Colloidal processing of Al2O3-doped zirconia ceramics with CaO–P2O5–SiO2 glass as additive

Well dispersed concentrated aqueous suspensions of Al2O3-doped Y-TZP (AY-TZP), AY-TZP with 5.4 vol% of CaO-P2O5-SiO2 (CaPSi) glass (AY-TZP5) and 10.5 vol% CaPSi glass (AY-TZP10), with ammonium polyacrylate (NH4PA) dispersant were prepared to produce slip cast compacts. The rheological properties of 35 and 40 vol% slips were studied. The densification, microstructure as well as hardness and fracture toughness were investigated as a function of CaPSi glass content at 1300-1500 oC. The optimum NH4PA concentration of 35 vol% AY-TZP5 and AY-TZP10 slips at pH ~9 was found to be about 43 and 67 % greater than that of AY-TZP slips, this behaviour was related to the greater amounts of Ca2+ ions leached out from the CaPSi glass surface. The viscosity of stabilized 40 vol% slips with NH4PA attained a minimum value at 5.4 vol% CaPSi glass addition, and resulted in a more dense packing of cast samples. AY-TZP5 can be sintered at a lower temperature (1300 oC) compared to that of AY-TZP. AY-TZP5 exhibited a fine microstructure of tetragonal ZrO2 (grain sizes below 0.3 m), and ZrSiO4 - Ca2P2O7 particles homogeneously distributed within the zirconia matrix. Its presented similar fracture toughness and a slightly lower hardness compared to those of AY-TZP.Fil: Soubelet, Clara Gabriela. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; ArgentinaFil: Albano, Maria Patricia. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; Argentin

CFTR founder mutation causes protein trafficking defects in Chinese patients with cystic fibrosis

published_or_final_versio

Regional and local emissions in red river delta, Northern Vietnam

Fine (PM2.2) and coarse (PM2.2–10) particles concurrently collected in urban (Hanoi) and rural (Lucnam) areas were analyzed for ionic and elemental compositions to provide input for PMF receptor modeling of emission sources in the Red River Delta (RRD), a key economic development region in Vietnam. Long-range transport (LRT) aerosol, coal fly ash from major coal-fired plants in RRD, and marine aerosols are regional sources, which explain the minor variability of the mass concentrations of fine particles across the region. Local sources include soil/resuspended road dust, local coal fly ash, and biomass burning. Soil/resuspended road dust is the largest source component of coarse particles at the two sites. It is more abundant in Hanoi than in Lucnam reflecting the urban–rural contrast in traffic and construction works. Receptor models reveal the incorporation of secondary sulfate, nitrate, and ammonium into the various primary particles, i.e., soot, minerals, soil organic matter, and sea salt. Soot particles from LRT carry the largest amounts of sulfate and ammonium mass concentrations measured at the two sites. Based on receptor models, the yields and possible chemical forms of secondary sulfate, nitrate, and ammonium in different types of primary particles can be inferred

Factors determining the survival of nasopharyngeal carcinoma with lung metastasis alone: does combined modality treatment benefit?

<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carcinoma (NPC) with lung metastasis alone has been reported as a relatively favorable prognostic group, and combined modality treatment might be indicated for selected cases. However, the prognostic factors determining survival of this group and the indication of combined therapy have not been thoroughly studied.</p> <p>Methods</p> <p>We retrospectively reviewed 246 patients of NPC with lung metastasis(es) alone presented at diagnosis or as the first failure after primary treatment from 1993 to 2008 in an academic tertiary hospital. Univariate and multivariate survival analyses of post-metastasis survival (PMS) and overall survival (OS) were carried out to determine the prognostic factors.</p> <p>Results</p> <p>The 3-year, 5-year, and 10-year of PMS and OS for the whole cohort were 34.3%, 17.0%, 8.6% and 67.8%, 45.4%, 18.5%, respectively. The median PMS (45.6 months <it>vs</it>. 23.7 months) and OS (73.7 months <it>vs</it>. 46.2 months) of patients treated with combined therapy was significantly longer than that of those treated with chemotherapy alone (<it>P </it>< 0.001). Age, disease-free interval (DFI) and treatment modality were evaluated as independent prognostic factors of OS, while only age and treatment modality retain their independent significance in PMS analysis. In stratified survival analysis, compared to chemotherapy alone, combined therapy could benefit the patients with DFI > 1 year, but not those with DFI ≤ 1 year.</p> <p>Conclusions</p> <p>Age ≤ 45 years, DFI > 1 year, and the combined therapy were good prognostic factors for NPC patients with lung metastasis(es) alone. The combination of local therapy and the basic chemotherapy should be considered for these patients with DFI > 1 year.</p

Inherent Interfacial Mechanical Gradients in 3D Hydrogels Influence Tumor Cell Behaviors

Cells sense and respond to the rigidity of their microenvironment by altering their morphology and migration behavior. To examine this response, hydrogels with a range of moduli or mechanical gradients have been developed. Here, we show that edge effects inherent in hydrogels supported on rigid substrates also influence cell behavior. A Matrigel hydrogel was supported on a rigid glass substrate, an interface which computational techniques revealed to yield relative stiffening close to the rigid substrate support. To explore the influence of these gradients in 3D, hydrogels of varying Matrigel content were synthesized and the morphology, spreading, actin organization, and migration of glioblastoma multiforme (GBM) tumor cells were examined at the lowest (<50 µm) and highest (>500 µm) gel positions. GBMs adopted bipolar morphologies, displayed actin stress fiber formation, and evidenced fast, mesenchymal migration close to the substrate, whereas away from the interface, they adopted more rounded or ellipsoid morphologies, displayed poor actin architecture, and evidenced slow migration with some amoeboid characteristics. Mechanical gradients produced via edge effects could be observed with other hydrogels and substrates and permit observation of responses to multiple mechanical environments in a single hydrogel. Thus, hydrogel-support edge effects could be used to explore mechanosensitivity in a single 3D hydrogel system and should be considered in 3D hydrogel cell culture systems

