycobacterial species and an isolate of M. flavescens were found as new sub-types in hsp65 PRA.

Conclusions

This effective and novel identification algorithm using combined rpoB DPRA and hsp65 PRA with capillary electrophoresis can rapidly identify mycobacteria and find new sub-types in hsp65 PRA. In addition, it is complementary to 16 S rDNA sequencing.

One-dimensional pure zinc oxide (ZnO) and Y-doped ZnO nanorod arrays have been successfully fabricated on the silicon substrate for comparison by a simple hydrothermal process at the low temperature of 90°C. The Y-doped nanorods exhibit the same c-axis-oriented wurtzite hexagonal structure as pure ZnO nanorods. Based on the results of photoluminescence, an enhancement of defect-induced green-yellow visible emission is observed for the Y-doped ZnO nanorods. The decrease of E2(H) mode intensity and increase of E1(LO) mode intensity examined by the Raman spectrum also indicate the increase of defects for the Y-doped ZnO nanorods. As compared to pure ZnO nanorods, Y-doped ZnO nanorods show a remarked increase of saturation magnetization. The combination of visible photoluminescence and ferromagnetism measurement results indicates the increase of oxygen defects due to the Y doping which plays a crucial role in the optical and magnetic performances of the ZnO nanorods.

Plasmodium falciparum, the major causative agent of human malaria contains three separate genomes. The apicoplast, an intracellular organelle contains a ∼35kb circular DNA genome of unusually high A/T content (>86%) that is replicated by the nuclear encoded replication complex Pfprex. Herein, we have expressed and purified the DNA polymerase domain of Pfprex (KPom1) and measured its fidelity using a LacZ based forward mutation assay. In addition, we analyzed the kinetic parameters for the incorporation of both complementary and non-complementary nucleotides incorporation using Kpom1 lacking the 3′→5′ exonucleolytic activity. KPom1 exhibits a strongly biased mutational spectrum in which the T → C is the most frequent single-base substitution and differs significantly from the closely related E. coli DNA polymerase I (pol I). Using E. coli harboring a temperature sensitive pol I allele, we established that KPom1 can complement the growth defective phenotype at an elevated temperature. We propose that the error bias of KPom1 may be exploited in the complementation assay to identify nucleoside analogs that mimic this base-mispairing and preferentially inhibit apicoplast DNA replication.

Background

The long-term survival in hepatocellullar carcinoma (HCC) patients after transarterial chemoembolization (TACE) remains dismal due to local and/or regional recurrence as well as distant metastasis. The efficacy of sorafenib in advanced HCC has been demonstrated and brought great hope. Recently, the use of sorafenib in combination with TACE for BCLC stage B and C HCC patients was recommended. However, data on this dual-modality treatment is little, and its advantage over TACE alone has not been addressed. The present study sought to understand the efficacy of the combination of TACE and sorafenib in the treatment of advanced HCC.

Methods

Between June 2008 and Feb 2011, 45 patients with advanced HCC were enrolled and treated with sorafenib in combination with TACE according to an institutional protocol of the Zhongshan hospital, Fudan University. The control group of 45 other HCC patients with similar characteristics treated with TACE alone in the same period of time in our institute were selected for retrospective comparison of the treatment outcomes especially overall survival time. Adverse reactions induced by sorafenib were observed and recorded.

Results

The median overall survival time of the combined treatment group was 27 (95% Confidence Interval: 21.9–32.1) months, and that of TACE alone group was 17 months (95% Confidence Interval: 8.9–25.0) months (P = 0.001). Patients required significantly less frequent TACE for their symptomatic treatment after the initiation of sorafenib therapy. The most common adverse events associated with sorafenib were hand-foot skin reaction, rash and diarrhea. Of CTCAE grade IV or V toxicity was observed.

Conclusion

TACE combined sorafenib significantly prolonged median overall survival time of patients with advanced HCC.

The gene segment encoding avian infectious bronchitis virus nonstructural protein 9 has been cloned and expressed in Escherichia coli. The protein has been crystallized and the crystals diffracted X-rays to 2.44 Å resolution.

Avian infectious bronchitis virus (IBV), which causes respiratory disease in infected birds, belongs to coronavirus group 3. IBV encodes 15 nonstructural proteins (nsp2–nsp16) which play crucial roles in RNA transcription and genome replication. Nonstructural protein 9 (nsp9) has been identified as a protein that is essential to viral replication because of its single-stranded RNA-binding ability. The gene segment encoding IBV nsp9 has been cloned and expressed in Escherichia coli. The protein has been crystallized and the crystals diffracted X-rays to 2.44 Å resolution. They belonged to the cubic space group I432, with unit-cell parameters a = b = c = 123.4 Å, α = β = γ = 90°. The asymmetric unit appeared to contain one molecule, with a solvent content of 62% (V M = 3.26 Å3 Da−1).