High efficient sedimentary basin simulations on hybrid CPU-GPU clusters

The key to achieving high performance on a GPU-enhanced cluster is efficient exploitation of each GPU’s powerful computing capability. Moreover, rationally balancing the workload between CPUs and GPUs can release additional computing power, which arises from the CPUs. In this paper, we extend our earlier work on using a hybrid CPU-GPU cluster for real-world sedimentary basin simulation, by further improving the involved CUDA implementations. A thorough analysis of the achieved new performance is also carried out. By using 1024 GPUs and 12288 CPU cores together, our best CPU-GPU hybrid implementation is able to achieve a double-precision performance of 72.8 TFlops, in connection with simulations on a huge 131072×131072 mesh.     

Higher level of plasma bioactive molecule sphingosine 1-phosphate in women is associated with estrogen

Both sphingosine 1-phosphate (S1P) and estrogen have been documented to play endothelial protective roles. However, it remains unclear whether estrogen could regulate the anabolism of the bioactive molecule S1P and the underlying mechanisms. In this study, 108 healthy participants were separated into three age groups, and their plasma S1P levels were analyzed by liquid chromatography tandem mass spectrometry. Results showed that the plasma S1P levels were significantly higher in women than those in men within the age of 16–55 years old and higher in pre-menopausal than post-menopausal women. The experiment in C57 BL/6 mice confirmed the gender difference of plasma S1P level. In vitro study demonstrated that after the stimulation of 17β-estradiol (E2), S1P levels both in EA.hy926 cells and the culture media were increased about 9 and 3 times, respectively; the mRNA expression, the protein level and the activity of sphingosine kinase (SphK) 1, not SphK2, were markedly increased; the mRNA and protein expression of ATP-binding cassette transporter (ABC) C1, G2 and S1P transporter spinster homolog 2 (Spns2) were significantly elevated; furthermore, the mRNA and protein expressions of S1P receptors (S1PRs) 1–2 were increased in a time-dependent manner. This study suggests that E2 markedly improves S1P synthesis by activating SphK1 and induces S1P export via activating ABCC1, G2 and Spns2 from endothelium system, which may consequently lead to the gender difference of plasma S1P in adult human and mouse. The results of this study suggest that E2 may exert its vasculoprotective function by activation of the SphK1–S1P–S1PR signaling axis.     

Mixed Polyethylene Glycol-Modified Breviscapine-Loaded Solid Lipid Nanoparticles for Improved Brain Bioavailability: Preparation,Characterization, and In Vivo Cerebral Microdialysis Evaluation in Adult Sprague Dawley Rats

Breviscapine is used in the treatment of ischemic cerebrovascular diseases, but it has a low bioavailability in the brain due to its poor physicochemical properties and the activity of P-glycoprotein efflux pumps located at the blood–brain barrier. In the present study, breviscapine-loaded solid lipid nanoparticles (SLN) coated with polyethylene glycol (PEG) derivatives were formulated and evaluated for their ability to enhance brain bioavailability. The SLNs were either coated with polyethylene glycol (40) (PEG-40) stearate alone (Bre-GBSLN-PS) or a mixture of PEG-40 stearate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 (DSPE-PEG₂₀₀₀) (Bre-GBSLN-PS-DSPE) and were characterized both in vitro and in vivo. The mean particle size, polydispersity index, and entrapment efficiency for Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE were 21.60 ± 0.10 and 22.60 ± 0.70 nm, 0.27 ± 0.01 and 0.26 ± 0.04, and 46.89 ± 0.73% and 47.62 ± 1.86%, respectively. The brain pharmacokinetic parameters revealed that the brain bioavailability of breviscapine from the Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE was significantly enhanced (p < 0.01) with the area under concentration–time curve (AUC) of 1.59 ± 0.39 and 1.42 ± 0.58 μg h/mL of breviscapine, respectively, in comparison to 0.11 ± 0.02 μg h/mL from the commercial breviscapine injection. The ratios of the brain AUC for scutellarin in comparison with the plasma scutellarin AUC for commercial breviscapine injection, Bre-GBSLN-PS, and Bre-GBSLN-PS-DSPE were 0.66%, 2.82%, and 4.51%, respectively. These results showed that though both SLN formulations increased brain uptake of breviscapine, Bre-GBSLN-PS-DSPE which was coated with a binary combination of PEG-40 stearate and DSPE-PEG₂₀₀₀ had a better brain bioavailability than Bre-GBSLN-PS. Thus, the coating of SLNs with the appropriate PEG derivative combination could improve brain bioavailability of breviscapine and can be a promising tool for brain drug delivery.KEY WORDS: breviscapine, microdialysis, mixed PEGylation, P-glycoprotein (P-gp), solid lipid nanoparticles     

Regulatory Phenotype,PD-1 and TLR3 Expression in T Cells and Monocytes from HCV Patients Undergoing Antiviral Therapy: A Randomized Clinical Trial

Background & Aims

The cellular immunity has a profound impact on the status of hepatitis C virus (HCV) infection. However, the response of cellular immunity on the virological response in patients with antiviral treatment remains largely unclear. We aimed to clarify the response of peripheral T cells and monocytes in chronic hepatitis C patients with antiviral treatment.

Methods

Patients with chronic hepatitis C were treated either with interferon alpha-2b plus ribavirin (n = 37) or with pegylated interferon alpha-2a plus ribavirin (n = 33) for up to 24 weeks. Frequencies of peripheral regulatory T-cells (Tregs), programmed death-1 (PD-1) expressing CD4⁺ T-cells or CD8⁺ T-cells and toll-like receptor (TLR) 3 expressing CD14⁺ monocytes were evaluated by flow cytometry in patients at baseline, 12 and 24 weeks following treatment and in 20 healthy controls.

Results

Frequencies of Tregs, PD-1 and TLR3 expressing cells were higher in patients than those in control subjects (P<0.05). Patients with complete early virological response (cEVR) showed lower Tregs, PD-1 expressing CD4⁺ or CD8⁺ T-cells than those without cEVR at 12 weeks (P<0.05). Patients with low TLR3 expressing CD14⁺ monocytes at baseline had a high rate of cEVR (P<0.05).

Conclusions

Low peripheral TLR3 expressing CD14⁺ monocytes at baseline could serve as a predictor for cEVR of antiviral therapy in chronic HCV-infected patients. The cEVR rates were significantly increased in the patients with reduced circulating Tregs, PD-1 expressing CD4⁺ or CD8⁺ T-cells.

Trial Registration

Chinese Clinical Trial Registry ChiCTR10001090.     

Correlates of Chlamydia and Gonorrhea Infection among Female Sex Workers: The Untold Story of Jiangsu,China

Objective(s)

To estimate the prevalence of sexually transmitted infections (STIs) among female sex workers (FSWs) in the Jiangsu Province, China and measure the association of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections with their potential correlates.

Design

A cross-sectional study on a representative sample of FSWs in Yangzhou and Changzhou cities of Jiangsu was conducted.

Methods

185 sex-work venues in Yangzhou and 174 in Changzhou were selected by stratified random sampling. 2972 FSWs (1108 in Yangzhou and 1864 in Changzhou), aged 15 years or more, who agreed to participate and provided blood sample for HIV and syphilis testing were interviewed in these venues. Cervical specimens from 849 randomly chosen participants were then tested for CT and NG.

Results

Proportions of young, school-educated, currently married FSWs who were living alone, migrated from other provinces and engaged in unprotected vaginal intercourse in past 3 months (UVI) were relatively high. Prevalence of HIV, syphilis, CT and NG were 0.20%, 4.88%, 14.61% and 5.42% respectively. Younger age, living alone or with persons other than partners/family members, engaging in UVI and having other STIs seemed to be associated with higher risk of CT or NG infection. Being divorced/widowed and working in middle/low-level venues were identified as additional risk factors for NG.

Conclusions

Based on a representative sample, this initial effort to identify the correlates of CT/NG infections among FSWs of Jiangsu revealed that focused interventions targeting high-risk FSWs are urgently required for controlling STI epidemics in Yangzhou and Changzhou where substantial number of STI cases were identified.     

