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Shaped film cooling holes are used extensively in gas turbines to reduce component temperatures. These holes generally consist of a metering section through the material and a diffuser to spread coolant over the surface. These two hole features are created separately using electrical discharge machining, and occasionally an offset can occur between the meter and diffuser due to misalignment. The current study examines the potential impact of this manufacturing defect to the film cooling effectiveness for a well-characterized shaped hole known as the 7-7-7 hole. Five meter-diffuser offset directions and two offset sizes were examined, both computationally and experimentally. Adiabatic effectiveness measurements were obtained at a density ratio of 1.2 and blowing ratios ranging from 0.5 to 3. The detriment in cooling relative to the baseline 7-7-7 hole was worst when the diffuser was shifted upstream (aft meter-diffuser offset), and least when the diffuser was shifted downstream (fore meter-diffuser offset). At some blowing ratios and offset sizes, the fore meter-diffuser offset resulted in slightly higher adiabatic effectiveness than the baseline hole, due to a reduction in the high-momentum region of the coolant jet caused by a separation region created inside the hole by the fore meter-diffuser offset. Steady RANS predictions did not accurately capture the levels of adiabatic effectiveness or the trend in the offsets, but it did predict the fore offset’s improved performance.Copyright © 2016 by ASME

Turbine vanes and blades are generally manufactured as single or double airfoil sections that must each be installed onto a turbine disk. Between each section, a gap at the endwalls through the blade passage is present, through which high pressure coolant is leaked. Furthermore, sections can become misaligned due to thermal expansion or centrifugal forces. Flow and heat transfer around the gap is complicated due to the interaction of the mainstream and the leakage flow. An experimental and computational study was undertaken to determine the physics of the leakage flow interaction for a realistic turbine blade endwall, and assess whether steady RANS CFD, commonly used for non-axisymmetric endwall design, can be used to accurately model this interaction. Computational models were compared against experimental observations of endwall heat transfer on a contoured endwall with a midpassage gap. Endwall heat transfer coefficients were determined experimentally by using infrared thermography to capture spatially-resolved surface temperatures on a uniform heat flux surface (heater) attached to the endwall. Predictions and measurements both indicated an increase in endwall heat transfer with increasing gap leakage flow, although the distribution of heat transfer coefficients along the gap was not well captured by CFD. A misalignment of the blade endwall causing a forward-facing step for the near-endwall flow resulted in a large highly turbulent recirculation region downstream of the step and high local heat transfer that was overpredicted by CFD. Conversely, a backward-facing step reduced turbulence and local heat transfer. The misprediction of local heat transfer around the gap is thought to be caused by unsteady interaction of the passage secondary flow and gap leakage flow, which cannot be well-captured by a steady RANS approach.

Film cooling and sprayed thermal barrier coatings (TBCs) protect gas turbine components from the hot combustion gas temperatures. As gas turbine designers pursue higher turbine inlet temperatures, film cooling and thermal barrier coatings are critical in protecting the durability of turbomachinery hardware. One obstacle to the synergy of these technologies is that TBC coatings can block cooling holes when applied to the components, causing a decrease in the film cooling flow area thereby reducing coolant flow for a given pressure ratio. In this study the effect of TBC blockages was simulated on film cooling holes for widely spaced cylindrical and shaped holes. At low blowing ratios for shaped holes the blockages were found to have very little effect on adiabatic effectiveness. At high blowing ratios, the area-averaged effectiveness of shaped and cylindrical holes decreased as much as 75% from blockage. The decrease in area-averaged effectiveness was found to scale best with the effective momentum flux ratio of the jet exiting the film cooling hole for the shaped holes.Copyright © 2014 by ASME

