Microdissected "cuboids" for microfluidic drug testing of intact tissues

As preclinical animal tests often do not accurately predict drug effects later observed in humans, most drugs under development fail to reach the market. Thus there is a critical need for functional drug testing platforms that use human, intact tissues to complement animal studies. To enable future multiplexed delivery of many drugs to one small biopsy, we have developed a multi-well microfluidic platform that selectively treats cuboidal-shaped microdissected tissues or “cuboids” with well-preserved tissue microenvironments. We create large numbers of uniformly-sized cuboids by semi-automated sectioning of tissue with a commercially available tissue chopper. Here we demonstrate the microdissection method on normal mouse liver, which we characterize with quantitative 3D imaging, and on human glioma xenograft tumors, which we evaluate after time in culture for viability and preservation of the microenvironment. The benefits of size uniformity include lower heterogeneity in future biological assays as well as facilitation of their physical manipulation by automation. Our prototype platform consists of a microfluidic circuit whose hydrodynamic traps immobilize the live cuboids in arrays at the bottom of a multi-well plate. Fluid dynamics simulations enabled the rapid evaluation of design alternatives and operational parameters. We demonstrate the proof-of-concept application of model soluble compounds such as dyes (CellTracker, Hoechst) and the cancer drug cisplatin. Upscaling of the microfluidic platform and microdissection method to larger arrays and numbers of cuboids could lead to direct testing of human tissues at high throughput, and thus could have a significant impact on drug discovery and personalized medicine.The National Cancer Institute; Juno Therapeutics; CoMotion at the University of Washington; a Hong Kong Research Grant Council; an International Scholars award from the Consejo Nacional de Ciencia y Tecnología of Mexico; a Department of Defense Prostate Cancer Research Program and the National Science Foundation Graduate Research Fellowship Program.http://pubs.rsc.org/en/Journals/JournalIssues/LChj2022Mechanical and Aeronautical Engineerin

Another look at the two Egyptian pyramid volume ‘formulas’ of 1850 BCE

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Orthogonal dissection into few rectangles

We describe a polynomial time algorithm that takes as input a polygon with axis-parallel sides but irrational vertex coordinates, and outputs a set of as few rectangles as possible into which it can be dissected by axis-parallel cuts and translations. The number of rectangles is the rank of the Dehn invariant of the polygon. The same method can also be used to dissect an axis-parallel polygon into a simple polygon with the minimum possible number of edges. When rotations or reflections are allowed, we can approximate the minimum number of rectangles to within a factor of two.Comment: 18 pages, 8 figures. This version adds results on dissection with rotations and reflection

Contribution of spanwise and cross-span vortices to the lift generation of low-aspect-ratio wings: Insights from force partitioning

This study reports on the vortex-induced lift production mechanisms in low Reynolds number flows over low aspect-ratio rectangular wings. We use a rigorous force partitioning method which allows for the estimation of the pressure-induced aerodynamic loads due to distinct flow features or vortex structures in the flow around the wing. The specific focus of this work is on distinguishing the effect of spanwise and cross-span oriented vortex structures on pressure-induced lift production. We quantify the lift induced on the wing by these different vortices, and also estimate their influence within different regions of the flow-field around the wing and in the wake. By varying the aspect-ratio and angle-of-attack of the wing, we show that for most cases, the spanwise oriented vorticity contributes less to the total lift than cross-span oriented vortices. Furthermore, the spanwise vorticity in the near wake is capable of producing net negative lift on the wing and this is explained by separating and quantifying the influence of vortex cores and regions of strain in the wake. The results demonstrate the utility of the force partitioning method for dissecting the flow physics of vortex dominated flows

Pathways to folding, nucleation events and native geometry

We perform extensive Monte Carlo simulations of a lattice model and the Go potential to investigate the existence of folding pathways at the level of contact cluster formation for two native structures with markedly different geometries. Our analysis of folding pathways revealed a common underlying folding mechanism, based on nucleation phenomena, for both protein models. However, folding to the more complex geometry (i.e. that with more non-local contacts) is driven by a folding nucleus whose geometric traits more closely resemble those of the native fold. For this geometry folding is clearly a more cooperative process.Comment: Accepted in J. Chem. Phy

Spinning of Endless Bioactive Silicate Glass Fibres for Fibre Reinforcement Applications

Bioactive glasses have been used for many years in the human body as bone substitute. Since bioactive glasses are not readily available in the form of endless thin fibres with diameters below 20 µm, their use is limited to mainly non-load-bearing applications in the form of particles or granules. In this study, the spinnability of four bioactive silicate glasses was evaluated in terms of crystallisation behaviour, characteristic processing temperatures and viscosity determined by thermal analysis. The glass melts were drawn into fibres and their mechanical strength was measured by single fibre tensile tests before and after the surface treatment with different silanes. The degradation of the bioactive glasses was observed in simulated body fluid and pure water by recording the changes of the pH value and the ion concentration by inductively coupled plasma optical emission spectrometry; further, the glass degradation process was monitored by scanning electron microscopy. Additionally, first in vitro experiments using murine pre-osteoblast cell line MC3T3E1 were carried out in order to evaluate the interaction with the glass fibre surface. The results achieved in this work show up the potential of the manufacturing of endless bioactive glass fibres with appropriate mechanical strength to be applied as reinforcing fibres in new innovative medical implants