Science.gov

Sample records for apparent deep stroma

  1. Deep stroma investigation by confocal microscopy

    NASA Astrophysics Data System (ADS)

    Rossi, Francesca; Tatini, Francesca; Pini, Roberto; Valente, Paola; Ardia, Roberta; Buzzonetti, Luca; Canovetti, Annalisa; Malandrini, Alex; Lenzetti, Ivo; Menabuoni, Luca

    2015-03-01

    Laser assisted keratoplasty is nowadays largely used to perform minimally invasive surgery and partial thickness keratoplasty [1-3]. The use of the femtosecond laser enables to perform a customized surgery, solving the specific problem of the single patient, designing new graft profiles and partial thickness keratoplasty (PTK). The common characteristics of the PTKs and that make them eligible respect to the standard penetrating keratoplasty, are: the preservation of eyeball integrity, a reduced risk of graft rejection, a controlled postoperative astigmatism. On the other hand, the optimal surgical results after these PTKs are related to a correct comprehension of the deep stroma layers morphology, which can help in the identification of the correct cleavage plane during surgeries. In the last years some studies were published, giving new insights about the posterior stroma morphology in adult subjects [4,5]. In this work we present a study performed on two groups of tissues: one group is from 20 adult subjects aged 59 +/- 18 y.o., and the other group is from 15 young subjects, aged 12+/-5 y.o.. The samples were from tissues not suitable for transplant in patients. Confocal microscopy and Environmental Scanning Electron Microscopy (ESEM) were used for the analysis of the deep stroma. The preliminary results of this analysis show the main differences in between young and adult tissues, enabling to improve the knowledge of the morphology and of the biomechanical properties of human cornea, in order to improve the surgical results in partial thickness keratoplasty.

  2. Simple test to confirm cleavage with air between Descemet's membrane and stroma during big-bubble deep anterior lamellar keratoplasty.

    PubMed

    Fontana, Luigi; Parente, Gabriella; Tassinari, Giorgio

    2007-04-01

    We describe a simple test to confirm big-bubble formation in deep anterior lamellar keratoplasty by observing the position and movements of small air bubbles injected into the anterior chamber through a limbal paracentesis. The test also allows evaluation of the extension of Descemet's membrane cleavage from the posterior stroma relative to the margins of the corneal trephination.

  3. Fine structure of the developing avian corneal stroma as revealed by quick-freeze, deep-etch electron microscopy.

    PubMed

    Hirsch, M; Noske, W; Prenant, G; Renard, G

    1999-09-01

    Corneal transparency depends on the precise organization of the stromal extracellular matrix. The morphology of the extracellular matrix of the embryonic and adult avian secondary posterior cornea was studied in glutaraldehyde-fixed, quick-frozen, deep-etched replicas with the electron microscope. Although the collagen fibrils changed from a loose network to a more ordered parallel lamellar arrangement during development, their mean diameter remained constant between 30.3 and 31.2 nm. Besides collagen fibrils, other extracellular matrix components were observed: (i) straight or Y-shaped cross-bridging interfibrillar 8-10 nm filaments with 18-22 nm globules; (ii) relatively loose networks of 10-20 nm beaded filaments, with a mean periodicity of 107 nm, often running perpendicular to the collagen fibrils and adhering to the plasma membrane of stromal cells at early developmental stages; (iii) straight or curved 6-12 nm strands forming sheets within the stromal matrix that progressively disappeared, whereas similar structures persisted at the Descemet's membrane-stroma interface; (iv) dense networks of filaments with 6-8 nm filaments, sometimes polygonally arranged, and a substructure of 2-3 nm filaments with globular domains, which progressively disappeared with maturation but remained at the Descemet's membrane-stroma interface; (v) polygonal networks of 9-10 nm filaments with globular domains adherent to the surface of cell plasma membranes at early developmental stages. The temporal expression of deep-etched supramolecular structural assemblies is compatible with that of the so-called 'interstitial basement membrane components' previously described. The quick-freeze and deep-etching method can reveal important aspects of the in situ organization of the corneal extracellular matrix.

  4. Apparent Anisotropic Diffusion of SF6 in a Deep Arid Unsaturated Zone

    NASA Astrophysics Data System (ADS)

    Green, C. T.; Walvoord, M. A.; Andraski, B. J.; Striegl, R. G.; Stonestrom, D. A.

    2014-12-01

    Gas transport in the unsaturated zone affects contaminant dispersal, remediation, interpretation of groundwater travel times from atmospheric tracers, and mass-budgets of environmentally important gases. Although deep unsaturated zone transport of gases is commonly treated as dominated by Fickian diffusion, previous observations at the Amargosa Desert Research Site have shown that the transport rates of various gas phase contaminants are faster than expected from standard models of diffusive transport. In this study, we use a multi-model approach to analyze results of a gas-tracer (SF6) test to clarify factors affecting gas transport in a deep unsaturated zone. Thirteen separate models with distinct diffusivity structures were calibrated to the tracer-test data. Models were compared on the basis of Akaike Information Criteria estimates of posterior model probability. The greatest posterior probability occurred for a model with significant anisotropy of diffusivity in addition to varying apparent diffusivity among vertically distributed sampling locations. Some horizontal diffusivities were greater than expected for purely diffusive transport, with values approaching free-air diffusivity (tortuosity ≈ 0.6 to 1). The magnitudes of the high apparent diffusivities were consistent with advective oscillations propagating through unsaturated-zone strata based on an analysis of barometric and unsaturated-zone air pressure time series. These results indicate that point source gases in layered unsaturated zones can spread laterally more quickly, and produce higher peak concentrations, than predicted by isotropic Fickian diffusion models.

  5. Apparent break in earthquake scaling due to path and site effects on deep borehole recordings

    USGS Publications Warehouse

    Ide, S.; Beroza, G.C.; Prejean, S.G.; Ellsworth, W.L.

    2003-01-01

    We reexamine the scaling of stress drop and apparent stress, rigidity times the ratio between seismically radiated energy to seismic moment, with earthquake size for a set of microearthquakes recorded in a deep borehole in Long Valley, California. In the first set of calculations, we assume a constant Q and solve for the corner frequency and seismic moment. In the second set of calculations, we model the spectral ratio of nearby events to determine the same quantities. We find that the spectral ratio technique, which can account for path and site effects or nonconstant Q, yields higher stress drops, particularly for the smaller events in the data set. The measurements determined from spectral ratios indicate no departure from constant stress drop scaling down to the smallest events in our data set (Mw 0.8). Our results indicate that propagation effects can contaminate measurements of source parameters even in the relatively clean recording environment of a deep borehole, just as they do at the Earth's surface. The scaling of source properties of microearthquakes made from deep borehole recordings may need to be reevaluated.

  6. Apparently-deep events in the Middle Atlas resolved to be shallow: Implications for lithospheric deformation

    NASA Astrophysics Data System (ADS)

    Singh, Shashwat K.; Bezada, Maximiliano J.; Elouai, Driss; Harnafi, Mimoun

    2016-11-01

    The occurrence of intermediate depth seismicity in intracontinental settings is rare, but it has been postulated with various degrees of certainty in several regions. One such region is the Middle Atlas of Morocco. Since 1960, 75 intermediate depth earthquakes have been reported in this region by Spain's National Geographic Institute (IGN). The apparent deep nature of these events is hard to reconcile with well-established geophysical evidence of a thin lithosphere under the Middle Atlas, but has been associated with mantle delamination processes. We relocate 4 events with IGN-reported depths > 80 km that were recorded by a relatively dense temporary deployment; using a recent regional 3D velocity model obtained through teleseismic body and surface wave tomography. The relocation procedure uses a grid-search approach to minimize the mean normalized misfit, where each travel-time misfit is normalized by the estimated pick uncertainty. We find that our observed arrivals are much better fit by shallow (< 5 km) depths than the reported depths of > 80 km. We propose that these shallow foci earthquakes are the result of regional crustal deformation of this region caused by the present convergence between Africa and Eurasian Plate. We infer that if there are any ongoing delamination processes in the area, they are aseismic. This study is an example of how local earthquake locations in tectonically complex areas can be significantly improved by using a dense local seismic array and a well-constrained 3-D velocity model.

  7. Stroma in Breast Development and Disease

    PubMed Central

    Arendt, Lisa M.; Rudnick, Jenny A.; Keller, Patricia J.; Kuperwasser, Charlotte

    2009-01-01

    It is increasingly apparent that normal and malignant breast tissues require complex local and systemic stromal interactions for development and progression. During development, mammary cell fate specification and differentiation require highly regulated contextual signals derived from the stroma. Likewise, during breast carcinoma development, the tissue stroma can provide tumor suppressing and tumor-promoting environments that serve to regulate neoplastic growth of the epithelium. This review focuses on the role of the stroma as a mediator of normal mammary development, as well as a critical regulator of malignant conversion and progression in breast cancer. Recognition of the important role of the stroma during the progression of breast cancers leads to the possibility of new targets for treatment of the initial breast cancer lesion as well as prevention of recurrence. PMID:19857593

  8. Deep-sea record of impact apparently unrelated to mass extinction in the Late Triassic

    PubMed Central

    Onoue, Tetsuji; Sato, Honami; Nakamura, Tomoki; Noguchi, Takaaki; Hidaka, Yoshihiro; Shirai, Naoki; Ebihara, Mitsuru; Osawa, Takahito; Hatsukawa, Yuichi; Toh, Yosuke; Koizumi, Mitsuo; Harada, Hideo; Orchard, Michael J.; Nedachi, Munetomo

    2012-01-01

    The 34-million-year (My) interval of the Late Triassic is marked by the formation of several large impact structures on Earth. Late Triassic impact events have been considered a factor in biotic extinction events in the Late Triassic (e.g., end-Triassic extinction event), but this scenario remains controversial because of a lack of stratigraphic records of ejecta deposits. Here, we report evidence for an impact event (platinum group elements anomaly with nickel-rich magnetite and microspherules) from the middle Norian (Upper Triassic) deep-sea sediment in Japan. This includes anomalously high abundances of iridium, up to 41.5 parts per billion (ppb), in the ejecta deposit, which suggests that the iridium-enriched ejecta layers of the Late Triassic may be found on a global scale. The ejecta deposit is constrained by microfossils that suggest correlation with the 215.5-Mya, 100-km-wide Manicouagan impact crater in Canada. Our analysis of radiolarians shows no evidence of a mass extinction event across the impact event horizon, and no contemporaneous faunal turnover is seen in other marine planktons. However, such an event has been reported among marine faunas and terrestrial tetrapods and floras in North America. We, therefore, suggest that the Manicouagan impact triggered the extinction of terrestrial and marine organisms near the impact site but not within the pelagic marine realm. PMID:23129649

  9. Deep-sea record of impact apparently unrelated to mass extinction in the Late Triassic.

    PubMed

    Onoue, Tetsuji; Sato, Honami; Nakamura, Tomoki; Noguchi, Takaaki; Hidaka, Yoshihiro; Shirai, Naoki; Ebihara, Mitsuru; Osawa, Takahito; Hatsukawa, Yuichi; Toh, Yosuke; Koizumi, Mitsuo; Harada, Hideo; Orchard, Michael J; Nedachi, Munetomo

    2012-11-20

    The 34-million-year (My) interval of the Late Triassic is marked by the formation of several large impact structures on Earth. Late Triassic impact events have been considered a factor in biotic extinction events in the Late Triassic (e.g., end-Triassic extinction event), but this scenario remains controversial because of a lack of stratigraphic records of ejecta deposits. Here, we report evidence for an impact event (platinum group elements anomaly with nickel-rich magnetite and microspherules) from the middle Norian (Upper Triassic) deep-sea sediment in Japan. This includes anomalously high abundances of iridium, up to 41.5 parts per billion (ppb), in the ejecta deposit, which suggests that the iridium-enriched ejecta layers of the Late Triassic may be found on a global scale. The ejecta deposit is constrained by microfossils that suggest correlation with the 215.5-Mya, 100-km-wide Manicouagan impact crater in Canada. Our analysis of radiolarians shows no evidence of a mass extinction event across the impact event horizon, and no contemporaneous faunal turnover is seen in other marine planktons. However, such an event has been reported among marine faunas and terrestrial tetrapods and floras in North America. We, therefore, suggest that the Manicouagan impact triggered the extinction of terrestrial and marine organisms near the impact site but not within the pelagic marine realm.

  10. Corneal Stroma Microfibrils

    PubMed Central

    Hanlon, Samuel D.; Behzad, Ali R.; Sakai, Lynn Y.; Burns, Alan R.

    2015-01-01

    Elastic tissue was first described well over a hundred years ago and has since been identified in nearly every part of the body. In this review, we examine elastic tissue in the corneal stroma with some mention of other ocular structures which have been more thoroughly described in the past. True elastic fibers consist of an elastin core surrounded by fibrillin microfibrils. However, the presence of elastin fibers is not a requirement and some elastic tissue is comprised of non-elastin-containing bundles of microfibrils. Fibers containing a higher relative amount of elastin are associated with greater elasticity and those without elastin, with structural support. Recently it has been shown that the microfibrils, not only serve mechanical roles, but are also involved in cell signaling through force transduction and the release of TGF-β. A well characterized example of elastin-free microfibril bundles (EFMBs) is found in the ciliary zonules which suspend the crystalline lens in the eye. Through contraction of the ciliary muscle they exert enough force to reshape the lens and thereby change its focal point. It is believed that the molecules comprising these fibers do not turn-over and yet retain their tensile strength for the life of the animal. The mechanical properties of the cornea (strength, elasticity, resiliency) would suggest that EFMBs are present there as well. However, many authors have reported that, although present during embryonic and early postnatal development, EFMBs are generally not present in adults. Serial-block-face imaging with a scanning electron microscope enabled 3D reconstruction of elements in murine corneas. Among these elements were found fibers that formed an extensive network throughout the cornea. In single sections these fibers appeared as electron dense patches. Transmission electron microscopy provided additional detail of these patches and showed them to be composed of fibrils (∼10nm diameter). Immunogold evidence clearly

  11. Epithelium-stroma classification via convolutional neural networks and unsupervised domain adaptation in histopathological images.

    PubMed

    Huang, Yue; Zheng, Han; Liu, Chi; Ding, Xinghao; Rohde, Gustavo

    2017-04-06

    Epithelium-stroma classification is a necessary preprocessing step in histopathological image analysis. Current deep learning based recognition methods for histology data require collection of large volumes of labeled data in order to train a new neural network when there are changes to the image acquisition procedure. However, it is extremely expensive for pathologists to manually label sufficient volumes of data for each pathology study in a professional manner, which results in limitations in real-world applications. A very simple but effective deep learning method, that introduces the concept of unsupervised domain adaptation to a simple convolutional neural network (CNN), has been proposed in this paper. Inspired by transfer learning, our work assumes that the training data and testing data follow different distributions, and there is an adaptation operation to more accurately estimate the kernels in CNN in feature extraction, in order to enhance performance by transferring knowledge from labeled data in source domain to unlabeled data in target domain. The model has been evaluated using three independent public epithelium-stroma datasets by cross-dataset validations. The experimental results demonstrate that for epithelium-stroma classification, the proposed framework outperforms the state-of-the-art deep neural network model, and it also achieves better performance than other existing deep domain adaptation methods. The proposed model can be considered to be a better option for real-world applications in histopathological image analysis, since there is no longer a requirement for large-scale labeled data in each specified domain.

  12. Polypeptides of the Maize Amyloplast Stroma1

    PubMed Central

    Yu, Ying; He Mu, Helen; Mu-Forster, Chen; Wasserman, Bruce P.

    1998-01-01

    In the developing endosperm of monocotyledonous plants, starch granules are synthesized and deposited within the amyloplast. A soluble stromal fraction was isolated from amyloplasts of immature maize (Zea mays L.) endosperm and analyzed for enzyme activities and polypeptide content. Specific activities of starch synthase and starch-branching enzyme (SBE), but not the cytosolic marker alcohol dehydrogenase, were strongly enhanced in soluble amyloplast stromal fractions relative to soluble extracts obtained from homogenized kernels or endosperms. Immunoblot analysis demonstrated that starch synthase I, SBEIIb, and sugary1, the putative starch-debranching enzyme, were each highly enriched in the amyloplast stroma, providing direct evidence for the localization of starch-biosynthetic enzymes within this compartment. Analysis of maize mutants shows the deficiency of the 85-kD SBEIIb polypeptide in the stroma of amylose extender cultivars and that the dull mutant lacks a >220-kD stromal polypeptide. The stromal fraction is distinguished by differential enrichment of a characteristic group of previously undocumented polypeptides. N-terminal sequence analysis revealed that an abundant 81-kD stromal polypeptide is a member of the Hsp70 family of stress-related proteins. Moreover, the 81-kD stromal polypeptide is strongly recognized by antibodies specific for an Hsp70 of the chloroplast stroma. These findings are discussed in light of implications for the correct folding and assembly of soluble, partially soluble, and granule-bound starch-biosynthetic enzymes during import into the amyloplast. PMID:9536063

  13. Reproduction in rare bathyal octopods Pteroctopus tetracirrhus and Scaeurgus unicirrhus (Cephalopoda: Octopoda) in the east Mediterranean as an apparent response to extremely oligotrophic deep seas

    NASA Astrophysics Data System (ADS)

    Laptikhovsky, Vladimir; Salman, Alp; Önsoy, Bahadir; Akalin, Meryem; Ceylan, Beytullah

    2014-10-01

    Reproductive patterns of two benthic bathyal octopods, Pteroctopus tetracirrhus and Scaeurgus unicirrhus have been studied in extremely nutrient-poor environment of the deep-sea Eastern Mediterranean. Both species were found to exhibit a reproductive tactics of producing eggs much larger than in the western part of the sea which likely results in larger hatchlings with higher viability. P. tetracirrhus exhibited a typical “deep-sea” spawning strategy of simultaneous maturation of a single batch of large eggs with atresia of excessive oocytes, whereas reproductive strategy of S. unicirrhus is particular for shelf octopodids: asynchronous maturation of numerous batches of small eggs with no obvious regulatory atresia. Existence of these two types of ovary development and utilisation of fecundity are closely related to two types of evolutionary stable reproductive strategies based on existence of either very large or very small eggs with a few species occupying the “intermediate” position.

  14. Role of Reactive Stroma in Prostate Cancer Progression

    DTIC Science & Technology

    2008-02-01

    AD_________________ Award Number: W81XWH-04-1-0189 TITLE: Role of Reactive Stroma in Prostate Cancer Progression PRINCIPAL INVESTIGATOR: David R...REPORT TYPE Final 3. DATES COVERED 12 JAN 2004 - 11 JAN 2008 4. TITLE AND SUBTITLE Role of Reactive Stroma in Prostate Cancer Progression 5a. CONTRACT...the reactive stroma of experimental prostate cancer . Using a modified approach, we are placing an inducible Cre recombinase behind the FAP gene

  15. Stroma Targeting Nuclear Imaging and Radiopharmaceuticals

    PubMed Central

    Shetty, Dinesh; Jeong, Jae-Min; Shim, Hyunsuk

    2012-01-01

    Malignant transformation of tumor accompanies profound changes in the normal neighboring tissue, called tumor stroma. The tumor stroma provides an environment favoring local tumor growth, invasion, and metastatic spreading. Nuclear imaging (PET/SPECT) measures biochemical and physiologic functions in the human body. In oncology, PET/SPECT is particularly useful for differentiating tumors from postsurgical changes or radiation necrosis, distinguishing benign from malignant lesions, identifying the optimal site for biopsy, staging cancers, and monitoring the response to therapy. Indeed, PET/SPECT is a powerful, proven diagnostic imaging modality that displays information unobtainable through other anatomical imaging, such as CT or MRI. When combined with coregistered CT data, [18F]fluorodeoxyglucose ([18F]FDG)-PET is particularly useful. However, [18F]FDG is not a target-specific PET tracer. This paper will review the tumor microenvironment targeting oncologic imaging such as angiogenesis, invasion, hypoxia, growth, and homing, and also therapeutic radiopharmaceuticals to provide a roadmap for additional applications of tumor imaging and therapy. PMID:22685650

  16. Vascular Hyperpermeability, Angiogenesis, and Stroma Generation

    PubMed Central

    Nagy, Janice A.; Dvorak, Ann M.; Dvorak, Harold F.

    2012-01-01

    It has been known for more than half a century that the tumor microvasculature is hyperpermeable to plasma proteins. However, the identity of the leaky vessels and the consequences of vascular hyperpermeability have received little attention. This article places tumor vascular hyperpermeability in a broader context, relating it to (1) the low-level “basal” permeability of the normal vasculature; (2) the “acute,” short-term hyperpermeability induced by vascular permeability factor/vascular endothelial growth factor (VPF/VEGF-A) and other vascular permeabilizing agents; and (3) the “chronic” hyperpermeability associated with longer-term exposure to agents such as VPF/VEGF-A that accompanies many types of pathological angiogenesis. Leakage of plasma protein-rich fluids is important because it activates the clotting system, depositing an extravascular fibrin gel provisional matrix that serves as the first step in stroma generation. PMID:22355795

  17. Neutral Peptidases in the Stroma of Pea Chloroplasts 1

    PubMed Central

    Liu, Xiang-Qin; Jagendorf, André T.

    1986-01-01

    One endopeptidase (EP1) and at least three aminopeptidases (AP1, AP2, and AP3) were discovered in the stroma of chloroplasts isolated from pea seedlings (Pisum sativum L.), and purified over 100-fold. EP1 requires added Mg2+ or Ca2+ for activity, may have an additional tightly bound metal atom, and is inhibited by sulfhydryl reagents but not by serine residue-directed inhibitors. It is reversibly inhibited by dithiothreitol. Its specificity is for the bond between two adjacent Ala or Gly residues. Its molecular mass is 93 kilodaltons, estimated on a gel filtration column. Aminopeptidase activities were detected with the aid of different amino acyl-β-naphthylamides as substrates. They were resolved into at least three individual proteins by gel filtration and DEAE-cellulose chromatography, having apparent molecular masses of 269,000 (AP1), 84,000 (AP2), and 42,000 (AP3) daltons, respectively. Each has a unique specificity for substrates, with AP1 hydrolyzing only the Prolyl-β-naphthylamide. None of the APs require added divalent cations for activity, but the possibility of a tightly bound metal function was suggested in AP2 and AP3 (not AP1) from effects of inhibitors. A probable sulfhydryl residue function was indicated for all three, from inhibition by p-hydroxymercuribenzoate and Zn2+. All these peptidases had pH optima at 7.7. PMID:16664864

  18. Anterior and posterior corneal stroma elasticity assessed using nanoindentation

    PubMed Central

    Dias, Janice; Ziebarth, Noël M.

    2013-01-01

    Corneal biomechanics is an essential parameter for developing diagnostic and treatment methods of corneal-related diseases. It is widely accepted that corneal mechanical strength stems from the stroma's collagenous composition. However, more comprehensive insight into the mechanical properties within the stroma is needed to improve current corneal diagnostic and treatment techniques. The purpose of this study was to perform elasticity characterization of anterior and posterior stromal regions of human corneas using atomic force microscopy (AFM). Nine pairs of human whole globes were placed in 20% Dextran solution, cornea side down, to restore the corneal thickness to physiological levels (400-600μm). The epithelium and Bowman's membrane were removed from all eyes. Anterior stromal AFM elasticity testing was then performed on left (OS) eyes. Additional stroma was removed from right (OD) eyes to allow posterior stromal measurements at a depth of 50% of the original thickness. All experiments were performed with corneas submerged in 15% Dextran to maintain corneal hydration. The results of the study showed that the Young's modulus of elasticity of the anterior stroma (average: 281 ± 214kPa; range: 59-764kPa) was significantly higher than that of the posterior stroma (average: 89.5 ± 46.1kPa; range: 29-179kPa) (p=0.014). In addition, a linear relationship was found between the posterior stromal elasticity and anterior stromal elasticity (p=0.0428). On average, the elasticity of the posterior stroma is 39.3% of the anterior stroma. In summary, there appears to be an elasticity gradient within the corneal stroma, which should be considered in the design and development of corneal diagnostic and treatment methods to enhance efficacy. PMID:23800511

  19. Role of Reactive Stroma in Prostate Cancer Progression

    DTIC Science & Technology

    2007-02-01

    approach, we are placing an inducible Cre recombinase behind the FAP gene promoter to target expression to reactive stroma. We will cross this mouse...using the FAP gene to specifically target the expression of an inducible Cre recombinase to cancer associated reactive stroma. Three Specific Aims and...inducible Cre recombinase (CrePR1) into the fibroblast activation protein (FAP) locus. This Aim is to generate a transgenic mouse that uses the FAP

  20. The autophagic tumor stroma model of cancer

    PubMed Central

    Pavlides, Stephanos; Tsirigos, Aristotelis; Migneco, Gemma; Whitaker-Menezes, Diana; Chiavarina, Barbara; Flomenberg, Neal; Frank, Philippe G; Casimiro, Mathew C; Wang, Chenguang; Pestell, Richard G; Martinez-Outschoorn, Ubaldo E; Howell, Anthony

    2010-01-01

    A loss of stromal caveolin-1 (Cav-1) in the tumor fibroblast compartment is associated with early tumor recurrence, lymphnode metastasis and tamoxifen-resistance, resulting in poor clinical outcome in breast cancer patients. Here, we have used Cav-1 (−/−) null mice as a pre-clinical model for this “lethal tumor micro-environment”. Metabolic profiling of Cav-1 (−/−) mammary fat pads revealed the upregulation of numerous metabolites (nearly 100), indicative of a major catabolic phenotype. Our results are consistent with the induction of oxidative stress, mitochondrial dysfunction and autophagy/mitophagy. The two most prominent metabolites that emerged from this analysis were ADMA (asymmetric dimethyl arginine) and BHB (beta-hydroxybutyrate; a ketone body), which are markers of oxidative stress and mitochondrial dysfunction, respectively. Transcriptional profiling of Cav-1 (−/−) stromal cells and human tumor stroma from breast cancer patients directly supported an association with oxidative stress, mitochondrial dysfunction and autophagy/mitophagy, as well as ADMA and ketone production. MicroRNA profiling of Cav-1 (−/−) stromal cells revealed the upregulation of two key cancer-related miR's, namely miR-31 and miR-34c. Consistent with our metabolic findings, these miR's are associated with oxidative stress (miR-34c) or activation of the hypoxic response/HIF1α (miR-31), which is sufficient to drive authophagy/mitophagy. Thus, via an unbiased comprehensive analysis of a lethal tumor micro-environment, we have identified a number of candidate biomarkers (ADMA, ketones and miR-31/34c) that could be used to identify high-risk cancer patients at diagnosis, for treatment stratification and/or for evaluating therapeutic efficacy during anti-cancer therapy. We propose that the levels of these key biomarkers (ADMA, ketones/BHB, miR-31 and miR-34c) could be (1) assayed using serum or plasma from cancer patients or (2) performed directly on excised tumor

  1. Proteins of the corneal stroma: importance in visual function.

    PubMed

    Xuan, Meng; Wang, Shurong; Liu, Xin; He, Yuxi; Li, Ying; Zhang, Yan

    2016-04-01

    The human cornea, consisting of five layers, is the transparent tissue that refracts and transmits light to the lens and retina, providing about two thirds of the refractive power of the eye. The stroma layer comprises nearly 90 % of the thickness of the cornea and thus plays a pivotal role in normal visual function. The bulk of this layer is constituted by proteins in the extracellular martrix secreted by the corneal epithelial, stroma, and endothelial cells. Clinical research has shown that corneal stroma diseases are common and involve conditions such as infections, injuries, and genetic defects, which cause severe visual disturbances or even blindness. To improve our understanding of the basic molecular mechanisms involved in the physiological and pathological activities of the corneal stroma, its proteins have been brought into the limelight to determine their crucial and irreplaceable roles. The data presented in a previous study have demonstrated the presence of 1679 proteins in the stroma, and this data set has subsequently been perfected by utilizing a highly sensitive isobaric peptide-labeling approach. According to their manifestations, these proteins can be classified as a gel-like organic material composed of proteoglycans, enzymes, and hemocyanin-binding proteins and a network of filaments composed of collagen, elastin, keratin, vimentin, and interconnected filaments comprising fibronectin and laminin. The aim of this review is to describe some corneal stroma proteins by highlighting their major functions and valuable applications in ophthalmologic research toward the better characterization and treatment of eye diseases.

  2. Pancreatic cancer: Stroma and its current and emerging targeted therapies.

    PubMed

    Kota, Janaiah; Hancock, Julie; Kwon, Jason; Korc, Murray

    2017-04-10

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies with a 5-year survival rate of 8%. Dense, fibrotic stroma associated with pancreatic tumors is a major obstacle for drug delivery to the tumor bed and plays a crucial role in pancreatic cancer progression. Targeting stroma is considered as a potential therapeutic strategy to improve anti-cancer drug efficacy and patient survival. Although numerous stromal depletion therapies have reached the clinic, they add little to overall survival and are often associated with toxicity. Furthermore, increasing evidence suggests the anti-tumor properties of stroma. Its complete ablation enhanced tumor progression and reduced survival. Consequently, efforts are now focused on developing stromal-targeted therapies that normalize the reactive stroma and avoid the extremes: stromal abundance vs. complete depletion. In this review, we summarized the state of current and emerging anti-stromal targeted therapies, with major emphasis on the role of miRNAs in PDAC stroma and their potential use as novel therapeutic agents to modulate PDAC tumor-stromal interactions.

  3. Emerging concepts in pancreatic cancer medicine: targeting the tumor stroma

    PubMed Central

    Neesse, Albrecht; Krug, Sebastian; Gress, Thomas M; Tuveson, David A; Michl, Patrick

    2014-01-01

    Pancreatic ductal adenocarcinoma is a stroma-rich and highly challenging cancer to treat. Over recent years, it has become increasingly evident that the complex network of soluble cytokines, growth factors, proteases, and components of the extracellular matrix collaboratively interact within the tumor microenvironment, sustaining and driving cancer cell proliferation, invasion, and early metastasis. More recently, the tumor microenvironment has also been appreciated to mediate therapeutic resistance in pancreatic ductal adenocarcinoma, thus opening numerous avenues for novel therapeutic explorations. Inert and soluble components of the tumor stroma have been targeted in order to break down the extracellular matrix scaffold, relieve vessel compression, and increase drug delivery to hypovascular tumors. Moreover, targeting of antiapoptotic, immunosuppressive, and pro-proliferative effects of the tumor stroma provides novel vantage points of attack. This review focuses on current and future developments in pancreatic cancer medicine, with a particular emphasis on biophysical and biochemical approaches that target the tumor microenvironment. PMID:24379681

  4. Technique for the selective heating of corneal stroma

    SciTech Connect

    Doss, J.D.; Albillar, J.I.

    1980-01-01

    Conventional thermokeratoplasty, which relies upon thermal conduction from the epithelium into the stroma, does not generate a desirable temperature profile through the cornea. Previous reports show that temperature levels in the epithelium and in Bowman's membrane are excessive, often resulting in damage to these structures. In addition, this study shows that when corneal thickness exceeds approximately 300 microns, the central portion of the stroma probably will not reach critical shrinkage temperature. Shrinkage only in the superficial stroma may result in minimal and transitory alterations of corneal shape. Variation in treatment results may also occur due to the difficulty in precise control of treatment duration. An alternative corneal heating technique is discussed which appears to solve these three basic problems.

  5. Thymus organogenesis and development of the thymic stroma.

    PubMed

    Nowell, Craig S; Farley, Alison M; Blackburn, C Clare

    2007-01-01

    T-cell development occurs principally in the thymus. Here, immature progenitor cells are guided through the differentiation and selection steps required to generate a complex T-cell repertoire that is both self-tolerant and has propensity to bind self major histocompatibility complex. These processes depend on an array of functionally distinct epithelial cell types within the thymic stroma, which have a common developmental origin in the pharyngeal endoderm. Here, we describe the structural and phenotypic attributes of the thymic stroma, and review current cellular and molecular understanding of thymus organogenesis.

  6. Cancer-stroma evolutionary dynamics in stress-gradient microenvironment

    NASA Astrophysics Data System (ADS)

    Wu, Amy; Lambert, Guillaume; Austin, Robert; Sturm, James; Khin, Zayar; Silva, Ariosto

    2012-02-01

    In order to study the evolution of drug resistance in cancer, it is important to mimic the tumor microenvironment, in which cells are exposed to not uniform concentrations but rather gradients of drugs, nutrients, and other factors Compared to traditional in-vitro methods, microfluidic structure enables better control of the temporal and spatial profile of gradients. Here we demonstrate a microfluidic Doxorubicin gradient environment with heterogeneous landscape, and culture multiple myeloma (8226-S, expressing RFP) and bone marrow stroma (HS-5, expressing GFP) cell lines together. The myeloma cells are not directly motile, but they are able to migrate via the adhesion to motile stroma cells. The indirect motility mechanism of the myeloma cells is crucial for the adaptation to stress environment. Finally, we will report the co-culture dynamics under the stress of doxorubicin gradients, observing for cellular migrations and growth

  7. Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma

    PubMed Central

    Sartakhti, Javad Salimi; Manshaei, Mohammad Hossein; Bateni, Soroosh; Archetti, Marco

    2016-01-01

    Cancer cells and stromal cells cooperate by exchanging diffusible factors that sustain tumor growth, a form of frequency-dependent selection that can be studied in the framework of evolutionary game theory. In the case of multiple myeloma, three types of cells (malignant plasma cells, osteoblasts and osteoclasts) exchange growth factors with different effects, and tumor-stroma interactions have been analysed using a model of cooperation with pairwise interactions. Here we show that a model in which growth factors have autocrine and paracrine effects on multiple cells, a more realistic assumption for tumor-stroma interactions, leads to different results, with implications for disease progression and treatment. In particular, the model reveals that reducing the number of malignant plasma cells below a critical threshold can lead to their extinction and thus to restore a healthy balance between osteoclast and osteoblast, a result in line with current therapies against multiple myeloma. PMID:28030607

  8. The Functional Role of Reactive Stroma in Benign Prostatic Hyperplasia

    PubMed Central

    Schauer, Isaiah G.; Rowley, David R.

    2011-01-01

    The human prostate gland is one of the only internal organs that continue to enlarge throughout adulthood. The specific mechanisms that regulate this growth, as well as the pathological changes leading to the phenotype observed in the disease benign prostatic hyperplasia (BPH), are essentially unknown. Recent studies and their associated findings have made clear that many complex alterations occur, involving persistent and chronic inflammation, circulating hormonal level deregulation, and aberrant wound repair processes. BPH has been etiologically characterized as a progressive, albeit discontinuous, hyperplasia of both the glandular epithelial and stromal cell compartments coordinately yielding an expansion of the prostate gland and clinical symptoms. Interestingly, the inflammatory and repair responses observed in BPH are also key components of general wound repair in post-natal tissues. These responses include altered expression of chemokines, cytokines, matrix remodeling factors, chronic inflammatory processes, altered immune surveillance and recognition, as well as the formation of a prototypical ‘reactive’ stroma which is similar to that observed across various fibroplasias and malignancies of a variety of tissue sites. Stromal tissue, both embryonic mesenchyme, and adult reactive stroma myofibroblasts, has been shown to exert potent and functional regulatory control over epithelial proliferation and differentiation as well as immunoresponsive modulation. Thus, the functional biology of a reactive stroma, within the context of an adult disease typified by epithelial and stromal aberrant hyperplasia, is critical to understand within the context of prostate disease and beyond. The mechanisms that regulate reactive stroma biology in BPH represent targets of opportunity for new therapeutic approaches that may extend to other tissue contexts. Accordingly, this review seeks to address the dissection of important factors, signaling pathways, genes, and other

  9. Pancreatic cancer and its stroma: a conspiracy theory.

    PubMed

    Xu, Zhihong; Pothula, Srinivasa P; Wilson, Jeremy S; Apte, Minoti V

    2014-08-28

    Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on pancreatic cancer cells alone have failed to significantly improve patient outcome over many decades, research efforts have now moved to understanding the pathophysiology of the stromal reaction and its role in cancer progression. In this regard, our Group was the first to identify the cells (pancreatic stellate cells, PSCs) that produced the collagenous stroma of pancreatic cancer and to demonstrate that these cells interacted closely with cancer cells to facilitate local tumour growth and distant metastasis. Evidence is accumulating to indicate that stromal PSCs may also mediate angiogenesis, immune evasion and the well known resistance of pancreatic cancer to chemotherapy and radiotherapy. This review will summarise current knowledge regarding the critical role of pancreatic stellate cells and the stroma in pancreatic cancer biology and the therapeutic approaches being developed to target the stroma in a bid to improve the outcome of this devastating disease.

  10. STROMAS: A Series of Microgravity Experiments on Bone Forming Cells

    NASA Astrophysics Data System (ADS)

    Yi, Liu; Massimilano, Monticone; Federico, Tortelli; Matalija, Pujic; Alessandra, Ruggiu; Ranieri, Cancedda

    2008-06-01

    We developed a novel 3D in vitro culture system by seeding cells onto porous bioceramics, mimicking the physiological niche of bone turn-over and enhancing cellular differentiation respective to conventional 2D Petri Dish cultures. Having overcome several technological difficulties, in a series of STROMA spaceflight experiments 3D cultures of bone marrow derived mesenchymal stem cells (BMSC) and co-cultures of osteoblasts and osteoclast precursors were maintained and conserved in automated bioreactors on orbit. Genechip analysis revealed an inhibition of cell proliferation in microgravity. Unexpectedly, genes related to various processes of neural development were significantly upregulated in microgravity, raising the question on the lineage restriction in BMSC.

  11. Classification of breast cancer stroma as a tool for prognosis

    NASA Astrophysics Data System (ADS)

    Reis, Sara; Gazinska, Patrycja; Hipwell, John H.; Mertzanidou, Thomy; Naidoo, Kalnisha; Pinder, Sarah; Hawkes, David J.

    2016-03-01

    It has been shown that the tumour microenvironment plays a crucial role in regulating tumour progression by a number of different mechanisms, including the remodeling of collagen fibres in tumour-associated stroma. It is still unclear, however, if these stromal changes are of benefit to the host or the tumour. We hypothesise that stromal maturity is an important reflection of tumour biology, and thus can be used to predict prognosis. The aim of this study is to develop a texture analysis methodology which will automatically classify stromal regions from images of hematoxylin and eosin-stained (H and E) sections into two categories: mature and immature. Subsequently we will investigate whether stromal maturity could be used as a predictor of survival and also as a means to better understand the relationship between the radiological imaging signal and the underlying tissue microstructure. We present initial results for 118 regions-of-interest from a dataset of 39 patients diagnosed with invasive breast cancer.

  12. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    PubMed Central

    Chen, Ying; Zhang, Lei; Liu, Wenxin; Liu, Xiangyu

    2015-01-01

    Tumor-stroma ratio (TSR) has recently been identified as a promising prognostic parameter for several solid tumors. This study aimed to evaluate the prognostic role of TSR in epithelial ovarian cancer (EOC) and 838 EOC patients were enrolled in this study. TSR was estimated on hematoxylin-and-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients were classified as stroma-rich or stroma-poor according to the proportion of stroma ≥50% or <50%. Chi-square test analysis revealed that TSR were significantly associated with FIGO stage, LN status, and recurrence or not (all of them P < 0.001). The higher stroma-rich proportions were found in EOC patients with advanced stage (36.13% versus 19.75%), LN metastasis (51.93% versus 27.25%), and recurrence (34.27% versus 6.82%). Stroma-rich EOC patients had obvious shorter median time of progression-free survival (29 versus 39 months) and overall survival (50 versus 58 months), respectively. TSR was an independent prognostic factor for the evaluation of PFS in EOC. Stroma-rich tumors had worse prognosis and higher risk of relapse compared with those in stroma-poor tumors in EOC patients. Considered easy to determine for routine pathological examination, TSR may serve as a new prognostic histological parameter in EOC. PMID:26609529

  13. IL-33 activates tumor stroma to promote intestinal polyposis

    PubMed Central

    Maywald, Rebecca L.; Doerner, Stephanie K.; Pastorelli, Luca; De Salvo, Carlo; Benton, Susan M.; Dawson, Emily P.; Lanza, Denise G.; Berger, Nathan A.; Markowitz, Sanford D.; Lenz, Heinz-Josef; Nadeau, Joseph H.; Pizarro, Theresa T.; Heaney, Jason D.

    2015-01-01

    Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the ApcMin/+ mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in ApcMin/+ polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in ApcMin/+ polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment. PMID:25918379

  14. Ultrastructure Organization of Collagen Fibrils and Proteoglycans of Stingray and Shark Corneal Stroma

    PubMed Central

    Alanazi, Saud A.; Almubrad, Turki; AlIbrahim, Ahmad I. A.; Khan, Adnan A.; Akhtar, Saeed

    2015-01-01

    We report here the ultrastructural organization of collagen fibrils (CF) and proteoglycans (PGs) of the corneal stroma of both the stingray and the shark. Three corneas from three stingrays and three corneas from three sharks were processed for electron microscopy. Tissues were embedded in TAAB 031 resin. The corneal stroma of both the stingray and shark consisted of parallel running lamellae of CFs which were decorated with PGs. In the stingray, the mean area of PGs in the posterior stroma was significantly larger than the PGs of the anterior and middle stroma, whereas, in the shark, the mean area of PGs was similar throughout the stroma. The mean area of PGs of the stingray was significantly larger compared to the PGs, mean area of the shark corneal stroma. The CF diameter of the stingray was significantly smaller compared to the CF diameter in the shark. The ultrastructural features of the corneal stroma of both the stingray and the shark were similar to each other except for the CFs and PGs. The PGs in the stingray and shark might be composed of chondroitin sulfate (CS)/dermatan sulfate (DS) PGs and these PGs with sutures might contribute to the nonswelling properties of the cornea of the stingray and shark. PMID:26167294

  15. Ultrastructure Organization of Collagen Fibrils and Proteoglycans of Stingray and Shark Corneal Stroma.

    PubMed

    Alanazi, Saud A; Almubrad, Turki; AlIbrahim, Ahmad I A; Khan, Adnan A; Akhtar, Saeed

    2015-01-01

    We report here the ultrastructural organization of collagen fibrils (CF) and proteoglycans (PGs) of the corneal stroma of both the stingray and the shark. Three corneas from three stingrays and three corneas from three sharks were processed for electron microscopy. Tissues were embedded in TAAB 031 resin. The corneal stroma of both the stingray and shark consisted of parallel running lamellae of CFs which were decorated with PGs. In the stingray, the mean area of PGs in the posterior stroma was significantly larger than the PGs of the anterior and middle stroma, whereas, in the shark, the mean area of PGs was similar throughout the stroma. The mean area of PGs of the stingray was significantly larger compared to the PGs, mean area of the shark corneal stroma. The CF diameter of the stingray was significantly smaller compared to the CF diameter in the shark. The ultrastructural features of the corneal stroma of both the stingray and the shark were similar to each other except for the CFs and PGs. The PGs in the stingray and shark might be composed of chondroitin sulfate (CS)/dermatan sulfate (DS) PGs and these PGs with sutures might contribute to the nonswelling properties of the cornea of the stingray and shark.

  16. Tumor reactive stroma in cholangiocarcinoma: The fuel behind cancer aggressiveness

    PubMed Central

    Brivio, Simone; Cadamuro, Massimiliano; Strazzabosco, Mario; Fabris, Luca

    2017-01-01

    Cholangiocarcinoma (CCA) is a highly aggressive epithelial malignancy still carrying a dismal prognosis, owing to early lymph node metastatic dissemination and striking resistance to conventional chemotherapy. Although mechanisms underpinning CCA progression are still a conundrum, it is now increasingly recognized that the desmoplastic microenvironment developing in conjunction with biliary carcinogenesis, recently renamed tumor reactive stroma (TRS), behaves as a paramount tumor-promoting driver. Indeed, once being recruited, activated and dangerously co-opted by neoplastic cells, the cellular components of the TRS (myofibroblasts, macrophages, endothelial cells and mesenchymal stem cells) continuously rekindle malignancy by secreting a huge variety of soluble factors (cyto/chemokines, growth factors, morphogens and proteinases). Furthermore, these factors are long-term stored within an abnormally remodeled extracellular matrix (ECM), which in turn can deleteriously mold cancer cell behavior. In this review, we will highlight evidence for the active role played by reactive stromal cells (as well as by the TRS-associated ECM) in CCA progression, including an overview of the most relevant TRS-derived signals possibly fueling CCA cell aggressiveness. Hopefully, a deeper knowledge of the paracrine communications reciprocally exchanged between cancer and stromal cells will steer the development of innovative, combinatorial therapies, which can finally hinder the progression of CCA, as well as of other cancer types with abundant TRS, such as pancreatic and breast carcinomas.

  17. Hhip regulates tumor-stroma-mediated upregulation of tumor angiogenesis

    PubMed Central

    Agrawal, Vijayendra; Kim, Dong Young; Kwon, Young-Guen

    2017-01-01

    Tumor growth is governed by the coordinated action of various types of cells that are present in the tumor environment. Fibroblasts, which constitute a major fraction of the stroma, participate actively in various signaling events and regulate tumor development and metastasis. The Hedgehog (Hh) pathway plays an important role in promoting tumor malignancy via fibroblasts; however, the role of hedgehog interacting protein (hhip; inhibitor of Hh pathway) in tumor growth is poorly understood. Here we implanted B16F10 tumors in hhip+/− mice to study the tumor growth characteristics and the vascular phenotype. Furthermore, the mechanism involved in the observed phenomena was explored to reveal the role of hhip in tumor growth. The tumors that were implanted in hhip+/− mice exhibited accelerated growth and increased tumor angiogenesis. Although we observed a decrease in hypoxia, blood vessels still had abnormal phenotype. We found that increased Hh signaling in tumor fibroblasts induced a high expression of vascular endothelial growth factor (VEGF), which subsequently resulted in an increased proliferation of endothelial cells. Thus, the heterozygous knockdown of hhip in mice could affect Hh signaling in tumor fibroblasts, which could cause the increased production of the growth factor VEGF. This signaling, via a paracrine effect on endothelial cells, increased tumor vascular density. PMID:28127049

  18. Deep Fish.

    PubMed

    Ishaq, Omer; Sadanandan, Sajith Kecheril; Wählby, Carolina

    2017-01-01

    Zebrafish ( Danio rerio) is an important vertebrate model organism in biomedical research, especially suitable for morphological screening due to its transparent body during early development. Deep learning has emerged as a dominant paradigm for data analysis and found a number of applications in computer vision and image analysis. Here we demonstrate the potential of a deep learning approach for accurate high-throughput classification of whole-body zebrafish deformations in multifish microwell plates. Deep learning uses the raw image data as an input, without the need of expert knowledge for feature design or optimization of the segmentation parameters. We trained the deep learning classifier on as few as 84 images (before data augmentation) and achieved a classification accuracy of 92.8% on an unseen test data set that is comparable to the previous state of the art (95%) based on user-specified segmentation and deformation metrics. Ablation studies by digitally removing whole fish or parts of the fish from the images revealed that the classifier learned discriminative features from the image foreground, and we observed that the deformations of the head region, rather than the visually apparent bent tail, were more important for good classification performance.

  19. Overcoming Bone Marrow Stroma-Mediated Chemoresistance in Metastatic Breast Cancer Cells

    DTIC Science & Technology

    2004-08-01

    AD Award Number: DAMD17-03- 1 -0524 .TITLE: Overcoming Bone Marrow Stroma- Mediated Chemoresistance in Metastatic Breast Cancer Cells PRINCIPAL...SUBTITLE 5. FUNDING NUMBERS Overcoming Bone Marrow Stroma- Mediated Chemoresistance in DAMD17-03- 1 -0524 Metastatic Breast Cancer Cells 6. AUTHOR(S) Robert...the compound (Figure 1 ). The inhibitor was slightly more effective in T-47D cells than in MCF-7 cells, but did not eradicate dormant clones much past

  20. Defining the Recruitment of Reactive Stroma Progenitor Cells to the Tumor Microenvironment of Human Prostate Cancer

    DTIC Science & Technology

    2009-02-01

    AD Award Number: W81XWH-08-1-0059 TITLE: Defining the Recruitment of Reactive Stroma Progenitor Cells to the Tumor Microenvironment of Human...2008 - 6 Jan 2009 4. TITLE AND SUBTITLE Defining the Recruitment of Reactive Stroma Progenitor Cells to the Tumor Microenvironment of Human...Symposium on Stem Cells , Cancer, and Aging in Singapore RESEARCH EXPERIENCE 2001 Baylor College of Medicine, Department of Pulmonary and Critical

  1. Prognostic significance of tumour stroma ratio in inflammatory breast cancer.

    PubMed

    Downey, Candice L; Thygesen, Helene H; Sharma, Nisha; Shaaban, Abeer M

    2015-01-01

    Tumour stroma ratio (TSR) is emerging as an important prognostic indicator in cancer. We have previously shown TSR to be prognostic in oestrogen receptor positive breast cancer. Its role in inflammatory breast cancer, a rare but aggressive form of breast cancer, has not been identified. Here we aimed to determine the prognostic significance of TSR in a cohort of patients with inflammatory breast carcinoma. TSR was measured by point counting virtual H&E stained tissue sections in 45 inflammatory breast cancer cases. The whole tumour area was sampled. Optimum cut-offs to distinguish high and low TSR was determined by log-rank test. The relationship of TSR to overall survival and disease-free survival (DFS) was analysed alongside multivariate analysis. The optimal cut-offs between high and low TSR were determined to be 31% for OS and 46% for DFS. There was no significant difference in OS (p = 0.53) nor DFS (p = 0.66) between high and low TSR groups. Multivariate analysis did not demonstrate any new trends, within the limits of a small data sample. A significant correlation was found between pathological response to neoadjuvant chemotherapy and survival (p = 0.008). There is no evidence that TSR has prognostic significance in inflammatory breast cancer. When compared with published data in non-inflammatory breast carcinoma, this supports the view that differences in stromal biology exist between tumour types and highlights the importance of considering this when interpreting the prognostic value of TSR. However, these findings must be interpreted in the light of the small sample size.

  2. Size-Dependent Diffusion of Dextrans in Excised Porcine Corneal Stroma.

    PubMed

    Rajapakshal, Ajith; Fink, Michael; Todd, Brian A

    2015-09-01

    Delivery of therapeutic agents to the eye requires efficient transport through cellular and extracellular barriers. We evaluated the rate of diffusive transport in excised porcine corneal stroma using fluorescently labeled dextran molecules with hydrodynamic radii ranging from 1.3 to 34 nm. Fluorescence correlation spectroscopy (FCS) was used to measure diffusion coefficients of dextran molecules in the excised porcine corneal stroma. The preferential sensitivity of FCS to diffusion along two dimensions was used to differentially probe diffusion along the directions parallel to and perpendicular to the collagen lamellae of the corneal stroma. In order to develop an understanding of how size affects diffusion in cornea, diffusion coefficients in cornea were compared to diffusion coefficients measured in a simple buffer solution. Dextran molecules diffuse more slowly in cornea as compared to buffer solution. The reduction in diffusion coefficient is modest however (67% smaller), and is uniform over the range of sizes that we measured. This indicates that, for dextrans in the 1.3 to 34 nm range, the diffusion landscape of corneal stroma can be represented as a simple liquid with a viscosity approximately 1.5 times that of water. Diffusion coefficients measured parallel vs. perpendicular to the collagen lamellae were indistinguishable. This indicates that diffusion in the corneal stroma is not highly anisotropic. Our results support the notion that the corneal stroma is highly permeable and isotropic to transport of hydrophilic molecules and particles with hydrodynamic radii up to at least 34 nm.

  3. Key players in pancreatic cancer-stroma interaction: Cancer-associated fibroblasts, endothelial and inflammatory cells

    PubMed Central

    Nielsen, Michael Friberg Bruun; Mortensen, Michael Bau; Detlefsen, Sönke

    2016-01-01

    Pancreatic cancer (PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of PC cases, is characterized by an intense stromal desmoplastic reaction surrounding the cancer cells. Cancer-associated fibroblasts (CAFs) are the main effector cells in the desmoplastic reaction, and pancreatic stellate cells are the most important source of CAFs. However, other important components of the PC stroma are inflammatory cells and endothelial cells. The aim of this review is to describe the complex interplay between PC cells and the cellular and non-cellular components of the tumour stroma. Published data have indicated that the desmoplastic stroma protects PC cells against chemotherapy and radiation therapy and that it might promote the proliferation and migration of PC cells. However, in animal studies, experimental depletion of the desmoplastic stroma and CAFs has led to more aggressive cancers. Hence, the precise role of the tumour stroma in PC remains to be elucidated. However, it is likely that a context-dependent therapeutic modification, rather than pure depletion, of the PC stroma holds potential for the development of new treatment strategies for PC patients. PMID:26973408

  4. FGFR1-WNT-TGF-β signaling in prostate cancer mouse models recapitulates human reactive stroma

    PubMed Central

    Carstens, Julienne L.; Shahi, Payam; Van Tsang, Susan; Smith, Billie; Creighton, Chad J.; Zhang, Yiqun; Seamans, Amber; Seethammagari, Mamatha; Vedula, Indira; Levitt, Jonathan M.; Ittmann, Michael M.; Rowley, David R.; Spencer, David M.

    2014-01-01

    The reactive stroma surrounding tumor lesions performs critical roles ranging from supporting tumor cell proliferation to inducing tumorigenesis and metastasis. Therefore, it is critical to understand the cellular components and signaling control mechanisms that underlay the etiology of reactive stroma. Previous studies have individually implicated fibroblast growth factor receptor 1 (FGFR1) and canonical WNT/β-catenin signaling in prostate cancer progression and the initiation and maintenance of a reactive stroma; however, both pathways are frequently found co-activated in cancer tissue. Using autochthonous transgenic mouse models for inducible FGFR1 (JOCK1) and prostate-specific and ubiquitously expressed inducible β-catenin (Pro-Cat and Ubi-Cat, respectively) and bigenic crosses between these lines (Pro-Cat × JOCK1 and Ubi-Cat × JOCK1), we describe WNT-induced synergistic acceleration of FGFR1-driven adenocarcinoma, associated with a pronounced fibroblastic reactive stroma activation surrounding prostatic intraepithelial neoplasia (mPIN) lesions found both in situ and reconstitution assays. Both mouse and human reactive stroma exhibited increased transforming growth factor-beta (TGF-β) signaling adjacent to pathologic lesions likely contributing to invasion. Furthermore, elevated stromal TGF-β signaling was associated with higher Gleason scores in archived human biopsies, mirroring murine patterns. Our findings establish the importance of the FGFR1-WNT-TGF-β signaling axes as driving forces behind reactive stroma in aggressive prostate adenocarcinomas, deepening their relevance as therapeutic targets. PMID:24305876

  5. Multiscale Investigation of the Depth-Dependent Mechanical Anisotropy of the Human Corneal Stroma

    PubMed Central

    Labate, Cristina; Lombardo, Marco; De Santo, Maria P.; Dias, Janice; Ziebarth, Noel M.; Lombardo, Giuseppe

    2015-01-01

    Purpose. To investigate the depth-dependent mechanical anisotropy of the human corneal stroma at the tissue (stroma) and molecular (collagen) level by using atomic force microscopy (AFM). Methods. Eleven human donor corneas were dissected at different stromal depths by using a microkeratome. Mechanical measurements were performed in 15% dextran on the surface of the exposed stroma of each sample by using a custom-built AFM in force spectroscopy mode using both microspherical (38-μm diameter) and nanoconical (10-nm radius of curvature) indenters at 2-μm/s and 15-μm/s indentation rates. Young's modulus was determined by fitting force curve data using the Hertz and Hertz-Sneddon models for a spherical and a conical indenter, respectively. The depth-dependent anisotropy of stromal elasticity was correlated with images of the corneal stroma acquired by two-photon microscopy. Results. The force curves were obtained at stromal depths ranging from 59 to 218 μm. At the tissue level, Young's modulus (ES) showed a steep decrease at approximately 140-μm stromal depth (from 0.8 MPa to 0.3 MPa; P = 0.03) and then was stable in the posterior stroma. At the molecular level, Young's modulus (EC) was significantly greater than at the tissue level; EC decreased nonlinearly with increasing stromal depth from 3.9 to 2.6 MPa (P = 0.04). The variation of microstructure through the thickness correlated highly with a nonconstant profile of the mechanical properties in the stroma. Conclusions. The corneal stroma exhibits unique anisotropic elastic behavior at the tissue and molecular levels. This knowledge may benefit modeling of corneal behavior and help in the development of biomimetic materials. PMID:26098472

  6. Integrated Bioinformatics Approach Reveals Crosstalk Between Tumor Stroma and Peripheral Blood Mononuclear Cells in Breast Cancer.