The aim of the study is to determine the bioactivity and effects of PEGylation on the pharmacokinetics in rabbit aqueous humor and plasma of an aptamer directed against TGFbeta2.Pharmacological activity of anti-TGFbeta2 aptamer in rabbit ocular fluid was demonstrated using a mink lung epithelial cell proliferation assay. For pharmacokinetic analyses, concentrations of aptamers in plasma and aqueous humor were determined over time following bilateral subconjunctival administration to Dutch-belted rabbits using a hybridization-based pseudo-enzyme-linked immunosorbent assay (ELISA) assay.Anti-TGFbeta2 aptamer (ARC81) binds to human TGFbeta2 with a K(D) of approximately 5 nM and inhibits the activity of human TGFbeta2 in vitro in a cell-based assay with an IC(50) of approximately 100 nM. ARC81 blocks endogenously derived TGFbeta2 in rabbit aqueous humor in vitro with an IC(50) of approximately 200 nM and an IC(90) of approximately 1 microM. In vivo in rabbit, ARC81 [no polyethylene glycol (PEG)] entered systemic circulation rapidly (t(max) = 1 h in plasma) relative to aptamer conjugates ARC117 (20 kDa PEG) and ARC119 (40 kDa PEG), which showed prolonged residence in the subconjunctival space and aqueous compartment (t(max) = 6 and 12 h, respectively, in plasma). Both 20- and 40-kDa aptamer conjugates reached maximal concentrations (C(max)) in aqueous humor of 23-30 nM and remained at or above 1 nM for as long as 12 h.Pharmacologically active levels of anti-TGFbeta2 aptamers can be sustained in the ocular fluid and local tissue environment over a 12-h period after single administration. Daily subconjunctival administration of PEGylated anti-TGFbeta2 aptamers should allow further pharmacological evaluation of these agents in a rabbit conjunctival scarring model. Perioperative administration, via subconjunctival injection, may prove to be an effective means to deliver therapeutic quantities of TGFbeta2 aptamer conjugates in trabeculectomy procedures.

Aptamers are highly selective nucleic acid-based drugs that are currently being developed for numerous therapeutic indications. Here, we determine plasma pharmacokinetics and tissue distribution in rat of several novel aptamer compositions, including fully 2'-O-methylated oligonucleotides and conjugates bearing high-molecular weight polyethylene glycol (PEG) polymers, cell-permeating peptides, and cholesterol.Levels of aptamer conjugates in biological samples were quantified radiometrically and by a hybridization-based dual probe capture assay with enzyme-linked fluorescent readout. Intact aptamer in urine was detected by capillary gel electrophoresis and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF).Aptamer compositions examined exhibited a wide range of mean residence times in circulation (0.6-16 h) and significant variation in distribution levels among organs and tissues. Among the conjugates tested, in vivo properties of aptamers were altered most profoundly by conjugation with PEG groups. Complexation with a 20 kDa PEG polymer proved nearly as effective as a 40 kDa PEG polymer in preventing renal clearance of aptamers. Conjugation with 20 kDa PEG prolonged aptamer circulatory half-life, while reducing both the extent of aptamer distribution to the kidneys and the rate of urinary elimination. In contrast, the fully 2'-O-Me aptamer composition showed rapid clearance from circulation, and elimination with intact aptamer detectable in urine at 48 h post-administration.We find that conjugation and chemical composition can alter fundamental aspects of aptamer residence in circulation and distribution to tissues. Though the primary effect of PEGylation was on aptamer clearance, the prolonged systemic exposure afforded by presence of the 20 kDa moiety appeared to facilitate distribution of aptamer to tissues, particularly those of highly perfused organs.

Deposition on film-cooled turbine components was studied in an accelerated test facility. The accelerated deposition facility seeds a natural-gas burning combustor with finely-ground coal ash particulate at 1180°C and 180 m/s (M = 0.25). Both cylindrical and shaped holes, with and without TBC coating, were studied over a range of blowing ratios from 0.5 to 4.0. Coolant density ratios were maintained at values from 2.1 to 2.4. Deposition patterns generated with the cylindrical film cooling holes indicated regions of low deposition in the path of the coolant, with heightened deposition between film holes. This distinctive pattern was more accentuated at higher blowing ratios. Optical temperature measurements of the turbine component surface during deposition showed elevated temperatures between coolant paths. This temperature non-uniformity became more accentuated as deposition increased, highlighting a mechanism for deposition growth that has been documented on in-service turbines as well. The shaped-hole components exhibited little or no deposition in the region just downstream of the holes, due to the distributed coolant film. Close cylindrical hole spacing of 2.25d displayed similar behavior to the shaped hole configuration.Copyright © 2008 by ASME

Experiments were conducted to determine the impact of synfuel deposits on film cooling effectiveness and heat transfer. Scaled up models were made of synfuel deposits formed on film-cooled turbine blade coupons exposed to accelerated deposition. Three distinct deposition patterns were modeled: a large deposition pattern (maximum deposit peak≅2 hole diameters) located exclusively upstream of the holes, a large deposition pattern (maximum deposit peak≅1.25 hole diameters) extending downstream between the cooling holes, and a small deposition pattern (maximum deposit peak≅0.75 hole diameter) also extending downstream between the cooling holes. The models featured cylindrical holes inclined at 30 deg to the surface and aligned with the primary flow direction. The spacing of the holes were 3, 3.35, and 4.5 hole diameters, respectively. Flat models with the same film cooling hole geometry and spacing were used for comparison. The models were tested using blowing ratios of 0.5–2 with a turbulent approach boundary layer and 0.5% freestream turbulence. The density ratio was approximately 1.1 and the primary flow Reynolds number at the film cooling row location was 300,000. An infrared camera was used to obtain the film cooling effectiveness from steady state tests and surface convective heat transfer coefficients using transient tests. The model with upstream deposition caused the primary flow to lift off the surface over the roughness peaks and allowed the coolant to stay attached to the model. Increasing the blowing ratio from 0.5 to 2 only expanded the region that the coolant could reach and improved the cooling effectiveness. Though the heat transfer coefficient also increased at high blowing ratios, the net heat flux ratio was still less than unity, indicating film cooling benefit. For the two models with deposition between the cooling holes, the freestream air was forced into the valleys in line with the coolant holes and degraded area-averaged coolant performance at lower blowing ratios. It is concluded that the film cooling effectiveness is highest when deposition is limited to upstream of the cooling holes. When accounting for the insulating effect of the deposits between the film holes, even the panels with deposits downstream of the film holes can yield a net decrease in heat flux for some cases.

Four series of tests were performed in an accelerated deposition test facility to study the independent effects of particle size, gas temperature, and metal temperature on ash deposits from two candidate power turbine synfuels (coal and petcoke). The facility matches the gas temperature and velocity of modern first stage high pressure turbine vanes while accelerating the deposition process. Particle size was found to have a significant effect on capture efficiency with larger particles causing significant thermal barrier coating (TBC) spallation durin ga4h accelerated test. In the second series of tests, particle deposition rate was found to decrease with decreasing gas temperature. The threshold gas temperature for deposition was approximately 960°C. In the third and fourth test series, impingement cooling was applied to the back side of the target coupon to simulate internal vane cooling. Capture efficiency was reduced with increasing mass flow of coolant air; however, at low levels of cooling, the deposits attached more tenaciously to the TBC layer. Postexposure analyses of the third test series (scanning electron microscopy and X-ray spectroscopy) show decreasing TBC damage with increased cooling levels. DOI: 10.1115/1.2903901

Four series of tests were performed in an accelerated deposition test facility to study the independent effects of particle size, gas temperature, and metal temperature on ash deposits from two candidate power turbine synfuels. The facility matches the gas temperature and velocity of modern first stage high pressure turbine vanes while accelerating the deposition process. This is done by matching the net throughput of particulate out of the combustor with that experienced by a modern power turbine. In the first series of tests, four different size particles were studied by seeding a natural-gas combustor with finely-ground coal ash particulate. The entrained ash particles were accelerated to a combustor exit flow Mach number of 0.25 before impinging on a thermal barrier coated (TBC) target coupon at 1183°C. Particle size was found to have a significant effect on capture efficiency with larger particles causing significant TBC spallation during a 4-hour accelerated test. In the second series of tests, different gas temperatures were studied while the facility maintained a constant exit velocity of 170m/s (Mach = 0.23–0.26). Coal ash with a mass mean diameter of 3 μm was used. Particle deposition rate was found to decrease with decreasing gas temperature. The threshold gas temperature for deposition was approximately 960°C. In the third and fourth test series impingement cooling was applied to the backside of the target coupon to simulate internal vane cooling. Ground coal and petcoke ash particulates were used for the two tests respectively. Capture efficiency was reduced with increasing massflow of coolant air, however at low levels of cooling the deposits attached more tenaciously to the TBC layer. Post exposure analyses of the third test series (scanning electron microscopy and x-ray spectroscopy) show decreasing TBC damage with increased cooling levels. Implications for the power generation goal of fuel flexibility are discussed.Copyright © 2007 by ASME

OPO performance in 2-micron-pumped OPGaAs samples grown on different templates was found to be comparable, but exhibited significant variation within and between samples. Measured signal and idler wavelength values agreed closely with theory.

Aptamers are short oligonucleotides that fold into well-defined three-dimensional architectures thereby enabling specific binding to molecular targets such as proteins. To be successful as a novel therapeutic modality, it is important for aptamers to not only bind their targets with high specificity and affinity, but also to exhibit favorable properties with respect to in vivo stability, cost-effective synthesis, and tolerability (i.e., safety). We describe methods for generating aptamers comprising 2 - deoxy purines and 2 -O-methyl pyrimidines (dRmY) that broadly satisfy many of these additional constraints. Conditions under which dRmY transcripts can be efficiently synthesized using mutant T7 RNA polymerases have been identified and used to generate large libraries from which dRmY aptamers to multiple target proteins, including interleukin (IL)-23 and thrombin, have been successfully discovered using the SELEX process. dRmY aptamers are shown to be highly nuclease-resistant, long-lived in vivo, efficiently synthesized, and capable of binding protein targets in a manner that inhibits their biologic activity with K(D) values in the low nM range. We believe that dRmY aptamers have considerable potential as a new class of therapeutic aptamers.

Here, we examine biodistribution of radiolabeled aptamers and assess the relative ability of different stabilized aptamer compositions (mixed 2'-F/2'-O-Me; fully 2'-O-Me modified) to access inflamed tissues in a murine inflammation model. Biodistribution of 3H-labeled aptamers, including pegylated and unpegylated compositions, was assessed 3 hours postadministration using quantitative whole body autoradiography (QWBA). Aptamer penetration of cells in kidney and liver was also examined at a qualitative level by microautoradiography. To evaluate aptamer distribution to diseased tissues, inflammation was induced locally in animal hind limbs by treatment with carrageenan just prior to aptamer dosing. Aptamer compositions examined exhibited significant variation in distribution levels among organs and tissues. Highest concentrations of radioactivity in whole body tissues for all animals were observed in the kidney and urinary bladder contents. Relatively little radioactivity was associated with brain, spinal cord, and adipose tissue. Overall, the total level of radioactivity in whole body tissues was significantly higher for a 20-kDa PEG conjugate than for other aptamers. Comparatively high levels of the 20-kDa conjugate were seen in well-perfused organs and tissues, including liver, lungs, spleen, bone marrow, and myocardium. A fully 2'-O-Me composition aptamer had the lowest level of radioactivity in whole body tissues but distributed to higher concentrations in the gastrointestinal tract contents relative to other aptamers. Interestingly, the 20-kDa PEG-conjugated aptamer showed significantly higher levels of distribution to inflamed paw tissues than did either unconjugated or fully 2'-O-Me-modified aptamers.

Aptamers (protein binding oligonucleotides) have potential as a new class of targeted therapeutics. For applications requiring chronic systemic administration, aptamers must achieve high-affinity target binding while simultaneously retaining high in vivo stability, tolerability, and ease of chemical synthesis. To this end, we describe a method for generating aptamers composed entirely of 2'-O-methyl nucleotides (mRmY). We present conditions under which 2'-O-methyl transcripts can be generated directly and use these conditions to select a fully 2'-O-methyl aptamer from a library of 3 x 10(15) unique 2'-O-methyl transcripts. This aptamer, ARC245, is 23 nucleotides in length, binds to vascular endothelial growth factor (VEGF) with a Kd of 2 nM, and inhibits VEGF activity in cellular assays. Notably, ARC245 is so stable that degradation cannot be detected after 96 hr in plasma at 37 degrees C or after autoclaving at 125 degrees C. We believe ARC245 has considerable potential as an antiangiogenesis therapeutic.

Following coronary artery damage, von Willebrand Factor (vWF) multimers adhere to exposed collagen via the vWF A3 domain. Platelets passing through damaged vessels under the conditions of high shear force associated with stenosed arteries will adhere to the vWF A1 domain via GPIb receptors. This initial platelet binding event triggers the formation of a thrombus that can limit blood flow to the myocardium and produce the symptoms of acute coronary syndrome (ACS). Through in vitro selection (SELEX) and subsequent lead optimization, we have generated a nuclease-resistant DNA aptamer that binds to the vWF A1 domain with high affinity. The anti-vWF aptamer inhibits both botrocetin-induced platelet aggregation of platelet rich plasma and shear force-induced platelet aggregation in citrated whole blood. Continuous intravenous infusion of the aptamer in cynomolgus macaques is able to effectively inhibit thrombus formation induced by electrical injury to the carotid artery. Modest effects on template bleeding are observed with the vWF-specific aptamer relative to anti-GPIIb/IIIa therapy. Based upon these results, this aptamer is an excellent candidate for treatment of ACS.