Vortex merging and splitting: A route to elastoinertial turbulence in Taylor-Couette flow

We report experimental evidence of a new merge-split transition (MST) to elastoinertial turbulence (EIT) in Taylor-Couette flows of viscoelastic polymer solutions, caused by merging and splitting of base Taylor vortices when crossed by elastic axial waves (rotating standing waves, RSW). These vortex merging and splitting events are not due to transient behavior, finite aspect ratio, or shear-thinning behavior. They are random in nature and increase in frequency with Re; when superimposed on a RSW flow state they cause abrupt changes in the axial spatial wavelength, leading to the transition from a RSW to the EIT state. We thus identify MST as an inertial feature solely triggered by elasticity and independent of any shear-thinning behavior

Introducing a variable speed of sound in single-component lattice Boltzmann simulations of isothermal fluid flows

To simulate the hydrodynamics and mixing characteristics of chemical reactors by means of a lattice Boltzmann method (LBM), it is essential to consider components with varying molecular weights (and therefore speeds of sound). This option requires modification of the standard equilibrium distribution function and the use of an extended velocity set. In this paper, we show that, for isothermal incompressible single-component non-reactive flows, tuning the speed of sound with a modified equilibrium distribution and an extended velocity set allows for reproducing the proper flow characteristics with strongly reduced errors (compared to LBM simulations on standard lattices). This is done for two isothermal benchmarks, viz. a damped standing pressure wave and a decaying viscous Taylor–Green Vortex. The convergence as a function of the number of lattice nodes used improves substantially for varying values of the speed of sound

Taylor-Couette instability in disk suspensions: Experimental observation and theory

Using the well-known hydrodynamic theory for dilute suspensions of spheroids, we have previously predicted the destabilization of Taylor-Couette flow due to anisotropic viscous stresses induced by suspended disk-shaped particles [Gillissen and Wilson, Phys. Rev. Fluids 3, 113903 (2018)]. Here we provide experimental evidence for the destabilization mechanism using suspensions of mica flakes. There is good qualitative agreement between the experiment and theory in the mica concentration dependence of the critical speed for instability onset and of the axial wavelength of the corresponding Taylor vortices. Quantitative differences are attributed to hydrodynamic interactions between the disks, which we account for in the theory in an ad hoc fashion using rotary diffusion

Enhanced Apoptosis and Loss of Cell Viability in Melanoma Cells by Combined Inhibition of ERK and Mcl-1 Is Related to Loss of Mitochondrial Membrane Potential, Caspase Activation and Upregulation of Proapoptotic Bcl-2 Proteins

Targeting of MAP kinase pathways by BRAF inhibitors has evolved as a key therapy for BRAF-mutated melanoma. However, it cannot be applied for BRAF-WT melanoma, and also, in BRAF-mutated melanoma, tumor relapse often follows after an initial phase of tumor regression. Inhibition of MAP kinase pathways downstream at ERK1/2, or inhibitors of antiapoptotic Bcl-2 proteins, such as Mcl-1, may serve as alternative strategies. As shown here, the BRAF inhibitor vemurafenib and the ERK inhibitor SCH772984 showed only limited efficacy in melanoma cell lines, when applied alone. However, in combination with the Mcl-1 inhibitor S63845, the effects of vemurafenib were strongly enhanced in BRAF-mutated cell lines, and the effects of SCH772984 were enhanced in both BRAF-mutated and BRAF-WT cells. This resulted in up to 90% loss of cell viability and cell proliferation, as well as in induction of apoptosis in up to 60% of cells. The combination of SCH772984/S63845 resulted in caspase activation, processing of poly (ADP-ribose) polymerase (PARP), phosphorylation of histone H2AX, loss of mitochondrial membrane potential, and cytochrome c release. Proving the critical role of caspases, a pan-caspase inhibitor suppressed apoptosis induction, as well as loss of cell viability. As concerning Bcl-2 family proteins, SCH772984 enhanced expression of the proapoptotic Bim and Puma, as well as decreased phosphorylation of Bad. The combination finally resulted in downregulation of antiapoptotic Bcl-2 and enhanced expression of the proapoptotic Noxa. In conclusion, combined inhibition of ERK and Mcl-1 revealed an impressive efficacy both in BRAF-mutated and WT melanoma cells, and may thus represent a new strategy for overcoming drug resistance

Hydrodynamic Propulsion of Liposomes Electrostatically Attracted to a Lipid Membrane Reveals Size-Dependent Conformational Changes

The efficiency of lipid nanoparticle uptake across cellular membranes is strongly dependent on the very first interaction step. Detailed understanding of this step is in part hampered by the large heterogeneity in the physicochemical properties of lipid nanoparticles, such as liposomes, making conventional ensemble-averaging methods too blunt to address details of this complex process. Here, we contribute a means to explore whether individual liposomes become deformed upon binding to fluid cell-membrane mimics. This was accomplished by using hydrodynamic forces to control the propulsion of nanoscale liposomes electrostatically attracted to a supported lipid bilayer. In this way, the size of individual liposomes could be determined by simultaneously measuring both their individual drift velocity and diffusivity, revealing that for a radius of ∼45 nm, a close agreement with dynamic light scattering data was observed, while larger liposomes (radius ∼75 nm) displayed a significant deformation unless composed of a gel-phase lipid. The relevance of being able to extract this type of information is discussed in the context of membrane fusion and cellular uptake

A total blood volume or more transfused during pregnancy or after childbirth: Individual patient data from six international population-based observational studies.

BackgroundThis study aimed to compare incidence, management and outcomes of women transfused their blood volume or more within 24 hours during pregnancy or following childbirth.MethodsCombined analysis of individual patient data, prospectively collected in six international population-based studies (France, United Kingdom, Italy, Australia, the Netherlands and Denmark). Massive transfusion in major obstetric haemorrhage was defined as transfusion of eight or more units of red blood cells within 24 hours in a pregnant or postpartum woman. Causes, management and outcomes of women with massive transfusion were compared across countries using descriptive statistics.FindingsThe incidence of massive transfusion was approximately 21 women per 100,000 maternities for the United Kingdom, Australia and Italy; by contrast Denmark, the Netherlands and France had incidences of 82, 66 and 69 per 100,000 maternities, respectively. There was large variation in obstetric and haematological management across countries. Fibrinogen products were used in 86% of women in Australia, while the Netherlands and Italy reported lower use at 35-37% of women. Tranexamic acid was used in 75% of women in the Netherlands, but in less than half of women in the UK, Australia and Italy. In all countries, women received large quantities of colloid/crystalloid fluids during resuscitation (>3·5 litres). There was large variation in the use of compression sutures, embolisation and hysterectomy across countries. There was no difference in maternal mortality; however, variable proportions of women had cardiac arrests, renal failure and thrombotic events from 0-16%.InterpretationThere was considerable variation in the incidence of massive transfusion associated with major obstetric haemorrhage across six high-income countries. There were also large disparities in both transfusion and obstetric management between these countries. There is a requirement for detailed evaluation of evidence underlying current guidance. Furthermore, cross-country comparison may empower countries to reference their clinical care against that of other countries

Distributional theory for the DIA method

The DIA method for the detection, identification and adaptation of model misspecifications combines estimation with testing. The aim of the present contribution is to introduce a unifying framework for the rigorous capture of this combination. By using a canonical model formulation and a partitioning of misclosure space, we show that the whole estimation–testing scheme can be captured in one single DIA estimator. We study the characteristics of this estimator and discuss some of its distributional properties. With the distribution of the DIA estimator provided, one can then study all the characteristics of the combined estimation and testing scheme, as well as analyse how they propagate into final outcomes. Examples are given, as well as a discussion on how the distributional properties compare with their usage in practice

A Comparative Study on Three Analytical Methods for the Determination of the Neurotoxin BMAA in Cyanobacteria

The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) has been considered a serious health threat because of its putative role in multiple neurodegenerative diseases. First reports on BMAA concentrations in cyanobacteria were alarming: nearly all cyanobacteria were assumed to contain high BMAA concentrations, implying ubiquitous exposure. Recent studies however question this presence of high BMAA concentrations in cyanobacteria. To assess the real risk of BMAA to human health, this discrepancy must be resolved. We therefore tested whether the differences found could be caused by the analytical methods used in different studies. Eight cyanobacterial samples and two control samples were analyzed by three commonly used methods: HPLC-FLD analysis and LC-MS/MS analysis of both derivatized and underivatized samples. In line with published results, HPLC-FLD detected relatively high BMAA concentrations in some cyanobacterial samples, while both LC-MS/MS methods only detected BMAA in the positive control (cycad seed sarcotesta). Because we could eliminate the use of different samples and treatments as causal factors, we demonstrate that the observed differences were caused by the analytical methods. We conclude that HPLC-FLD overestimated BMAA concentrations in some cyanobacterial samples due to its low selectivity and propose that BMAA might be present in (some) cyanobacteria, but in the low µg/g or ng/g range instead of the high µg/g range as sometimes reported before. We therefore recommend to use only selective and sensitive analytical methods like LC-MS/MS for BMAA analysis. Although possibly present in low concentrations in cyanobacteria, BMAA can still form a health risk. Recent evidence on BMAA accumulation in aquatic food chains suggests human exposure through consumption of fish and shellfish which expectedly exceeds exposure through cyanobacteria