Coupled discrete-continuum method for studying load-deformation of a stone column reinforces rail track embankments

Stone columns are being increasingly used as a cost-effective and environmentally friendly method for reinforcing soft soils of rail track embankments. Deformation behavior of stone columns reinforced soft clay has been the subject of an extensive number of experimental and modelling studies during last decades. A continuum-based numerical method provides valuable insights into the settlement, lateral deformation, stress and strain-rate dependent behavior of stone column at macroscopic scale. However, due to the discrete nature of stone columns, which are comprised of granular aggregates, they cannot be properly modelled by the continuum methods. This paper presents a novel coupling model of discrete element method (DEM) and finite difference method (FDM) to investigate the load-deformation behavior of stone columns considering micromechanical analysis. In the coupled discrete-continuum model, the soft soil domain under track embankment is modelled by the continuum method using FLAC and stone column is modelled by the discrete element method using PFC2D. A force-displacement transmission mechanism is introduced to achieve the interaction of both domains in which the DEM transfers forces and moment to the FDM and then the FDM updates displacements back to the DEM. The predicted load-deformation results are in good agreement with the data measured experimentally; indicating that the proposed coupling discrete-continuum model could capture the deformation behavior of stone column reinforced soft soils

High magnetisation, monodisperse and water-dispersible CoFe@Pt core/shell nanoparticles

High magnetisation and monodisperse CoFe alloy nanoparticles are desired for a wide range of biomedical applications. However, these CoFe nanoparticles are prone to oxidation, resulting in the deterioration of their magnetic properties. In the current work, CoFe alloy nanoparticles were prepared by thermal decomposition of cobalt and iron carbonyls in organic solvents at high temperatures. Using a seeded growth method, we successfully synthesised chemically stable CoFe@Pt core/shell nanostructures. The obtained core/shell nanoparticles have high saturation magnetisation up to 135 emu g−1. The magnetisation value of the core/shell nanoparticles remains 93 emu g−1 after being exposed to air for 12 weeks. Hydrophobic CoFe@Pt nanoparticles were rendered water-dispersible by encapsulating with poly(maleic anhydride-alt-1-octadecene) (PMAO). These nanoparticles were stable in water for at least 3 months and in a wide range of pH from 2 to 11

DMSA-coated cubic iron oxide nanoparticles as potential therapeutic agents

AIM: Superparamagnetic cubic iron oxide nanoparticles (IONPs) were synthesized and functionalized with meso-2,3-dimercaptosuccinic acid (DMSA) as a potential agent for cancer treatment. METHODS: Monodisperse cubic IONPs with a high value of saturation magnetization were synthesized by thermal decomposition method and functionalized with DMSA via ligand exchange reaction, and their cytotoxic effects on HeLa cells were investigated. RESULTS: DMSA functionalized cubic IONPs with an edge length of 24.5 ± 1.9 nm had a specific absorption rate value of 197.4 W/gFe (15.95 kA/m and 488 kHz) and showed slight cytotoxicity on HeLa cells when incubated with 3.3 × 10^{10}, 6.6 × 10^{10} and 9.9 × 10^{10} NP/mL for 24, 48 and 72 h. CONCLUSION: To the best of our knowledge, this is the first study to investigate both the cytotoxic effects of DMSA-coated cubic IONPs on HeLa cells and hyperthermia performance of these nanoparticles

Synthesis of magnetic cobalt ferrite nanoparticles with controlled morphology, monodispersity and composition: the influence of solvent, surfactant, reductant and synthetic conditions

In our present work, magnetic cobalt ferrite (CoFe2O4) nanoparticles have been successfully synthesised by thermal decomposition of Fe(III) and Co(II) acetylacetonate compounds in organic solvents in the presence of oleic acid (OA)/ oleylamine (OLA) as surfactants and 1,2-hexadecanediol (HDD) or octadecanol (OCD-ol) as an accelerating agent. As a result, CoFe2O4 nanoparticles of different shapes were tightly controlled in size (range of 4–30 nm) and monodispersity (standard deviation only at ca. 5%). Experimental parameters, such as reaction time, temperature, surfactant concentration, solvent, precursor ratio, and accelerating agent, in particular, the role of HDD, OCD-ol, and OA/OLA have been intensively investigated in detail to discover the best conditions for the synthesis of the above magnetic nanoparticles. The obtained nanoparticles have been successfully applied for producing oriented carbon nanotubes (CNTs), and they have potential to be used in biomedical applications

Estimation of progression of multi-state chronic disease using the Markov model and prevalence pool concept

<p>Abstract</p> <p>Background</p> <p>We propose a simple new method for estimating progression of a chronic disease with multi-state properties by unifying the prevalence pool concept with the Markov process model.</p> <p>Methods</p> <p>Estimation of progression rates in the multi-state model is performed using the E-M algorithm. This approach is applied to data on Type 2 diabetes screening.</p> <p>Results</p> <p>Good convergence of estimations is demonstrated. In contrast to previous Markov models, the major advantage of our proposed method is that integrating the prevalence pool equation (that the numbers entering the prevalence pool is equal to the number leaving it) into the likelihood function not only simplifies the likelihood function but makes estimation of parameters stable.</p> <p>Conclusion</p> <p>This approach may be useful in quantifying the progression of a variety of chronic diseases.</p

A hidden HIV epidemic among women in Vietnam

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic in Vietnam is still concentrated among high risk populations, including IDU and FSW. The response of the government has focused on the recognized high risk populations, mainly young male drug users. This concentration on one high risk population may leave other populations under-protected or unprepared for the risk and the consequences of HIV infection. In particular, attention to women's risks of exposure and needs for care may not receive sufficient attention as long as the perception persists that the epidemic is predominantly among young males. Without more knowledge of the epidemic among women, policy makers and planners cannot ensure that programs will also serve women's needs.</p> <p>Methods</p> <p>More than 300 documents appearing in the period 1990 to 2005 were gathered and reviewed to build an understanding of HIV infection and related risk behaviors among women and of the changes over time that may suggest needed policy changes.</p> <p>Results</p> <p>It appears that the risk of HIV transmission among women in Vietnam has been underestimated; the reported data may represent as little as 16% of the real number. Although modeling predicted that there would be 98,500 cases of HIV-infected women in 2005, only 15,633 were accounted for in reports from the health system. That could mean that in 2005, up to 83,000 women infected with HIV have not been detected by the health care system, for a number of possible reasons. For both detection and prevention, these women can be divided into sub-groups with different risk characteristics. They can be infected by sharing needles and syringes with IDU partners, or by having unsafe sex with clients, husbands or lovers. However, most new infections among women can be traced to sexual relations with young male injecting drug users engaged in extramarital sex. Each of these groups may need different interventions to increase the detection rate and thus ensure that the women receive the care they need.</p> <p>Conclusion</p> <p>Women in Vietnam are increasingly at risk of HIV transmission but that risk is under-reported and under-recognized. The reasons are that women are not getting tested, are not aware of risks, do not protect themselves and are not being protected by men. Based on this information, policy-makers and planners can develop better prevention and care programs that not only address women's needs but also reduce further spread of the infection among the general population.</p

Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts

<p>Abstract</p> <p>Background</p> <p>To investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.</p> <p>Methods</p> <p>A total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.</p> <p>Results</p> <p>We newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/μl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/μl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/μl, p = 0.004).</p> <p>Conclusions</p> <p>TLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.</p

Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition

INTRODUCTION Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS). METHODS CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system

Anti-cancer drug validation: the contribution of tissue engineered models

Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Glucose-induced posttranslational activation of protein phosphatases PP2A and PP1 in yeast

The protein phosphatases PP2A and PP1 are major regulators of a variety of cellular processes in yeast and other eukaryotes. Here, we reveal that both enzymes are direct targets of glucose sensing. Addition of glucose to glucose-deprived yeast cells triggered rapid posttranslational activation of both PP2A and PP1. Glucose activation of PP2A is controlled by regulatory subunits Rts1, Cdc55, Rrd1 and Rrd2. It is associated with rapid carboxymethylation of the catalytic subunits, which is necessary but not sufficient for activation. Glucose activation of PP1 was fully dependent on regulatory subunits Reg1 and Shp1. Absence of Gac1, Glc8, Reg2 or Red1 partially reduced activation while Pig1 and Pig2 inhibited activation. Full activation of PP2A and PP1 was also dependent on subunits classically considered to belong to the other phosphatase. PP2A activation was dependent on PP1 subunits Reg1 and Shp1 while PP1 activation was dependent on PP2A subunit Rts1. Rts1 interacted with both Pph21 and Glc7 under different conditions and these interactions were Reg1 dependent. Reg1-Glc7 interaction is responsible for PP1 involvement in the main glucose repression pathway and we show that deletion of Shp1 also causes strong derepression of the invertase gene SUC2. Deletion of the PP2A subunits Pph21 and Pph22, Rrd1 and Rrd2, specifically enhanced the derepression level of SUC2, indicating that PP2A counteracts SUC2 derepression. Interestingly, the effect of the regulatory subunit Rts1 was consistent with its role as a subunit of both PP2A and PP1, affecting derepression and repression of SUC2, respectively. We also show that abolished phosphatase activation, except by reg1Δ, does not completely block Snf1 dephosphorylation after addition of glucose. Finally, we show that glucose activation of the cAMP-PKA (protein kinase A) pathway is required for glucose activation of both PP2A and PP1. Our results provide novel insight into the complex regulatory role of these two major protein phosphatases in glucose regulation