Apatite-Polymer Composites for the Controlled Dual Delivery of BMP-2 and BMP-6 for Bone Tissue Engineering

The release of growth factors from tissue engineering scaffolds provides signals that influence the migration, differentiation, and proliferation of cells. The incorporation of a drug delivery platform that is capable of tunable release will give tissue engineers greater versatility in the direction of tissue regeneration. We have prepared a novel composite of two biomaterials with proven track records - apatite and poly(lactic-co-glycolic acid) (PLGA) – as a drug delivery platform with promising controlled release properties. These composites have been tested in the delivery of a model protein, bovine serum albumin (BSA), as well as therapeutic proteins, recombinant human bone morphogenetic protein-2 (rhBMP-2) and rhBMP-6. The controlled release strategy is based on the use of a polymer with acidic degradation products to control the dissolution of the basic apatitic component, resulting in protein release. Therefore, any parameter that affects either polymer degradation or apatite dissolution can be used to control protein release. We have modified the protein release profile systematically by varying the polymer molecular weight, polymer hydrophobicity, apatite loading, apatite particle size, and other material and processing parameters. Biologically active rhBMP-2 was released from these composite microparticles over 100 days, in contrast to conventional collagen sponge carriers, which were depleted in approximately 2 weeks. The released rhBMP-2 was able to induce elevated alkaline phosphatase and osteocalcin expression in pluripotent murine embryonic fibroblasts. To augment tissue engineering scaffolds with tunable and sustained protein release capabilities, these composite microparticles can be dispersed in the scaffolds in different combinations to obtain a superposition of the release profiles. We have loaded rhBMP-2 into composite microparticles with a fast release profile, and rhBMP-6 into slow-releasing composite microparticles. An equi-mixture of these two sets of composite particles was then injected into a collagen sponge, allowing for dual release of the proteins from the collagenous scaffold. The ability of these BMP-loaded scaffolds to induce osteoblastic differentiation in vitro and ectopic bone formation in a rat model is being investigated. We anticipate that these apatite-polymer composite microparticles can be extended to the delivery of other signalling molecules, and can be incorporated into other types of tissue engineering scaffolds.Singapore-MIT Alliance (SMA

Environmental Effects on Real-Space and Redshift-Space Galaxy Clustering

Galaxy formation inside dark matter halos, as well as the halo formation itself, can be affected by large-scale environments. Evaluating the imprints of environmental effects on galaxy clustering is crucial for precise cosmological constraints with data from galaxy redshift surveys. We investigate such an environmental impact on both real-space and redshift-space galaxy clustering statistics using a semi-analytic model derived from the Millennium Simulation. We compare clustering statistics from original SAM galaxy samples and shuffled ones with environmental influence on galaxy properties eliminated. Among the luminosity-threshold samples examined, the one with the lowest threshold luminosity (~0.2L_*) is affected by environmental effects the most, which has a ~10% decrease in the real-space two-point correlation function (2PCF) after shuffling. By decomposing the 2PCF into five different components based on the source of pairs, we show that the change in the 2PCF can be explained by the age and richness dependence of halo clustering. The 2PCFs in redshift space are found to change in a similar manner after shuffling. If the environmental effects are neglected, halo occupation distribution modeling of the real-space and redshift-space clustering may have a less than 6.5% systematic uncertainty in constraining beta from the most affected SAM sample and have substantially smaller uncertainties from the other, more luminous samples. We argue that the effect could be even smaller in reality. In the Appendix, we present a method to decompose the 2PCF, which can be applied to measure the two-point auto-correlation functions of galaxy sub-samples in a volume-limited galaxy sample and their two-point cross-correlation functions in a single run utilizing only one random catalog.Comment: 13 pages, 6 figures, Accepted by AP

Compact and Low-Cost 3-D Printed Antennas Metalized Using Spray-Coating Technology for 5G mm-Wave Communication Systems

