Large-eddy simulation of a particle-laden turbulent channel flow

Large-eddy simulations of a vertical turbulent channel flow with 420,000 solid particles are performed in order to get insight into fundamental aspects of a riser flow The question is addressed whether collisions between particles are important for the ow statistics. The turbulent channel ow corresponds to a particle volume fraction of 0.013 and a mass load ratio of 18, values that are relatively high compared to recent literature on large-eddy simulation of two-phase ows. In order to simulate this ow, we present a formulation of the equations for compressible ow in a porous medium including particle forces. These equations are solved with LES using a Taylor approximation of the dynamic subgrid-model. The results show that due to particle-uid interactions the boundary layer becomes thinner, leading to a higher skin-friction coefcient. Important effects of the particle collisions are also observed, on the mean uid prole, but even more o on particle properties. The collisions cause a less uniform particle concentration\ud and considerably atten the mean solids velocity prole

Breakdown of Fermi-liquid theory in a cuprate superconductor

The behaviour of electrons in solids is remarkably well described by Landau's Fermi-liquid theory, which says that even though electrons in a metal interact they can still be treated as well-defined fermions, called ``quasiparticles''. At low temperature, the ability of quasiparticles to transport heat is strictly given by their ability to transport charge, via a universal relation known as the Wiedemann-Franz law, which no material in nature has been known to violate. High-temperature superconductors have long been thought to fall outside the realm of Fermi-liquid theory, as suggested by several anomalous properties, but this has yet to be shown conclusively. Here we report on the first experimental test of the Wiedemann-Franz law in a cuprate superconductor, (Pr,Ce)$_2$CuO$_4$. Our study reveals a clear departure from the universal law and provides compelling evidence for the breakdown of Fermi-liquid theory in high-temperature superconductors.Comment: 7 pages, 3 figure

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

On the effects of the fix geometric constraint in 2D profiles on the reusability of parametric 3D CAD models