    PubMed

    He, Lang; Wang, Dan; Wei, Na; Guo, Zheng

    2016-01-01

    Breast cancer is now the leading cause of cancer death in women worldwide. Cancer progression is driven not only by cancer cell intrinsic alterations and interactions with tumor microenvironment, but also by systemic effects. Integration of multiple profiling data may provide insights into the underlying molecular mechanisms of complex systemic processes. We performed a bioinformatic analysis of two public available microarray datasets for breast tumor stroma and peripheral blood mononuclear cells, featuring integrated transcriptomics data, protein-protein interactions (PPIs) and protein subcellular localization, to identify genes and biological pathways that contribute to dialogue between tumor stroma and the peripheral circulation. Genes of the integrin family as well as CXCR4 proved to be hub nodes of the crosstalk network and may play an important role in response to stroma-derived chemoattractants. This study pointed to potential for development of therapeutic strategies that target systemic signals travelling through the circulation and interdict tumor cell recruitment.

  7. Quantitative analysis of thermally-induced alterations of corneal stroma by second-harmonic generation imaging

    NASA Astrophysics Data System (ADS)

    Matteini, P.; Rossi, F.; Ratto, F.; Cicchi, R.; Kapsokalyvas, D.; Pavone, F. S.; Pini, R.

    2010-02-01

    Thermal modifications induced in the corneal stroma were investigated by means of second harmonic generation (SHG) imaging. Whole fresh cornea samples were heated in a water bath at temperatures in the 35-80 °C range for a 4-min time. SHG images of the structural modifications induced at each temperature were acquired from different areas of cross-sectioned corneal stroma by using an 880 nm linearly- and circularly-polarized excitation light emitted by a mode-locked Ti:Sapphire laser. The SHG images were then analyzed by means of both an empirical approach and a 2D-theoretical model. The proposed analyses provide a detailed description of the changes occurring in the structural architecture of the cornea during the thermal treatment. Our results allow us to depict a temperature-dependent biochemical model for the progressive destructuration occurring to collagen fibrils and nonfibrillar components of the stroma.

  8. Thylakoid direct photobioelectrocatalysis: utilizing stroma thylakoids to improve bio-solar cell performance.

    PubMed

    Rasmussen, Michelle; Minteer, Shelley D

    2014-08-28

    Thylakoid membranes from spinach were separated into grana and stroma thylakoid fractions which were characterized by several methods (pigment content, protein gel electrophoresis, photosystem activities, and electron microscopy analysis) to confirm that the intact thylakoids were differentiated into the two domains. The results of photoelectrochemical experiments showed that stroma thylakoid electrodes generate photocurrents more than four times larger than grana thylakoids (51 ± 4 nA cm(-2) compared to 11 ± 1 nA cm(-2)). A similar trend was seen in a bio-solar cell configuration with stroma thylakoids giving almost twice the current (19 ± 3 μA cm(-2)) as grana thylakoids (11 ± 2 μA cm(-2)) with no change in open circuit voltage.

  9. Gene expression in local stroma reflects breast tumor states and predicts patient outcome

    PubMed Central

    Bainer, Russell; Frankenberger, Casey; Rabe, Daniel; An, Gary; Gilad, Yoav; Rosner, Marsha Rich

    2016-01-01

    The surrounding microenvironment has been implicated in the progression of breast tumors to metastasis. However, the degree to which metastatic breast tumors locally reprogram stromal cells as they disrupt tissue boundaries is not well understood. We used species-specific RNA sequencing in a mouse xenograft model to determine how the metastasis suppressor RKIP influences transcription in a panel of paired tumor and stroma tissues. We find that gene expression in metastatic breast tumors is pervasively correlated with gene expression in local stroma of both mouse xenografts and human patients. Changes in stromal gene expression elicited by tumors better predicts subtype and patient survival than tumor gene expression, and genes with coordinated expression in both tissues predict metastasis-free survival. These observations support the use of stroma-based strategies for the diagnosis and prognosis of breast cancer. PMID:27982086

  10. Penrose inequality and apparent horizons

    SciTech Connect

    Ben-Dov, Ishai

    2004-12-15

    A spherically symmetric spacetime is presented with an initial data set that is asymptotically flat, satisfies the dominant energy condition, and such that on this initial data M<{radical}(A/16{pi}), where M is the total mass and A is the area of the apparent horizon. This provides a counterexample to a commonly stated version of the Penrose inequality, though it does not contradict the true Penrose inequality.

  11. Second harmonic generation imaging of corneal stroma after infection by Pseudomonas aeruginosa

    PubMed Central

    Robertson, Danielle M.; Rogers, Nathan A.; Petroll, W. Matthew; Zhu, Meifang

    2017-01-01

    Pseudomonas aeruginosa is a pathogenic gram-negative organism that has the ability to cause blinding corneal infections following trauma and during contact lens wear. In this study, we investigated the directional movement and orientation of an invasive corneal isolate of P. aeruginosa in the corneal stroma during infection of ex vivo and in vivo rabbit corneas using multiphoton fluorescence and second harmonic generation (SHG) imaging. Ex vivo, rabbit corneas were subject to three partial thickness wounds prior to inoculation. In vivo, New Zealand white rabbits were fit with P. aeruginosa laden contact lenses in the absence of a penetrating wound. At all time points tested, infiltration of the corneal stroma by P. aeruginosa revealed a high degree of alignment between the bacteria and collagen lamellae ex vivo (p < 0.001). In vivo, P. aeruginosa traveled throughout the stroma in discrete regions or bands. Within each region, the bacteria showed good alignment with collagen lamellae (P = 0.002). Interestingly, in both the in vitro and in vivo models, P. aeruginosa did not appear to cross the corneal limbus. Taken together, our findings suggest that P. aeruginosa exploits the precise spacing of collagen lamellae in the central cornea to facilitate spread throughout the stroma.

  12. Tic40 is important for reinsertion of proteins from the chloroplast stroma into the inner membrane

    PubMed Central

    Chiu, Chi-Chou; Li, Hsou-min

    2008-01-01

    Chloroplast inner-membrane proteins Tic40 and Tic110 are first imported from the cytosol into the chloroplast stroma, and subsequently reinserted from the stroma into the inner membrane. However, the mechanism of reinsertion remains unclear. Here we show that Tic40 itself is involved in this reinsertion process. When precursors of either Tic40 or a Tic110 C-terminal truncate, tpTic110-Tic110N, were imported into chloroplasts isolated from a tic40-null mutant, soluble Tic40 and Tic110N intermediates accumulated in the stroma of tic40-mutant chloroplasts, due to a slower rate of reinsertion. We further show that a larger quantity of soluble Tic21 intermediates also accumulated in the stroma of tic40-mutant chloroplasts. In contrast, inner-membrane insertion of the triose-phosphate/phosphate translocator was not affected by the tic40 mutation. Our data suggest that multiple pathways exist for the insertion of chloroplast inner-membrane proteins. PMID:18657235

  13. Understanding tumor-stroma interplays for targeted therapies by armed mesenchymal stromal progenitors: the Mesenkillers

    PubMed Central

    Grisendi, Giulia; Bussolari, Rita; Veronesi, Elena; Piccinno, Serena; Burns, Jorge S; De Santis, Giorgio; Loschi, Pietro; Pignatti, Marco; Di Benedetto, Fabrizio; Ballarin, Roberto; Di Gregorio, Carmela; Guarneri, Valentina; Piccinini, Lino; Horwitz, Edwin M; Paolucci, Paolo; Conte, PierFranco; Dominici, Massimo

    2011-01-01

    A tumor represents a complex structure containing malignant cells strictly coupled with a large variety of surrounding cells constituting the tumor stroma (TS). In recent years, the importance of TS for cancer initiation, development, local invasion and metastases has become increasingly clear allowing the identification of TS as one of the possible ways to indirectly target tumors. Inside the heterogeneous stromal cell population, tumor associated fibroblasts (TAF) play a crucial role providing both functional and supportive environments. During both tumor and stroma development, several findings suggest that TAF could be recruited from different sources such as locally derived host fibroblasts, via epithelial/endothelial mesenchymal transitions or from circulating pools of fibroblasts deriving form mesenchymal progenitors, namely mesenchymal stem/stromal cells (MSC). These insights prompted scientists to identify multimodal approaches to target TS by biomolecules, monoclonal antibodies, and more recently via cell based strategies. These latter strategies appear extremely promising, although still associated with debated and unclear findings. This review discusses crosstalk between cancers and their stroma, dissecting specific tumor types, such as sarcoma, pancreatic and breast carcinoma, where stroma plays distinct paradigmatic roles. The recognition of these distinct stromal functions may help in planning effective and safer approaches aimed either to eradicate or to substitute TS by novel compounds and/or MSC having specific killing activities. PMID:22016827

  14. Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment

    PubMed Central

    Truong, Danh; Puleo, Julieann; Llave, Alison; Mouneimne, Ghassan; Kamm, Roger D.; Nikkhah, Mehdi

    2016-01-01

    In this study, to model 3D chemotactic tumor-stroma invasion in vitro, we developed an innovative microfluidic chip allowing side-by-side positioning of 3D hydrogel-based matrices. We were able to (1) create a dual matrix architecture that extended in a continuous manner, thus allowing invasion from one 3D matrix to another, and (2) establish distinct regions of tumor and stroma cell/ECM compositions, with a clearly demarcated tumor invasion front, thus allowing us to quantitatively analyze progression of cancer cells into the stroma at a tissue or single-cell level. We showed significantly enhanced cancer cell invasion in response to a transient gradient of epidermal growth factor (EGF). 3D tracking at the single-cell level displayed increased migration speed and persistence. Subsequently, we analyzed changes in expression of EGF receptors, cell aspect ratio, and protrusive activity. These findings show the unique ability of our model to quantitatively analyze 3D chemotactic invasion, both globally by tracking the progression of the invasion front, and at the single-cell level by examining changes in cellular behavior and morphology using high-resolution imaging. Taken together, we have shown a novel model recapitulating 3D tumor-stroma interactions for studies of real-time cell invasion and morphological changes within a single platform. PMID:27678304

  15. Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis

    PubMed Central

    Desterke, Christophe; Martinaud, Christophe; Ruzehaji, Nadira; Le Bousse-Kerdilès, Marie-Caroline

    2015-01-01

    Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm where severity as well as treatment complexity is mainly attributed to a long lasting disease and presence of bone marrow stroma alterations as evidenced by myelofibrosis, neoangiogenesis, and osteosclerosis. While recent understanding of mutations role in hematopoietic cells provides an explanation for pathological myeloproliferation, functional involvement of stromal cells in the disease pathogenesis remains poorly understood. The current dogma is that stromal changes are secondary to the cytokine “storm” produced by the hematopoietic clone cells. However, despite therapies targeting the myeloproliferation-sustaining clones, PMF is still regarded as an incurable disease except for patients, who are successful recipients of allogeneic stem cell transplantation. Although the clinical benefits of these inhibitors have been correlated with a marked reduction in serum proinflammatory cytokines produced by the hematopoietic clones, further demonstrating the importance of inflammation in the pathological process, these treatments do not address the role of the altered bone marrow stroma in the pathological process. In this review, we propose hypotheses suggesting that the stroma is inflammatory-imprinted by clonal hematopoietic cells up to a point where it becomes “independent” of hematopoietic cell stimulation, resulting in an inflammatory vicious circle requiring combined stroma targeted therapies. PMID:26640324

  16. Survival and integration of tissue-engineered corneal stroma in a model of corneal ulcer.

    PubMed

    Zhang, Chao; Nie, Xin; Hu, Dan; Liu, Yuan; Deng, Zhihong; Dong, Rui; Zhang, Yongjie; Jin, Yan

    2007-08-01

    Tissue-engineered replacement of diseased or damaged tissue has become a reality for some types of tissue, such as skin and cartilage. Tissue-engineered corneal stroma represents a promising concept to overcome the limitations of cornea replacement with allograft. In this study, porcine cornea was decellularized by a series of extraction methods, and the in vivo biocompatibility of the scaffold was measured subcutaneously in rabbits (n = 8). These were not acutely rejected and no abscesses were observed by hematoxylin and eosin staining at the 8th week, indicating that the scaffolds had good biocompatibility. To investigate the potential value of clinical applications, rabbit stromal keratocytes were implanted onto decellularized scaffolds to fabricate tissue-engineered corneal stroma. Allograft, tissue-engineered corneal stroma, or scaffolds were implanted into a model of corneal ulcer. The survival and reconstruction of corneal transplantation were morphologically evaluated by light and electron microscopy until the 32nd week after implantation. Experiments involving transplantation indicated that the epithelial and stromal defect healed quickly, with improvement in corneal clarity. The integration of the graft was accompanied by neurite ingrowth from the host tissue. By 16 weeks after transplantation, the cornea had gradually regained an intact state similar to that of normal cornea. Our results demonstrate that the tissue-engineered corneal stroma with allogenetic cells is a promising therapeutic method for corneal injury.

  17. Elastic microfibril distribution in the cornea: Differences between normal and keratoconic stroma.

    PubMed

    White, Tomas L; Lewis, Philip N; Young, Robert D; Kitazawa, Koji; Inatomi, Tsutomu; Kinoshita, Shigeru; Meek, Keith M

    2017-03-14

    The optical and biomechanical properties of the cornea are largely governed by the collagen-rich stroma, a layer that represents approximately 90% of the total thickness. Within the stroma, the specific arrangement of superimposed lamellae provides the tissue with tensile strength, whilst the spatial arrangement of individual collagen fibrils within the lamellae confers transparency. In keratoconus, this precise stromal arrangement is lost, resulting in ectasia and visual impairment. In the normal cornea, we previously characterised the three-dimensional arrangement of an elastic fiber network spanning the posterior stroma from limbus-to-limbus. In the peripheral cornea/limbus there are elastin-containing sheets or broad fibers, most of which become microfibril bundles (MBs) with little or no elastin component when reaching the central cornea. The purpose of the current study was to compare this network with the elastic fiber distribution in post-surgical keratoconic corneal buttons, using serial block face scanning electron microscopy and transmission electron microscopy. We have demonstrated that the MB distribution is very different in keratoconus. MBs are absent from a region of stroma anterior to Descemet's membrane, an area that is densely populated in normal cornea, whilst being concentrated below the epithelium, an area in which they are absent in normal cornea. We contend that these latter microfibrils are produced as a biomechanical response to provide additional strength to the anterior stroma in order to prevent tissue rupture at the apex of the cone. A lack of MBs anterior to Descemet's membrane in keratoconus would alter the biomechanical properties of the tissue, potentially contributing to the pathogenesis of the disease.

  18. Double-bubble technique to facilitate Descemet membrane exposure in deep anterior lamellar keratoplasty.

    PubMed

    Shimazaki, Jun

    2010-02-01

    Safe and efficient exposure of Descemet membrane is the key to success in deep anterior lamellar keratoplasty. Although widely used, the big-bubble technique has the drawback of difficulty in maintaining appropriate needle insertion depth in the corneal stroma, resulting in injected air sometimes escaping to the peripheral cornea without separation of Descemet membrane. We describe a variation of the big-bubble technique in which air is injected into the anterior chamber before it is injected into the stroma. By observing the reflection created on the surface of the air, a needle can be inserted deep into the stroma without puncturing Descemet membrane. This allows safe and efficient separation of Descemet membrane. Moreover, air in the anterior chamber can be used as an indicator of successful Descemet membrane separation as air is shifted to the periphery with creation of the big bubble.

  19. The autophagic tumor stroma model of cancer or “battery-operated tumor growth”

    PubMed Central

    Martinez-Outschoorn, Ubaldo E; Whitaker-Menezes, Diana; Pavlides, Stephanos; Chiavarina, Barbara; Bonuccelli, Gloria; Trimmer, Casey; Tsirigos, Aristotelis; Migneco, Gemma; Witkiewicz, Agnieszka K; Balliet, Renee; Mercier, Isabelle; Wang, Chengwang; Flomenberg, Neal; Howell, Anthony; Lin, Zhao; Caro, Jaime; Pestell, Richard G

    2010-01-01

    The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the “Autophagy Paradox.” We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. We have termed this new paradigm “The Autophagic Tumor Stroma Model of Cancer Cell Metabolism” or “Battery-Operated Tumor Growth.” In this sense, autophagy in the tumor stroma serves as a “battery” to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients—both effectively “starving” cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy by the upregulation of natural, endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor

  20. Characterization of the Tumor Microenvironment and Tumor–Stroma Interaction by Non-invasive Preclinical Imaging

    PubMed Central

    Ramamonjisoa, Nirilanto; Ackerstaff, Ellen

    2017-01-01

    Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression. The resulting altered metabolic content in tumors has the ability to affect cell signaling and block cellular differentiation. Additional emerging evidence reveals that the interaction between tumor and stroma cells can alter tumor metabolism (leading to metabolic reprograming) as well as tumor growth and vascular features. This review will summarize previous and current preclinical, non-invasive, multimodal imaging efforts to characterize the tumor microenvironment, including its stromal components and understand tumor–stroma interaction in cancer development, progression, and treatment response. PMID:28197395

  1. Steroid hormones and the stroma-vascular cells of the adipose tissue.

    PubMed

    Volat, Fanny; Bouloumié, Anne

    2013-09-01

    The stroma-vascular fraction (SVF) of adipose tissue (AT) is a heterogeneous cell fraction composed of progenitor cells, endothelial cells, and immune cells. SVF plays a key role in AT homeostasis and growth as well as in obesity-associated pathologies. The SVF cell composition and phenotype are distinct according to AT location and adiposity. Such discrepancies influence AT function and are involved in obesity-associated disorders such as chronic inflammation. Investigations performed in recent years in rodents and humans provided evidence that the stroma-vascular cells contribute to the conversion of steroid hormones in AT and are also steroid targets. This review describes the link between steroids and SVF depending on gender, adiposity, and AT location and highlights the potential role of sex and corticosteroid hormones in adipogenesis, angiogenesis, and their contributions in AT inflammation.

  2. Identification of tumor epithelium and stroma in tissue microarrays using texture analysis

    PubMed Central

    2012-01-01

    Background The aim of the study was to assess whether texture analysis is feasible for automated identification of epithelium and stroma in digitized tumor tissue microarrays (TMAs). Texture analysis based on local binary patterns (LBP) has previously been used successfully in applications such as face recognition and industrial machine vision. TMAs with tissue samples from 643 patients with colorectal cancer were digitized using a whole slide scanner and areas representing epithelium and stroma were annotated in the images. Well-defined images of epithelium (n = 41) and stroma (n = 39) were used for training a support vector machine (SVM) classifier with LBP texture features and a contrast measure C (LBP/C) as input. We optimized the classifier on a validation set (n = 576) and then assessed its performance on an independent test set of images (n = 720). Finally, the performance of the LBP/C classifier was evaluated against classifiers based on Haralick texture features and Gabor filtered images. Results The proposed approach using LPB/C texture features was able to correctly differentiate epithelium from stroma according to texture: the agreement between the classifier and the human observer was 97 per cent (kappa value = 0.934, P < 0.0001) and the accuracy (area under the ROC curve) of the LBP/C classifier was 0.995 (CI95% 0.991-0.998). The accuracy of the corresponding classifiers based on Haralick features and Gabor-filter images were 0.976 and 0.981 respectively. Conclusions The method illustrates the capability of automated segmentation of epithelial and stromal tissue in TMAs based on texture features and an SVM classifier. Applications include tissue specific assessment of gene and protein expression, as well as computerized analysis of the tumor microenvironment. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4123422336534537 PMID:22385523

  3. Periostin and tumor-stroma interactions in non-small cell lung cancer

    PubMed Central

    Nitsche, Ulrich; Stangel, Daniela; Pan, Zheng; Schlitter, Anna Melissa; Esposito, Irene; Regel, Ivonne; Raulefs, Susanne; Friess, Helmut; Kleeff, Jörg; Erkan, Mert

    2016-01-01

    Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-associated mortality globally. Interactions of the cancer cells with the tumor microenvironment are essential carcinogenic features for the majority of solid tumors, such as pancreatic cancer. The present study investigated the role of stromal activation in NSCLC and analyzed the surgical specimens of 93 patients by immunohistochemistry with regard to periostin (an extracellular matrix protein), α-smooth muscle actin (α-SMA; a marker of myofibroblasts) and cluster of differentiation 31 (CD31; a marker of endothelial cells), and the activated stroma index. There was a trend towards reduced overall survival for patients with high periostin expression (hazard ratio, 1.80; 95% confidence interval, 0.99–3.27; P=0.050). No significant correlations with overall survival were identified for α-SMA (P=0.930), CD31 (P=0.923), collagen (P=0.441) or the activated stroma index (P=0.706). In a multivariable analysis, the histological tumor subtype, tumor stage, lymph node involvement and resection status were independent prognostic factors in NSCLC, but none of the investigated immunohistochemical markers were prognostic factors. Thus, the tumor microenvironment and stroma activation did not prove to be of prognostic relevance for lung cancer, as it has been previously described for pancreatic cancer. Other markers of the microenvironment of NSCLC may be of higher prognostic value, pointing towards tumor-type specific effects. PMID:27895734

  4. Targeting Enox1 in tumor stroma increases the efficacy of fractionated radiotherapy

    PubMed Central

    Smith, Clayton A.; Mont, Stacey; Traver, Geri; Sekhar, Konjeti R.; Crooks, Peter A.; Freeman, Michael L.

    2016-01-01

    The goal of this investigation was to clarify the question of whether targeting Enox1 in tumor stroma would synergistically enhance the survival of tumor-bearing mice treated with fractionated radiotherapy. Enox1, a NADH oxidase, is expressed in tumor vasculature and stroma. However, it is not expressed in many tumor types, including HT-29 colorectal carcinoma cells. Pharmacological inhibition of Enox1 in endothelial cells inhibited repair of DNA double strand breaks, as measured by γH2AX and 53BP1 foci formation, as well as neutral comet assays. For 4 consecutive days athymic mice bearing HT-29 hindlimb xenografts were injected with a small molecule inhibitor of Enox1 or solvent control. Tumors were then administered 2 Gy of x-rays. On day 5 tumors were administered a single ‘top-up’ fraction of 30 Gy, the purpose of which was to amplify intrinsic differences in the radiation fractionation regimen produced by Enox1 targeting. Pharmacological targeting of Enox1 resulted in 80% of the tumor-bearing mice surviving at 90 days compared to only 40% of tumor-bearing mice treated with solvent control. The increase in survival was not a consequence of reoxygenation, as measured by pimonidazole immunostaining. These results are interpreted to indicate that targeting of Enox1 in tumor stroma significantly enhances the effectiveness of 2 Gy fractionated radiotherapy and identifies Enox1 as a potential therapeutic target. PMID:27788492

  5. Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma

    PubMed Central

    Chen, Yulong; Terajima, Masahiko; Yang, Yanan; Sun, Li; Ahn, Young-Ho; Pankova, Daniela; Puperi, Daniel S.; Watanabe, Takeshi; Kim, Min P.; Blackmon, Shanda H.; Rodriguez, Jaime; Liu, Hui; Behrens, Carmen; Wistuba, Ignacio I.; Minelli, Rosalba; Scott, Kenneth L.; Sanchez-Adams, Johannah; Guilak, Farshid; Pati, Debananda; Thilaganathan, Nishan; Burns, Alan R.; Creighton, Chad J.; Martinez, Elisabeth D.; Zal, Tomasz; Grande-Allen, K. Jane; Yamauchi, Mitsuo; Kurie, Jonathan M.

    2015-01-01

    Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde–derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde–derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma. PMID:25664850

  6. Lactoferrin at basal side of mouse mammary epithelium derives in part from stroma cells.

    PubMed

    Pecorini, Chiara; Delpal, Serge; Truchet, Sandrine; Le Provost, Fabienne; Baldi, Antonella; Ollivier-Bousquet, Michèle

    2009-11-01

    Lactoferrin is synthesized by glandular epithelial cells and neutrophils and is also present on both sides of the mammary epithelium. We have studied the origin of lactoferrin detected in the various compartments of mouse mammary tissue. As revealed by immunogold electron microscopy, lactoferrin is present in mammary epithelial cells and in the basal region of the epithelium, associated with connective tissue and stroma cells at all physiological stages studied. A perturbation of protein synthesis or transport after in vitro treatment with cycloheximide or brefeldin A does not abrogate lactoferrin labelling in the basal region of the epithelium. The expression of lactoferrin has also been observed in the fat pads of mammary glands from mice surgically depleted of epithelial cells. The sealing of one teat for 24 h is accompanied by an increase in both the number of stroma cells and the labelling of myoepithelial cells. Thus, the lactoferrin present in the interstitial space of the mouse mammary epithelium originates in part from stroma cells. Possible roles of lactoferrin at the basal side of the mammary epithelium are discussed.

  7. Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription

    PubMed Central

    Kaukonen, Riina; Mai, Anja; Georgiadou, Maria; Saari, Markku; De Franceschi, Nicola; Betz, Timo; Sihto, Harri; Ventelä, Sami; Elo, Laura; Jokitalo, Eija; Westermarck, Jukka; Kellokumpu-Lehtinen, Pirkko-Liisa; Joensuu, Heikki; Grenman, Reidar; Ivaska, Johanna

    2016-01-01

    Tissue homeostasis is dependent on the controlled localization of specific cell types and the correct composition of the extracellular stroma. While the role of the cancer stroma in tumour progression has been well characterized, the specific contribution of the matrix itself is unknown. Furthermore, the mechanisms enabling normal—not cancer—stroma to provide tumour-suppressive signals and act as an antitumorigenic barrier are poorly understood. Here we show that extracellular matrix (ECM) generated by normal fibroblasts (NFs) is softer than the CAF matrix, and its physical and structural features regulate cancer cell proliferation. We find that normal ECM triggers downregulation and nuclear exit of the histone demethylase JMJD1a resulting in the epigenetic growth restriction of carcinoma cells. Interestingly, JMJD1a positively regulates transcription of many target genes, including YAP/TAZ (WWTR1), and therefore gene expression in a stiffness-dependent manner. Thus, normal stromal restricts cancer cell proliferation through JMJD1a-dependent modulation of gene expression. PMID:27488962

  8. Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

    PubMed

    Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L; Midkiff, Bentley; Troester, Melissa A

    2016-02-01

    Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P < 0.0001), with an approximate 0.7% change in area for each component, until age 55 years when these area measures reached a steady state. Although epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period.

  9. Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma

    PubMed Central

    Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L.; Midkiff, Bentley; Troester, Melissa A.

    2015-01-01

    Complete age-related regression of mammary epithelium, often termed post-menopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study (NBS). High-resolution digital images of normal breast Hematoxylin & Eosin stained slides were partitioned into epithelium, adipose tissue, and non-fatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models Stromal area decreased (p=0.0002) and adipose tissue area increased (p<0.0001), with an approximate 0.7% change in area for each component, until age 55 when these area measures reached a steady state. While epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period. PMID:26772400

  10. Galectin-1 drives pancreatic carcinogenesis through stroma remodeling and Hedgehog signaling activation

    PubMed Central

    Martínez-Bosch, Neus; Fernández-Barrena, Maite G.; Moreno, Mireia; Ortiz-Zapater, Elena; André, Sabine; Gabius, Hans-Joachim; Hwang, Rosa F.; Poirier, Françoise; Munné-Collado, Jessica; Iglesias, Mar; Navas, Carolina; Guerra, Carmen; Fernández-Zapico, Martin E.; Navarro, Pilar

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDA) is the most aggressive tumor, showing incidence and mortality values almost identical. Despite remarkable advances in PDA molecular characterization, this disease is still refractory to current treatments. Desmoplastic stroma, a constant hallmark of PDA, has recently emerged as the major responsible for PDA therapeutic resistance, therefore representing a promising target. Galectin-1 (Gal1), a glycan-binding protein, is highly expressed in PDA stroma but its role remains unknown. Here, we aim to understand in vivo Gal1 functions and the molecular pathways responsible for its oncogenic properties. Genetic ablation of Gal1 in Ela-myc mice dampens tumor progression through inhibition of proliferation, angiogenesis, desmoplasia and stimulation of tumor-associated immune response, resulting in a 20% increase on the animal life span. In vitro and in vivo studies unveil that these effects are mediated by modulation of the tumor microenvironment in a non-cell autonomous manner. Importantly, acinar-to-ductal metaplasia, a crucial step for PDA initiation, is also regulated by Gal1. Finally, high-throughput gene expression studies and molecular analysis aimed at identifying the underlying mechanism revealed that Gal1 promotes Hedgehog pathway both in PDA cells and stromal fibroblasts. In summary, our studies define a novel role of Gal1 in PDA tumor epithelium-stroma crosstalk and suggest this lectin as potential molecular target for therapy of neoplasms overexpressing Gal1. PMID:24812270

  11. A novel method in preparation of acellularporcine corneal stroma tissue for lamellar keratoplasty

    PubMed Central

    Shao, Yi; Tang, Jing; Zhou, Yueping; Qu, Yangluowa; He, Hui; Liu, Qiuping; Tan, Gang; Li, Wei; Liu, Zuguo

    2015-01-01

    Our objective was to develop a novel lamellar cornealbiomaterial for corneal reconstruction.Theporcine acellular corneal stroma discs (ACSDs) were prepared from de-epithelized fresh porcine corneas (DFPCs) by incubation with 100% fresh human serum and additional electrophoresis at 4°C. Such manipulation removed theanterior corneal stromal cells without residual of DNA content and α-Galantigen. Human serum decellularizing activity on porcineanterior corneal stroma cells is through apoptosis, and associated with the presence of α-Gal epitopes in anterior stroma. ACSDs displayed similar optical, biomechanical properties and ultrastructure to DFPCs, and showed good histocompatibility in rabbit corneal stromal pockets and anterior chamber. Rabbit corneallamellar keratoplasty (LKP) using ACSDs showed no rejection and high transparency of cornea at 2 months after surgery. In vivo confocal laser scanning microscopy and immunostaining analysis showed complete re-epithelization and stromal cell in growth of ACSDs without inflammatory cell infiltration, new blood vessel ingrowth and excessive wound healing. In conclusion, this novel decellularization method may be valuable for preparation of xenogenic corneal tissue for clinical application, ACSDs resulted from this method may be served as a matrix equivalent for LKP in corneal xenotransplantation. PMID:26885261

  12. Three-dimensional arrangement of elastic fibers in the human corneal stroma.

    PubMed

    Lewis, Philip N; White, Tomas L; Young, Robert D; Bell, James S; Winlove, C Peter; Meek, Keith M

    2016-05-01

    The cornea is the main refracting lens in the eye. As part of the outer tunic it has to be resilient, a property conferred by the organisation of the constituent collagen. It also has to be sufficiently elastic to regain its exact shape when deformed, in order not to distort the retinal image. The basis of this elasticity is not fully understood. The purpose of this study was to characterise in three dimensions the arrangement and distribution of elastic fibers in the human corneal stroma, using serial block face scanning electron microscopy. We have demonstrated that there exists a complex network of elastic fibers that appear to originate in the sclera or limbus. These appear as elastic sheets in the limbus and peripheral cornea immediately above the trabecular meshwork which itself appears to extend above Descemet's membrane in the peripheral stroma. From these sheets, elastic fibers extend into the cornea; moving centrally they bifurcate and trifurcate into narrower fibers and are concentrated in the posterior stroma immediately above Descemet's membrane. We contend that elastic sheets will play an important role in the biomechanical deformation and recovery of the peripheral cornea. The network may also have practical implications for understanding the structural basis behind a number of corneal surgeries.

  13. Protease-Activated Receptor-1 is Upregulated in Reactive Stroma of Primary Prostate Cancer and Bone Metastasis

    PubMed Central

    Zhang, Xiaotun; Wang, Wenbin; True, Lawrence D.; Vessella, Robert L.; Takayama, Thomas K.

    2009-01-01

    BACKGROUND Prostate cancer progression is partly facilitated by tumor-stroma interactions. We recently reported that protease-activated receptors (PAR-1 and PAR-2) are overexpressed in prostate cancer, and PAR-1 expression in peritumoral stroma is associated with biochemical recurrence. However, the nature of PAR expression in prostate tumor microenvironment is not fully understood. We therefore evaluated PAR-1 and PAR-2 expression in primary prostate cancer and bone metastasis. METHODS PAR-1 and PAR-2 expression in normal, primary prostate cancer and the corresponding bone metastatic tissues were examined by immunohistochemistry, and double-label immunohistochemistry with the use of additional markers. RESULTS PAR-1 was expressed in peritumoral stroma in the majority of primary cancer tissues (83%). Serial sections and double-label immunohistochemistry determined that these PAR-1 expressing stromal cells were predominantly myofibroblasts, the primary cell type in reactive stroma. Analysis of cancer glands revealed that PAR-1 expression was significantly increased in the reactive stroma around higher Gleason grade cancers. PAR-2 was predominantly expressed in the primary cancer cells as well as smooth muscle cells but not in reactive stroma. In bone metastasis, PAR-1 expression in cancer cells was elevated compared to the primary site from the same patient. In the bone reactive stroma, PAR-1 was present in vascular endothelial cells and fibroblasts, while both PAR-1 and PAR-2 were expressed in osteoblasts and osteoclasts. CONCLUSIONS In primary prostate cancer and bone metastasis, PAR-1 is upregulated in reactive stroma and PAR-2 is uniformly overexpressed in carcinoma cells, suggesting these receptors may play potentially different roles in prostate cancer development and metastasis. PMID:19170048

  14. Chlorophyll composition and photochemical activity of photosystems detached from chloroplast grana and stroma lamellae.

    PubMed

    Gasanov, R A; French, C S

    1973-07-01

    A stroma fraction that has photosystem 1 activity and grana lamellae fractions that have activities for both photosystems were isolated by differential centrifugation of a needle valve homogenate. Subsequent fractions, corresponding to photosystems 1 (F-1D) and 2 (F-2D) were isolated by digitonin treatment of the grana lamellae (P-10K) and compared with respect to their chlorophyll composition and electron transport activities.Fraction F-2D from grana lamellae having photosystem 2 activity is primarily active in photosystem 2 and contains only the four major forms of chlorophyll a with a predominance of chlorophyll a 677 nm. This fraction differs from the original grana membranes in the absence of the longwavelength form of chlorophyll a and in the widening of the absorption band of chlorophyll a 682 nm from 10.9 to 15.6 nm.Photosystem 1 particles from grana and stroma both have high photosystem 1 activity but differ from each other in the proportions of the four major forms of chlorophyll a. The short-wavelength forms of chlorophyll a and also chlorophyll b 650 nm in particles from grana lamellae comprise relatively more total area than these same forms in the particles from stroma. In addition, the fraction corresponding to photosystem 1 from grana lamellae is not shifted to the long-wavelength side of the main absorption maximum, as compared to the photosystem 2 particles from grana and the original grana membrane fraction; this is usually observed in fractions that have photosystem 1 activity. Furthermore, the longest wavelength form of chlorophyll a in the photosystem 1 particles from grana is at 700 nm, while in the same fraction from stroma, it is at 706 nm.The half-width of the four main forms of chlorophyll a and both forms of chlorophyll b in the photosystem 1 fraction from grana is narrower than that of the corresponding forms in the same fraction from stroma. This may indicate a different packing of pigment molecules that are aggregated on the surface

  15. The hematopoietic defect in PNH is not due to defective stroma, but is due to defective progenitor cells.

    PubMed

    Nishimura, Jun-ichi; Ware, Russell E; Burnette, Angela; Pendleton, Andrew L; Kitano, Kiyoshi; Hirota, Toshiyuki; Machii, Takashi; Kitani, Teruo; Smith, Clay A; Rosse, Wendell F

    2002-01-01

    Although paroxysmal nocturnal hemoglobinuria (PNH) is often associated with aplastic anemia (AA), the nature of the pathogenetic link between PNH and AA remains unclear. Moreover, the PIG-A mutation appears to be necessary but not sufficient for the development of PNH, suggesting other factors are involved. The ability of PNH marrow cells to form in vitro hematopoietic colonies and the ability of PNH marrow to generate stroma that could support hematopoiesis of normal or PNH marrow in cross culture were investigated. PNH marrow from both post-Ficoll and post-lineage depleted hematopoietic progenitor cells grew similarly significantly fewer colonies than normal marrow. Sorting of CD59(+) and CD59(-) CD34(+) CD38(-) cells from patients with PNH showed similarly impaired clonogenic efficiency, indicating that the hematopoietic defect in PNH does not directly relate to GPI-anchored protein expression. PNH marrow readily grew stroma similar to marrow from normal donors. Cross culture experiments revealed that PNH stroma appears to function normally in vitro; it can support growth of normal marrow cells as well as normal stroma does, but neither PNH nor normal stroma could support the growth of PNH marrow cells. The hematopoietic defect in PNH is not due to defective stroma, but is due to defective progenitor cell growth related to additional unknown factors.

  16. Assessment of oestrogen and progestin effects on epithelium and stroma from pre- and postmenopausal endometria.

    PubMed

    King, R J; Lane, G; Siddle, N; Taylor, R W; Townsend, P T; Whitehead, M I

    1981-12-01

    The efficacy of commercially available progestin preparations were investigated with a view toward determining the optimum type, dose, duration, and route of administration required to protect the endometrium. Biochemical indices of estrogen and progestin action in endometria from postmenopausal women receiving various hormone therapies were monitored. The premenopausal samples obtained during the proliferative and secretory phases of the cycle can be compared with physiologically normal activities. Estrogen effects were monitored by nuclear estradiol receptor (REN) and soluble progesterone receptor (RP) content and DNA synthesis by autoradiography after [3-H]-thymidine labelling. Progestin action was assayed by inhibition of estrogen-induced REN and DNA synthesis by induction of isocritic and estradiol dehydrogenases and by morphological criteria. Postmenopausal patients were attending the menopause clinics at King's College Hospital or the Chelsea Hospital for Women in London for symptoms associated with the climacteric. Premenopausal samples were obtained from women attending the above hospitals as well as St. Thomas Hospital in London. There are no differences in REN or estradiol receptor content (RET) between epithelium and stroma for any of the groups. Progestins, regardless of whether they are derived from exogenous (postmenopausal) or endogenous (premenopausal sources, decrease REN and RET in both fractions. Progestins also decreased DNA synthesis in both cell types and this suppression correlates with the fall in REN. The RP content of epithelium is greater than stroma, but the 2 enzymes are markedly stimulated by progestins in epithelium but not stroma. The lower RP content of the stromal fraction could be because of cellular heterogeneity, differential loss of receptor during processing, or to genuine differences between epithelium and stroma. Estrogen induced DNA synthesis is inhibited by progestins in both epithelium ans stroma but the induction of

  17. Roles of limbal microvascular net and limbal stroma in regulating maintenance of limbal epithelial stem cells.

    PubMed

    Huang, Minghai; Wang, Bowen; Wan, Pengxia; Liang, Xuanwei; Wang, Xiaoran; Liu, Ying; Zhou, Qiang; Wang, Zhichong

    2015-02-01

    Knowledge of the microenvironment (niche) of stem cells is helpful for stem-cell-based regenerative medicine. In the eye, limbal epithelial stem cells (corneal epithelial stem cells) provide the self-renewal capacity of the corneal epithelium and are essential for maintaining corneal transparency and vision. Limbal epithelial stem cell deficiency results in significant visual deterioration. Successful treatment of this type of blinding disease requires studies of the limbal epithelial stem cells and their microenvironment. We investigate the function of the limbal microvascular net and the limbal stroma in the maintenace of the limbal epithelial stem cell niche in vivo and examine the regulation of limbal epithelial stem cell survival, proliferation and differentiation in vivo. We assess the temporal and spatial changes in the expression patterns of the following markers during a six-month follow-up of various rabbit limbal autograft transplantation models: vascular endothelial cell marker CD31, corneal epithelium differentiation marker K3, limbal epithelial stem-cell-associated markers P63 and ABCG2 and proliferating cell nuclear marker Ki67. Our results suggest that limbal epithelial stem cells cannot maintain their stemness or proliferation without the support of the limbal microvascular net microenvironment. Thus, both the limbal microvascular net and the limbal stroma play important roles as components of the limbal epithelial stem cell niche maintaining limbal epithelial stem cell survival and proliferation and the avoidance of differentiation. The limbal stroma constitutes the structural basis of the limbal epithelial stem cell niche and the limbal microvascular net is a requirement for this niche. These new insights should aid the eventual construction of tissue-engineered cornea for corneal blind patients in the future.

  18. Antagonizing the Hedgehog Pathway with Vismodegib Impairs Malignant Pleural Mesothelioma Growth In Vivo by Affecting Stroma.

    PubMed

    Meerang, Mayura; Bérard, Karima; Felley-Bosco, Emanuela; Lauk, Olivia; Vrugt, Bart; Boss, Andreas; Kenkel, David; Broggini-Tenzer, Angela; Stahel, Rolf A; Arni, Stephan; Weder, Walter; Opitz, Isabelle

    2016-05-01

    An autocrine-driven upregulation of the Hedgehog (Hh) signaling pathway has been described in malignant pleural mesothelioma (MPM), in which the ligand, desert Hh (DHH), was produced from tumor cells. However, our investigation revealed that the Hh pathway is activated in both tumor and stroma of MPM tumor specimens and an orthotopic immunocompetent rat MPM model. This was demonstrated by positive immunohistochemical staining of Glioma-associated oncogene 1 (GLI1) and Patched1 (PTCH1) in both tumor and stromal fractions. DHH was predominantly expressed in the tumor fractions. To further investigate the role of the Hh pathway in MPM stroma, we antagonized Hh signaling in the rat model of MPM using a Hh antagonist, vismodegib, (100 mg/kg orally). Daily treatment with vismodegib efficiently downregulated Hh target genes Gli1, Hedgehog Interacting Protein (Hhip), and Ptch1, and caused a significant reduction of tumor volume and tumor growth delay. Immunohistochemical analyses revealed that vismodegib treatment primarily downregulated GLI1 and HHIP in the stromal compartment along with a reduced expression of previously described fibroblast Hh-responsive genes such as Fibronectin (Fn1) and Vegfa Primary cells isolated from the rat model cultured in 3% O2 continued to express Dhh but did not respond to vismodegib in vitro However, culture supernatant from these cells stimulated Gli1, Ptch1, and Fn1 expression in mouse embryonic fibroblasts, which was suppressed by vismodegib. Our study provides new evidence regarding the role of Hh signaling in MPM stroma in the maintenance of tumor growth, emphasizing Hh signaling as a treatment target for MPM. Mol Cancer Ther; 15(5); 1095-105. ©2016 AACR.

  19. Evaluation of Stroma-Free Hemoglobin Solutions as Resuscitative Fluids for the Injured Soldier

    DTIC Science & Technology

    1988-11-01

    sri -~ S. i~ -~I *1*~-. - -~ ti- H -~ S - - +1-i-i ~ .--.- -~ ~ .4 ~’ ~ - -Cl -- - :4 - I; I :4 - :4 .44- :4 I :4 . - ~f1 :4 ti- H - H ...hemoglobin solutions have FWo .𔄁~i if !t 1V& lt-j: di aised the question of non-stroma related n:z i i, L𔃼 !, A i h ,7,, ! \\,ycr 4dm’, toxicity in the...animal, wecre anesthetized andsl_ that peratia all\\ prepared as prex.iou’ dcscrillci by- 1_71(2(_bi solta iW P x th px’ I U, \\kit h the modification th

  20. Altered Proteomic Polymorphisms in the Caterpillar Body and Stroma of Natural Cordyceps sinensis during Maturation

    PubMed Central

    Wu, Zi-Mei; Gao, Ling; Yao, Yi-Sang; Tan, Ning-Zhi; Wu, Jian-Yong; Ni, Luqun; Zhu, Jia-Shi

    2014-01-01

    Objective To examine the maturational changes in proteomic polymorphisms resulting from differential expression by multiple intrinsic fungi in the caterpillar body and stroma of natural Cordyceps sinensis (Cs), an integrated micro-ecosystem. Methods The surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) biochip technique was used to profile the altered protein compositions in the caterpillar body and stroma of Cs during its maturation. The MS chromatograms were analyzed using density-weighted algorithms to examine the similarities and cluster relationships among the proteomic polymorphisms of the Cs compartments and the mycelial products Hirsutella sinensis (Hs) and Paecilomyces hepiali (Ph). Results: SELDI-TOF MS chromatograms displayed dynamic proteomic polymorphism alterations among samples from the different Cs compartments during maturation. More than 1,900 protein bands were analyzed using density-weighted ZUNIX similarity equations and clustering methods, revealing integral polymorphism similarities of 57.4% between the premature and mature stromata and 42.8% between the premature and mature caterpillar bodies. The across-compartment similarity was low, ranging from 10.0% to 18.4%. Consequently, each Cs compartment (i.e., the stroma and caterpillar body) formed a clustering clade, and the 2 clades formed a Cs cluster. The polymorphic similarities ranged from 0.51% to 1.04% between Hs and the Cs compartments and were 2.8- to 4.8-fold higher (1.92%–4.34%) between Ph and the Cs compartments. The Hs and Ph mycelial samples formed isolated clades outside of the Cs cluster. Conclusion Proteomic polymorphisms in the caterpillar body and stroma of Cs change dynamically during maturation. The proteomic polymorphisms in Hs and Ph differ from those in Cs, suggesting the presence of multiple Cs-associated fungi and multiple Ophiocordyceps sinensis genotypes with altered differential protein expression in the Cs compartments

  1. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin.

    PubMed

    Kobayashi, Hanako; Liu, Qingdu; Binns, Thomas C; Urrutia, Andres A; Davidoff, Olena; Kapitsinou, Pinelopi P; Pfaff, Andrew S; Olauson, Hannes; Wernerson, Annika; Fogo, Agnes B; Fong, Guo-Hua; Gross, Kenneth W; Haase, Volker H

    2016-05-02

    Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2-/- renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2-/- mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation.

  2. Regulation of dendritic-cell differentiation by bone marrow stroma via different Notch ligands

    PubMed Central

    Cheng, Pingyan; Nefedova, Yulia; Corzo, Cesar A.; Gabrilovich, Dmitry I.

    2007-01-01

    Notch is a major factor mediating interaction between hematopoietic progenitor cells (HPCs) and bone marrow stroma (BMS). However its contribution to dendritic cell (DC) differentiation is controversial. We found that main Notch ligands Delta-1 and Jagged-1 had the opposite effect on DC differentiation. Delta-1 promoted generation of fully differentiated DCs, whereas Jagged-1 stimulated accumulation of DC precursors but prevented their transition to terminally differentiated DCs. BMS expressed a substantially higher level of Jagged-1 than Delta-1. Just the opposite expression pattern was observed in spleen stroma (SS). The BMS effect on DC differentiation was similar to that of Jagged-1, whereas the effect of SS was similar to the effect of Delta-1. Down-regulation of Jagged-1 in BMS substantially increased DC differentiation. Experiments in vivo with adoptive transfer of DC precursors further supported the different roles of BMS and SS in DC development. Jagged-1 and Delta-1 equally activated CBF-1/RBPJκ transcription factor, which is a major Notch target. However, they produced a different pattern of activation of Notch target gene Hes1. Overexpression of Hes1 resulted in increased DC differentiation from HPCs. Thus, this study not only revealed the different role of Notch ligands in DC differentiation but also may provide a new insight into regulation of DC differentiation by BMS. PMID:16973960

  3. FGFR4 promotes stroma-induced epithelial-to-mesenchymal transition in colorectal cancer.

    PubMed

    Liu, Rui; Li, Jingyi; Xie, Ke; Zhang, Tao; Lei, Yunlong; Chen, Yi; Zhang, Lu; Huang, Kai; Wang, Kui; Wu, Hong; Wu, Min; Nice, Edouard C; Huang, Canhua; Wei, Yuquan

    2013-10-01

    Tumor cells evolve by interacting with the local microenvironment; however, the tumor-stroma interactions that govern tumor metastasis are poorly understood. In this study, proteomic analyses reveal that coculture with tumor-associated fibroblasts (TAF) induces significant overexpression of FGFR4, but not other FGFRs, in colorectal cancer cell lines. Mechanistic study shows that FGFR4 plays crucial roles in TAF-induced epithelial-to-mesenchymal transition (EMT) in colorectal cancer cell lines. Accumulated FGFR4 in cell membrane phosphorylates β-catenin, leading to translocation of β-catenin into the nucleus. Further, TAF-derived CCL2 and its downstream transcription factor, Ets-1, are prerequisites for TAF-induced FGFR4 upregulation. Furthermore, FGFR4-associated pathways are shown to be preferentially activated in colorectal tumor samples, and direct tumor metastasis in a mouse metastasis model. Our study shows a pivotal role of FGFR4 in tumor-stroma interactions during colorectal cancer metastasis, and suggests novel therapeutic opportunities for the treatment of colorectal cancer.

  4. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin

    PubMed Central

    Liu, Qingdu; Binns, Thomas C.; Davidoff, Olena; Kapitsinou, Pinelopi P.; Pfaff, Andrew S.; Olauson, Hannes; Fogo, Agnes B.; Fong, Guo-Hua; Gross, Kenneth W.

    2016-01-01

    Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2–/– renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2–/– mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801

  5. In vitro 3D corneal tissue model with epithelium, stroma, and innervation.

    PubMed

    Wang, Siran; Ghezzi, Chiara E; Gomes, Rachel; Pollard, Rachel E; Funderburgh, James L; Kaplan, David L

    2017-01-01

    The interactions between corneal nerve, epithelium, and stroma are essential for maintaining a healthy cornea. Thus, corneal tissue models that more fully mimic the anatomy, mechanical properties and cellular components of corneal tissue would provide useful systems to study cellular interactions, corneal diseases and provide options for improved drug screening. Here a corneal tissue model was constructed to include the stroma, epithelium, and innervation. Thin silk protein film stacks served as the scaffolding to support the corneal epithelial and stromal layers, while a surrounding silk porous sponge supported neuronal growth. The neurons innervated the stromal and epithelial layers and improved function and viability of the tissues. An air-liquid interface environment of the corneal tissue was also mimicked in vitro, resulting in a positive impact on epithelial maturity. The inclusion of three cell types in co-culture at an air-liquid interface provides an important advance for the field of in vitro corneal tissue engineering, to permit improvements in the study of innervation and corneal tissue development, corneal disease, and tissue responses to environmental factors.

  6. Microscopic analysis of structural changes in diode-laser-welded corneal stroma

    NASA Astrophysics Data System (ADS)

    Matteini, Paolo; Rossi, Francesca; Menabuoni, Luca; Pini, Roberto

    2007-02-01

    Diode laser welding of the cornea is a technique used to provide immediate sealing of corneal wounds: the cut is stained with a water solution of Indocyanine Green and is then irradiated with an 810 nm laser at low power densities (12-16 W/cm2), which induces a localized heating of the stroma in the range 55-66 °C range. In this study, we present a microscopic analysis aimed at evaluating the structural modifications induced in the stromal collagen of pig eyes during the laser welding of corneal wounds. Cornea samples obtained from twenty freshly-enucleated eyes were cut with a pre-calibrated knife and subjected to the laser welding procedure. Histological slices of the laser-welded stroma were examined by means of optical and transmission electron microscopy. These analyses indicated that bridges of lamellar structures crossed the wound edges with no presence of a coagulation effect. After laser welding, collagen fibrils appeared differently oriented among themselves in comparison with those of the control samples, but with similar mean fibril diameters. The laser-induced effect appeared to be confined to the ICG stained area of the cut walls, and no heat damage was observed at the operative power levels of laser corneal welding.

  7. Using genipin-crosslinked acellular porcine corneal stroma for cosmetic corneal lens implants.

    PubMed

    Liu, Zhao; Zhou, Qiang; Zhu, Jixiang; Xiao, Jianhui; Wan, Pengxia; Zhou, Chenjing; Huang, Zheqian; Qiang, Na; Zhang, Wei; Wu, Zheng; Quan, Daping; Wang, Zhichong

    2012-10-01

    Acellular porcine corneal stroma (APCS) has been proven to maintain the matrix microenvironment and is therefore an ideal biomaterial for the repair and reconstruction of corneal stroma. This study aims to develop a method to prepare cosmetic corneal lens implants for leukoma using genipin-crosslinked APCS (Gc-APCS). The Gc-APCS was prepared from APCS immersed in 1.0% genipin aqueous solution (pH 5.5) for 4 h at 37 °C, followed by lyophilization at -10 °C. The color of the Gc-APCS gradually deepened to dark-blue. The degree of crosslinking was 45.7 ± 4.6%, measured by the decrease of basic and hydroxy amino acids. The porous structure and ultrastructure of collagenous lamellae were maintained, and the porosity and BET SSA were 72.7 ± 4.6% and 23.01 ± 3.45 m(2)/g, respectively. The Gc-APCS rehydrated to the physiological water content within 5 min and was highly resistant to collagenase digestion. There were no significant differences in the areal modulus and curvature variation between Gc-APCS and nature porcine cornea. The dark-blue pigments were stable to pH, light and implantation in vivo. Gc-APCS extracts had no inhibitory effects on the proliferation of keratocytes. Corneal neovascularization, graft degradation and corneal rejection were not observed within 6 months.

  8. Antitumor Effects of Chimeric Receptor Engineered Human T Cells Directed to Tumor Stroma

    PubMed Central

    Kakarla, Sunitha; Chow, Kevin KH; Mata, Melinda; Shaffer, Donald R; Song, Xiao-Tong; Wu, Meng-Fen; Liu, Hao; Wang, Lisa L; Rowley, David R; Pfizenmaier, Klaus; Gottschalk, Stephen

    2013-01-01

    Cancer-associated fibroblasts (CAFs), the principle component of the tumor-associated stroma, form a highly protumorigenic and immunosuppressive microenvironment that mediates therapeutic resistance. Co-targeting CAFs in addition to cancer cells may therefore augment the antitumor response. Fibroblast activation protein-α (FAP), a type 2 dipeptidyl peptidase, is expressed on CAFs in a majority of solid tumors making it an attractive immunotherapeutic target. To target FAP-positive CAFs in the tumor-associated stroma, we genetically modified T cells to express a FAP-specific chimeric antigen receptor (CAR). The resulting FAP-specific T cells recognized and killed FAP-positive target cells as determined by proinflammatory cytokine release and target cell lysis. In an established A549 lung cancer model, adoptive transfer of FAP-specific T cells significantly reduced FAP-positive stromal cells, with a concomitant decrease in tumor growth. Combining these FAP-specific T cells with T cells that targeted the EphA2 antigen on the A549 cancer cells themselves significantly enhanced overall antitumor activity and conferred a survival advantage compared to either alone. Our study underscores the value of co-targeting both CAFs and cancer cells to increase the benefits of T-cell immunotherapy for solid tumors. PMID:23732988

  9. On Orbit Osteobiology Experiments: from "STROMA" to "MDS" -from in vitro to in vivo

    NASA Astrophysics Data System (ADS)

    Liu, Yi; Cancedda, Ranieri

    Spaceflight causes profound changes in the skeleton, in particular, in the weight-loading bones. Uncoupling of bone remodeling equilibrium between bone formation and resorption is con-sidered responsible for the microgravity-induced bone loss. These changes result in weak-ened and brittle bones prone to fracture on re-entry and in accelerated osteoporosis, making bone deterioration a major problem obstructing the prospects of long-duration manned space flight. Osteoblasts (bone forming cells) and osteocytes (bone resorption cells) are known to be mechano-sensors. Short-exposure of osteoblasts to simulated microgravity ensnarled cell adhe-sion and cytoskeleton. Also osteoblast precursors such as bone marrow stroma cells (BMSC) were shown to be sensitive to mechanical loading. We performed a series of STROMA space-flight experiments by culturing BMSC or co-culturing osteoblasts and osteoclast precursors in automated bioreactors on orbit. Genechip analysis revealed an inhibition of cell proliferation and an unexpected activation of nervous system development genes by spaceflight. To unravel effects of microgravity on genes governing bone mass, transgenic mice with a higher bone mass were flown to orbit inside the Mice Drawer System (MDS) payload. The MDS experiment was launched inside Shuttle Discovery in STS-128 on August 28 2009 at 23:58 EST, and returned to earth by Shuttle Atlantis in STS129 on November 27 2009 at 9:47 EST, marking it as the first long duration animal experiment on the International Space Station (ISS).