This letter presents a design of two compact, light, rigid, and low-cost three-dimensionally (3-D) printed millimeter-wave antennas for a fifth-generation (5G) communication system. The proposed antennas consist of a radiating slot that is surrounded by a rectangular cavity and corrugations, which boost the gain performance of the antennas. Furthermore, the proposed antennas are fabricated using 3-D printing technology, and they are metalized using novel, simple, and low-cost techniques, which utilize the commercial conducive spray-coating technology. The proposed antennas operate at a 28 GHz band, where the first design is fed by a waveguide to prove the performance, whereas the second design is fed by a microstrip line to demonstrate the ability to be integrated into a compact structure. Measurement results show a wide impedance bandwidth, which enables the proposed antenna design to be a strong candidate for 5G applications

Inhibition of Aldose Reductase Activates Hepatic Peroxisome Proliferator-Activated Receptor-α and Ameliorates Hepatosteatosis in Diabetic db/db Mice

We previously demonstrated in streptozotocin-induced diabetic mice that deficiency or inhibition of aldose reductase (AR) caused significant dephosphorylation of hepatic transcriptional factor PPARα, leading to its activation and significant reductions in serum lipid levels. Herein, we report that inhibition of AR by zopolrestat or by a short-hairpin RNA (shRNA) against AR caused a significant reduction in serum and hepatic triglycerides levels in 10-week old diabetic db/db mice. Meanwhile, hyperglycemia-induced phosphorylation of hepatic ERK1/2 and PPARα was significantly attenuated in db/db mice treated with zopolrestat or AR shRNA. Further, in comparison with the untreated db/db mice, the hepatic mRNA expression of Aco and ApoA5, two target genes for PPARα, was increased by 93% (P < 0.05) and 73% (P < 0.05) in zopolrestat-treated mice, respectively. Together, these data indicate that inhibition of AR might lead to significant amelioration in hyperglycemia-induced dyslipidemia and nonalcoholic fatty liver disease

Corrigendum: miR156/SPL10 Modulates Lateral Root Development, Branching and Leaf Morphology in Arabidopsis by Silencing AGAMOUS-LIKE 79

The developmental functions of miR156-SPL regulatory network have been extensively studied in Arabidopsis, but the downstream genes regulated by each SPL have not been well characterized. In this study, Next Generation Sequencing-based transcriptome analysis was performed on roots of wild type (WT) and miR156 overexpression (miR156OE) plants. One of the SPL genes, SPL10, which represses lateral root growth in Arabidopsis, was significantly downregulated in miR156OE plants. A transcription factor, AGAMOUS-like MADS box protein 79 (AGL79), was also significantly downregulated in the miR156OE plants, but was upregulated in the SPL10 overexpression (SPL10OE) Arabidopsis plants. In addition, SPL10 was found to bind to the core consensus SPL binding sequences in AGL79 gene. Moreover, analyses of complementation lines revealed a linear relationship between SPL10 and AGL79 in regulating Arabidopsis plant development. In addition, it was observed that plant phenotypes are AGL79 dose-dependent, with higher expression causing narrow leaf shape, less number of leaves and early flowering time, whereas relatively lower AGL79 overexpression produce plants with more rosette leaves and more lateral branches. Our findings revealed direct binding of SPL10 to AGL79 promoter, which further suggests a role for miR156/SPL10 module in plant lateral root growth by directly regulating AGL79

Epidemiological and virological characteristics of pandemic influenza A (H1N1) 2009 in school outbreaks in China

Background: During the 2009 pandemic influenza H1N1 (2009) virus (pH1N1) outbreak, school students were at an increased risk of infection by the pH1N1 virus. However, the estimation of the attack rate showed significant variability. Methods: Two school outbreaks were investigated in this study. A questionnaire was designed to collect information by interview. Throat samples were collected from all the subjects in this study 6 times and sero samples 3 times to confirm the infection and to determine viral shedding. Data analysis was performed using the software STATA 9.0. Findings: The attack rate of the pH1N1 outbreak was 58.3% for the primary school, and 52.9% for the middle school. The asymptomatic infection rates of the two schools were 35.8% and 37.6% respectively. Peak virus shedding occurred on the day of ARI symptoms onset, followed by a steady decrease over subsequent days (p = 0.026). No difference was found either in viral shedding or HI titer between the symptomatic and the asymptomatic infectious groups. Conclusions: School children were found to be at a high risk of infection by the novel virus. This may be because of a heightened risk of transmission owing to increased mixing at boarding school, or a lack of immunity owing to socioeconomic status. We conclude that asymptomatically infectious cases may play an important role in transmission of the pH1N1 virus