Analytical and discrete solutions for the incipient motion of ellipsoidal sediment particles

[EN] This work introduces analytical and numerical approaches to compute the incipient motion of ellipsoidal sediment particles. Initiation of motion of spherical particles is dominated by rolling mode. However, solutions for initiation of motion for non-spherical grains have to incorporate rolling, sliding, and mixed modes. The proposed approaches include a wide variety of shapes and inclinations that represent realistic configurations of sediment bed layers. The numerical procedure is based on the discrete element method, simulating the micro-mechanics of the sediment as an aggregate of rigid ellipsoids interacting by contact. The numerical solution covers a range of incipient movements that cannot be covered by the analytical approach. Hence, some trapped modes observed in analytical calculations are complemented by the numerical computation of threshold stresses. The main results are organized as novel extended Shields diagrams for non-spherical grains, where non-dimensional critical shear stress is represented in terms of friction Reynolds number.This work was supported by the Ministerio de Ciencia e Innovación Grant [#BIA-2012-32918 and #BIA-2015-64994-P (MINECO/FEDER)].Bravo, R.; Ortiz, P.; Pérez-Aparicio, JL. (2018). Analytical and discrete solutions for the incipient motion of ellipsoidal sediment particles. Journal of Hydraulic Research. 56(1):29-43. https://doi.org/10.1080/00221686.2017.1289263S2943561Belytschko, T., & Neal, M. O. (1991). Contact-impact by the pinball algorithm with penalty and Lagrangian methods. International Journal for Numerical Methods in Engineering, 31(3), 547-572. doi:10.1002/nme.1620310309Bravo, R., Ortiz, P., & Pérez-Aparicio, J. L. (2014). Incipient sediment transport for non-cohesive landforms by the discrete element method (DEM). Applied Mathematical Modelling, 38(4), 1326-1337. doi:10.1016/j.apm.2013.08.010Bravo, R., Pérez-Aparicio, J. L., & Gómez-Hernández, J. J. (2015). Numerical sedimentation particle-size analysis using the Discrete Element Method. Advances in Water Resources, 86, 58-72. doi:10.1016/j.advwatres.2015.09.024Bravo, R., Pérez-Aparicio, J. L., & Laursen, T. A. (2012). An energy consistent frictional dissipating algorithm for particle contact problems. International Journal for Numerical Methods in Engineering, 92(9), 753-781. doi:10.1002/nme.4346Buffington, J. M., & Montgomery, D. R. (1997). A systematic analysis of eight decades of incipient motion studies, with special reference to gravel-bedded rivers. Water Resources Research, 33(8), 1993-2029. doi:10.1029/96wr03190Cheng, N.-S., & Chiew, Y.-M. (1999). Incipient sediment motion with upward seepage. Journal of Hydraulic Research, 37(5), 665-681. doi:10.1080/00221689909498522Chiew, Y.-M., & Parker, G. (1994). Incipient sediment motion on non-horizontal slopes. Journal of Hydraulic Research, 32(5), 649-660. doi:10.1080/00221689409498706Derksen, J. J. (2015). Simulations of granular bed erosion due to a mildly turbulent shear flow. Journal of Hydraulic Research, 53(5), 622-632. doi:10.1080/00221686.2015.1077354Dey, S. (1999). Sediment threshold. Applied Mathematical Modelling, 23(5), 399-417. doi:10.1016/s0307-904x(98)10081-1Dey, S. (2003). Threshold of sediment motion on combined transverse and longitudinal sloping beds. Journal of Hydraulic Research, 41(4), 405-415. doi:10.1080/00221680309499985Dey, S., Sarker, H. K. D., & Debnath, K. (1999). Sediment Threshold under Stream Flow on Horizontal and Sloping Beds. Journal of Engineering Mechanics, 125(5), 545-553. doi:10.1061/(asce)0733-9399(1999)125:5(545)Hölzer, A., & Sommerfeld, M. (2008). New simple correlation formula for the drag coefficient of non-spherical particles. Powder Technology, 184(3), 361-365. doi:10.1016/j.powtec.2007.08.021James, C. S. (1990). Prediction of entrainment conditions for nonuniform, noncohesive sediments. Journal of Hydraulic Research, 28(1), 25-41. doi:10.1080/00221689009499145Ji, C., Munjiza, A., Avital, E., Ma, J., & Williams, J. J. R. (2013). Direct numerical simulation of sediment entrainment in turbulent channel flow. Physics of Fluids, 25(5), 056601. doi:10.1063/1.4807075Klamkin, M. S. (1971). Elementary Approximations to the Area of N-Dimensional Ellipsoids. The American Mathematical Monthly, 78(3), 280. doi:10.2307/2317530Mandø, M., & Rosendahl, L. (2010). On the motion of non-spherical particles at high Reynolds number. Powder Technology, 202(1-3), 1-13. doi:10.1016/j.powtec.2010.05.001MILLER, M. C., McCAVE, I. N., & KOMAR, P. D. (1977). Threshold of sediment motion under unidirectional currents. Sedimentology, 24(4), 507-527. doi:10.1111/j.1365-3091.1977.tb00136.xWan Mohtar, W. H. M., & Munro, R. J. (2013). Threshold criteria for incipient sediment motion on an inclined bedform in the presence of oscillating-grid turbulence. Physics of Fluids, 25(1), 015103. doi:10.1063/1.4774341Ortiz, P., & Smolarkiewicz, P. K. (2006). Numerical simulation of sand dune evolution in severe winds. International Journal for Numerical Methods in Fluids, 50(10), 1229-1246. doi:10.1002/fld.1138Ortiz, P., & Smolarkiewicz, P. K. (2009). Coupling the dynamics of boundary layers and evolutionary dunes. Physical Review E, 79(4). doi:10.1103/physreve.79.041307Van Rijn, L. C. (1984). Sediment Transport, Part I: Bed Load Transport. Journal of Hydraulic Engineering, 110(10), 1431-1456. doi:10.1061/(asce)0733-9429(1984)110:10(1431)Shi, G.-H., & Goodman, R. E. (1985). Two dimensional discontinuous deformation analysis. International Journal for Numerical and Analytical Methods in Geomechanics, 9(6), 541-556. doi:10.1002/nag.1610090604Shields, A. (1936). Application of similarity principles and turbulence research to bed-load movement (Tech. Rep.). Lab. for Hydraulic Water Resources.Wellmann, C., Lillie, C., & Wriggers, P. (2008). A contact detection algorithm for superellipsoids based on the common‐normal concept. Engineering Computations, 25(5), 432-442. doi:10.1108/02644400810881374Wiberg, P. L., & Smith, J. D. (1985). A theoretical model for saltating grains in water. Journal of Geophysical Research, 90(C4), 7341. doi:10.1029/jc090ic04p0734

