Turbulent Flow Promotes Cleavage of VWF (von Willebrand Factor) by ADAMTS13 (A Disintegrin and Metalloproteinase With a Thrombospondin Type-1 Motif, Member 13).

Objective- Acquired von Willebrand syndrome is defined by excessive cleavage of the VWF (von Willebrand Factor) and is associated with impaired primary hemostasis and severe bleeding. It often develops when blood is exposed to nonphysiological flow such as in aortic stenosis or mechanical circulatory support. We evaluated the role of laminar, transitional, and turbulent flow on VWF cleavage and the effects on VWF function. Approach and Results- We used a vane rheometer to generate laminar, transitional, and turbulent flow and evaluate the effect of each on VWF cleavage in the presence of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type-1 motif, member 13). We performed functional assays to evaluate the effect of these flows on VWF structure and function. Computational fluid dynamics was used to estimate the flow fields and forces within the vane rheometer under each flow condition. Turbulent flow is required for excessive cleavage of VWF in an ADAMTS13-dependent manner. The assay was repeated with whole blood, and the turbulent flow had the same effect. Our computational fluid dynamics results show that under turbulent conditions, the Kolmogorov scale approaches the size of VWF. Finally, cleavage of VWF in this study has functional consequences under flow as the resulting VWF has decreased ability to bind platelets and collagen. Conclusions- Turbulent flow mediates VWF cleavage in the presence of ADAMTS13, decreasing the ability of VWF to sustain platelet adhesion. These findings impact the design of mechanical circulatory support devices and are relevant to pathological environments where turbulence is added to circulation.

Assessing pretreatment reactor scaling through empirical analysis.

BACKGROUND: Pretreatment is a critical step in the biochemical conversion of lignocellulosic biomass to fuels and chemicals. Due to the complexity of the physicochemical transformations involved, predictively scaling up technology from bench- to pilot-scale is difficult. This study examines how pretreatment effectiveness under nominally similar reaction conditions is influenced by pretreatment reactor design and scale using four different pretreatment reaction systems ranging from a 3 g batch reactor to a 10 dry-ton/days continuous reactor. The reactor systems examined were an automated solvent extractor (ASE), steam explosion reactor (SER), ZipperClave®Reactor (ZCR), and large continuous horizontal screw reactor (LHR). To our knowledge, this is the first such study performed on pretreatment reactors across a range of reaction conditions and at different reactor scales. RESULTS: The comparative pretreatment performance results obtained for each reactor system were used to develop response surface models for total xylose yield after pretreatment and total sugar yield after pretreatment followed by enzymatic hydrolysis. Near- and very-near-optimal regions were defined as the set of conditions that the model identified as producing yields within one and two standard deviations of the optimum yield. Optimal conditions identified in the smallest scale system (the ASE) were within the near-optimal region of the largest scale reactor system evaluated. The maximum total sugar yields for the ASE and LHR were [Formula: see text], while [Formula: see text] was the optimum observed in the ZipperClave. CONCLUSIONS: The optimum condition identified using the automated and less costly to operate ASE system was within the very-near-optimal space for the total xylose yield of both the ZCR and the LHR, and was within the near-optimal space for total sugar yield for the LHR. This indicates that the ASE is a good tool for cost effectively finding near-optimal conditions for operating pilot-scale systems. Additionally, using a severity factor approach to optimization was found to be inadequate compared to a multivariate optimization method. Finally, the ASE and the LHR were able to enable significantly higher total sugar yields after enzymatic hydrolysis relative to the ZCR, despite having similar optimal conditions and total xylose yields. This underscores the importance of mechanical disruption during pretreatment to improvement of enzymatic digestibility.

Shear-induced structures and thickening in fumed silica slurries.

Chemical mechanical polishing (CMP) is an essential technology used in the semiconductor industry to polish and planarize a variety of materials for the fabrication of microelectronic devices (e.g., computer chips). During the high shear (~1,000,000 s(-1)) CMP process, it is hypothesized that individual slurry particles are driven together to form large agglomerates (≥0.5 µm), triggering a shear thickening effect. These shear-induced agglomerates are believed to cause defects during polishing. In this study, we examined the shear thickening of a 25 wt % fumed silica slurry with 0.17 M added KCl using in situ small-angle light scattering during rheological characterization (rheo-SALS). The salt-adjusted slurry displays a ~3-fold increase in viscosity at a critical shear rate of 20,000 s(-1) during a stepped shear rate ramp from 100 to 25,000 s(-1). As the shear rate is reduced back to 100 s(-1), the slurry displays irreversible thickening behavior with a final viscosity that is 100-times greater than the initial viscosity. Corresponding rheo-SALS images indicate the formation of micrometer scale structures (2-3 µm) that directly correlate with the discontinuous and irreversible shear thickening behavior of the fumed silica slurry; these micrometer scale structures are 10-times the nominal particle diameter (~0.2 µm). The scattering patterns from the 25 wt % slurry were corroborated through rheo-SALS examination of 27 and 29 wt % slurries (C(KCl) = 0.1 M). All slurries, regardless of ionic strength and solids loading, display scattering patterns that are directly associated with the observed thickening behavior. Scattering was only observable during and after thickening (i.e., no scattering was detected in the absence of thickening). This work serves as the first in situ observation of micrometer scale structures within the fumed silica CMP slurry while under shear.

Shear thickening of corn starch suspensions: does concentration matter?

Suspensions of corn starch and water are the most common example of a shear thickening system. Investigations into the non-Newtonian flow behavior of corn starch slurries have ranged from simplistic elementary school demonstrations to in-depth rheological examinations that use corn starch to further elucidate the mechanisms that drive shear thickening. Here, we determine how much corn starch is required for the average person to ''walk on water'' (or in this case, run across a pool filled with corn starch and water). Steady shear rate rheological measurements were employed to monitor the thickening of corn starch slurries at concentrations ranging from 0 to 55 wt.% (0-44 vol.%). The steady state shear rate ramp experiments revealed a transition from continuous to discontinuous thickening behavior that exists at 52.5 wt.%. The rheological data was then compared to macro-scopic (~5 gallon) pool experiments, in which thickening behavior was tested by dropping a 2.1 kg rock onto the suspension surface. Impact-induced thickening in the ''rock drop'' study was not observed until the corn starch concentration reached at least 50 wt.%. At 52.5 wt.%, the corn starch slurry displayed true solid-like behavior and the falling rock ''bounced'' as it impacted the surface. The corn starch pool studies were fortified by steady state stress ramps which were extrapolated out to a critical stress value of 67,000 Pa (i.e., the force generated by an 80 kg adult while running). Only the suspensions containing at least 52.5 wt.% (42 vol.%) thickened to high enough viscosities (50-250 Pa s) that could reasonably be believed to support the impact of a man's foot while running. Therefore, we conclude that at least 52.5 wt.% corn starch is required to induce strong enough thickening behavior to safely allow the average person to ''walk on water''.