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Psychische Erkrankungen sind von zunehmender Bedeutung in der deutschen Bevolkerung. Trotzdem ist die Datenlage zur psychotherapeutischen Versorgungssituation im ambulanten Bereich insbesondere auch im Bereich der Richtlinien-Psychotherapie durch Psychologische Psychotherapeuten und Kinder- und Jugendlichenpsychotherapeuten unzureichend. Der Beitrag stellt die Ergebnisse einer fragebogengestutzten Befragung der Mitglieder der Deutschen PsychotherapeutenVereinigung (DPtV) vor, an der 2 497 Psychotherapeuten teilnahmen (Rucklaufquote von 33,3%). Die Datenerhebung erfolgte mittels Selbstangaben der Therapeuten. Schwerpunkte der Befragung lagen auf den Charakteristika des psychotherapeutischen Versorgungsangebots sowie Umfang und Nutzung von Therapiekontingenten und dem soziookonomischen Status der Patienten. In der Auswertung wurden die Ergebnisse der Studie nach demografischen Merkmalen der Therapeuten, ihrer Approbation und spezifischen Ausbildung sowie nach regionalen Kriterien differenziert analysiert. Hierbei wurden sowohl bivariate als auch multivariate Methoden angewendet. Die Ergebnisse der Studie liefern Hinweise auf eine Unterversorgung im Bereich der ambulanten Psychotherapie. Bei den Therapeuten, die aufgrund eines fehlenden zeitnahen Therapieplatzangebots eine Warteliste fuhren, betrug die Wartezeit uber 2,5 Monate. Zusatzlich ist die Situation durch Versorgungsunterschiede zwischen verschiedenen Patientengruppen gekennzeichnet. Die Versorgungssituation mit ambulanter Psychotherapie in weniger dicht besiedelten Regionen ist ungunstiger als in Grosstadten. Im Vergleich der Studienergebnisse mit epidemiologischen Daten ergibt sich auserdem, dass Manner, alte Menschen und Menschen aus niedrigeren sozialen Schichten unterdurchschnittlich an der Versorgung mit ambulanter Psychotherapie partizipieren. Die Untersuchung liefert Hinweise auf Unterversorgung im Bereich der ambulanten Psychotherapie. Zusatzlich lassen sich Versorgungsunterschiede feststellen, sowohl was verschiedene Patientengruppen angeht, als auch unter re­gionalen Aspekten. Ausgehend von diesen Ergebnissen empfiehlt sich eine Evaluation von vorliegenden Hemmschwellen und Masnahmen zu ihrer Uberwindung.

This paper describes a portion of an experimental and computational program (ADLARF), which incorporates, for the first time, measurements of all aspects of the forced response of an airfoil row, i.e., the flow defect, the unsteady pressure loadings, and the vibratory response. The purpose of this portion was to extend the knowledge of the unsteady aerodynamics associated with a low-aspect-ratio transonic fan where the flow defects were generated by inlet distortions. Measurements of screen distortion patterns were obtained with total pressure rakes and casing static pressures. The unsteady pressure loadings on the blade were determined from high response pressure transducers. The resulting blade vibrations were measured with strain gages. The steady flow was analyzed using a three-dimensional Navier–Stokes solver while the unsteady flow was determined with a quasi-three-dimensional linearized Euler solver. Experimental results showed that the distortions had strong vortical, moderate entropic, and weak acoustic parts. The three-dimensional Navier–Stokes analyses showed that the steady flow is predominantly two-dimensional, with radially outward flow existing only in the blade surface boundary layers downstream of shocks and in the aft part of the suction surface. At near resonance conditions, the strain gage data showed blade-to-blade motion variations and thus, linearized unsteady Euler solutions showed poorer agreement with the unsteady loading data than comparisons at off-resonance speeds. Data analysis showed that entropic waves generated unsteady loadings comparable to vortical waves in the blade regions where shocks existed.

Mental-health problems are of increasing importance in the German population. Nonetheless there is a lack of data concerning outpatient psychotherapeutic care, especially with a focus on psychotherapy sessions approved by social health insurances and performed by psychological psychotherapists and paediatric psychotherapists.The study presents the results of a survey among all members of the German Association of Psychotherapists (DPtV) and is based on questionnaires filled in by 2,497 psychotherapists (return rate 33.3%). The assessment is based on the therapists' data without an external validation. Main topics of the survey were characteristics of the supply of psychotherapeutic care, therapeutic time contingents per patient and their utilisation and demographic and socio-economic features of patients. Evaluating the survey, the results were analysed overall and by groups of therapists varying in demographic features, professional qualifications and regional criteria, using bivariate as well as multivariate methods.The study provides evidence indicating an underprovision of outpatient psychotherapeutic care. Psychotherapists who use a waiting list reported average waiting times of more than 2.5 months. Additionally there are differences in psychotherapeutic care between various patient groups. In regions with lower population density we found less provision of psychotherapeutic care compared to regions with higher population density. Taking into account epidemiological data, the study indicates that the participation of men, persons of older age and patients with lower levels of education in psychotherapeutic care is below average.The results suggest a considerable degree of underprovision and inadequate provision of outpatient psychotherapeutic care. With regard to special population groups, further research is necessary to identify utilisation barriers towards psychotherapy.

Purpose The receptors for hepatocyte and vascular endothelial cell growth factors (MET and VEGFR2, respectively) are critical oncogenic mediators in gastric adenocarcinoma. The purpose is to examine the safety and efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR2 receptors, for the treatment of metastatic gastric adenocarcinoma. Patients and Methods Foretinib safety and tolerability, and objective response rate (ORR) were evaluated in patients using intermittent (240 mg/day, for 5 days every 2 weeks) or daily (80 mg/day) dosing schedules. Thirty evaluable patients were required to achieve alpha = 0.10 and beta = 0.2 to test the alternative hypothesis that single-agent foretinib would result in an ORR of ≥25%. Up to 10 additional patients could be enrolled to ensure at least eight with MET amplification. Correlative studies included tumor MET amplification, MET signaling, pharmacokinetics and plasma biomarkers of foretinib activity. Results From March 2007 until October 2009, 74 patients were enrolled; 74% male; median age, 61 years (range, 25–88); 93% had received prior therapy. Best response was stable disease (SD) in 10 (23%) patients receiving intermittent dosing and five (20%) receiving daily dosing; SD duration was 1.9–7.2 months (median 3.2 months). Of 67 patients with tumor samples, 3 had MET amplification, one of whom had SD. Treatment-related adverse events occurred in 91% of patients. Rates of hypertension (35% vs. 15%) and elevated aspartate aminotransferase (23% vs. 8%) were higher with intermittent dosing. In both patients with high baseline tumor phospho-MET (pMET), the pMET:total MET protein ratio decreased with foretinib treatment. Conclusion These results indicate that few gastric carcinomas are driven solely by MET and VEGFR2, and underscore the diverse molecular oncogenesis of this disease. Despite evidence of MET inhibition by foretinib, single-agent foretinib lacked efficacy in unselected patients with metastatic gastric cancer. Trial Registration ClinicalTrials.gov NCT00725712