A mammalianized synthetic nitroreductase gene for high-level expression

Background The nitroreductase/5-(azaridin-1-yl)-2,4-dinitrobenzamide (NTR/CB1954) enzyme/prodrug system is considered as a promising candidate for anti-cancer strategies by gene-directed enzyme prodrug therapy (GDEPT) and has recently entered clinical trials. It requires the genetic modification of tumor cells to express the E. coli enzyme nitroreductase that bioactivates the prodrug CB1954 to a powerful cytotoxin. This metabolite causes apoptotic cell death by DNA interstrand crosslinking. Enhancing the enzymatic NTR activity for CB1954 should improve the therapeutical potential of this enzyme-prodrug combination in cancer gene therapy. Methods We performed de novo synthesis of the bacterial nitroreductase gene adapting codon usage to mammalian preferences. The synthetic gene was investigated for its expression efficacy and ability to sensitize mammalian cells to CB1954 using western blotting analysis and cytotoxicity assays. Results In our study, we detected cytoplasmic protein aggregates by expressing GFP-tagged NTR in COS-7 cells, suggesting an impaired translation by divergent codon usage between prokaryotes and eukaryotes. Therefore, we generated a synthetic variant of the nitroreductase gene, called ntro, adapted for high-level expression in mammalian cells. A total of 144 silent base substitutions were made within the bacterial ntr gene to change its codon usage to mammalian preferences. The codon-optimized ntro either tagged to gfp or c-myc showed higher expression levels in mammalian cell lines. Furthermore, the ntro rendered several cell lines ten times more sensitive to the prodrug CB1954 and also resulted in an improved bystander effect. Conclusion Our results show that codon optimization overcomes expression limitations of the bacterial ntr gene in mammalian cells, thereby improving the NTR/CB1954 system at translational level for cancer gene therapy in humans