[EN] In order to be reusable, history-based feature-based parametric CAD models must reliably allow for modifications while maintaining their original design intent. In this paper, we demonstrate that relations that fix the location of geometric entities relative to the reference system produce inflexible profiles that reduce model reusability. We present the results of an experiment where novice students and expert CAD users performed a series of modifications in different versions of the same 2D profile, each defined with an increasingly higher number of fix geometric constraints. Results show that the amount of fix constraints in a 2D profile correlates with the time required to complete reusability tasks, i.e., the higher the number of fix constraints in a 2D profile, the less flexible and adaptable the profile becomes to changes. In addition, a pilot software tool to automatically track this type of constraints was developed and tested. Results suggest that the detection of fix constraint overuse may result in a new metric to assess poor quality models with low reusability. The tool provides immediate feedback for preventing high semantic level quality errors, and assistance to CAD users. Finally, suggestions are introduced on how to convert fix constraints in 2D profiles into a negative metric of 3D model quality.The authors would like to thank Raquel Plumed for her support in the statistical analysis. This work has been partially funded by Grant UJI-A02017-15 (Universitat Jaume I) and DPI201784526-R (MINECO/AEI/FEDER, UE), project CAL-MBE. The authors also wish to thank the editor and reviewers for their valuable comments and suggestions that helped us improve the quality of the paper.González-Lluch, C.; Company, P.; Contero, M.; Pérez Lopez, DC.; Camba, JD. (2019). On the effects of the fix geometric constraint in 2D profiles on the reusability of parametric 3D CAD models. 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A comparison of manual vs. online grading for solid models. Paper presented at 120th ASEE annual conference and exposition, Atlanta, GA, June 23–26, 2013, Paper ID #7233.Barbero, B. R., Pedrosa, C. M., & Samperio, R. Z. (2016). Learning CAD at university through summaries of the rules of design intent. International Journal of Technology and Design Education. https://doi.org/10.1007/s10798-016-9358-z .Bodein, Y., Bertrand, R., & Caillaud, E. (2014). Explicit reference modeling methodology in parametric CAD system. Computers in Industry, 65(1), 136–147. https://doi.org/10.1016/j.compind.2013.08.004 .Bouma, W., Fudos, I., Hoffmann, C., Cai, J., & Paige, R. (1995). Geometric constraint solver. Computer-Aided Design, 27(6), 487–501. https://doi.org/10.1016/0010-4485(94)00013-4 .Briggs, J. C., Hepworth, A. I., Stone, B. R., Cobum, J. Q., Jensen, C. G., & Red, E. (2015). Integrated, synchronous multi-user design and analysis. Journal of Computing and Information Science in Engineering, 15(3), 031002. https://doi.org/10.1115/1.4029801 .Buckley, J., Seery, N., & Canty, D. (2017). Heuristics and CAD modelling: An examination of student behaviour during problem solving episodes within CAD modelling activities. International Journal of Technology and Design Education. https://doi.org/10.1007/s10798-017-9423-2 .Camba, J. D., & Contero, M. (2015). Assessing the impact of geometric design intent annotations on parametric model alteration activities. Computers in Industry, 71, 35–45. https://doi.org/10.1016/j.compind.2015.03.006 .Camba, J. D., Contero, M., & Company, P. (2016). Parametric CAD modeling: An analysis of strategies for design reusability. Computer-Aided Design, 74, 18–31. https://doi.org/10.1016/j.cad.2016.01.003 .Camba, J. D., Contero, M., & Company, P. (2017). CAD reusability and the role of modeling information in the MBE context. Model-based enterprise summit 2017. 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(Colección Sapientia, Núm. 86). http://cad3dconsolidworks.uji.es .Contero, M., Company, P., Vila, C., & Aleixos, N. (2002). Product data quality and collaborative engineering. IEEE Computer Graphics Applications, 22(3), 32–42. https://doi.org/10.1109/MCG.2002.999786 .Dixon, B. M., & Dannenhoffer, J. F., III. (2014). Geometric sketch constraint solving with user feedback. Journal of Aerospace Information Systems, 11(5), 316–325. https://doi.org/10.2514/1.I010110 .Fudos, I., & Hoffmann, C. M. (1997). A graph-constructive approach to solving systems of geometric constraints. ACM Transactions on Graphics, 16(2), 179–216. https://doi.org/10.1145/248210.248223 .Ge, J. X., Chou, S. C., & Gao, X. S. (1999). Geometric constraint satisfaction using optimization methods. Computer-Aided Design, 31(14), 867–879. https://doi.org/10.1016/S0010-4485(99)00074-3 .González-Lluch, C., Company, P., Contero, M., Camba, J. D., & Colom, J. (2017a). A case study on the use of model quality testing tools for the assessment of MCAD models and drawings. International Journal of Engineering Education, 33(5), 1643–1653.González-Lluch, C., Company, P., Contero, M., Camba, J. D., & Plumed, R. (2017b). A survey on 3D CAD model quality assurance and testing tools. Computer-Aided Design, 83, 64–79. https://doi.org/10.1016/j.cad.2016.10.003 .Hamade, R. F. (2009). Profiling the desirable CAD trainee: Technical background, personality attributes, and learning preferences. Journal of Mechanical Design, 131(12), 121009–121019. https://doi.org/10.1115/1.4000455 .Hekman, K. A., & Gordon, M. T. (2013). Automated grading of first year student CAD work. Paper presented at the 120th ASEE annual conference and exposition 2013, Atlanta, GA, June 23–26. Paper ID #6379.Hepworth, A., Tew, K., Trent, M., Ricks, R., Jensen, C. G., & Red, E. R. (2014). Model consistency and conflict resolution with data preservation in multi-user computer aided design. 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Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

In vitro synergistic cytotoxicity of gemcitabine and pemetrexed and pharmacogenetic evaluation of response to gemcitabine in bladder cancer patients

The present study was performed to investigate the capability of gemcitabine and pemetrexed to synergistically interact with respect to cytotoxicity and apoptosis in T24 and J82 bladder cancer cells, and to establish a correlation between drug activity and gene expression of selected genes in tumour samples. The interaction between gemcitabine and pemetrexed was synergistic; indeed, pemetrexed favoured gemcitabine cytotoxicity by increasing cellular population in S-phase, reducing Akt phosphorylation as well as by inducing the expression of a major gemcitabine uptake system, the human equilibrative nucleoside transporter-1 (hENT1), and the key activating enzyme deoxycytidine kinase (dCK) in both cell lines. Bladder tumour specimens showed an heterogeneous gene expression pattern and patients with higher levels of dCK and hENT1 had better response. Moreover, human nucleoside concentrative transporter-1 was detectable only in 3/12 patients, two of whom presented a complete response to gemcitabine. These data provide evidence that the chemotherapeutic activity of the combination of gemcitabine and pemetrexed is synergistic against bladder cancer cells in vitro and that the assessment of the expression of genes involved in gemcitabine uptake and activation might be a possible determinant of bladder cancer response and may represent a new tool for treatment optimization

Biomineralisation by earthworms: an investigation into the stability and distribution of amorphous calcium carbonate

Background Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions. Granule elemental composition was determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and electron microprobe analysis (EMPA). Mass of ACC present in solid granules was quantified using FTIR and compared to granule elemental and amino acid compositions. Bulk analysis of granules was of powdered bulk material. Spatially resolved analysis was of thin sections of granules using synchrotron-based μ-FTIR and EMPA electron microprobe analysis. Results The milky fluid from which granules form is amino acid-rich (≤ 136 ± 3 nmol mg−1 (n = 3; ± std dev) per individual amino acid); the CaCO3 phase present is ACC. Even four years after production, granules contain ACC. No correlation exists between mass of ACC present and granule elemental composition. Granule amino acid concentrations correlate well with ACC content (r ≥ 0.7, p ≤ 0.05) consistent with a role for amino acids (or the proteins they make up) in ACC stabilisation. Intra-granule variation in ACC (RSD = 16%) and amino acid concentration (RSD = 22–35%) was high for granules produced by the same earthworm. Maps of ACC distribution produced using synchrotron-based μ-FTIR mapping of granule thin sections and the relative intensity of the ν2: ν4 peak ratio, cluster analysis and component regression using ACC and calcite standards showed similar spatial distributions of likely ACC-rich and calcite-rich areas. We could not identify organic peaks in the μ-FTIR spectra and thus could not determine whether ACC-rich domains also had relatively high amino acid concentrations. No correlation exists between ACC distribution and elemental concentrations determined by EMPA. Conclusions ACC present in earthworm CaCO3 granules is highly stable. Our results suggest a role for amino acids (or proteins) in this stability. We see no evidence for stabilisation of ACC by incorporation of inorganic components

Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan

Protracted venous infusion 5-fluorouracil (5FU) combined with mitomycin C (MMC) has demonstrated significant activity against metastatic colorectal cancer. Owing to potential synergy based upon upregulation of thymidine phosphorylase by MMC, the combination of capecitabine and MMC may improve outcomes in irinotecan-refractory disease. Eligible patients with progressive disease during or within 6 months of second-line chemotherapy were treated with capecitabine (1250 mg m−2 twice daily) days 1–14 every 3 weeks and MMC (7 mg m−2 IV bolus) once every 6 weeks. A total of 36 patients were recruited, with a median age of 64 years (range 40–77), and 23 patients (78%) were performance status 0–1. The objective response rate was 15.2%. In all, 48.5% of patients had stable disease. Median failure-free survival was 5.4 months (95% CI 4.6–6.2). Median overall survival was 9.3 months (95% CI: 6.9–11.7). Grade 3 toxicities were palmar-plantar erythema 16.7%, vomiting 8.3%, diarrhoea 2.8%, anaemia 8.3%, and neutropenia 2.8%. No patients developed haemolytic uraemic syndrome. Symptomatic improvement occurred for pain, bowel symptoms, and dyspnoea. Capecitabine in combination with MMC is an effective regimen for metastatic colorectal cancer resistant to 5FU and irinotecan with an acceptable toxicity profile and a convenient administration schedule