Lift Response of a Stalled Wing to Pulsatile Disturbances

The transient lift response of a low-Reynolds-number wing subjected to small amplitude pulsatile disturbances is investigated. The wing has a small aspect ratio and a semicircular planform, and it is fully stalled at a 20 deg angle of attack. Microvalve actuators distributed along the leading edge of the wing produce the transient disturbance. It is shown that the lift response to a single pulse increases with increasing actuator supply pressure and that the lift response curves are similar to each other when scaled by the total impulse. Furthermore, for fixed actuator supply pressure, the amplitude and total impulse of the transient lift response curve increases with increasing external flow speed. In this case, the lift response curves are similar when scaled by the dynamic pressure. The lift response to a single pulse can be treated as a filter kernel, and it can be used to predict the lift time history for the arbitrary actuator input signals. The kernel is similar in shape to transient measurements obtained by other investigators on two-dimensional wings and flaps. Comparisons between the model predictions and the experiments using multiple pulse inputs and square-wave modulated input signals at low frequencies are presented

Closed-Loop Control of a Wing in an Unsteady Flow

The lift response of the separated flow over a wing to different actuator input disturbances is used to obtain linear models useful for closed-loop control design. The wing has a small aspect ratio, a semi-circular planform, and is fully stalled at a 20° angle of attack. Individual pulse-like disturbances and step-input disturbances with randomized frequency were inputs to the actuator, and the lift coefficient increments were output signals. The "prediction error method" system identification technique was used to obtain two linear models of the separated flow. A 4th order model reproduced the non-minimum phase behavior of the pulse input, but did not work well for control purposes. The second model identified was limited to first order. The first order model proved to be useful for designing a proportional-integral feedback controller capable of suppressing lift oscillations in unsteady flows. Good suppression of lift oscillations was observed in the experiment after a step change in wind tunnel flow speed occurred. When the control system was tested with a randomized freestream velocity, it reduced the root-mean-square lift oscillation by 50 percent relative to the uncontrolled case

Orientation Distribution of Highly Oriented Type I Collagen Deposited on Flat Samples with Different Geometries

The structural arrangement of type I collagen in vivo is critical for the normal functioning of tissues, such as bone, cornea, tendons and blood vessels. At present, there are no established low-cost techniques for fabricating aligned collagen structures for applications in regenerative medicine. Here, we report on a straightforward approach to fabricate collagen films, with defined orientation distributions of collagen fibrillar aggregates within a matrix of oriented collagen molecules on flat sample surfaces. Langmuir Blodgett (LB) technology was used to deposit thin films of oriented type I collagen onto flat substrates exhibiting various shapes. By varying the shapes of the substrates (e.g. rectangles, squares, circles, parallelograms, and various shaped triangles) as well as their sizes, a systematic study on collagen alignment patterns was conducted. It was found that the orientation and the orientation distribution of collagen along these various shaped substrates is directly depending on the geometry of the substrate and the dipping direction of that sample with respect to the collagen/water subphase. An important factor in tissue engineering is the stability, durability and endurance of the constructed artificial tissue, and thus its functioning in regenerative medicine applications. By testing these criteria we found that the coated films and their alignments were stable for at least three months under different conditions and, moreover, that these films can withstand temperatures of up to 60°C for a short time. Therefore, these constructs may have widespread applicability in the engineering of collagen-rich tissues

Use of an automated, integrated laboratory environment to enable predictive modeling approaches for identifying critical process parameters and controlling key quality attributes

An essential part of ensuring a high quality medicine is being able to reliably control Critical Quality Attributes (CQA’s). In the cell culture process, bioreactor conditions, feeds, cell state are some of the many variables that affect CQA’s. Out of this very large set of possible variables, the small subset of these (i.e., critical process parameters, or CPP’s) that have a large effect on the CQA’s must be identified and understood such that those CPP’s can be controlled to ensure quality product. Here, we demonstrate the use of predictive modeling techniques to supplement experimental bioreactor studies when defining critical process parameters (CPP’s) and generating process control strategies. Using predictive models to relate culture process conditions to CQA’s has the benefit of enabling both: 1) using model predictions to supplement experimental data when determining critical process parameters (CPP’s) and the resulting control strategy, and 2) active control of CQA’s based on model forecasts to achieve finer control of CQA’s. In order to support this predictive forecasting approach for bioreactor process definition and control, Bend Research has developed a new bioreactor laboratory environment that allows us to run the right experiments, take the right data, and determine which measurements are actually important in determining CQA’s, and to generate model predictions based on those data sets. Here we demonstrate the application of this new laboratory paradigm in practice, using galactosylation, an important product quality attribute, as the “CQA” of interest. We show how through using automated, perfusion-type systems identification experiments, combined with automated data-generation and reduction tools, we can generate a prediction of the effect of galactose feeding on product qualit

A Data-Driven Computational Model for Engineered Cardiac Microtissues

Engineered heart tissues (EHTs) present a potential solution to some of the current challenges in the treatment of heart disease; however, the development of mature, adult-like cardiac tissues remains elusive. Mechanical stimuli have been observed to improve whole-tissue function and cardiomyocyte (CM) maturation, although our ability to fully utilize these mechanisms is hampered, in part, by our incomplete understanding of the mechanobiology of EHTs. In this work, we leverage the experimental data produced by a mechanically tunable experimental setup to generate tissue-specific computational models of EHTs. Using imaging and functional data, our modeling pipeline generates models with tissue-specific ECM and myofibril structure, allowing us to estimate CM active stress. We use this experimental and modeling pipeline to study different mechanical environments, where we contrast the force output of the tissue with the computed active stress of CMs. We show that the significant differences in measured experimental forces can largely be explained by the levels of myofibril formation achieved by the CMs in the distinct mechanical environments, with active stress showing more muted variations across conditions. The presented model also enables us to dissect the relative contributions of myofibrils and extracellular matrix to tissue force output, a task difficult to address experimentally. These results highlight the importance of tissue-specific modeling to augment EHT experiments, providing deeper insights into the mechanobiology driving EHT function.Comment: 19 pages, 7 figure

Prevalence of renal impairment and use of nephrotoxic agents among patients with bone metastases from solid tumors in the United States

The renal status of patients with bone metastases secondary to solid tumors and their treatment with nephrotoxic agents is not well characterized. This retrospective study analyzed electronic medical records data from US‐based oncology clinics to identify adult (age ≥18) solid tumor patients with first bone metastasis diagnosis and ≥1 serum creatinine recorded between January 1, 2009 and December 31, 2013. Patients with multiple myeloma, multiple primary tumor types, acute renal failure, and/or end‐stage renal disease were excluded. Using the Chronic Kidney Disease Epidemiology Collaboration formula, we determined the prevalence of renal impairment (RI: single estimated glomerular filtration rate [eGFR] value <60 mL/min per 1.73 m2) and chronic kidney disease (CKD: ≥2 eGFR values <60, at least 90 days apart). We also examined the use of intravenous bisphosphonates (IV BP) and other nephrotoxic agents. Approximately half of the 11,809 patients were female. Breast (34%) and lung (28%) tumors were the most common. At bone metastasis diagnosis, mean age was 67 years and 24% of patients exhibited RI. The 5‐year prevalence was 43% for RI and 71% for CKD among RI patients. Nearly half (46%) of CKD patients received IV BP in the 12 months following their confirming eGFR and 13% of these patients received at least one other nephrotoxic agent during that period. This is the first US‐based study to examine the prevalence of RI among patients with bone metastases from solid tumors. RI is common at bone metastases diagnosis, and a substantial proportion of patients develop RI or CKD as their disease progresses. Whenever possible, treatments that are potentially less damaging for the kidney should be considered for patients with or predisposed to RI.In patients with bone metastases secondary to solid tumors, the 5‐year prevalence was 43% for renal impairment (RI) and 71% for chronic kidney disease among evaluable RI patients. Whenever possible, treatments that are potentially less damaging for the kidney should be considered for patients with or predisposed to RI.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111794/1/cam4403.pd

Direct, biomimetic synthesis of (+)-artemone via a stereoselective, organocatalytic cyclization

We present a four-step synthesis of (+)-artemone from (–)- linalool, featuring iminium organocatalysis of a doubly diastereoselective conjugate addition reaction. The strategy follows a proposed biosynthetic pathway, rapidly generates stereochemical complexity, uses no protecting groups, and minimizes redox manipulations