  10. The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma

    PubMed Central

    Chen, Xin; McClelland, Michael; Jia, Zhenyu; Rahmatpanah, Farah B.; Sawyers, Anne; Trent, Jeffrey; Duggan, David; Mercola, Dan

    2015-01-01

    Here we tested the hypothesis that SNPs associated with prostate cancer risk, might differentially affect RNA expression in prostate cancer stroma. The most significant 35 SNP loci were selected from Genome Wide Association (GWA) studies of ~40,000 patients. We also selected 4030 transcripts previously associated with prostate cancer diagnosis and prognosis. eQTL analysis was carried out by a modified BAYES method to analyze the associations between the risk variants and expressed transcripts jointly in a single model. We observed 47 significant associations between eight risk variants and the expression patterns of 46 genes. This is the first study to identify associations between multiple SNPs and multiple in trans gene expression differences in cancer stroma. Potentially, a combination of SNPs and associated expression differences in prostate stroma may increase the power of risk assessment for individuals, and for cancer progression. PMID:25638161

  11. Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers

    PubMed Central

    Allaoui, Roni; Bergenfelz, Caroline; Mohlin, Sofie; Hagerling, Catharina; Salari, Kiarash; Werb, Zena; Anderson, Robin L.; Ethier, Stephen P.; Jirström, Karin; Påhlman, Sven; Bexell, Daniel; Tahin, Balázs; Johansson, Martin E.; Larsson, Christer; Leandersson, Karin

    2016-01-01

    Triple-negative (TN) breast cancers (ER−PR−HER2−) are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback loop amplifies the formation of a reactive stroma, contributing to the aggressive phenotype of TN breast tumours. These insights could help select more suitable therapies targeting the stromal component of these tumours, and could aid prediction of drug resistance. PMID:27725631

  12. Microkeratome assisted deep lamellar keratoprosthesis

    PubMed Central

    Shimmura, S; Miyashita, H; Uchino, Y; Taguchi, T; Kobayashi, H; Shimazaki, J; Tanaka, J; Tsubota, K

    2006-01-01

    Aims To establish a keratoprosthesis (Kpro) surgical technique that maintains an intact superficial corneal layer. Methods A manual microkeratome (Moria LSK‐1) was used to create a 130 μm flap of approximately 10 mm diameter in the right eye of Japanese white rabbits. The stoma beneath the flap area was dissected before the removal of a 5.0 mm stromal disc. A 5.0 mm collagen I immobilised poly(vinyl alcohol) (COL‐PVA) disc was placed on the exposed posterior stroma close to Descemet's membrane. The flap was repositioned and fixed using 10‐0 nylon sutures, which were removed 2 days following surgery. The corneas were followed clinically by slit lamp microscopy and photographs. Rabbits were sacrificed after 6 months, and the transplanted corneas were examined histologically by haematoxylin and eosin staining and immunohistochemistry against vimentin and α‐smooth muscle actin (α‐SMA). Results The transplanted COL‐PVA discs remained transparent throughout the study, with no complications related to the flap or overlying epithelium. The interface between COL‐PVA and Descemet's membrane remained clear without signs of opacification caused by scarring or cellular deposition. Pathology revealed the intact COL‐PVA polymer in the posterior stroma, with minimal cellular infiltration along the anterior and posterior interfaces. Immunohistology shows vimentin and α‐SMA staining at levels comparable to lamellar keratoplasty control. Conclusions Microkeratome assisted deep lamellar keratoprosthesis may be a safe technique for the transplantation of artificial hydrogels for therapeutic purposes. PMID:16597665

  13. Friedmann equations and thermodynamics of apparent horizons.

    PubMed

    Gong, Yungui; Wang, Anzhong

    2007-11-23

    With the help of a masslike function which has a dimension of energy and is equal to the Misner-Sharp mass at the apparent horizon, we show that the first law of thermodynamics of the apparent horizon dE=T(A)dS(A) can be derived from the Friedmann equation in various theories of gravity, including the Einstein, Lovelock, nonlinear, and scalar-tensor theories. This result strongly suggests that the relationship between the first law of thermodynamics of the apparent horizon and the Friedmann equation is not just a simple coincidence, but rather a more profound physical connection.

  14. Systems Analysis of a Mouse Xenograft Model Reveals Annexin A1 as a Regulator of Gene Expression in Tumor Stroma

    PubMed Central

    Yi, Ming

    2012-01-01

    Annexin A1 is a multi functional molecule which is involved in inflammation, innate and adaptive immune systems, tumor progression and metastasis. We have previously showed the impaired tumor growth, metastasis, angiogenesis and wound healing in annexin A1 knockout mice. While tumor is a piece of heterogeneous mass including not only malignant tumor cells but also the stroma, the importance of the tumor stroma for tumor progression and metastasis is becoming increasingly clear. The tumor stroma is comprised by various components including extracellular matrix and non-malignant cells in the tumor, such as endothelial cells, fibroblasts, immune cells, inflammatory cells. Based on our previous finding of pro-angiogenic functions for annexin A1 in vascular endothelial cell sprouting, wound healing, tumor growth and metastasis, and the previously known properties for annexin A1 in immune cells and inflammation, this study hypothesized that annexin A1 is a key functional player in tumor development, linking the various components in tumor stroma by its actions in endothelial cells and immune cells. Using systems analysis programs commercially available, this paper further compared the gene expression between tumors from annexin A1 wild type mice and annexin A1 knockout mice and found a list of genes that significantly changed in the tumor stroma that lacked annexin A1. This revealed annexin A1 to be an effective regulator in tumor stroma and suggested a mechanism that annexin A1 affects tumor development and metastasis through interaction with the various components in the microenvironment surrounding the tumor cells. PMID:23077482

  15. Identification of Stress Change Within a Rock Mass Through Apparent Stress of Local Seismic Events

    NASA Astrophysics Data System (ADS)

    Brown, Laura; Hudyma, Martin

    2017-01-01

    Mine blasting produces excavation geometry changes which induce stress change that can be observed in the seismic source parameter apparent stress calculated for local seismic events. Using high apparent stress as a proxy for increasing stress within a rock mass, areas experiencing increases in the local stress conditions can be determined. This paper presents the use of apparent stress of seismic events to identify areas within a rock mass experiencing local stress change. Examples from a deep Canadian mine, operating in excess of 2900 m below surface, are provided.

  16. Ectopic micronodular thymoma with lymphoid stroma in the cervical region: a rare case associated with Langerhans cells proliferation

    PubMed Central

    Yu, Min; Meng, Yuan; Xu, Bin; Zhao, Lin; Zhang, Qingfu

    2016-01-01

    Micronodular thymoma (MNT) with lymphoid stroma is a rare thymic epithelial neoplasm with the characteristics of multiple nodules separated by abundant lymphoid stroma. MNTs mainly arise in the anterior mediastinum and thymus, while ectopic MNTs are extremely rarely seen. Here, we report an ectopic MNT that occurred in the neck of a 62-year-old woman. There were also scattered eosinophilic granulocytes and S100+/CD1a+ Langerhans cells within the tumor. This case provides a better understanding of such rare, poorly understood cases. PMID:27486334

  17. Preparation of High-Density Fibrillar Collagen Matrices that Mimic Desmoplastic Tumor Stroma

    PubMed Central

    Artym, Vira V.

    2016-01-01

    The stroma of invasive tumors becomes enriched in dense fibrillar collagen as a result of the desmoplastic reaction. This desmoplastic collagen exerts profound effects on tumor and normal cells. In view of these findings, it is important to develop novel in vitro cell systems that mimic this desmoplastic extracellular matrix in order to permit cell studies under in vivo-like conditions. This Unit provides a protocol and troubleshooting guide for the preparation of high density fibrillar collagen (HDFC) matrices that closely model the desmoplastic collagenous matrix of malignant tumors. It then describes the use of this HDFC matrix for in vitro cell studies of invadopodia formation and function in extracellular matrix invasion. In addition, this Unit also provides a detailed protocol for immuno-labeling of invadopodial proteins and detection of HDFC matrix degradation associated with invadopodia to permit invadopodia visualization using fluorescence microscopy. PMID:26930554

  18. [The radioprotective effect of hypoxia on clonogenic cells of rat bone marrow stroma (KOE-F)].

    PubMed

    Konopliannikov, A G; Waĭnson, A A; Kolesnikova, A I; Zaĭtsev, A V; Kal'sina, S Sh; Lepekhina, L A

    1992-01-01

    A comparative study was made on the survival rate of cell-precursors of haemopoietic stroma, that form, in a rat bone marrow culture, colonies (clones) of fibroblasts (CFU-F) after gamma-irradiation of animals in the air or in a gas hypoxic mixture, containing 8% of O2 (GHM-8). Irradiation in GHM-8 was shown to increase the survival rate of CFU-F by 1.7 times (as compared to exposure in the air) as estimated by the total number of colonies that are formed in a culture; the radioprotective effect of GHM-8 was more pronounced for CFU-F which form dense colonies: DMF for dense and loose clones was 2.4 and 1.6 respectively.

  19. Squamous cell carcinoma with sarcomatous stroma in the nasal cavity of a dog.

    PubMed

    Bosward, K L; Kessell, A E; Lucy, R J

    2004-09-01

    This is a report of an unusual squamous cell carcinoma in the nasal cavity of a dog. A 13-year-old Golden Retriever was presented with a unilateral nasal and ocular discharge. Although a nasal tumour was suspected, initial diagnostic investigations were unrewarding, and, with worsening clinical signs, the dog was euthanatized. Necropsy examination confirmed the presence of a nasal tumour that was composed histologically of both a well-differentiated squamous cell carcinoma component blending with a predominant spindle cell component. Immunohistochemical staining with anti-human keratin/cytokeratin (AE1/AE3, CAM 5.2 and broad spectrum cytokeratin), Vimentin, Desmin, smooth muscle actin and S-100 protein supported a diagnosis of a squamous cell carcinoma with (pseudo) sarcomatous stroma.

  20. Sclerotic fibroma (storiform collagenoma)-like stroma in a fibroadenoma of axillary accessory breast tissue.

    PubMed

    Val-Bernal, José Fernando; González-Vela, María Carmen; De Grado, Mauricio; Garijo, María Francisca

    2012-08-01

    Accessory breast tissue is a subcutaneous remnant persisting after normal embryological development of the breast. It occurs most frequently in the axilla. Fibroadenomas in axillary breast tissue are rare. We report the case of a 29-year-old female patient who presented a fibroadenoma arising in the accessory breast tissue of the right axillary fossa. The neoplasm showed foci of sclerotic fibroma-like stroma. The patient had no signs of Cowden's syndrome. To the best of our knowledge, a lesion of this kind has not been previously reported. This stromal change suggests an uncommon involutional phase of the fibroadenoma with production of sclerotic and hypocellular collagen. The lesion should be differentiated from extraneural perineuroma, from the changes in fibroadenomas in Cowden's syndrome, from sclerosing lobular hyperplasia (fibroadenomatoid mastopathy) and from pseudoangiomatous stromal hyperplasia.

  1. Antigen archiving by lymph node stroma: a novel function for the lymphatic endothelium

    PubMed Central

    Kedl, Ross M.; Tamburini, Beth A.

    2015-01-01

    Secondary lymphoid stroma performs far more functions than simple structural support for lymphoid tissues, providing a host of soluble and membrane-bound cues to trafficking leukocytes during inflammation and homeostasis. More recently it has become clear that stromal cells can manipulate T cell responses, either through direct antigen-mediated stimulation of T cells or more indirectly through the retention and management of antigen after viral infection or vaccination. In light of recent data, this review provides an overview of stromal cell subsets and functions during the progression of an adaptive immune response with particular emphasis on antigen capture and retention by follicular dendritic cells (FDC) as well as the recently described “antigen archiving” function of lymphatic endothelial cells (LEC). Given its impact on the maintenance of protective immune memory, we conclude by discussing the most pressing questions pertaining to LEC antigen capture, archiving and exchange with hematopoetically derived antigen-presenting cells. PMID:26278423

  2. Multifocal epithelial tumors and field cancerization: stroma as a primary determinant

    PubMed Central

    Dotto, G. Paolo

    2014-01-01

    It is increasingly evident that cancer results from altered organ homeostasis rather than from deregulated control of single cells or groups of cells. This applies especially to epithelial cancer, the most common form of human solid tumors and a major cause of cancer lethality. In the vast majority of cases, in situ epithelial cancer lesions do not progress into malignancy, even if they harbor many of the genetic changes found in invasive and metastatic tumors. While changes in tumor stroma are frequently viewed as secondary to changes in the epithelium, recent evidence indicates that they can play a primary role in both cancer progression and initiation. These processes may explain the phenomenon of field cancerization, i.e., the occurrence of multifocal and recurrent epithelial tumors that are preceded by and associated with widespread changes of surrounding tissue or organ “fields.” PMID:24691479

  3. Immunosuppressive therapy in bone marrow aplasia: the stroma functions normally to support hematopoiesis.

    PubMed

    Novitzky, N; Jacobs, P

    1995-12-01

    In aplastic anemia (AA) patients responsive to antilymphocyte globulin (ALG) therapy, abnormalities in both stroma and progenitor cell (PC) pool have been described. The relevance of each pathophysiologic defect was characterized in 16 individuals, and data were compared to results from seven normal volunteers. Bone marrow mononuclear cells were split into two fractions. Stromal layers (SL) were prepared from the first, and a CD34+ enriched population was obtained by immunomagnetic selection from the second. In cross-culture experiments, 1 x 10(4) of the latter from patients or controls were seeded on preformed SL, and adhesive PC were scored for the formation of blast colonies (CFU-Bl) on day 5 of culture. Nonadherent progenitors were recovered and quantitated in a standard clonogenic assay (CFU-GM). There were significantly fewer CD34+ cells in the AA group (median 0.65%, SD 0.39%, vs. 1.62%, SD 1.4%; p = 0.002). No morphological or cytologic differences between normal and aplastic SL were detected. Both equally supported the growth of CFU-Bl from normal progenitors (mean 117, SD 20.4, and 103.1, SD 30.4), while this value was reduced for the aplastic PC (mean 41.06, SD 42.9; p = 0.0002, exact two-tailed test). Similarly, the AA nonadherent PC had a decreased CFU-GM growth (mean 142.6, SD 104.8, vs. mean 361.7; SD 91.3), with a lower total clonogenic output (p = 0.0009). We conclude that aplastic stroma appropriately supports the growth of normal progenitors, whereas the depressed clonogenicity of the corresponsing population derived from AA is unrelated to their attachment to SL but intrinsic to the CD34+ cells, whether adherent or not.

  4. Characterization of cooperative bicarbonate uptake into chloroplast stroma in the green alga Chlamydomonas reinhardtii

    PubMed Central

    Yamano, Takashi; Sato, Emi; Iguchi, Hiro; Fukuda, Yuri; Fukuzawa, Hideya

    2015-01-01

    The supply of inorganic carbon (Ci; CO2 and HCO3–) is an environmental rate-limiting factor in aquatic photosynthetic organisms. To overcome the difficulty in acquiring Ci in limiting-CO2 conditions, an active Ci uptake system called the CO2-concentrating mechanism (CCM) is induced to increase CO2 concentrations in the chloroplast stroma. An ATP-binding cassette transporter, HLA3, and a formate/nitrite transporter homolog, LCIA, are reported to be associated with HCO3– uptake [Wang and Spalding (2014) Plant Physiol 166(4):2040–2050]. However, direct evidence of the route of HCO3– uptake from the outside of cells to the chloroplast stroma remains elusive owing to a lack of information on HLA3 localization and comparative analyses of the contribution of HLA3 and LCIA to the CCM. In this study, we revealed that HLA3 and LCIA are localized to the plasma membrane and chloroplast envelope, respectively. Insertion mutants of HLA3 and/or LCIA showed decreased Ci affinities/accumulation, especially in alkaline conditions where HCO3– is the predominant form of Ci. HLA3 and LCIA formed protein complexes independently, and the absence of LCIA decreased HLA3 mRNA accumulation, suggesting the presence of unidentified retrograde signals from the chloroplast to the nucleus to maintain HLA3 mRNA expression. Furthermore, although single overexpression of HLA3 or LCIA in high CO2 conditions did not affect Ci affinity, simultaneous overexpression of HLA3 with LCIA significantly increased Ci affinity/accumulation. These results highlight the HLA3/LCIA-driven cooperative uptake of HCO3– and a key role of LCIA in the maintenance of HLA3 stability as well as Ci affinity/accumulation in the CCM. PMID:26015566

  5. Tumor stroma with senescence-associated secretory phenotype in steatohepatitic hepatocellular carcinoma

    PubMed Central

    Lee, Jee San; Yoo, Jeong Eun; Kim, Haeryoung; Rhee, Hyungjin; Koh, Myoung Ju; Nahm, Ji Hae; Choi, Jin Sub; Lee, Kee-Ho; Park, Young Nyun

    2017-01-01

    Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC), a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP) were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs). The expression of α-smooth muscle actin (α-SMA), p21Waf1/Cif1, γ-H2AX, and IL-6 was investigated by immunohistochemistry or immunofluorescence. SH-HCCs were associated with older age, higher body mass index, and a higher incidence of metabolic syndrome, compared to C-HCC (P <0.05, all). The numbers of α-SMA-positive cancer-associated fibroblasts (CAFs) (P = 0.049) and α-SMA-positive CAFs co-expressing p21Waf1/Cif1 (P = 0.038), γ-H2AX (P = 0.065), and IL-6 (P = 0.048) were greater for SH-HCCs than C-HCCs. Additionally, non-tumoral liver from SH-HCCs showed a higher incidence of non-alcoholic fatty liver disease and a higher number of α-SMA-positive stellate cells expressing γ-H2AX and p21Waf1/Cif1 than that from C-HCCs (P <0.05, all). In conclusion, SH-HCCs are considered to occur more frequently in metabolic syndrome patients. Therein, senescent and damaged CAFs, as well as non-tumoral stellate cells, expressing SASP including IL-6 may contribute to the development of SH-HCC. PMID:28273155

  6. A technique to salvage big-bubble deep anterior lamellar keratoplasty after inadvertent full-thickness trephination.

    PubMed

    Zarei-Ghanavati, Siamak; Zarei-Ghanavati, Mehran

    2011-01-01

    Herein we describe a technique for management of large inadvertent full-thickness trephination during deep anterior lamellar keratoplasty using the big-bubble technique without converting to penetrating keratoplasty. First, the anterior chamber is formed with an ophthalmic viscosurgical device (OVD). Then, the full-thickness wound is secured with one X-type 10-0 nylon suture. A 27-gauge needle is attached to a 2 ml air-filled syringe and inserted into the corneal stroma in the meridian opposite to the site of full-thickness trephination. Air is gently injected to produce a limited area of "big-bubble" detaching Descemet's membrane (DM) from the corneal stroma. The "big bubble" is slowly expanded with injection of OVD. Finally, the recipient stroma is removed, the donor lenticule is placed and the DM tear is secured with one full thickness 10-0 nylon suture.

  7. Bidirectional Signaling of Mammary Epithelium and Stroma: Implications for Breast Cancer—Preventive Actions of Dietary Factors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mammary gland is composed of two major cellular compartments: a highly dynamic epithelium that undergoes cycles of proliferation, differentiation, and apoptosis in response to local and endocrine signals and the underlying stroma comprised of fibroblasts, endothelial cells, and adipocytes that c...

  8. Membrane-to-Nucleus Signals and Epigenetic Mechanisms for Myofibroblastic Activation and Desmoplastic Stroma: Potential Therapeutic Targets for Liver Metastasis?

    PubMed Central

    Kang, Ningling; Shah, Vijay H.; Urrutia, Raul

    2015-01-01

    Cancer associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment (TME), are a key source of extracellular matrix (ECM) that constitutes the desmoplastic stroma. Through remodeling of the reactive tumor stroma and paracrine actions, CAFs regulate cancer initiation, progression, and metastasis, as well as tumor resistance to therapies. The CAFs found in stroma-rich primary hepatocellular carcinomas (HCCs) and liver metastases of primary cancers of other organs predominantly originate from hepatic stellate cells (HSTCs), which are pericytes associated with hepatic sinusoids. During tumor invasion, HSTCs transdifferentiate into myofibroblasts in response to paracrine signals emanating from either tumor cells or a heterogenous cell population within the hepatic tumor microenvironment. Mechanistically, HSTC-to-myofibroblast transdifferentiation, also known as, HSTC activation, requires cell surface receptor activation, intracellular signal transduction, gene transcription and epigenetic signals, which combined ultimately modulate distinct gene expression profiles that give rise to and maintain a new phenotype. The current review, defines a paradigm that explains how HSTCs are activated into CAFs to promote liver metastasis. Furthermore, focus on the most relevant intracellular signaling networks and epigenetic mechanisms that control HSTC activation is provided. Finally, we discuss the feasibility of targeting CAF/activated HSTCs, in isolation or in conjunction with targeting cancer cells, which constitutes a promising and viable therapeutic approach for the treatment of primary stroma-rich liver cancers and liver metastasis. PMID:25548101

  9. Characterization of reactive stroma in prostate cancer: involvement of growth factors, metalloproteinase matrix, sexual hormones receptors and prostatic stem cells

    PubMed Central

    da Silva, Maurício Moreira; Matheus, Wagner Eduardo; Garcia, Patrick Vianna; Stopiglia, Rafael Mamprim; Billis, Athanase; Ferreira, Ubirajara; Fávaro, Wagner José

    2015-01-01

    ABSTRACT Introduction and Objectives: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. Materials and Methods: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: α-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Erα and ERβ. Results: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERα. Conclusions: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells. PMID:26689510

  10. High temperature strain gage apparent strain compensation

    NASA Technical Reports Server (NTRS)

    Holmes, Harlan K.; Moore, T. C., Sr.

    1992-01-01

    Once an installed strain gage is connected to a strain indicating device and the instrument is balanced, a subsequent change in temperature of the gage installation will generally produce a resistance change in the gage. This purely temperature-induced resistance will be registered by the indicating device as a strain and is referred to as 'apparent strain' to distinguish it from strain due to applied stress. One desirable technique for apparent strain compensation is to employ two identical gages with identical mounting procedures which are connected with a 'half bridge' configuration where gages see the same thermal environment but only one experiences a mechanical strain input. Their connection in adjacent arms of the bridge will then balance the thermally induced apparent strains and, in principle, only the mechanical strain remains. Two approaches that implement this technique are discussed.

  11. Deep Earthquakes.

    ERIC Educational Resources Information Center

    Frohlich, Cliff

    1989-01-01

    Summarizes research to find the nature of deep earthquakes occurring hundreds of kilometers down in the earth's mantle. Describes further research problems in this area. Presents several illustrations and four references. (YP)

  12. Ectopic pregnancy in an apparently healthy bitch.

    PubMed

    Eddey, Philip D

    2012-01-01

    This case describes an extrauterine fetus that was discovered in an apparently healthy bitch 5 mo after whelping. The extrauterine fetus was surgically removed, and the bitch made a complete recovery. The topic of canine ectopic pregnancy is discussed, and a review of previously reported cases is presented.

  13. Means for improving apparent resolution of television

    NASA Technical Reports Server (NTRS)

    Hilborn, E. H.

    1967-01-01

    Technique using short term temporal integration characteristics of the observers visual system improves the apparent resolution of television video presentations. The raster is displaced slightly on each frame so the eye can integrate the information in each raster grain. This phase shift uses a switching time delay.

  14. The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox.

    PubMed

    Martinez-Outschoorn, Ubaldo E; Whitaker-Menezes, Diana; Pavlides, Stephanos; Chiavarina, Barbara; Bonuccelli, Gloria; Casey, Trimmer; Tsirigos, Aristotelis; Migneco, Gemma; Witkiewicz, Agnieszka; Balliet, Renee; Mercier, Isabelle; Wang, Chengwang; Flomenberg, Neal; Howell, Anthony; Lin, Zhao; Caro, Jaime; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

    2010-11-01

    The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the "Autophagy Paradox". We have recently reported a simple solution to this paradox. We demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. We have termed this new paradigm "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism" or "Battery-Operated Tumor Growth". In this sense, autophagy in the tumor stroma serves as a "battery" to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients-both effectively "starving" cancer cells. We discuss the idea that tumor cells could become resistant to the systemic induction of autophagy, by the upregulation of natural endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy, by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. If autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor stroma. As such, an

  15. Flyby Delivers Multiple Deep Jupiter Probes

    NASA Technical Reports Server (NTRS)

    Spilker, T. R.; Hubbard, W. B.; Ingersoll, A. P.

    2001-01-01

    In situ probes are the most reliable means for sampling composition and conditions deep in giant planet atmospheres. While exceeding its baseline mission, the Galileo probe entered a distinctly non-representative region of Jupiter (a 'hot spot') and apparently did not measure the full deep abundances of such important species as H2O and H2S, whose measured abundances were still increasing at the deepest datum. Multiple deep (approx. 100 bar) in situ probes minimize the hot spot risk, and address spatial variations and deep constituent abundances. Additional information is contained in the original extended abstract.

  16. SU-E-J-248: Contributions of Tumor and Stroma Phenotyping in Computer-Aided Diagnosis

    SciTech Connect

    Li, H; Lan, L; Sennett, C; Giger, M

    2015-06-15

    Purpose: To gain insight into the role of parenchyma stroma in the characterization of breast tumors by incorporating computerized mammographic parenchyma assessment into breast CADx in the task of distinguishing between malignant and benign lesions. Methods: This study was performed on 182 biopsy-proven breast mass lesions, including 76 benign and 106 malignant lesions. For each full-field digital mammogram (FFDM) case, our quantitative imaging analysis was performed on both the tumor and a region-of-interest (ROI) from the normal contralateral breast. The lesion characterization includes automatic lesion segmentation and feature extraction. Radiographic texture analysis (RTA) was applied on the normal ROIs to assess the mammographic parenchymal patterns of these contralateral normal breasts. Classification performance of both individual computer extracted features and the output from a Bayesian artificial neural network (BANN) were evaluated with a leave-one-lesion-out method using receiver operating characteristic (ROC) analysis with area under the curve (AUC) as the figure of merit. Results: Lesion characterization included computer-extracted phenotypes of spiculation, size, shape, and margin. For parenchymal pattern characterization, five texture features were selected, including power law beta, contrast, and edge gradient. Merging of these computer-selected features using BANN classifiers yielded AUC values of 0.79 (SE=0.03) and 0.67 (SE=0.04) in the task of distinguishing between malignant and benign lesions using only tumor phenotypes and texture features from the contralateral breasts, respectively. Incorporation of tumor phenotypes with parenchyma texture features into the BANN yielded improved classification performance with an AUC value of 0.83 (SE=0.03) in the task of differentiating malignant from benign lesions. Conclusion: Combining computerized tumor and parenchyma phenotyping was found to significantly improve breast cancer diagnostic accuracy

  17. Apparent extended body motions in depth

    NASA Technical Reports Server (NTRS)

    Hecht, Heiko; Proffitt, Dennis R.

    1991-01-01

    Five experiments were designed to investigate the influence of three-dimensional (3-D) orientation change on apparent motion. Projections of an orientation-specific 3-D object were sequentially flashed in different locations and at different orientations. Such an occurrence could be resolved by perceiving a rotational motion in depth around an axis external to the object. Consistent with this proposal, it was found that observers perceived curved paths in depth. Although the magnitude of perceived trajectory curvature often fell short of that required for rotational motions in depth (3-D circularity), judgments of the slant of the virtual plane on which apparent motions occurred were quite close to the predictions of a model that proposes circular paths in depth.

  18. Predicting apparent Sherwood numbers for fluidized beds

    SciTech Connect

    Groenewold, H.; Tsotsas, E.

    1999-09-01

    Mass transfer data of bubbling fluidized beds have been reevaluated with a new model which is completely predictive. The model is based on a two-phase approach with active bypass, formally plug flow for the suspension gas and a consideration of backmixing in the main kinetic coefficient, i.e. in the apparent particle-to-fluid Sherwood number. A good agreement with experimental results of various authors with a broad range of Reynolds numbers and particle diameters is demonstrated.

  19. Comment: An Apparent Controversy in Auroral Physics

    NASA Astrophysics Data System (ADS)

    Haerendel, Gerhard

    2007-03-01

    In his article ``A turning point in auroral physics,'' Bryant argued against what he called the `standard' theory of auroral acceleration, according to which the electrons ``gain their energy from static electric fields,'' and offered wave acceleration as an alternative. Because of the importance of the process, not only for the aurora borealis but also for other cosmic plasmas, a clarification of this apparent controversy seems to be in place.

  20. Apparent exchange rate mapping with diffusion MRI.

    PubMed

    Lasič, Samo; Nilsson, Markus; Lätt, Jimmy; Ståhlberg, Freddy; Topgaard, Daniel

    2011-08-01

    Water exchange through the cell membranes is an important feature of cells and tissues. The rate of exchange is determined by factors such as membrane lipid composition and organization, as well as the type and activity of aquaporins. A method for noninvasively estimating the rate of water exchange would be useful for characterizing pathological conditions, e.g., tumors, multiple sclerosis, and ischemic stroke, expected to be associated with a change of the membrane barrier properties. This study describes the filter exchange imaging method for determining the rate of water exchange between sites having different apparent diffusion coefficients. The method is based on the filter-exchange pulsed gradient spin-echo NMR spectroscopy experiment, which is here modified to be compatible with the constraints of clinical MR scanners. The data is analyzed using a model-free approach yielding maps of the apparent exchange rate, here being introduced in analogy with the concept of the apparent diffusion coefficient. Proof-of-principle experiments are performed on microimaging and whole-body clinical scanners using yeast suspension phantoms. The limitations and appropriate experimental conditions are examined. The results demonstrate that filter exchange imaging is a fast and reliable method for characterizing exchange, and that it has the potential to become a powerful diagnostic tool.

  1. Deep learning.

    PubMed

    LeCun, Yann; Bengio, Yoshua; Hinton, Geoffrey

    2015-05-28

    Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.

  2. Deep learning

    NASA Astrophysics Data System (ADS)

    Lecun, Yann; Bengio, Yoshua; Hinton, Geoffrey

    2015-05-01

    Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.

  3. Deep earthquakes

    SciTech Connect

    Frohlich, C.

    1989-01-01

    Earthquakes are often recorded at depths as great as 650 kilometers or more. These deep events mark regions where plates of the earth's surface are consumed in the mantle. But the earthquakes themselves present a conundrum: the high pressures and temperatures at such depths should keep rock from fracturing suddenly and generating a tremor. This paper reviews the research on this problem. Almost all deep earthquakes conform to the pattern described by Wadati, namely, they generally occur at the edge of a deep ocean and define an inclined zone extending from near the surface to a depth of 600 kilometers of more, known as the Wadati-Benioff zone. Several scenarios are described that were proposed to explain the fracturing and slipping of rocks at this depth.

  4. Fabrication and characterization of biodegradable polymeric films as a corneal stroma substitute

    PubMed Central

    Salehi, Sahar; Fathi, Mohammadhossein; Javanmard, Shaghayegh Haghjooy; Barneh, Farnaz; Moshayedi, Mona

    2015-01-01

    Background: Biodegradable elastomeric materials such as poly glycerol sebacate (PGS) have gained much current attention in the field of soft tissue engineering. The present study reports the synthesis of PGS with molar ratios of 1:1, 2:3, and 3:2 of glycerol and sebacic acid via polycondensation reaction and tests the effect of PGS on human corneal epithelial (HCE) cells viability in vitro. Materials and Methods: PGS films were prepared by the casting method. We tried to fabricate PGS with different compositions and various properties as being a viable alternative to the corneal stroma in cornea tissue engineering. The chemical properties of the prepared polymer were investigated by means of attenuated total reflectance – Fourier transform infrared spectroscopy (ATR-FTIR) analysis and the in vitro cytotoxicity was investigated by the Alamarblue method. Results: The functional groups observed in the PGS FTIR spectrums of PGS with various molar ratios were the same. However, the main difference was the time of completing the cross-linking reaction. The PGS prepared by 2:3 ratio as a molar ratio had the fastest and the 3:2 ratio had the lowest cross-linking rate because of the higher amount of sebacic acid. Results of the Alamarblue cytotoxicity test assay showed no deleterious effect on HCE cell viability and proliferation. Conclusions: PGS is a potentially good candidate material for corneal tissue engineering because of its lack of in vitro HCE cell toxicity. PMID:25625115

  5. Pulsed cavity ringdown spectroscopy of thin films and ultrafast thermalization in corneal stroma

    NASA Astrophysics Data System (ADS)

    Marcus, George Alexander

    2005-07-01

    The mid-IR spectral region is of great spectroscopic interest as it corresponds to the energy scales associated with vibrational absorption resonances in molecules. Using the ultrafast mid-IR laser sources at the Stanford Picosecond Free Electron Laser Center, we have pursued two distinct research projects. In one project, we have extended the techniques of cavity ringdown spectroscopy (CRDS), an ultrasensitive linear absorption spectroscopy technique, to the study of condensed matter systems, in the form of thin films. We have compared two different approaches to thin-film CRDS: normal incidence coupled-cavity CRDS and Brewster's angle CRDS. Additionally, we demonstrated the viability of thin film CRDS as a calibrated ultrasensitve absorption measurement technique. In order to overcome the absorption sensitivity limitations imposed by poor optical throughput in CRDS, we have developed and demonstrated two throughput enhancement techniques, cavity-enhancement and pulse-stacking. In the second project, we have developed a two-color mid-IR pump mid-IR probe technique for studying ultrafast temperature changes in the components of biological tissue. We have made measurements that establish the use of transient absorption as an ultrafast thermometer in both water and protein. We have used this method to measure the thermalization between the constituents of corneal stroma in order to examine the assumptions underlying the differential heating model of pulsed mid-IR ablation of soft tissue.

  6. Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma

    PubMed Central

    Hua, Yuanyuan; Choi, Pui-Wah; Trachtenberg, Alexander J.; Ng, Allen C.; Kuo, Winston P.; Ng, Shu-Kay; Dinulescu, Daniela M.; Matzuk, Martin M.; Berkowitz, Ross S.; Ng, Shu-Wing

    2016-01-01

    Epithelial ovarian carcinoma accounts for 90% of all ovarian cancer and is the most deadly gynecologic malignancy. Recent studies have suggested that fallopian tube fimbriae can be the origin of cells for high-grade serous subtype of epithelial ovarian carcinoma (HGSOC). A mouse HGSOC model with conditional Dicer-Pten double knockout (Dicer-Pten DKO) developed primary tumors, intriguingly, from the fallopian tube stroma. We examined the growth and epithelial phenotypes of the Dicer-Pten DKO mouse tumor cells contributable by each gene knockout. Unlike human ovarian epithelial cancer cells that expressed full-length E-cadherin, the Dicer-Pten DKO stromal tumor cells expressed cleaved E-cadherin fragments and metalloproteinase 2, a mixture of epithelial and mesenchymal markers. Although the Dicer-Pten DKO tumor cells lost the expression of mature microRNAs as expected, they showed high levels of tRNA fragment expression and enhanced AKT activation due to the loss of PTEN function. Introduction of a Dicer1-expressing construct into the DKO mouse tumor cells significantly reduced DNA synthesis and the cell growth rate, with concurrent diminished adhesion and ZO1 epithelial staining. Hence, it is likely that the loss of Dicer promoted mesenchymal-epithelial transition in fallopian tube stromal cells, and in conjunction with Pten loss, further promoted cell proliferation and epithelial-like tumorigenesis. PMID:27602775

  7. Irreversible optical clearing of rabbit dermis for autogenic corneal stroma transplantation.

    PubMed

    Tanaka, Yuji; Shi, Dong; Kubota, Akira; Takano, Yoshimasa; Fuse, Nobuo; Yamato, Masayuki; Okano, Teruo; Nishida, Kohji

    2011-10-01

    Tissue engineering and transplantation of autogenic grafts have been widely investigated for solving problems on current allograft treatments (i.g., donor shortage and rejection). However, it is difficult to obtain an autogenic corneal stromal replacement that is composed of transparent, tough, and thick collagen constructs by current cell culture-based tissue engineering. Aim of this study is to develop transparent dermis for an autogenic corneal stroma transplantation. This study examined dehydration at 4-8°C and carbodiimide cross-linking on cloudy rabbit dermis (approx. 1.8%-3.8% light transmittance at 550 nm) for dermis optical clearing. Transparency of dehydrated rabbit dermis was founded to be approx. 37.9%-41.4% at 550 nm. Additional cross-linking treatment on dehydrated dermis prevented from swelling and clouding in saline, and improved its transparency to be 56.9% at 550 nm. Rabbit corneal epithelium was found to regenerate on optically cleared dermis in vitro. Furthermore, no abnormal biological response (i.e., inflammation, vascularization, and the barrier defect of epithelia) or no optical functional change on optically cleared dermis was observed during its 4-week autogenic transplantation into rabbit corneal stromal pocket.

  8. Hyaluronan in Peritumoral Stroma and Malignant Cells Associates with Breast Cancer Spreading and Predicts Survival

    PubMed Central

    Auvinen, Päivi; Tammi, Raija; Parkkinen, Jyrki; Tammi, Markku; Ågren, Ulla; Johansson, Risto; Hirvikoski, Pasi; Eskelinen, Matti; Kosma, Veli-Matti

    2000-01-01

    Hyaluronan (HA) is an extracellular matrix polysaccharide that promotes cell migration through its cell surface receptors and by effecting changes in the physical environment. HA expression is frequently increased in malignant tumors, whereas its association with the invasive potential and patient outcome in breast cancer has not been reported. The localization and signal intensity of HA was analyzed in 143 paraffin-embedded tumor samples of human breast carcinoma using a biotinylated HA-specific probe. In the immediate peritumoral stroma, HA signal was moderately or strongly increased in 39% and 56% of the cases, respectively. Normal ductal epithelium showed no HA, whereas in 57% of the tumors at least some of the carcinoma cells were HA positive. The intensity of the stromal HA signal and the presence of cell-associated HA were both significantly related to poor differentiation of the tumors, axillary lymph node positivity, and short overall survival of the patients. In Cox’s multivariate analysis, both the intensity of stromal HA signal alone and that combined with the HA positivity in tumor cells were independent prognostic factors for overall survival. These results suggest that HA is directly involved in the spreading of breast cancer and may offer a potential target for new therapies. PMID:10666382

  9. Radiation-enhanced therapeutic targeting of galectin-1 enriched malignant stroma in triple negative breast cancer

    PubMed Central

    Upreti, Meenakshi; Jyoti, Amar; Johnson, Sara E.; Swindell, Elden P.; Napier, Dana; Sethi, Pallavi; Chan, Ryan; Feddock, Jonathan M.; Weiss, Heidi L.; O'Halloran, Thomas V.; Mark Evers, B.

    2016-01-01

    Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis in response to the multimodal nanotherapeutic strategy using a TNBC model with orthotopic tumors originating from 3D tumor tissue analogs (TTA) comprised of tumor cells, endothelial cells and fibroblasts. The ‘rigorous’ combined treatment regimen of radiation and targeted liposomes is also shown to be well tolerated. More importantly, the results presented provide a means to exploit clinically relevant radiation dose for concurrent receptor mediated enhanced delivery of chemotherapy while limiting overall toxicity. The proposed study is significant as it falls in line with developing combinatorial therapeutic approaches for stroma-directed tumor targeting using tumor models that have an appropriate representation of the TNBC microenvironment. PMID:27223428

  10. Mapping the Extracellular and Membrane Proteome Associated with the Vasculature and the Stroma in the Embryo*

    PubMed Central

    Soulet, Fabienne; Kilarski, Witold W.; Roux-Dalvai, Florence; Herbert, John M. J.; Sacewicz, Izabela; Mouton-Barbosa, Emmanuelle; Bicknell, Roy; Lalor, Patricia; Monsarrat, Bernard; Bikfalvi, Andreas

    2013-01-01

    In order to map the extracellular or membrane proteome associated with the vasculature and the stroma in an embryonic organism in vivo, we developed a biotinylation technique for chicken embryo and combined it with mass spectrometry and bioinformatic analysis. We also applied this procedure to implanted tumors growing on the chorioallantoic membrane or after the induction of granulation tissue. Membrane and extracellular matrix proteins were the most abundant components identified. Relative quantitative analysis revealed differential protein expression patterns in several tissues. Through a bioinformatic approach, we determined endothelial cell protein expression signatures, which allowed us to identify several proteins not yet reported to be associated with endothelial cells or the vasculature. This is the first study reported so far that applies in vivo biotinylation, in combination with robust label-free quantitative proteomics approaches and bioinformatic analysis, to an embryonic organism. It also provides the first description of the vascular and matrix proteome of the embryo that might constitute the starting point for further developments. PMID:23674615

  11. Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma. Report of three cases.

    PubMed

    Chan, J K; Carcangiu, M L; Rosai, J

    1991-03-01

    Three examples of an unusual morphologic variant of papillary thyroid carcinoma (PTC) are reported. The presence of a prominent stromal component resulted in low-power microscopic appearances resembling fibroadenoma, phyllodes tumor, or fibrocystic disease of the breast in two cases. The carcinomatous component grew in the form of anastomosing narrow tubules, clustered glands, solid sheets with or without squamous differentiation, and/or papillae, and exhibited the typical nuclear features of PTC. The abundant stroma had a nodular fasciitis-like quality and was composed of short fascicles of spindle cells separated by varying amounts of mucoid matrix, collagen, and extravasated red blood cells; this was interpreted as an exuberant mesenchymal reaction to the carcinoma. The importance of recognizing this variant of PTC is that, when one encounters a fibroproliferative lesion of the thyroid, a diligent search should be made for papillary carcinoma. This variant also must be distinguished from the vastly more aggressive papillary carcinomas with anaplastic transformation and the so-called carcinosarcomas.

  12. Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues.

    PubMed

    Gabrielson, Marike; Chiesa, Flaminia; Paulsson, Janna; Strell, Carina; Behmer, Catharina; Rönnow, Katarina; Czene, Kamila; Östman, Arne; Hall, Per

    2016-07-01

    Following female sex and age, mammographic density is considered one of the strongest risk factors for breast cancer. Despite the association between mammographic density and breast cancer risk, little is known about the underlying histology and biological basis of breast density. To better understand the mechanisms behind mammographic density we assessed morphology, proliferation and hormone receptor status in relation to mammographic density in breast tissues from healthy women. Tissues were obtained from 2012-2013 by ultrasound-guided core needle biopsy from 160 women as part of the Karma (Karolinska mammography project for risk prediction for breast cancer) project. Mammograms were collected through routine mammography screening and mammographic density was calculated using STRATUS. The histological composition, epithelial and stromal proliferation status and hormone receptor status were assessed through immunohistochemical staining. Higher mammographic density was significantly associated with a greater proportion of stromal and epithelial tissue and a lower proportion of adipose tissue. Epithelial expression levels of Ki-67, oestrogen receptor (ER) and progesterone receptor (PR) were not associated with mammographic density. Epithelial Ki-67 was associated with a greater proportion of epithelial tissue, and epithelial PR was associated with a greater proportion of stromal and a lower proportion of adipose tissue. Epithelial ER was not associated with any tissues. In contrast, expression of ER in the stroma was significantly associated with a greater proportion of stroma, and negatively associated with the amount of adipose tissue. High mammographic density is associated with higher amount of stroma and epithelium and less amount of fat, but is not associated with a change in epithelial proliferation or receptor status. Increased expressions of both epithelial PR and stromal ER are associated with a greater proportion of stroma, suggesting hormonal involvement

  13. Regulation of Leukocyte Infiltration into Ovarian Cancer by Tumour-Stroma Interactions: A Microarray View of Cancer Microenvironment

    DTIC Science & Technology

    2006-03-01

    HEPPES, supplemented with Insulin, Transferin, Albumin, and Selenium from SIGMA®). After 48 hours, epithelial cells from 80% confluence are...microarray data from hundreds of tumor specimens ( Lamb et al., 2003). For this analysis we used the co-culture responsive gene list described in supplement...exclusive in the stroma of breast carcinomas. Nat Genet 32, 355-357. Lamb , J., Ramaswamy, S., Ford, H. L., Contreras, B., Martinez, R. V., Kittrell

  14. PD-L1/PD-1 check-point in gastric carcinoma with lymphoid stroma case report with immunochemical study

    PubMed Central

    Crescenzi, Anna; Taffon, Chiara; Donati, Michele; Guarino, Michele Pier Luca; Valeri, Sergio; Coppola, Roberto

    2017-01-01

    Abstract Introduction: Gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas. The hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response. The programmed death 1–programmed death-ligand 1 (PD-1/PD-L1) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms. Patient's concerns case study and outcome: We report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis. He is alive without disease 10 months after surgery. We focused the study on factors that potentially modulate the prognosis. In this setting we demonstrate, for the first time in this type of tumor, by immunohistochemistry a strong PD-L1 expression in neoplastic cell and the presence of PD-1 positive infiltrating lymphocytes. Conclusion: The applied approach may contribute to the knowledge about host reaction in such tumor and it may also be used for tumor precise identification on the endoscopic biopsy time before excision surgery. PMID:28207501

  15. Functional units in rainbow trout (Salmo gairdneri, Richardson) liver: III. Morphometric analysis of parenchyma, stroma, and component cell types.

    PubMed

    Hampton, J A; Lantz, R C; Hinton, D E

    1989-05-01

    Hepatic stroma and parenchyma with its component cell types were quantitatively described in adult male and female actively-spawning 5-year-old rainbow trout (Salmo gairdneri, Richardson). Point-count morphometry of glycol methacrylate sections estimated volume compartments for stroma and parenchyma. Veins composed 85% of the stroma while arteries and bile ducts occupied approximately 6-7% each. Parenchyma accounted for 95% of hepatic volume. Point-count morphometry of transmission electron micrographs estimated volume compartments as well as numerical and surface density measurements for parenchymal components. Within the hepatic parenchymal compartment, hepatocytes occupied 85% and showed significant sex differences. Female hepatocytes were significantly more numerous but were smaller, only 60% of the volume of male hepatocytes. Since hepatocyte nuclear volume was equal in both sexes, differences were due to reduced cytoplasmic volume in females. Perisinusoidal macrophages of females occupied larger volumes of their respective parenchymal compartments, and their larger mean cytoplasmic volumes suggested activation. Biliary epithelial cells of preductules and ductules were numerous. Ratios of numerical density of hepatocytes to biliary epithelial cells were consistent with a tubular arrangement of hepatocytes. Factors possibly mediating the sexual dimorphism are discussed.

  16. Micro-RNA-21 regulates TGF-β-induced myofibroblast differentiation by targeting PDCD4 in tumor-stroma interaction.

    PubMed

    Yao, Qin; Cao, Siyu; Li, Chun; Mengesha, Asferd; Kong, Beihua; Wei, Mingqian

    2011-04-15

    Transforming growth factor-β1 (TGF-β1) induces stromal fibroblast-to-myofibroblast transdifferentiation in the tumor-stroma interactive microenvironment via modulation of multiple phenotypic and functional genes, which plays a critical role in tumor progression. Up to now, the involvement of micro-RNAs (miRNAs) and their roles in TGF-β1-induced myofibroblast differentiation in tumor-stroma interaction are unclear. Using quantitative real-time RT-PCR, we demonstrated that the expression of micro-RNA-21 (miR-21) was upregulated in activated fibroblasts after treatment with TGF-β1 or conditioned medium from cancer cells. To determine the potential roles of miR-21 in TGF-β1-mediated gene regulation during myofibroblast conversion, we showed that miR-21 expression was downregulated by miR-21 inhibitor and upregulated by miR-21 mimic. Interestingly, downregulation of miR-21 with the inhibitor effectively inhibited TGF-β1-induced myofibroblast differentiation while upregulation of miR-21 with a mimic significantly promoted myofibroblast differentiation. We further demonstrated that MiR-21 directly targeted and downregulated programmed cell death 4 (PDCD4) gene, which in turn acted as a negative regulator of several phenotypic and functional genes of myofibroblasts. Taken together, these results suggested that miR-21 participated in TGF-β1-induced myofibroblast transdifferentiation in cancer stroma by targeting PDCD4.

  17. Deep Trouble.

    ERIC Educational Resources Information Center

    Popke, Michael

    2002-01-01

    Discusses how the safety-related ruling by the National Federation of State High School Associations to eliminate the option of using 18-inch starting platforms in pools less than 4 feet deep may affect operators of swimming pools and the swim teams who use them. (EV)

  18. Deep Lysimeter

    DOEpatents

    Hubbell, Joel M.; Sisson, James B.

    2004-06-01

    A deep lysimeter including a hollow vessel having a chamber, a fill conduit extending into the chamber through apertures, a semi-permeable member mounted on the vessel and in fluid communication with the fill conduit, and a line connection for retrieving the lysimeter.

  19. Apparent Geocenter Variations from IGS Analysis

    NASA Astrophysics Data System (ADS)

    Ferland, R.

    2001-12-01

    Natural Resources Canada's (NRCan) Geodetic Survey Division (GSD), on behalf of the International GPS Service (IGS) and its Reference Frame Working Group, combines a consistent set of station coordinates, velocities, Earth Rotation Parameters (ERP) and apparent geocenter to produce the IGS official station position/ERP solutions in the Software Independent Exchange (SINEX) format The weekly Analysis Centers (AC) solutions include estimates of weekly station coordinates, apparent geocenter positions and daily ERPs. All the AC products are required to be in a consistent reference frame. The combination of station coordinates originating from different ACs involves removing all available constraints and re-scaling the covariance information. The weekly combination generally includes estimates of coordinates for 120 to 140 globally distributed stations. While the cumulative solution currently includes approximately 280 stations, about 215 of them have complete information and reliable velocity estimates. The IGS combined products are required to be consistent with the most recent realization of ITRF (currently ITRF97, soon in ITRF2000). This is done by transforming the weekly and cumulative solutions, respectively using 7 and 14 Helmert transformation parameters (3 translations, 3 rotations, 1 scale and their respective rates). The transformation parameters are determined from a subset of 51 high quality, globally distributed and generally collocated (with other space techniques) stations, also known as Reference Frame (RF) stations. The weekly estimated IGS apparent geocenter for the period between 99/08/01 (Wk 1012) and 01/08/04 (Wk 1025) has been analyzed. The apparent X, Y and Z geocenter components were estimated with respect to the realization of ITRF97. The estimated weekly geocenter positions relied on COD, ESA and JPL SINEX solutions for the period of interest. The formal error for the weekly geocenter is about 6-8mm for the XY components and 8-10mm for the Z

  20. Apparent magnitude of earthshine: a simple calculation

    NASA Astrophysics Data System (ADS)

    Agrawal, Dulli Chandra

    2016-05-01

    The Sun illuminates both the Moon and the Earth with practically the same luminous fluxes which are in turn reflected by them. The Moon provides a dim light to the Earth whereas the Earth illuminates the Moon with somewhat brighter light which can be seen from the Earth and is called earthshine. As the amount of light reflected from the Earth depends on part of the Earth and the cloud cover, the strength of earthshine varies throughout the year. The measure of the earthshine light is luminance, which is defined in photometry as the total luminous flux of light hitting or passing through a surface. The expression for the earthshine light in terms of the apparent magnitude has been derived for the first time and evaluated for two extreme cases; firstly, when the Sun’s rays are reflected by the water of the oceans and secondly when the reflector is either thick clouds or snow. The corresponding values are -1.30 and -3.69, respectively. The earthshine value -3.22 reported by Jackson lies within these apparent magnitudes. This paper will motivate the students and teachers of physics to look for the illuminated Moon by earthlight during the waning or waxing crescent phase of the Moon and to reproduce the expressions derived here by making use of the inverse-square law of radiation, Planck’s expression for the power in electromagnetic radiation, photopic spectral luminous efficiency function and expression for the apparent magnitude of a body in terms of luminous fluxes.

  1. Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior

    PubMed Central

    2012-01-01

    Background Colon cancer patients with the same stage show diverse clinical behavior due to tumor heterogeneity. We aimed to discover distinct classes of tumors based on microarray expression patterns, to analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters and to study differences in the survival. Methods Hierarchical clustering was performed for class discovery in 88 colon tumors (stages I to IV). Pathways analysis and correlations between clinical parameters and our classification were analyzed. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the main subtype was generated using the 3-Nearest-Neighbor method. Coincidences with other prognostic predictors were assesed. Results Hierarchical clustering identified four robust tumor subtypes with biologically and clinically distinct behavior. Stromal components (p < 0.001), nuclear β-catenin (p = 0.021), mucinous histology (p = 0.001), microsatellite-instability (p = 0.039) and BRAF mutations (p < 0.001) were associated to this classification but it was independent of Dukes stages (p = 0.646). Molecular subtypes were established from stage I. High-stroma-subtype showed increased levels of genes and altered pathways distinctive of tumour-associated-stroma and components of the extracellular matrix in contrast to Low-stroma-subtype. Mucinous-subtype was reflected by the increased expression of trefoil factors and mucins as well as by a higher proportion of MSI and BRAF mutations. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the Low-stroma-subtype distinguished low risk patients from high risk patients in the external cohort (Dukes B and C:HR = 8.56(2.53-29.01); Dukes B,C and D:HR = 1.87(1.07-3.25)). Eight different reported survival gene signatures segregated our tumors into two groups the Low-stroma-subtype and

  2. Stroma-conditioned media improve expansion of human primitive hematopoietic stem cells and progenitor cells.

    PubMed

    Breems, D A; Blokland, E A; Ploemacher, R E

    1997-01-01

    It has been reported that stroma-dependent cultures support proliferation of hematopoietic stem cells (HSC). In order to investigate the effect of soluble stromal factors, we developed short-term serum-low liquid cultures in which the effect of stroma-conditioned media (SCM) from the murine FBMD-1, and human L87/4 and L88/5 cell lines was studied on the maintenance and expansion of various human HSC subsets in CD34-positive selected mobilized peripheral blood stem cells (PBSC) from autologous transplants of lymphoma and multiple myeloma patients. The human cobblestone area forming cell (CAFC) assay was employed to determine the frequencies of both the CAFC weeks 2 to 4 as tentative indicators of progenitor and transiently repopulating HSC, and the more primitive CAFC weeks 6 to 8 as indicators of long-term repopulating HSC. In 7-day liquid cultures containing interleukin-3 (IL-3), stem cell factor (SCF) and IL-6, we recovered 3.0-fold more colony-forming cells (CFC) and 1.7- to 1.9-fold more CAFC weeks 2 and 4. The absolute number of primitive CAFC weeks 6 and 8 were only maintained (1.1- to 1.4-fold) in these liquid cultures. This modest expansion was significantly improved by the addition of SCM from the FBMD-1, L87/4 or L88/5 cell lines. Output CFC numbers were 6.8-, 5.8- and 9.9-fold higher, respectively, than the input values, while absolute CAFC week 2 to 4 numbers were 4.5-, 10.2- and 10.2-fold expanded, respectively. The addition of SCM also improved expansion of the more primitive CAFC week 6 to 8 stem cell subsets by 2.2-, 4.5- and 4.9-fold, respectively. The addition of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), IL-1beta, IL-11 or macrophage inflammatory protein-1alpha to cultures containing IL-3, SCF and IL-6 could not explain the SCM effect and in all these combinations SCM addition further increased the recovery of HSC subsets. Similarly, addition of anti-cytokine antibodies (ie alpha-G-CSF, alpha-GM-CSF, alpha

  3. Apparent contact angle of an evaporating drop

    NASA Astrophysics Data System (ADS)

    Morris, S. J. S.

