Extension of Murray's law using a non-Newtonian model of blood flow

<p>Abstract</p> <p>Background</p> <p>So far, none of the existing methods on Murray's law deal with the non-Newtonian behavior of blood flow although the non-Newtonian approach for blood flow modelling looks more accurate.</p> <p>Modeling</p> <p>In the present paper, Murray's law which is applicable to an arterial bifurcation, is generalized to a non-Newtonian blood flow model (power-law model). When the vessel size reaches the capillary limitation, blood can be modeled using a non-Newtonian constitutive equation. It is assumed two different constraints in addition to the pumping power: the volume constraint or the surface constraint (related to the internal surface of the vessel). For a seek of generality, the relationships are given for an arbitrary number of daughter vessels. It is shown that for a cost function including the volume constraint, classical Murray's law remains valid (i.e. Σ<it>R</it>^{<it>c </it>}= <it>cste </it>with <it>c </it>= 3 is verified and is independent of <it>n</it>, the dimensionless index in the viscosity equation; <it>R </it>being the radius of the vessel). On the contrary, for a cost function including the surface constraint, different values of <it>c </it>may be calculated depending on the value of <it>n</it>.</p> <p>Results</p> <p>We find that <it>c </it>varies for blood from 2.42 to 3 depending on the constraint and the fluid properties. For the Newtonian model, the surface constraint leads to <it>c </it>= 2.5. The cost function (based on the surface constraint) can be related to entropy generation, by dividing it by the temperature.</p> <p>Conclusion</p> <p>It is demonstrated that the entropy generated in all the daughter vessels is greater than the entropy generated in the parent vessel. Furthermore, it is shown that the difference of entropy generation between the parent and daughter vessels is smaller for a non-Newtonian fluid than for a Newtonian fluid.</p

An analytical approach for prediction of elastohydrodynamic friction with inlet shear heating and starvation

An analytical friction model is presented, predicting the coefficient of friction in elastohydrodynamic (EHD) contacts. Three fully formulated SAE 75W-90 axle lubricants are examined. The effect of inlet shear heating (ISH) and starvation is accounted for in the developed friction model. The film thickness and the predicted friction are compared with experimental measurements obtained through optical interferometry and use of a mini traction machine. The results indicate the significant contribution of ISH and starvation on both the film thickness and coefficient of friction. A strong interaction between those two phenomena is also demonstrated, along with their individual and combined contribution on the EHD friction

Variation in RNA Virus Mutation Rates across Host Cells

It is well established that RNA viruses exhibit higher rates of spontaneous mutation than DNA viruses and microorganisms. However, their mutation rates vary amply, from 10−6 to 10−4 substitutions per nucleotide per round of copying (s/n/r) and the causes of this variability remain poorly understood. In addition to differences in intrinsic fidelity or error correction capability, viral mutation rates may be dependent on host factors. Here, we assessed the effect of the cellular environment on the rate of spontaneous mutation of the vesicular stomatitis virus (VSV), which has a broad host range and cell tropism. Luria-Delbrück fluctuation tests and sequencing showed that VSV mutated similarly in baby hamster kidney, murine embryonic fibroblasts, colon cancer, and neuroblastoma cells (approx. 10−5 s/n/r). Cell immortalization through p53 inactivation and oxygen levels (1–21%) did not have a significant impact on viral replication fidelity. This shows that previously published mutation rates can be considered reliable despite being based on a narrow and artificial set of laboratory conditions. Interestingly, we also found that VSV mutated approximately four times more slowly in various insect cells compared with mammalian cells. This may contribute to explaining the relatively slow evolution of VSV and other arthropod-borne viruses in nature

Screening out irrelevant cell-based models of disease

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates