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Traditional 3D printing based on Digital Light Processing Stereolithography (DLP-SL) is unnecessarily limiting as applied to microfluidic device fabrication, especially for high-resolution features. This limitation is due primarily to inherent tradeoffs between layer thickness, exposure time, material strength, and optical penetration that can be impossible to satisfy for microfluidic features. We introduce a generalized 3D printing process that significantly expands the accessible spatially distributed optical dose parameter space to enable the fabrication of much higher resolution 3D components without increasing the resolution of the 3D printer. Here we demonstrate component miniaturization in conjunction with a high degree of integration, including 15 μm × 15 μm valves and a 2.2 mm × 1.1 mm 10-stage 2-fold serial diluter. These results illustrate our approach’s promise to enable highly functional and compact microfluidic devices for a wide variety of biomolecular applications., The ever-growing need for highly functional, compact, and integrated microfluidic devices often incurs lengthy and expensive manufacturing processes. Here, authors introduce a generalized 3D printing process that enables fast parallel fabrication of miniaturized, high resolution 3D components.

Photoreceptors are light-sensitive cells in the retina converting visual stimuli into electrochemical signals. These signals are evaluated and interpreted in the visual pathway, a process referred to as visual processing. Phosphodiesterase type 5 and 6 (PDE5 and 6) are abundant enzymes in retinal vessels and notably photoreceptors where PDE6 is exclusively present. The effects of the PDE inhibitor sildenafil on the visual system, have been studied using electroretinography and a variety of clinical visual tasks. Here we evaluate effects of sildenafil administration by electrophysiological recordings of flash visual evoked potentials (VEPs) and steady-state visual evoked potentials (SSVEPs) from key regions in the rodent visual pathway. Progressive changes were investigated in female Sprague-Dawley rats at 10 timepoints from 30 min to 28 h after peroral administration of sildenafil (50 mg/kg). Sildenafil caused a significant reduction in the amplitude of VEPs in both visual cortex and superior colliculus, and a significant delay of the VEPs as demonstrated by increased latency of several VEP peaks. Also, sildenafil-treatment significantly reduced the signal-to-noise ratio of SSVEPs. The effects of sildenafil were dependent on the wavelength condition in both assays. Our results support the observation that while PDE6 is a key player in phototransduction, near full inhibition of PDE6 is not enough to abolish the complex process of visual processing. Taken together, VEPs and SSVEPs are effective in demonstrating progressive effects of drug-induced changes in visual processing in rats and as the same paradigms may be applied in humans, representing a promising tool for translational research.

Biomarkers suitable for early diagnosis and monitoring disease progression are the cornerstone of developing disease-modifying treatments for neurodegenerative diseases such as Parkinson’s disease (PD). Besides motor complications, PD is also characterized by deficits in visual processing. Here, we investigate how virally-mediated overexpression of α-synuclein in the substantia nigra pars compacta impacts visual processing in a well-established rodent model of PD. After a unilateral injection of vector, human α-synuclein was detected in the striatum and superior colliculus (SC). In parallel, there was a significant delay in the latency of the transient VEPs from the affected side of the SC in late stages of the disease. Inhibition of leucine-rich repeat kinase using PFE360 failed to rescue the VEP delay and instead increased the latency of the VEP waveform. A support vector machine classifier accurately classified rats according to their `disease state’ using frequency-domain data from steady-state visual evoked potentials (SSVEP). Overall, these findings indicate that the latency of the rodent VEP is sensitive to changes mediated by the increased expression of α-synuclein and especially when full overexpression is obtained, whereas the SSVEP facilitated detection of α-synuclein across reflects all stages of PD model progression.

We report a non-cytotoxic resin compatible with and designed for use in custom high-resolution 3D printers that follow the design approach described in Gong et al., Lab Chip 17, 2899 (2017). The non-cytotoxic resin is based on a poly(ethylene glycol) diacrylate (PEGDA) monomer with avobenzone as the UV absorber instead of 2-nitrophenyl phenyl sulfide (NPS). Both NPS-PEGDA and avobenzone-PEGDA (A-PEGDA) resins were evaluated for cytotoxicity and cell adhesion. We show that NPS-PEGDA can be made effectively non-cytotoxic with a post-print 12-hour ethanol wash, and that A-PEGDA, as-printed, is effectively non-cytotoxic. 3D prints made with either resin do not support strong cell adhesion in their as-printed state; however, cell adhesion increases dramatically with a short plasma treatment. Using A-PEGDA, we demonstrate spheroid formation in ultra-low adhesion 3D printed wells, and cell migration from spheroids on plasma-treated adherent surfaces. Given that A-PEGDA can be 3D printed with high resolution, it has significant promise for a wide variety of cell-based applications using 3D printed microfluidic structures.

BackgroundThe gold standard for symptomatic relief of Parkinson’s disease is L-DOPA. However, long-term treatment often leads to motor complications such as L-DOPA-induced dyskinesia (LID). While amantadine (Gocovri™) is the only approved therapy for dyskinesia in people with Parkinson’s disease on the American market, it is associated with neurological side effects and limited efficacy. Thus, there remains a high unmet need for addressing LID in Parkinson’s disease patients worldwide.ObjectiveThe objective of this study was to evaluate the efficacy, safety and performance compared to approved treatments of the serotonin receptor 1A (5-HT1A) and 5-HT1B/D agonists buspirone and zolmitriptan in the 6-hydroxydopamine unilaterally lesioned rat model for Parkinson’s disease.MethodsThe hemi-parkinsonian 6-OHDA lesioned rats underwent chronic treatment with L-DOPA to induce dyskinesia and were subsequently used for efficacy testing of buspirone, zolmitriptan and comparison with amantadine, measured as abnormal involuntary movement (AIM) scores after L-DOPA challenge. Safety testing was performed in model and naive animals using forelimb adjusting, rotarod and open field tests.Results5-HT1A and 5-HT1B/D agonism effectively reduced AIM scores in a synergistic manner. The drug combination of buspirone and zolmitriptan was safe and did not lead to tolerance development following sub-chronic administration. Head-to-head comparison with amantadine showed superior performance of buspirone and zolmitriptan in the model.ConclusionsThe strong anti-dyskinetic effect found with combined 5-HT1A and 5-HT1B/D agonism renders buspirone and zolmitriptan a potential clinical candidate for LID in Parkinson’s disease.