    2012-11-01

    In experiments by Poulard et al. (2005), a sessile drop of perfectly wetting liquid evaporates from a non-heated substrate into an under-saturated mixture of vapour with an inert gas; evaporation is limited by vapour diffusion. The system exhibits an apparent contact angle θ that is a flow property. Under certain conditions, the apparent contact line was stationary relative to the substrate; we predict θ for this case. Observed values of θ are small, allowing lubrication analysis of the liquid film. The liquid and vapour flows are coupled through conditions holding at the phase interface; in particular, vapour partial pressure there is related to the local value of liquid pressure through the Kelvin condition. Because the droplet is shallow, the interfacial conditions can be transferred to the solid-liquid interface at y = 0 . We show that the dimensionless partial pressure p (x , y) and the film thickness h (x) are determined by solving ∇2 p = 0 for y > 0 subject to a matching condition at infinity, and the conditions - p = L hxx +h-3 and (h3px) x + 3py = 0 at y = 0 . The parameter L controls the ratio of Laplace to disjoining pressure. We analyse this b.v.p. for the experimentally-relevant case L --> 0 .

  4. Apparent mass in viscous, vortical flows

    NASA Astrophysics Data System (ADS)

    Noca, Flavio

    2001-11-01

    The concept of added, virtual, apparent, or additional mass is well known in potential flow theory. It is added mass (or more exactly, the time derivative of virtual momentum) that wholly contributes to fluid dynamic forces in unsteady, potential flow configurations. While the force contribution from added mass can be easily evaluated in potential flows, it has always been thought that in real (vortical and viscous) flows, the contribution of added mass to the fluid dynamic force is intertwined in a complex way with the force resulting from wake and boundary layer vorticity. Recently, Shiels, Leonard, and Roshko (Journal of Fluids and Structures, vol 15, pp 3-21, 2001) [henceforth SLR] showed that the fluid dynamic lift force on a circular cylinder performing transverse oscillations in a steady stream can actually be decomposed into a lift force due to apparent mass (as evaluated from potential theory) and a ``wake'' force resulting from frictional as well as altered pressure forces caused by the boundary layer and wake growth in viscous flow. Through a rigorous formalism analogous to SLR’s, we will confirm that the SLR decomposition is correct and valid for any body shape in arbitrary motion. The SLR decomposition is a seminal discovery in the science of unsteady aero/hydrodynamics, as it allows to clearly distinguish the force contributions from added mass and from the ``wake''. The result is particularly important for understanding the flight and swimming mechanics of animals.

  5. Apparent brightness distribution of GRB host galaxies

    NASA Astrophysics Data System (ADS)

    Bagoly, Zsolt; Rácz, István I.; Balázs, Lajos G.; Horváth, István; Tóth, L. Viktor

    We studied the unbiased optical brightness distribution which was calculated from the survival analysis of host galaxies (HGs) data and its relationship with the Swift GRB data of the host galaxies observed by the Keck telescope. Based on the sample obtained from merging the Swift GRB table and the Keck optical data we also studied the dependence of this distribution on the GRB's data. Finally, we compared the HGs distribution with standard galaxies distribution of the DEEP2 redshift survey and checked the result with the VIPERS catalogue too.

  6. Detecting thermal phase transitions in corneal stroma by fluorescence micro-imaging analysis

    NASA Astrophysics Data System (ADS)

    Matteini, P.; Rossi, F.; Ratto, F.; Bruno, I.; Nesi, P.; Pini, R.

    2008-02-01

    Thermal modifications induced in corneal stroma were investigated by the use of fluorescence microscopy. Freshly extracted porcine corneas were immersed for 5 minutes in a water bath at temperatures in the 35-90°C range and stored in formalin. The samples were then sliced in 200-μm-thick transversal sections and analyzed under a stereomicroscope to assess corneal shrinkage. Fluorescence images of the thermally treated corneal samples were acquired using a slow-scan cooled CCD camera, after staining the slices with Indocyanine Green (ICG) fluorescent dye which allowed to detect fluorescence signal from the whole tissue. All measurements were performed using an inverted epifluorescence microscope equipped with a mercury lamp. The thermally-induced modifications to the corneal specimens were evaluated by studying the grey level distribution in the fluorescence images. For each acquired image, Discrete Fourier Transform (DFT) and entropy analyses were performed. The spatial distribution of DFT absolute value indicated the spatial orientation of the lamellar planes, while entropy was used to study the image texture, correlated to the stromal structural transitions. As a result, it was possible to indicate a temperature threshold value (62°C) for high thermal damage, resulting in a disorganization of the lamellar planes and in full agreement with the measured temperature for corneal shrinkage onset. Analysis of the image entropy evidenced five strong modifications in stromal architecture at temperatures of ~45°C, 53°C, 57°C, 66°C, 75°C. The proposed procedure proved to be an effective micro-imaging method capable of detecting subtle changes in corneal tissue subjected to thermal treatment.

  7. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent.

    PubMed

    Chen, Jane Q; Mori, Hidetoshi; Cardiff, Robert D; Trott, Josephine F; Hovey, Russell C; Hubbard, Neil E; Engelberg, Jesse A; Tepper, Clifford G; Willis, Brandon J; Khan, Imran H; Ravindran, Resmi K; Chan, Szeman R; Schreiber, Robert D; Borowsky, Alexander D

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1(tm1Rds) homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment.

  8. Unique metabolic features of pancreatic cancer stroma: relevance to the tumor compartment, prognosis, and invasive potential

    PubMed Central

    Knudsen, Erik S.; Balaji, Uthra; Freinkman, Elizaveta; McCue, Peter; Witkiewicz, Agnieszka K.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The aggressiveness and therapeutic recalcitrance of this malignancy has been attributed to multiple factors including the influence of an active desmoplastic stroma. How the stromal microenvironment of PDAC contributes to the fatal nature of this disease is not well defined. In the analysis of clinical specimens, we observed diverse expression of the hypoxic marker carbonic anhydrase IX and the lactate transporter MCT4 in the stromal compartment. These stromal features were associated with the epithelial to mesenchymal phenotype in PDAC tumor cells, and with shorter patient survival. Cultured cancer-associated fibroblasts (CAFs) derived from primary PDAC exhibited a high basal level of hypoxia inducible factor 1a (HIF1α) that was both required and sufficient to modulate the expression of MCT4. This event was associated with increased transcription and protein synthesis of HIF1α in CAFs relative to PDAC cell lines, while surprisingly the protein turnover rate was equivalent. CAFs utilized glucose predominantly for glycolytic intermediates, whereas glutamine was the preferred metabolite for the TCA cycle. Unlike PDAC cell lines, CAFs were resistant to glucose withdrawal but sensitive to glutamine depletion. Consistent with the lack of reliance on glucose, CAFs could survive the acute depletion of MCT4. In co-culture and xenograft studies CAFs stimulated the invasive potential and metastatic spread of PDAC cell lines through a mechanism dependent on HIF1α and MCT4. Together, these data indicate that stromal metabolic features influence PDAC tumor cells to promote invasiveness and metastatic potential and associate with poor outcome in patients with PDAC. PMID:27623078

  9. Proteomic analysis of patient tissue reveals PSA protein in the stroma of benign prostatic hyperplasia

    PubMed Central

    O’Malley, Katherine J.; Eisermann, Kurtis; Pascal, Laura E.; Parwani, Anil V.; Majima, Tsuyoshi; Graham, Lara; Hrebinko, Katherine; Acquafondata, Marie; Stewart, Nicolas A.; Nelson, Joel B.; Yoshimura, Naoki; Wang, Zhou

    2014-01-01

    BACKGROUND Benign prostatic hyperplasia (BPH) is an age-related disease frequently associated with lower urinary tract symptoms (LUTS) that involves hyperplasia of both epithelial and stromal cells. Stromal fibrosis is a distinctive feature of BPH, but the exact mechanisms underlying this phenomenon are poorly understood. METHODS In the current study, proteomics analyses were utilized to identify proteins altered in the BPH stromal compartment from patients with symptomatic BPH. Stromal cells were isolated from histological nodules of BPH by laser capture microdissection (LCM) and subjected to liquid chromatography/mass spectrometry. RESULTS Proteins identified included several stromal-specific proteins involved in extracellular matrix remodeling, focal adhesion and cellular junctions. Additionally, the proteomics array identified the presence of luminal epithelial secretory protein PSA. Immunostaining, ELISA, and in situ hybridization analyses of BPH tissues verified the presence of PSA protein but absence of PSA mRNA in the stromal compartment. E-cadherin was down-regulated in BPH epithelial cells compared to normal adjacent tissues, suggesting that alteration of cellular junctions could contribute to the presence of luminal epithelial secreted proteins PSA and KLK2 in the stromal compartment. CONCLUSIONS The above findings suggest that the presence of secreted proteins PSA and KLK2 from prostate luminal epithelial cells in BPH stroma is a hallmark of BPH nodules which could in part be due to alterations in cellular junction proteins and/or increased epithelial barrier permeability. Elucidating the cause and consequence of these secreted proteins in the stromal compartment of BPH may lead to new understanding of BPH pathogenesis as well as approaches to prevent and/or treat this common disease. PMID:24711254

  10. Porphyromonas gingivalis within Placental Villous Mesenchyme and Umbilical Cord Stroma Is Associated with Adverse Pregnancy Outcome

    PubMed Central

    Vanterpool, Sizzle F.; Been, Jasper V.; Houben, Michiel L.; Nikkels, Peter G. J.; De Krijger, Ronald R.; Zimmermann, Luc J. I.; Kramer, Boris W.; Progulske-Fox, Ann; Reyes, Leticia

    2016-01-01

    Intrauterine presence of Porphyromonas gingivalis (Pg), a common oral pathobiont, is implicated in preterm birth. Our aim was to determine if the location of Pg within placental and/or umbilical cord sections was associated with a specific delivery diagnosis at preterm delivery (histologic chorioamnionitis, chorioamnionitis with funisitis, preeclampsia, and preeclampsia with HELLP-syndrome, small for gestational age). The prevalence and location of Pg within archived placental and umbilical cord specimens from preterm (25 to 32 weeks gestation) and term control cohorts were evaluated by immunofluorescent histology. Detection of Pg was performed blinded to pregnancy characteristics. Multivariate analyses were performed to evaluate independent effects of gestational age, being small for gestational age, specific preterm delivery diagnosis, antenatal steroids, and delivery mode, on the odds of having Pg in the preterm tissue. Within the preterm cohort, 49 of 97 (51%) placentas and 40 of 97 (41%) umbilical cord specimens were positive for Pg. Pg within the placenta was significantly associated with shorter gestation lengths (OR 0.63 (95%CI: 0.48–0.85; p = 0.002) per week) and delivery via caesarean section (OR 4.02 (95%CI: 1.15–14.04; p = 0.03), but not with histological chorioamnionitis or preeclampsia. However, the presence of Pg in the umbilical cord was significantly associated with preeclampsia: OR 6.73 (95%CI: 1.31–36.67; p = 0.02). In the term cohort, 2 of 35 (6%) placentas and no umbilical cord term specimens were positive for Pg. The location of Pg within the placenta was different between preterm and term groups in that Pg within the villous mesenchyme was only detected in the preterm cohort, whereas Pg associated with syncytiotrophoblasts was found in both preterm and term placentas. Taken together, our results suggest that the presence of Pg within the villous stroma or umbilical cord may be an important determinant in Pg-associated adverse pregnancy

  11. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent

    PubMed Central

    Cardiff, Robert D.; Trott, Josephine F.; Hovey, Russell C.; Hubbard, Neil E.; Engelberg, Jesse A.; Tepper, Clifford G.; Willis, Brandon J.; Khan, Imran H.; Ravindran, Resmi K.; Chan, Szeman R.; Schreiber, Robert D.; Borowsky, Alexander D.

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. PMID:26075897

  12. Clear cell papillary renal cell carcinoma, renal angiomyoadenomatous tumor, and renal cell carcinoma with leiomyomatous stroma relationship of 3 types of renal tumors: a review.

    PubMed

    Hes, Ondrej; Compérat, Eva Maria; Rioux-Leclercq, Nathalie

    2016-04-01

    Renal angiomyoadenomatous tumor has been described in 2000, followed by description of clear cell papillary renal cell carcinoma in 2006. Discussions about possible relationship of both tumors were published since their description. The main differential diagnostic feature was considered presence/absence of fibroleiomyomatous stroma-relationship of renal angiomyoadenomatous tumor in stroma-rich tumors. However, it was shown that stroma is reactive and nonneoplastic by its nature and that all other histologic, immunohistochemical, and molecular-genetic features of both entities are identical. In upcoming World Health Organization classification of renal tumors (2016), both lesions are considered as a single entity (clear cell papillary renal cell carcinoma [CCPRCC]). Most published cases followed the benign/indolent clinical course. In addition, most tumors has normal status of VHL gene (methylation, LOH 3p, mutations); however, CCPRCC was referred in patients with VHL syndrome. Another issue covered by this review is possible relationship of CCPRCC and "renal cell carcinoma with leiomyomatous stroma" (RCCLS). Renal cell carcinoma with leiomyomatous stroma shows clear cell cytology and abundant leiomyomatous stroma. Some of RCCLS are positive for cytokeratin 7; some are negative. Similar situation exists for relation of RCCLS and VHL gene abnormalities. It is so far unclear whether any relation between CCPRCC and RCCLS exists. From all published studies, it seems that these tumors are less likely related to each other.

  13. Deep anterior lamellar keratoplasty of dog eyes using the big-bubble technique

    PubMed Central

    Kim, Soohyun; Kwak, Ji Yoon; Jeong, Manbok

    2016-01-01

    This study was conducted to establish the feasibility of corneal transplantation using the big-bubble technique (BBT) to perform deep anterior lamellar keratoplasty (DALK) in three dogs. After the cornea was trephined 750 µm, 4 mL of air was injected, and the blanched stroma was removed to expose Descemet's membrane (DM). The donor corneal button, which was gently stripped off the DM, was sutured onto the bare DM of the recipient cornea. The dogs received topical antibiotics every 6 h for 7 days and 2% cyclosporine ointment every 12 h for 1 month. The eyes were examined post-operatively at 7, 14, 21, 28 and 150 days. The central portion of the transplanted cornea stayed transparent while corneal haze developed around the transplanted margin. Menace response was normal even though the transplanted cornea was edematous until 3 weeks after surgery. A marginal haze was rarely observed between the donor and recipient corneas at 150 days after the operation. A spotted haze developed in the central part of the deep stroma near the DM. Upon histopathological examination, the stroma and epithelium of the donor cornea had normal structures. Corneal transplantation using DALK with BBT can be performed in dogs preserving the healthy endothelium. PMID:26645335

  14. Computing the apparent centroid of radar targets

    SciTech Connect

    Lee, C.E.

    1996-12-31

    A high-frequency multibounce radar scattering code was used as a simulation platform for demonstrating an algorithm to compute the ARC of specific radar targets. To illustrate this simulation process, several targets models were used. Simulation results for a sphere model were used to determine the errors of approximation associated with the simulation; verifying the process. The severity of glint induced tracking errors was also illustrated using a model of an F-15 aircraft. It was shown, in a deterministic manner, that the ARC of a target can fall well outside its physical extent. Finally, the apparent radar centroid simulation based on a ray casting procedure is well suited for use on most massively parallel computing platforms and could lead to the development of a near real-time radar tracking simulation for applications such as endgame fuzing, survivability, and vulnerability analyses using specific radar targets and fuze algorithms.

  15. Ambiguity in Tactile Apparent Motion Perception

    PubMed Central

    Liaci, Emanuela; Bach, Michael; Tebartz van Elst, Ludger; Heinrich, Sven P.; Kornmeier, Jürgen

    2016-01-01

    Background In von Schiller’s Stroboscopic Alternative Motion (SAM) stimulus two visually presented diagonal dot pairs, located on the corners of an imaginary rectangle, alternate with each other and induce either horizontal, vertical or, rarely, rotational motion percepts. SAM motion perception can be described by a psychometric function of the dot aspect ratio (“AR”, i.e. the relation between vertical and horizontal dot distances). Further, with equal horizontal and vertical dot distances (AR = 1) perception is biased towards vertical motion. In a series of five experiments, we presented tactile SAM versions and studied the role of AR and of different reference frames for the perception of tactile apparent motion. Methods We presented tactile SAM stimuli and varied the ARs, while participants reported the perceived motion directions. Pairs of vibration stimulators were attached to the participants’ forearms and stimulator distances were varied within and between forearms. We compared straight and rotated forearm conditions with each other in order to disentangle the roles of exogenous and endogenous reference frames. Results Increasing the tactile SAM’s AR biased perception towards vertical motion, but the effect was weak compared to the visual modality. We found no horizontal disambiguation, even for very small tactile ARs. A forearm rotation by 90° kept the vertical bias, even though it was now coupled with small ARs. A 45° rotation condition with crossed forearms, however, evoked a strong horizontal motion bias. Discussion Existing approaches to explain the visual SAM bias fail to explain the current tactile results. Particularly puzzling is the strong horizontal bias in the crossed-forearm conditions. In the case of tactile apparent motion, there seem to be no fixed priority rule for perceptual disambiguation. Rather the weighting of available evidence seems to depend on the degree of stimulus ambiguity, the current situation and on the perceptual

  16. Apparent Attenuation Beneath the United States and its Correlation with Lithospheric Provinces

    NASA Astrophysics Data System (ADS)

    Kowalke, S.; Bezada, M. J.

    2015-12-01

    We map apparent attenuation beneath the continental United States through an analysis of ~16 deep-focus teleseismic events recorded by the USArray Transportable Array. For each event, we stack the best quality recordings to generate a source estimate and then apply an attenuation operator to the source estimate using a range of t* values to fit the record at each station. The regional attenuation pattern is extracted from the ensemble of observations using a regularized inversion scheme. Preliminary results from the analysis of four events show good correlation with tectonic boundaries. The lowest apparent attenuation occurs in the upper Midwest, and corresponds to the Superior Craton; while high apparent attenuation dominates outside the cratonic continent as defined by the Rocky Mountain, Ouachita and Appalachian fronts. Our results indicate that different lithospheric provinces have distinct attenuation signatures that are consistent with expectations.

  17. Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution

    PubMed Central

    Martinez-Outschoorn, Ubaldo E; Balliet, Renee M; Rivadeneira, Dayana B; Chiavarina, Barbara; Pavlides, Stephanos; Wang, Chenguang; Whitaker-Menezes, Diana; Daumer, Kristin M; Lin, Zhao; Witkiewicz, Agnieszka K; Flomenberg, Neal; Howell, Anthony; Pestell, Richard G; Knudsen, Erik S; Lisanti, Michael P

    2010-01-01

    Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a “lethal tumor microenvironment.” Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a “metabolic” and “mutagenic” motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the “Reverse Warburg effect”). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use “oxidative stress” in adjacent fibroblasts (1) as an “engine” to fuel their own

  18. Development of a Reactive Stroma Associated with Prostatic Intraepithelial Neoplasia in EAF2 Deficient Mice

    PubMed Central

    Pascal, Laura E.; Ai, Junkui; Masoodi, Khalid Z.; Wang, Yujuan; Wang, Dan; Eisermann, Kurtis; Rigatti, Lora H.; O’Malley, Katherine J.; Ma, Hei M.; Wang, Xinhui; Dar, Javid A.; Parwani, Anil V.; Simons, Brian W.; Ittman, Michael M.; Li, Luyuan; Davies, Benjamin J.; Wang, Zhou

    2013-01-01

    ELL-associated factor 2 (EAF2) is an androgen-responsive tumor suppressor frequently deleted in advanced prostate cancer that functions as a transcription elongation factor of RNA Pol II through interaction with the ELL family proteins. EAF2 knockout mice on a 129P2/OLA-C57BL/6J background developed late-onset lung adenocarcinoma, hepatocellular carcinoma, B-cell lymphoma and high-grade prostatic intraepithelial neoplasia. In order to further characterize the role of EAF2 in the development of prostatic defects, the effects of EAF2 loss were compared in different murine strains. In the current study, aged EAF2−/− mice on both the C57BL/6J and FVB/NJ backgrounds exhibited mPIN lesions as previously reported on a 129P2/OLA-C57BL/6J background. In contrast to the 129P2/OLA-C57BL/6J mixed genetic background, the mPIN lesions in C57BL/6J and FVB/NJ EAF2−/− mice were associated with stromal defects characteristic of a reactive stroma and a statistically significant increase in prostate microvessel density. Stromal inflammation and increased microvessel density was evident in EAF2-deficient mice on a pure C57BL/6J background at an early age and preceded the development of the histologic epithelial hyperplasia and neoplasia found in the prostates of older EAF2−/− animals. Mice deficient in EAF2 had an increased recovery rate and a decreased overall response to the effects of androgen deprivation. EAF2 expression in human cancer was significantly down-regulated and microvessel density was significantly increased compared to matched normal prostate tissue; furthermore EAF2 expression was negatively correlated with microvessel density. These results suggest that the EAF2 knockout mouse on the C57BL/6J and FVB/NJ genetic backgrounds provides a model of PIN lesions associated with an altered prostate microvasculature and reactive stromal compartment corresponding to that reported in human prostate tumors. PMID:24260246

  19. Deep smarts.

    PubMed

    Leonard, Dorothy; Swap, Walter

    2004-09-01

    When a person sizes up a complex situation and rapidly comes to a decision that proves to be not just good but brilliant, you think, "That was smart." After you watch him do this a few times, you realize you're in the presence of something special. It's not raw brainpower, though that helps. It's not emotional intelligence, either, though that, too, is often involved. It's deep smarts. Deep smarts are not philosophical--they're not"wisdom" in that sense, but they're as close to wisdom as business gets. You see them in the manager who understands when and how to move into a new international market, in the executive who knows just what kind of talk to give when her organization is in crisis, in the technician who can track a product failure back to an interaction between independently produced elements. These are people whose knowledge would be hard to purchase on the open market. Their insight is based on know-how more than on know-what; it comprises a system view as well as expertise in individual areas. Because deep smarts are experienced based and often context specific, they can't be produced overnight or readily imported into an organization. It takes years for an individual to develop them--and no time at all for an organization to lose them when a valued veteran walks out the door. They can be taught, however, with the right techniques. Drawing on their forthcoming book Deep Smarts, Dorothy Leonard and Walter Swap say the best way to transfer such expertise to novices--and, on a larger scale, to make individual knowledge institutional--isn't through PowerPoint slides, a Web site of best practices, online training, project reports, or lectures. Rather, the sage needs to teach the neophyte individually how to draw wisdom from experience. Companies have to be willing to dedicate time and effort to such extensive training, but the investment more than pays for itself.

  20. Apparent anisotropy in inhomogeneous isotropic media

    NASA Astrophysics Data System (ADS)

    Lin, Fan-Chi; Ritzwoller, Michael H.

    2011-09-01

    Surface waves propagating through a laterally inhomogeneous medium undergo wavefield complications such as multiple scattering, wave front healing, and backward scattering. Unless accounted for accurately, these effects will introduce a systematic isotropic bias in estimates of azimuthal anisotropy. We demonstrate with synthetic experiments that backward scattering near an observing station will introduce an apparent 360° periodicity into the azimuthal distribution of anisotropy near strong lateral variations in seismic wave speeds that increases with period. Because it violates reciprocity, this apparent 1ψ anisotropy, where ψ is the azimuthal angle, is non-physical for surface waves and is, therefore, a useful indicator of isotropic bias. Isotropic bias of the 2ψ (180° periodicity) component of azimuthal anisotropy, in contrast, is caused mainly by wave front healing, which results from the broad forward scattering part of the surface wave sensitivity kernel. To test these predictions, we apply geometrical ray theoretic (eikonal) tomography to teleseismic Rayleigh wave measurements across the Transportable Array component of USArray to measure the directional dependence of phase velocities between 30 and 80 s period. Eikonal tomography accounts for multiple scattering (ray bending) but not finite frequency effects such as wave front healing or backward scattering. At long periods (>50 s), consistent with the predictions from the synthetic experiments, a significant 1ψ component of azimuthal anisotropy is observed near strong isotropic structural contrasts with fast directions that point in the direction of increasing phase speeds. The observed 2ψ component of azimuthal anisotropy is more weakly correlated with synthetic predictions of isotropic bias, probably because of the imprint of intrinsic structural anisotropy. The observation of a 1ψ component of azimuthal anisotropy is a clear indicator of isotropic bias in the inversion caused by unmodelled

  1. Stromal Response to Prostate Cancer: Nanotechnology-Based Detection of Thioredoxin-Interacting Protein Partners Distinguishes Prostate Cancer Associated Stroma from That of Benign Prostatic Hyperplasia

    PubMed Central

    Singer, Elizabeth; Linehan, Jennifer; Babilonia, Gail; Imam, S. Ashraf; Smith, David; Loera, Sofia; Wilson, Timothy; Smith, Steven

    2013-01-01

    Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in prostate cancer, however, molecular markers of the stromal response to prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal biomarkers detected with a thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate tumor tissue sections. To accomplish this, random frozen prostate tissue sections from each of 35 patients who underwent resection were incubated with the nanodevice and graded for fluorescent intensity. An adjacent section from each case was stained with Hematoxylin & Eosin to confirm the diagnosis. Select cases were stained with Masson's Trichrome or immunohistochemically using antibodies to thioredoxin reductase 1, thioredoxin reductase 2 or peroxiredoxin 1. Our results demonstrate that the graded intensity of nanodevice binding to the stroma associated with PCA was significantly higher (p = 0.0127) than that of benign prostatic hyperplasia using the t-test. Immunohistochemical staining of adjacent sections in representative cases showed that none of the two commonly studied thioredoxin interacting protein partners mirrored the fluorescence pattern seen with the nanodevice. However, thioredoxin reductase 2 protein was clearly shown to be a biomarker of prostate cancer-associated reactive stroma whose presence distinguishes the stroma associated with benign prostatic hyperplasia from that associated with prostate cancer. We conclude that the signal detected by the nanodevice, in contrast to individual targets detected with antibodies used in this study, originates from multiple thioredoxin interacting protein partners that distinguish the M2 neutrophil and

  2. Stromal response to prostate cancer: nanotechnology-based detection of thioredoxin-interacting protein partners distinguishes prostate cancer associated stroma from that of benign prostatic hyperplasia.

    PubMed

    Singer, Elizabeth; Linehan, Jennifer; Babilonia, Gail; Imam, S Ashraf; Smith, David; Loera, Sofia; Wilson, Timothy; Smith, Steven

    2013-01-01

    Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in prostate cancer, however, molecular markers of the stromal response to prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal biomarkers detected with a thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate tumor tissue sections. To accomplish this, random frozen prostate tissue sections from each of 35 patients who underwent resection were incubated with the nanodevice and graded for fluorescent intensity. An adjacent section from each case was stained with Hematoxylin & Eosin to confirm the diagnosis. Select cases were stained with Masson's Trichrome or immunohistochemically using antibodies to thioredoxin reductase 1, thioredoxin reductase 2 or peroxiredoxin 1. Our results demonstrate that the graded intensity of nanodevice binding to the stroma associated with PCA was significantly higher (p = 0.0127) than that of benign prostatic hyperplasia using the t-test. Immunohistochemical staining of adjacent sections in representative cases showed that none of the two commonly studied thioredoxin interacting protein partners mirrored the fluorescence pattern seen with the nanodevice. However, thioredoxin reductase 2 protein was clearly shown to be a biomarker of prostate cancer-associated reactive stroma whose presence distinguishes the stroma associated with benign prostatic hyperplasia from that associated with prostate cancer. We conclude that the signal detected by the nanodevice, in contrast to individual targets detected with antibodies used in this study, originates from multiple thioredoxin interacting protein partners that distinguish the M2 neutrophil and

  3. SPARC independent delivery of nab-paclitaxel without depleting tumor stroma in patient-derived pancreatic cancer xenografts

    PubMed Central

    Kim, Harrison; Samuel, Sharon L.; Lopez-Casas, Pedro P.; Grizzle, William E.; Hidalgo, Manuel; Kovar, Joy; Oelschlager, Denise K.; Zinn, Kurt R.; Warram, Jason M.; Buchsbaum, Donald J.

    2016-01-01

    The study goal was to examine the relationship between nab-paclitaxel delivery and SPARC (secreted protein acidic and rich in cysteine) expression in pancreatic tumor xenografts and to determine the anti-stromal effect of nab-paclitaxel, which may affect tumor vascular perfusion. SPARC positive and negative mice bearing Panc02 tumor xenografts (n=5–6/group) were injected with IRDye 800CW (IR800)-labeled nab-paclitaxel. After 24 hours, tumors were collected and stained with DL650-labeled anti-SPARC antibody, and the correlation between nab-paclitaxel and SPARC distributions was examined. Eight groups of mice bearing either Panc039 or Panc198 patient-derived xenografts (PDXs) (4 groups/model, 5 animals/group) were untreated (served as control) or treated with gemcitabine (100 mg/kg BW, i.p., twice per week), nab-paclitaxel (30 mg/kg BW, i.v., for 5 consecutive days), and these agents in combination, respectively, for 3 weeks, and tumor volume and perfusion changes were assessed using T2-weighted magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE) MRI, respectively. All tumors were collected and stained with Masson’s Trichrome Stain, followed by a blinded comparative analysis of tumor stroma density. IR800-nab-paclitaxel was mainly distributed in tumor stromal tissue, but nab-paclitaxel and SPARC distributions were minimally correlated in either SPARC positive or negative animals. Nab-paclitaxel treatment did not decrease tumor stroma nor increase tumor vascular perfusion in either PDX model when compared to control groups. These data suggest that the specific tumor delivery of nab-paclitaxel is not directly related to SPARC expression, and nab-paclitaxel does not deplete tumor stroma in general. PMID:26832793

  4. Apparent life-threatening event in infancy

    PubMed Central

    Choi, Hee Joung

    2016-01-01

    An apparent life-threatening event (ALTE) is defined as the combination of clinical presentations such as apnea, marked change in skin and muscle tone, gagging, or choking. It is a frightening event, and it predominantly occurs during infancy at a mean age of 1–3 months. The causes of ALTE are categorized into problems that are: gastrointestinal (50%), neurological (30%), respiratory (20%), cardiovascular (5%), metabolic and endocrine (2%–5%), or others such as child abuse. Up to 50% of ALTEs are idiopathic, where the cause cannot be diagnosed. Infants with an ALTE are often asymptomatic at hospital and there is no standard workup protocol for ALTE. Therefore, a detailed initial history and physical examination are important to determine the extent of the medical evaluation and treatment. Regardless of the cause of an ALTE, all infants with an ALTE should require hospitalization and continuous cardiorespiratory monitoring and evaluation for at least 24 hours. The natural course of ALTEs has seemed benign, and the outcome is generally associated with the affected infants' underlying disease. In conclusion, systemic diagnostic evaluation and adequate treatment increases the survival and quality of life for most affected infants. PMID:27721838

  5. Apparent speed increases at low luminance

    PubMed Central

    Vaziri-Pashkam, Maryam; Cavanagh, Patrick

    2009-01-01

    To investigate the effect of luminance on apparent speed, subjects adjusted the speed of a low-luminance rotating grating (0.31 cd/m2) to match that of a high-luminance one (1260 cd/m2). Above 4 Hz, subjects overestimated the speed of the low-luminance grating. This overestimation increased as a function of temporal rate and reached 30% around 10 Hz temporal rates. The speed overestimation became significant once the lower luminance was 2.4 log units lower than the high luminance comparison. Next the role of motion smear in speed overestimation was examined. First it was shown that the length of the perceived motion smear increased at low luminances. Second, the length of the visible smear was manipulated by changing the presentation time of the stimuli. Speed overestimation was reduced at shorter presentation times. Third the speed of a blurred stimulus was compared to a stimulus with sharp edges and the blurred stimulus was judged to move faster. These results indicate that the length of motion smear following a target contributes to its perceived speed and that this leads to speed overestimation at low luminance where motion traces lengthen because of increased persistence. PMID:19146275

  6. Biochemical characterization of nuclear receptors for vitamin D{sub 3} and glucocorticoids in prostate stroma cell microenvironment

    SciTech Connect

    Hidalgo, Alejandro A.; Montecinos, Viviana P.; Paredes, Roberto; Godoy, Alejandro S.; McNerney, Eileen M.; Tovar, Heribelt; Pantoja, Diego; Johnson, Candace; Trump, Donald; Onate, Sergio A.

    2011-08-19

    Highlights: {yields} Fibroblasts from benign and carcinoma-associated stroma were biochemically characterized for VDR and GR function as transcription factors in prostate stroma cell microenvironment. {yields} Decreased SRC-1/CBP coactivators recruitment to VDR and GR may result in hormone resistance to 1,25D{sub 3} in stromal cell microenvironment prostate cancer. {yields} 1a,25-Dyhidroxyvitamin D{sub 3} (1,25D{sub 3}) and glucocorticoids, either alone or in combination, may not be an alternative for 'some' advanced prostate cancers that fails androgen therapies. -- Abstract: The disruption of stromal cell signals in prostate tissue microenvironment influences the development of prostate cancer to androgen independence. 1{alpha},25-Dihydroxyvitamin D{sub 3} (1,25D{sub 3}) and glucocorticoids, either alone or in combination, have been investigated as alternatives for the treatment of advanced prostate cancers that fails androgen therapies. The effects of glucocorticoids are mediated by the intracellular glucocorticoid receptor (GR). Similarly, the effect of 1,25D{sub 3} is mediated by the 1,25D{sub 3} nuclear receptor (VDR). In this study, fibroblasts from benign- (BAS) and carcinoma-associated stroma (CAS) were isolated from human prostates to characterize VDR and GR function as transcription factors in prostate stroma. The VDR-mediated transcriptional activity assessed using the CYP24-luciferase reporter was limited to 3-fold induction by 1,25D{sub 3} in 9 out of 13 CAS (70%), as compared to >10-fold induction in the BAS clinical sample pair. Expression of His-tagged VDR (Ad-his-VDR) failed to recover the low transcriptional activity of the luciferase reporter in 7 out of 9 CAS. Interestingly, expression of Ad-his-VDR successfully recovered receptor-mediated induction in 2 out of the 9 CAS analyzed, suggesting that changes in the receptor protein itself was responsible for decreased response and resistance to 1,25D{sub 3} action. Conversely, VDR

  7. An apparent hiatus in global warming?

    NASA Astrophysics Data System (ADS)

    Trenberth, Kevin E.; Fasullo, John T.

    2013-12-01

    Global warming first became evident beyond the bounds of natural variability in the 1970s, but increases in global mean surface temperatures have stalled in the 2000s. Increases in atmospheric greenhouse gases, notably carbon dioxide, create an energy imbalance at the top-of-atmosphere (TOA) even as the planet warms to adjust to this imbalance, which is estimated to be 0.5-1 W m-2 over the 2000s. Annual global fluctuations in TOA energy of up to 0.2 W m-2 occur from natural variations in clouds, aerosols, and changes in the Sun. At times of major volcanic eruptions the effects can be much larger. Yet global mean surface temperatures fluctuate much more than these can account for. An energy imbalance is manifested not just as surface atmospheric or ground warming but also as melting sea and land ice, and heating of the oceans. More than 90% of the heat goes into the oceans and, with melting land ice, causes sea level to rise. For the past decade, more than 30% of the heat has apparently penetrated below 700 m depth that is traceable to changes in surface winds mainly over the Pacific in association with a switch to a negative phase of the Pacific Decadal Oscillation (PDO) in 1999. Surface warming was much more in evidence during the 1976-1998 positive phase of the PDO, suggesting that natural decadal variability modulates the rate of change of global surface temperatures while sea-level rise is more relentless. Global warming has not stopped; it is merely manifested in different ways.

  8. Apparent diffusion coefficient of normal adrenal glands*

    PubMed Central

    Teixeira, Sara Reis; Elias, Paula Condé Lamparelli; Leite, Andrea Farias de Melo; de Oliveira, Tatiane Mendes Gonçalves; Muglia, Valdair Francisco; Elias Junior, Jorge

    2016-01-01

    Objective To assess the feasibility and reliability of apparent diffusion coefficient (ADC) measurements of normal adrenal glands. Materials and methods This was a retrospective study involving 32 healthy subjects, divided into two groups: prepubertal (PreP, n = 12), aged from 2 months to 12.5 years (4 males; 8 females); and postpubertal (PostP, n = 20), aged from 11.9 to 61 years (5 males; 15 females). Diffusion-weighted magnetic resonance imaging (DW-MRI) sequences were acquired at a 1.5 T scanner using b values of 0, 20, 500, and 1000 s/mm2. Two radiologists evaluated the images. ADC values were measured pixel-by-pixel on DW-MRI scans, and automatic co-registration with the ADC map was obtained. Results Mean ADC values for the right adrenal glands were 1.44 × 10-3 mm2/s for the PreP group and 1.23 × 10-3 mm2/s for the PostP group, whereas they were 1.58 × 10-3 mm2/s and 1.32 × 10-3 mm2/s, respectively, for the left glands. ADC values were higher in the PreP group than in the PostP group (p < 0.05). Agreement between readers was almost perfect (intraclass correlation coefficient, 0.84-0.94; p < 0.05). Conclusion Our results demonstrate the feasibility and reliability of performing DW-MRI measurements of normal adrenal glands. They could also support the feasibility of ADC measurements of small structures. PMID:28057963

  9. Apparent exchange rate for breast cancer characterization.

    PubMed

    Lasič, Samo; Oredsson, Stina; Partridge, Savannah C; Saal, Lao H; Topgaard, Daniel; Nilsson, Markus; Bryskhe, Karin

    2016-05-01

    Although diffusion MRI has shown promise for the characterization of breast cancer, it has low specificity to malignant subtypes. Higher specificity might be achieved if the effects of cell morphology and molecular exchange across cell membranes could be disentangled. The quantification of exchange might thus allow the differentiation of different types of breast cancer cells. Based on differences in diffusion rates between the intra- and extracellular compartments, filter exchange spectroscopy/imaging (FEXSY/FEXI) provides non-invasive quantification of the apparent exchange rate (AXR) of water between the two compartments. To test the feasibility of FEXSY for the differentiation of different breast cancer cells, we performed experiments on several breast epithelial cell lines in vitro. Furthermore, we performed the first in vivo FEXI measurement of water exchange in human breast. In cell suspensions, pulsed gradient spin-echo experiments with large b values and variable pulse duration allow the characterization of the intracellular compartment, whereas FEXSY provides a quantification of AXR. These experiments are very sensitive to the physiological state of cells and can be used to establish reliable protocols for the culture and harvesting of cells. Our results suggest that different breast cancer subtypes can be distinguished on the basis of their AXR values in cell suspensions. Time-resolved measurements allow the monitoring of the physiological state of cells in suspensions over the time-scale of hours, and reveal an abrupt disintegration of the intracellular compartment. In vivo, exchange can be detected in a tumor, whereas, in normal tissue, the exchange rate is outside the range experimentally accessible for FEXI. At present, low signal-to-noise ratio and limited scan time allows the quantification of AXR only in a region of interest of relatively large tumors.

  10. Deep blast

    NASA Astrophysics Data System (ADS)

    From southern New Mexico to the Great Slave Lake of Canada, scientists from the United States and Canada recently detonated 10 underground chemical explosions to generate a clearer picture of the Earth's crust and upper mantle. Called Project Deep Probe, the experiment is designed to see through the crust and into the upper mantle to a depth of 300 miles.In the United States, Earth scientists from Rice University, Purdue University, and the University of Oregon are participating in the project. “Researchers hope to get a picture of the upper mantle beneath the Rocky Mountains and the Colorado Plateau, to understand the role the mantle played in formation and uplift,” says Alan Levander of Rice. To enhance that “picture,” 750 portable seismographs were placed along a roughly north-south line extending from Crownpoint, New Mexico to Edmonton, Alberta. The seismic recordings will be used to enhance weak seismic waves that penetrated the upper mantle.

  11. Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma.

    PubMed

    Liu, Yaling; Strecker, Sara; Wang, Liping; Kronenberg, Mark S; Wang, Wen; Rowe, David W; Maye, Peter

    2013-01-01

    We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued existence of their progeny up to 10 months of age, suggesting that fate mapped, labeled embryonic precursors gave rise to long lived bone marrow progenitor cells. To provide further evidence for the marking of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9 mice showed that stromal cells retained Cre reporter expression and yielded a FACS sorted population that was able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and perivascular stromal cells after transplantation. Collectively, our studies reveal the developmental process by which Osterix-Cre labeled embryonic progenitors give rise to adult bone marrow progenitors which establish and maintain the bone marrow stroma.

  12. High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence

    PubMed Central

    Nordby, Yngve; Richardsen, Elin; Rakaee, Mehrdad; Ness, Nora; Donnem, Tom; Patel, Hiten R. H.; Busund, Lill-Tove; Bremnes, Roy M.; Andersen, Sigve

    2017-01-01

    Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the prognostic impact of PDGFR-β and its ligands (PDGF-B and PDGF-D) in a multicenter prostatectomy cohort of 535 Norwegian patients. Using tissue microarrays and immunohistochemistry, the expression of ligands PDGF-B and PDGF-D and their corresponding receptor, PDGFR-β, was assessed in neoplastic tissue and tumor-associated stroma. PDGFR-β was expressed in benign and tumor associated stroma, but not in epithelium. High stromal expression of PDGFR-β was independently associated with clinical relapse (HR = 2.17, p = 0.010) and biochemical failure (HR = 1.58, p = 0.002). This large study highlights the prognostic importance of PDGFR-β expression, implicating its involvement in prostate cancer progression even in early stage disease. Hence, analyses of PDGFR-β may help distinguish which patients will benefit from radical treatment, and since PDGFR-β is associated with relapse and shorter survival, it mandates a focus as a therapeutic target. PMID:28233816

  13. Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis

    SciTech Connect

    Santamaria-Martinez, Albert; Barquinero, Jordi; Barbosa-Desongles, Anna; Hurtado, Antoni; Pinos, Tomas; Seoane, Joan; Poupon, Marie-France; Morote, Joan; Reventos, Jaume; Munell, Francina

    2009-10-15

    Cancer stem cells are a distinct cellular population that is believed to be responsible for tumor initiation and maintenance. Recent data suggest that solid tumors also contain another type of stem cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs), which contribute to the formation of tumor-associated stroma. The Hoechst 33342 efflux assay has proved useful to identify a rare cellular fraction, named Side Population (SP), enriched in cells with stem-like properties. Using this assay, we identified SP cells in a prostate cancer xenograft containing human prostate cancer cells and mouse stromal cells. The SP isolation, subculture and sequential sorting allowed the generation of single-cell-derived clones of murine origin that were recognized as MSC by their morphology, plastic adherence, proliferative potential, adipogenic and osteogenic differentiation ability and immunophenotype (CD45{sup -}, CD81{sup +} and Sca-1{sup +}). We also demonstrated that SP clonal cells secrete transforming growth factor {beta}1 (TGF-{beta}1) and that their inhibition reduces proliferation and accelerates differentiation. These results reveal the existence of SP cells in the stroma of a cancer xenograft, and provide evidence supporting their MSC nature and the role of TGF-{beta}1 in maintaining their proliferation and undifferentiated status. Our data also reveal the usefulness of the SP assay to identify and isolate MSC cells from carcinomas.

  14. IP-10/CXCL10 induction in human pancreatic cancer stroma influences lymphocytes recruitment and correlates with poor survival.

    PubMed

    Lunardi, Serena; Jamieson, Nigel B; Lim, Su Yin; Griffiths, Kristin L; Carvalho-Gaspar, Manuela; Al-Assar, Osama; Yameen, Sabira; Carter, Ross C; McKay, Colin J; Spoletini, Gabriele; D'Ugo, Stefano; Silva, Michael A; Sansom, Owen J; Janssen, Klaus-Peter; Muschel, Ruth J; Brunner, Thomas B

    2014-11-30

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant desmoplastic reaction driven by pancreatic stellate cells (PSCs) that contributes to tumor progression. Here we sought to characterize the interactions between pancreatic cancer cells (PCCs) and PSCs that affect the inflammatory and immune response in pancreatic tumors. Conditioned media from mono- and cocultures of PSCs and PCCs were assayed for expression of cytokines and growth factors. IP-10/CXCL10 was the most highly induced chemokine in coculture of PSCs and PCCs. Its expression was induced in the PSCs by PCCs. IP-10 was elevated in human PDAC specimens, and positively correlated with high stroma content. Furthermore, gene expression of IP-10 and its receptor CXCR3 were significantly associated with the intratumoral presence of regulatory T cells (Tregs). In an independent cohort of 48 patients with resectable pancreatic ductal adenocarcinoma, high IP-10 expression levels correlated with decreased median overall survival. Finally, IP-10 stimulated the ex vivo recruitment of CXCR3+ effector T cells as well as CXCR3+ Tregs derived from patients with PDAC. Our findings suggest that, in pancreatic cancer, CXCR3+ Tregs can be recruited by IP-10 expressed by PSCs in the tumor stroma, leading to immunosuppressive and tumor-promoting effects.

  15. Human Cornea Proteome: Identification and Quantitation of the Proteins of the Three Main Layers Including Epithelium, Stroma, and Endothelium

    PubMed Central

    2012-01-01

    Diseases of the cornea are common and refer to conditions like infections, injuries and genetic defects. Morphologically, many corneal diseases affect only certain layers of the cornea and separate analysis of the individual layers is therefore of interest to explore the basic molecular mechanisms involved in corneal health and disease. In this study, the three main layers including, the epithelium, stroma and endothelium of healthy human corneas were isolated. Prior to analysis by LC–MS/MS the proteins from the different layers were either (i) separated by SDS-PAGE followed by in-gel trypsinization, (ii) in-solution digested without prior protein separation or, (iii) in-solution digested followed by cation exchange chromatography. A total of 3250 unique Swiss-Prot annotated proteins were identified in human corneas, 2737 in the epithelium, 1679 in the stroma, and 880 in the endothelial layer. Of these, 1787 proteins have not previously been identified in the human cornea by mass spectrometry. In total, 771 proteins were quantified, 157 based on in-solution digestion and 770 based on SDS-PAGE separation followed by in-gel digestion of excised gel pieces. Protein analysis showed that many of the identified proteins are plasma proteins involved in defense responses. PMID:22698189

  16. Targeted Disruption of Orchestration between Stroma and Tumor Cells in Pancreatic Cancer: Molecular Basis and Therapeutic Implications

    PubMed Central

    Kong, Xiangyu; Li, Lei; Li, Zhaoshen; Xie, Keping

    2012-01-01

    Pancreatic cancer is one of the most lethal malignancies, with a prominent desmoplastic reaction as the defining hallmark of the disease. The past several decades have seen dramatic progress in understanding of pancreatic cancer pathogenesis, including the identification of precursor lesions, sequential transformation from normal pancreas to invasive pancreatic cancer and corresponding signature genetic events, and the biological impact of those alterations on malignant behaviors. However, the current therapeutic strategies for epithelial tumor cells, which have exhibited potent antitumor activity in cell culture and animal models, have failed to have significant effects in the clinic. The desmoplastic stroma surrounding pancreatic cancer cells, which accounts for about 90% of a tumor’s mass, clearly is not a passive scaffold for cancer cells but an active contributor to carcinogenesis. Improved understanding of the dynamic interaction between cancer cells and their stroma will be important to designing new, effective therapeutic strategies for pancreatic cancer. This review focuses on the origination of stromal molecular and cellular components in pancreatic tumors, their biological effects on pancreatic cancer cells, and the orchestration between these two components. PMID:22749856

  17. Biocompatibility and Biomechanical Effect of Single Wall Carbon Nanotubes Implanted in the Corneal Stroma: A Proof of Concept Investigation

    PubMed Central

    Rodriguez, Alejandra E.; Rodriguez-Reinoso, Francisco; Gomez-Tejedor, Jose A.; Antolinos-Turpin, Carmen M.; Bataille, Laurent; Alio, Jorge L.

    2016-01-01

    Corneal ectatic disorders are characterized by a progressive weakening of the tissue due to biomechanical alterations of the corneal collagen fibers. Carbon nanostructures, mainly carbon nanotubes (CNTs) and graphene, are nanomaterials that offer extraordinary mechanical properties and are used to increase the rigidity of different materials and biomolecules such as collagen fibers. We conducted an experimental investigation where New Zealand rabbits were treated with a composition of CNTs suspended in balanced saline solution which was applied in the corneal tissue. Biocompatibility of the composition was assessed by means of histopathology analysis and mechanical properties by stress-strain measurements. Histopathology samples stained with blue Alcian showed that there were no fibrous scaring and no alterations in the mucopolysaccharides of the stroma. It also showed that there were no signs of active inflammation. These were confirmed when Masson trichrome staining was performed. Biomechanical evaluation assessed by means of tensile test showed that there is a trend to obtain higher levels of rigidity in those corneas implanted with CNTs, although these changes are not statistically significant (p > 0.05). Implanting CNTs is biocompatible and safe procedure for the corneal stroma which can lead to an increase in the rigidity of the collagen fibers. PMID:28116139

  18. Apparent diffusion coefficient normalization of normal liver

    PubMed Central

    Zhu, Jie; Zhang, Jie; Gao, Jia-Yin; Li, Jin-Ning; Yang, Da-Wei; Chen, Min; Zhou, Cheng; Yang, Zheng-Han

    2017-01-01

    Abstract Apparent diffusion coefficient (ADC) measurement in diffusion-weighted imaging (DWI) has been reported to be a helpful biomarker for detection and characterization of lesion. In view of the importance of ADC measurement reproducibility, the aim of this study was to probe the variability of the healthy hepatic ADC values measured at 3 MR scanners from different vendors and with different field strengths, and to investigate the reproducibility of normalized ADC (nADC) value with the spleen as the reference organ. Thirty enrolled healthy volunteers received DWI with GE 1.5T, Siemens 1.5T, and Philips 3.0T magnetic resonance (MR) systems on liver and spleen (session 1) and were imaged again after 10 to 14 days using only GE 1.5T MR and Philips 3.0T MR systems (session 2). Interscan agreement and reproducibility of ADC measurements of liver and the calculated nADC values (ADCliver/ADCspleen) were statistically evaluated between 2 sessions. In session 1, ADC and nADC values of liver were evaluated for the scanner-related variability by 2-way analysis of variance and intraclass correlation coefficients (ICCs). Coefficients of variation (CVs) of ADCs and nADCs of liver were calculated for both 1.5 and 3.0-T MR system. Interscan agreement and reproducibility of ADC measurements of liver and related nADCs between 2 sessions were found to be satisfactory with ICC values of 0.773 to 0.905. In session 1, the liver nADCs obtained from different scanners were consistent (P = 0.112) without any significant difference in multiple comparison (P = 0.117 to >0.99) by using 2-way analysis of variance with post-hoc analysis of Bonferroni method, although the liver ADCs varied significantly (P < 0.001). nADCs measured by 3 scanners were in good interscanner agreements with ICCs of 0.685 to 0.776. The mean CV of nADCs of both 1.5T MR scanners (9.6%) was similar to that of 3.0T MR scanner (8.9%). ADCs measured at 3 MR scanners with different field strengths and vendors

  19. 48 CFR 14.407-2 - Apparent clerical mistakes.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.407-2 Apparent clerical mistakes. (a) Any clerical mistake, apparent on its face in the bid, may be corrected by the... the bid intended. Examples of apparent mistakes are— (1) Obvious misplacement of a decimal point;...

  20. 48 CFR 14.407-2 - Apparent clerical mistakes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.407-2 Apparent clerical mistakes. (a) Any clerical mistake, apparent on its face in the bid, may be corrected by the... the bid intended. Examples of apparent mistakes are— (1) Obvious misplacement of a decimal point;...

  1. 48 CFR 14.407-2 - Apparent clerical mistakes.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.407-2 Apparent clerical mistakes. (a) Any clerical mistake, apparent on its face in the bid, may be corrected by the... the bid intended. Examples of apparent mistakes are— (1) Obvious misplacement of a decimal point;...

  2. 48 CFR 14.407-2 - Apparent clerical mistakes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.407-2 Apparent clerical mistakes. (a) Any clerical mistake, apparent on its face in the bid, may be corrected by the... the bid intended. Examples of apparent mistakes are— (1) Obvious misplacement of a decimal point;...

  3. 48 CFR 14.407-2 - Apparent clerical mistakes.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.407-2 Apparent clerical mistakes. (a) Any clerical mistake, apparent on its face in the bid, may be corrected by the... the bid intended. Examples of apparent mistakes are— (1) Obvious misplacement of a decimal point;...

  4. Expression of Autoactivated Stromelysin-1 in Mammary Glands of Transgenic Mice Leads to a Reactive Stroma During Early Development

    SciTech Connect

    Thomasset, N.; Lochter, A.; Sympson, C.J.; Lund, L.R.; Williams, D.R.; Behrendtsen, O.; Werb, Z.; Bissell, M.J.

    1998-04-24

    Extracellular matrix and extracellular matrix-degrading matrix metalloproteinases play a key role in interactions between the epithelium and the mesenchyme during mammary gland development and disease. In patients with breast cancer, the mammary mesenchyme undergoes a stromal reaction, the etiology of which is unknown. We previously showed that targeting of an autoactivating mutant of the matrix metalloproteinase stromelysin-1 to mammary epithelia of transgenic mice resulted in reduced mammary function during pregnancy and development of preneoplastic and neoplastic lesions. Here we examine the cascade of alterations before breast tumor formation in the mammary gland stroma once the expression of the stromelysin-1 transgene commences. Beginning in postpubertal virgin animals, low levels of transgene expression in mammary epithelia led to increased expression of endogenous stromelysin-1 in stromal fibroblasts and up-regulation of other matrix metalloproteinases, without basement membrane disruption. These changes were accompanied by the progressive development of a compensatory reactive stroma, characterized by increased collagen content and vascularization in glands from virgin mice. This remodeling of the gland affected epithelial-mesenchymal communication as indicated by inappropriate expression of tenascin-C starting by day 6 of pregnancy. This, together with increased transgene expression, led to basement membrane disruption starting by day 15 of pregnancy. We propose that the highly reactive stroma provides a prelude to breast epithelial tumors observed in these animals. Epithelial development depends on an exquisite series of inductive and instructive interactions between the differentiating epithelium and the mesenchymal (stromal) compartment. The epithelium, which consists of luminal and myoepithelial cells, is separated from the stroma by a basement membrane (BM), which plays a central role in mammary gland homeostasis and gene expression. In vivo, stromal

  5. Deep breathing after surgery

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000440.htm Deep breathing after surgery To use the sharing features on ... way to do so is by doing deep breathing exercises. Deep breathing keeps your lungs well-inflated ...

  6. Preventing Deep Vein Thrombosis

    MedlinePlus

    ... Education & Events Advocacy For Patients About ACOG Preventing Deep Vein Thrombosis Home For Patients Search FAQs Preventing ... Vein Thrombosis FAQ174, August 2011 PDF Format Preventing Deep Vein Thrombosis Women's Health What is deep vein ...

  7. Efficient Generation of Multipotent Mesenchymal Stem Cells from Umbilical Cord Blood in Stroma-Free Liquid Culture

    PubMed Central

    van den Broek, Maries; Nuvolone, Mario; Dannenmann, Stefanie; Stieger, Bruno; Rapold, Reto; Konrad, Daniel; Rubin, Arnold; Bertino, Joseph R.; Aguzzi, Adriano; Heikenwalder, Mathias; Knuth, Alexander K.