Chemical Interference with Iron Transport Systems to Suppress Bacterial Growth of Streptococcus pneumoniae

Iron is an essential nutrient for the growth of most bacteria. To obtain iron, bacteria have developed specific iron-transport systems located on the membrane surface to uptake iron and iron complexes such as ferrichrome. Interference with the iron-acquisition systems should be therefore an efficient strategy to suppress bacterial growth and infection. Based on the chemical similarity of iron and ruthenium, we used a Ru(II) complex R-825 to compete with ferrichrome for the ferrichrome-transport pathway in Streptococcus pneumoniae. R-825 inhibited the bacterial growth of S. pneumoniae and stimulated the expression of PiuA, the iron-binding protein in the ferrichrome-uptake system on the cell surface. R-825 treatment decreased the cellular content of iron, accompanying with the increase of Ru(II) level in the bacterium. When the piuA gene (SPD_0915) was deleted in the bacterium, the mutant strain became resistant to R-825 treatment, with decreased content of Ru(II). Addition of ferrichrome can rescue the bacterial growth that was suppressed by R-825. Fluorescence spectral quenching showed that R-825 can bind with PiuA in a similar pattern to the ferrichrome-PiuA interaction in vitro. These observations demonstrated that Ru(II) complex R-825 can compete with ferrichrome for the ferrichrome-transport system to enter S. pneumoniae, reduce the cellular iron supply, and thus suppress the bacterial growth. This finding suggests a novel antimicrobial approach by interfering with iron-uptake pathways, which is different from the mechanisms used by current antibiotics.     

Myeloid Mineralocorticoid Receptor Deficiency Inhibits Aortic Constriction-Induced Cardiac Hypertrophy in Mice

Mineralocorticoid receptor (MR) blockade has been shown to suppress cardiac hypertrophy and remodeling in animal models of pressure overload (POL). This study aims to determine whether MR deficiency in myeloid cells modulates aortic constriction-induced cardiovascular injuries. Myeloid MR knockout (MMRKO) mice and littermate control mice were subjected to abdominal aortic constriction (AAC) or sham operation. We found that AAC-induced cardiac hypertrophy and fibrosis were significantly attenuated in MMRKO mice. Expression of genes important in generating reactive oxygen species was decreased in MMRKO mice, while that of manganese superoxide dismutase increased. Furthermore, expression of genes important in cardiac metabolism was increased in MMRKO hearts. Macrophage infiltration in the heart was inhibited and expression of inflammatory genes was decreased in MMRKO mice. In addition, aortic fibrosis and inflammation were attenuated in MMRKO mice. Taken together, our data indicated that MR deficiency in myeloid cells effectively attenuated aortic constriction-induced cardiac hypertrophy and fibrosis, as well as aortic fibrosis and inflammation.     

Annexin5 Plays a Vital Role in Arabidopsis Pollen Development via Ca2+-Dependent Membrane Trafficking

The regulation of pollen development and pollen tube growth is a complicated biological process that is crucial for sexual reproduction in flowering plants. Annexins are widely distributed from protists to higher eukaryotes and play multiple roles in numerous cellular events by acting as a putative “linker” between Ca²⁺ signaling, the actin cytoskeleton and the membrane, which are required for pollen development and pollen tube growth. Our recent report suggested that downregulation of the function of Arabidopsis annexin 5 (Ann5) in transgenic Ann5-RNAi lines caused severely sterile pollen grains. However, little is known about the underlying mechanisms of the function of Ann5 in pollen. This study demonstrated that Ann5 associates with phospholipid membrane and this association is stimulated by Ca²⁺ in vitro. Brefeldin A (BFA) interferes with endomembrane trafficking and inhibits pollen germination and pollen tube growth. Both pollen germination and pollen tube growth of Ann5-overexpressing plants showed increased resistance to BFA treatment, and this effect was regulated by calcium. Overexpression of Ann5 promoted Ca²⁺-dependent cytoplasmic streaming in pollen tubes in vivo in response to BFA. Lactrunculin (LatB) significantly prohibited pollen germination and tube growth by binding with high affinity to monomeric actin and preferentially targeting dynamic actin filament arrays and preventing actin polymerization. Overexpression of Ann5 did not affect pollen germination or pollen tube growth in response to LatB compared with wild-type, although Ann5 interacts with actin filaments in a manner similar to some animal annexins. In addition, the sterile pollen phenotype could be only partially rescued by Ann5 mutants at Ca²⁺-binding sites when compared to the complete recovery by wild-type Ann5. These data demonstrated that Ann5 is involved in pollen development, germination and pollen tube growth through the promotion of endomembrane trafficking modulated by calcium. Our results provide reliable molecular mechanisms that underlie the function of Ann5 in pollen.