Intracellular Serotonin Modulates Insulin Secretion from Pancreatic β-Cells by Protein Serotonylation

Non-neuronal, peripheral serotonin deficiency causes diabetes mellitus and identifies an intracellular role for serotonin in the regulation of insulin secretion

Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism

Both single and multicellular organisms depend on anti-stress mechanisms that enable them to deal with sudden changes in the environment, including exposure to heat and oxidants. Central to the stress response are dynamic changes in metabolism, such as the transition from the glycolysis to the pentose phosphate pathway—a conserved first-line response to oxidative insults1,2. Here we report a second metabolic adaptation that protects microbial cells in stress situations. The role of the yeast polyamine transporter Tpo1p3,4,5 in maintaining oxidant resistance is unknown6. However, a proteomic time-course experiment suggests a link to lysine metabolism. We reveal a connection between polyamine and lysine metabolism during stress situations, in the form of a promiscuous enzymatic reaction in which the first enzyme of the polyamine pathway, Spe1p, decarboxylates lysine and forms an alternative polyamine, cadaverine. The reaction proceeds in the presence of extracellular lysine, which is taken up by cells to reach concentrations up to one hundred times higher than those required for growth. Such extensive harvest is not observed for the other amino acids, is dependent on the polyamine pathway and triggers a reprogramming of redox metabolism. As a result, NADPH—which would otherwise be required for lysine biosynthesis—is channelled into glutathione metabolism, leading to a large increase in glutathione concentrations, lower levels of reactive oxygen species and increased oxidant tolerance. Our results show that nutrient uptake occurs not only to enable cell growth, but when the nutrient availability is favourable it also enables cells to reconfigure their metabolism to preventatively mount stress protection

The catatonic dilemma expanded

Catatonia is a common syndrome that was first described in the literature by Karl Kahlbaum in 1874. The literature is still developing and remains unclear on many issues, especially classification, diagnosis, and pathophysiology. Clinicians caring for psychiatric patients with catatonic syndromes continue to face many dilemmas in diagnosis and treatment. We discuss many of the common problems encountered in the care of a catatonic patient, and discuss each problem with a review of the literature. Focus is on practical aspects of classification, epidemiology, differential diagnosis, treatment, medical comorbidity, cognition, emotion, prognosis, and areas for future research in catatonic syndromes

Flourishing in the now: Initial validation of a present-eudaimonic time perspective scale

Introduction: A positive focus on the present, the only time zone which we experience directly and permanently, is at least as relevant as perspectives on the past and future in a balanced time perspective and its relation to wellbeing. Yet, few instruments examining a positive present time perspective exist. Two present-directed concepts, mindfulness and flow, that are intrinsically linked to mental wellbeing were analyzed and used to formulate a present-eudaimonic scale that complements the past and future scales of the balanced time perspective scale. The present study addresses the psychometric properties of the present-eudaimonic scale and the modified balanced time perspective scale. Method: 131 participants filled out the present-eudaimonic scale, the balanced time perspective scale, the Zimbardo time perspective inventory, the five facet mindfulness questionnaire – short form, the Swedish flow proneness questionnaire and the mental health continuum – short form. Balanced time perspective was operationalized using the deviation from a balanced time perspective coefficient. Results: The present-eudaimonic scale showed good psychometric properties including internal consistency, factor structure, and convergent validity. The present-eudaimonic scale explained an additional eleven percent of variance in mental health beyond the other time perspective scales. Balanced time perspective as measured with the modified balanced time perspective scale correlated significantly stronger with mental health than balanced time perspective measured with the Zimbardo time perspective inventory. Conclusions: The present-eudaimonic scale fills a gap in the assessment of time perspective and the modified balanced time perspective scale is a promising way to study balanced time perspective