    2010-01-01

    Background Haematopoiesis is sustained by haematopoietic (HSC) and mesenchymal stem cells (MSC). HSC are the precursors for blood cells, whereas marrow, stroma, bone, cartilage, muscle and connective tissues derive from MSC. The generation of MSC from umbilical cord blood (UCB) is possible, but with low and unpredictable success. Here we describe a novel, robust stroma-free dual cell culture system for long-term expansion of primitive UCB-derived MSC. Methods and Findings UCB-derived mononuclear cells (MNC) or selected CD34+ cells were grown in liquid culture in the presence of serum and cytokines. Out of 32 different culture conditions that have been tested for the efficient expansion of HSC, we identified one condition (DMEM, pooled human AB serum, Flt-3 ligand, SCF, MGDF and IL-6; further denoted as D7) which, besides supporting HSC expansion, successfully enabled long-term expansion of stromal/MSC from 8 out of 8 UCB units (5 MNC-derived and 3 CD34+ selected cells). Expanded MSC displayed a fibroblast-like morphology, expressed several stromal/MSC-related antigens (CD105, CD73, CD29, CD44, CD133 and Nestin) but were negative for haematopoietic cell markers (CD45, CD34 and CD14). MSC stemness phenotype and their differentiation capacity in vitro before and after high dilution were preserved throughout long-term culture. Even at passage 24 cells remained Nestin+, CD133+ and >95% were positive for CD105, CD73, CD29 and CD44 with the capacity to differentiate into mesodermal lineages. Similarly we show that UCB derived MSC express pluripotency stem cell markers despite differences in cell confluency and culture passages. Further, we generated MSC from peripheral blood (PB) MNC of 8 healthy volunteers. In all cases, the resulting MSC expressed MSC-related antigens and showed the capacity to form CFU-F colonies. Conclusions This novel stroma-free liquid culture overcomes the existing limitation in obtaining MSC from UCB and PB enabling so far unmet therapeutic

  8. Self-renewal and differentiation of a novel bipotent myeloid progenitor clone in the stroma-dependent culture.

    PubMed

    Okubo, T; Yanai, N; Obinata, M

    2000-06-01

    To understand regulation of myeloid development, it is necessary to obtain the myeloid progenitor cell lines with self-renewal and differentiation capacities. Because prolonged hematopoiesis occurs with the production of myeloid cells at all stages of differentiation in the Dexter-type long-term bone marrow cultures, we tried to obtain stroma-dependent myeloid progenitor cells starting from the long-term bone marrow culture. Murine cobblestone areas generated in long-term bone marrow cultures were serially passaged every 10 days. After 4 months, the resultant hematopoietic cells, designated as DFC, were passaged on a monolayer of established spleen stromal cell line, MSS62. After 10-12 passages of DFC cells on MSS62, several clones were obtained by colony formation on MSS62 cell layer. Among these clones, DFC-a cells could be maintained for a long period by coculturing with the established stromal cell line, MSS62.DFC-a cells proliferated by forming cobblestones and contained blast cells, granulocytes, and macrophages. Cell sorting and coculture experiments indicated that the blast type cells exhibiting c-Kit(+) Gr-1(-) Mac-1(-), stroma-dependently self-renewed, and spontaneously differentiated toward granulocytes (c-Kit(+) Gr-1(+) Mac-1(+)) and macrophages (c-Kit(low/+) Gr-1(-) Mac-1(high)). Although most of DFC-a cells expressed c-Kit, SCF-c-Kit interaction was not always necessary for their growth. In the presence of stromal cells, growth and differentiation of DFC-a cells were stimulated by GM-CSF or IL-3. Without stromal cells, DFC-a was transiently expanded by GM-CSF or IL-3 but could not be maintained constantly by these cytokines. The present study demonstrated that DFC-a is a novel bipotent myeloid progenitor cell clone as a simple model system of stroma-dependent myeloid development. It may reflect distinct properties for the earliest myeloid progenitor cells in vivo. It is of interest to know what signals are provided by MSS62 stromal cells to maintain

  9. Periostin in the Cancer Stroma of Mycosis Fungoides Palmaris et Plantaris: A Case Report and Immunohistochemical Study

    PubMed Central

    Tanita, Kayo; Fujimura, Taku; Kakizaki, Aya; Furudate, Sadanori; Mizuashi, Masato; Watabe, Akiko; Aiba, Setsuya

    2016-01-01

    Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of mycosis fungoides limited to the palms and soles. Although little is known about the pathogenesis of MFPP, this variant of mycosis fungoides presents a relatively good prognosis. In this report, we describe an 85-year-old Japanese man with MFPP. Immunohistochemical staining revealed the dense deposition of periostin in the cancer stroma, as well as infiltration of CD163+CD206− tumor-associated macrophages (TAMs), which suggested the phenotypes of TAMs were not polarized to the M2 phenotype in the lesional skin of MFPP. Our present case might suggest one of the possible reasons for the good prognosis of MFPP. PMID:27293391

  10. Changing concepts about the distribution of Photosystems I and II between grana-appressed and stroma-exposed thylakoid membranes.

    PubMed

    Anderson, Jan M

    2002-01-01

    Thylakoid membranes of higher plants and some green algae, which house the light-harvesting and energy transducing functions of the chloroplast, are structurally unique. The concept of the photosynthetic unit of the 1930s (Robert Emerson, William Arnold and Hans Gaffron), needing one reaction center per hundreds of antenna molecules, was modified by the discovery of the Enhancement effect in oxygen evolution in two different wavelengths of light (Robert Emerson and his coworkers) in the late 1950s, followed by the 1960 Z scheme of Robin Hill and Fay Bendall. It was realized that two light reactions and two pigment systems were needed for oxygenic photosynthesis. Changing ideas about the distribution of Photosystem II (PS II) and PS I between the green-appressed and stroma-exposed thylakoid membrane domains, which led to the concept of lateral heterogeneity, are discussed.

  11. Apparent lethal concentrations of pyrolysis products of some polymeric materials

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Marcussen, W. H.; Furst, A.; Kourtides, D. A.; Parker, J. A.

    1976-01-01

    Thirty-nine samples of polymeric materials were evaluated to determine the apparent lethal concentrations of their pyrolysis products. The materials were compared on the basis of the apparent lethal concentration for 50 percent of the test animals. Relative toxicity rankings based o apparent lethal concentration values can differ significantly depending on whether they are based on weight of sample charged or weight of sample pyrolyzed. The ranking of polyphenylene sulfide is particularly sensitive to this difference.

  12. Resistance of leukemia cells to cytarabine chemotherapy is mediated by bone marrow stroma, involves cell-surface equilibrative nucleoside transporter-1 removal and correlates with patient outcome.

    PubMed

    Macanas-Pirard, Patricia; Broekhuizen, Richard; González, Alfonso; Oyanadel, Claudia; Ernst, Daniel; García, Patricia; Montecinos, Viviana P; Court, Felipe; Ocqueteau, Mauricio; Ramirez, Pablo; Nervi, Bruno

    2017-02-01

    The interaction between acute myeloid leukemia cells (AML) with the bone marrow stroma cells (BMSCs) determines a protective environment that favors tumor development and resistance to conventional chemotherapy. We showed that BMSCs secrete soluble factors that protect AML cells from Ara-C induced cytotoxicity. This leukemia chemoresistance is associated with a decrease in the equilibrative nucleoside transporter (ENT1) activity by inducing removal of ENT1 from the cell surface. Reduction of cell proliferation was also observed with activation of AKT and mTOR-dependent cell survival pathways, which may also contribute to the tumor chemoprotection. Analysis of primary BMSC cultures has demonstrated that AML patients with stroma capable to confer Ara-C resistance in vitro compared to AML patients without this stroma capacity were associated with a worse prognosis. The two year overall survival rate was 0% versus 80% respectively (p=0.0001). This is the first report of a chemoprotection mechanism based on the removal of a drug transporter from the cell surface and most importantly the first time that a stroma phenotype has correlated with prognostic outcome in cancer.

  13. Probing tumor-stroma interactions and response to photodynamic therapy in a 3D pancreatic cancer-fibroblast co-culture model

    NASA Astrophysics Data System (ADS)

    Glidden, Michael D.; Massodi, Iqbal; Rizvi, Imran; Celli, Jonathan P.; Hasan, Tayyaba

    2012-02-01

    Pancreatic ductal adenocarcinoma is a lethal disease that is often unresectable by the time of diagnosis and is typically non-responsive to chemo- and radiotherapy, resulting in a five year survival of only 3%. Tumors of the pancreas are characterized by a dense fibrous stroma rich in extracellular matrix proteins, which is implicated in poor therapeutic response, though its precise roles remain poorly understood. Indeed, while the use of therapeutics that target the stroma is an emerging paradigm in the clinical management of this disease, the primary focus of such efforts is to enhance drug penetration through dense fibrous stroma and it is unclear to what extent the characteristically rigid stroma of pancreatic tumors imparts drug resistance by acting as a complex signaling partner, or merely as a physical barrier for drug delivery. Here we use 3D in vitro co-cultures of pancreatic cancer cells and normal human fibroblasts as a model system to study heterotypic interactions between these populations. Leveraging this in vitro model along with image-based methods for quantification of growth and therapeutic endpoints, we characterize these co-cultures and examine the role of verteporfin-based photodynamic therapy (PDT) for targeting tumor-fibroblast interactions in pancreatic tumors.

  14. Targeting of metastasis-promoting tumor-associated fibroblasts and modulation of pancreatic tumor-associated stroma with a carboxymethylcellulose-docetaxel nanoparticle.

    PubMed

    Ernsting, Mark J; Hoang, Bryan; Lohse, Ines; Undzys, Elijus; Cao, Pinjiang; Do, Trevor; Gill, Bethany; Pintilie, Melania; Hedley, David; Li, Shyh-Dar

    2015-05-28

    Pancreatic ductal adenocarcinomas are characterized by the desmoplastic reaction, a dense fibrous stroma that has been shown to be supportive of tumor cell growth, invasion, and metastasis, and has been associated with resistance to chemotherapy and reduced patient survival. Here, we investigated targeted depletion of stroma for pancreatic cancer therapy via taxane nanoparticles. Cellax-DTX polymer is a conjugate of docetaxel (DTX), polyethylene glycol (PEG), and acetylated carboxymethylcellulose, a construct which condenses into well-defined 120nm particles in an aqueous solution, and is suitable for intravenous injection. We examined Cellax-DTX treatment effects in highly stromal primary patient-derived pancreatic cancer xenografts and in a metastatic PAN02 mouse model of pancreatic cancer, focusing on specific cellular interactions in the stroma, pancreatic tumor growth and metastasis. Greater than 90% of Cellax-DTX particles accumulate in smooth muscle actin (SMA) positive cancer-associated fibroblasts which results in long-term depletion of this stromal cell population, an effect not observed with Nab-paclitaxel (Nab-PTX). The reduction in stromal density leads to a >10-fold increase in tumor perfusion, reduced tumor weight and a reduction in metastasis. Consentingly, Cellax-DTX treatment increased survival when compared to treatment with gemcitabine or Nab-PTX in a metastatic PAN02 mouse model. Cellax-DTX nanoparticles interact with the tumor-associated stroma, selectively interacting with and depleting SMA positive cells and macrophage, effects of which are associated with significant changes in tumor progression and metastasis.

  15. Microstructural models for diffusion MRI in breast cancer and surrounding stroma: an ex vivo study

    PubMed Central

    Siow, Bernard; Panagiotaki, Eleftheria; Hipwell, John H.; Mertzanidou, Thomy; Owen, Julie; Gazinska, Patrycja; Pinder, Sarah E.; Alexander, Daniel C.; Hawkes, David J.

    2016-01-01

    The diffusion signal in breast tissue has primarily been modelled using apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) and diffusion tensor (DT) models, which may be too simplistic to describe the underlying tissue microstructure. Formalin‐fixed breast cancer samples were scanned using a wide range of gradient strengths, durations, separations and orientations. A variety of one‐ and two‐compartment models were tested to determine which best described the data. Models with restricted diffusion components and anisotropy were selected in most cancerous regions and there were no regions in which conventional ADC or DT models were selected. Maps of ADC generally related to cellularity on histology, but maps of parameters from more complex models suggest that both overall cell volume fraction and individual cell size can contribute to the diffusion signal, affecting the specificity of ADC to the tissue microstructure. The areas of coherence in diffusion anisotropy images were small, approximately 1 mm, but the orientation corresponded to stromal orientation patterns on histology. PMID:28000292

  16. Apparent-Strain Correction for Combined Thermal and Mechanical Testing

    NASA Technical Reports Server (NTRS)

    Johnson, Theodore F.; O'Neil, Teresa L.

    2007-01-01

    Combined thermal and mechanical testing requires that the total strain be corrected for the coefficient of thermal expansion mismatch between the strain gage and the specimen or apparent strain when the temperature varies while a mechanical load is being applied. Collecting data for an apparent strain test becomes problematic as the specimen size increases. If the test specimen cannot be placed in a variable temperature test chamber to generate apparent strain data with no mechanical loads, coupons can be used to generate the required data. The coupons, however, must have the same strain gage type, coefficient of thermal expansion, and constraints as the specimen to be useful. Obtaining apparent-strain data at temperatures lower than -320 F is challenging due to the difficulty to maintain steady-state and uniform temperatures on a given specimen. Equations to correct for apparent strain in a real-time fashion and data from apparent-strain tests for composite and metallic specimens over a temperature range from -450 F to +250 F are presented in this paper. Three approaches to extrapolate apparent-strain data from -320 F to -430 F are presented and compared to the measured apparent-strain data. The first two approaches use a subset of the apparent-strain curves between -320 F and 100 F to extrapolate to -430 F, while the third approach extrapolates the apparent-strain curve over the temperature range of -320 F to +250 F to -430 F. The first two approaches are superior to the third approach but the use of either of the first two approaches is contingent upon the degree of non-linearity of the apparent-strain curve.

  17. Use of indocyanine green in deep lamellar endothelial keratoplasty.

    PubMed

    John, Thomas

    2003-03-01

    A new technique using indocyanine green (ICG) during deep lamellar endothelial keratoplasty (DLEK) to stain the corneal stroma of the donor disk facilitated surgical placement of the disk in the host corneal opening created to match the donor disk. Two female patients, aged 82 and 77 years, had ICG staining of the donor corneal disk during DLEK for pseudophakic bullous keratopathy and Fuchs' corneal dystrophy. By 24 hours postoperatively, no ICG was detected clinically by biomicroscopy of the sutureless (no corneal sutures) lamellar transplanted corneas. This is the first report of the use of ICG during DLEK and the first intrastromal use of ICG in the human cornea. The use of ICG facilitated the DLEK procedure and appears to be safe for intraoperative use in the cornea.

  18. Transcriptional evidence for the "Reverse Warburg Effect" in human breast cancer tumor stroma and metastasis: similarities with oxidative stress, inflammation, Alzheimer's disease, and "Neuron-Glia Metabolic Coupling".

    PubMed

    Pavlides, Stephanos; Tsirigos, Aristotelis; Vera, Iset; Flomenberg, Neal; Frank, Philippe G; Casimiro, Mathew C; Wang, Chenguang; Pestell, Richard G; Martinez-Outschoorn, Ubaldo E; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

    2010-04-01

    Caveolin-1 (-/-) null stromal cells are a novel genetic model for cancer-associated fibroblasts and myofibroblasts. Here, we used an unbiased informatics analysis of transcriptional gene profiling to show that Cav-1 (-/-) bone-marrow derived stromal cells bear a striking resemblance to the activated tumor stroma of human breast cancers. More specifically, the transcriptional profiles of Cav-1 (-/-) stromal cells were most closely related to the primary tumor stroma of breast cancer patients that had undergone lymph-node (LN) metastasis. This is consistent with previous morphological data demonstrating that a loss of stromal Cav-1 protein (by immuno-histochemical staining in the fibroblast compartment) is significantly associated with increased LN-metastasis. We also provide evidence that the tumor stroma of human breast cancers shows a transcriptional shift towards oxidative stress, DNA damage/repair, inflammation, hypoxia, and aerobic glycolysis, consistent with the "Reverse Warburg Effect". Finally, the tumor stroma of "metastasis-prone" breast cancer patients was most closely related to the transcriptional profiles derived from the brains of patients with Alzheimer's disease. This suggests that certain fundamental biological processes are common to both an activated tumor stroma and neuro-degenerative stress. These processes may include oxidative stress, NO over-production (peroxynitrite formation), inflammation, hypoxia, and mitochondrial dysfunction, which are thought to occur in Alzheimer?s disease pathology. Thus, a loss of Cav-1 expression in cancer-associated myofibroblasts may be a protein biomarker for oxidative stress, aerobic glycolysis, and inflammation, driving the "Reverse Warburg Effect" in the tumor micro-environment and cancer cell metastasis.

  19. TβRIII Expression in Human Breast Cancer Stroma and the Role of Soluble TβRIII in Breast Cancer Associated Fibroblasts

    PubMed Central

    Jovanović, Bojana; Pickup, Michael W.; Chytil, Anna; Gorska, Agnieszka E.; Johnson, Kimberly C.; Moses, Harold L.; Owens, Philip

    2016-01-01

    The TGF-β pathway plays a major role in tumor progression through regulation of epithelial and stromal cell signaling. Dysfunction of the pathway can lead to carcinoma progression and metastasis. To gain insight into the stromal role of the TGF-β pathway in breast cancer, we performed laser capture microdissection (LCM) from breast cancer patients and reduction mammoplasty patients. Microdissected tumor stroma and normal breast stroma were examined for gene expression. Expression of the TGF-β type III receptor (TGFBR3) was greatly decreased in the tumor stroma compared to control healthy breast tissue. These results demonstrated a 44-fold decrease in TGFBR3 mRNA in tumor stroma in comparison to control tissue. We investigated publicly available databases, and have identified that TGFBR3 mRNA levels are decreased in tumor stroma. We next investigated fibroblast cell lines derived from cancerous and normal breast tissue and found that in addition to mRNA levels, TβRIII protein levels were significantly reduced. Having previously identified that cancer-associated fibroblasts secrete greater levels of tumor promoting cytokines, we investigated the consequences of soluble-TβRIII (sTβRIII) on fibroblasts. Fibroblast conditioned medium was analyzed for 102 human secreted cytokines and distinct changes in response to sTβRIII were observed. Next, we used the fibroblast-conditioned medium to stimulate human monocyte cell line THP-1. These results indicate a distinct transcriptional response depending on sTβRIII treatment and whether it was derived from normal or cancerous breast tissue. We conclude that the effect of TβRIII has distinct roles not only in cancer-associated fibroblasts but that sTβRIII has distinct paracrine functions in the tumor microenvironment. PMID:27827906

  20. Apparent mass and cross-axis apparent mass of standing subjects during exposure to vertical whole-body vibration

    NASA Astrophysics Data System (ADS)

    Subashi, G. H. M. J.; Matsumoto, Y.; Griffin, M. J.

    2006-05-01

    The effects of posture and vibration magnitude on the vertical apparent mass and the fore-and-aft cross-axis apparent mass of the standing human body during exposure to vertical vibration have been investigated. Twelve male subjects were exposed to random vertical vibration over the frequency range 2.0-20 Hz at three vibration magnitudes: 0.125, 0.25 and 0.5 m s -2 rms. Subjects stood in five different postures: upright, lordotic, anterior lean, knees bent and knees more bent. The vertical acceleration at the floor and the forces in the vertical and fore-and-aft directions at the floor were used to obtain the apparent mass and the cross-axis apparent mass. The resonance frequency of the apparent mass was significantly reduced with knees bent and knees more bent postures, but there were only minor effects on the resonance frequency by changing the position of the upper body. Considerable cross-axis apparent mass, up to about 30% of the static mass of subjects, was found. The cross-axis apparent mass was influenced by all postural changes used in the study. In all postures the resonance frequencies of the apparent mass and the cross-axis apparent mass tended to decrease with increasing vibration magnitude. This nonlinear characteristic tended to be less clear in some postures in which subjects increased muscle tension.

  1. Patterns in life history traits of deep-water chondrichthyans

    NASA Astrophysics Data System (ADS)

    Rigby, Cassandra; Simpfendorfer, Colin A.

    2015-05-01

    Life history traits are important indicators of the productivity of species, and their ability to tolerate fishing pressure. Using a variety of life history traits (maximum size, size and age at maturity, longevity, growth rate, litter and birth size) we demonstrated differences in chondrichthyan life histories between shelf, pelagic and deep-water habitats and within the deep habitat down the continental slope and across geographic regions. Deep-water species had lower growth rates, later age at maturity, and higher longevity than both shelf and pelagic species. In the deep habitat, with increasing depth, species matured later, lived longer, had smaller litters and bred less frequently; regional differences in traits were also apparent. Deep-water species also had a smaller body size and the invariants of relative size and age at maturity were higher in deep water. The visual interaction hypothesis offers a potential explanation for these findings and it is apparent habitat influences the trade-offs in allocation of energy for survival and reproduction. Body size is not appropriate as a predictor of vulnerability in deep-water chondrichthyans and regional trait differences are possibly due to a fishing pressure response. Deep-water chondrichthyans are more vulnerable to exploitation than shelf and pelagic species and this vulnerability markedly increases with increasing depth. The life history traits of deep-water chondrichthyans are unique and reflect adaptations driven by both mortality and resource limitations of their habitat.

  2. Climate control of decadal-scale increases in apparent ages of eogenetic karst spring water

    NASA Astrophysics Data System (ADS)

    Martin, Jonathan B.; Kurz, Marie J.; Khadka, Mitra B.

    2016-09-01

    Water quantity and quality in karst aquifers may depend on decadal-scale variations in recharge or withdrawal, which we hypothesize could be assessed through time-series measurements of apparent ages of spring water. We tested this hypothesis with analyses of various age tracers (3H/3He, SF6, CFC-11, CFC-12, CFC-113) and selected solute concentrations [dissolved oxygen (DO), NO3, Mg, and SO4] from 6 springs in a single spring complex (Ichetucknee springs) in northern Florida over a 16-yr period. These springs fall into two groups that reflect shallow short (Group 1) and deep long (Group 2) flow paths. Some tracer concentrations are altered, with CFC-12 and CFC-113 concentrations yielding the most robust apparent ages. These tracers show a 10-20-yr monotonic increase in apparent age from 1997 to 2013, including the flood recession that followed Tropical Storm Debby in mid-2012. This increase in age indicates most water discharged during the study period recharged the aquifer within a few years of 1973 for Group 2 springs and 1980 for Group 1 springs. Inverse correlations between apparent age and DO and NO3 concentrations reflect reduced redox state in older water. Positive correlations between apparent age and Mg and SO4 concentrations reflect increased water-rock reactions. Concentrated recharge in the decade around 1975 resulted from nearly 2 m of rain in excess of the monthly average that fell between 1960 and 2014, followed by a nearly 4 m deficit to 2014. This excess rain coincided with two major El Niño events during the maximum cool phase in the Atlantic Multidecadal Oscillation. Although regional water withdrawal increased nearly 5-fold between 1980 and 2005, withdrawals represent only 2-5% of Ichetucknee River flow and are less important than decadal-long variations in precipitation. These results suggest that groundwater management should consider climate cycles as predictive tools for future water resources.

  3. Masking and color inheritance along the apparent motion path.

    PubMed

    Souto, David; Johnston, Alan

    2012-07-30

    Long-range apparent motion is the illusory motion that can be perceived when two static and distant stimuli are presented in succession. Within some spatiotemporal range not only is motion sensed, but it appears as if one stimulus is displaced from one place to another (termed beta or optimal motion). Several groups have found that this illusory percept can interact with perception of a physically present stimulus, but some disagree on the origin of these interactions. We know little about how suppressive effects depend on feature-similarity between a target and the stimuli in apparent motion (inducers)-which would indicate an early perceptual locus-or even about the minimal conditions under which to obtain this effect. Unlike early studies that used a two-stroke apparent motion paradigm, we were able to demonstrate that motion can mask stimuli presented at interpolated locations along the apparent motion path, as shown by the elevation of contrast thresholds compared to a control condition. Apparent motion masking depended on color similarity between target and inducers. Further, we found evidence that the color of inducers alters the apparent color of intervening gray probes, indicating some inheritance or chromatic averaging across distant locations, but no clear evidence of predictive updating. Finally, the analysis of the presentation times delivering maximal masking effects suggests a predictive interpolation process is responsible for interference by apparent motion filling-in. We discuss alternative mechanisms, in particular the possible role of apparent-motion-induced metacontrast masking in generating this pattern of results.

  4. Multiple Weather Factors Affect Apparent Survival of European Passerine Birds

    PubMed Central

    Salewski, Volker; Hochachka, Wesley M.; Fiedler, Wolfgang

    2013-01-01

    Weather affects the demography of animals and thus climate change will cause local changes in demographic rates. In birds numerous studies have correlated demographic factors with weather but few of those examined variation in the impacts of weather in different seasons and, in the case of migrants, in different regions. Using capture-recapture models we correlated weather with apparent survival of seven passerine bird species with different migration strategies to assess the importance of selected facets of weather throughout the year on apparent survival. Contrary to our expectations weather experienced during the breeding season did not affect apparent survival of the target species. However, measures for winter severity were associated with apparent survival of a resident species, two short-distance/partial migrants and a long-distance migrant. Apparent survival of two short distance migrants as well as two long-distance migrants was further correlated with conditions experienced during the non-breeding season in Spain. Conditions in Africa had statistically significant but relatively minor effects on the apparent survival of the two long-distance migrants but also of a presumably short-distance migrant and a short-distance/partial migrant. In general several weather effects independently explained similar amounts of variation in apparent survival for the majority of species and single factors explained only relatively low amounts of temporal variation of apparent survival. Although the directions of the effects on apparent survival mostly met our expectations and there are clear predictions for effects of future climate we caution against simple extrapolations of present conditions to predict future population dynamics. Not only did weather explains limited amounts of variation in apparent survival, but future demographics will likely be affected by changing interspecific interactions, opposing effects of weather in different seasons, and the potential for

  5. Multiple weather factors affect apparent survival of European passerine birds.

    PubMed

    Salewski, Volker; Hochachka, Wesley M; Fiedler, Wolfgang

    2013-01-01

    Weather affects the demography of animals and thus climate change will cause local changes in demographic rates. In birds numerous studies have correlated demographic factors with weather but few of those examined variation in the impacts of weather in different seasons and, in the case of migrants, in different regions. Using capture-recapture models we correlated weather with apparent survival of seven passerine bird species with different migration strategies to assess the importance of selected facets of weather throughout the year on apparent survival. Contrary to our expectations weather experienced during the breeding season did not affect apparent survival of the target species. However, measures for winter severity were associated with apparent survival of a resident species, two short-distance/partial migrants and a long-distance migrant. Apparent survival of two short distance migrants as well as two long-distance migrants was further correlated with conditions experienced during the non-breeding season in Spain. Conditions in Africa had statistically significant but relatively minor effects on the apparent survival of the two long-distance migrants but also of a presumably short-distance migrant and a short-distance/partial migrant. In general several weather effects independently explained similar amounts of variation in apparent survival for the majority of species and single factors explained only relatively low amounts of temporal variation of apparent survival. Although the directions of the effects on apparent survival mostly met our expectations and there are clear predictions for effects of future climate we caution against simple extrapolations of present conditions to predict future population dynamics. Not only did weather explains limited amounts of variation in apparent survival, but future demographics will likely be affected by changing interspecific interactions, opposing effects of weather in different seasons, and the potential for

  6. The apparent groundwater age rejuvenation caused by the human activity in Jakarta area, Indonesia

    NASA Astrophysics Data System (ADS)

    Kagabu, M.; Shimada, J.; Nakamura, T.; Delinom, R.; Taniguchi, M.

    2010-12-01

    The rapid urbanization in Jakarta area has become a serious subsurface environmental issues such as groundwater level decline and land subsidence due to excessive groundwater pumping. These problems began to emerge recently by some hydrological studies. The comparison of 14C activity between 1985 and 2008 shows the apparent groundwater age rejuvenation in the deep aquifer under the DKI Jakarta. We discussed by using a numerical groundwater flow model to evaluate the process of this rejuvenation in the urbanized area. Since the groundwater pumping was not performed intensely, the groundwater discharge flow toward the sea coast was dominant until 1983, however, this outward flux switched to intrusion flux into deeper aquifer after mid-1980s because of over-pumping in the urban area. The most largest flux among six flux directions toward the deep aquifer under the DKI Jakarta became “vertical downward flux” which means the shallower groundwater intrude into the deep one due to the excessive groundwater pumping from mid-1980s and this flux grows about 50% in 2000s. This result is consistent with the detection of chlorofluorocarbon (CFC)-12, which works as an indicator of young groundwater even in the deep groundwater. As the rejuvenation ratio “R” was determined by using 14C activity in the groundwater, R increase with the CFC-12 concentration and boths have good correlation. Besides, we estimated the “vertical downward flux” at each well's screen depth by the model estimation. The result shows that this flux has larger in the urban groundwater depression area and especially at shallower part of the deep aquifer, and it affects the magnitude of the shallow groundwater intrusion. Relationship between R and CFC-12 concentration. The diameter of cube shows the magnitude of the “vertical downward flux”

  7. Does Apparent Stress Vary With Earthquake Size? Possible Mechanism of Artificial Size Dependency

    NASA Astrophysics Data System (ADS)

    Ide, S.; Beroza, G. C.; Prejean, S. G.; Ellsworth, W. L.

    2001-12-01

    The energy radiated from the seismic source (Es) has been estimated for a wide range of earthquake sizes. Many studies have found that the ratio between Es and seismic moment (apparent stress) increases as seismic moment increases. Es is distributed across a wide frequency band, reliable estimates require broadband recordings relative to the corner frequency. There are several possible mechanisms that could bias estimates of Es: 1) data bandwidth is too narrow, 2) a constant upper cutoff on the corner frequency affects event selection, and 3) unmodeled elastic/anelastic wave propagation effects may obscure source properties. We can attempt to account for 1) by estimating the missing energy based on the assumption of an omega-square spectral model. For 2) we know the minimum energy of missing events and can show where these events should be located in the moment-apparent stress relation. These two factors act to diminish the size dependency of apparent stress suggested by previous studies. For 3), we re-examined the data of Prejean and Ellsworth (2001) from a 2-km deep borehole in Long Valley Caldera, California. First, assuming an omega-square model with a constant Q, we determined the stress drop and apparent stress of 41 events (0.5 < Mw < 5.0). We find that some small events have small apparent stresses of about 0.003-0.03 MPa, and also find that these events have low stress drops of 0.01 to 0.1 MPa. Most larger events have both larger stress drops of 1-10 MPa and larger apparent stresses. This analysis supports the decline of Es with declining moment. It is natural that stress drop would have a strong relationship to the apparent stress---we find (apparent stress) = 0.3 x (stress drop)---since we assumed an omega-square model. Insofar as no systematic change in the spectral shape is observed with seismic moment in the data, it is unlikely that stress drop and apparent stress will have different dependencies on seismic moment. We also estimated stress drops

  8. Deep vein thrombosis - discharge

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000027.htm Deep vein thrombosis - discharge To use the sharing features ... page, please enable JavaScript. You were treated for deep vein thrombosis ( DVT ). This is a condition in ...

  9. Taoism and Deep Ecology.

    ERIC Educational Resources Information Center

    Sylvan, Richard; Bennett, David

    1988-01-01

    Contrasted are the philosophies of Deep Ecology and ancient Chinese. Discusses the cosmology, morality, lifestyle, views of power, politics, and environmental philosophies of each. Concludes that Deep Ecology could gain much from Taoism. (CW)

  10. Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

    SciTech Connect

    Greene, Carol Ann Chang, Chuan-Yuan; Fraser, Cameron J.; Nelidova, Dasha E.; Chen, Jing A.; Lim, Angela; Brebner, Alex; McGhee, Jennifer; Sherwin, Trevor; Green, Colin R.

    2014-03-10

    Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.

  11. Gluteal and abdominal subcutaneous adipose tissue depots as stroma cell source: gluteal cells display increased adipogenic and osteogenic differentiation potentials.

    PubMed

    Iwen, Karl Alexander; Priewe, Anna-Christin; Winnefeld, Marc; Rose, Christian; Siemers, Frank; Rohwedel, Jürgen; Cakiroglu, Figen; Lehnert, Hendrik; Schepky, Andreas; Klein, Johannes; Kramer, Jan

    2014-06-01

    Human adipose-derived stroma cells (ADSCs) have successfully been employed in explorative therapeutic studies. Current evidence suggests that ADSCs are unevenly distributed in subcutaneous adipose tissue; therefore, the anatomical origin of ADSCs may influence clinical outcomes. This study was designed to investigate proliferation and differentiation capacities of ADSCs from the gluteal and abdominal depot of 8 females. All had normal BMI (22.01 ± 0.39 kg/m(2) ) and waist circumference (81.13 ± 2.33 cm). Examination by physicians and analysis of 31 laboratory parameters did not reveal possibly confounding medical disorders. Gluteal and abdominal adipose tissue was sampled by en bloc resection on day 7 (±1) after the last menses. Histological examination did not reveal significant depot-specific differences. As assessed by BrdU assay, proliferation of cells from both depots was similar after 24 h and analysis of 15 cell surface markers by flow cytometry identified the isolated cells as ADSCs, again without depot-specific differences. ADSCs from both depots differentiated poorly to chondroblasts. Gluteal ADSCs displayed significantly higher adipogenic differentiation potential than abdominal cells. Osteogenic differentiation was most pronounced in gluteal cells, whereas differentiation of abdominal ADSCs was severely impaired. Our data demonstrate a depot-specific difference in ADSC differentiation potential with abdominal cells failing to meet the criteria of multipotent ADSCs. This finding should be taken into account in future explorations of ADSC-derived therapeutic strategies.

  12. Abnormalities of Thymic Stroma may Contribute to Immune Dysregulation in Murine Models of Leaky Severe Combined Immunodeficiency

    PubMed Central

    Rucci, Francesca; Poliani, Pietro Luigi; Caraffi, Stefano; Paganini, Tiziana; Fontana, Elena; Giliani, Silvia; Alt, Frederick W.; Notarangelo, Luigi Daniele

    2011-01-01

    Lymphostromal cross-talk in the thymus is essential to allow generation of a diversified repertoire of T lymphocytes and to prevent autoimmunity by self-reactive T cells. Hypomorphic mutations in genes that control T cell development have been associated with immunodeficiency and immune dysregulation both in humans and in mice. We have studied T cell development and thymic stroma architecture and maturation in two mouse models of leaky severe combined immune deficiency, carrying hypomorphic mutations in rag1 and lig4 genes. Defective T cell development was associated with abnormalities of thymic architecture that predominantly affect the thymic medulla, with reduction of the pool of mature medullary thymic epithelial cells (mTECs). While the ability of mTECs to express autoimmune regulator (Aire) is preserved in mutant mice, the frequency of mature mTECs expressing Aire and tissue-specific antigens is severely reduced. Similarly, the ability of CD4+ T cells to differentiate into Foxp3+ natural regulatory T cells is preserved in rag1 and lig4 mutant mice, but their number is greatly reduced. These data indicate that hypomorphic defects in T cell development may cause defective lymphostromal cross-talk and impinge on thymic stromal cells maturation, and thus favor immune dysregulation. PMID:21822418

  13. Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma.

    PubMed

    Chmielewski, Markus; Hombach, Andreas A; Abken, Hinrich

    2014-01-01

    Adoptive T-cell therapy recently achieved impressive efficacy in early phase trials, in particular in hematologic malignancies, strongly supporting the notion that the immune system can control cancer. A current strategy of favor is based on ex vivo-engineered patient T cells, which are redirected by a chimeric antigen receptor (CAR) and recognize a predefined target by an antibody-derived binding domain. Such CAR T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. However, given the tremendous phenotypic diversity in solid tumor lesions, a reasonable number of cancer cells are not recognized by a given CAR, considerably reducing the therapeutic success. This article reviews a recently described strategy for overcoming this shortcoming of the CAR T-cell therapy by modulating the tumor stroma by a CAR T-cell-secreted transgenic cytokine like interleukin-12 (IL-12). The basic process is that CAR T cells, when activated by their CAR, deposit IL-12 in the targeted tumor lesion, which in turn attracts an innate immune cell response toward those cancer cells that are invisible to CAR T cells. Such TRUCKs, T cells redirected for universal cytokine-mediated killing, exhibited remarkable efficacy against solid tumors with diverse cancer cell phenotypes, suggesting their evaluation in clinical trials.

  14. Tumor Stroma Engraftment of Gene-Modified Mesenchymal Stem Cells as Anti-Tumor Therapy against Ovarian Cancer

    PubMed Central

    Dembinski, Jennifer L.; Wilson, Shanna M.; Spaeth, Erika L.; Studeny, Matus; Zompetta, Claudia; Samudio, Ismael; Roby, Katherine; Andreeff, Michael; Marini, Frank C.

    2013-01-01

    Many ovarian cancers originate from ovarian surface epithelium, where they develop from cysts intermixed with stroma. The stromal layer is critical to the progression and survival of the neoplasm and consequently is recruited into the tumor microenvironment. Using both syngenic mouse tumors (ID8-R), and human xenograft (OVCAR3, SKOV3) tumor models, we first confirmed intraperitoneally-circulating MSC could target, preferentially engraft and differentiate into α-SMA+ myofibroblasts, suggesting their role as “reactive stroma” in ovarian carcinoma development and confirming their potential as a targeted delivery vehicle for the intratumoral production of interferon-beta (IFNβ). Then, mice with ovarian carcinomas received weekly IP injections of IFNβ expressing MSC, resulting in complete eradication of tumors in 70% of treated OVCAR3 mice (P = 0.004) and an increased survival of treated SKOV3 mice compared with controls (P = 0.01). Similar tumor growth control was observed using murine IFNβ delivered by murine MSC in ID8-R ovarian carcinoma. As a potential mechanism of tumor killing, MSC produced IFNβ induced caspase-dependent tumor cell apoptosis. Our results demonstrate that ovarian carcinoma engraft MSC to participate in myofibrovascular networks and that IFNβ produced by MSC intratumorally modulates tumor kinetics, resulting in prolonged survival. PMID:23260083

  15. Comparison of in vitro-cultivation of human mesenchymal stroma/stem cells derived from bone marrow and umbilical cord.

    PubMed

    Hoffmann, Andrea; Floerkemeier, Thilo; Melzer, Catharina; Hass, Ralf

    2016-04-28

    Cell-mediated therapy is currently considered as a novel approach for many human diseases. Potential uses range from topic applications with the regeneration of confined tissue areas to systemic applications. Stem cells including mesenchymal stroma/stem cells (MSCs) represent a highly attractive option. Their potential to cure or alleviate human diseases is investigated in a number of clinical trials. A wide variety of methods has been established in the past years for isolation, cultivation and characterization of human MSCs as expansion is presently deemed a prerequisite for clinical application with high numbers of cells carrying reproducible properties. MSCs have been retrieved from various tissues and used in a multitude of settings whereby numerous experimental protocols are available for expansion of MSCs in vitro. Accordingly, different isolation, culture and upscaling techniques contribute to the heterogeneity of MSC characteristics and the, sometimes, controversial results. Therefore, this review discusses and summarizes certain experimental conditions for MSC in vitro culture focusing on adult bone marrow-derived and neonatal umbilical cord-derived MSCs in order to enhance our understanding for MSC tissue sources and to stratify different procedures. Copyright © 2016 John Wiley & Sons, Ltd.

  16. A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR.

    PubMed

    Lau, T-S; Chan, L K-Y; Wong, E C-H; Hui, C W-C; Sneddon, K; Cheung, T-H; Yim, S-F; Lee, J H-S; Yeung, C S-Y; Chung, T K-H; Kwong, J

    2017-02-06

    Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-α) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-α induces TGF-α transcription in stromal fibroblasts through nuclear factor-κB (NF-κB). We further show that TGF-α secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNFα-TGFα-EGFR interacting loop between tumor and stromal compartments of human omental metastases. Our results therefore demonstrate cancer epigenetics induces a loop of cancer-stroma-cancer interaction in omental microenvironment that promotes peritoneal metastasis of ovarian cancer cells via TNFα-TGFα-EGFR.Oncogene advance online publication, 6 February 2017; doi:10.1038/onc.2016.509.

  17. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer

    NASA Astrophysics Data System (ADS)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M.; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui; Yang, Lily

    2016-05-01

    Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer.

  18. Concentrative uptake of cyclic ADP-ribose generated by BST-1+ stroma stimulates proliferation of human hematopoietic progenitors.

    PubMed

    Podestà, Marina; Benvenuto, Federica; Pitto, Anna; Figari, Osvaldo; Bacigalupo, Andrea; Bruzzone, Santina; Guida, Lucrezia; Franco, Luisa; Paleari, Laura; Bodrato, Nicoletta; Usai, Cesare; De Flora, Antonio; Zocchi, Elena

    2005-02-18

    Cyclic ADP-ribose (cADPR) is an intracellular calcium mobilizer generated from NAD(+) by the ADP-ribosyl cyclases CD38 and BST-1. cADPR, both exogenously added and paracrinally produced by a CD38(+) feeder layer, has recently been demonstrated to stimulate the in vitro proliferation of human hemopoietic progenitors (HP) and also the in vivo expansion of hemopoietic stem cells. The low density of BST-1 expression on bone marrow (BM) stromal cells and the low specific activity of the enzyme made it unclear whether cADPR generation by a BST-1(+) stroma could stimulate HP proliferation in the BM microenvironment. We developed and characterized two BST-1(+) stromal cell lines, expressing an ectocellular cyclase activity similar to that of BST-1(+) human mesenchymal stem cells, the precursors of BM stromal cells. Long term co-culture of cord blood-derived HP over these BST-1(+) feeders determined their expansion. Influx of paracrinally generated cADPR into clonogenic HP was mediated by a concentrative, nitrobenzylthioinosine- and dipyridamole-inhibitable nucleoside transporter, this providing a possible explanation to the effectiveness of the hormone-like concentrations of the cyclic nucleotide measured in the medium conditioned by BST-1(+) feeders. These results suggest that the BST-1-catalyzed generation of extracellular cADPR, followed by the concentrative uptake of the cyclic nucleotide by HP, may be physiologically relevant in normal hemopoiesis.

  19. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer

    PubMed Central

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M.; Zhou, Zhiyang; Wang, Liya; Wang, Andrew; Mao, Hui

    2016-01-01

    Low drug delivery efficiency and drug resistance from highly heterogeneous cancer cells and tumor microenvironment represent major challenges in clinical oncology. Growth factor receptor, IGF-1R, is overexpressed in both human tumor cells and tumor associated stromal cells. The level of IGF-1R expression is further up-regulated in drug resistant tumor cells. We have developed IGF-1R targeted magnetic iron oxide nanoparticles (IONPs) carrying multiple anticancer drugs into human tumors. This IGF-1R targeted theranostic nanoparticle delivery system has an iron core for non-invasive MR imaging, amphiphilic polymer coating to ensure the biocompatibility as well as for drug loading and conjugation of recombinant human IGF-1 as targeting molecules. Chemotherapy drugs, Doxorubicin (Dox), was encapsulated into the polymer coating and/or conjugated to the IONP surface by coupling with the carboxyl groups. The ability of IGF1R targeted theranostic nanoparticles to penetrate tumor stromal barrier and enhance tumor cell killing has been demonstrated in human pancreatic cancer patient tissue derived xenograft (PDX) models. Repeated systemic administrations of those IGF-1R targeted theranostic IONP carrying Dox led to breaking the tumor stromal barrier and improved therapeutic effect. Near infrared (NIR) optical and MR imaging enabled noninvasive monitoring of nanoparticle-drug delivery and therapeutic responses. Our results demonstrated that IGF-1R targeted nanoparticles carrying multiple drugs are promising combination therapy approaches for image-guided therapy of stroma-rich and drug resistant human cancer, such as pancreatic cancer. PMID:27313332

  20. Proteome Analysis During Chondrocyte Differentiation in a New Chondrogenesis Model Using Human Umbilical Cord Stroma Mesenchymal Stem Cells*

    PubMed Central

    De la Fuente, Alexandre; Mateos, Jesús; Lesende-Rodríguez, Iván; Calamia, Valentina; Fuentes-Boquete, Isaac; de Toro, Francisco J.; Arufe, Maria C.; Blanco, Francisco J.

    2012-01-01

    Umbilical cord stroma mesenchymal stem cells were differentiated toward chondrocyte-like cells using a new in vitro model that consists of the random formation of spheroids in a medium supplemented with fetal bovine serum on a nonadherent surface. The medium was changed after 2 days to one specific for the induction of chondrocyte differentiation. We assessed this model using reverse transcriptase-polymerase chain reaction, flow cytometry, immunohistochemistry, and secretome analyses. The purpose of this study was to determine which proteins were differentially expressed during chondrogenesis. Differential gel electrophoresis analysis was performed, followed by matrix-assisted laser desorption/ionization mass spectrometry protein identification. A total of 97 spots were modulated during the chondrogenesis process, 54 of these spots were identified as 39 different proteins and 15 were isoforms. Of the 39 different proteins identified 15 were down-regulated, 21 were up-regulated, and 3 were up- and down-regulated during the chondrogenesis process. Using Pathway Studio 7.0 software, our results showed that the major cell functions modulated during chondrogenesis were cellular differentiation, proliferation, and migration. Five proteins involved in cartilage extracellular matrix metabolism found during the differential gel electrophoresis study were confirmed using Western blot. The results indicate that our in vitro chondrogenesis model is an efficient and rapid technique for obtaining cells similar to chondrocytes that express proteins characteristic of the cartilage extracellular matrix. These chondrocyte-like cells could prove useful for future cell therapy treatment of cartilage pathologies. PMID:22008206

  1. Proteome analysis during chondrocyte differentiation in a new chondrogenesis model using human umbilical cord stroma mesenchymal stem cells.

    PubMed

    De la Fuente, Alexandre; Mateos, Jesús; Lesende-Rodríguez, Iván; Calamia, Valentina; Fuentes-Boquete, Isaac; de Toro, Francisco J; Arufe, Maria C; Blanco, Francisco J

    2012-02-01

    Umbilical cord stroma mesenchymal stem cells were differentiated toward chondrocyte-like cells using a new in vitro model that consists of the random formation of spheroids in a medium supplemented with fetal bovine serum on a nonadherent surface. The medium was changed after 2 days to one specific for the induction of chondrocyte differentiation. We assessed this model using reverse transcriptase-polymerase chain reaction, flow cytometry, immunohistochemistry, and secretome analyses. The purpose of this study was to determine which proteins were differentially expressed during chondrogenesis. Differential gel electrophoresis analysis was performed, followed by matrix-assisted laser desorption/ionization mass spectrometry protein identification. A total of 97 spots were modulated during the chondrogenesis process, 54 of these spots were identified as 39 different proteins and 15 were isoforms. Of the 39 different proteins identified 15 were down-regulated, 21 were up-regulated, and 3 were up- and down-regulated during the chondrogenesis process. Using Pathway Studio 7.0 software, our results showed that the major cell functions modulated during chondrogenesis were cellular differentiation, proliferation, and migration. Five proteins involved in cartilage extracellular matrix metabolism found during the differential gel electrophoresis study were confirmed using Western blot. The results indicate that our in vitro chondrogenesis model is an efficient and rapid technique for obtaining cells similar to chondrocytes that express proteins characteristic of the cartilage extracellular matrix. These chondrocyte-like cells could prove useful for future cell therapy treatment of cartilage pathologies.

  2. Quantitation of Murine Stroma and Selective Purification of the Human Tumor Component of Patient-Derived Xenografts for Genomic Analysis.

    PubMed

    Schneeberger, Valentina E; Allaj, Viola; Gardner, Eric E; Poirier, J T; Rudin, Charles M

    2016-01-01

    Patient-derived xenograft (PDX) mouse models are increasingly used for preclinical therapeutic testing of human cancer. A limitation in molecular and genetic characterization of PDX tumors is the presence of integral murine stroma. This is particularly problematic for genomic sequencing of PDX models. Rapid and dependable approaches for quantitating stromal content and purifying the malignant human component of these tumors are needed. We used a recently developed technique exploiting species-specific polymerase chain reaction (PCR) amplicon length (ssPAL) differences to define the fractional composition of murine and human DNA, which was proportional to the fractional composition of cells in a series of lung cancer PDX lines. We compared four methods of human cancer cell isolation: fluorescence-activated cell sorting (FACS), an immunomagnetic mouse cell depletion (MCD) approach, and two distinct EpCAM-based immunomagnetic positive selection methods. We further analyzed DNA extracted from the resulting enriched human cancer cells by targeted sequencing using a clinically validated multi-gene panel. Stromal content varied widely among tumors of similar histology, but appeared stable over multiple serial tumor passages of an individual model. FACS and MCD were superior to either positive selection approach, especially in cases of high stromal content, and consistently allowed high quality human-specific genomic profiling. ssPAL is a dependable approach to quantitation of murine stromal content, and MCD is a simple, efficient, and high yield approach to human cancer cell isolation for genomic analysis of PDX tumors.

  3. Quantitation of Murine Stroma and Selective Purification of the Human Tumor Component of Patient-Derived Xenografts for Genomic Analysis

    PubMed Central

    Schneeberger, Valentina E.; Allaj, Viola; Gardner, Eric E.; Rudin, Charles M.

    2016-01-01

    Patient-derived xenograft (PDX) mouse models are increasingly used for preclinical therapeutic testing of human cancer. A limitation in molecular and genetic characterization of PDX tumors is the presence of integral murine stroma. This is particularly problematic for genomic sequencing of PDX models. Rapid and dependable approaches for quantitating stromal content and purifying the malignant human component of these tumors are needed. We used a recently developed technique exploiting species-specific polymerase chain reaction (PCR) amplicon length (ssPAL) differences to define the fractional composition of murine and human DNA, which was proportional to the fractional composition of cells in a series of lung cancer PDX lines. We compared four methods of human cancer cell isolation: fluorescence-activated cell sorting (FACS), an immunomagnetic mouse cell depletion (MCD) approach, and two distinct EpCAM-based immunomagnetic positive selection methods. We further analyzed DNA extracted from the resulting enriched human cancer cells by targeted sequencing using a clinically validated multi-gene panel. Stromal content varied widely among tumors of similar histology, but appeared stable over multiple serial tumor passages of an individual model. FACS and MCD were superior to either positive selection approach, especially in cases of high stromal content, and consistently allowed high quality human-specific genomic profiling. ssPAL is a dependable approach to quantitation of murine stromal content, and MCD is a simple, efficient, and high yield approach to human cancer cell isolation for genomic analysis of PDX tumors. PMID:27611664

  4. Role of Human Corneal Stroma-Derived Mesenchymal-Like Stem Cells in Corneal Immunity and Wound Healing

    PubMed Central

    Veréb, Zoltán; Póliska, Szilárd; Albert, Réka; Olstad, Ole Kristoffer; Boratkó, Anita; Csortos, Csilla; Moe, Morten C.; Facskó, Andrea; Petrovski, Goran

    2016-01-01

    Corneal tissue regeneration is of crucial importance for maintaining normal vision. We aimed to isolate and cultivate human corneal stroma-derived mesenchymal stem-like cells (CSMSCs) from the central part of cadaver corneas and study their phenotype, multipotency, role in immunity and wound healing. The isolated cells grew as monolayers in vitro, expressed mesenchymal- and stemness-related surface markers (CD73, CD90, CD105, CD140b), and were negative for hematopoietic markers as determined by flow cytometry. CSMSCs were able to differentiate in vitro into fat, bone and cartilage. Their gene expression profile was closer to bone marrow-derived MSCs (BMMSCs) than to limbal epithelial stem cells (LESC) as determined by high-throughput screening. The immunosuppressive properties of CSMSCs were confirmed by a mixed lymphocyte reaction (MLR), while they could inhibit proliferation of activated immune cells. Treatment of CSMSCs by pro-inflammatory cytokines and toll-like receptor ligands significantly increased the secreted interleukin-6 (IL-6), interleukin-8 (IL-8) and C-X-C motif chemokine 10 (CXCL-10) levels, as well as the cell surface adhesion molecules. CSMSCs were capable of closing a wound in vitro under different stimuli. These cells thus contribute to corneal tissue homeostasis and play an immunomodulatory and regenerative role with possible implications in future cell therapies for treating sight-threatening corneal diseases. PMID:27195722

  5. Stroma derived COL6A3 is a potential prognosis marker of colorectal carcinoma revealed by quantitative proteomics

    PubMed Central

    Chen, Sun-Xia; Wang, Xiao-Qing; Cui, Shu-Jian; Liu, Xiao-Hui; Jiang, Ying-Hua; Wang, Jie; Zhang, Yang; Yang, Peng-Yuan; Liu, Feng

    2015-01-01

    Colorectal cancer (CRC) represents the third most common cancer in males and second in females worldwide. Here, we performed a quantitative 8-plex iTRAQ proteomics analysis of the secreted proteins from five colonic fibroblast cultures and three colon cancer epithelial cell lines. We identified 1114 proteins at 0% FDR, including 587 potential secreted proteins. We further recognized 116 fibroblast-enriched proteins which were significantly associated with cell movement, angiogenesis, proliferation and wound healing, and 44 epithelial cell-enriched proteins. By interrogation of Oncomine database, we found that 20 and 8 fibroblast-enriched proteins were up- and downregulated in CRC, respectively. Western blots confirmed the fibroblast-specific secretion of filamin C, COL6A3, COL4A1 and spondin-2. Upregulated mRNA and stroma expression of COL6A3 in CRC, which were revealed by Oncomine analyses and tissue-microarray-immunohistochemistry, indicated poor prognosis. COL6A3 expression was significantly associated with Dukes stage, T stage, stage, recurrence and smoking status. Circulating plasma COL6A3 in CRC patients was upregulated significantly comparing with healthy peoples. Receiver operating characteristic curve analysis revealed that COL6A3 has better predictive performance for CRC with an area under the curve of 0.885 and the best sensitivity/specificity of 92.9%/81.3%. Thus we demonstrated that COL6A3 was a potential diagnosis and prognosis marker of CRC. PMID:26338966

  6. Apparent Biological Motion in First and Third Person Perspective

    PubMed Central

    Scandola, Michele; Orvalho, Veronica; Candidi, Matteo

    2016-01-01

    Apparent biological motion is the perception of plausible movements when two alternating images depicting the initial and final phase of an action are presented at specific stimulus onset asynchronies. Here, we show lower subjective apparent biological motion perception when actions are observed from a first relative to a third visual perspective. These findings are discussed within the context of sensorimotor contributions to body ownership. PMID:27708754

  7. Deep Space Telecommunications

    NASA Technical Reports Server (NTRS)

    Kuiper, T. B. H.; Resch, G. M.

    2000-01-01

    The increasing load on NASA's deep Space Network, the new capabilities for deep space missions inherent in a next-generation radio telescope, and the potential of new telescope technology for reducing construction and operation costs suggest a natural marriage between radio astronomy and deep space telecommunications in developing advanced radio telescope concepts.

  8. Deep Web video

    SciTech Connect

    None Available

    2009-06-01

    To make the web work better for science, OSTI has developed state-of-the-art technologies and services including a deep web search capability. The deep web includes content in searchable databases available to web users but not accessible by popular search engines, such as Google. This video provides an introduction to the deep web search engine.

  9. Deep Web video

    ScienceCinema

    None Available

    2016-07-12

    To make the web work better for science, OSTI has developed state-of-the-art technologies and services including a deep web search capability. The deep web includes content in searchable databases available to web users but not accessible by popular search engines, such as Google. This video provides an introduction to the deep web search engine.

  10. An Improved Comprehensive Model for the Apparent Viscosity of Blood

    NASA Astrophysics Data System (ADS)

    Jacobitz, Frank; Anderson, Spencer

    2008-11-01

    An improved comprehensive model for the apparent viscosity of blood is developed and used in simulations of the microcirculation in capillary bundles of rat spinotrapezius muscle fascia. In the microcirculation, the apparent viscosity of blood depends on the local vessel diameter, hematocrit, and shear rate. The proposed comprehensive model extends the apparent viscosity model developed by Pries, Secomb, Gaehtgens, and Gross (Circulation Research, 67, 826-834, 1990), which describes the effect of vessel diameter and hematocrit on the apparent viscosity. A shear thinning term is developed using the experimental data of Lipowsky, Usami, and Chien (Microvascular Research, 19, 297-319, 1980). Curve fits of this data can be combined with equations given in the Pries et al. work to create a system of equations that can be used to find the shear thinning factor. The simulations based on the improved apparent viscosity model use realistic vessel topology for the microvasculature, reconstructed from microscope images of tissue samples, and consider passive and active vessel properties. The numerical method is based on a Hagen-Poiseuille balance in the microvessels and a sparse matrix solver is used to obtain the solution. It was found that the inclusion of the shear factor decreases the overall flowrate in the capillary bundle. Many vessel connections in the fascia are characterized by relatively low shear rates and therefore increased apparent viscosity.

  11. Toward automatic segmentation and quantification of tumor and stroma in whole-slide images of H and E stained rectal carcinomas

    NASA Astrophysics Data System (ADS)

    Geessink, Oscar G. F.; Baidoshvili, Alexi; Freling, Gerard; Klaase, Joost M.; Slump, Cornelis H.; van der Heijden, Ferdinand

    2015-03-01

    Visual estimation of tumor and stroma proportions in microscopy images yields a strong, Tumor-(lymph)Node- Metastasis (TNM) classification-independent predictor for patient survival in colorectal cancer. Therefore, it is also a potent (contra)indicator for adjuvant chemotherapy. However, quantification of tumor and stroma through visual estimation is highly subject to intra- and inter-observer variability. The aim of this study is to develop and clinically validate a method for objective quantification of tumor and stroma in standard hematoxylin and eosin (H and E) stained microscopy slides of rectal carcinomas. A tissue segmentation algorithm, based on supervised machine learning and pixel classification, was developed, trained and validated using histological slides that were prepared from surgically excised rectal carcinomas in patients who had not received neoadjuvant chemotherapy and/or radiotherapy. Whole-slide scanning was performed at 20× magnification. A total of 40 images (4 million pixels each) were extracted from 20 whole-slide images at sites showing various relative proportions of tumor and stroma. Experienced pathologists provided detailed annotations for every extracted image. The performance of the algorithm was evaluated using cross-validation by testing on 1 image at a time while using the other 39 images for training. The total classification error of the algorithm was 9.4% (SD = 3.2%). Compared to visual estimation by pathologists, the algorithm was 7.3 times (P = 0.033) more accurate in quantifying tissues, also showing 60% less variability. Automatic tissue quantification was shown to be both reliable and practicable. We ultimately intend to facilitate refined prognostic stratification of (colo)rectal cancer patients and enable better personalized treatment.

  12. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression.

    PubMed

    Ayala, Gustavo; Morello, Matteo; Frolov, Anna; You, Sungyong; Li, Rile; Rosati, Fabiana; Bartolucci, Gianluca; Danza, Giovanna; Adam, Rosalyn M; Thompson, Timothy C; Lisanti, Michael P; Freeman, Michael R; Di Vizio, Dolores

    2013-09-01

    Levels of caveolin-1 (Cav-1) in tumour epithelial cells increase during prostate cancer progression. Conversely, Cav-1 expression in the stroma can decline in advanced and metastatic prostate cancer. In a large cohort of 724 prostate cancers, we observed significantly decreased levels of stromal Cav-1 in concordance with increased Gleason score (p = 0.012). Importantly, reduced expression of Cav-1 in the stroma correlated with reduced relapse-free survival (p = 0.009), suggesting a role for stromal Cav-1 in inhibiting advanced disease. Silencing of Cav-1 by shRNA in WPMY-1 prostate fibroblasts resulted in up-regulation of Akt phosphorylation, and significantly altered expression of genes involved in angiogenesis, invasion, and metastasis, including a > 2.5-fold increase in TGF-β1 and γ-synuclein (SNCG) gene expression. Moreover, silencing of Cav-1 induced migration of prostate cancer cells when stromal cells were used as attractants. Pharmacological inhibition of Akt caused down-regulation of TGF-β1 and SNCG, suggesting that loss of Cav-1 in the stroma can influence Akt-mediated signalling in the tumour microenvironment. Cav-1-depleted stromal cells exhibited increased levels of intracellular cholesterol, a precursor for androgen biosynthesis, steroidogenic enzymes, and testosterone. These findings suggest that loss of Cav-1 in the tumour microenvironment contributes to the metastatic behaviour of tumour cells by a mechanism that involves up-regulation of TGF-β1 and SNCG through Akt activation. They also suggest that intracrine production of androgens, a process relevant to castration resistance, may occur in the stroma.

  13. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression

    PubMed Central

    Frolov, Anna; You, Sungyong; Li, Rile; Rosati, Fabiana; Bartolucci, Gianluca; Danza, Giovanna; Adam, Rosalyn M; Thompson, Timothy C; Lisanti, Michael P; Freeman, Michael R; Vizio, Dolores Di

    2014-01-01

    Levels of caveolin-1 (Cav-1) in tumour epithelial cells increase during prostate cancer progression. Conversely, Cav-1 expression in the stroma can decline in advanced and metastatic prostate cancer. In a large cohort of 724 prostate cancers, we observed significantly decreased levels of stromal Cav-1 in concordance with increased Gleason score (p = 0.012). Importantly, reduced expression of Cav-1 in the stroma correlated with reduced relapse-free survival (p = 0.009), suggesting a role for stromal Cav-1 in inhibiting advanced disease. Silencing of Cav-1 by shRNA in WPMY-1 prostate fibroblasts resulted in up-regulation of Akt phosphorylation, and significantly altered expression of genes involved in angiogenesis, invasion, and metastasis, including a > 2.5-fold increase in TGF-β1 and γ-synuclein (SNCG) gene expression. Moreover, silencing of Cav-1 induced migration of prostate cancer cells when stromal cells were used as attractants. Pharmacological inhibition of Akt caused down-regulation of TGF-β1 and SNCG, suggesting that loss of Cav-1 in the stroma can influence Akt-mediated signalling in the tumour microenvironment. Cav-1-depleted stromal cells exhibited increased levels of intracellular cholesterol, a precursor for androgen biosynthesis, steroidogenic enzymes, and testosterone. These findings suggest that loss of Cav-1 in the tumour microenvironment contributes to the metastatic behaviour of tumour cells by a mechanism that involves up-regulation of TGF-β1 and SNCG through Akt activation. They also suggest that intracrine production of androgens, a process relevant to castration resistance, may occur in the stroma. PMID:23729330

  14. Prognostic value, localization and correlation of PD-1/PD-L1, CD8 and FOXP3 with the desmoplastic stroma in pancreatic ductal adenocarcinoma

    PubMed Central

    Diana, Angela; Wang, Lai Mun; D'Costa, Zenobia; Allen, Paul; Azad, Abul; Silva, Michael A.; Soonawalla, Zahir; Liu, Stanley; McKenna, W. Gillies; Muschel, Ruth J.; Fokas, Emmanouil

    2016-01-01

    We examined the prognostic value of programmed cell death-1 (PD-1) and its ligand (PD-L1) together with CD8+ tumor-infiltrating lymphocytes (TILs) and FOXP3+ Tregs in resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with adjuvant chemotherapy. Whole-mount FFPE tissue sections from 145 pancreatectomies were immunohistochemically stained for PD-1, PD-L1, CD8 and FOXP3. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin) and in regard to intratumoral lymphoid aggregates. The median OS was 21 months after a mean follow-up of 20 months (range, 2-69 months). In multivariate analysis, high PD-1+ TILs expression was associated with better OS (p = 0.049), LPFS (p = 0.017) and DMFS (p = 0.021). Similar findings were observed for CD8+ TILs, whereas FOXP3 and PD-L1 lacked prognostic significance. Although TIL distribution was heterogeneous, tumors of high stroma density had higher infiltration of CD8+ TILs than loose density stroma and vice versa (p < 0.001), whereas no correlation was found with stromal activity. Sixty (41.4%) tumors contained lymphoid aggregates and the presence of PD-1+ TILs was associated with better OS (p = 0.030), LPFS (p = 0.025) and DMFS (p = 0.033), whereas CD8+ TILs only correlated with superior LPFS (p = 0.039). PD-1+ and CD8+ TILs constitute independent prognostic markers in patients with PDAC treated with adjuvant chemotherapy. Our study provides important insight on the role of PD-1/PD-L1 in the context of desmoplastic stroma and could help guide future immunotherapies in PDAC. PMID:27329602

  15. Multipotent nestin-positive stem cells reside in the stroma of human eccrine and apocrine sweat glands and can be propagated robustly in vitro.

    PubMed

    Nagel, Sabine; Rohr, Franziska; Weber, Caroline; Kier, Janina; Siemers, Frank; Kruse, Charli; Danner, Sandra; Brandenburger, Matthias; Matthiessen, Anna Emilia

    2013-01-01

    Human skin harbours multiple different stem cell populations. In contrast to the relatively well-characterized niches of epidermal and hair follicle stem cells, the localization and niches of stem cells in other human skin compartments are as yet insufficiently investigated. Previously, we had shown in a pilot study that human sweat gland stroma contains Nestin-positive stem cells. Isolated sweat gland stroma-derived stem cells (SGSCs) proliferated in vitro and expressed Nestin in 80% of the cells. In this study, we were able to determine the precise localization of Nestin-positive cells in both eccrine and apocrine sweat glands of human axillary skin. We established a reproducible isolation procedure and characterized the spontaneous, long-lasting multipotent differentiation capacity of SGSCs. Thereby, a pronounced ectodermal differentiation was observed. Moreover, the secretion of prominent cytokines demonstrated the immunological potential of SGSCs. The comparison to human adult epidermal stem cells (EpiSCs) and bone marrow stem cells (BMSCs) revealed differences in protein expression and differentiation capacity. Furthermore, we found a coexpression of the stem cell markers Nestin and Iα6 within SGSCs and human sweat gland stroma. In conclusion the initial results of the pilot study were confirmed, indicating that human sweat glands are a new source of unique stem cells with multilineage differentiation potential, high proliferation capacity and remarkable self renewal. With regard to the easy accessibility of skin tissue biopsies, an autologous application of SGSCs in clinical therapies appears promising.

  16. The effects of stroma-free and dextran-conjugated hemoglobin on hemodynamics and carotid blood flow in hemorrhaged guinea pigs.

    PubMed

    Caron, A; Menu, P; Faivre-Fiorina, B; Labrude, P; Vigneron, C

    1999-01-01

    Hemoglobin solutions are potential resuscitative fluids with volume expanding and oxygen delivery abilities developed to reduce the use of blood transfusion. Most hemoglobin solutions in clinical trials increase transiently arterial pressure by inhibiting nitric oxide-dependent vasodilation. Our objective was to compare the effects on central hemodynamics and carotid blood flow of two hemoglobin solutions after resuscitation from hemorrhage in anesthetized guinea pigs. After anesthesia and instrumentation, severe hemorrhage was induced by withdrawing 50% of the blood volume. Resuscitation was performed after 15 min of hypovolemia with 5% albumin, stroma-free hemoglobin, or hemoglobin conjugated to dextran-benzenetetracarboxylate (Dex-BTC-Hb). The mean arterial pressure (MAP), carotid blood flow (CBF), vascular resistance index and heart rate (HR) were monitored for 3 hours after resuscitation. After hemorrhage, MAP and CBF dropped to 57.6 +/- 4.4% and 58.9 +/- 3.7% of control values respectively. Albumin failed to maintain hemodynamics in the decompensatory phase of shock. Both hemoglobin solutions gave rise to a transient increase in MAP (35%); stroma-free hemoglobin increased the CBF (150%) and resistance index (24%) whereas Dex-BTC-Hb had no effect on CBF and vascular resistances. None of the solutions affected the HR. Modified hemoglobin has attenuated effects on CBF and resistance index compared to stroma-free hemoglobin. This may be due to a balance between the stimulation of nitric oxide synthesis by shear-stress and the inhibition of vasodilation by nitric oxide trapping.

  17. Prognostic value and clinicopathological features of PD-1/PD-L1 expression with mismatch repair status and desmoplastic stroma in Chinese patients with pancreatic cancer.

    PubMed

    Wang, Yu; Lin, Jiacheng; Cui, Jiujie; Han, Ting; Jiao, Feng; Meng, Zhuo; Wang, Liwei

    2017-02-07

    Pancreatic cancer (PC) is a highly lethal cancer. Thus, the immune molecular markers which help to select PC patients are especially important. In this study, we aimed at systematically analyzing the expression of MLH1, MSH2, PD-L1 and PD-1, investigate their clinical significance and prognostic value. We found that high expression of PD-L1 on cancer cell membranes correlated with lymph node metastasis (P = 0.033) and strongly correlated with poor-differentiation (P = 0.008); high expression of PD-1 on cell membranes of T-cells correlated with well-differentiation (P = 0.018) and strongly correlated with advanced T stage (P = 0.004); high PD-1 expression was associated with a significantly superior OS and was an independent prognostic factor (P = 0.031). Then we found an inverse correlation between MSH2 expression and PD-L1 expression (Spearman correlation coefficient r = -0.295, P = 0.004). In subgroup analyses, we observed that PD-1 expression level was associated with OS only at low PD-L1 expression subgroup (P = 0.021). Finally, when we stratified the cases into four subgroups based on PD-1 expression and stroma density, we found that patients with high PD-1 expression and dense stroma had a better OS, while patients with low PD-1 expression and moderate stroma showed a worst outcome. Our result may provide more effective molecular markers for immunotherapeutic strategies of PC patients in clinical practice.

  18. Reflection and transmission at the apparent horizon during gravitational collapse

    SciTech Connect

    Vaz, Cenalo; Wijewardhana, L. C. R.

    2010-10-15

    We examine the wave functionals describing the collapse of a self-gravitating dustball in an exact quantization of the gravity-dust system. We show that ingoing (collapsing) dust shell modes outside the apparent horizon must necessarily be accompanied by outgoing modes inside the apparent horizon, whose amplitude is suppressed by the square root of the Boltzmann factor at the Hawking temperature. Likewise, ingoing modes in the interior must be accompanied by outgoing modes in the exterior, again with an amplitude suppressed by the same factor. A suitable superposition of the two solutions is necessary to conserve the dust probability flux across the apparent horizon; thus, each region contains both ingoing and outgoing dust modes. If one restricts oneself to considering only the modes outside the apparent horizon then one should think of the apparent horizon as a partial reflector, the probability for a shell to reflect being given by the Boltzmann factor at the Hawking temperature determined by the mass contained within it. However, if one considers the entire wave function, the outgoing wave in the exterior is seen to be the transmission through the horizon of the interior outgoing wave that accompanies the collapsing shells. This transmission could allow information from the interior to be transferred to the exterior.

  19. The Molecular Signature of the Stroma Response in Prostate Cancer-Induced Osteoblastic Bone Metastasis Highlights Expansion of Hematopoietic and Prostate Epithelial Stem Cell Niches

    PubMed Central

    Secondini, Chiara; Wetterwald, Antoinette; Schwaninger, Ruth; Fleischmann, Achim; Raffelsberger, Wolfgang; Poch, Olivier; Delorenzi, Mauro; Temanni, Ramzi; Mills, Ian G.; van der Pluijm, Gabri; Thalmann, George N.; Cecchini, Marco G.

    2014-01-01

    The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature (“Core” OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this

  20. Climate Influence on Deep Sea Populations

    PubMed Central

    Company, Joan B.; Puig, Pere; Sardà, Francesc; Palanques, Albert; Latasa, Mikel; Scharek, Renate

    2008-01-01

    Dynamics of biological processes on the deep-sea floor are traditionally thought to be controlled by vertical sinking of particles from the euphotic zone at a seasonal scale. However, little is known about the influence of lateral particle transport from continental margins to deep-sea ecosystems. To address this question, we report here how the formation of dense shelf waters and their subsequent downslope cascade, a climate induced phenomenon, affects the population of the deep-sea shrimp Aristeus antennatus. We found evidence that strong currents associated with intense cascading events correlates with the disappearance of this species from its fishing grounds, producing a temporary fishery collapse. Despite this initial negative effect, landings increase between 3 and 5 years after these major events, preceded by an increase of juveniles. The transport of particulate organic matter associated with cascading appears to enhance the recruitment of this deep-sea living resource, apparently mitigating the general trend of overexploitation. Because cascade of dense water from continental shelves is a global phenomenon, we anticipate that its influence on deep-sea ecosystems and fisheries worldwide should be larger than previously thought. PMID:18197243

  1. Climate influence on deep sea populations.

    PubMed

    Company, Joan B; Puig, Pere; Sardà, Francesc; Palanques, Albert; Latasa, Mikel; Scharek, Renate

    2008-01-16

    Dynamics of biological processes on the deep-sea floor are traditionally thought to be controlled by vertical sinking of particles from the euphotic zone at a seasonal scale. However, little is known about the influence of lateral particle transport from continental margins to deep-sea ecosystems. To address this question, we report here how the formation of dense shelf waters and their subsequent downslope cascade, a climate induced phenomenon, affects the population of the deep-sea shrimp Aristeus antennatus. We found evidence that strong currents associated with intense cascading events correlates with the disappearance of this species from its fishing grounds, producing a temporary fishery collapse. Despite this initial negative effect, landings increase between 3 and 5 years after these major events, preceded by an increase of juveniles. The transport of particulate organic matter associated with cascading appears to enhance the recruitment of this deep-sea living resource, apparently mitigating the general trend of overexploitation. Because cascade of dense water from continental shelves is a global phenomenon, we anticipate that its influence on deep-sea ecosystems and fisheries worldwide should be larger than previously thought.

  2. A clinically suitable ex vivo expansion culture system for LTC-IC and CFC using stroma-conditioned medium.

    PubMed

    Bhatia, R; McGlave, P B; Miller, J S; Wissink, S; Lin, W N; Verfaillie, C M

    1997-08-01

    FACS-selected CD34+ HLA-DR- cells (DR- cells) may provide a source of benign stem cells suitable for autografting in chronic myelogenous leukemia (CML) and other hematological malignancies. However, DR- cell selection depletes the majority of committed hematopoietic progenitors, which may be important for early engraftment. Furthermore, only a small number of DR- cells may be selectable in certain patients. These impediments to the use of DR- cells for autografting may be overcome through the development of ex vivo culture systems that support expansion and initial differentiation of primitive progenitors. Because 2-week culture of DR- cells in a stroma "noncontact" system supplemented with interleukin-3 (IL-3) and macrophage inflammatory protein 1-alpha (MIP-1alpha) expands both long-term culture-initiating cells (LTC-ICs) and colony-forming cells (CFCs), we adapted this system to a clinically applicable method for expanding LTC-ICs and CFCs ex vivo. In initial small-scale studies, DR cells were grown in stroma conditioned medium (SCM) supplemented with IL-3 with or without additional growth-promoting cytokines and the chemokines PF-4 and BB10010, all approved for clinical use. An IL-3 dose-dependent expansion of committed progenitors and LTC-ICs was observed when DR- cells were cultured in tissue culture plates in SCM+IL-3 for 2 weeks. Similar CFC expansion along with increased (5-fold) LTC-IC expansion was observed following addition of PF-4 to SCM+IL-3 cultures. The addition of stem cell factor (SCF), but not of IL-6, IL-11, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, IL-1, and IL-7, increased CFC and LTC-IC expansion beyond the levels observed with SCM+IL-3 alone. We next evaluated the suitability of this culture system for scale-up. Culture of 2-6 x 10(5) DR- cells in gas-permeable bags with SCM+IL-3 resulted in similar CFC and LTC-IC expansion as seen in small-scale cultures. In addition, we observed that progenitors

  3. A phenotype from tumor stroma based on the expression of metalloproteases and their inhibitors, associated with prognosis in breast cancer

    PubMed Central

    Eiró, Noemí; Fernandez-Garcia, Belen; Vázquez, Julio; del Casar, José M; González, Luis O; Vizoso, Francisco J

    2015-01-01

    The objective of the present work was to evaluate the impact of the phenotype of both mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs) in early breast cancer patients, specifically assessed as to their expression of MMP/TIMP relative to their position within the tumor (i.e., localization at the tumor center or invasive front) and the occurrence of distant metastases.. An immunohistochemical study was performed using tissue arrays and specific antibodies against matrix metalloproteinase (MMP)−1, −2, −7, −9, −11, −13 and −14, tissue inhibitors of metalloproteinase (TIMP)−1, −2 and −3, both at tumor center and at invasive front, in 107 patients with primary ductal invasive breast tumors. Data were analyzed by unsupervised hierarchical clustering analysis. Our results indicated that MMP-11 expression by MICs, and TIMP-2 expression by CAFs at either the tumor center or the invasive front, were the most potent independent prognostic factors for predicting the clinical outcome of patients. Using the unsupervised hierarchical clustering analysis, we found well-defined clusters of cases identifying subgroups of tumors showing a high molecular profile of MMPs/TIMPs expression by stromal cells (CAFs and MICs), both at the tumor center and at the invasive front, which were strongly associated with a higher prevalence of distant metastasis. In addition, we found combinations of these clusters defining subpopulations of breast carcinomas differing widely in their clinical outcome. The results presented here identify biologic markers useful to categorize patients into different subgroups based on their tumor stroma, which may contribute to improved understanding of the prognosis of breast cancer patients. PMID:26140253

  4. SCCOHT tumors acquire chemoresistance and protection by interacting mesenchymal stroma/stem cells within the tumor microenvironment.

    PubMed

    Otte, Anna; Yang, Yuanyuan; von der Ohe, Juliane; Melzer, Catharina; Hillemanns, Peter; Feuerhake, Friedrich; Hass, Ralf

    2016-12-01

    Chemotherapeutic drug testing of SCCOHT-1 and BIN-67 tumor cells revealed synergistic growth-inhibition of >95% in vitro with a combination of foretinib and FK228. Application of this drug combination in vivo in NODscid mice-induced SCCOHT-1GFP tumors was associated with ~6-fold reduction in tumor mass within 10 days, whereby synergistic effects of the two compounds remained undetectable compared to previous results with foretinib treatment alone. Histopathologic evaluation revealed a reduced vascularization and a lower amount of proliferating cells in the treated tumors. Surprisingly, a simultaneous significant accumulation of extracellular matrix structures with positive elastin-van Gieson staining was observed following foretinib/FK228 exposure. Expression analysis of treated animal tumors exhibited various changes including increased mouse transcript levels of elastin, laminin, and fibronectin. In parallel, markers for mesenchymal stroma/stem cells (MSC) including CD73 and CD90 were detectable in all mouse tumors suggesting a possible involvement of these cells in extracellular matrix restructure. Indeed, incubation of MSC with FK228 or foretinib/FK228 demonstrated morphologic alterations and enhanced expression of laminin and fibronectin. Moreover, a co-culture of MSC with lentiviral-labeled SCCOHT-1GFP cells contributed to protection of the tumor cells against FK228-mediated cytotoxicity. Furthermore, explant cultures of SCCOHT-1GFP-induced tumors acquired an increased resistance to FK228 and a combination of foretinib/FK228 in contrast to foretinib alone. Together, these data suggested that FK228-mediated extracellular matrix protein expression by MSC contributes to increased protection and enhanced resistance of SCCOHT tumors which could represent a more general mechanism of MSC during drug-induced alterations of a tumor microenvironment.

  5. Human mesenchymal stroma/stem cells exchange membrane proteins and alter functionality during interaction with different tumor cell lines.

    PubMed

    Yang, Yuanyuan; Otte, Anna; Hass, Ralf

    2015-05-15

    To analyze effects of cellular interaction between human mesenchymal stroma/stem cells (MSC) and different cancer cells, direct co-cultures were performed and revealed significant growth stimulation of the tumor populations and a variety of protein exchanges. More than 90% of MCF-7 and primary human HBCEC699 breast cancer cells as well as NIH:OVCAR-3 ovarian adenocarcinoma cells acquired CD90 proteins during MSC co-culture, respectively. Furthermore, SK-OV-3 ovarian cancer cells progressively elevated CD105 and CD90 proteins in co-culture with MSC. Primary small cell hypercalcemic ovarian carcinoma cells (SCCOHT-1) demonstrated undetectable levels of CD73 and CD105; however, both proteins were significantly increased in the presence of MSC. This co-culture-mediated protein induction was also observed at transcriptional levels and changed functionality of SCCOHT-1 cells by an acquired capability to metabolize 5'cAMP. Moreover, exchange between tumor cells and MSC worked bidirectional, as undetectable expression of epithelial cell adhesion molecule (EpCAM) in MSC significantly increased after co-culture with SK-OV-3 or NIH:OVCAR-3 cells. In addition, a small population of chimeric/hybrid cells appeared in each MSC/tumor cell co-culture by spontaneous cell fusion. Immune fluorescence demonstrated nanotube structures and exosomes between MSC and tumor cells, whereas cytochalasin-D partially abolished the intercellular protein transfer. More detailed functional analysis of FACS-separated MSC and NIH:OVCAR-3 cells after co-culture revealed the acquisition of epithelial cell-specific properties by MSC, including increased gene expression for cytokeratins and epithelial-like differentiation factors. Vice versa, a variety of transcriptional regulatory genes were down-modulated in NIH:OVCAR-3 cells after co-culture with MSC. Together, these mutual cellular interactions contributed to functional alterations in MSC and tumor cells.

  6. Proteomics of the human endometrial glandular epithelium and stroma from the proliferative and secretory phases of the menstrual cycle.

    PubMed

    Hood, Brian L; Liu, Baoquan; Alkhas, Addie; Shoji, Yutaka; Challa, Rusheeswar; Wang, Guisong; Ferguson, Susan; Oliver, Julie; Mitchell, Dave; Bateman, Nicholas W; Zahn, Christopher M; Hamilton, Chad A; Payson, Mark; Lessey, Bruce; Fazleabas, Asgerally T; Maxwell, G Larry; Conrads, Thomas P; Risinger, John I

    2015-04-01

    Despite its importance in reproductive biology and women's health, a detailed molecular-level understanding of the human endometrium is lacking. Indeed, no comprehensive studies have been undertaken to elucidate the important protein expression differences between the endometrial glandular epithelium and surrounding stroma during the proliferative and midsecretory phases of the menstrual cycle. We utilized laser microdissection to harvest epithelial cells and stromal compartments from proliferative and secretory premenopausal endometrial tissue and performed a global, quantitative mass spectrometry-based proteomics analysis. This analysis identified 1224 total proteins from epithelial cells, among which 318 were differentially abundant between the proliferative and secretory phases (q < 0.05), and 1005 proteins from the stromal compartments, 19 of which were differentially abundant between the phases (q < 0.05). Several proteins were chosen for validation by immunohistochemistry in an independent set of uterine tissues, including carboxypeptidase M, tenascin C, neprilysin, and ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3). ENPP3, which was elevated in epithelial glandular cells in the secretory phase, was confirmed to be elevated in midsecretory-phase baboon uterine lavage samples and also observed to have an N-linked glycosylated form that was not observed in the proliferative phase. This study provides a detailed view into the global proteomic alterations of the epithelial cells and stromal compartments of the cycling premenopausal endometrium. These proteomic alterations during endometrial remodeling provide a basis for numerous follow-up investigations on the function of these differentially regulated proteins and their role in reproductive biology and endometrial pathologies.

  7. Analysis of the chondrogenic potential and secretome of mesenchymal stem cells derived from human umbilical cord stroma.

    PubMed

    Arufe, Maria C; De la Fuente, Alexandre; Mateos, Jesus; Fuentes, Isaac; De Toro, Francisco J; Blanco, Francisco J

    2011-07-01

    Mesenchymal stem cells (MSCs) from umbilical cord stroma were isolated by plastic adherence and characterized by flow cytometry, looking for cells positive for OCT3/4 and SSEA-4 as well as the classic MSC markers CD44, CD73, CD90, Ki67, CD105, and CD106 and negative for CD34 and CD45. Quantitative reverse transcriptase-polymerase chain reaction analysis of the genes ALP, MEF2C, MyoD, LPL, FAB4, and AMP, characteristic for the differentiated lineages, were used to evaluate early and late differentiation of 3 germ lines. Direct chondrogenic differentiation was achieved through spheroid formation by MSCs in a chondrogenic medium and the presence of chondrogenic markers at 4, 7, 14, 28, and 46 days of culture was tested. Immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analyses were utilized to assess the expression of collagen type I, collagen type II, and collagen type X throughout the time studied. We found expression of all the markers as early as 4 days of chondrogenic differentiation culture, with their expression increasing with time, except for collagen type I, which decreased in expression in the formed spheroids after 4 days of differentiation. The signaling role of Wnt during chondrogenic differentiation was studied by western blot. We observed that β-catenin expression decreased during the chondrogenic process. Further, a secretome study to validate our model of differentiation in vitro was performed on spheroids formed during the chondrogenesis process. Our results indicate the multipotential capacity of this source of human cells; their chondrogenic capacity could be useful for future cell therapy in articular diseases.

  8. Two-wave nanotherapy to target the stroma and optimize gemcitabine delivery to a human pancreatic cancer model in mice.

    PubMed

    Meng, Huan; Zhao, Yang; Dong, Juyao; Xue, Min; Lin, Yu-Shen; Ji, Zhaoxia; Mai, Wilson X; Zhang, Haiyuan; Chang, Chong Hyun; Brinker, C Jeffrey; Zink, Jeffrey I; Nel, Andre E

    2013-11-26

    Pancreatic ductal adenocarcinoma (PDAC) elicits a dense stromal response that blocks vascular access because of pericyte coverage of vascular fenestrations. In this way, the PDAC stroma contributes to chemotherapy resistance in addition to causing other problems. In order to improve the delivery of gemcitabine, a first-line chemotherapeutic agent, a PEGylated drug-carrying liposome was developed, using a transmembrane ammonium sulfate gradient to encapsulate the protonated drug up to 20% w/w. However, because the liposome was precluded from entering the xenograft site due to the stromal interference, we developed a first-wave nanocarrier that decreases pericyte coverage of the vasculature through interference in the pericyte recruiting TGF-β signaling pathway. This was accomplished using a polyethyleneimine (PEI)/polyethylene glycol (PEG)-coated mesoporous silica nanoparticle (MSNP) for molecular complexation to a small molecule TGF-β inhibitor, LY364947. LY364947 contains a nitrogen atom that attaches, through H-bonding, to PEI amines with a high rate of efficiency. The copolymer coating also facilitates systemic biodistribution and retention at the tumor site. Because of the high loading capacity and pH-dependent LY364947 release from the MSNPs, we achieved rapid entry of IV-injected liposomes and MSNPs at the PDAC tumor site. This two-wave approach provided effective shrinkage of the tumor xenografts beyond 25 days, compared to the treatment with free drug or gemcitabine-loaded liposomes only. Not only does this approach overcome stromal resistance to drug delivery in PDAC, but it also introduces the concept of using a stepwise engineered approach to address a range of biological impediments that interfere in nanocancer therapy in a spectrum of cancers.

  9. Optimizing apparent display resolution enhancement for arbitrary videos.

    PubMed

    Stengel, Michael; Eisemann, Martin; Wenger, Stephan; Hell, Benjamin; Magnor, Marcus

    2013-09-01

    Display resolution is frequently exceeded by available image resolution. Recently, apparent display resolution enhancement (ADRE) techniques show how characteristics of the human visual system can be exploited to provide super-resolution on high refresh rate displays. In this paper, we address the problem of generalizing the ADRE technique to conventional videos of arbitrary content. We propose an optimization-based approach to continuously translate the video frames in such a way that the added motion enables apparent resolution enhancement for the salient image region. The optimization considers the optimal velocity, smoothness, and similarity to compute an appropriate trajectory. In addition, we provide an intuitive user interface that allows to guide the algorithm interactively and preserves important compositions within the video. We present a user study evaluating apparent rendering quality and show versatility of our method on a variety of general test scenes.

  10. Role of surface in apparent viscosity of glasses

    NASA Astrophysics Data System (ADS)

    Avramov, I.

    2014-03-01

    Two problems have intrigued experts for a long time: The one is within the context of the legend of flowing cathedral glass windows and the second is the inaccuracy appearing in very old thermometers of famous scientists. We relate this with the role of the surface on the apparent viscosity of glasses. The apparent viscosity could deviate from the bulk viscosity if the fraction w of the surface molecules, of small samples, is sufficiently large. The effect is more prominent at low temperatures, correspondingly at high viscosities. The interpretation is within the Avramov and Milchev viscosity model, combined with the predictions of the change of heat capacity for extremely small samples. We find that the apparent glass transition temperature could depend on the sample size, in agreement with experimental observations existing in the literature. In addition to glasses, the present results could be of importance for thin films and foams.

  11. Role of surface in apparent viscosity of glasses.

    PubMed

    Avramov, I

    2014-03-01

    Two problems have intrigued experts for a long time: The one is within the context of the legend of flowing cathedral glass windows and the second is the inaccuracy appearing in very old thermometers of famous scientists. We relate this with the role of the surface on the apparent viscosity of glasses. The apparent viscosity could deviate from the bulk viscosity if the fraction w of the surface molecules, of small samples, is sufficiently large. The effect is more prominent at low temperatures, correspondingly at high viscosities. The interpretation is within the Avramov and Milchev viscosity model, combined with the predictions of the change of heat capacity for extremely small samples. We find that the apparent glass transition temperature could depend on the sample size, in agreement with experimental observations existing in the literature. In addition to glasses, the present results could be of importance for thin films and foams.

  12. Foliation dependence of black hole apparent horizons in spherical symmetry

    NASA Astrophysics Data System (ADS)

    Faraoni, Valerio; Ellis, George F. R.; Firouzjaee, Javad T.; Helou, Alexis; Musco, Ilia

    2017-01-01

    Numerical studies of gravitational collapse to black holes make use of apparent horizons, which are intrinsically foliation dependent. We expose the problem and discuss possible solutions using the Hawking-Hayward quasilocal mass. In spherical symmetry, we present a physically sensible approach to the problem by restricting to spherically symmetric spacetime slicings. In spherical symmetry, the apparent horizons enjoy a restricted gauge independence in any spherically symmetric foliation, but physical quantities associated with them, such as surface gravity and temperature, are fully gauge dependent. The widely used comoving and Kodama foliations, which are of particular interest, are discussed in detail as examples.

  13. Identification of Deep Earthquakes

    DTIC Science & Technology

    2010-09-01

    develop a ground truth dataset of earthquakes at both normal crustal depths and earthquakes from subduction zones , below the overlying crust. Many...deep earthquakes (depths between about 50 and 300 km). These deep earthquakes are known to occur in the Asia-India continental collision zone ...and/or NIL, as these stations are within a few hundred km of the zone where deep earthquakes are known to occur. To date we have selected about 300

  14. Deep Water Ocean Acoustics

    DTIC Science & Technology

    2016-04-30

    OASIS, INC. 1 Report No. QSR-14C0172-Ocean Acoustics-043016 Quarterly Progress Report Technical and Financial Deep Water Ocean Acoustics...understanding of the impact of the ocean and seafloor environmental variability on deep- water (long-range) ocean acoustic propagation and to...improve our understanding. During the past few years, the physics effects studied have been three-dimensional propagation on global scales, deep water

  15. Deep Water Ocean Acoustics

    DTIC Science & Technology

    2015-10-19

    OASIS, INC. 1 Report No. QSR-14C0172-Ocean Acoustics-093015 Quarterly Progress Report Technical and Financial Deep Water Ocean Acoustics...number. 1. REPORT DATE OCT 2015 2. REPORT TYPE 3. DATES COVERED 01-07-2015 to 30-09-2015 4. TITLE AND SUBTITLE Deep Water Ocean Acoustics...understanding of the impact of the ocean and seafloor environmental variability on deep- water (long-range) ocean acoustic propagation and to develop

  16. The deep space network

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Presented is Deep Space Network (DSN) progress in flight project support, tracking and data acquisition (TDA) research and technology, network engineering, hardware and software implementation, and operations.

  17. Deep Space Communication

    NASA Technical Reports Server (NTRS)

    Manshadi, Farzin

    2012-01-01

    ITU defines deep space as the volume of Space at distances from the Earth equal to, or greater than, 2 106 km. Deep Space Spacecraft have to travel tens of millions of km from Earth to reach the nearest object in deep space. Spacecraft mass and power are precious. Large ground-based antennas and very high power transmitters are needed to overcome large space loss and spacecraft's small antennas and low power transmitters. Navigation is complex and highly dependent on measurements from the Earth. Every deep space mission is unique and therefore very costly to develop.

  18. The deep space network

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Summaries are given of Deep Space Network progress in flight project support, tracking and data acquisition research and technology, network engineering, hardware and software implementation, and operations.

  19. A deep reef in deep trouble

    USGS Publications Warehouse

    Menza, Charles; Kendall, M.; Rogers, C.; Miller, J.

    2007-01-01

    The well-documented degradation of shallower reefs which are often closer to land and more vulnerable to pollution, sewage and other human-related stressors has led to the suggestion that deeper, more remote offshore reefs could possibly serve as sources of coral and fish larvae to replenish the shallower reefs. Yet, the distribution, status, and ecological roles of deep (>30 m) Caribbean reefs are not well known. In this report, an observation of a deep reef which has undergone a recent extensive loss of coral cover is presented. In stark contrast to the typical pattern of coral loss in shallow reefs, the deeper corals were most affected. This report is the first description of such a pattern of coral loss on a deep reef.

  20. Apparent horizons in D-dimensional Robinson-Trautman spacetime

    SciTech Connect

    Svitek, Otakar

    2009-05-01

    We derive the higher dimensional generalization of Penrose-Tod equation describing apparent horizons in Robinson-Trautman spacetimes. New results concerning the existence and uniqueness of its solutions in four dimensions are proven. Namely, previous results of Tod [1] are generalized to nonvanishing cosmological constant.

  1. Independent Discovery of an Apparent Nova in M81

    NASA Astrophysics Data System (ADS)

    Hornoch, K.; Kucakova, H.; Vrastil, J.; Williams, S. C.; Henze, M.; Meusinger, H.; Pohl, C.; Darnley, M. J.; Kaur, A.; Hartmann, D. H.; Sala, G.; Jose, J.; Figueira, J.; Sin, P.; Hernanz, M.; Shafter, A. W.

    2017-02-01

    The M81 nova monitoring collaboration reports the independent discovery of an apparent nova in M81 on a co-added 3510-s unfiltered CCD frame taken on 2017 Feb. 24.119 UT with the 0.65-m telescope at Ondrejov.

  2. Independent Discovery of an Apparent Nova in M81

    NASA Astrophysics Data System (ADS)

    Hornoch, K.; Kucakova, H.; Williams, S. C.; Henze, M.; Darnley, M. J.; Kaur, A.; Hartmann, D. H.; Sala, G.; Jose, J.; Figueira, J.; Sin, P.; Hernanz, M.; Shafter, A. W.; Meusinger, H.

    2017-02-01

    The M81 nova monitoring collaboration reports the independent discovery of an apparent nova in M81 on a co-added 5400-s unfiltered CCD frame taken on 2017 Feb. 19.962 UT with the 0.65-m telescope at Ondrejov (OND).

  3. An Apparent Paradox: Catt's Anomaly

    ERIC Educational Resources Information Center

    Pieraccini, M.; Selleri, S.

    2013-01-01

    Catt's anomaly is a sort of "thought experiment" (a "gedankenexperiment") where electrons seem to travel at the speed of light. Although its author argued with conviction for many years, it has a clear and satisfactory solution and it can be considered indubitably just an apparent paradox. Nevertheless, it is curious and…

  4. Discovery of an Apparent Nova in M81

    NASA Astrophysics Data System (ADS)

    Hornoch, K.; Alfaro, M. Diaz; Ordonez-Etxeberria, I.; Vaduvescu, O.

    2015-01-01

    We report the discovery of an apparent nova in M81 on a co-added 1600-s narrow-band H-alpha CCD image taken with the 2.5-m Isaac Newton Telescope (INT) + WFC at La Palma under ~2.4" seeing on 2015 Jan. 15.126 UT.

  5. Apparent digestible energy value of crude glycerol fed to pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The apparent digestible energy of crude glycerol, a co-product of biodiesel production, was determined in two studies conducted at the Iowa State University Swine Nutrition Research Farm, Ames, IA. In the first study, 24 barrows with an average body weight of 11.0 kg were fed 376 g/d of a basal corn...

  6. A New Theory of Leadership: "Realwert" Versus Apparent Good.

    ERIC Educational Resources Information Center

    Lang, Donald

    1999-01-01

    "Realwert" ("real good") stems from an understanding of humanity's "raison d'etre"--treating others with respect and dignity. It can be contrasted with "apparent good," a condition wherein one mistakenly thinks real good is being pursued. Drawing on Aquinas and Hodginson, this paper argues for a…

  7. Changes in apparent duration follow shifts in perceptual timing

    PubMed Central

    Bruno, Aurelio; Ayhan, Inci; Johnston, Alan

    2015-01-01

    It is well established that the apparent duration of moving visual objects is greater at higher as compared to slower speeds. Here we report the effects of acceleration and deceleration on the perceived duration of a drifting grating with average speed kept constant (10°/s).For acceleration, increasing the speed range progressively reduced perceived duration. The magnitude of apparent duration compression was determined by speed rather than temporal frequency and was proportional to speed range (independent of standard duration) rather than acceleration. The perceived duration reduction was also proportional to the standard length. The effects of increases and decreases in speed were highly asymmetric. Reducing speed through the interval induced a moderate increase in perceived duration. These results could not be explained by changes in apparent onset or offset or differences in perceived average speed between intervals containing increasing speed and intervals containing decreasing speed. Paradoxically, for intervals combining increasing speed and decreasing speed, compression only occurred when increasing speed occurred in the second half of the interval. We show that this pattern of results in the duration domain was concomitant with changes in the reported direction of apparent motion of Gaussian blobs, embedded in intervals of increasing or decreasing speed, that could be predicted from adaptive changes in the temporal impulse response function. We detected similar changes after flicker adaptation, suggesting that the two effects might be linked through changes in the temporal tuning of visual filters. PMID:26024450

  8. Temperature and depth mediate resource competition and apparent competition between Mysis diluviana and kokanee.

    PubMed

    Schoen, Erik R; Beauchamp, David A; Buettner, Anna R; Overman, Nathanael C

    2015-10-01

    In many food webs, species in similar trophic positions can interact either by competing for resources or boosting shared predators (apparent competition), but little is known about how the relative strengths of these interactions vary across environmental gradients. Introduced Mysis diluviana shrimp interact with planktivorous fishes such as kokanee salmon (lacustrine Oncorhynchus nerka) through both of these pathways, and effective management depends on understanding which interaction is more limiting under different conditions. An "environmental matching" hypothesis predicts the ecological impacts of Mysis are maximized under cool conditions near its thermal optimum. In addition, we hypothesized Mysis is more vulnerable to predation by lake trout in relatively shallow waters, and therefore Mysis enhances lake trout density and limits kokanee through apparent competition more strongly in shallower habitats. We tested whether these hypotheses could explain food web differences between two connected lake basins, one relatively shallow and the other extremely deep. The shallower basin warmed faster, thermally excluded Mysis from surface waters for 75% longer, and supported 2.5-18 times greater seasonal production of cladoceran zooplankton than the deeper basin, standardized by surface area. Mysis consumed 14-22% less zooplankton in the shallower basin, and lower ratios of total planktivore consumption to zooplankton production (C:P) indicated less potential for resource competition with kokanee, consistent with environmental matching. Lake trout diets contained more Mysis in the shallower basin and at shallower sampling sites within both basins. The catch rate of lake trout was seven times greater and the predation risk for kokanee was 4-5 times greater in the shallower basin than in the deeper basin, consistent with stronger apparent competition in shallower habitats. Understanding how the strengths of these interactions are mediated by temperature and depth would

  9. Hubble Deep Fields

    NASA Astrophysics Data System (ADS)

    Ferguson, H.; Murdin, P.

    2000-11-01

    The Hubble Deep Fields are two small areas of the sky that were carefully selected for deep observations by the HUBBLE SPACE TELESCOPE (HST). They represent the deepest optical observations to date and reveal galaxies as faint as V=30, 4 billion times fainter than can be seen with the unaided eye....

  10. Deep sea waste disposal

    SciTech Connect

    Kester, D.R.; Burt, W.V.; Capuzzo, J.M.; Park, P.K.; Ketchum, B.W.; Duedall, I.W.

    1985-01-01

    The book presents papers on the marine disposal of wastes. Topics considered include incineration at sea, the modelling and biological effects of industrial wastes, microbial studies of ocean dumping, deep-sea mining wastes, the chemical analysis of ferromanganese nodules, and economic aspects of deep-sea disposal.

  11. Deep-diving dinosaurs

    NASA Astrophysics Data System (ADS)

    Hayman, John

    2012-08-01

    Dysbaric bone necrosis demonstrated in ichthyosaurs may be the result of prolonged deep diving rather than rapid ascent to escape predators. The bone lesions show structural and anatomical similarity to those that may occur in human divers and in the deep diving sperm whale, Physeter macrocephalus.

  12. The Deep Space Network

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Deep Space Network progress in flight project support, tracking and data acquisition, research and technology, network engineering, hardware and software implementation, and operations is cited. Topics covered include: tracking and ground based navigation; spacecraft/ground communication; station control and operations technology; ground communications; and deep space stations.

  13. The deep space network

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The progress is reported of Deep Space Network (DSN) research in the following areas: (1) flight project support, (2) spacecraft/ground communications, (3) station control and operations technology, (4) network control and processing, and (5) deep space stations. A description of the DSN functions and facilities is included.

  14. Deep Impact Spots Quarry

    NASA Technical Reports Server (NTRS)

    2005-01-01

    Sixty-nine days before it gets up-close-and-personal with a comet, NASA's Deep Impact spacecraft successfully photographed its quarry, comet Tempel 1, at a distance of 39.7 million miles. The image, taken on April 25, 2005, is the first of many comet portraits Deep Impact will take leading up to its historic comet encounter on July 4.

  15. Deep venous thrombosis

    MedlinePlus

    ... ncbi.nlm.nih.gov/pubmed/22315257 . Kline JA. Pulmonary embolism and deep vein thrombosis. In: Marx JA, Hockberger RS, Walls RM, et al, eds. Rosen's Emergency Medicine: Concepts and Clinical Practice . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 88. ... Instructions Deep vein thrombosis - discharge ...

  16. Oxygen isotopes in deep-sea spherules

    NASA Technical Reports Server (NTRS)

    Clayton, Robert N.; Mayeda, Toshiko K.; Brownlee, Donald E.

    1986-01-01

    Oxygen isotopic compositions have been measured on several size fractions of deep-sea spherules of extraterrestrial origin. The silicate spherules have an isotopic composition unlike that of any known macrometeorite. Their pre-terrestrial compositions may have been similar to those of C3 chondrites or the anhydrous component of C2 chondrites, the latter being preferred on chemical grounds. Metallic particles oxidize in the upper atmosphere, and sample a region for which no previous oxygen isotope data exist. This part of the atmosphere, above about 100 km, is apparently strongly enriched in the heavy isotopes of oxygen.

  17. A role for stroma-derived annexin A1 as mediator in the control of genetic susceptibility to T-cell lymphoblastic malignancies through prostaglandin E2 secretion.

    PubMed

    Santos, Javier; González-Sánchez, Laura; Matabuena-Deyzaguirre, María; Villa-Morales, María; Cozar, Patricia; López-Nieva, Pilar; Fernández-Navarro, Pablo; Fresno, Manuel; Díaz-Muñoz, Manuel D; Guenet, Jean-Louis; Montagutelli, Xavier; Fernández-Piqueras, José

    2009-03-15

    Cancer susceptibility is essentially attributable to multiple low-penetrance genes. Using interspecific consomic and congenic mice between the tumor-resistant SEG/Pas and the tumor-sensitive C57BL/6J strains, a region on chromosome 19 involved in the genetic resistance to gamma-irradiation-induced T-cell lymphomas (Tlyr1) has been identified. Through the development of nonoverlapping subcongenic strains, it has been further shown that Anxa1 may be a candidate resistance gene on the basis of its differential expression in thymus stroma cells after gamma-radiation exposure. In addition, thymus stroma cells of thymic lymphomas exhibited a significant reduction in the expression levels of Anxa1. Interestingly, the activity of Anxa1 relies on prostaglandin E(2) (PGE(2)) induction that brings about apoptosis in thymocytes. In fact, in vitro transfection experiments revealed that PGE(2) production was enhanced when HEK 293 cells were transfected with full-length cDNAs of Anxa1, with PGE(2) production in the cells transfected with the allele of the resistant strain (Anxa1(Tyr)) being higher than that in cells transfected with the allele of the susceptible strain (Anxa1(Phe)). Furthermore, the presence of this compound in the medium induced apoptosis of immature CD4(+)CD8(+)CD3(low) cells in a dose-dependent manner. These results improve our knowledge of the molecular mechanisms triggering T-cell lymphoblastic lymphoma development while highlighting the relevance of the stroma in controlling genetic susceptibility and the use of PGE(2) as a new therapeutic approach in T-cell hematologic malignancies.

  18. Prognostic role and correlation of CA9, CD31, CD68 and CD20 with the desmoplastic stroma in pancreatic ductal adenocarcinoma

    PubMed Central

    D'Costa, Zenobia; Azad, Abul; Silva, Michael A.; Soonawalla, Zahir; Allen, Paul; Liu, Stanley; McKenna, W. Gillies; Muschel, Ruth J.; Fokas, Emmanouil

    2016-01-01

    We assessed the prognostic value of hypoxia (carbonic anhydrase 9; CA9), vessel density (CD31), with macrophages (CD68) and B cells (CD20) that can interact and lead to immune suppression and disease progression using scanning and histological mapping of whole-mount FFPE pancreatectomy tissue sections from 141 primarily resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with surgery and adjuvant chemotherapy. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin). The median OS was 21 months after a mean follow-up of 20 months (range, 2–69 months). The median tumor surface area positive for CA9 and CD31 was 7.8% and 8.1%, respectively. Although total expression of these markers lacked prognostic value in the entire cohort, nevertheless, high tumor compartment CD68 expression correlated with worse PFS (p = 0.033) and DMFS (p = 0.047). Also, high CD31 expression predicted for worse OS (p = 0.004), PFS (p = 0.008), LPFS (p = 0.014) and DMFS (p = 0.004) in patients with moderate density stroma. High stromal and peripheral compartment CD68 expression predicted for significantly worse outcome in patients with loose and moderate stroma density, respectively. Altogether, in contrast to the current notion, hypoxia levels in PDAC appear to be comparable to other malignancies. CD31 and CD68 constitute prognostic markers in patient subgroups that vary according to tumor compartment and stromal density. Our study provides important insight on the pathophysiology of PDAC and should be exploited for future treatments. PMID:27637082

  19. Expression of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa co-determines the prognosis of colon cancer patients.

    PubMed

    Peng, Yong-hai; Li, Jian-jun; Xie, Fang-wei; Chen, Jian-fang; Yu, Ying-hao; Ouyang, Xue-nong; Liang, Hou-jie

    2013-01-01

    Provirus integration site for Moloney murine leukemia virus (pim-1) is a proto-oncogene that is linked to the development and progression of several cancers. In this study, we evaluated pim-1 expression in tumors, tumor stroma and tumor-adjacent mucosa together as an independent prognostic factor for colon cancer patients. The study included 343 colon cancer patients. Immunohistochemical staining was used to detect pim-1. Multivariate cox regression for disease-free survival (DFS) were used to identify independent prognostic factors. Analytic hierarchy process (AHP) was used to calculate the weight of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa in order to obtain a Pim-1 total score (PTS) for recurrence and survival. Kaplan-Meier DFS curves and OS curves for patients with different pim-1 expression levels were compared using the log-rank test. In this study, four independent prognostic factors were identified for colon cancer patients: pim-1 expression in tumors, tumor stroma, tumor-adjacent mucosa, as well as tumor stage. It has been established that clinical stage is an important prognostic factor for colon cancer patients. However, PTS can identify the patients who are likely to recur not only in the whole radical excision group but also within each stage of this group. Based on the results of this study we can conclude that the PTS combined with clinical staging system may be a better predictor of colon cancer patients' prognosis than using the clinical stage system alone. ClinicalTrials.gov Number: ChiCTR-PRCH-12002842.

  20. Effects of Apparent Supersonic Ruptures for Strike-slip Rupture: Should We Consider it in the Seismic Hazard Analysis?

    NASA Astrophysics Data System (ADS)

    Barrows, M. B.; Shao, G.; Ji, C.

    2009-12-01

    Recent numerical studies indicated that the supersonic rupture could produce larger off-fault damage at distant sites than the sub-shear rupture, due to the famous "mach cone" effect (Dunham and Archuleta, 2005; Bhat et al, 2007). These results were obtained using the steady-state rupture simulations in a half-space earth. For more realistic layered or 3D earth models, we should also consider the effects of apparent supersonic rupture, i.e., the deep rupture is still in a speed slower than the local shear velocity, but faster than the near surface S or even the P wave velocity. The apparent super-shear rupture could excite the mach effect, but how large it is has not yet been quantitatively addressed. In this study, we explore this possibility by performing numerical simulations for pure strike-slip ruptures on a vertical fault inside various layered earth models.

  1. Supra-organization and optical anisotropies of the extracellular matrix in the amniotic membrane and limbal stroma before and after explant culture

    PubMed Central

    Valdetaro, Gisele P.; Aldrovani, Marcela; Padua, Ivan R. M.; Cristovam, Priscila C.; Gomes, José A. P.; Laus, José L.

    2016-01-01

    In this research we evaluated the supramolecular organizations and the optical anisotropical properties of the de-epithelialized human amniotic membrane and rabbit limbal stroma, before and after explant culture. Birefringence, monochromatic light spectral absorption and linear dichroism of the main extracellular matrix biopolymers, that is, the fibrillar collagens and proteoglycans, were investigated by polarized light microscopy combined with image analysis. Our results demonstrated that the culture procedure–induced stimuli altered the supra-organizational characteristics (in terms of collagens/proteoglycans spatial orientation and ordered-aggregational state) of the amniotic and limbal extracellular matrix, which led to changes in optical anisotropical properties. PMID:28018719

  2. Wavelength dependence of the apparent diameter of retinal blood vessels

    NASA Astrophysics Data System (ADS)

    Park, Robert; Twietmeyer, Karen; Chipman, Russell; Beaudry, Neil; Salyer, David

    2005-04-01

    Imaging of retinal blood vessels may assist in the diagnosis and monitoring of diseases such as glaucoma, diabetic retinopathy, and hypertension. However, close examination reveals that the contrast and apparent diameter of vessels are dependent on the wavelength of the illuminating light. In this study multispectral images of large arteries and veins within enucleated swine eyes are obtained with a modified fundus camera by use of intravitreal illumination. The diameters of selected vessels are measured as a function of wavelength by cross-sectional analysis. A fixed scale with spectrally independent dimension is placed above the retina to isolate the chromatic effects of the imaging system and eye. Significant apparent differences between arterial and venous diameters are found, with larger diameters observed at shorter wavelengths. These differences are due primarily to spectral absorption in the cylindrical blood column.