Metastatic progression of tumors is the major cause of death in patients with triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer. However, since metastasis is a multi-step process, unraveling its complexity is a major challenge. One effective way of tackling this question is to study natural blockers of the metastatic process, metastasis suppressors, and identify the mechanisms by which they regulate metastasis. Raf kinase inhibitory protein (RKIP), a protein that regulates kinase activity, is a suppressor of TNBC metastasis. Although RKIP inhibits the activity of key kinases such as Raf-1, GRK2, NIK/IKK in cultured cells, the kinase targets of RKIP in tumors are not known. To address this question, we used a mass spectrometry approach involving inhibitor-conjugated beads to identify kinases that are down-regulated by RKIP in human TNBC xenograft tumors. Our results identified novel targets of RKIP whose kinase activity is either down-regulated or up-regulated by RKIP. We used bioinformatics analysis to build RKIP-regulated signaling networks based upon RKIP-induced changes in kinase activity and related gene expression. Elucidating RKIP function at a systems level reveals the interplay between key metastatic signaling cascades, particularly in relation to cell migration and invasion, and can potentially identify novel anti-metastatic target combinations in TNBCs. Citation Format: Ali E. Yesilkanal, Casey Frankenberger, Daniel C. Rabe, Gary L. Johnson, Marsha Rosner. Elucidating metastatic signaling networks in TNBC by investigating RKIP-regulated kinome. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1620.

Triple-negative breast cancer (TNBC) patients have the highest risk of recurrence and metastasis. Because they cannot be treated with targeted therapies, and many do not respond to chemotherapy, they represent a clinically underserved group. While physiological inhibitors of metastasis (metastasis suppressors) play key roles in regulating tumor growth, invasion and metastasis, their role in regulating the tumor microenvironment and immune system is unknown. We hypothesized that the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP) regulates stromal cells, which then affect tumor invasiveness. Using species-specific RNAseq we determined that expression of RKIP in tumors markedly reduces the number and metastatic potential of infiltrating TAMs. While TAMs isolated from TNBC xenografts drive in vitro invasion, RKIP+ derived TAMs did not drive invasion and had decreased secretion of pro-metastatic factors including SLPI, OPN, MMP-12, Galectin-3, VEGF-A, VEGF-D, TNFR2, and PGRN. We determined that RKIP regulates TAM recruitment by blocking HMGA2, which activates CCL5 expression. CCL5 rescued pro-metastatic TAM infiltration as well as tumor intravasation. We additionally showed that factors decreased in RKIP-derived TAMs were restored in CCL5-derived TAMs. CCL5 derived TAMs were also able to promote metastasis when co-injected with MDA-MB-231 tumors. These tumor cells demonstrated permanent increases in both growth and invasive potential after co-injection with highly pro-metastatic CCL5 derived TAMs. To determine the clinical utility of these TAM genes we combined their expression with RKIP signaling in the tumor to create a signature that strikingly separates TNBC patients based on outcome. Our results demonstrate for the first time that metastasis suppressors can regulate the microenvironment, regulating invasion through TAMs. Our results also suggest aggressive triple negative breast cancers could be controlled by attacking CCL5 derived TAMs crucial for promoting metastasis. Funded by: GM087630, CA184494, and CA192780 Citation Format: Daniel C. Rabe, Casey Frankenberger, Russell Bainer, Devipriya Sankarasharma, Kiran Chada, Thomas Krausz, Yoav Gilad, Lev Becker, Marsha R. Rosner. Metastasis suppressors regulate the tumor microenvironment by blocking recruitment of prometastatic TAMs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1557.

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR02) of the Conference Proceedings. Citation Format: Daniel C. Rabe, Casey Frankenberger, Russell Bainer, Devipriya Sankarasharma, Kiran Chada, Thomas Krausz, Yoav Gilad, Lev Becker, Marsha Rich Rosner. Metastasis suppressors regulate the tumor microenvironment by blocking recruitment of pro-metastatic tumor-associated macrophages. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A01.

s: AACR Special Conference on Tumor Metastasis; November 30-December 3, 2015; Austin, TX Metastatic progression of tumors is the major cause of death in patients with triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer. However, since metastasis is a multi-step process, unraveling its complexity is a major challenge. One effective way of tackling this question is to study natural blockers of the metastatic process, metastasis suppressors, and identify the mechanisms by which they regulate metastasis. Raf kinase inhibitory protein (RKIP), a protein that regulates kinase activity, is a suppressor of TNBC metastasis. Although RKIP inhibits the activity of key kinases such as Raf-1, GRK2, NIK/IKK in cultured cells, the kinase targets of RKIP in tumors are not known. To address this question, we used a mass spectrometry approach involving inhibitor-conjugated beads to identify kinases that are down-regulated by RKIP in human TNBC xenograft tumors. Our results identified novel targets of RKIP whose kinase activity is either down-regulated or up-regulated by RKIP. We used bioinformatics analysis to build RKIP-regulated signaling networks based upon RKIP-induced changes in kinase activity and related gene expression. Elucidating RKIP function at a systems level reveals the interplay between key metastatic signaling cascades, particularly in relation to cell migration and invasion, and can potentially identify novel anti-metastatic target combinations in TNBCs. Citation Format: Ali E. Yesilkanal, Casey Frankenberger, Daniel C. Rabe, Gary L. Johnson, Marsha R. Rosner. Elucidating metastatic signaling networks in TNBC by investigating RKIP-regulated kinome. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B23.

