219 research outputs found
Recommended from our members
Modeling nonuniform bleed in axial compressors
The coupling between the bleed system and the flowfield of a downstream compressor stage is studied using two approaches. In the first approach, three-dimensional, full annulus, unsteady computations simulate the flow in a low-speed research compressor with nonuniform bleed extraction. Comparisons with experimental data show that the flow prediction in the main annulus is accurate to within 0.005 of flow coefficient and 0.5deg of flow angle. The computational fluid dynamics (CFD) is then used to provide a description of flow within the bleed system itself. In the second approach, a two-dimensional mean radius model, similar to that adopted by Hynes and Greitzer in the previous work on compressor stability, is used to simulate the response of the compressor to nonuniform bleed. This model is validated against experimental data for a single-stage compressor, and despite the inherent assumptions (two-dimensional flow and simplified compressor response), provides a satisfactory prediction of the flow for preliminary design purposes with orders of magnitude less computational cost than full 3D CFD. The model is then used to investigate the effect of different levels of bleed nonuniformity and of varying the axial distance between the bleed and the downstream stage. Reducing bleed nonuniformity and moving the stage away from the bleed slot are predicted to reduce the circumferential nonuniformity of the flow entering the stage.This is the author accepted manuscript. The final version is available from the American Society of Mechanical Engineers via http://dx.doi.org/10.1115/1.403284
Acoustic sources and far-field noise of chevron and round jets
This paper investigates numerically the acoustic sources and far-field noise of chevron and round jets. The acoustic sources are described by the fourth-order space–time velocity cross correlations, which are calculated based on a large-eddy simulation flowfield. Gaussian functions are found to fit the axial, radial, and azimuthal cross correlations reasonably well. The axial length scales are three to four times the radial and azimuthal length scales. For the chevron jet, the cross-correlation scales vary with azimuthal angle up to six jet diameters downstream; beyond that, they become axisymmetric like those for a round jet. The fourth-order space–time cross correlation of the axial velocity R_1111 is the dominant source component, and there are considerable contributions from other source components such as R_2222, R_3333, R_1212, R_1313, and R_2323 cross correlations where 1, 2, and 3 represent axial, radial, and azimuthal directions, respectively. For the chevron jet, these cross correlations decay rapidly with axial distance whereas for the round jet, they remain roughly constant over the first 10 jet diameters. The chevron jet intensifies both the R_2222 and R_3333 cross correlations within two jet diameters of the jet exit. The amplitude, length, and time scales of the cross-correlations of a large-eddy simulation velocity field are investigated as functions of position and are found to be proportional to the turbulence amplitude, length, and time scales that are determined from a Reynolds-averaged Navier–Stokes calculation. The constants of proportionality are found to be independent of position within the jet, and they are quite close for chevron and round jets. The scales derived from Reynolds-averaged Navier–Stokes are used for source description, and an acoustic analogy is used for sound propagation. There is an excellent agreement between the far-field noise predictions and measurements. At low frequencies, the chevron nozzle significantly reduces the far-field noise by 5–6 dB at 30 deg and 2–3 dB at 90 deg to the jet axis. However, the chevron nozzle slightly increases high-frequency noise. It was found that R_1212 and R_1313 cross correlations have the largest contribution to the jet noise at 30 deg to the jet axis, whereas the R_2323 cross correlation has the largest contribution to the jet noise at 90 deg to the jet axis. The Reynolds-averaged Navier–Stokes calculations are repeated with different turbulence models, and the noise prediction is found to be almost insensitive to the turbulence model. The results indicate that the modeling approach is capable of assessing advanced noise-reduction concepts.Depuru Mohan expresses his sincere gratitude to St John’s College, University of Cambridge, for the award of a Manmohan Singh Scholarship; as well as Cambridge Commonwealth, European, and International Trust for the award of an Honorary Cambridge International Scholarship. S. A. Karabasov wishes to thank the Royal Society of London for the award of a University Research Fellowship. H. Xia acknowledges the computational time on the European High Performance Computing systems, Partnership for Advanced Computing in Europe, under project 2010PA0649. The authors are grateful to J. Bridges, C. Brown, N. Georgiadis, and J. DeBonis of the NASA John H. Glenn Research Center for providing the experimental data
Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation
Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications
Reduction of peritoneal carcinomatosis by intraperitoneal administration of phospholipids in rats