  3. On the apparent molar volumes of nonelectrolytes in water

    SciTech Connect

    Anderko, A.; Chan, J.P.; Pitzer, K.S. )

    1993-04-01

    Apparent molar volumes of aqueous solutions of argon and xenon have been calculated using a previously developed comprehensive equation of state for nonelectrolyte systems. The equation consists of a virial expansion truncated after the fourth virial coefficient and a closed-form term approximating higher coefficients. Mixing rules are based on the composition dependence of virial coefficients, which is known from statistical mechanics. The equation accurately represents vapor-liquid and gas-gas equilibria for the Ar + H[sub 2]O and Xe + H[sub 2]O systems over wide ranges of pressure and temperature using two binary parameters. With the binary parameters determined from phase equilibrium data, the equation accurately predicts apparent molar volumes V[sub [phi

  4. Apparent motion enhances visual rhythm discrimination in infancy.

    PubMed

    Brandon, Melissa; Saffran, Jenny R

    2011-05-01

    Many studies have demonstrated that infants exhibit robust auditory rhythm discrimination, but research on infants' perception of visual rhythm is limited. In particular, the role of motion in infants' perception of visual rhythm remains unknown, despite the prevalence of motion cues in naturally occurring visual rhythms. In the present study, we examined the role of motion in 7-month-old infants' discrimination of visual rhythms by comparing experimental conditions with apparent motion in the stimuli versus stationary rhythmic stimuli. Infants succeeded at discriminating visual rhythms only when the visual rhythm occurred with an apparent motion component. These results support the view that motion plays a role in infants' perception of visual temporal information, consistent with the manner in which natural rhythms appear in the visual world.

  5. Apparent optical density of the scattering medium: influence of scattering

    NASA Astrophysics Data System (ADS)

    Kiseleva, Irina A.; Sinichkin, Yurii P.

    2002-07-01

    Comparative analysis of manifestation of finite absorption in scattering media is carried out for different detection geometries. Reflectance spectra were studied for phantom scattering media containing blood and melanin as absorbers. Apparent optical density spectra of phantom media are compared with similar spectra of water solutions of the blood and melanin for same concentrations of absorbers. The influence of scattering properties on optical density spectra is discussed with use of the model of diffuse light propagation in semi-infinite media.

  6. Apparent Explosion Moments from Rg Waves Recorded on SPE

    DOE PAGES

    Larmat, Carene; Rougier, Esteban; Patton, Howard John

    2016-11-29

    Seismic moments for the first four chemical tests making up phase I of the Source Physics Experiments (SPE) are estimated from 6-Hz Rg waves recorded along a single radial line of geophones under the assumption that the tests are pure explosions. These apparent explosion moments are compared with moments determined from the reduced displacement potential method applied to free-field data. Light detection and ranging (lidar) observations, strong ground motions on the free surface in the vicinity of ground zero, and moment tensor inversion results are evidence that the fourth test SPE-4P is a pure explosion, and the moments show goodmore » agreement, 8×1010 N·m for free-field data versus 9×1010 N·m for Rg waves. In stark contrast, apparent moments for the first three tests are smaller than near-field moments by factors of 3–4. Relative amplitudes for the three tests determined from Rg interferometry using SPE-4P as an empirical Green’s function indicate that radiation patterns are cylindrically symmetric within a factor of 1.25 (25%). This fact assures that the apparent moments are reliable even though they were measured on just one azimuth. Spallation occurred on the first three tests, and ground-based lidar detected permanent deformations. As such, the source medium suffered late-time damage. In conclusion, destructive interference between Rg waves radiated by explosion and damage sources will reduce amplitudes and explain why apparent moments are smaller than near-field moments based on compressional energy emitted directly from the source.« less

  7. Apparent Explosion Moments from Rg Waves Recorded on SPE

    SciTech Connect

    Larmat, Carene; Rougier, Esteban; Patton, Howard John

    2016-11-29

    Seismic moments for the first four chemical tests making up phase I of the Source Physics Experiments (SPE) are estimated from 6-Hz Rg waves recorded along a single radial line of geophones under the assumption that the tests are pure explosions. These apparent explosion moments are compared with moments determined from the reduced displacement potential method applied to free-field data. Light detection and ranging (lidar) observations, strong ground motions on the free surface in the vicinity of ground zero, and moment tensor inversion results are evidence that the fourth test SPE-4P is a pure explosion, and the moments show good agreement, 8×1010 N·m for free-field data versus 9×1010 N·m for Rg waves. In stark contrast, apparent moments for the first three tests are smaller than near-field moments by factors of 3–4. Relative amplitudes for the three tests determined from Rg interferometry using SPE-4P as an empirical Green’s function indicate that radiation patterns are cylindrically symmetric within a factor of 1.25 (25%). This fact assures that the apparent moments are reliable even though they were measured on just one azimuth. Spallation occurred on the first three tests, and ground-based lidar detected permanent deformations. As such, the source medium suffered late-time damage. In conclusion, destructive interference between Rg waves radiated by explosion and damage sources will reduce amplitudes and explain why apparent moments are smaller than near-field moments based on compressional energy emitted directly from the source.

  8. Mass density at geostationary orbit and apparent mass refilling

    NASA Astrophysics Data System (ADS)

    Denton, R. E.; Takahashi, Kazue; Amoh, Justice; Singer, H. J.

    2016-04-01

    We used the inferred equatorial mass density ρm,eq based on measurements of Alfvén wave frequencies measured by the GOES satellites during 1980-1991 in order to construct a number of different models of varying complexity for the equatorial mass density at geostationary orbit. The most complicated models are able to account for 66% of the variance with a typical variation from actual values of a factor of 1.56. The factors that influenced ρm,eq in the models were, in order of decreasing importance, the F10.7 EUV index, magnetic local time, the solar wind dynamic pressure Pdyn, the phase of the year, and the solar wind BZ (GSM Z direction). During some intervals, some of which were especially geomagnetically quiet, ρm,eq rose to values that were significantly higher than those predicted by our models. For 10 especially quiet intervals, we examined long-term (>1 day) apparent refilling, the increase in ρm,eq at a fixed location. We found that the behavior of ρm,eq varies for different events. In some cases, there is significant apparent refilling, whereas in other cases ρm,eq stays the same or even decreases slightly. Nevertheless, we showed that on average, ρm,eq increases exponentially during quiet intervals. There is variation of apparent refilling with respect to the phase of the solar cycle. On the third day of apparent refilling, ρm,eq has on average a similar value at solar maximum or solar minimum, but at solar maximum, ρm,eq begins with a larger value and rises relatively less than at solar minimum.

  9. Apparent competition with an exotic plant reduces native plant establishment.

    PubMed

    Orrock, John L; Witter, Martha S; Reichman, O J

    2008-04-01

    Biological invasions can change ecosystem function, have tremendous economic costs, and impact human health; understanding the forces that cause and maintain biological invasions is thus of immediate importance. A mechanism by which exotic plants might displace native plants is by increasing the pressure of native consumers on native plants, a form of indirect interaction termed "apparent competition." Using experimental exclosures, seed addition, and monitoring of small mammals in a California grassland, we examined whether exotic Brassica nigra increases the pressure of native consumers on a native bunchgrass, Nassella pulchra. Experimental plots were weeded to focus entirely on indirect effects via consumers. We demonstrate that B. nigra alters the activity of native small-mammal consumers, creating a gradient of consumption that dramatically reduces N. pulchra establishment. Previous work has shown that N. pulchra is a strong competitor, but that it is heavily seed limited. By demonstrating that consumer pressure is sufficient to curtail establishment, our work provides a mechanism for this seed limitation and suggests that, despite being a good competitor, N. pulchra cannot reestablish close to B. nigra within its old habitats because exotic-mediated consumption preempts direct competitive exclusion. Moreover, we find that apparent competition has a spatial extent, suggesting that consumers may dictate the rate of invasion and the area available for restoration, and that nonspatial studies of apparent competition may miss important dynamics.

  10. Coherent and random apparent stresses in periodically unsteady flows

    NASA Astrophysics Data System (ADS)

    Kehoe, Anthony Byrd

    1990-08-01

    The transitional flow field downstream of a smooth, symmetrically constricted Sylgard pipe was measured with a two color, two component Laser Doppler Anemometer for both pulsatile and steady flows. Vibrations in the flow system were induced with an exciter/shaker and were monitored with an accelerator. The vibration has little effect on the value of the maximum axial and radial turbulence intensities. A frequency domain signal processing technique to separate the disturbance velocity into coherent and random components was modified to guarantee that the sum of the decomposed velocity components equaled the original disturbance velocity. Results of the velocity separation demonstrated that the velocity disturbances prior to turbulent transition consisted almost entirely of coherent velocity fluctuations. The maximum apparent shear stress was found to occur just after the turbulent transition and consisted almost entirely of the random component. The data suggest that if the absolute magnitude of the apparent stress is the determining factor in red blood cell destruction, then the coherent apparent stress is not a significant destruction mechanism. However, the exact mechanism in hemolysis are not identified.

  11. Product design enhancement using apparent usability and affective quality.

    PubMed

    Seva, Rosemary R; Gosiaco, Katherine Grace T; Santos, Ma Crea Eurice D; Pangilinan, Denise Mae L

    2011-03-01

    In this study, apparent usability and affective quality were integrated in a design framework called the Usability Perception and Emotion Enhancement Model (UPEEM). The UPEEM was validated using structural equation modeling (SEM). The methodology consists of four phases namely product selection, attribute identification, design alternative generation, and design alternative evaluation. The first stage involved the selection of a product that highly involves the consumer. In the attribute identification stage, design elements of the product were identified. The possible values of these elements were also determined for use in the experimentation process. Design of experiments was used to identify how the attributes will be varied in the design alternative stage and which of the attributes significantly contribute to affective quality, apparent usability, and desirability in the design evaluation stage. Results suggest that product attributes related to form are relevant in eliciting intense affect and perception of usability in mobile phones especially those directly related to functionality and aesthetics. This study considered only four product attributes among so many due to the constraints of the research design employed. Attributes related to aesthetic perception of a product enhance apparent usability such as those related to dimensional ratios.

  12. Deep learning in bioinformatics.

    PubMed

    Min, Seonwoo; Lee, Byunghan; Yoon, Sungroh

    2016-07-29

    In the era of big data, transformation of biomedical big data into valuable knowledge has been one of the most important challenges in bioinformatics. Deep learning has advanced rapidly since the early 2000s and now demonstrates state-of-the-art performance in various fields. Accordingly, application of deep learning in bioinformatics to gain insight from data has been emphasized in both academia and industry. Here, we review deep learning in bioinformatics, presenting examples of current research. To provide a useful and comprehensive perspective, we categorize research both by the bioinformatics domain (i.e. omics, biomedical imaging, biomedical signal processing) and deep learning architecture (i.e. deep neural networks, convolutional neural networks, recurrent neural networks, emergent architectures) and present brief descriptions of each study. Additionally, we discuss theoretical and practical issues of deep learning in bioinformatics and suggest future research directions. We believe that this review will provide valuable insights and serve as a starting point for researchers to apply deep learning approaches in their bioinformatics studies.

  13. Deep subsurface microbial processes

    USGS Publications Warehouse

    Lovley, D.R.; Chapelle, F.H.

    1995-01-01

    Information on the microbiology of the deep subsurface is necessary in order to understand the factors controlling the rate and extent of the microbially catalyzed redox reactions that influence the geophysical properties of these environments. Furthermore, there is an increasing threat that deep aquifers, an important drinking water resource, may be contaminated by man's activities, and there is a need to predict the extent to which microbial activity may remediate such contamination. Metabolically active microorganisms can be recovered from a diversity of deep subsurface environments. The available evidence suggests that these microorganisms are responsible for catalyzing the oxidation of organic matter coupled to a variety of electron acceptors just as microorganisms do in surface sediments, but at much slower rates. The technical difficulties in aseptically sampling deep subsurface sediments and the fact that microbial processes in laboratory incubations of deep subsurface material often do not mimic in situ processes frequently necessitate that microbial activity in the deep subsurface be inferred through nonmicrobiological analyses of ground water. These approaches include measurements of dissolved H2, which can predict the predominant microbially catalyzed redox reactions in aquifers, as well as geochemical and groundwater flow modeling, which can be used to estimate the rates of microbial processes. Microorganisms recovered from the deep subsurface have the potential to affect the fate of toxic organics and inorganic contaminants in groundwater. Microbial activity also greatly influences 1 the chemistry of many pristine groundwaters and contributes to such phenomena as porosity development in carbonate aquifers, accumulation of undesirably high concentrations of dissolved iron, and production of methane and hydrogen sulfide. Although the last decade has seen a dramatic increase in interest in deep subsurface microbiology, in comparison with the study of

  14. Ultrafine fibrous gelatin scaffolds with deep cell infiltration mimicking 3D ECMs for soft tissue repair.

    PubMed

    Jiang, Qiuran; Xu, Helan; Cai, Shaobo; Yang, Yiqi

    2014-07-01

    In this research, ultrafine fibrous scaffolds with deep cell infiltration and sufficient water stability have been developed from gelatin, aiming to mimic the extracellular matrices (ECMs) as three dimensional (3D) stromas for soft tissue repair. The ultrafine fibrous scaffolds produced from the current technologies of electrospinning and phase separation are either lack of 3D oriented fibrous structure or too compact to be penetrated by cells. Whilst electrospun scaffolds are able to emulate two dimensional (2D) ECMs, they cannot mimic the 3D ECM stroma. In this work, ultralow concentration phase separation (ULCPS) has been developed to fabricate gelatin scaffolds with 3D randomly oriented ultrafine fibers and loose structures. Besides, a non-toxic citric acid crosslinking system has been established for the ULCPS method. This system could endow the scaffolds with sufficient water stability, while maintain the fibrous structures of scaffolds. Comparing with electrospun scaffolds, the ULCPS scaffolds showed improved cytocompatibility and more importantly, cell infiltration. This research has proved the possibility of using gelatin ULCPS scaffolds as the substitutes of 3D ECMs.

  15. Apparent chlorofluorocarbon age of ground water of the shallow aquifer system, Naval Weapons Station Yorktown, Yorktown, Virginia

    USGS Publications Warehouse

    Nelms, David L.; Harlow,, George E.; Brockman, Allen R.

    2001-01-01

    reporting limit of 0.3 to 15.9 tritium units (TU) with a median value of 10.8 TU. Water-quality field properties are highly variable for ground water with apparent CFC ages less than 15 years because of geochemical processes within local flow systems. Ground water with apparent CFC ages greater than 15 years represents more stable conditions in subregional flow systems. The range of apparent CFC ages is slightly greater than the ranges in time of travel of ground water calculated for shallow wells (less than 60- feet deep) from flow-path analysis. Calculated travel times to springs can be up to two orders of magnitude greater than the CFC-based apparent ages. Reasonable assumptions of values for hydraulic parameters can result in substantial overestimates for time of travel to springs. Recharge rates computed from apparent CFC ages range from 0.29 to 0.89 feet per year (ft/ yr) with an average value of 0.54 ft/yr. The analysis of apparent CFC ages in conjunction with geohydrologic data indicates that young water (less than 50 years) is present at depth (nearly 120 feet) and that both local and subregional flow systems occur in the shallow aquifer system at the Station. The addition of the dimension of time to the three-dimensional framework of Brockman and others (1997) will benefit current (2001) and future remediation activities by providing estimates of advective transport rates and how these rates vary depending upon geohydrologic setting and position within the ground-water-flow system. Estimated ground-water apparent ages and recharge rates can be used as calibration criteria in simulations of ground-water flow on the Station to refine and constrain future ground-water-flow models of the shallow aquifer system.

  16. A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice.

    PubMed

    Lopez, M Veronica; Rivera, Angel A; Viale, Diego L; Benedetti, Lorena; Cuneo, Nicasio; Kimball, Kristopher J; Wang, Minghui; Douglas, Joanne T; Zhu, Zeng B; Bravo, Alicia I; Gidekel, Manuel; Alvarez, Ronald D; Curiel, David T; Podhajcer, Osvaldo L

    2012-12-01

    Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 10(10) v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15-40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression.

  17. Functional and molecular mapping of uncoupling between vascular permeability and loss of vascular maturation in ovarian carcinoma xenografts: the role of stroma cells in tumor angiogenesis.

    PubMed

    Gilad, Assaf A; Israely, Tomer; Dafni, Hagit; Meir, Gila; Cohen, Batya; Neeman, Michal

    2005-11-01

    Maintaining homogeneous perfusion in tissues undergoing remodeling and vascular expansion requires tight orchestration of the signals leading to endothelial sprouting and subsequent recruitment of perivascular contractile cells and vascular maturation. This regulation, however, is frequently disrupted in tumors. We previously demonstrated the role of tumor-associated myofibroblasts in vascularization and exit from dormancy of human ovarian carcinoma xenografts in nude mice. The aim of this work was to determine the contribution of stroma- and tumor cell-derived angiogenic growth factors to the heterogeneity of vascular permeability and maturation in MLS human ovarian carcinoma tumors. We show by RT-PCR and by in situ hybridization that VEGF was expressed by the tumor cells, while angiopoietin-1 and -2 were expressed only by the infiltrating host stroma cells. Vascular maturation was detected in vivo by vasoreactivity to hypercapnia, measured by BOLD contrast MRI and validated by immunostaining of histologic sections to alpha-smooth muscle actin. Vascular permeability was measured in vivo by dynamic contrast-enhanced MRI using albumin-based contrast material and validated in histologic sections by fluorescent staining of the biotinylated contrast material. MRI as well as histologic correlation maps between vascular maturation and vascular permeability revealed a wide range of vascular phenotypes, in which the distribution of vascular maturation and vasoreactivity did not overlap spatially with reduced permeability. The large heterogeneity in the degree of vascular maturation and permeability is consistent with the differential expression pattern of VEGF and angiopoietins during tumor angiogenesis.

  18. Photosynthesis under osmotic stress : Effect of high solute concentrations on the permeability properties of the chloroplast envelope and on activity of stroma enzymes.

    PubMed

    Kaiser, W M; Heber, U

    1981-12-01

    1. Increasing the sorbitol concentration in a suspension of intact chloroplasts induced a fast, transient and not very specific efflux of metabolites from chloroplasts to the medium. Stroma proteins were retained by the chloroplasts. 2. Within the first 30 s following hypertonic stress, the chloroplast volume decreased according to the Boyle-Mariotte relation. A subsequent and transient increase suggested some influx of external solute. 3. Dark reactions of intact chloroplasts such as starch degradation and formation of labelled 3-phosphoglycerate from dihydroxyacetone phosphate or ribose-5-phosphate and (14)CO2 were inhibited at low water potentials. After chloroplast rupture, the activity of stromal enzymes was decreased by high solute concentrations. Ribulose bisphosphate carboxylase exhibited a decrease of Vmax, while KmCO 2 remained unaltered. With sorbitol, sucrose, glycerol or glycinebetaine, 50% inhibition of enzymes was observed at osmotic potentials between 40 and 50 bar, with ethyleneglycol at about 70 bar. With salts such as KCl, 50% inhibition was found at 15 to 20 bar. 4. A comparison between inhibition of photosynthesis in intact chloroplasts and inhibition of enzymes in stroma extracts by solutes supports the notion that inhibition of photosynthesis at high osmotic potentials is mainly a solute effect. Another factor contributing to inhibition of photosynthesis in isolated chloroplasts is the loss of intermediates and cofactors which occurs during rapid osmotic dehydration.

  19. A Tumor-stroma Targeted Oncolytic Adenovirus Replicated in Human Ovary Cancer Samples and Inhibited Growth of Disseminated Solid Tumors in Mice

    PubMed Central

    Lopez, M Veronica; Rivera, Angel A; Viale, Diego L; Benedetti, Lorena; Cuneo, Nicasio; Kimball, Kristopher J; Wang, Minghui; Douglas, Joanne T; Zhu, Zeng B; Bravo, Alicia I; Gidekel, Manuel; Alvarez, Ronald D; Curiel, David T; Podhajcer, Osvaldo L

    2012-01-01

    Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 1010 v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15–40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression. PMID:22948673

  20. Ovarian steroids, mitogen-activated protein kinases, and/or aspartic proteinases cooperate to control endometrial remodeling by regulating gene expression in the stroma and glands.

    PubMed

    Gaide Chevronnay, Héloïse P; Lemoine, Pascale; Courtoy, Pierre J; Marbaix, Etienne; Henriet, Patrick

    2010-09-01

    Explants from nonmenstrual endometria cultured in the absence of ovarian hormones undergo tissue breakdown. Addition of estradiol and progesterone (EP) prevents proteolysis. Explants include stromal and epithelial compartments which play different but complementary roles in endometrial physiology, including tissue remodeling and hormonal response. In order to characterize the cell type-specific contribution to regulation of tissue breakdown, we characterized the transcriptomes of microdissected stromal and glandular areas from endometrial explants cultured with or without EP. The datasets were also compared to other published endometrial transcriptomes. Finally, the contribution of proteolysis, hypoxia, and MAPKs to the regulation of selected genes was further investigated in explant culture. This analysis identified distinct gene expression profiles in stroma and glands, with differential response to EP, but functional clustering underlined convergence in biological processes, further indicating that endometrial remodeling requires cooperation between the two compartments through expression of cell type-specific genes. Only partial overlaps were observed between lists of genes involved in different occurrences of endometrial breakdown, pointing to a limited number of potentially crucial regulators but also to the requirement for additional mechanisms controlling tissue remodeling. We identified a group of genes differentially regulated by EP in stroma and glands among which some were sensitive to MAPKs and/or aspartic proteinases and were not induced by hypoxia. In conclusion, MAPKs and/or aspartic proteinases likely act in concert with EP to locally and specifically control differential expression of genes between degrading and preserved areas of the human endometrium.

  1. The deep space network

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Progress is reported in flight project support, tracking and data acquisition research and technology, network engineering, hardware and software implementation, and operations. The functions and facilities of the Deep Space Network are emphasized.

  2. Nurturing Deep Connections.

    ERIC Educational Resources Information Center

    Kessler, Rachael

    2002-01-01

    Argues that the missing ingredient in school reform is soul, that is, deep connections among students, teachers, and administrators. Discusses five principles of leadership with soul: Personalize, pacing, permission, protection, and paradox. (PKP)

  3. The deep space network

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The functions and facilities of the Deep Space Network are considered. Progress in flight project support, tracking and data acquisition research and technology, network engineering, hardware and software implementation, and operations is reported.

  4. Deep Vein Thrombosis

    MedlinePlus

    ... vein swells, the condition is called thrombophlebitis. A deep vein thrombosis can break loose and cause a serious problem in the lung, called a pulmonary embolism. Sitting still for a long time can make ...

  5. The deep space network

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The facilities, programming system, and monitor and control system for the deep space network are described. Ongoing planetary and interplanetary flight projects are reviewed, along with tracking and ground-based navigation, communications, and network and facility engineering.

  6. Deep Vein Thrombosis (DVT)

    MedlinePlus

    ... helps reduce the chances that your blood will pool and clot. You should wear these stockings during ... Make lifestyle changes. Lose weight and quit smoking. Obesity and smoking increase your risk of deep vein ...

  7. The Deep Space Network

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Progress on the Deep Space Network (DSN) supporting research and technology, advanced development, engineering and implementation, and DSN operations is presented. The functions and facilities of the DSN are described.

  8. The deep space network

    NASA Technical Reports Server (NTRS)

    1979-01-01

    A report is given of the Deep Space Networks progress in (1) flight project support, (2) tracking and data acquisition research and technology, (3) network engineering, (4) hardware and software implementation, and (5) operations.

  9. The Deep Space Network

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The various systems and subsystems are discussed for the Deep Space Network (DSN). A description of the DSN is presented along with mission support, program planning, facility engineering, implementation and operations.

  10. The deep space network

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A Deep Space Network progress report is presented dealing with in flight project support, tracking and data acquisition research and technology, network engineering, hardware and software implementation, and operations.

  11. The deep space network

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The objectives, functions, and organization of the Deep Space Network are summarized along with deep space station, ground communication, and network operations control capabilities. Mission support of ongoing planetary/interplanetary flight projects is discussed with emphasis on Viking orbiter radio frequency compatibility tests, the Pioneer Venus orbiter mission, and Helios-1 mission status and operations. Progress is also reported in tracking and data acquisition research and technology, network engineering, hardware and software implementation, and operations.

  12. Exploration for deep coal

    SciTech Connect

    2008-12-15

    The most important factor in safe mining is the quality of the roof. The article explains how the Rosebud Mining Co. conducts drilling and exploration in 11 deep coal mine throughout Pennsylvania and Ohio. Rosebud uses two Atlas Copco CS10 core drilling rigs mounted on 4-wheel drive trucks. The article first appeared in Atlas Copco's in-house magazine, Deep Hole Driller. 3 photos.

  13. Diagnosing Deep Venous Thrombosis

    PubMed Central

    Doyle, D. Lynn

    1992-01-01

    Patients often present with unexplained lower limb pain and swelling. It is important to exclude deep venous thrombosis in the diagnosis because of the threat of sudden death. Simple clinical diagnosis is unacceptable, and noninvasive tests should be used initially. Serial testing detects proximal extension of isolated calf thrombi. Multiple diagnostic modalities are employed to diagnose a new deep venous thrombosis in patients with postphlebitic syndrome. PMID:21221369

  14. The Deep Space Network

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The objectives, functions, and organization, of the Deep Space Network are summarized. Deep Space stations, ground communications, and network operations control capabilities are described. The network is designed for two-way communications with unmanned spacecraft traveling approximately 1600 km from earth to the farthest planets in the solar system. It has provided tracking and data acquisition support for the following projects: Ranger, Surveyor, Mariner, Pioneer, Apollo, Helios, Viking, and the Lunar Orbiter.

  15. Deep divergence and apparent sex-biased dispersal revealed by a Y-linked marker in rainbow trout

    PubMed Central

    Brunelli, Joseph P.; Steele, Craig A.; Thorgaard, Gary H.

    2010-01-01

    Y-chromosome and mitochondrial DNA markers can reveal phylogenetic patterns by allowing tracking of male and female lineages, respectively. We used sequence data from a recently discovered Y-linked marker and a mitochondrial marker to examine phylogeographic structure in the widespread and economically important rainbow trout (Oncorhynchus mykiss). Two distinct geographic groupings that generally correspond to coastal and inland subspecies were evident within the Y marker network while the mtDNA haplotype network showed little geographic structure. Our results suggest that male-specific behavior has prevented widespread admixture of Y haplotypes and that gene flow between the coastal and inland subspecies has largely occurred through females. This new Y marker may also aid conservation efforts by genetically identifying inland populations that have not hybridized with widely stocked coastal-derived hatchery fish. PMID:20546904

  16. Identifying apparent velocity changes in cross correlated microseism noise data

    NASA Astrophysics Data System (ADS)

    Friderike Volk, Meike; Bean, Christopher; Lokmer, Ivan; Pérez, Nemesio; Ibáñez, Jesús

    2015-04-01

    Currently there is a strong interest of using cross correlation of ambient noise to retrieve Green's functions. These are usually used to calculate the seismic wave velocity of the subsurface and therefore can be used for subsurface imaging or monitoring of various geological settings where we expect rapid velocity changes (e.g. reservoirs or volcanoes). The assumption of this method is that the wavefields which are correlated must be diffuse. This criterion is fulfilled if the ambient noise sources are uniformly distributed or the scattering in the medium is high enough to mitigate any source directivity. The location of the sources is usually unknown and it can change in time. These temporal and spatial variations of the microseism noise sources may lead to changes in the retrieved Green's functions, and so, to the apparent changes in seismic wave velocities. To further investigate the apparent changes in Green's functions we undertook an active seismic experiment in Tenerife lasting three months. A small airgun was used as an active source and was shooting repeatedly every 15 minutes. The shots and the microseism noise were recorded at several seismic stations at the same time. That data set gives us the opportunity to compare the changes in seismic wave velocity recovered through cross correlation of ambient noise and changes we measure through active shots from the airgun. The aim is to distinguish between apparent seismic velocity changes and seismic velocity changes caused by changes in the medium. We also use the data set to track the direction of the microseism noise sources to see if changes which are only recovered through cross correlation can be related to temporal and spatial variations of the microseism noise sources.

  17. Laryngospasm With Apparent Aspiration During Sedation With Nitrous Oxide.

    PubMed

    Babl, Franz E; Grindlay, Joanne; Barrett, Michael Joseph

    2015-11-01

    Nitrous oxide and oxygen mixture has become increasingly popular for the procedural sedation and analgesia of children in the emergency department. In general, nitrous oxide is regarded as a very safe agent according to large case series. We report a case of single-agent nitrous oxide sedation of a child, complicated by laryngospasm and radiographically confirmed bilateral upper lobe pulmonary opacities. Although rarely reported with parenteral sedative agents, laryngospasm and apparent aspiration has not been previously reported in isolated nitrous oxide sedation. This case highlights that, similar to other sedative agents, nitrous oxide administration also needs to be conducted by staff and in settings in which airway emergencies can be appropriately managed.

  18. Apparent asystole: are we missing a lifesaving opportunity?

    PubMed Central

    Limb, Christopher; Siddiqui, Muhammad A

    2015-01-01

    The use of ultrasonography is rapidly expanding in emergency medicine. Real-time assessment offers clues to prompt diagnosis and creates opportunities for speedy intervention. We present a case of ‘cardiac monitor asystole’ that proved to be ventricular fibrillation on ultrasound examination. Uniquely this case demonstrates that this, typically unrecognised, form of ventricular fibrillation responds to desynchronised defibrillation, with restoration of perfusion for approximately 30 min. With increasing access to ultrasound we believe that further research is indicated to determine whether some cases of apparent asystole may best be treated by defibrillation, presenting an opportunity to save more lives than current protocols achieve. PMID:25777487

  19. Study on Apparent Viscosity and Structure of Foaming Slag

    NASA Astrophysics Data System (ADS)

    Martinsson, Johan; Glaser, Björn; Sichen, Du

    2016-10-01

    Foaming slag was generated using induction heating. The foam was found non-Newtonian having much higher apparent viscosity compared to the dynamic viscosity of pure slag. Quenched foam was examined. The appearance of the foaming slag was very different from silicone oil-gas foam. The size of gas bubbles ranged from 0.1 to 4 mm (while in the case of silicone oil, 1 to 2 mm). The gas fraction in the foam was considerably lower than in the case of silicone oil.

  20. Apparent evaporative resistance at critical conditions for five clothing ensembles.

    PubMed

    Caravello, Victor; McCullough, Elizabeth A; Ashley, Candi D; Bernard, Thomas E

    2008-09-01

    A limiting factor for clothing ensembles inherent during heat stress exposures is the evaporative resistance, which can be used to compare candidate ensembles and in rational models of heat exchange. In this study, the apparent total evaporative resistance of five clothing ensembles (cotton work clothes, cotton coveralls, and coveralls made of Tyvek 1424 and 1427, NexGen and Tychem QC was estimated empirically from wear trials using a progressive heat stress protocol and from clothing insulation adjustments based on ISO 9920 (2007) and wetness. The metabolic rate was moderate at 165 W m(-2) and relative humidity was held at 50%. Twenty-nine heat-acclimated participants (20 men and 9 women) completed trials for all clothing ensembles. A general linear mixed effects model (ensemble and participants as a random effect) was used to analyze the data. Significant differences (p < 0.0001) among ensembles were observed for apparent total evaporative resistance. As expected, Tychem QC had the highest apparent total evaporative resistance at 0.033 kPa m(2) W(-1). NexGen was next at 0.017 kPa m(2) W(-1). These were followed by Tyvek 1424 at 0.015 kPa m(2) W(-1), and Tyvek 1427, Cotton Coveralls and Work Clothes all at 0.013 kPa m(2) W(-1). This wear test method improves on past methods using the progressive protocol to determine evaporative resistance by including the effects of movement, air motion and wetness on the estimate of clothing insulation. The pattern of evaporative resistance is the same as that for critical WBGTs and a linear relationship between apparent total evaporative resistance and WBGT clothing adjustment factor is suggested. With the large sample size, a good estimate of sample variance associated with progressive method can be made, where the standard error is 0.0044 kPa m(2) W(-1) with a 95% confidence interval of 0.0040-0.0050 kPa m(2) W(-1).

  1. Downscaling Smooth Tomographic Models: Separating Intrinsic and Apparent Anisotropy

    NASA Astrophysics Data System (ADS)

    Bodin, Thomas; Capdeville, Yann; Romanowicz, Barbara

    2016-04-01

    In recent years, a number of tomographic models based on full waveform inversion have been published. Due to computational constraints, the fitted waveforms are low pass filtered, which results in an inability to map features smaller than half the shortest wavelength. However, these tomographic images are not a simple spatial average of the true model, but rather an effective, apparent, or equivalent model that provides a similar 'long-wave' data fit. For example, it can be shown that a series of horizontal isotropic layers will be seen by a 'long wave' as a smooth anisotropic medium. In this way, the observed anisotropy in tomographic models is a combination of intrinsic anisotropy produced by lattice-preferred orientation (LPO) of minerals, and apparent anisotropy resulting from the incapacity of mapping discontinuities. Interpretations of observed anisotropy (e.g. in terms of mantle flow) requires therefore the separation of its intrinsic and apparent components. The "up-scaling" relations that link elastic properties of a rapidly varying medium to elastic properties of the effective medium as seen by long waves are strongly non-linear and their inverse highly non-unique. That is, a smooth homogenized effective model is equivalent to a large number of models with discontinuities. In the 1D case, Capdeville et al (GJI, 2013) recently showed that a tomographic model which results from the inversion of low pass filtered waveforms is an homogenized model, i.e. the same as the model computed by upscaling the true model. Here we propose a stochastic method to sample the ensemble of layered models equivalent to a given tomographic profile. We use a transdimensional formulation where the number of layers is variable. Furthermore, each layer may be either isotropic (1 parameter) or intrinsically anisotropic (2 parameters). The parsimonious character of the Bayesian inversion gives preference to models with the least number of parameters (i.e. least number of layers, and

  2. An apparently gluten-induced photosensitivity in horses.

    PubMed

    Yeruham, I; Avidar, Y; Perl, S

    1999-12-01

    Primary photosensitization was observed in 3 Appaloosa mares. The skin lesions were diffuse erythema followed by edema and subsequently weeping and finally dry gangrene and ulceration. The severe photosensitivity dermatitis was apparently induced by gluten ingestion. Resolution of lesions occurred after withdrawal of the suspected dairy concentrate feed and prevention of exposure to sunlight. Neither the ponies nor donkey, which were not fed with the suspected concentrate, exhibited similar skin lesions or other clinical abnormalities. Gluten metabolites may contain photodynamic agents that cause photosensitization in horses.

  3. Mechanical Components from Highly Recoverable, Low Apparent Modulus Materials

    NASA Technical Reports Server (NTRS)

    Padula, Santo, II (Inventor); Noebe, Ronald D. (Inventor); Stanford, Malcolm K. (Inventor); DellaCorte, Christopher (Inventor)

    2015-01-01

    A material for use as a mechanical component is formed of a superelastic intermetallic material having a low apparent modulus and a high hardness. The superelastic intermetallic material is conditioned to be dimensionally stable, devoid of any shape memory effect and have a stable superelastic response without irrecoverable deformation while exhibiting strains of at least 3%. The method of conditioning the superelastic intermetallic material is described. Another embodiment relates to lightweight materials known as ordered intermetallics that perform well in sliding wear applications using conventional liquid lubricants and are therefore suitable for resilient, high performance mechanical components such as gears and bearings.

  4. Fingerprints of determinism in an apparently stochastic corrosion process.

    PubMed

    Rivera, M; Uruchurtu-Chavarín, J; Parmananda, P

    2003-05-02

    We detect hints of determinism in an apparently stochastic corrosion problem. This experimental system has industrial relevance as it mimics the corrosion processes of pipelines transporting water, hydrocarbons, or other fuels to remote destinations. We subject this autonomous system to external periodic perturbations. Keeping the amplitude of the superimposed perturbations constant and varying the frequency, the system's response is analyzed. It reveals the presence of an optimal forcing frequency for which maximal response is achieved. These results are consistent with those for a deterministic system and indicate a classical resonance between the forcing signal and the autonomous dynamics. Numerical studies using a generic corrosion model are carried out to complement the experimental findings.

  5. Apparent quasar disc sizes in the "bird's nest" paradigm

    NASA Astrophysics Data System (ADS)

    Abolmasov, P.

    2017-04-01

    Context. Quasar microlensing effects make it possible to measure the accretion disc sizes around distant supermassive black holes that are still well beyond the spatial resolution of contemporary instrumentation. The sizes measured with this technique appear inconsistent with the standard accretion disc model. Not only are the measured accretion disc sizes larger, but their dependence on wavelength is in most cases completely different from the predictions of the standard model. Aims: We suggest that these discrepancies may arise not from non-standard accretion disc structure or systematic errors, as it was proposed before, but rather from scattering and reprocession of the radiation of the disc. In particular, the matter falling from the gaseous torus and presumably feeding the accretion disc may at certain distances become ionized and produce an extended halo that is free from colour gradients. Methods: A simple analytical model is proposed assuming that a geometrically thick translucent inflow acts as a scattering mirror changing the apparent spatial properties of the disc. This inflow may be also identified with the broad line region or its inner parts. Results: Such a model is able to explain the basic properties of the apparent disc sizes, primarily their large values and their shallow dependence on wavelength. The only condition required is to scatter a significant portion of the luminosity of the disc. This can easily be fulfilled if the scattering inflow has a large geometrical thickness and clumpy structure.

  6. Pore fluid pressure, apparent friction, and Coulomb failure

    USGS Publications Warehouse

    Beeler, N.M.; Simpson, R.W.; Hickman, S.H.; Lockner, D.A.

    2000-01-01

    Many recent studies of stress-triggered seismicity rely on a fault failure model with a single free parameter, the apparent coefficient of friction, presumed to be a material constant with possible values 0 ≤ μ′ ≤ 1. These studies may present a misleading view of fault strength and the role of pore fluid pressure in earthquake failure. The parameter μ′ is intended to incorporate the effects of both friction and pore pressure, but is a material constant only if changes in pore fluid pressure induced by changes in stress are proportional to the normal stress change across the potential failure plane. Although specific models of fault zones permit such a relation, neither is it known that fault zones within the Earth behave this way, nor is this behavior expected in all cases. In contrast, for an isotropic homogeneous poroelastic model the pore pressure changes are proportional to changes in mean stress, μ′ is not a material constant, and −∞ ≤ μ′ ≤ +∞. Analysis of the change in Coulomb failure stress for tectonically loaded reverse and strike-slip faults shows considerable differences between these two pore pressure models, suggesting that such models might be distinguished from one another using observations of triggered seismicity (e.g., aftershocks). We conclude that using the constant apparent friction model exclusively in studies of Coulomb failure stress is unwise and could lead to significant errors in estimated stress change and seismic hazard.

  7. Cause of heart murmurs in 57 apparently healthy cats.

    PubMed

    Dirven, M J M; Cornelissen, J M M; Barendse, M A M; van Mook, M C; Sterenborg, J A E M

    2010-11-15

    Heart murmurs are caused by turbulent blood flow or by vibration of cardiac structures. Turbulent blood flow may originate from structural heart disease or from physiological phenomena. The aims of this study were to establish the cause of heart murmurs in apparently healthy adult cats and to determine whether a heart murmur is a reliable indicator of heart disease. In this retrospective study, we reviewed the medical records of cats in which a heart murmur was detected during physical examination by one of the authors in the period January 2008 to December 2009. Cats younger than 6 months and those with systemic disease were excluded. Timing, grade, and point of maximum intensity of the murmur were determined by one observer (MD) before 2D-, M-mode and Doppler echocardiography. Fifty-seven cats (median age 76 months, range 6-194) were included, 30 neutered females and 27 neutered males. All murmurs were systolic and varied in intensity from 2/6 to 5/6. The point of maximum intensity was the left or right parasternal region in 34/57 (61%) of murmurs. Murmurs were caused by dynamic left ventricular outflow tract obstruction in 25/57 (44%) cats, dynamic right ventricular outflow tract obstruction in 9/57 (16%) cats, and combined dynamic left and right outflow tract obstruction in 11/57 (19%) cats. In 5 (9%) cats the cause of the murmur could not be identified. Heart disease was present in 50 (88%) cats, namely, left ventricular hypertrophy in 44 (77%) and congenital defects in 6 (11%) cats. In conclusion, most heart murmurs in apparently healthy cats are detected in the left or right parasternal region and are caused by dynamic left and right ventricular outflow tract obstruction. Because most cats (88%) with a heart murmur had heart disease in this study, if a heart murmur is detected in an apparently healthy cat, echocardiography is recommended to determine the cause of the heart murmur and the presence of heart disease.

  8. The hidden face of Kanizsa's triangle: apparent movement of subjective figures in three-dimensional space.

    PubMed

    Vallortigara, G

    1987-01-01

    Several demonstrations on the apparent movement in depth of subjective figures are presented. They include: (a) apparent rotational movement as a result of shape invariance or rigidity; (b) apparent rotational movement with three-dimensional subjective figures not accompanied by a brightness gradient; and (c) apparent rotational movement by kinetic occlusion.

  9. Increased Expression of CCN2, Epithelial Membrane Antigen, and Fibroblast Activation Protein in Hepatocellular Carcinoma with Fibrous Stroma Showing Aggressive Behavior

    PubMed Central

    Yoo, Jeong Eun; Ko, Jung Eun; Lee, Jee San; Kim, Hyunki; Choi, Jin Sub; Park, Young Nyun

    2014-01-01

    Tumor behavior is affected by the tumor microenvironment, composed of cancer-associated fibroblasts (CAFs). Meanwhile, hepatocellular carcinomas (HCC) with fibrous stroma reportedly exhibit aggressive behavior suggestive of tumor-stroma interaction. However, evidence of the crosstalk remains unclear. In this study, CCN2, epithelial membrane antigen (EMA), fibroblast activation protein (FAP), and keratin 19 (K19) expression was studied in 314 HCCs (cohort 1), 42 scirrhous HCCs (cohort 2), and 36 chronic hepatitis/cirrhosis specimens by immunohistochemistry. Clinicopathological parameters were analyzed according to the expressions of these markers. In tumor epithelial cells from cohort 1, CCN2 and EMA were expressed in 15.3% and 17.2%, respectively, and their expressions were more frequent in HCCs with fibrous stroma (≥5% of tumor area) than those without (P<0.05 for all); CCN2 expression was well correlated with K19 and EMA expression. In tumor stromal cells, FAP expression was found in 6.7%. In cohort 2, CCN2, EMA, and FAP expression was noted in 40.5%, 40.5%, and 66.7%, respectively, which was more frequent than that in cohort 1 (P<0.05 for all). Additionally, EMA expression was associated with the expression of K19, CCN2, and FAP (P<0.05 for all); EMA expressing tumor epithelial cells showed a topographic closeness to FAP-expressing CAFs. Analysis of disease-free survival revealed CCN2 expression to be a worse prognostic factor in both cohort 1 (P = 0.005) and cohort 2 (P = 0.023), as well as EMA as a worse prognostic factor in cohort 2 (P = 0.048). In conclusion, expression of CCN2, EMA, and FAP may be involved in the activation of CAFs in HCC, giving rise to aggressive behavior. Significant correlation between EMA-expressing tumor cells and FAP-expressing CAFs and their topographic closeness suggests possible cross-talk between tumor epithelial cells and stromal cells in the tumor microenvironment of HCC. PMID:25126747

  10. Timing of the apparent effects of cloud seeding.

    PubMed

    Lovasich, J L; Neyman, J; Scott, E L; Smith, J A

    1969-08-29

    The average hourly precipitation amounts, on 96 experimental days without cloud seeding in the Whitetop experiment, show a marked maximum between 4 and 7 o'clock in the afternoon, presumably reflecting the convection activity caused by heating of the ground occurring during an earlier period. No such maximum is observed on the 102 days with seeding. The hypothetical explanation presupposes that seeding with silver iodide creates early general cloudiness, which prevents ground temperatures from rising to levels usually attained on days without seeding. This hypothesis may explain not only the mechanism of the loss in rain in the Whitetop experiment, apparently induced by seeding, but also may explain certain phenomena noticed in the Grossversuch III experiment.

  11. Multidisciplinary investigation of an unusual apparent homicide/suicide.

    PubMed

    Harding, Brett E; Sullivan, Linda M; Adams, Susan; Middleberg, Robert A; Wolf, Barbara C

    2011-09-01

    The investigation of deaths of individuals whose bodies are decomposed, mummified, or skeletonized is particularly difficult for medical examiners and medicolegal death investigators. Determination of the cause and manner of death in such cases frequently requires consultation with experts in a variety of disciplines in the forensic sciences and necessitates correlation of the autopsy results, scene investigation, medical and social history of the deceased, and laboratory studies. The authors report an unusual case of an apparent homicide/suicide involving 2 individuals and a canine that went undetected for almost 4 years. Determination of the cause and manner of death in these cases involved a multidisciplinary, intercontinental investigation and necessitated the performance of toxicologic studies on specimens not commonly analyzed. These cases illustrate the importance of the multidisciplinary approach to medicolegal death investigations and the necessity of considering nontraditional sources of potential information and specimens for laboratory analysis in selected cases.

  12. Galvanic apparent internal impedance: an intrinsic tissue property.

    PubMed

    Golberg, Alex; Rabinowitch, Haim D; Rubinsky, Boris

    2009-11-06

    Using basic galvanic cell principles, the ability of tissues to generate electrical current through electrolysis was characterized. Studying Zn/Cu electrolysis in animal organs revealed a fundamental and measurable tissue-specific property - the galvanic apparent internal impedance (GAII), that is most likely related to the salt bridge function of tissues delineated by electrodes. Further to the fundamental knowledge acquired, GAII enables a new diagnostic method to distinguish between tissue types and to determine their health status without a need for expensive calibration, as often required when external power source is used. We demonstrated the GAII sensitivity in detecting tissue ablation with microwave heating or irreversible electroporation. The results open the way for a novel, inexpensive self-powered tissue diagnostic system for a wide range of applications such as minimally invasive tissue health status, ischemia, hydration, real time intra-operative control of minimally invasive surgery, medical imaging, virtual biopsy and many others.

  13. Apparent symptom overreporting in combat veterans evaluated for PTSD.

    PubMed

    Frueh, B C; Hamner, M B; Cahill, S P; Gold, P B; Hamlin, K L

    2000-10-01

    Psychometric studies have consistently shown that combat veterans evaluated for posttraumatic stress disorder (PTSD) appear to overreport psychopathology as exhibited by (a) extreme and diffuse levels of psychopathology across instruments measuring different domains of mental illness, and (b) extreme elevations on the validity scale of the MMPI-MMPI-2, in a "fake-bad" direction. The phenomenon of this ubiquitous presentational style is not well understood at present. In this review we describe and delineate the assessment problem posed by this apparent symptom overreporting, and we review the literature regarding several potential explanatory factors. Finally, we address conceptual and practical issues relevant to reaching a better understanding of the phenomenon, and ultimately the clinical syndrome of combat-related PTSD, in both research and clinical settings.

  14. Observations of an apparent SN in NGC 2276

    NASA Astrophysics Data System (ADS)

    Manzini, F.; Dimai, A.; Migliardi, M.

    2005-08-01

    Federico Manzini (SAS obs., IAUC A12) report the observation by Alessandro Dimai, Cortina (Italy), and Marco Migliardi, Tour Tour (France), of an apparent SN in NGC 2276 (m. = +17.1), on four unfiltered CCD images taken on 2005 august 25.1 (lim. magn. about +19,5) with the 0.5-m "Ullrich" telescope of the Col Druscié observatory (Cortina d'Ampezzo, Italy). The observation is confirmed by other three unfiltered CCD images, taken on 2005 august 26.13 (m = +16.8 and limiting magnitude about +19.8), with the same telescope on behalf of the CROSS (Col drusciè Remote Observatory Supernovae Search) program.

  15. Effect of structured visual environments on apparent eye level

    NASA Technical Reports Server (NTRS)

    Stoper, A. E.; Cohen, M. M.

    1989-01-01

    Each of 12 subjects set a binocularly viewed target to apparent eye level; the target was projected on the rear wall of an open box, the floor of which was horizontal or pitched up and down at angles of 7.5 degrees and 15 degrees. Settings of the target were systematically biased by 60% of the pitch angle when the interior of the box was illuminated, but by only 5% when the interior of the box was darkened. Within-subjects variability of the settings was less under illuminated viewing conditions than in the dark, but was independent of box pitch angle. In a second experiment, 11 subjects were tested with an illuminated pitched box, yielding biases of 53% and 49% for binocular and monocular viewing conditions, respectively. The results are discussed in terms of individual and interactive effects of optical, gravitational, and extraretinal eye-position information in determining judgements of eye level.

  16. Use of aspartame by apparently healthy children and adolescents.

    PubMed

    Frey, G H

    1976-11-01

    This study was conducted to determine the effects and the differences, if any, resulting from the ingestion of aspartame (sweetener) versus sucrose. A 13-wk, double-blind study was conducted using 126 apparently healthy children and adolescents as panelists. Individuals were randomly assigned in a double-blind design to aspartame or sucrose in each of five age groups; dosage levels were assigned according to age and weight groups. Physical examinations and special eye examinations were performed at the beginning and end of the study. Other parameters determined including laboratory tests of liver and renal function, hematologic status, and plasma levels of phenylalanine and tyrosine. Clinically significant differences in laboratory parameters measured could not be demonstrated; all mean values were within normal limits. No unusual findings were observed in phenylalanine or tyrosine levels. All phenylpyruvic acid and methanol determinations were negative. No important physical changes occurred, and no product-related side effects were reported.

  17. Vitrectomy for bilateral macular schisis without apparent optic disc anomalies

    PubMed Central

    Andonegui, José; Maya, José Ramón; Echeverría, Marta; Alcaine, Araceli

    2016-01-01

    A 78-year-old man complained of bilateral visual acuity loss. Optical coherence tomography examination showed bilateral macular schisis with fluid accumulation in the external retinal layers without vitreous traction. Fundus examination and fluorescein angiography were normal in both eyes. Both eyes were treated by phacoemulsification, intraocular lens implantation, and vitrectomy without laser, gas exchange, or retinal fenestration. Slow and progressive fluid resorption and improvement in VA were observed in both eyes. Macular schisis similar to the one associated with optic disc anomalies is a possibility in patients without apparent disc anomalies. Vitrectomy without laser, gas, or retinal fenestration may be a good therapeutic option even in patients with a PVD preoperatively. PMID:27703873

  18. Species-barrier-independent prion replication in apparently resistant species

    NASA Astrophysics Data System (ADS)

    Hill, Andrew F.; Joiner, Susan; Linehan, Jackie; Desbruslais, Melanie; Lantos, Peter L.; Collinge, John

    2000-08-01

    Transmission of prions between mammalian species is thought to be limited by a "species barrier," which depends on differences in the primary structure of prion proteins in the infecting inoculum and the host. Here we demonstrate that a strain of hamster prions thought to be nonpathogenic for conventional mice leads to prion replication to high levels in such mice but without causing clinical disease. Prions pathogenic in both mice and hamsters are produced. These results demonstrate the existence of subclinical forms of prion infection with important public health implications, both with respect to iatrogenic transmission from apparently healthy humans and dietary exposure to cattle and other species exposed to bovine spongiform encephalopathy prions. Current definitions of the species barrier, which have been based on clinical end-points, need to be fundamentally reassessed.

  19. Too early? On the apparent conflict of astrobiology and cosmology

    NASA Astrophysics Data System (ADS)

    Cirkovic, Milan M.

    2006-06-01

    An interesting consequence of the modern cosmological paradigm is the spatial infinity of the universe. When coupled with naturalistic understanding of the origin of life and intelligence, which follows the basic tenets of astrobiology, and with some fairly incontroversial assumptions in the theory of observation selection effects, this infinity leads, as Ken Olum has recently shown, to a paradoxical conclusion. Olum's paradox is related, to the famous Fermi's paradox in astrobiology and SETI studies. We, hereby, present an evolutionary argument countering the apparent inconsistency, and show how, in the framework of a simplified model, deeper picture of the coupling between histories of intelligent/technological civilizations and astrophysical evolution of the Galaxy, can be achieved. This strategy has consequences of importance for both astrobiological studies and philosophy.

  20. Random variability explains apparent global clustering of large earthquakes

    USGS Publications Warehouse

    Michael, A.J.

    2011-01-01

    The occurrence of 5 Mw ≥ 8.5 earthquakes since 2004 has created a debate over whether or not we are in a global cluster of large earthquakes, temporarily raising risks above long-term levels. I use three classes of statistical tests to determine if the record of M ≥ 7 earthquakes since 1900 can reject a null hypothesis of independent random events with a constant rate plus localized aftershock sequences. The data cannot reject this null hypothesis. Thus, the temporal distribution of large global earthquakes is well-described by a random process, plus localized aftershocks, and apparent clustering is due to random variability. Therefore the risk of future events has not increased, except within ongoing aftershock sequences, and should be estimated from the longest possible record of events.

  1. The Dependence of the Apparent Contact Angles on Gravity.

    PubMed

    Sakai; Fujii

    1999-02-01

    We have studied theoretically the effect of gravity on the rough solid-liquid interface and have shown that its tension is enhanced by gravity when gas is adsorbed at it. As a result, the apparent contact angle on rough surfaces, which has been considered not to be influenced by gravity so far, can be raised by gravity. The calculated dependence of contact angles on gravity under the ordinary conditions of the sessile drop method is large enough to detect by experiment. The observed asymmetrical deviations from Wenzel's contact angle caused by the gas adsorption at the solid-liquid interface and by the liquid adsorption at the solid-gas interface are explained in terms of this gravitational effect. Copyright 1999 Academic Press.

  2. When luminance increment thresholds depend on apparent lightness.

    PubMed

    Maertens, Marianne; Wichmann, Felix A

    2013-05-31

    A fundamental question in visual perception research is whether the sensitivity to stimulus differences is limited by the sensory representation of the external stimulus, that is, the proximal stimulus, or by its perceptual representation, i.e., stimulus appearance. In the domain of lightness perception, the question translates into whether discrimination thresholds depend on the local luminance in the retinal image or on the apparent lightness of the corresponding image region. The majority of findings seem to indicate that sensitivity is limited by the sensory stimulus representation, which would imply different mechanisms for stimulus discrimination and appearance. We think this conclusion needs to be qualified. We report data suggesting that the relationship between discrimination and appearance judgments depends on how exactly they are being measured. We propose a theoretical account that provides a common mechanism for appearance and sensitivity. An interesting corollary of this model is that it also accounts for the perceptual phenomenon of assimilation.

  3. Apparent Acceleration and an Alternative Concordance from Causal Backreaction

    NASA Astrophysics Data System (ADS)

    Bochner, Brett

    2015-01-01

    A phenomenological formalism is presented in which the apparent acceleration of the universe is generated by cosmic structure formation, without resort to Dark Energy, modifications to gravity, or a local void. The observed acceleration results from the combined effect of innumerable local perturbations due to individually virializing systems, overlapping together in a smoothly-inhomogeneous adjustment of the FRW metric, in a process governed by the causal flow of inhomogeneity information outward from each clumped system. After noting how common arguments claiming to limit backreaction are physically unrealistic, models are presented which fit the supernova luminosity distance data essentially as well as ΛCDM, while bringing several important cosmological parameters to a new Concordance. These goals are all achieved with a second-generation version of our formalism that accounts for the negative feedback of Causal Backreaction upon itself due to the slowed propagation of gravitational inhomogeneity information.

  4. Active suppression of an 'apparent shock induced instability'

    NASA Technical Reports Server (NTRS)

    Adams, William M., Jr.; Tiffany, Sherwood H.; Bardusch, Richard E.

    1987-01-01

    A control law was designed, using constrained optimization techniques, to suppress an apparent shock induced instability of a sweptback, aeroelastic wing with supercritical airfoil sections. The controller design was based on an approximate linear plant representation obtained using forced response data from a previous entry in the Langley Transonic Dynamics tunnel. During a second tunnel entry, it was found that there was not an instability in the uncontrolled case but there was a region of very low damping (high dynamic response) near a Mach number of 0.92. Controller performance was obtained during the test in near real-time and revealed that the controller attenuated the open-loop response and provided a small but significant amount of damping over a Mach number range from M = 0.70 to M = 0.92.