Triple-negative breast cancer (TNBC) patients have the highest risk of recurrence and metastasis. Because they cannot be treated with targeted therapies, and many do not respond to chemotherapy, they represent a clinically underserved group. While physiological inhibitors of metastasis (metastasis suppressors) play key roles in regulating tumor growth, invasion and metastasis, their role in regulating the tumor microenvironment and immune system is unknown. We hypothesized that the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP) regulates stromal cells, which then affect tumor invasiveness. Using species-specific RNAseq we determined that expression of RKIP in tumors markedly reduces the number and metastatic potential of infiltrating TAMs. While TAMs isolated from TNBC xenografts drive in vitro invasion, RKIP+ derived TAMs did not drive invasion and had decreased secretion of pro-metastatic factors including SLPI, OPN, MMP-12, Galectin-3, VEGF-A, VEGF-D, TNFR2, and PGRN. We determined that RKIP regulates TAM recruitment by blocking HMGA2, which activates CCL5 expression. CCL5 rescued pro-metastatic TAM infiltration as well as tumor intravasation. We additionally showed that factors decreased in RKIP-derived TAMs were restored in CCL5-derived TAMs. CCL5 derived TAMs were also able to promote metastasis when co-injected with MDA-MB-231 tumors. These tumor cells demonstrated permanent increases in both growth and invasive potential after co-injection with highly pro-metastatic CCL5 derived TAMs. To determine the clinical utility of these TAM genes we combined their expression with RKIP signaling in the tumor to create a signature that strikingly separates TNBC patients based on outcome. Our results demonstrate for the first time that metastasis suppressors can regulate the microenvironment, regulating invasion through TAMs. Our results also suggest aggressive triple negative breast cancers could be controlled by attacking CCL5 derived TAMs crucial for promoting metastasis. Citation Format: Daniel C. Rabe, Casey Frankenberger, Russell Bainer, Devipriya Sankarasharma, Kiran Chada, Thomas Krausz, Yoav Gilad, Lev Becker, Marsha Rich Rosner. Metastasis suppressors regulate the tumor microenvironment by blocking recruitment of pro-metastatic tumor-associated macrophages. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr PR02.

Renal or kidney cancer accounts for about 3% of all cancer cases reported each year in the U.S. Molecular signatures that define the cancer, such as the loss of functional VHL, are found in both sporadic and familial cases of cancer. In clear cell renal cancer, the transcription factor HIF-2α has been shown to have a distinct role in tumorigenesis. Our laboratories developed a cell-based screen to identify modulators of HIF-2α. Screening of the NCI's Natural Product Extract Repository resulted in the identification of 10 sponge extracts, from which 12 compounds were isolated. The biological evaluation of these compounds will be discussed including evaluation of HIF-1α vs HIF-2α selectivity and the isolated compounds' effects on mRNA from several pathways regulated by HIF.

Under normal conditions, hepatocyte growth factor (HGF)-induced activation of its cell surface receptor, the Met tyrosine kinase (TK), is tightly regulated by paracrine ligand delivery, ligand activation at the target cell surface, and ligand-activated receptor internalization and degradation. Despite these controls, HGF/Met signaling contributes to oncogenesis and tumor progression in several cancers and promotes aggressive cellular invasiveness that is strongly linked to tumor metastasis.The prevalence of HGF/Met pathway activation in human malignancies has driven rapid growth in cancer drug development programs. The authors review Met structure and function, the basic properties of HGF/Met pathway antagonists now in preclinical and clinical development, as well as the latest clinical trial results.Clinical trials with HGF/Met pathway antagonists show that as a class these agents are well tolerated. Although widespread efficacy was not seen in several completed Phase II studies, promising results have been reported in lung, gastric, prostate and papillary renal cancer patients treated with these agents. The main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment are optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of optimal therapy combinations. The wealth of basic information, analytical reagents, and model systems available concerning HGF/Met oncogenic signaling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective disease control.

Review on HGF (hepatocyte growth factor (hepapoietin A; scatter factor)), with data on DNA, on the protein encoded, and where the gene is implicated.

A new trimethoxycinnamoyl-2-pyrrolidinone alkaloid, named langkamide (I), is isolated along with two known trimethoxycinnamoyl derivatives from roots and stems of the pepper shrub Piper sarmentosum.

The extraction of three active marine soft corals of the order Alcyonacea (Sarcophyton sp., L.

There is an increasing interest in design methods and performance prediction for aircraft engine turbines operating at low Reynolds numbers. In this regime, boundary layer separation may be more likely to occur in the turbine flow passages. For accurate computational fluid dynamics (CFD) predictions of the flow, correct modeling of laminar-turbulent boundary layer transition is essential to capture the details of the flow. To investigate possible improvements in model fidelity, CFD models were created for the flow over two low pressure turbine blade designs. A new three-equation eddy-viscosity type turbulent transitional flow model, originally developed by Walters and Leylek (2004, “A New Model for Boundary Layer Transition Using a Single Point RANS Approach,” ASME J. Turbomach., 126(1), pp. 193–202), was employed for the current Reynolds averaged Navier–Stokes (RANS) CFD calculations. Previous studies demonstrated the ability of this model to accurately predict separation and boundary layer transition characteristics of low Reynolds number flows. The present research tested the capability of CFD with the Walters and Leylek turbulent transitional flow model to predict the boundary layer behavior and performance of two different turbine cascade configurations. Flows over low pressure turbine (LPT) blade airfoils with different blade loading characteristics were simulated over a Reynolds number range of 15,000–100,000 and predictions were compared with experimental cascade results. Part I of this paper discusses the prediction methodology that was developed and its validation using a lightly loaded LPT blade airfoil design. The turbulent transitional flow model sensitivity to turbulent flow parameters was investigated and showed a strong dependence on freestream turbulence intensity with a second-order effect of turbulent length scale. Focusing on the calculation of the total pressure loss coefficients to judge performance, the CFD simulation incorporating Walters and Leylek’s turbulent transitional flow model produced adequate prediction of the Reynolds number performance for the lightly loaded LPT blade cascade geometry. Significant improvements in performance were shown over predictions of conventional RANS turbulence models. Historically, these models cannot adequately predict boundary layer transition.

Considering the paradox of drinking what you drive and driving what you drink, Coors Brewing Company’s conversion of spilt beer into ethanol is interesting and timely because of today’s intensified need for alternate fuels. The decision of investment in a sustainable project was present in 1996 as well as today. It is evident that Coors considered sustainability before it became popular. Their ethanol project allows an examination of several business issues that pertain to finance, accounting, operations management and environmental management students. This case has provided students sufficient information to practice the whole capital budgeting process which includes identifying and forecasting cash flows, applying capital budgeting tools and performing sensitivity and scenario analysis. Finance students will focus on cash flows and the capital budgeting aspect of the case. The potential reduction of waste disposal cost and generation of revenues from ethanol production will also be of interest to cost accounting students who focus on cutting costs in the production process. From a management standpoint, the Coors Brewing Company and Merrick’s ethanol project serves as an example of how a company can make a profit while engaging in environmentally safe projects. This illustrates the coexistence of company performance and ethicality.

There has been a need for improved prediction methods for low pressure turbine (LPT) blades operating at low Reynolds numbers. This is known to occur when LPT blades are subjugated to high altitude operations causing a decrease in the inlet Reynolds number. Boundary layer separation is more likely to be present within the flowfield of the LPT stages due to increase in the region adverse pressure gradients on the blade suction surface. Accurate CFD predictions are needed in order to improve design methods and performance prediction of LPT stages operating at low Reynolds numbers. CFD models were created for the flow over two low pressure turbine blade designs using a new turbulent transitional flow model, originally developed by Walters and Leylek (2004, “A New Model for Boundary Layer Transition Using a Single Point RANS Approach,” ASME J. Turbomach., 126(1), pp. 193–202). Part I of this study applied Walters and Leylek’s model to a cascade CFD model of a LPT blade airfoil with a light loading level. Flows were simulated over a Reynolds number range of 15,000–100,000 and predicted the laminar-to-turbulent transitional flow behavior adequately. It showed significant improvement in performance prediction compared to conventional RANS turbulence models. Part II of this paper presents the application of the prediction methodology developed in Part I to both two-dimensional and three-dimensional cascade models of a largely separated LPT blade geometry with a high blade loading level. Comparisons were made with available experimental cascade results on the prediction of the inlet Reynolds number effect on surface static pressure distribution, suction surface boundary layer behavior, and the wake total pressure loss coefficient. The kT-kL-ω transitional flow model accuracy was judged sufficient for an understanding of the flow behavior within the flow passage, and can identify when and where a separation event occurs. This model will provide the performance prediction needed for modeling of low Reynolds number effects on more complex geometries.

The outcomes of binary collisions of water droplets are investigated experimentally for the range of parameters of a spray system used during a severe nuclear reactor accident. Droplets diameters range from 220 to 450 μm with a diameter ratio between 0.5 and 1 and impact velocities between 3 and 10 m s-1. Values of the Weber number based on the small droplet size are between 20 and 280. For droplets with a Weber number up to 120, results in a map of impact parameters versus Weber number show the various regimes, namely, stretching separation, coalescence and reflexive separation. For a higher Weber number, between 120 and 280, the only observed outcomes are the two separation regimes. It is shown that results obtained for unequal droplet sizes match on a single map in terms of the impact parameter and of a new "symmetric" Weber number based on the sum of kinetic energies in the frame of the center of mass and on the sum of surface energies of the two droplets. Ashgriz and Poo ["Coalescence and separation in binary collisions of liquid drops," J. Fluid Mech.221, 183 (1990)] models are in agreement with our results, within experimental error. However, in this map, their representative curves depend on the diameter ratio. Simple formulas independent of the diameter ratio are therefore proposed to describe the transitions between regions representing outcomes of collisions. © 2010 American Institute of Physics.

Under normal conditions, hepatocyte growth factor (HGF)-induced Met tyrosine kinase (TK) activation is tightly regulated by paracrine ligand delivery, ligand activation at the target cell surface, and ligand activated receptor internalisation and degradation. Despite these controls, HGF/Met signalling contributes to oncogenesis and tumour progression in several cancers and promotes aggressive cellular invasiveness that is strongly linked to tumour metastasis. The prevalence of HGF/Met pathway activation in human malignancies has driven rapid growth in cancer drug development programmes. Pathway inhibitors can be divided broadly into biologicals and low molecular weight synthetic TK inhibitors; of these, the latter now outnumber all other inhibitor types. We review here the basic properties of HGF/Met pathway antagonists now in preclinical and clinical development as well as the latest clinical trial results. The main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment include optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of optimal therapy combinations. The wealth of basic information, analytical reagents and model systems available concerning HGF/Met oncogenic signalling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective disease control.

There has been a need for improved flow prediction methods for low pressure turbine (LPT) blades operating at high altitudes with a reduced inlet Reynolds number. These conditions present an increased amount of laminar-to-turbulent transitional flow within the boundary layers on the LPT blade surfaces. Also, boundary layer separation is more likely to occur within the flowfield of the LPT stages due to the lower freestream velocities in the regions of adverse pressure gradients on the suction surfaces. More accurate predictions of aerodynamic losses due to low Reynolds effects are needed for CFD to provide more accurate input to the design process for LPT stages operating at high altitudes. Steady flow CFD simulations of flow in a multistage LPT geometry were completed at nominal and high altitude conditions with the conventional Spalart-Allmaras turbulence model and a recentlydeveloped three-equation eddy-viscosity type transitional flow model. These models were used in combination with a mixing plane model for the simulation of flow through a three stage low pressure turbine. Flow visualizations were completed using surface flow and streamline calculations to help identify vortical structures present within the flowfield. Also, the total pressure loss coefficient was calculated for each blade row. Qualitative comparisons indicate the amount and the location of the flow separation differed significantly depending on the chosen turbulence model. Overall, the high altitude condition had an increased amount of separated flow compared to the nominal altitude condition resulting in an increase in the loss coefficient. The altitude effect on the laminar-to-turbulent transition location was studied using the three-equation model. The model provided a more detailed understanding of the aerodynamic loss mechanisms present in low Reynolds number flows, since it accounted for transitional boundary layer flow effects. Based on the these results, the CFD using the three-equation model has the potential to be a more effective method for turbine flow prediction at low Reynolds numbers compared to conventional RANS turbulence models.

Flow separation with increased losses is known to occur when low pressure turbine (LPT) blades are operated at high altitudes with a reduced inlet Reynolds number. Under these conditions, boundary layer separation is more likely to be present within the flowfield of the LPT stages due to thickening of the boundary layers and an increase in the portion of the airfoil experiencing laminar flow. More accurate CFD predictions are needed in order to improve design methods and performance prediction for LPT stages operating at low Reynolds numbers. Steady flow CFD simulations of multistage LPT flow were completed at nominal and high altitude conditions with the conventional Spalart-Allmaras turbulence model. This model was used in combination with a mixing plane model for the simulation of flow through domains with one or more regions in relative rotational motion. Flow visualizations were completed using surface flow and streamline calculations to help identify vortical structures present within the flowfield. Also, the total pressure loss coefficient was calculated for each blade row. Qualitative comparisons indicate that the simulated high altitude condition had an increase in the amount of separated flow present within the flowfield compared to the nominal altitude condition. This can be attributed to the reduction in the inlet Reynolds number. Initial investigations with a recently-developed three-equation eddy-viscosity type turbulent transitional flow model are also reported. Comparisons of flow predictions for the 1st turbine stage with the two models revealed that large vortices predicted with the Spalart-Allmaras model were not present, and the wake loss coefficient was significantly lower with the three-equation turbulence model. Based on these and previous results, the CFD with the three-equation model is considered to have potential to provide improved prediction of separation and transitional flow in low Reynolds number turbine applications.

The molecular interactions between cancer and stromal cells within the tumor microenvironment enable tumor invasion, intravasation, and metastasis at distant sites. However, the degree to which metastatic breast tumors reprogram stromal cells both locally and at distant mammary tissues is not well understood. To address this question, we used species-specific RNA sequencing in a mouse xenograft model to determine how the metastasis suppressor RKIP influences transcription in tumor and stroma tissues. Here we show that metastatic tumors prime mammary tissue at a distant site in a manner that reflects local stromal responses. In addition, gene expression in metastatic breast tumors is pervasively correlated with gene expression in local stroma of both mouse xenografts and human patients. Changes in local and distant stromal gene expression elicited by metastatic tumors are better predictors of subtype and patient survival than tumor gene expression, supporting the use of stromal-based strategies for the diagnosis and prognosis of breast cancer. One mechanism by which changes at contralateral distal mammary breast occur is through exosomes secreted by tumor cells. These results indicate that tumors prime contralateral mammary tissue in a manner that reflects local stromal changes and predicts metastatic disease. This study has future application to our understanding of contralateral breast cancer. Citation Format: Jiyoung Lee, Russell Bainer, Casey Frankenberger, Daniel Rabe, sadiq Saleh, Morag Park, Gary An, Yoav Gilad, Marsha Rich Rosner. Metastatic breast tumors regulate gene expression at distal mammary sites that predicts patient outcome. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B15.

Foretinib is an oral multi-kinase inhibitor targeting MET, vascular endothelial growth factor receptor (VEGFR)-2, RON, KIT, and AXL kinases. In this Phase 1, open-label, non-randomized study, foretinib was administered once daily at doses of 60 mg, 80 mg, 100 mg, or 120 mg for 28 days. The primary objectives were to determine the maximum tolerated dose (MTD) and assess the safety and tolerability of the daily oral administration schedule. Secondary objectives included pharmacokinetics, pharmacodynamics, and assessment of tumor response. Patients had histologically confirmed metastatic or unresectable solid tumors for which no standard treatments existed and all received oral foretinib once daily. Dose escalation was planned as a conventional "3+3" design with an expansion at the MTD for collection of additional safety and pharmacokinetic information. Thirty-seven patients were treated across four dose levels. The MTD was established as 80 mg foretinib. Dose-limiting toxicities were hypertension, dehydration, and diarrhea. The most common adverse events included fatigue, hypertension, nausea, and diarrhea. Twenty-three of 31 patients (74 %) had a best response of stable disease. No patient had a confirmed partial or complete response. At the MTD, steady state was achieved by approximately 2 weeks, with average post-dose time to maximum concentration, peak concentration, and trough concentration of 4 h, 46 ng/mL, and 24 ng/mL, respectively. In patients treated at the MTD, soluble MET and VEGF-A plasma levels significantly increased (P

Triple-negative breast cancer (TNBC) patients have the highest risk of recurrence and metastasis. Because they cannot be treated with targeted therapies, and many do not respond to chemotherapy, they represent a clinically underserved group. While physiological inhibitors of metastasis (metastasis suppressors) play key roles in regulating tumor growth, invasion and metastasis, their role in regulating the tumor microenvironment and immune system is unknown. We hypothesized that the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP) regulates stromal cells, which then affect tumor invasiveness. Using species-specific RNAseq we determined that expression of RKIP in tumors markedly reduces the number and metastatic potential of infiltrating TAMs. While TAMs isolated from TNBC xenografts drive in vitro invasion, RKIP+ derived TAMs did not drive invasion and had decreased secretion of pro-metastatic factors including SLPI, OPN, MMP-12, Galectin-3, VEGF-A, VEGF-D, TNFR2, and PGRN. We determined that RKIP regulates TAM recruitment by blocking HMGA2, which activates CCL5 expression. CCL5 rescued TAM infiltration as well as tumor intravasation. We additionally showed that factors decreased in RKIP-derived TAMs were restored in CCL5-derived TAMs. Finally, we demonstrated the TAM secreted factor PGRN is both necessary and sufficient for TAM driven invasiveness. To determine the clinical utility of these TAM genes we combined their expression with RKIP signaling in the tumor to create a signature that strikingly separates TNBC patients based on outcome. Our results demonstrate for the first time that metastasis suppressors can regulate the microenvironment, regulating invasion through TAMs. Our results also suggest TNBC patients with decreased RKIP activity and increased TAM infiltration may respond to therapies targeting CCL5 or PGRN. Citation Format: Daniel C. Rabe, Casey Frankenberger, Russell Bainer, Devipriya Sankarasharma, Kiran Chada, Thomas Krausz, Yoav Gilad, Lev Becker, Marsha R. Rosner. Metastasis suppressors regulate the tumor microenvironment by blocking recruitment of pro-metastatic TAMs. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5077. doi:10.1158/1538-7445.AM2015-5077

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with very low survival rates. Metastatic progression of tumors is the major cause of death in TNBC patients. Metastatic spread of tumor cells is generally associated with resistance to therapy and poor prognosis. Therefore, there is a clinical need for understanding the molecular and cellular basis of metastasis and developing effective therapies against metastatic progression. However, since metastasis is a multi-step process, unraveling its complexity is a major challenge. One effective way of tackling this question is to study natural blockers of the metastatic process, metastasis suppressors, and identify the mechanisms by which they regulate metastasis. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor in TNBC, which acts as a homeostatic factor that regulates kinase activity. RKIP blocks invasion in vitro and experimental metastasis in vivo. Therefore, RKIP constitutes a powerful tool for studying metastatic signaling pathways in cancer cells. RKIP is known to regulate the activity of certain kinases such as Raf-1, GRK2, NIK, and GSK3β, affecting major pathways such as MAPK, NFκB, and WNT. However, our preliminary data suggests that RKIP affects a much larger part of the TNBC kinome. Using proteomics approaches, we have identified putative novel kinase targets of RKIP, and used bioinformatics analysis to build RKIP-regulated signaling networks. Elucidating RKIP's function at a systems level will reveal the interplay between key metastatic signaling cascades and potentially identify novel anti-metastatic target combinations in TNBCs. Citation Format: Ali E. Yesilkanal, Casey Frankenberger, Daniel Rabe, Gary L. Johnson, Marsha R. Rosner. Regulation of TNBC kinome by the metastasis suppressor Raf kinase inhibitory protein (RKIP). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3251. doi:10.1158/1538-7445.AM2015-3251

To evaluate the efficacy and tolerance of iodine-131-lipiodol ((131)I-lipiodol) for hepatocellular carcinoma (HCC) in German long term patients and comparison with medically treated controls.38 courses of intra-arterial (131)I-lipiodol therapy with a total activity up to 6.7 GBq were performed in 18 patients with HCC (6 with portal vein thrombosis). Liver and tumour volume and lipiodol deposition were measured by computed tomography and (131)I activity by scintigraphy. Therapeutic efficacy was determined by tumour volume change and matched-pairs analysis in comparison to medically (i.e. tamoxifen or medical support) treated patients.Tumour volume decreased in 20/32 index nodules (63%) after the first course. Repeated therapy frequently resulted in further tumour reduction. Overall response to treatment was partial in 11 nodules, minor response in 4 nodules, and disease was stable in 12 and progressive in 5. Significant response was associated with pretherapeutic nodule volume up to 150 ml (diameter of 6.6 cm). Survival rate after 3, 6, 9, 12, 24 and 36 months was 78, 61, 50, 39, 17, and 6%. Matched-pairs analysis of survival revealed (131)I-lipiodol to be superior to medical treatment. The most important side effect was a pancreatitis-like syndrome whereas overall tolerance was good.The long term results confirm that HCC therapy with (131)I-lipiodol is effective and probably superior to medical treatment. Tumour nodules of up to 6 cm diameter are well suited for this therapy even in the presence of portal vein thrombosis.

To assess characteristics and outcome of emergency patients with acute malaria.We retrospectively assessed the clinical and laboratory parameters of 137 consecutive patients (87 males, 50 females; median age 37 years, range 17 - 67 years) presenting with acute malaria to our tertiary care center between 1992 and 2002.Falciparum malaria was diagnosed in 116/137 and tertian malaria in 19/137 patients; a single patient was infected with both parasites while in another case the type of parasite remained unclear. Infections were acquired in Africa (121), Asia , and in the Americas . One traveler visited multiple continents. Only 36 % (50/137) of patients had used malaria chemoprophylaxis. 128/137 patients were treated as in-patients; 22 of these had to be treated on an intensive care unit. According to the criteria of the German Society of Tropical Medicine, 44/137 (32 %; 95 % confidence interval (CI): 25 - 40 %) patients suffered from complicated malaria. The overall mortality rate was 2/137 (1.5 %; 95 % CI: 0,4 - 5.2 %); the mortality rate of complicated malaria tropica was 2/44 (4,5 %; 95 % CI 1,3 - 15 %). Patients with complicated malaria were significantly older than those with uncomplicated malaria. Median length of hospital stay was 4 days in uncomplicated and 9 days in complicated cases. Based on costs of EUR 2500 per case, an attack rate of3 % in East African travelers and a cost of EUR 55 for a chemoprophylaxis with mefloquine, chemoprophylaxis is cost-effective.In our retrospective analysis, complicated malaria tropica was associated with older age. Although malaria causes considerable morbidity, the overall mortality from severe malaria is low. Reinforcement of chemoprophylaxis especially in travelers to Africa could reduce malaria cases and is cost-effective.

The extraction of depth is a prerequisite for many applications in robotics and driver assistance. Examples are obstacle detection, collision avoidance, and parking. This paper presents a new Kalman filter based depth from motion approach. Thanks to multiple filters running in parallel the rate of convergence is significantly higher than in direct methods, especially if the vehicle drives slowly. A goodness-of-fit test fuses the states of the different filters in an optimum manner. In addition, this test allows to distinguish between static and moving obstacles.

The current paper reports on investigations aimed at advancing the understanding of the flow field near the casing of a forward-swept transonic compressor rotor. The role of tip clearance flow and its interaction with the passage shock on stall inception are analyzed in detail. Steady and unsteady three-dimensional viscous flow calculations are applied to obtain flow fields at various operating conditions. The numerical results are first compared with available measured data. Then, the numerically obtained flow fields are interrogated to identify the roles of flow interactions between the tip clearance flow, the passage shock, and the blade/endwall boundary layers. In addition to the flow field with nominal tip clearance, two more flow fields are analyzed in order to identify the mechanisms of blockage generation: one with zero tip clearance, and one with nominal tip clearance on the forward portion of the blade and zero clearance on the aft portion. The current study shows that the tip clearance vortex does not break down, even when the rotor operates in a stalled condition. Interaction between the shock and the suction surface boundary layer causes the shock, and therefore the tip clearance vortex, to oscillate. However, for the currently investigated transonic compressor rotor, so-called breakdown of the tip clearance vortex does not occur during stall inception. The tip clearance vortex originates near the leading edge tip, but moves downward in the spanwise direction inside the blade passage. A low momentum region develops above the tip clearance vortex from flow originating from the casing boundary layer. The low momentum area builds up immediately downstream of the passage shock and above the core vortex. This area migrates toward the pressure side of the blade passage as the flow rate is decreased. The low momentum area prevents incoming flow from passing through the pressure side of the passage and initiates stall inception. It is well known that inviscid effects dominate tip clearance flow. However, complex viscous flow structures develop inside the casing boundary layer at operating conditions near stall.Copyright © 2004 by ASME

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer. While five-year survival rates have reached 98% in patients treated with anti-ER or anti-HER2 therapies, patients with TNBC have a five-year survival rate of only 24%. Currently, the only form of therapy for these patients is surgery and platinum based chemotherapy. However, patient outcome is generally poor. Additionally, this disease disproportionately affects African-American women and lower income women, with rates seen approximately three times higher in African-American women compared to the rest of the population. An alternative strategy for treating TNBC patients involves targeting the tumor stroma. To better understand interaction between the tumor and stroma necessary for metastasis and invasion, we employed a triple-negative breast cancer (TNBC) model in which the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP) controls primary tumor invasiveness. RKIP expression, which converts invasive tumors to non-invasive tumors, dramatically inhibits macrophage infiltration. The mechanism, which is dependent on Let-7 suppression of HMGA2, involves decreased expression of the chemokine CCL5. Furthermore, overexpression of CCL5 partially rescued the infiltration of macrophages into the tumor and intravasation of tumor cells into the blood stream. The relationships of the genes in the RKIP, HMGA2, CCL5, and macrophage pathways were observed in multiple sets of expression array data from breast cancer patients. Regulation of macrophage infiltration was observed in tumors from an HMGA2 knockout mouse model. These results show that RKIP regulates macrophage recruitment by tumors and demonstrate for the first time that metastasis suppressor genes can regulate the tumor microenvironment. Citation Format: Daniel C. Rabe, Casey A. Frankenberger, Russell Bainer, Devipriya Sankarasharma, Kiran Chada, Thomas Krausz, Yoav Gilad, Marsha Rich Rosner. The role of tumor associated macrophages (TAMs) in triple-negative breast cancer (TNBC) invasion revealed by species-specific RNA sequencing. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B35. doi:10.1158/1538-7445.CHTME14-B35

Cancer progression is critically dependent on specific molecular interactions between tumor cells and their microenvironment, but little is known about the global dynamics of this crosstalk within and across individuals. Here, we used an RNA sequencing approach with species-of-origin information in a xenograft mouse model to computationally resolve and compare tumor versus stromal transcriptional changes. Our study employed a triple-negative breast cancer (TNBC) model in which primary tumor invasiveness is controlled by the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP) allowing systemic observation of stromal response to invasive or noninvasive breast tumours at both proximal and distal sites. Initially, we observed that expression levels of gene homologs in human tumor and mouse stroma are highly synchronized. Surprisingly, the set of genes most prognostic for metastasis-free survival in multiple clinical data sets were those whose mRNA expression was inversely correlated between tumor and stroma. These results were confirmed in an independent set of microarray data from tumor and stroma micro-dissected from primary human breast cancer patient tissue. Additionally, we found broad-based and invasion-specific gene expression changes in stromal tissues far from the primary lesion, with these results being confirmed in an independent set of samples. Of note, genes differentially expressed in the tumor-associated stroma were better classifiers of tumor phenotype than genes differentially expressed in the tumor alone. As well, stromal genes differentially expressed both locally and distally, are significant predictors of patient prognosis. These findings demonstrate the potential for using patient tissue remote from the primary tumor as indicators of disease aggressiveness. Furthermore, these results suggest that stromal gene expression, acting to compensate for changes in the tumor, may have both prognostic and therapeutic implications. Citation Format: Casey A. Frankenberger, Russell O. Bainer, Daniel C. Rabe, Sadiq Saleh, Morag Park, Yoav Gilad, Marsha R. Rosner. Systemic tumor-stroma interactions are prognostic indicators of breast tumor invasiveness. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A43. doi:10.1158/1538-7445.CHTME14-A43

Experimental and numerical investigations were conducted to study the fundamental flow mechanisms of circumferential grooves in the casing of a transonic compressor and their influence on compressor stall margin. Three different groove configurations were tested in a highly loaded transonic compressor. Experimental results show that circumferential grooves increase the stall margin of the compressor at the tested operating condition. Grooves with a much smaller depth than conventional designs are shown to be similarly effective in increasing the stall margin. Steady-state Navier-Stokes analyses were performed to study flow structures associated with each casing treatment. The numerical procedure calculates the overall effects of the circumferential grooves correctly. Detailed investigation of calculated flow fields indicates that losses are generated by interaction between the main passage flow and flow exiting the grooves. The grooves increase the stall margin by reducing the flow incidence angle on the pressure side of the leading edge, despite an overall increase in the endwall boundary layer thickness. This is due to complex interaction of the main passage flow with the additional radial and tangential flows created by the grooves.Copyright © 2002 by ASME

Previous experimental and analytical studies conducted to compare the performance of transonic swept rotors in single stage fans have demonstrated the potential of significant improvements in both efficiency and stall margin with forward swept blading. This paper extends the assessment of the payoff derived from forward sweep with respect to aerodynamic performance and stability to multistage configurations. The experimental investigation compares, on a back-to-back test basis, two builds of an advanced good efficiency, high pressure ratio, two-stage fan configuration tested alternately with a radial and a forward swept stage 1 blade. In the two-stage evaluations, the testing was extended to include the effect on inlet flow distortion. While the common second stage among the two builds prevented the overall fan from showing clean inlet performance and stability benefits with the forward swept rotor 1, this configuration did demonstrate superior front stage efficiency and tolerance to inlet distortion. Having obtained an already low distortion sensitivity with the radial rotor 1 configuration relative to current production military fan standards, the sensitivity to inlet distortion was halved with the forward swept rotor 1 configuration. In the case of the 180-degree one-per-rev distortion pattern, the two-stage configuration was evaluated both with and without inlet guide vanes (IGVs). The presence of the inlet guide vanes had a profound impact in lowering the two stage fan’s sensitivity with inlet distortion.Copyright © 2002 by ASME

A new trimethoxycinnamoyl-2-pyrrolinone alkaloid, langkamide (1), along with the known compounds piplartine (2) and 3,4,5-trimethoxycinnamic acid (3) were isolated from the roots and stems of the shrub Piper sarmentosum Roxb. The structures were established by spectroscopic analyses and comparison of their spectral data with values reported in the literature. The compounds were tested for their ability to modulate hypoxia inducible factor-2 (HIF-2) transcription activity and all three showed HIF-2 inhibitory activity with EC50 values of 14.0, 4.8, and 60.6 μM, respectively, for compounds 1, 2, and 3.

An innovative pressure-measurement technique that employs the tools of molecular spectroscopy has been widely investigated by the aerospace community. Measurements are made via oxygen-sensitive molecules attached to the surface of interest as a coating, or paint. The pressure-sensitive-paint (PSP) technique is now commonly used in stationary wind-tunnel tests; this paper presents the use of this technique in advanced turbomachinery applications. New pressure- and temperature-sensitive paints (P/TSPs) have been developed for application to a state-of-the-art transonic compressor where pressures up to 1.4 atm and surface temperatures to 90°C are expected for the suction surface of the first-stage rotor. PSP and TSP data images have been acquired from the suction surface of the first-stage rotor at 85% of the corrected design speed for the compressor near-stall condition. A comparison to over-the-rotor pressure transducer measurements will be presented.

Blade-to-blade variations in blade resonant frequencies, known as mistuning, and how these variations are related to vibratory stress amplitude and viscous damping variations were investigated for an integrally bladed disk, or blisk. Blade response to an inlet total pressure distortion was measured using dynamic strain gauges with the blisk at operating conditions. In addition, a reduced-order analytical model of the blisk was used to predict the blade resonant stress variations. The measured stress variations were found to be strongly ine uenced by unsteady aerodynamic coupling. Bladestructural mistuning and mechanical coupling through hub motion weredetermined to have only a minor ine uence on blade-to-blade stress variations. Stress distribution patterns at resonance and at constant speeds above and below resonance suggested a relationship between stress variations and unsteady aerodynamics. Tosupportthis,aerodynamicdamping variationsmeasured atresonancewereshown to correspond roughly to stress variations. Experimental results were compared to the predicted variations from the reducedorder model. Results from the model indicated that unsteady aerodynamic coupling played an important role in the mistuned response of the blisk.