Parkinson’s disease (PD) is a progressive neurodegenerative disease that is typically diagnosed late in its progression. There is a need for biomarkers suitable for monitoring the disease progression at earlier stages to guide the development of novel neuroprotective therapies. One potential biomarker, α-synuclein, has been found in both the familial cases of PD, as well as the sporadic cases and is considered a key feature of PD. α-synuclein is naturally present in the retina, and it has been suggested that early symptoms of the visual system may be used as a biomarker for PD. Here, we use a viral vector to induce a unilateral expression of human wildtype α-synuclein in rats as a mechanistic model of protein aggregation in PD. We employed functional magnetic resonance imaging (fMRI) to investigate whether adeno-associated virus (AAV) mediated expression of human wildtype α-synuclein alter functional activity in the visual system. 16 rats were injected with either AAV-α-synuclein (n=7) or AAV-null (n=9) in the substantia nigra pars compacta of the left hemisphere. The expression of α-synuclein was validated by a motor assay and post-mortem immunohistochemistry. Five months after the introduction of the AAV-vector, fMRI showed robust blood oxygen level dependent (BOLD) responses to light stimulation in the visual systems of both control and AAV-α-synuclein animals. However, our results demonstrate that the expression of AAV-α-synuclein does not affect functional activation of the visual system. This negative finding suggests that fMRI-based read-outs of visual responses may not be a sensitive biomarker for PD. Significance statement We injected an adeno-associated virus (AAV) vector in rats to induce unilateral expression of human wildtype α-synuclein in the substantia nigra, and in the ipsilateral striatum and superior colliculus (SC). This did not affect functional activation of SC as probed with functional MRI. This negative finding discourages the use of functional brain mapping of visually evoked activity as an indicator of regional expression of human α-synuclein.

Plenoptic particle image velocimetry was used to perform instantaneous three-dimensional velocity measurements in the near wake of a wall-mounted hemispherical roughness element at a Reynolds numbe...

Sumitomo Dainippon Pharma Oncology (f/k/a Tolero Pharmaceuticals), Lehi, UTTNK1 is a poorly understood member of the ACK family of non-receptor tyrosine kinases with a unusual domain arrangement, but no known mechanism of regulation nor conclusive link to disease. We initially identified TNK1 as a mediator of cell survival in a subset of primary patient cancer samples. In an effort to understand how TNK1 is regulated, we discovered a MARK-mediated phosphorylation at S502 near the TNK1 C-terminus that mediates an interaction with 14-3-3. We found that 14-3-3 binding inhibitsTNK1 kinase activity, whereas disruption of this interaction renders TNK1 highly active and capable of driving tumor growth in vivo. In support of this idea, kinase substrate profiling at the proteome level revealed a variety of pro-growth and motility substrates for active TNK1. One unique feature of TNK1 is a ubiquitin-association domain (UBA) on its C-terminus, which sits adjacent to the 14-3-3 binding site. We found that the TNK1 UBA has a high affinity for a variety of poly-ubiquitin linkages—making TNK1the first kinase, to our knowledge, that directly interacts (non-covalently) with ubiquitin. Remarkably, point mutations within the UBA that disrupt ubiquitin binding inhibit TNK1 activation and oncogenic signaling, revealing a unique UBA-centric mechanism of tyrosine kinase regulation, in which TNK1toggles between 14-3-3-bound (inactive) and ubiquitin-bound (active) states. Finally, we used a structure-guided approach to identify novel small molecule TNK1 inhibitors with high potency and selectivity. One such compound, TP-5809, inhibits TNK1 dependent STAT5 phosphorylation in vitro and in vivo in L540, a Hodgkin lymphoma cell line with a TNK1-activating mutation. TP-5809 also potently inhibits the in vitro growth of mutant TNK1-driven pro-B cells and reduces disease burden and prolongs survival in mice with xenografted tumors. Together, our data elucidate the first mechanism of TNK1regulation and identify lead compounds for the development of a TNK1 inhibitor. Citation Format: Tsz-Yin Chan, Christina Egbert, Logan Larsen, Jeremy Tsang, Julia Maxson, Eranga Roshan, Clifford J. Whatcott, Kim Wontak, Gaelle Mercenne, Savannah Free, Adam Siddiqui, Tetyana Forostyan, Ethika Tyagi, Kenneth A. Christensen, David J. Bearss, James Moody, Jeffrey Tyner, Jason M. Foulks, Steven L. Warner, Joshua Lyon Andersen. Elucidation of a unique regulatory mechanism for TNK1 provides potential therapeutic targeting opportunities in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2307.

A turbulent boundary layer developed over a herringbone patterned riblet surface is investigated using stereoscopic particle image velocimetry in the cross-stream plane at$Re_{\unicode[STIX]{x1D70F}}\approx 3900$. The three velocity components resulting from this experiment reveal a pronounced spanwise periodicity in all single-point velocity statistics. Consistent with previous hot-wire studies over similar-type riblets, we observe a weak time-average secondary flow in the form of$\unicode[STIX]{x1D6FF}$-filling streamwise vortices. The observed differences in the surface and secondary flow characteristics, compared to other heterogeneous-roughness studies, may suggest that different mechanisms are responsible for the flow modifications in this case. Observations of instantaneous velocity fields reveal modified and rearranged turbulence structures. The instantaneous snapshots also suggest that the time-average secondary flow may be an artefact arising from superpositions of much stronger instantaneous turbulent events enhanced by the surface texture. In addition, the observed instantaneous secondary motions seem to have promoted a free-stream-engulfing behaviour in the outer layer, which would indicate an increase turbulent/non-turbulent flow mixing. It is overall demonstrated that the presence of large-scale directionality in transitional surface roughness can cause a modification throughout the entire boundary layer, even when the roughness height is 0.5 % of the layer thickness.

Parkinson's disease (PD) is a progressive neurodegenerative disorder for which there is no existing therapeutic approach to delay or stop progression. Genetic, biochemical and pre-clinical studies have provided evidence that leucine-rich-repeat-kinase-2 (LRRK2) kinase is involved in the pathogenesis of PD, and small molecule LRRK2 inhibitors represent a novel potential therapeutic approach. However, potentially adverse target-related effects have been discovered in the lung and kidneys of LRRK2 knock-out (ko) mice and rats. It is unclear if the LRRK2 ko effect in the kidneys and lung is also induced by pharmacological inhibition of the LRRK2 kinase. Here, we show that treatment with the LRRK2 inhibitor PFE-360 in rats induces a morphological kidney phenotype resembling that of the LRRK2 ko rats, whereas no effects were observed in the lung. The PFE-360 treatment induced morphological changes characterised by darkened kidneys and progressive accumulation of hyaline droplets in the renal proximal tubular epithelium. However, no histopathological evidence of renal tubular injury or changes in the blood and urine parameters that would be indicative of kidney toxicity or impaired kidney function were observed after up to 12 weeks of treatment. Morphological changes were detected in the kidney after 2 weeks of treatment and were partially reversible within a 30 day treatment-free period. Our findings suggest that pharmacological LRRK2 inhibition may not have adverse consequences for kidney function.

The existence of meandering superstructures in a turbulent boundary layer overlying irregular roughness is explored with high-frame-rate particle-image velocimetry measurements within the roughness sublayer at moderate Reynolds number. Elongated streamwise fields of view reconstructed from this data using a Taylor’s hypothesis approach revealed spanwise-meandering regions of low-streamwise-momentum fluid that extended several boundary-layer thicknesses in the streamwise direction. Such signatures are consistent with previous observations of superstructures in smooth-wall turbulence. Counter-rotating wall-normal vortex cores were found to reside along the spanwise boundaries of these superstructure patterns, consistent with the spatial characteristics of hairpin vortex packets.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with impaired motor function and several non-motor symptoms, with no available disease modifying treatment. Intracellular accumulation of pathological α-synuclein inclusions is a hallmark of idiopathic PD, whereas, dominant mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with familial PD that is clinically indistinguishable from idiopathic PD., Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with impaired motor function and several non-motor symptoms, with no available disease modifying treatment. Intracellular accumulation of pathological α-synuclein inclusions is a hallmark of idiopathic PD, whereas, dominant mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with familial PD that is clinically indistinguishable from idiopathic PD. Recent evidence supports the hypothesis that an increase in LRRK2 kinase activity is associated with the development of not only familial LRRK2 PD, but also idiopathic PD. Previous reports have shown preclinical effects of LRRK2 modulation on α-synuclein-induced neuropathology. Increased subthalamic nucleus (STN) burst firing in preclinical neurotoxin models and PD patients is hypothesized to be causally involved in the development of the motor deficit in PD. To study a potential pathophysiological relationship between α-synuclein pathology and LRRK2 kinase activity in PD, we investigated the effect of chronic LRRK2 inhibition in an AAV-α-synuclein overexpression rat model. In this study, we report that chronic LRRK2 inhibition using PFE-360 only induced a marginal effect on motor function. In addition, the aberrant STN burst firing and associated neurodegenerative processes induced by α-synuclein overexpression model remained unaffected by chronic LRRK2 inhibition. Our findings do not strongly support LRRK2 inhibition for the treatment of PD. Therefore, the reported beneficial effects of LRRK2 inhibition in similar α-synuclein overexpression rodent models must be considered with prudence and additional studies are warranted in alternative α-synuclein-based models.

Vortex organization in the outer layer of a turbulent boundary layer overlying sparse, hemispherical roughness elements is explored with two-component particle-image velocimetry (PIV) in multiple streamwise–wall-normal measurement planes downstream and between elements. The presence of sparse roughness elements causes a shortening of the streamwise length scale in the near-wall region. These measurements confirm that vortex packets exist in the outer layer of flow over rough walls, but that their organization is altered, and this is interpreted as the underlying cause of the length-scale reduction. In particular, the elements shed vortices which appear to align in the near-wall region, but are distinct from the packets. Further, it is observed that ejection events triggered in the element wakes are more intense compared to the ejection events in smooth wall. We speculate that this may initiate a self-sustaining mechanism leading to the formation of hairpin packets as a much more effective instability comp...

This effort explores the impact of dilute polymer solutions on the turbulence characteristics in a submerged liquid impinging-jet configuration. Turbulent impinging jets are commonly used in technological applications such as drying, scouring, cooling, or heating due to an enhancement in transport characteristics in the impingement region under certain nozzle-to-wall configurations. Previous efforts have identified significant turbulence modifications in the presence of dilute concentrations of polymer in both bounded and unbounded flows, though the former has received considerably more attention. To this end, particle-image velocimetry measurements were taken for an axisymmetric turbulent impinging jet with a nozzle-to-wall distance H/D = 6.8 and nominal Reynolds number of 26,000. Measurements were performed for both plain water and dilute polymer solutions of polyethylene oxide at concentrations of 50 and 100 ppm. The mean and turbulence characteristics of these three flows are contrasted and it is observed that the two polymer solutions modify both the mean and turbulent characteristics of the jet in all three regions of interest (the free-jet, impingement, and wall-jet regions). Of interest, the 50 ppm case yielded a slight suppression of the turbulence in the free-jet region accompanied by a longer axial length of the potential core compared to the case of plain water. In contrast, the 100 ppm case exhibits clear enhancement of the turbulence in the free-jet region and a shortening of the potential core length. The effect of polymer was opposite in the impingement and wall-jet regions wherein the turbulence was slightly suppressed in the 100 ppm case in a manner consistent with the onset of the Toms effect in this wall-bounded region of the flow.