<p>Abstract</p> <p>Background</p> <p>Intraperitoneal tumor cell attachment after resection of gastrointestinal cancer may lead to a developing of peritoneal carcinosis. Intraabdominal application of phospholipids shows a significant decrease of adhesion formation even in case of rising tumor cell concentration.</p> <p>Methods</p> <p>In experiment A 2*10<sup>6 </sup>colonic tumor cells (DHD/K12/Trb) were injected intraperitonely in female BD-IX-rats. A total of 30 rats were divided into three groups with treatments of phospholipids at 6% or 9% and the control group. In experiment B a total of 100 rats were divided into ten groups with treatments of phospholipids at 9% and the control group. A rising concentration of tumor cells (10,000, 50,000, 100,000, 250,000 and 500,000) were injected intraperitonely in female BD-IX-rats of the different groups. After 30 days, the extent of peritoneal carcinosis was determined by measuring the tumor volume, the area of attachment and the Peritoneal Cancer Index (PCI).</p> <p>Results</p> <p>In experiment A, we found a significant reduction (control group: tumor volume: 12.0 ± 4.9 ml; area of tumor adhesion: 2434.4 ± 766 mm<sup>2</sup>; PCI 28.5 ± 10.0) of peritoneal dissemination according to all evaluation methods after treatment with phospholipids 6% (tumor volume: 5.2 ± 2.2 ml; area of tumor adhesion: 1106.8 ± 689 mm<sup>2</sup>; PCI 19.0 ± 5.0) and phospholipids 9% (tumor volume: 4.0 ± 3.5 ml; area of tumor adhesion: 362.7 ± 339 mm<sup>2</sup>; PCI 13.8 ± 5.1). In experiment B we found a significant reduction of tumor volume in all different groups of rising tumor cell concentration compared to the control. As detected by the area of attachment we found a significant reduction in the subgroups 1*10<sup>4</sup>, 25*10<sup>4 </sup>and 50*10<sup>4</sup>. The reduction in the other subgroups shows no significance. The PCI could be reduced significantly in all subgroups apart from 5*10<sup>4</sup>.</p> <p>Conclusion</p> <p>In this animal study intraperitoneal application of phospholipids resulted in reduction of the extent of peritoneal carcinomatosis after intraperitoneal administration of free tumor cells. This effect was exceptionally noticed when the amount of intraperitoneal tumor cells was limited. Consequently, intraperitoneal administration of phospholipids might be effective in reducing peritoneal carcinomatosis after surgery of gastrointestinal tumors in humans.</p
Spatial and Temporal Variability of Macroinvertebrates in Spawning and Non-Spawning Habitats during a Salmon Run in Southeast Alaska
Spawning salmon create patches of disturbance through redd digging which can reduce macroinvertebrate abundance and biomass in spawning habitat. We asked whether displaced invertebrates use non-spawning habitats as refugia in streams. Our study explored how the spatial and temporal distribution of macroinvertebrates changed during a pink salmon (Oncorhynchus gorbuscha) spawning run and compared macroinvertebrates in spawning (riffle) and non-spawning (refugia) habitats in an Alaskan stream. Potential refugia included: pools, stream margins and the hyporheic zone, and we also sampled invertebrate drift. We predicted that macroinvertebrates would decline in riffles and increase in drift and refugia habitats during salmon spawning. We observed a reduction in the density, biomass and taxonomic richness of macroinvertebrates in riffles during spawning. There was no change in pool and margin invertebrate communities, except insect biomass declined in pools during the spawning period. Macroinvertebrate density was greater in the hyporheic zone and macroinvertebrate density and richness increased in the drift during spawning. We observed significant invertebrate declines within spawning habitat; however in non-spawning habitat, there were less pronounced changes in invertebrate density and richness. The results observed may be due to spawning-related disturbances, insect phenology, or other variables. We propose that certain in-stream habitats could be important for the persistence of macroinvertebrates during salmon spawning in a Southeast Alaskan stream
Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells
The ErbB3 binding protein (Ebp1) is a transcriptional corepressor that inhibits the activity of proliferation-associated genes and the growth of human breast cancer cell lines. Treatment of breast cancer cells with the ErbB3 ligand heregulin (HRG) results in increased phosphorylation of Ebp1 and transcriptional repression. The p21-activated serine/threonine kinase 1 (PAK1), which plays an important role in breast cancer progression and resistance to the anti-oestrogen tamoxifen, is also activated by HRG. We therefore examined the ability of PAK1 to phosphorylate and regulate the function of Ebp1. We found that PAK1 phosphorylated Ebp1 in vitro and mapped the phosphorylation site to threonine 261. Both HRG treatment and expression of a constitutively activated PAK1 in MCF-7 breast cancer cells enhanced threonine phosphorylation of Ebp1. In MCF-7 cells, ectopically expressed Ebp1 bound endogenous PAK1 and this association was enhanced by treatment with HRG. Mutation of the PAK1 phosphorylation site to glutamic acid, mimicking a phosphorylated state, completely abrogated the ability of Ebp1 to repress transcription, inhibit growth of breast cancer cell lines and contribute to tamoxifen sensitivity. These studies demonstrate for the first time that Ebp1 is a substrate of PAK1 and the importance of the PAK1 phosphorylation site for the functional activity of Ebp1 in breast cancer cells
Expression of NRG1 and its receptors in human bladder cancer
BACKGROUND: Therapies targeting ERBB2 have shown success in the clinic. However, response is not determined solely by expression of ERBB2. Levels of ERBB3, its preferred heterodimerisation partner and ERBB ligands may also have a role. METHODS: We measured NRG1 expression by real-time quantitative RT–PCR and ERBB receptors by western blotting and immunohistochemistry in bladder tumours and cell lines. RESULTS: NRG1a and NRG1b showed significant coordinate expression. NRG1b was upregulated in 78 % of cell lines. In tumours, there was a greater range of expression with a trend towards increased NRG1a with higher stage and grade. Increased expression o
Chaperonin Containing T-Complex Polypeptide Subunit Eta (CCT-eta) Is a Specific Regulator of Fibroblast Motility and Contractility
Integumentary wounds in mammalian fetuses heal without scar; this scarless wound healing is intrinsic to fetal tissues and is notable for absence of the contraction seen in postnatal (adult) wounds. The precise molecular signals determining the scarless phenotype remain unclear. We have previously reported that the eta subunit of the chaperonin containing T-complex polypeptide (CCT-eta) is specifically reduced in healing fetal wounds in a rabbit model. In this study, we examine the role of CCT-eta in fibroblast motility and contractility, properties essential to wound healing and scar formation. We demonstrate that CCT-eta (but not CCT-beta) is underexpressed in fetal fibroblasts compared to adult fibroblasts. An in vitro wound healing assay demonstrated that adult fibroblasts showed increased cell migration in response to epidermal growth factor (EGF) and platelet derived growth factor (PDGF) stimulation, whereas fetal fibroblasts were unresponsive. Downregulation of CCT-eta in adult fibroblasts with short inhibitory RNA (siRNA) reduced cellular motility, both basal and growth factor-induced; in contrast, siRNA against CCT-beta had no such effect. Adult fibroblasts were more inherently contractile than fetal fibroblasts by cellular traction force microscopy; this contractility was increased by treatment with EGF and PDGF. CCT-eta siRNA inhibited the PDGF-induction of adult fibroblast contractility, whereas CCT-beta siRNA had no such effect. In each of these instances, the effect of downregulating CCT-eta was to modulate the behavior of adult fibroblasts so as to more closely approximate the characteristics of fetal fibroblasts. We next examined the effect of CCT-eta modulation on alpha-smooth muscle actin (α-SMA) expression, a gene product well known to play a critical role in adult wound healing. Fetal fibroblasts were found to constitutively express less α-SMA than adult cells. Reduction of CCT-eta with siRNA had minimal effect on cellular beta-actin but markedly decreased α-SMA; in contrast, reduction of CCT-beta had minimal effect on either actin isoform. Direct inhibition of α-SMA with siRNA reduced both basal and growth factor-induced fibroblast motility. These results indicate that CCT-eta is a specific regulator of fibroblast motility and contractility and may be a key determinant of the scarless wound healing phenotype by means of its specific regulation of α-SMA expression
Molecular imaging of angiogenesis with SPECT
Single-photon emission computed tomography (SPECT) and position emission tomography (PET) are the two main imaging modalities in nuclear medicine. SPECT imaging is more widely available than PET imaging and the radionuclides used for SPECT are easier to prepare and usually have a longer half-life than those used for PET. In addition, SPECT is a less expensive technique than PET. Commonly used gamma emitters are: 99mTc (Emax 141 keV, T1/2 6.02 h), 123I (Emax 529 keV, T1/2 13.0 h) and 111In (Emax 245 keV, T1/2 67.2 h). Compared to clinical SPECT, PET has a higher spatial resolution and the possibility to more accurately estimate the in vivo concentration of a tracer. In preclinical imaging, the situation is quite different. The resolution of microSPECT cameras (<0.5 mm) is higher than that of microPET cameras (>1.5 mm). In this report, studies on new radiolabelled tracers for SPECT imaging of angiogenesis in tumours are reviewed
Platinum resistance in breast and ovarian cancer cell lines
Breast and ovarian cancers are among the 10 leading cancer types in females with mortalities of 15% and 6%, respectively. Despite tremendous efforts to conquer malignant diseases, the war on cancer declared by Richard Nixon four decades ago seems to be lost. Approximately 21,800 women in the US will be diagnosed with ovarian cancer in 2011. Therefore, its incidence is relatively low compared to breast cancer with 207.090 prognosed cases in 2011. However, overall survival unmasks ovarian cancer as the most deadly gynecological neoplasia. Platinum-based chemotherapy is emerging as an upcoming treatment modality especially in triple negative breast cancer. However, in ovarian cancer Platinum-complexes for a long time are established as first line treatment. Emergence of a resistant phenotype is a major hurdle in curative cancer therapy approaches and many scientists around the world are focussing on this issue. This review covers new findings in this field during the past decade
- …