The effects of stepped tip gaps and clearance levels on the flowfield of a transonic axial-flow compressor rotor were experimentally and computationally determined. This paper complements a previous experimental study by the authors regarding the effects of stepped tip gaps and clearance levels on the performance of an axial-flow compressor rotor. In the current study, the generation of blockage associated with the variation of geometry in the rotor tip region was examined. The shock-vortex interaction generating the blockage was characterized, and a theory and mechanism for relocation of blockage in the rotor tip region was developed. A two-stage compressor with no inlet guide vanes was tested in a modern transonic compressor research facility. The first-stage rotor was unswept and was tested with stepped gaps machined into the casing near the aft tip region of the rotor. Nine casing geometries were investigated consisting of three step profiles at each of three clearance levels. Computational Fluid Dynamic modeling of tip geometry effects also was performed. Increased tip clearance was found to increase the amount of flow blockage near the rotor tip. Stepped tip gaps were found to be an effective means of reducing the effects of tip region blockage, resulting in improved pressure ratio, efficiency, and mass flow. This study provides guidelines for engineers to improve compressor performance for an existing design by applying an improved casing profile.Copyright © 1998 by ASME

The effects of stepped-tip gaps and clearance levels on the performance of transonic axial-flow compressor rotor were experimentally determined. A two-stage compressor with no inlet guide vanes was tested in a modern transonic compressor research facility. The first-stage rotor was unswept and was tested for an optimum tip clearance with variations in stepped gaps machined into the casing near the aft tip region of the rotor. Nine casing geometries were investigated consisting of three step profiles at each of three clearance levels. For small and intermediate clearances, stepped tip gaps were found to improve pressure ratio, efficiency, and flow range for most operating conditions. At 100 percent design rotor speed, stepped tip gaps produced a doubling of mass flow range with as much as a 2.0 percent increase in mass flow and a 1.5 percent improvement in efficiency. This study provides guidelines for engineers to improve compressor performance for an existing design by applying an optimum casing profile.

This paper describes a portion of an experimental and computational program (ADLARF) which incorporates, for the first time, measurements of all aspects of the forced response of an airfoil row, i.e., the flow defect, the unsteady pressure loadings and the vibratory response. The purpose of this portion was to extend the knowledge of the unsteady aerodynamics associated with a low aspect ratio transonic fan where the flow defects were generated by inlet distortions. Measurements of screen distortion patterns were obtained with total pressure rakes and casing static pressures. The unsteady pressure loadings on the blade were determined from high response pressure transducers. The resulting blade vibrations were measured with strain gages. The steady flow was analyzed using a 3D Navier–Stokes solver while the unsteady flow was determined with a quasi–3D linearized Euler solver. Experimental results showed that the distortions had strong vortical, moderate entropic and weak acoustic parts. The 3D Navier–Stokes analyses showed that the steady flow is predominantly two–dimensional, with radially outward flow existing only in the blade surface boundary layers downstream of shocks and in the aft part of the suction surface. At near resonance conditions, the strain gage data showed blade–to–blade motion variations and thus, linearized unsteady Euler solutions showed poorer agreement with the unsteady loading data than comparisons at off–resonance speeds. Data analysis showed that entropic waves generated unsteady loadings comparable to vortical waves in the blade regions where shocks existed.

Introduction Experimental data and computational predictions are used to characterize the flow field in the first-stage rotor of a two-stage, full-scale, low-aspect ratio, transonic compressor. Flow structures within the first stage rotor were measured using a laser anemometer at the following operating conditions: peak efficiency at 85% speed; near stall at peak-efficiency speed; and design pressure ratio and flow. Also measured were rotor inflow and outflow conditions. Numerical predictions for the peak-efficiency and near-stall operating conditions were generated using a threedimensional Navier Stokes algorithm. Experimental results and numerical predictions are analyzed at the 85% speed conditions to provide insights into the flow phenomena within this baseline rotor configuration. These complementary techniques effectively define primary flow features such as shock structure and tip flow field behavior. The resulting database establishes baseline performance for comparison with new rotor designs. Aerosvace Enaineer, WUPOTX. Senior Member AlAA The advancement of gas turbinc compressors into the transonic flow regime presents the designer with a number of new engineering problems that directly impact compressor performance. Ongoing efforts to improve overall performance, sensitive to such issues as blade row matching, would benefit from an improved understanding of the complex viscous flow phenomena prevalent in modern transonic compressors. Characterization of these complex viscous flow features necessitates the use of techniques, both experimental and numerical, capable of providing comprehensive flow information within blade passages. Recent studies have demonstrated the feasibility of defining primary flow structures within rotor blade passages using both laser velocity measurement techniques and Computational Fluid Dynamics (CFD) algorithms. Primary flow features such as shock waves, shockkhock and shwkhoundary layer interactions, separation zones, wakes, and vortices have been defined successfully. Use of both methods simultaneously can lead to an improved understanding of the flow physics, and to an increased confidence level in both interpretation and technique. Reseaich S c i e k s t . Computer Support Croup A proven laser velocity measurement technique for mapping intra-blade flow fields within rotating turbomachinery is laser anemometry (LA). A 'Senior Scientist. Internal Fluid Mechanics Division, Senior Member A l A A This Daper is declared a work of the U.S. Government and . . u i s not subject to copyright protection in the United States. detailed LA method geared towards compressor 1 American Institute of Aeronautics and Astronautics applications is presented by Strazisar :ind llowell.' Analogous LA tcchniques have been used h y ('liiina and Strazisar,' Williams,' Rabe, Wennerstroni atid O'Bricn,4 Rahc, Hoying and Koff, and Russlcr et : I I . ~ to investigate detailed llow field hcliavior within compressor rotors. The latter is a study r c l a t c ~ l o the [present one, having investigated the tip tl(in t i c l t l s present in t l ic same transonic compressor rotor. I Although significant progress has been madc i n recent years. the accurate numerical prcdictiiin 0 1 llow structures within a transonic compressor rcmiins :I challenging problem ior C'FD. Viscous cf lcc ts dominate the Ilow development within a low q i c c t ratio transonic compressor. A thrcc~diiii~iiri(iiial viscous solver with accurate turbulence n i o d c l ~ r i ~ : n d sufficient grid resolution is required to i i ioi lcl the complex llow interactions. Advances i n ccriiiputcr performance nnd ulgorithm development iiavc i,iiahlcd CFD tools to directly impact compressor ilcsign. Steady-state CFD tcchniques have heen IIWI to optimizc compressor lhlading and Iluw lpath contouring, and unsteady techniques to