Two- and three-dimensional microvascular networks embedded within a polymer fin were fabricated via direct write assembly to demonstrate cooling potential of vascular polymer structures. Thin fin cooling experiments were carried out utilizing water and polyalphaolefin (PAO) oil-based coolant as the working fluids. The surface temperature of the fin was monitored using an infrared camera and flow distribution within the network was evaluated by microscopic particle image velocimetry. The effective heat transfer coefficient was increased 53-fold at low Reynolds number for water cooling in both 2D and 3D geometries. However, 3D architectures offer more uniform flow distribution and the ability to efficiently adapt to blockages and reroute flow within the network. Microvascular materials are excellent candidates for compact, efficient cooling platforms for a variety of applications and 3D architectures offer unique performance enhancements.

Modifications of fluid flow within microscale flow passages by internal surface roughness is investigated in the laminar, transitional, and turbulent regimes using pressure-drop measurements and instantaneous velocity fields acquired by microscopic particle-image velocimetry (micro-PIV). The microchannel under study is rectangular in cross-section with an aspect ratio of 1:2 (depth: width) and a hydraulic diameter of $$D_{\rm h} =600\,\upmu \hbox{m}.$$ Measurements are first performed under smooth-wall conditions to establish the baseline flow characteristics within the microchannel followed by measurements for two different rough-wall cases [with RMS roughness heights of $$7.51\,\upmu \hbox{m}$$ (0.0125D h) and $$15.1\,\upmu \hbox{m}$$ (0.025D h)]. The roughness patterns under consideration are unique in that they are reminiscent of surface irregularities one might encounter in practical microchannels due to imperfect fabrication methods. The pressure-drop results reveal the onset of transition above $$Re_{\rm cr}=1{,}800$$ for the smooth-wall case, consistent with the onset of transition at the macroscale, along with deviation from laminar behavior at progressively lower Re with increasing roughness. Mean velocity profiles computed from the micro-PIV ensembles at various Re for each surface condition confirm these trends, meaning $$Re_{\rm cr}$$ is a strong function of roughness. The ensembles of velocity fields at each Re and surface condition in the transitional regime are subdivided into fields embodying laminar behavior and fields containing disordered motions. This decomposition reveals a clear hastening of the flow toward a turbulent state due both to the roughness dependence of Re cr and an enhancement in the growth rate of the non-laminar fraction of the flow when the flow is in the early stages of transition. Nevertheless, the range of Re relative to Re cr over which the flow transitions from a laminar to a turbulent state is found to be essentially the same for all three surface conditions. From a structural viewpoint, instantaneous velocity fields embodying disordered behavior in the transitional regime are found to contain large-scale motions consistent with hairpin-vortex packets irrespective of surface condition. These observations are in accordance with the characteristics of transitional and turbulent flows at the macroscale and therefore indicate that the overall structural paradigm of the flow is relatively insensitive to roughness. From a quantitative viewpoint, however, the intensity of both the velocity fluctuations and structural activity appear to increase substantially with increasing roughness, particularly in the latter stages of transition. These differences are further supported by the trends of single-point statistics of the non-laminar ensembles and quadrant analysis in which an intensification of the velocity fluctuations by surface roughness is noted in the region close to the wall, particularly for the wall-normal fluctuations.

Low-order representations of surface roughness replicated from a turbine blade damaged by spallation (denoted as "full surface") are devised using singular value decomposition, and the impact of these low-order surface models is assessed in turbulent channel flow. The intent of this effort is to determine the level of topographical detail of the full surface that is required to reproduce the statistical character of turbulent flow over the full surface. Particle-image velocimetry measurements of flow at a fixed Reynolds number over a smooth surface, the full surface, and four low-order representations of the full surface reveal that a surface model based on the first 20 basis functions of the decomposition (9 % of the total number of modes) yields an accurate reproduction of the statistics of flow over the full surface. In particular, the mean velocity profile, profiles of the Reynolds normal and shear stresses, and even the instantaneous turbulent events that contribute heavily to the generation of turbulent shear stress as assessed via quadrant analysis show consistency for flow over this low-order model as well as the full surface. Because the low-order modes included in these models reflect only the large-scale topographical features of the full surface (meaning finer-scale topographical details are excluded), these observations indicate that the larger-scale features of the full surface predominantly dictate its impact on the flow.

Objectives Minimal hepatic encephalopathy (MHE), the preclinical stage of overt hepatic encephalopathy (OHE), is a significant condition affecting up to 60% of cirrhotics. All MHE therapies modify gut microflora, but consensus regarding MHE treatment and long-term adherence studies is lacking. The aim was to determine the effect of probiotic supplementation in the form of a food item, probiotic yogurt, on MHE reversal and adherence. Methods Nonalcoholic MHE cirrhotics (defined by a standard psychometric battery) were randomized with unblinded allocation to receive probiotic yogurt (with proven culture stability) or no treatment (no Rx) for 60 days in a 2:1 ratio. Quality of life (short form [SF]-36), adherence, venous ammonia, model of end-stage liver disease (MELD) scores, and inflammatory markers (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6) were also measured. Outcomes were MHE reversal using blinded scoring, OHE development, and adherence. Results Twenty-five patients (17 yogurt, 8 no Rx; 84% Child class A) were enrolled. A significantly higher percentage of yogurt patients reversed MHE compared to no Rx patients (71%vs 0%, P= 0.003, intention-to-treat). Yogurt patients demonstrated a significant improvement in number connection test-A (NCT-A), block design test (BDT), and digit symbol test (DST) compared to baseline/no Rx group. Twenty-five percent of no Rx versus 0% of yogurt patients developed OHE during the trial. Eighty-eight percent of yogurt patients were adherent. No adverse effects or change in covariates were observed. All patients who completed the yogurt arm were agreeable to continue yogurt for 6 months if needed. Conclusions This trial demonstrated a significant rate of MHE reversal and excellent adherence in cirrhotics after probiotic yogurt supplementation with potential for long-term adherence.

DOI: 10.2514/1.22357 Particle-image velocimetry experiments are performed to study the response of smooth-wall turbulent channel flow to a short fetch of roughness (10 outer length scales long). The roughness studied herein is replicated from a surface scan of a damaged turbine blade and contains both large- and small-scale surface defects attributable to pitting, deposition, and spallation. Quadrant analysis is used to investigate the characteristics of Reynolds-stressproducing events within the internal layer that develops over the roughness. The mean Reynolds stress is dramatically increased in the presence of the roughness as compared to the smooth-wall baseline owing to an increasednumberofextremelyintenseejectionsandsweeps.Incontrast,inwardandoutwardinteractions,aswellas relativelyweakejectionandsweepevents,arefoundtobeinsensitivetothesurfaceconditions.Whilestressandspace fractions are found to be insensitive to the surface topology when all Reynolds-stress-producing events are included, stressandspacefractionsforonlythemostintenseejectionandsweepeventsvarysignificantlywiththelocalsurface topology. Nomenclature H = hyperbolic hole size h = channel half-height, m I = indicator function k = roughness height, m M = total number of streamwise gridpoints in an ensemble N = space fraction Re� = friction Reynolds number S = stress fraction u = fluctuating streamwise velocity, m=s

The influence of peak-locking errors on turbulence statistics computed from ensembles of PIV data is considered. PIV measurements are made in the streamwise–wall-normal plane of turbulent channel flow. The PIV images are interrogated in three distinct ways, generating ensembles of velocity fields with absolute, moderate, and minimal peak locking. Turbulence statistics computed for all three ensembles of data indicate a general sensitivity to peak locking in the single-point statistics, except for the mean velocity profile. Peak-locking errors propagate into the fluctuations of velocity, rendering single-point statistics inaccurate when severe peak locking is present. Multi-point correlations of both streamwise and wall-normal velocity are also found to be influenced by severe levels of peak locking. The displacement range of the measurement, defined by the PIV time delay, appears to affect the influence of peak-locking errors on turbulence statistics. Smaller displacement ranges, particularly those that produce displacement fluctuations that are less than one pixel in magnitude, yield inaccurate turbulence statistics in the presence of peak locking.

It is shown that the magnitude of Rayleigh microstreaming convective drag on microparticles in water in a 3.2-MHz ultrasonic standing wave can be comparable to the lateral direct radiation force in the nodal plane (DRF 1 ) and can significantly influence the microparticle aggregation. The transducer of a single half-wavelength chamber was excited to give a single particle aggregate. The estimated sound pressure amplitude was 0.5 MPa. Particle image velocimetry (PIV) measurements gave the average microstreaming velocity in the nodal plane as 450 μm.s -1 , which is comparable to the 340- μm.s -1 value calculated from Rayleigh's theory. Movement of 25-μm latex particles was primarily determined by DRF 1 , while that of smaller 1.0 μm, particles was determined by Rayleigh microstreaming. A 15-μm latex particle velocity map, simulated from microstreaming data, the measured velocity map of 25-μm particles, and the cube-dependent relationship between DRF 1 's on particles of different sizes, was in reasonable agreement with a measured velocity map. Further evidence for the importance of microstreaming came from the result that velocities for 1- and 25-μm particles were of similar magnitude, but were opposite in direction.

Acceleration is a fundamental quantity in fluid mechanics because it reflects the sum of all forces (pressure and viscous) present within the flow. However, measurements of acceleration have been difficult to achieve relative to the ease with which fluid velocity can be measured. A particle image accelerometer (PIA) has been developed to measure Eulerian acceleration fields by time-differencing successive measurements of the Eulerian velocity field as measured by particle image velocimetry (PIV). The measurements can also be made in uniformly translating frames. With current video camera technology, it is often not possible to measure the two velocity fields with a time separation sufficiently small enough to permit accurate finite difference approximation of the time derivative. A two-CCD-camera system has been developed to alleviate this limitation. Polarization filtering is utilized to separate the particle images viewed by each camera. The polarization filtering is achieved using cross-polarized light-sheets and a polarization filter just upstream of the imaging optics of the cameras. In this manner, PIV measurements can be achieved easily at time delays several orders of magnitude smaller than the shutter-time of the CCD cameras. The accuracy of the acceleration measurements is determined by numerical finite differencing errors and random noise and bias errors associated with the measurement of velocity. These errors, and methods of compensating for them, are studied.

Nanosecond electroluminescence (EL) spikes observed at the voltage turn-off when multilayer blue DPVBi-based organic light-emitting devices (OLEDs) are excited by rectangular voltage pulses are described. The spikes exceed the cw brightness by up to an order of magnitude. Time-resolved images of the devices demonstrate that the emission from most of the sample surface decays with a single time constant τ 1 = 13 ± 3 ns. This decay is attributed to recombination of charges, which accumulate at the interface of the electron and hole transporting layers, possibly at intrinsic trapping sites. In areas of increased electron injection and EL such as cathode edges and morphological defects, a second slower decay time 20 ns < τ 2 < 1?s is observed, apparently due to release of carriers from localized trap states in the organic/cathode interface. Only marginal variations in τ 1 are found between bright and dim areas of the devices. At a bias of 10 V, the amplitude of the spike is found to peak at a pulse duration of ∼ 20 μs.

We describe a new super-resolution method of particle-image velocimetry (PIV) based on Kalman filtering and χ2-testing. Performance of the “super-resolution KC” method is evaluated by Monte-Carlo simulation and by applying the method to measurements of flow fields recorded in the form of double-pulse/single-frame and single-pulse/double-frame particle images. When the images have good contrast, and depending on the intensity of the velocity gradients present in the flow, the super-resolution KC method is able to extract valid measurements from 80 to 100% of the available image pairs. In these tests, the vector yield is increased by more than five times compared to standard PIV analysis.

The structural characteristics of a jet heated to 425 K and emitted from a raised, circular stack into a 300 K cross-flow were studied via cross-plane stereo particle-image velocimetry measurements at multiple streamwise locations downstream of the stack exit. Similar measurements of an unheated jet at equivalent Reynolds number and similar blowing ratio provided a baseline of comparison for the heated case. Instantaneous velocity fields for the heated and unheated jets were marked by intense, small-scale vortices and only a weak indication of a counter-rotating vortex pair (CVP). Upon filtering by proper orthogonal decomposition (POD) to recover only the large-scale flow features, the imprint of the CVP was clearly discerned in the instantaneous fields. The CVP of the heated jet was stronger as well as larger and advected further into the cross-flow compared to that of the unheated jet. While this large-scale reconstruction by POD embodied 35 % of the turbulent kinetic energy, it was found that these large-scale motions captured a vast majority of the Reynolds shear stress, indicating a predominance of the CVP in this regard.

In this paper we demonstrate FlowPredictor, a novel Continuous Query Processing Framework (CQPF) for continuous query processing of the actual and predicted flow of receptor-based moving objects in a symbolic space covering both indoor and outdoor space. FlowPredictor enables spatiotemporal selection, aggregate, nested, and complex queries to be evaluated using novel algorithms. We illustrate the use of a novel model, called Flow Representation Graph (FRG), in the context of an airport bag handling system using an interactive web interface in FlowPredictor. The web interface allows modelling the FRG as well as definition of continuous spatio-temporal queries. Furthermore, the interface enables the user to manually create readings or start real-time simulations of moving objects in the defined FRG. We conclude by presenting the performance of FlowPredictor under heavy load.

A 11 12 cm−1 bandpass electronically tunable liquid crystal dual-stage Fabry-Perot filter (DFPF) has been developed for use in Raman and fluorescence microscopic imaging. The imaging performance of the filter was demonstrated in the fluorescence and Raman modes. In the fluorescence mode, the filter was shown to give sharpened images using the nearest-neighbors deblurring algorithm. In the Raman imaging mode, background subtraction was shown to be useful for removal of the fluorescence from Raman images. With the use of a 100 × /1.25 objective, no significant decrease in the spatial resolution of the microscope was observed when the DFPF was inserted in the optical system.

Microvascular multinozzle arrays are designed and fabricated for high-throughput printing of functional materials. Ink-flow uniformity within these multigeneration, bifurcating microchannel arrays is characterized by computer modeling and microscopic particle image velocimetry (micro-PIV) measurements. Both single and dual multinozzle printheads are produced to enable rapid printing of multilayered periodic structures over large areas (≈1 m(2)).

The combined impact of irregular surface roughness and moderate favorable-pressuregradient conditions (K 3 3.5◊ 10 7 ) on the structure of a turbulent boundary layer was assessed using stereo particle image velocimetry (PIV) measurements in the wall-normal‐ spanwise plane. The roughness under consideration was replicated from a turbine blade damaged by deposition of foreign materials and contains a broad range of topographical scales. These measurements were compared to measurements of smooth-wall flow under the identical favorable-pressure gradient (FPG) condition to reveal the combined impact of roughness and FPG conditions on the underlying structure of the flow. Instantaneous fields revealed low momentum and high momentum regions (LMRs and HMRs) alternating in the spanwise direction that contribute heavily to the Reynolds shear stress. In the roughwall FPG case, more intense sweeps and ejection events were observed within the LMRs and HMRs compared with the smooth- wall case. Two point correlations were analyzed to explore the average spatial structure of the flow. While two-point correlations of velocity reflected the basic signature that LMRs are bounded by HMRs, and vice-versa, correlations of velocity fields only embodying the largest spatial scales revealed an even higher degree of spanwise coherence in these motions.

This effort explored the impact of topographical scales present within irregular surface roughness on a turbulent boundary layer. Low-order representations of a surface replicated from a turbine blade damaged by deposition of foreign materials were generated using singular value decomposition to decompose the complex topography into a set of basis functions of decreasing importance to the original ("full") surface. The low-order surface models were then formed by truncating the basis functions at the first 5 and 16 modes (containing 71 % and 95% of the full surface content, respectively), so that only the largest-scale topographical features were included. Physical replications of these surfaces were rapid prototyped and particle-image velocimetry was used to measure the flow over these surfaces in the streamwise-wall-normal plane and in a streamwise-spanwise plane deep within the roughness sublayer. A 16-mode model of the full surface faithfully reproduced most of the characteristics of flow over the full surface for both developing and developed flow conditions. However, both models failed to reproduce important details of the Reynolds-shear-stress-producing events within the roughness sublayer. The final report details these observations.

The present efiort employs singular value decomposition to decompose a highlyirregular surface topography replicated from a turbine blade damaged by spallation into topographical modes embodying successively smaller roughness length scales. These modes are then used to develop multiple reduced-order models of the original roughness that, at least in spirit, successively capture the evolution of the surface roughness from initial smaller-scale defects that would likely form just after deployment to the eventual cumulative formation of larger-scale roughness features. Particle-image velocimetry measurements of ∞ow at a friction Reynolds number around 1825 are gathered in turbulent channel ∞ow. The cumulative impact of these reduced-order models on wall turbulence is then assessed by comparing mean velocities, Reynolds normal stresses, and Reynolds shear stresses. It is found that the turbulence statistics of the ∞ow increase in magnitude as larger-scale features are introduced into the surface, leading up to the full, original surface.

Nanosecond electroluminescence (EL) overshoots observed when multilayer blue 4,4′-bis(2,2′-diphenyl vinyl)-1,1′-biphenyl (DPVBi)-based organic light-emitting devices (OLEDs) are excited by rectangular voltage pulses are described. The overshoots occur at the voltage turn-off and exceed the cw brightness by up to an order of magnitude. Time-resolved images of the OLEDs demonstrate that the emission from most of the sample surface decays with a single time constant τ1=13±3 ns. This decay is attributed to recombination of charges which accumulate at the interface of the electron and hole transporting layers, possibly at intrinsic trapping sites. In areas of increased electron injection and EL, such as cathode edges and morphological defects, a second slower decay time 20 ns

The velocity and temperature characteristics of a heated jet emitting from a raised circular stack into a cross∞ow are documented for Tstack=T1 = 1:25, Ustack=U1 = 2 and a blowing ratio, r = [(‰U 2 )stack=(‰U 2 )1] 1=2 , of 1.79. Point-wise temperature measurements with thermocouples are used to reconstruct mean temperature flelds at various locations downstream of the stack while particle image velocimetry (PIV) measurements of instantaneous velocity flelds along the spanwise centerline of the stack are used to assess the ∞ow development in the near-stack region. The temperature of the hot jet core diminishes quickly with downstream distance, most likely because of signiflcant entrainment of cooler ambient ∞uid into the jet core by the turbulent structures that dominate the downstream development of the jet. These results also highlight the dominance of downstream advection of the heated jet by the free-stream with little in∞uence of buoyancy evident in the jet’s downstream development. The mean velocity fleld downstream of the emitted jet is marked by a strong recirculation region due to \blockage" of the free-stream by the vertical jet emitting into the cross ∞ow. In addition, strong turbulence is noted on the downstream side of the heated jet due to the occurrence of intense vortical structures.

The maturation of ∞ow in microscale capillaries from a laminar to a fully-turbulent state is studied via extensive microscopic particle image velocimetry measurements spanning the Reynolds-number range 1900 < Re < 4500. Consistent with transitional wall-bounded ∞ows at the macroscale, transitional capillary ∞ow is found to contain patches of increasinglydisordered motion with increasing Re bounded by nominally laminar ∞ow. The intensity of these disordered motions grows with Re and quadrant analysis supports a gradual maturation of the instantaneous Reynolds-shear-stress-producing events as the ∞ow transitions toward a fully-turbulent state. Proper orthogonal decomposition of the transitional datasets indicates that large-scale structures play a vital role in the transport of both kinetic energy as well as Reynolds shear stress and visualization of these large-scale structures reveals spatial signatures consistent with hairpin vortex packets.

The present effort investigates the effects of practical roughness replicated from a turbine blade damaged by deposition of foreign materials or statistical and structural characteristics of wall turbulence. Two-dimensional particle image velocimetry (PIV) measurements are performed in the streamwise-wall-normal plane of turbulent boundary layers at momentum Reynolds numbers of 8000 and 13000. The surface conditions include a smooth wall and two highly-irregular rough walls. These rough surfaces have the same roughness topography but differ in spatial scaling. The validity of Townsend's wall similarity hypothesis in the presence of practical roughness is assessed and the impact of this roughness on the spatial structure of the flow is investigated. In addition, stereoscopic PIV measurements are made in streamwise-spanwise planes of smooth- and rough-wall turbulent boundary layers both within and at the outer edge of the roughness sublayer. This data is used to explore the impact of dominant topographical features on the near-wall flow as well as the influence of practical roughness on the spatial organization of the flow. Understanding such effects provides a steppingstone toward efficient modeling and control of practical flows in the presence of roughness.

The feasibility of implementing a two-color laser-induced ∞uorescence (LIF) technique to study thermal transport at the microscale is investigated. A temperature-sensitive ∞uorescent dye (Rhodamine B) and a temperature-insensitive ∞uorescent dye (Sulforhodamine101) are used in tandem to determine ∞uid temperature with high accuracy and low noise using a pulsed Nd:YAG laser as an illumination source. While the ∞uorescence intensity of the temperature-sensitive dye is proportional to temperature, it is also biased by variations in the illuminating intensity. Therefore, a second temperature-insensitive dye is required to compensate for such biases. Calibration of the two-color LIF system reveals that the two-dye mixture in ethanol yields a temperature sensitivity of 1.5%/K with volumetric illumination from a Nd:YAG laser. The feasibility of this methodology for conducting temperature measurements is explored by measuring a steady-state temperature gradient generated across a micro∞uidic channel array by two large hot and cold reservoirs. Preliminary measurements reveal that the mean steady-state temperatures in the microchannels are within §0.4 ‐ C of the predicted temperatures. The experimental uncertainties in the measurements are found to range from §0:5 ‐ C to §0:63 ‐ C.

The effects of surface roughness on both transitional and turbulent flows have been studied for decades using primarily highly-idealized (“simulated”) topologies, yet the surface roughness encountered in a wide range of practical flows of interest is often quite complex, hence the moniker “real” (random, stochastic, industrial) roughness. This review highlights the similarities and differences between “real” and “simulated” roughness characterizations. In particular, the appropriateness of the equivalent sandgrain roughness height as a universal standard is critiqued, while the behavior of real and simulated roughness in the transitionally-rough regime is explored. Finally, the possibility of outer-layer similarity for turbulent flow over “real” surfaces is considered. Implications for possible improvements to roughness modeling in CFD are summarized.

Stereoscopic particle image velocimetry measurements are made in two wall-parallel planes{one within and the other at the outer edge of the roughness sublayer{for ∞ow over a rough-wall topology replicated from a turbine blade damaged by deposition of foreign materials. The surface roughness studied herein is highly irregular, contains a broad range of topological scales and is therefore representative of what one might encounter in a variety of technologically-relevant ∞ows of interest. Signiflcant modiflcation of the turbulence within the roughness sublayer (y = 0:065‐ = 1:7k, where k is the characteristic roughness height) is observed at streamwise{spanwise locations that are coincident with dominant topological features, particularly strong enhancement of the wall-normal velocity ∞uctuations, the Reynolds shear stress and the swirling strength (a vortex identifler). These heterogeneities are found to diminish signiflcantly toward the outer edge of the roughness sublayer (y = 0:15‐), with the statistics of the turbulence relaxing toward a relatively homogeneous state in both the streamwise and spanwise directions. Interestingly, the heterogeneities observed within the roughness sublayer are quite localized around dominant topological features, indicating that sustained wakes are not generated downstream of these roughness features.

The design and characterization of a simple and robust hyperspectral Raman line imaging illumination system with the use of a Powell lens is reported. The generated line uniformity is ±5% of total intensity with a laser power density of 12 mW/μm2 at the sample with a 50×/0.8 NA (numerical aperture) objective. Similar results were obtained by using other objectives. Linewidths remained near the diffraction limit for all objectives tested. Significant decreases in image acquisition time are also reported with the use of a Powell lens-illuminated hyperspectral Raman line imaging microscope equipped with an intensified charge-coupled device (CCD) detector. Hyperspectral images (100 × 350 pixels) were acquired in as little as 8 with a corresponding signal-to-noise ratio of 24.