Ultra-porous titanium oxide scaffold with high compressive strength

Highly porous and well interconnected titanium dioxide (TiO2) scaffolds with compressive strength above 2.5 MPa were fabricated without compromising the desired pore architectural characteristics, such as high porosity, appropriate pore size, surface-to-volume ratio, and interconnectivity. Processing parameters and pore architectural characteristics were investigated in order to identify the key processing steps and morphological properties that contributed to the enhanced strength of the scaffolds. Cleaning of the TiO2 raw powder removed phosphates but introduced sodium into the powder, which was suggested to decrease the slurry stability. Strong correlation was found between compressive strength and both replication times and solid content in the ceramic slurry. Increase in the solid content resulted in more favourable sponge loading, which was achieved due to the more suitable rheological properties of the ceramic slurry. Repeated replication process induced only negligible changes in the pore architectural parameters indicating a reduced flaw size in the scaffold struts. The fabricated TiO2 scaffolds show great promise as load-bearing bone scaffolds for applications where moderate mechanical support is required

Trichostatin A enhances acetylation as well as protein stability of ERα through induction of p300 protein

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Introduction Trichostatin A (TSA) is a well-characterized histone deacetylase (HDAC) inhibitor. TSA modifies the balance between HDAC and histone acetyltransferase activities that is important in chromatin remodeling and gene expression. Although several previous studies have demonstrated the role of TSA in regulation of estrogen receptor alpha (ERα), the precise mechanism by which TSA affects ERα activity remains unclear. Methods Transient transfection was performed using the Welfect-EX™Plus procedure. The mRNA expression was determined using RT-PCR. Protein expression and interaction were determined by western blotting and immunoprecipitation. The transfection of siRNAs was performed using the Oligofectamine™ reagent procedure. Results TSA treatment increased acetylation of ERα in a dose-dependent manner. The TSA-induced acetylation of ERα was accompanied by an increased stability of ERα protein. Interestingly, TSA also increased the acetylation and the stability of p300 protein. Overexpression of p300 induced acetylation and stability of ERα by blocking ubiquitination. Knockdown of p300 by RNA interference decreased acetylation as well as the protein level of ERα, indicating that p300 mediated the TSA-induced stabilization of ERα. Conclusions We report that TSA enhanced acetylation as well as the stability of the ERα protein by modulating stability of p300. These results may provide the molecular basis for pharmacological functions of HDAC inhibitors in the treatment of human breast cancer

Validation of a new prognostic index score for disseminated nasopharyngeal carcinoma

Patients with metastatic nasopharyngeal carcinoma have variable survival outcomes. We previously designed a scoring system to better prognosticate these patients. Here, we report results on validation of this new prognostic index score in a separate cohort of patients. Clinical features and laboratory parameters were examined in 172 patients with univariate and multivariate analyses and a numerical score was derived for each independent prognostic variable. Significant independent prognostic variables and their scores assigned included poor performance status (score 5), haemoglobin <12 g dl−1 (score 4) and disease-free interval (DFI) (DFI⩽6 months (score 10) or metastases at initial diagnosis (score 1)). Maximum score was 19 and patients stratified into three prognostic groups: good, 0–3; intermediate, 4–8; poor, ⩾9. When applied to a separate cohort of 120 patients, 59 patients were good, 43 intermediate and 18 poor prognosis, with median survivals of 19.6 (95% CI 16.1, 23.1), 14.3 (95% CI 12.3, 16.2) and 7.9 (95% CI 6.6, 9.2) months, respectively. (logrank test: P=0.003). We have validated a new prognostic score with factors readily available in the clinics. This simple score will prove useful as a method to prognosticate and stratify patients as well as to promote consistent reporting among clinical trials

The lactose operon from Lactobacillus casei is involved in the transport and metabolism of the human milk oligosaccharide core-2 N-acetyllactosamine

The lactose operon (lacTEGF) from Lactobacillus casei strain BL23 has been previously studied. The lacT gene codes for a transcriptional antiterminator, lacE and lacF for the lactose-specific phosphoenolpyruvate: phosphotransferase system (PTSLac) EIICB and EIIA domains, respectively, and lacG for the phospho-β-galactosidase. In this work, we have shown that L. casei is able to metabolize N-acetyllactosamine (LacNAc), a disaccharide present at human milk and intestinal mucosa. The mutant strains BL153 (lacE) and BL155 (lacF) were defective in LacNAc utilization, indicating that the EIICB and EIIA of the PTSLac are involved in the uptake of LacNAc in addition to lactose. Inactivation of lacG abolishes the growth of L. casei in both disaccharides and analysis of LacG activity showed a high selectivity toward phosphorylated compounds, suggesting that LacG is necessary for the hydrolysis of the intracellular phosphorylated lactose and LacNAc. L. casei (lacAB) strain deficient in galactose-6P isomerase showed a growth rate in lactose (0.0293 ± 0.0014 h-1) and in LacNAc (0.0307 ± 0.0009 h-1) significantly lower than the wild-type (0.1010 ± 0.0006 h-1 and 0.0522 ± 0.0005 h-1, respectively), indicating that their galactose moiety is catabolized through the tagatose-6P pathway. Transcriptional analysis showed induction levels of the lac genes ranged from 130 to 320-fold in LacNAc and from 100 to 200-fold in lactose, compared to cells growing in glucose

A Directed Molecular Evolution Approach to Improved Immunogenicity of the HIV-1 Envelope Glycoprotein

A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences