213 research outputs found
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
Dependence of nucleosome mechanical stability on DNA mismatches
The organization of nucleosomes into chromatin and their accessibility are shaped by local DNA mechanics. Conversely, nucleosome positions shape genetic variations, which may originate from mismatches during replication and chemical modification of DNA. To investigate how DNA mismatches affect the mechanical stability and the exposure of nucleosomal DNA, we used an optical trap combined with single-molecule FRET and a single-molecule FRET cyclization assay. We found that a single base-pair C-C mismatch enhances DNA bendability and nucleosome mechanical stability for the 601-nucleosome positioning sequence. An increase in force required for DNA unwrapping from the histone core is observed for single base-pair C-C mismatches placed at three tested positions: at the inner turn, at the outer turn, or at the junction of the inner and outer turn of the nucleosome. The results support a model where nucleosomal DNA accessibility is reduced by mismatches, potentially explaining the preferred accumulation of single-nucleotide substitutions in the nucleosome core and serving as the source of genetic variation during evolution and cancer progression. Mechanical stability of an intact nucleosome, that is mismatch-free, is also dependent on the species as we find that yeast nucleosomes are mechanically less stable and more symmetrical in the outer turn unwrapping compared to Xenopus nucleosomes
Effect of dietary omega-3 fatty acids on castrate-resistant prostate cancer and tumor-associated macrophages.
BackgroundM2-like macrophages are associated with the pathogenesis of castrate-resistant prostate cancer (CRPC). We sought to determine if dietary omega-3 fatty acids (ω-3 FAs) delay the development and progression of CRPC and inhibit tumor-associated M2-like macrophages.MethodsMycCap cells were grown subcutaneously in immunocompetent FVB mice. Mice were castrated when tumors reached 300 mm2. To study effects of dietary ω-3 FAs on development of CRPC, ω-3 or ω-6 diets were started 2 days after castration and mice sacrificed after early regrowth of tumors. To study ω-3 FA effects on progression of CRPC, tumors were allowed to regrow after castration before starting the diets. M2 (CD206+) macrophages were isolated from allografts to examine ω-3 FA effects on macrophage function. Omega-3 fatty acid effects on androgen-deprived RAW264.7 M2 macrophages were studied by RT-qPCR and a migration/ invasion assay.ResultsThe ω-3 diet combined with castration lead to greater MycCap tumor regression (tumor volume reduction: 182.2 ± 33.6 mm3) than the ω-6 diet (tumor volume reduction: 148.3 ± 35.2; p = 0.003) and significantly delayed the time to CRPC (p = 0.006). Likewise, the ω-3 diet significantly delayed progression of established castrate-resistant MycCaP tumors (p = 0.003). The ω-3 diet (as compared to the ω-6 diet) significantly reduced tumor-associated M2-like macrophage expression of CSF-1R in the CRPC development model, and matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the CRPC progression model. Migration of androgen-depleted RAW264.7 M2 macrophages towards MycCaP cells was reversed by addition of docosahexaenoic acid (ω-3).ConclusionsDietary omega-3 FAs (as compared to omega-6 FAs) decreased the development and progression of CRPC in an immunocompetent mouse model, and had inhibitory effects on M2-like macrophage function. Clinical trials are warranted evaluating if a fish oil-based diet can delay the time to castration resistance in men on androgen deprivation therapy, whereas further preclinical studies are warranted evaluating fish oil for more advanced CRPC
Streptococcus suis contains multiple phase-variable methyltransferases that show a discrete lineage distribution
Streptococcus suis is a major pathogen of swine, responsible for a number of chronic and acute infections, and is also emerging as a major zoonotic pathogen, particularly in South-East Asia. Our study of a diverse population of S. suis shows that this organism contains both Type I and Type III phase-variable methyltransferases. In all previous examples, phase-variation of methyltransferases results in genome wide methylation differences, and results in differential regulation of multiple genes, a system known as the phasevarion (phase-variable regulon). We hypothesized that each variant in the Type I and Type III systems encoded a methyltransferase with a unique specificity, and could therefore control a distinct phasevarion, either by recombination-driven shuffling between different specificities (Type I) or by biphasic on-off switching via simple sequence repeats (Type III). Here, we present the identification of the target specificities for each Type III allelic variant from S. suis using single-molecule, real-time methylome analysis. We demonstrate phase-variation is occurring in both Type I and Type III methyltransferases, and show a distinct association between methyltransferase type and presence, and population clades. In addition, we show that the phase-variable Type I methyltransferase was likely acquired at the origin of a highly virulent zoonotic sub-population
Removing ammonium from water using modified corncob-biochar
© 2016 Elsevier B.V. Ammonium pollution in groundwater and surface water is of major concern in many parts of the world due to the danger it poses to the environment and people's health. This study focuses on the development of a low cost adsorbent, specifically a modified biochar prepared from corncob. Evaluated here is the efficiency of this new material for removing ammonium from synthetic water (ammonium concentration from 10 to 100 mg/L). The characteristics of the modified biochar were determined by Brunauer-Emmett-Teller (BET) test, Fourier transform infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM). It was found that ammonium adsorption on modified biochar strongly depended on pH. Adsorption kinetics of NH4+-N using modified biochar followed the pseudo-second order kinetic model. Both Langmuir and Sips adsorption isotherm models could simulate well the adsorption behavior of ammonium on modificated biochar. The highest adsorption capacity of 22.6 mg NH4+-N/g modified biochar was obtained when the biochar was modified by soaking it in HNO3 6 M and NaOH 0.3 M for 8 h and 24 h, respectively. The high adsorption capacity of the modified biochar suggested that it is a promising adsorbent for NH4+-N remediation from water
Providing High-Quality Care for Limited English Proficient Patients: The Importance of Language Concordance and Interpreter Use
Background: Provider–patient language discordance is related to worse quality care for limited English proficient (LEP) patients who speak Spanish. However, little is known about language barriers among LEP Asian-American patients. Objective: We examined the effects of language discordance on the degree of health education and the quality of interpersonal care that patients received, and examined its effect on patient satisfaction. We also evaluated how the presence/absence of a clinic interpreter affected these outcomes. Design: Cross-sectional survey, response rate 74%. Participants: A total of 2,746 Chinese and Vietnamese patients receiving care at 11 health centers in 8 cities. Measurements: Provider–patient language concordance, health education received, quality of interpersonal care, patient ratings of providers, and the presence/absence of a clinic interpreter. Regression analyses were used to adjust for potential confounding. Results: Patients with language-discordant providers reported receiving less health education (β = 0.17, p < 0.05) compared to those with language-concordant providers. This effect was mitigated with the use of a clinic interpreter. Patients with language-discordant providers also reported worse interpersonal care (β = 0.28, p < 0.05), and were more likely to give low ratings to their providers (odds ratio [OR] = 1.61; CI = 0.97–2.67). Using a clinic interpreter did not mitigate these effects and in fact exacerbated disparities in patients’ perceptions of their providers. Conclusion: Language barriers are associated with less health education, worse interpersonal care, and lower patient satisfaction. Having access to a clinic interpreter can facilitate the transmission of health education. However, in terms of patients’ ratings of their providers and the quality of interpersonal care, having an interpreter present does not serve as a substitute for language concordance between patient and provider
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Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.
MotivationMultiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.ResultsWe performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementationDatasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary informationSupplementary data are available at Bioinformatics online
Achievable rates optimization for broadcast channels using finite size constellations under transmission constraints
Conscious monitoring and control (reinvestment) in surgical performance under pressure.
Research on intraoperative stressors has focused on external factors without considering individual differences in the ability to cope with stress. One individual difference that is implicated in adverse effects of stress on performance is "reinvestment," the propensity for conscious monitoring and control of movements. The aim of this study was to examine the impact of reinvestment on laparoscopic performance under time pressure
Optical identification of electronic state levels of an asymmetric InAs/InGaAs/GaAs dot-in-well structure
We have studied the electronic state levels of an asymmetric InAs/InGaAs/GaAs dot-in-well structure, i.e., with an In0.15Ga0.85As quantum well (QW) as capping layer above InAs quantum dots (QDs), via temperature-dependent photoluminescence, photo-modulated reflectance, and rapid thermal annealing (RTA) treatments. It is shown that the carrier transfer via wetting layer (WL) is impeded according to the results of temperature dependent peak energy and line width variation of both the ground states (GS) and excited states (ES) of QDs. The quenching of integrated intensity is ascribed to the thermal escape of electron from the dots to the complex In0.15Ga0.85As QW + InAs WL structure. Additionally, as the RTA temperature increases, the peak of PL blue shifts and the full width at half maximum shrinks. Especially, the intensity ratio of GS to ES reaches the maximum when the energy difference approaches the energy of one or two LO phonon(s) of InAs bulk material, which could be explained by phonon-enhanced inter-sublevels carrier relaxation in such asymmetric dot-in-well structure
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