This grant supported the purchase of state-of-the-art particle-image velocimetry (PIV) equipment, necessary modifications to an existing boundary-layer wind tunnel and construction of roughness panels in Support of an AFOSR core grant (FA9550-05-1-0043). The equipment proposed was meant to significantly improve the PIV spatial dynamic range achievable in the Pi's lab as well as broaden the range of Reynolds numbers that could feasibly be studied to meet the goals of the Pi's current and future research efforts with AFOSR. In addition, significant modifications to an existing boundary- layer wind tunnel and construction of various roughness topologies were proposed to enhance the Pi's capabilities to study the influence of highly-irregular surface roughness on the character of wall-bounded turbulence. The PI is also utilizing the new PIV cameras procured with this DURIP funding to advance his development of microscale temperature-measurement methods in support of an AFOSR MURI grant (FA9550-05-1-O346) on which he is a co-PI.

The feasibility of implementing a two-color laser-induced fluorescence (LIF) technique to study thermal transport at the microscale is investigated. A temperature-sensitive fluorescent dye (Rhodamine B) and a temperature-insensitive dye (Nile Red) are used in tandem to determine fluid temperature with high accuracy and low noise using a pulsed Nd: YAG laser as an illumination source. While the fluorescence intensity of the temperature-sensitive dye is proportional to temperature, it can be biased by variations in the illuminating intensity. Therefore, a second, temperature-insensitive dye is required to account for noise associated with variations in illumination intensity. Calibration of the system reveals that the two-color dye mixture in ethanol yields 1.0%/K of temperature sensitivity with volume illumination from the Nd:YAG laser. The feasibility of this methodology is explored by measuring steady-state conduction in a heated micro-reservoir.Copyright © 2006 by ASME

Stereo particle-image velocimetry (PIV) has become a widely-used method for studying complex flows because it allows one to acquire instantaneous, three-component velocity data on a planar domain with high spatial resolution. However, the accuracy of such measurements must be carefully evaluated before stereo PIV data can be faithfully used in the development of sophisticated turbulence models, assessment of appropriate computational boundary conditions, and in the validation of advanced computations. To this end, the accuracy of stereo PIV is assessed directly in an actual turbulent environment: two-dimensional turbulent channel flow. This flow is a challenging test of stereo PIV because the turbulent velocity fluctuations are quite small compared to the mean (typically less than ten percent of the mean velocity) and strong velocity gradients exist in the near-wall region. Measurements are made in the streamwise–wall-normal plane along the channel’s spanwise centerline using both stereoscopic and conventional 2-D PIV. A large ensemble of statistically independent velocity realizations are acquired with each method at a friction Reynolds number Reτ = u*h/ν = 934. Single-point statistics are computed from the experimental data and compared to statistics determined from a direct numerical simulation (DNS) of turbulent channel flow at a nearly-identical friction Reynolds number of 940 [5]. Excellent agreement is found in the outer region of the flow (y/h > 0.15, where h is the half-height of the channel). For y/h < 0.15, both the conventional and stereo PIV results differ from the DNS data. These differences are most-likely a manifestation of errors associated with strong velocity gradients and intense turbulent events present in this region of the flow.

In studies of turbulent boundary layers at high Reynolds number, the term “roughness transition” is generally an implicit reference to the case of a streamwise step-change in roughness length (whether the roughness length is associated with surface fluxes of momentum, temperature, humidity, or some other quantity). This roughness configuration and flow response has received broad attention. Here, in contrast, we consider turbulent wall-bounded flows over transverse roughness transitions using large-eddy simulation. This is accomplished simply by aligning the boundary layer freestream direction parallel to momentum roughness length transitions, instead of perpendicular. In the present cases, the bounding surface is composed of two “high roughness” strips placed between three “low roughness” strips. The influences of two parameters are evaluated: (1) λ, the ratio of the high roughness length to the low roughness length; and (2) Ls, the width of the high roughness strips. In the immediate vicinity of the roughness change, the abrupt wallstress variation induces transverse turbulent mixing which is the source of a δ-scale secondary flow, recently described as a low momentum pathway (LMP) by Mejia-Alvarez et al. [“Structural attributes of turbulent flow over a complex topography,” Coherent Flow Structures at the Earth's Surface (Wiley-Blackwell, 2013), Chap. 3, pp. 25–42] and Mejia-Alvarez and Christensen [“Wall-parallel stereo PIV measurements in the roughness sublayer of turbulent flow overlying highly-irregular roughness,” Phys. Fluids, 25, 115109]. LMPs are spatially stationary and flanked by δ-scale counter-rotating vortices which serve to pump fluid vertically from the wall, ultimately leading to a spanwise variation in the boundary layer depth (for flows over surface roughness with a converging-diverging riblet pattern, spanwise variation of δ was also found in recent experiments by Nugroho et al. [“Large-scale spanwise periodicity in a turbulent boundary layer induced by highly ordered and direction surface roughness,” Int. J. Heat Fluid Flow 41, 90–102 (2013)]. Mean velocity and transverse Reynolds stresses are used to determine the mixing length associated with transverse mixing. In general, we find that variations in Ls and λ have a strong and mild impact on the secondary flow pattern, respectively.

Nanosecond electroluminescence (EL) spikes observed at the voltage turn-off when multilayer blue 4,4'-bis(2,2'diphenyl vinyl) -1,1'-biphenyl (DPVBi)-based organic light-emitting devices (OLED's) are excited by rectangular voltage pulses are described. The spikes exceed the cw brightness by up to an order of magnitude. Time-resolved images of the devices demonstrate that the emission from most of the sample surface decays with a single time constant (tau) 1 equals 13 +/- 3 ns. This decay is attributed to recombination of charges which accumulate at the interface of the electron and hole transporting layers, possibly at intrinsic trapping sites. In areas of increased electron injection and EL such as cathode edges and morphological defects, a second slower decay time 20 ns < (tau) 2 < 1 microsecond is observed, apparently due to release of carriers from localized trap states in the organic/cathode interface. Only marginal variations in (tau) 1 are found between bright and dim areas of the devices. At a bias of 10 V, the amplitude of the spike is found to peak at a pulse duration of approximately 20 microseconds. It is noted that similar OLED's, in which the DPVBi was replaced by tris-(8- hydroxyquinoline Al) (Alq3), did not exhibit such spikes.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.