  5. Apparent threshold of lead's effect on child intelligence

    SciTech Connect

    Rabinowitz, M.B. National Taiwan Univ., Taipei ); Wang, J.D.; Soong, W.T. )

    1992-05-01

    The developing human brain is perhaps the most sensitive of the many targets of lead toxicity. This particular sensitivity is a driving factor in setting health and environmental standards for lead. A recent compilation of studies of the association between lead and IQ has shown a consistent dose-response pattern across the range of reported exposures. In surveying the neurotoxicity of lead in humans and animals, there has been speculation of the existence of a threshold for these effects which may become apparent at lower lead levels. In that context we examined our data of tooth lead and IQ scores to determine whether there was any apparent threshold for this effect. This cohort's lead levels are among the lowest documented and provide the opportunity to extend downward the range of interest. Family factors are the strongest predictors of a child's intelligence, in particular the parent's intelligence. We therefore followed the model of Perino and Ernhart (1974) by examining whether at various levels of lead there is a disruption of the usual association between family and child intelligence. As noted by Bellinger and Needleman (1983), a difference in the correlations between parental and child intelligence in two groups, high and low lead, may be an artifact of other relationships among the predictor variables. Accordingly, they recommend a more appropriate test that would search for differences in the IQ deficits according to lead level, where the IQ deficit is the difference between a child's observed IQ and the IQ predicted from all available information about the child aside from lead. This is especially appropriate when the lead exposure correlates with the family's educational background. We examined our data this way. 12 refs., 1 fig., 2 tabs.

  6. Prehypertension and Its Determinants in Apparently Healthy Young Adults

    PubMed Central

    Senthil, Sunandha

    2016-01-01

    Introduction High incidence of prehypertension is reported in medical undergraduates. Prehypertension may progress to hypertension and eventually cardiovascular disease, a leading cause of morbidity and mortality. Therefore, identifying the risk factors of hypertension in prehypertensive state may aid in effective control of blood pressure. Aim To find whether clustering of known risk factors of hypertension or certain individual risk factors alone affect blood pressure in young adults. Materials and Methods This was a cross-sectional study done in 84 apparently healthy medical students of either sex aged between 18-23 years. It included students with at least one known risk factor of hypertension. Blood pressure levels of 120 to 139/80 to 89 mm Hg were defined as prehypertension. The risk factors considered were male gender, family history of cardiovascular disease, sedentary life, general and central obesity, sleep quality, perceived stress and dietary pattern. Clustering of risk factors was assessed based on collective scoring system in which each risk factor was scored appropriately. Statistical analysis was done by unpaired t, Chi-square and Pearson correlation coefficient tests. The p<0.05 was considered significant. Results There was a positive correlation between total risk factor score and systolic blood pressure (r = 0.266, p = 0.015). Among the risk factors, frequency of males with systolic and diastolic prehypertension was higher compared to females (p <0.0001,= 0.022 respectively). Body mass index was higher in systolic and diastolic prehypertensives compared to normotensives (p <0.001, 0.002, respectively). Waist circumference was higher in systolic and diastolic prehypertensives compared to normotensives (p< 0.0001). Conclusion In apparently healthy young adults, male gender and obesity are the major risk factors of elevated blood pressure. PMID:27790426

  7. Deep space laser communications

    NASA Astrophysics Data System (ADS)

    Biswas, Abhijit; Kovalik, Joseph M.; Srinivasan, Meera; Shaw, Matthew; Piazzolla, Sabino; Wright, Malcolm W.; Farr, William H.

    2016-03-01

    A number of laser communication link demonstrations from near Earth distances extending out to lunar ranges have been remarkably successful, demonstrating the augmented channel capacity that is accessible with the use of lasers for communications. The next hurdle on the path to extending laser communication and its benefits throughout the solar system and beyond is to demonstrate deep-space laser communication links. In this paper, concepts and technology development being advanced at the Jet Propulsion Laboratory (JPL) in order to enable deep-space link demonstrations to ranges of approximately 3 AU in the next decade, will be discussed.

  8. DEEP UNDERGROUND NEUTRINO EXPERIMENT

    SciTech Connect

    Wilson, Robert J.

    2016-03-03

    The Deep Underground Neutrino Experiment (DUNE) collaboration will perform an experiment centered on accelerator-based long-baseline neutrino studies along with nucleon decay and topics in neutrino astrophysics. It will consist of a modular 40-kt (fiducial) mass liquid argon TPC detector located deep underground at the Sanford Underground Research Facility in South Dakota and a high-resolution near detector at Fermilab in Illinois. This conguration provides a 1300-km baseline in a megawatt-scale neutrino beam provided by the Fermilab- hosted international Long-Baseline Neutrino Facility.

  9. The deep penetrating nevus.

    PubMed

    Strazzula, Lauren; Senna, Maryanne Makredes; Yasuda, Mariko; Belazarian, Leah

    2014-12-01

    The deep penetrating nevus (DPN), also known as the plexiform spindle cell nevus, is a pigmented lesion that commonly arises on the head and neck in the first few decades of life. Histopathologically, the DPN is wedge-shaped and contains melanocytes that exhibit deep infiltration into the dermis. Given these features, DPN may clinically and histopathologically mimic malignant melanoma, sparking confusion about the appropriate evaluation and management of these lesions. The goal of this review is to summarize the clinical and histopathological features of DPN and to discuss diagnostic and treatment strategies for dermatologists.

  10. The apparent anomalous, weak, long-range acceleration of Pioneer 10 and 11

    SciTech Connect

    Anderson, J.D.; Lau, E.L.; Turyshev, S.G.; Laing, P.A.; Liu, A.S.; Nieto, M.M.

    1999-07-01

    Recently the authors reported that radio Doppler data generated by NASA`s Deep Space Network (DSN) with the Pioneer 10 and 11 spacecraft indicate an apparent anomalous, constant, spacecraft acceleration with a magnitude {approximately}8.5 {times} 10{sup {minus}8} cm s{sup {minus}2}, directed towards the Sun. Analysis of similar Doppler and ranging data from the Galileo and Ulysses spacecraft yielded ambiguous results for the anomalous acceleration, but the analysis was useful in that it ruled out the possibility of a systematic error in the DSN Doppler system that could easily be mistaken as a spacecraft acceleration. Here they present some new results, including a critique of the suggestion that the anomalous acceleration could be caused by collimated thermal emission. Based on upgraded JPL software for the Pioneer 10 orbit determination, and on a new data interval from January 1987 to July 1998, their best estimate of the average Pioneer 10 acceleration directed towards the Sun is 7.20 {sup {minus}} 0.11 {times} 10{sup {minus}8} cm s{sup {minus}2}.

  11. Reflectance spectroscopy for diagnosis of epithelial precancer: model-based analysis of fiber-optic probe designs to resolve spectral information from epithelium and stroma

    PubMed Central

    Arifler, Dizem; Schwarz, Richard A.; Chang, Sung K.; Richards-Kortum, Rebecca

    2009-01-01

    Reflectance spectroscopy is a promising technology for detection of epithelial precancer. Fiber-optic probes that selectively collect scattered light from both the epithelium and the underlying stroma are likely to improve diagnostic performance of in vivo reflectance spectroscopy by revealing diagnostic features unique to each layer. We present Monte Carlo models with which to evaluate fiber-optic probe geometries with respect to sampling depth and depth resolution. We propose a probe design that utilizes half-ball lens coupled source and detector fibers to isolate epithelial scattering from stromal scattering and hence to resolve spectral information from the two layers. The probe is extremely compact and can provide easy access to different organ sites. PMID:16045217

  12. Membrane-bound ICAM-1 contributes to the onset of proinvasive tumor stroma by controlling acto-myosin contractility in carcinoma-associated fibroblasts

    PubMed Central

    Bonan, Stephanie; Albrengues, Jean; Grasset, Eloise; Kuzet, Sanya-Eduarda; Nottet, Nicolas; Bourget, Isabelle; Bertero, Thomas; Mari, Bernard; Meneguzzi, Guerrino; Gaggioli, Cedric

    2017-01-01

    Acto-myosin contractility in carcinoma-associated fibroblasts leads to assembly of the tumor extracellular matrix. The pro-inflammatory cytokine LIF governs fibroblast activation in cancer by regulating the myosin light chain 2 activity. So far, however, how LIF mediates cytoskeleton contractility remains unknown. Using phenotypic screening assays based on knock-down of LIF-dependent genes in fibroblasts, we identified the glycoprotein ICAM-1 as a crucial regulator of stroma fibroblast proinvasive matrix remodeling. We demonstrate that the membrane-bound ICAM-1 isoform is necessary and sufficient to promote inflammation-dependent extracellular matrix contraction, which favors cancer cell invasion. Indeed, ICAM-1 mediates generation of acto-myosin contractility downstream of the Src kinases in stromal fibroblasts. Moreover, acto-myosin contractility regulates ICAM-1 expression by establishing a positive feedback signaling. Thus, targeting stromal ICAM-1 might constitute a possible therapeutic mean to counteract tumor cell invasion and dissemination. PMID:27901489

  13. Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma.

    PubMed

    Hurt, Elaine M; Wiestner, Adrian; Rosenwald, Andreas; Shaffer, A L; Campo, Elias; Grogan, Tom; Bergsagel, P Leif; Kuehl, W Michael; Staudt, Louis M

    2004-02-01

    The oncogene c-maf is translocated in approximately 5%-10% of multiple myelomas. Unexpectedly, we observed c-maf expression in myeloma cell lines lacking c-maf translocations and in 50% of multiple myeloma bone marrow samples. By gene expression profiling, we identified three c-maf target genes: cyclin D2, integrin beta7, and CCR1. c-maf transactivated the cyclin D2 promoter and enhanced myeloma proliferation, whereas dominant inhibition of c-maf blocked tumor formation in immunodeficient mice. c-maf-driven expression of integrin beta7 enhanced myeloma adhesion to bone marrow stroma and increased production of VEGF. We propose that c-maf transforms plasma cells by stimulating cell cycle progression and by altering bone marrow stromal interactions. The frequent overexpression of c-maf in myeloma makes it an attractive target for therapeutic intervention.

  14. Analysis of Stroma Labeling During Multiple Passage of a Sarcoma Imageable Patient-derived Orthotopic Xenograft (iPDOX) in Red Fluorescent Protein Transgenic Nude Mice.

    PubMed

    Kiyuna, Tasuku; Murakami, Takashi; Tome, Yasunori; Kawaguchi, Kei; Igarashi, Kentaro; Miyake, Kentaro; Kanaya, Fuminori; Singh, Arun; Eilber, Fritz C; Hoffman, Robert M

    2017-03-16

    A patient-derived orthotopic xenograft (PDOX) model of undifferentiated pleomorphic sarcoma (UPS) was previously established that acquired red fluorescent protein (RFP)-expressing stroma by growth in an RFP transgenic nude mouse. In the present study, an imageable PDOX model (iPDOX) of UPS was established by orthotopic implantation in the biceps femoris of transgenic RFP nude mice. After the tumors grew to a diameter of 10 mm, they were harvested and the brightest portion of the tumors were subsequently orthotopically transplanted to both RFP and non-colored nude mice. The UPS PDOX tumor was again transplanted to RFP transgenic and non-colored nude mice and finally a 3(rd) passage was made in the same manner. Five UPS tumors from each passage in both RFP and non-colored mouse models were harvested. The FV1000 confocal microscope was used to visualize and quantitate the RFP area of the resected tumors. The average percent fluorescent area in the first passage of RFP mice was 34 ± 22%; in the second passage, 34 ± 20%; and 36 ± 11% in the third passage of RFP transgenic nude mice. The average tumor RFP area in the first passage from RFP mice to non-colored mice was 20 ± 7%; in the second passage, 28 ± 11%; in the third passage was 27 ± 13%. The present results demonstrate the extensive and stable acquisition of stroma by the UPS-tumor growing orthotopically in transgenic RFP nude mice (iPDOX). This model can be used for screening for effective drugs for individual patients and drug discovery. This article is protected by copyright. All rights reserved.

  15. Improved adipogenic in vitro differentiation: comparison of different adipogenic cell culture media on human fat and bone stroma cells for fat tissue engineering.

    PubMed

    Ghoniem, Amir-Alexander; Açil, Yahya; Wiltfang, Jörg; Gierloff, Matthias

    2015-06-01

    To date there is no sufficient in vitro fat tissue engineering and a protocol has not been well established for this purpose. Therefore, we evaluated the in vitro influence of two different adipogenic growth media for their stimulation potential on different cell lineages to clearly define the most potent adipogenic growth media for future in vitro tissue engineering approaches. The samples for differentiation were composed of human adipogenic-derived stroma cells (hADSCs) and human bone marrow mesenchymal stroma cells (hMSCs). A normal adipogenic medium (NAM) and a specific adipogenic medium (SAM) were tested for their adipogenic stimulation potential. After 10 days and 21 days the relative gene expression was measured for the adipogenic marker genes PPARγ2, C/EBPα, FABP4, LPL, and GLUT4 detected through real time reverse transcriptase polymease chain reaction (RT-PCR). Other study variables were the comparison between NAM and SAM and between the used cells hADSCs and hMSCs. Additionally an Oil-Red staining was performed after 21 days. Our results revealed that only SAM was significantly (P<0.05) superior in the differentiation process in contrast to NAM for 10 days and 21 days. As well was SAM superior to differentiate the used cell lineages. This was evaluated by the detected marker genes PPARγ2, C/EBPα, FABP4, LPL, and GLUT4 through real time RT-PCR and by Oil-Red staining. In addition, the hMSCs proofed to be equal donor cells for adipogenic differentiation especially when stimulated by SAM. The results suggest that the SAM should be established as a new standard medium for a more promising in vitro adipogenic differentiation.

  16. 3, 3', 5-triiodo-L-thyronine Increases In Vitro Chondrogenesis of Mesenchymal Stem Cells From Human Umbilical Cord Stroma Through SRC2.

    PubMed

    Fernández-Pernas, Pablo; Fafián-Labora, Juan; Lesende-Rodriguez, Iván; Mateos, Jesús; De la Fuente, Alexandre; Fuentes, Isaac; De Toro Santos, Javier; Blanco García, Fco; Arufe, María C

    2016-09-01

    Our group focuses on the study of mesenchymal stem cells (MSCs) from human umbilical cord stroma or Warthońs jelly and their directed differentiation toward chondrocyte-like cells capable of regenerating damaged cartilage when transplanted into an injured joint. This study aimed to determine whether lactogenic hormone prolactin (PRL) or 3, 3', 5-triiodo-L-thyronine (T3), the active thyroid hormone, modulates chondrogenesis in our in vitro model of directed chondrogenic differentiation, and whether Wnt signalling is involved in this modulation. MSCs from human umbilical cord stroma underwent directed differentiation toward chondrocyte-like cells by spheroid formation. The addition of T3 to the chondrogenic medium increased the expression of genes linked to chondrogenesis like collagen type 2, integrin alpha 10 beta 1, and Sox9 measured by quantitative real time polymerase chain reaction (qRT-PCR) analysis. Levels of collagen type 2 and aggrecane analyzed by immunohistochemistry, and staining by Safranin O were increased after 14 days in spheroid culture with T3 compared to those without T3 or only with PRL. B-catenin, Frizzled, and GSK-3β gene expressions were significantly higher in spheroids cultured with chondrogenic medium (CM) plus T3 compared to CM alone after 14 days in culture. The increase of chondrogenic differentiation was inhibited when the cells were treated with T3 plus ML151, an inhibitor of the T3 steroid receptor. This work demonstrates, for first time, that T3 promotes differentiation towards chondrocytes-like cells in our in vitro model, that this differentiation is mediated by steroid receptor co-activator 2 (SRC2) and does not induce hypertrophy. J. Cell. Biochem. 117: 2097-2108, 2016. © 2016 Wiley Periodicals, Inc.

  17. Understanding of the Viscoelastic Response of the Human Corneal Stroma Induced by Riboflavin/UV-A Cross-Linking at the Nano Level

    PubMed Central

    Labate, Cristina; De Santo, Maria Penelope; Lombardo, Giuseppe; Lombardo, Marco

    2015-01-01

    Purpose To investigate the viscoelastic changes of the human cornea induced by riboflavin/UV-A cross-linking using Atomic Force Microscopy (AFM) at the nano level. Methods Seven eye bank donor corneas were investigated, after gently removing the epithelium, using a commercial AFM in the force spectroscopy mode. Silicon cantilevers with tip radius of 10 nm and spring elastic constants between 26- and 86-N/m were used to probe the viscoelastic properties of the anterior stroma up to 3 µm indentation depth. Five specimens were tested before and after riboflavin/UV-A cross-linking; the other two specimens were chemically cross-linked using glutaraldehyde 2.5% solution and used as controls. The Young’s modulus (E) and the hysteresis (H) of the corneal stroma were quantified as a function of the application load and scan rate. Results The Young’s modulus increased by a mean of 1.1-1.5 times after riboflavin/UV-A cross-linking (P<0.05). A higher increase of E, by a mean of 1.5-2.6 times, was found in chemically cross-linked specimens using glutaraldehyde 2.5% (P<0.05). The hysteresis decreased, by a mean of 0.9-1.5 times, in all specimens after riboflavin/UV-A cross-linking (P<0.05). A substantial decrease of H, ranging between 2.6 and 3.5 times with respect to baseline values, was observed in glutaraldehyde-treated corneas (P<0.05). Conclusions The present study provides the first evidence that riboflavin/UV-A cross-linking induces changes of the viscoelastic properties of the cornea at the scale of stromal molecular interactions. PMID:25830534

  18. Evaluation of T, B and natural killer lymphocyte in the cervical stroma of HIV-positive and negative patients with cervical intraepithelial neoplasia.

    PubMed

    Lucena, Adriana A S; Guimarães, Mírian Viviane M B; Michelin, Márcia A; Lodi, Cláudia T C; Lima, Maria Inês M; Murta, Eddie Fernando Candido; Melo, Victor Hugo

    2016-01-01

    Cervical intraepithelial neoplasias (CIN) are closely associated with oncogenic subtypes of the human papillomavirus (HPV). In the presence of this virus, it is known that the activation or suppression of immune system is the key to the development, progression and/or regression of cervical lesions. Therefore, the objective of this study is to compare the local immune response among HIV-seropositive and seronegative patients with cervical intraepithelial neoplasia regarding the expression of T lymphocytes (CD3+, CD4+ and CD8+), B lymphocytes (CD20+) and natural killers cells (CD56+) in the cervical stroma. A cross-sectional study of paraffin blocks containing cervical tissue after conization by the Loop Electrosurgical Excision Procedure (LEEP) from 47 HIV-seropositive and 38 seronegative patients with CIN. Cervical stroma immunohistochemistry was performed in the CIN area. The Fisher's exact test was used for the statistical analysis. When HIV-seropositive and seronegative women were compared, the seropositive women had a higher count of CD8+ T lymphocytes (52.1% versus 28.9%, P<0.04). Considering CIN degree (CIN 1 and CIN 2/3), the HIV-seronegative patients with CIN 1 had a low count of CD20+B-lymphocytes (7.1%) in comparison with CIN 1 HIV seropositive and with CIN 2/3 HIV-seronegative patients, respectively 50% (P<0.018) and 54.5% (P<0.0048). The HIV infection and degree of CIN influenced the cytotoxic lymphocytes inducing an increase in the number of cells high count of CD20+ lymphocytes with CIN 1.

  19. Gray level entropy matrix is a superior predictor than multiplex ELISA in the detection of reactive stroma and metastatic potential of high-grade prostatic adenocarcinoma.

    PubMed

    Jia, Xiaopeng; Sun, Yanan; Wang, Baozhi

    2014-12-01

    Recent reports have indicated that not only the primary glandular tissue but also the surrounding stromal tissue plays an active role in the progression of carcinoma. Such is true for cancer tissues arising in the prostate. However, the precise role of stromal tissue in benign prostatic hyperplasia (BPH) and prostate adenocarcinoma is not well described. We undertook this current investigation to examine the changes in orientation of the extracellular matrix and correlate with prostatic cancer progression. We used a novel form of image analysis called gray level entropy matrix (GLEM) texture analysis to evaluate morphometric changes in stromal tissues. We used normal prostatic tissue obtained from cadaveric specimen and compared with BPH, prostatic intraepithelium neoplastic, hormone responsive prostatic adenocarcinoma and castration-resistant prostatic adenocarcinoma tissues. GLEM showed higher entropy in disease-resistant prostatic tissues, compared with benign forms of all spectra of pathologically diagnosed prostatic tissues (P < 0.05, ANOVA, between groups). Higher entropy is reflective of the disorganized morphological organization of the stroma, possibly reflecting the reactive matrix. In contrast, ELISA revealed that although individually correlated with the progressive stages of benign and carcinomatous prostatic tissues and trend correlation between groups, intergroup comparisons failed to arrive at statistical significance of comparisons between markers of neovasculogenesis, vascular endothelial growth factor, epithelial-mesenchymal transition (beta1-integrin, E-cadherin, MMP3) and osteogenic metastasis (RANKL and osteoprotegerin). The results of our study demonstrate the potential of GLEM entropy of gray level pixel in providing quasiquantitative estimate of a reactive stroma in advance stages of prostatic adenocarcinoma and thus can be routinely used in clinical decision making.

  20. Stroma-directed imatinib therapy impairs the tumor-promoting effect of bone marrow-derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer.

    PubMed

    Shinagawa, Kei; Kitadai, Yasuhiko; Tanaka, Miwako; Sumida, Tomonori; Onoyama, Mieko; Ohnishi, Mayu; Ohara, Eiji; Higashi, Yukihito; Tanaka, Shinji; Yasui, Wataru; Chayama, Kazuaki

    2013-02-15

    Bone marrow-derived mesenchymal stem cells (MSCs) are reported to contribute to formation of tumor-promoting stromal cells. We reported recently that, in an orthotopic nude mice model of colon cancer, MSCs traveled to tumor stroma, where they differentiated into carcinoma-associated fibroblast (CAF)-like cells. We also found that CAFs express platelet-derived growth factor receptor (PDGFR) at a high level and that imatinib therapy targeting PDGFR in CAFs inhibits growth and metastasis of human colon cancer. These findings led us to examine whether the tumor-promoting effect of MSCs is impaired by blockade of PDGFR signaling achieved with imatinib. Orthotopic transplantation and splenic injection of human MSCs along with KM12SM human colon cancer cells, in comparison with transplantation of KM12SM cells alone, resulted in significantly greater promotion of tumor growth and liver metastasis. The KM12SM + MSC xenograft enhanced cell proliferation and angiogenesis and inhibited tumor cell apoptosis. When tumor-bearing animals were treated with imatinib, there was no significant increase in primary tumor volume or total volume of liver metastases, despite the KM12SM+MSC xenograft, and survival in the mixed-cell group was prolonged by imatinib treatment. Moreover, the ability of MSCs to migrate to tumor stroma was impaired, and the number of MSCs surviving in the tumor microenvironment was significantly decreased. In in vitro experiments, treatment with imatinib inhibited migration of MSCs. Our data suggest that blockade of PDGF signaling pathways influences the interaction between bone marrow-derived MSCs and tumor cells in the tumor microenvironment and, hence, inhibits the progressive growth of colon cancer.

  1. Reading Knee-Deep

    ERIC Educational Resources Information Center

    Jewett, Pamela

    2007-01-01

    Freire told his audience at a seminar at the University of Massachusetts, "You need to read knee-deep in texts, for deeper than surface meanings, and you need to know the words to be able to do it" (quoted in Cleary, 2003). In a children's literature class, fifteen teachers and I traveled along a path that moved us toward reading…

  2. The Deep Space Network

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Work accomplished on the Deep Space Network (DSN) was described, including the following topics: supporting research and technology, advanced development and engineering, system implementation, and DSN operations pertaining to mission-independent or multiple-mission development as well as to support of flight projects.

  3. [Deep vein thrombosis prophylaxis.

    PubMed

    Sandoval-Chagoya, Gloria Alejandra; Laniado-Laborín, Rafael

    2013-01-01

    Background: despite the proven effectiveness of preventive therapy for deep vein thrombosis, a significant proportion of patients at risk for thromboembolism do not receive prophylaxis during hospitalization. Our objective was to determine the adherence to thrombosis prophylaxis guidelines in a general hospital as a quality control strategy. Methods: a random audit of clinical charts was conducted at the Tijuana General Hospital, Baja California, Mexico, to determine the degree of adherence to deep vein thrombosis prophylaxis guidelines. The instrument used was the Caprini's checklist for thrombosis risk assessment in adult patients. Results: the sample included 300 patient charts; 182 (60.7 %) were surgical patients and 118 were medical patients. Forty six patients (15.3 %) received deep vein thrombosis pharmacologic prophylaxis; 27.1 % of medical patients received deep vein thrombosis prophylaxis versus 8.3 % of surgical patients (p < 0.0001). Conclusions: our results show that adherence to DVT prophylaxis at our hospital is extremely low. Only 15.3 % of our patients at risk received treatment, and even patients with very high risk received treatment in less than 25 % of the cases. We have implemented strategies to increase compliance with clinical guidelines.

  4. Teaching for Deep Learning

    ERIC Educational Resources Information Center

    Smith, Tracy Wilson; Colby, Susan A.

    2007-01-01

    The authors have been engaged in research focused on students' depth of learning as well as teachers' efforts to foster deep learning. Findings from a study examining the teaching practices and student learning outcomes of sixty-four teachers in seventeen different states (Smith et al. 2005) indicated that most of the learning in these classrooms…

  5. Apparent solubility of drugs in partially crystalline systems.

    PubMed

    Mosharraf, Mitra; Nyström, Christer

    2003-07-01

    Using several griseofulvin samples, representing different solid-state structures, the solubility behavior of drugs in both one-state (totally ordered, semiordered or disordered) and two-state systems was studied. Special attention was directed towards the surface structure of the particles. The partially crystalline samples were obtained by milling the raw material (crystalline standard) or storing the quenched sample (amorphous standard). The solid-state structure of the materials was studied using x-ray diffraction (XRD), differential scanning calorimetry (DSC), isothermal microcalorimetry (IMC), and scanning electron microscopy (SEM). The saturation concentration of the materials was studied in suspensions containing different dispersion concentrations of drug after centrifugation and filtration, using spectrophotometry. In all cases these dispersion concentrations exceeded the solubility of the drug. The solubilities were plotted vs. dispersion concentrations for each sample. Several solubility plateaus were found. The lowest and highest solubility plateaus corresponded to the solubilities of crystalline and amorphous standards. These plateaus were reached at 8 and 44 microg/mL for crystalline and amorphous griseofulvin standards, respectively. An intermediate plateau served as an indication of the existence of a totally semiordered structure. This was reached at 19 microg/mL for griseofulvin. Any deviation from these plateaus was suggested to be indicative of the existence of heterogeneity on the surface structure, which in most cases could be described as a two state system. In such cases, the apparent solubility was a function of dispersion concentration, until at very high dispersion concentrations (4000-20,000 microg/mL) the saturation concentration of the totally disordered (44 microg/mL) or semiordered (19 microg/mL) one-state phase was reached. No reduction in these values was observed during storage for 50 days. It is thus concluded that, in partially

  6. Three different origins for apparent triploid/diploid mosaics.

    PubMed

    Daniel, Art; Wu, Zhanhe; Darmanian, Artur; Collins, Felicity; Jackson, Julianne

    2003-07-01

    Four apparent triploid/diploid mosaic cases were studied. Three of the cases were detected at prenatal diagnosis and the other was of an intellectually handicapped, dysmorphic boy. Karyotypes were performed in multiple tissues if possible, and the inheritance of microsatellites was studied with DNA from fetal tissues and parental blood. Non-mosaic triploids have a different origin from these mosaics with simple digyny or diandry documented in many cases. Three different mechanisms of origin for these apparent mosaics were detected: (1) chimaerism with karyotypes from two separate zygotes developing into a single individual, (2) delayed digyny, by incorporation of a pronucleus from a second polar body into one embryonic blastomere, and (3) delayed dispermy, similarly, by incorporation of a second sperm pronucleus into one embryonic blastomere. In three of the four cases, there was segregation within the embryos of triploid and diploid cell lines into different tissues from which DNA could be isolated. In case 2 originating by digyny, the same sperm allele at each locus could be detected in both triploid and diploid tissues, which is supportive evidence for the involvement of a single sperm and for true mosaicism rather than chimaerism. Similarly, in case 4 originating by dispermy, the same single ovum allele at each locus could be detected in diploid and triploid tissues, confirming mosaicism. In the chimaeric case (case 3), the diploid line had the karyotype 47,XY,+16 while the triploid line was 69,XXY. This suggests a chimaera, since, in a true mosaic, the triploid line should also contain the additional chromosome 16. Supporting the interpretation of a chimaeric origin for this case, the DNA data showed that the triploidy was consistent with MII non-disjunction (i.e. involving a diploid ovum). In the mosaic cases (1, 2, 4), there was no evidence of the involvement of a diploid sperm or a diploid ova, and in triploid/diploid mosaicism, an origin from a diploid

  7. Contribution of Chlorophyll Fluorescence to the Apparent Reflectance of Vegetation

    NASA Technical Reports Server (NTRS)

    Campbell, P. K. Entcheva; Middleton, E. M.; Kim, M. S.

    2007-01-01

    Current strategies for monitoring the physiologic status of terrestrial vegetation rely on remote sensing reflectance (R) measurements, whi ch provide estimates of relative vegetation vigor based primarily on chlorophyll content. Vegetation chlorophyll fluorescence (CF) offers a non-destructive alternative and a more direct approach for diagnosis of vegetation stress before a significant reduction in chlorophyll content has occurred. Thus, monitoring of vegetation vigor based on CF may allow earlier stress detection and more accurate carbon sequestra tion estimates, than is possible using R data alone. However, the observed apparent vegetation reflectance (Ra) in reality includes contrib utions from both the reflected and fluoresced radiation. The aim of t his study is to determine the relative R and CF fractions contributing to Ra from the vegetation in the red to near-infrared region of the spectrum. The practical objectives of the study are to: 1) evaluate t he relationship between CF and R at the foliar level for corn, soybean, maple; and 2) for corn, determine if the relationship established f or healthy (optimal N) vegetation changes under N defiiency. To obtai n generally applicable results, experimental measurements were conducted on unrelated crop and tree species (maple, soybean and corn), unde r controlled conditions and a gradient of inorganic N fertilization l evels. Optical R spectra and actively induced CF emissions were obtained on the same foliar samples, in conjunction with measurements of p hotosynthetic function, pigment levels, and C and N content. The comm on spectral trends or similarities were examined. On average, 10-20% of apparent R at 685 nm was actually due to CF. The spectral trends in steady and maximum F varied significantly, with Fs (especially red) showing higher ability for species and treatment separation. The relative contribution of ChF to R varied significantly among species, with maple emitting much higher F amounts, as

  8. A simple deep monitoring well dilution technique.

    NASA Astrophysics Data System (ADS)

    Rogiers, Bart; Labat, Serge; Gedeon, Matej; Vandersteen, Katrijn

    2015-04-01

    Well dilution techniques are well known and studied as one of the basic techniques to quantify groundwater fluxes. A typical well dilution test consists of the injection of a tracer, a mixing mechanism (e.g. water circulation with a pump) to achieve a homogeneous concentration distribution within the well, and monitoring of the evolution of tracer concentration with time. An apparent specific discharge can be obtained from such a test, and when details on the well construction are known, it can be converted into a specific discharge representative of the undisturbed aquifer. For deep wells however, the injection of tracer becomes less practical and the use of pumps for circulating and mixing the water becomes problematic. This is due to the limited pressure that common pumps can endure at the outlet, as well as the large volume of water that makes it difficult to achieve a homogeneous concentration, and the impracticalities of getting a lot of equipment to large depths in very small monitoring wells. Injection and monitoring of tracer at a specific depth omits several of the problems with deep wells. We present a very simple device that can be used to perform a dilution test at a specific depth in deep wells. The injection device consists of a PVC tube with a detachable rubber seal at its bottom. To minimize disturbance of the water column in the well, we integrated an EC sensor in this injection device, which enables us to use demineralized water or dissolved salts as a tracer. Once at the target depth, the PVC tube is retracted and the EC sensor and tracer become subject to groundwater flow. The device was tested on a shallow well, on which different types of dilution tests were performed. The results of the other tests agree well with the injection tube results. Finally, the device was used to perform a dilution test in a deep well in order to demonstrate the feasibility of the approach.

  9. Chlorofluorocarbon distributions in the deep Argentine Basin

    SciTech Connect

    Warner, M.J. ); Weiss, R.F. ); Smethie, W.M. Jr. )

    1990-01-09

    The seawater concentrations of the chlorofluorocarbons (CFCs) F-11 and F-12 were measured in the Argentine Basin during the Abyssal Boundary Current Studies (1986) and the South Atlantic Ventilation Experiment (1988-89) expeditions. In most regions of the basin, the CFC concentrations are above the detection limit (0.015 pmol/kg) in the entire water column. The main features of the F-11 and F-12 profiles in the deep waters of the Argentine Basin are concentration mixima at depths of 2 to 3 km and generally increasing concentrations towards the bottom. The mid-depth CFC minima are associated with the salinity maximum of Circumpolar Deep Water (CDW). The higher CFC concentrations at the seafloor are correlated with the colder temperatures of Antarctic Bottom Water (AABW). The CFC concentrations in AABW are highest on the eastern portion of the basin along 47[degrees]S and along the southern and western boundaries. These distributions are consistent with a separation of the inflowing AABW into a cyclonic gyre in the eastern portion of the basin and a western boundary current which carries a detectable CFC singal as far noth as 17[degrees]S. Between CDW and AABW, there are local CFC maxima and minima which are not associated with extrema in other hydrographic properties. The local minima are found on a mean density of 46.07 [sigma][sub 4], which is the upper bound of the water entering the Argentine Basin from the Weddell Sea (Reid, Deep-Sea Res., 1989 submitted). The local CFC maxima are found at about the 46.00 [sigma][sub 4] isopycnal surface. Water of this density apparently is of circumpolar origin. The presence of these local CFC extrema in this density range carries information on the time-dependent vertical mixing in the deep Argentine Basin.

  10. Earths Climate Sensitivity: Apparent Inconsistencies in Recent Assessments

    DOE PAGES

    Schwartz, Stephen E.; Charlson, Robert J.; Kahn, Ralph; ...

    2014-12-08

    Earth's equilibrium climate sensitivity (ECS) and forcing of Earth's climate system over the industrial era have been re-examined in two new assessments: the Fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change (IPCC), and a study by Otto et al. (2013). The ranges of these quantities given in these assessments and also in the Fourth (2007) IPCC Assessment are analyzed here within the framework of a planetary energy balance model, taking into account the observed increase in global mean surface temperature over the instrumental record together with best estimates of the rate of increase of planetary heat content.more » This analysis shows systematic differences among the several assessments and apparent inconsistencies within individual assessments. Importantly, the likely range of ECS to doubled CO₂ given in AR5, 1.5–4.5 K/(3.7 W m⁻²) exceeds the range inferred from the assessed likely range of forcing, 1.2–2.9 K/(3.7 W m⁻²), where 3.7 W ⁻² denotes the forcing for doubled CO₂. Such differences underscore the need to identify their causes and reduce the underlying uncertainties. Explanations might involve underestimated negative aerosol forcing, overestimated total forcing, overestimated climate sensitivity, poorly constrained ocean heating, limitations of the energy balance model, or a combination of effects.« less

  11. Apparent Optical Properties in Waters Influenced by the Mississippi River

    NASA Technical Reports Server (NTRS)

    D'Sa, E.; Miller, R. L.; McKee, B. A.; Trzaska, R.

    2002-01-01

    In-water downwelling irradiance (E(sub d)) and upwelling radiance (L(sub u)) were measured in coastal waters influenced by the Mississippi River at wavelengths corresponding to SeaWiFS spectral bands in April of 2000. Results of derived apparent optical properties (AOP's) such as spectral diffise attenuation coefficient for downwelling irradiance (K(sub d)) suggest that they are mainly influenced by phytoplankton chlorophyll. Large variations in chlorophyll concentrations (0.2 to greater than 10 mg per cubic meters) correspond to variations in K(sub d) at 443 nm ranging from about 0.1 to greater than 1.5 per meter. Attenuation values at 443 nm generally peaked (or were minimal at 555 nm) at depths where chlorophyll concentrations were high. Above water remote sensing reflectance R(sub rs) (443) derived from E(sub d) and L(sub u) shows good agreement to surface chlorophyll. Ratios of remote sensing reflectance, R(sub rs)(443/R(sub rs)(555)versus chlorophyll suggests a potential for obtaining a suitable bio-optical algorithm for the region influenced by the Mississippi River.

  12. Apparent mineralocorticoid excess: time of manifestation and complications despite treatment.

    PubMed

    Knops, Noël B B; Monnens, Leo A; Lenders, Jacques W; Levtchenko, Elena N

    2011-06-01

    Here we describe the case of a patient followed from birth because of a positive family history for apparent mineralocorticoid excess (AME) in an older brother. The patient, a girl, had normal serum electrolyte and blood pressure measurements in the first months after birth. Not until the age of 11 months did she develop anorexia and failure to thrive in combination with hypertension, hypokalemia, and metabolic alkalosis, which are consistent with the diagnosis of AME. This diagnosis was confirmed by mutation analysis of the HSD11B2 gene (C1228T). Treatment with amiloride and furosemide electrolyte disturbances normalized her blood pressure. At the age of 19 years she unexpectedly suffered a stroke. Additional investigations revealed no accepted risk factor for stroke. We discuss the possible underlying mechanisms for the delayed manifestation of hypertension and electrolyte disturbances in AME, propose an additional explanation for the stroke in this patient, and advise treatment with a mineralocorticoid receptor antagonist to reduce stroke risk in patients with AME.

  13. Detection of betanodaviruses in apparently healthy aquarium fishes and invertebrates

    PubMed Central

    Gomez, Dennis Kaw; Lim, Dong Joo; Baeck, Gun Wook; Youn, Hee Jeong; Shin, Nam Shik; Youn, Hwa Young; Hwang, Cheol Yong; Park, Jun Hong

    2006-01-01

    Betanodaviruses are the causative agents of viral nervous necrosis (VNN) in cultured marine fish. A total of 237 apparently healthy aquarium fish, marine (65 species) and freshwater (12 species) fishes and marine invertebrates (4 species), which were stocked in a commercial aquarium in Seoul, South Korea, were collected from November 2005 to February 2006. The brains of the fish and other tissues of the invertebrates were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR to detect betanodavirus. Positive nested PCR results were obtained from the brains of 8 marine fish species (shrimp fish Aeoliscus strigatus, milkfish Chanos chanos, three spot damsel Dascyllus trimaculatus, Japanese anchovy Engraulis japonicus, pinecone fish Monocentris japonica, blue ribbon eel Rhinomuraena quaesita, look down fish Selene vomer, yellow tang Zebrasoma flavesenes), 1 marine invertebrate species (spiny lobster Pamulirus versicolor), and 2 freshwater fish species (South American leaf fish Monocirrhus polyacanthus and red piranha Pygocentrus nattereri). The detection rate in nested PCR was 11/237 (4.64%). These subclinically infected aquarium fish and invertebrates may constitute an inoculum source of betanodaviruses for cultured fishes in the Korean Peninsula. PMID:17106229

  14. OH Column Abundance Apparent Response to Solar Cycle 23

    NASA Astrophysics Data System (ADS)

    Burnett, C. R.; Minschwaner, K. R.

    2009-12-01

    The 33-year series of high spectral resolution measurements of absorption of sunlight by OH at 308 nm has exhibited temporary decreases of column abundances in 1986, 1997, and 2008 near the times of minimum solar activity. These observations and analyses are of significance as they encompass three complete solar cycles for comparison. During solar cycle 23, the annual average abundances increased approximately 20% from the minimum abundance in 1997 to high-sun enhanced values in 2000-2006, then dropped approximately 15% in 2008. The abundances exhibited a pronounced reduction at solar minimum in August-October 2008, similar to that seen in fall 1986 and fall 1997. The average morning abundances on those occasions were 13% smaller than the 1980-88 corresponding average, about 0.9 x 1013 cm-2, with minimum values broadly consistent with model results. In contrast, high-sun OH abundances observed during periods of solar maximum are approximately 33% larger than modeled abundances. This discrepancy cannot be explained by reasonable adjustments of reaction rates or modeled constituent concentrations in the stratosphere or mesosphere. However, the observed responses to a tropopause fold event in 1988 and to the Pinatubo aerosol in 1991 do suggest an important contribution to the total OH column from the lower stratosphere. In addition to the apparent variations with solar activity, this OH column database contains a number of other effects such as diurnal and seasonal patterns, and geographic differences between observations from Colorado, Florida, Alaska, Micronesia, New Zealand, and New Mexico.

  15. Knoop Hardness - Apparent Yield Stress Relationship in Ceramics

    SciTech Connect

    Swab, Jeffrey J; LaSalvia, Jerry; Wereszczak, Andrew A; Strong, Kevin T; Danna, Dominic; Ragan, Meredith E; Ritt, Patrick J

    2012-01-01

    In Tabor's classical studies of the deformation of metals, the yield stress (Y) and hardness (H) were shown to be related according to H/Y {approx} 3 for complete or fully plastic deformation. Since then it has been anecdotally shown for ceramics that this ratio is <3. Interest exists to explore this further so Hertzian indentation was used to measure the apparent yield stress of numerous ceramics and metals and their results were compared with each material's load-dependent Knoop hardness. The evaluated ceramics included standard reference materials for hardness (silicon nitride and tungsten carbide), silicon carbide, alumina, and glass. Several steel compositions were also tested for comparison. Knoop hardness measurements at 19.6 N (i.e., toward 'complete or fully plastic deformation'), showed that 2 < H/Y < 3 for the metals and 0.8 < H/Y < 1.8 for the glasses and ceramics. Being that H/Y {ne} 3 for the ceramics indicates that Tabor's analysis is either not applicable to ceramics or that full plastic deformation is not achieved with a Knoop indentation or both.

  16. Pharmacokinetics of hexobarbital in acute hepatitis and after apparent recovery.

    PubMed

    Breimer, D D; Zilly, W; Richter, E

    1975-10-01

    The pharmacokinetics of hexobarbital were studied in 13 patients with acute hepatitis. Hexobarbital sodium was administered by zero order intravenous (iv) infusion, and plasma concentrations were determined regularly by gas chromatography. For each patient the data were fitted according to 2-compartment kinetics. The results were compared to those obtained for 14 healthy volunteers. The elimination half-life of hexobarbital was 490 +/- 186 min in the hepatitis patients and 261 +/- 69 min in the control group. Clearance was significantly reduced in the hepatitis group, whereas the volume of distribution at steady state was not significantly altered. For some patients the initial distribution volume was reduced. In 6 patients the experiment with hexobarbital was repeated after apparent recovery from hepatitis as judged by normal transaminase and bilirubin levels. Generally the half-life of hexobarbital was shorter and the clearance value was higher than during the acute illness, but the values had not yet returned to normal. Clinical recovery from liver disease is not accompanied by corresponding recovery of drug-metabolizing capability.

  17. Apparent thermal conductivity measurements by an unguarded technique

    NASA Astrophysics Data System (ADS)

    Graves, R. S.; Yarbrough, D. W.; McElroy, D. L.

    An unguarded longitudinal heat flow apparatus for measuring the apparent thermal conductivity (lambda/sub a) of insulations was tested. Heat flow is provided by a horizontal electrically heated Nichrome screen sandwiched between test samples that are bounded by temperature controlled copper plates and 9 cm of mineral fiber insulation. A determinate error analysis shows lambda/sub a/ measurement uncertainty to be less than + or - 1.7% for insulating materials as thin as 3 cm. Three-dimensional thermal modeling indicates negligible error in lambda/sub a/ due to edge loss for insulations up to 7.62 cm thick when the temperature difference across the sample is measured at the screen center. System repeatability and reproducibility were determined to be + or - 0.2%. Differences of lambda/sub a/ results from the screen tester and results from the National Bureau of Standards were 0.1% for a 10-kg/m(3) Calibration Transfer Standard and 0.9% for 127-kg/m(3) fibrous glass board (SRM 1450b). Measurements on fiberglass and rock wool batt insulations showed the dependence of lambda/sub a/ on density, temperature, temperature difference, plate emittance, and heat flow direction. Results obtained for lambda/sub a/ as a function of density at 240C differed by less than 2% from values obtained with a guarded hot plate. It is demonstrated that this simple technique has the accuracy and sensitivity needed for useful lambda/sub a/ measurements on thermal insulating materials.

  18. Apparent Transition Behavior of Widely-Used Turbulence Models

    NASA Technical Reports Server (NTRS)

    Rumsey, Christopher L.

    2006-01-01

    The Spalart-Allmaras and the Menter SST kappa-omega turbulence models are shown to have the undesirable characteristic that, for fully turbulent computations, a transition region can occur whose extent varies with grid density. Extremely fine two-dimensional grids over the front portion of an airfoil are used to demonstrate the effect. As the grid density is increased, the laminar region near the nose becomes larger. In the Spalart-Allmaras model this behavior is due to convergence to a laminar-behavior fixed point that occurs in practice when freestream turbulence is below some threshold. It is the result of a feature purposefully added to the original model in conjunction with a special trip function. This degenerate fixed point can also cause nonuniqueness regarding where transition initiates on a given grid. Consistent fully turbulent results can easily be achieved by either using a higher freestream turbulence level or by making a simple change to one of the model constants. Two-equation kappa-omega models, including the SST model, exhibit strong sensitivity to numerical resolution near the area where turbulence initiates. Thus, inconsistent apparent transition behavior with grid refinement in this case does not appear to stem from the presence of a degenerate fixed point. Rather, it is a fundamental property of the kappa-omega model itself, and is not easily remedied.

  19. Apparent Transition Behavior of Widely-Used Turbulence Models

    NASA Technical Reports Server (NTRS)

    Rumsey, Christopher L.

    2007-01-01

    The Spalart-Allmaras and the Menter SST k-omega turbulence models are shown to have the undesirable characteristic that, for fully turbulent computations, a transition region can occur whose extent varies with grid density. Extremely fine two-dimensional grids over the front portion of an airfoil are used to demonstrate the effect. As the grid density is increased, the laminar region near the nose becomes larger. In the Spalart-Allmaras model this behavior is due to convergence to a laminar-behavior fixed point that occurs in practice when freestream turbulence is below some threshold. It is the result of a feature purposefully added to the original model in conjunction with a special trip function. This degenerate fixed point can also cause non-uniqueness regarding where transition initiates on a given grid. Consistent fully turbulent results can easily be achieved by either using a higher freestream turbulence level or by making a simple change to one of the model constants. Two-equation k-omega models, including the SST model, exhibit strong sensitivity to numerical resolution near the area where turbulence initiates. Thus, inconsistent apparent transition behavior with grid refinement in this case does not appear to stem from the presence of a degenerate fixed point. Rather, it is a fundamental property of the k-omega model itself, and is not easily remedied.

  20. Short-duration radio bursts with apparent extragalactic dispersion

    SciTech Connect

    Saint-Hilaire, P.; Benz, A. O.; Monstein, C.

    2014-11-01

    We present the results of the longest yet undertaken search for apparently extragalactic radio bursts at the Bleien Radio Observatory covering 21,000 hr (898 days). The data were searched for events of less than 50 ms FWHM duration showing a ν{sup –2} drift in the spectrogram characteristic of the delay of radio waves in plasma. We have found five cases suggesting dispersion measures between 350 and 400 cm{sup –3} pc while searching in the range of 75-2000 cm{sup –3} pc. Four of the five events occurred between 10:27 and 11:24 a.m. local civil time. The only exception occurred at night with the full Moon in the beam. It was an event that poorly fits plasma dispersion, but had the characteristics of a solar Type III burst. However, we were not able to confirm that it was a lunar reflection. All events were observed with a log-periodic dipole within 6800 hr, but none with a more directional horn antenna observing the rest of the time. These properties suggest a terrestrial origin of the 'peryton' type reported before. However, the cause of these events remains ambiguous.

  1. Earths Climate Sensitivity: Apparent Inconsistencies in Recent Assessments

    SciTech Connect

    Schwartz, Stephen E.; Charlson, Robert J.; Kahn, Ralph; Rodhe, Henning

    2014-12-08

    Earth's equilibrium climate sensitivity (ECS) and forcing of Earth's climate system over the industrial era have been re-examined in two new assessments: the Fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change (IPCC), and a study by Otto et al. (2013). The ranges of these quantities given in these assessments and also in the Fourth (2007) IPCC Assessment are analyzed here within the framework of a planetary energy balance model, taking into account the observed increase in global mean surface temperature over the instrumental record together with best estimates of the rate of increase of planetary heat content. This analysis shows systematic differences among the several assessments and apparent inconsistencies within individual assessments. Importantly, the likely range of ECS to doubled CO₂ given in AR5, 1.5–4.5 K/(3.7 W m⁻²) exceeds the range inferred from the assessed likely range of forcing, 1.2–2.9 K/(3.7 W m⁻²), where 3.7 W ⁻² denotes the forcing for doubled CO₂. Such differences underscore the need to identify their causes and reduce the underlying uncertainties. Explanations might involve underestimated negative aerosol forcing, overestimated total forcing, overestimated climate sensitivity, poorly constrained ocean heating, limitations of the energy balance model, or a combination of effects.

  2. The influence of spontaneous brain oscillations on apparent motion perception.

    PubMed

    Sanders, Lia Lira Olivier; Auksztulewicz, Ryszard; Hohlefeld, Friederike U; Busch, Niko A; Sterzer, Philipp

    2014-11-15

    A good example of inferential processes in perception is long-range apparent motion (AM), the illusory percept of visual motion that occurs when two spatially distinct stationary visual objects are presented in alternating sequence. The AM illusion is strongest at presentation frequencies around 3 Hz. At lower presentation frequencies, the percept varies from trial to trial between AM and sequential alternation, while at higher frequencies perception varies between AM and two simultaneously flickering objects. Previous studies have demonstrated that prestimulus alpha oscillations explain trial-to-trial variability in detection performance for visual stimuli presented at threshold. In the present study, we investigated whether fluctuations of prestimulus alpha oscillations can also account for variations in AM perception. Prestimulus alpha power was stronger when observers reported AM perception in subsequent trials with low presentation frequencies, while at high presentation frequencies there were no significant differences in alpha power preceding AM and veridical flicker perception. Moreover, when observers perceived AM the prestimulus functional connectivity between frontal and occipital channels was increased in the alpha band, as revealed by the imaginary part of coherency, which is insensitive to artefacts from volume conduction. Dynamic causal modelling of steady-state responses revealed that the most likely direction of this fronto-occipital connectivity was from frontal to occipital sources. These results point to a role of ongoing alpha oscillations in the inferential process that gives rise to the perception of AM and suggest that fronto-occipital interactions bias perception towards internally generated predictions.

  3. Apparent Interfacial Fracture Toughness of Resin/Ceramic Systems

    PubMed Central

    Della Bona, A.; Anusavice, K.J.; Mecholsky, J.J.

    2008-01-01

    We suggest that the apparent interfacial fracture toughness (KA) may be estimated by fracture mechanics and fractography. This study tested the hypothesis that the KA of the adhesion zone of resin/ceramic systems is affected by the ceramic microstructure. Lithia disilicate-based (Empress2-E2) and leucite-based (Empress-E1) ceramics were surface-treated with hydrofluoric acid (HF) and/or silane (S), followed by an adhesive resin. Microtensile test specimens (n = 30; area of 1 ± 0.01 mm2) were indented (9.8 N) at the interface and loaded to failure in tension. We used tensile strength (σ) and the critical crack size (c) to calculate KA (KA = Yσc1/2) (Y = 1.65). ANOVA and Weibull analyses were used for statistical analyses. Mean KA (MPa•m1/2) values were: (E1HF) 0.26 ± 0.06; (E1S) 0.23 ± 0.06; (E1HFS) 0.30 ± 0.06; (E2HF) 0.31 ± 0.06; (E2S) 0.13 ± 0.05; and (E2HFS) 0.41 ± 0.07. All fractures originated from indentation sites. Estimation of interfacial toughness was feasible by fracture mechanics and fractography. The KA for the systems tested was affected by the ceramic microstructure and surface treatment. PMID:17062746

  4. Estimating phosphorus concentrations following alum treatment using apparent settling velocity

    USGS Publications Warehouse

    Panuska, John; Robertson, Dale M.

    2009-01-01

    he apparent settling velocity (Vs) is a term used in empirical, steady-state, mass-balance lake models to represent the net phosphorus flux from the water column. The Vollenweider (1969) mixed-reactor lake model was rearranged and used to calculate Vs values for total phosphorus (TP) for three lakes treated with alum to reduce the internal flux of P to the water column (Delavan Lake, Wisconsin; Lake Morey, Vermont; and West Twin Lake, Ohio). An analysis of Vs values was conducted using data from these three lakes for both the pre- and post-alum treated conditions. Analysis of Vs values for both the pre- and post-alum conditions in Lake Morey and West Twin Lake resulted in a post-treatment mean Vs value of 7 ± 2.0 m·yr−1. The effect of the alum treatment, although short-lived in Delavan Lake, resulted in a mean post-treatment Vs value of 3.4 ± 0.3 m·yr−1. The consistency in the post-treatment Vs values in Lake Morey and West Twin Lake is used to demonstrate a predictive analysis method for water column TP concentrations in lakes following a successful treatment of the anoxic sediment area with alum. Additional pre- and post-alum in-lake and watershed loading data are needed to advance this concept into a management model.

  5. Altered perception of apparent motion in schizophrenia spectrum disorder.

    PubMed

    Tschacher, Wolfgang; Dubouloz, Priscilla; Meier, Rahel; Junghan, Uli

    2008-06-30

    Apparent motion (AM), the Gestalt perception of motion in the absence of physical motion, was used to study perceptual organization and neurocognitive binding in schizophrenia. Associations between AM perception and psychopathology as well as meaningful subgroups were sought. Circular and stroboscopic AM stimuli were presented to 68 schizophrenia spectrum patients and healthy participants. Psychopathology was measured using the Positive and Negative Syndrome Scale (PANSS). Psychopathology was related to AM perception differentially: Positive and disorganization symptoms were linked to reduced gestalt stability; negative symptoms, excitement and depression had opposite regression weights. Dimensions of psychopathology thus have opposing effects on gestalt perception. It was generally found that AM perception was closely associated with psychopathology. No difference existed between patients and controls, but two latent classes were found. Class A members who had low levels of AM stability made up the majority of inpatients and control subjects; such participants were generally young and male, with short reaction times. Class B typically contained outpatients and some control subjects; participants in class B were older and showed longer reaction times. Hence AM perceptual dysfunctions are not specific for schizophrenia, yet AM may be a promising stage marker.

  6. Apparent target strength in long-rod penetration

    SciTech Connect

    Godwin, R.P.; Chapyak, E.J.

    1996-03-01

    The authors investigate the apparent enhancement of target strength in the steady-state Tate model of long-rod penetration. They show that computing the effective area over which the target behaves as a fluid provides an explanation of the effective 1-D target strength measured empirically. Expressing the effective target strength as R{sub t} = a {times} Y{sub t}, they postulate that a = A{sub e}/A{sub p}, where Y{sub t} is the nominal strength; A{sub e} is the effective target fluid cross-sectional area and A{sub p} the projectile cross-sectional area. For the case of a rod and projectile of the same material, they use the Tate model together with the jet model of Birkhoff et al. to show a {approx} 4 is likely. Simultaneously satisfying Newton`s Second Law and the Tate model yields a very general derivation of a = 4. By explicitly including strength terms in both the Tate equation and Newton`s Second Law, an even more general a = f(v,{rho}{sub p},{rho}{sub t},Y{sub p},Y{sub t}) can be derived.

  7. Tuning for temporal interval in human apparent motion detection.

    PubMed

    Bours, Roger J E; Stuur, Sanne; Lankheet, Martin J M

    2007-01-08

    Detection of apparent motion in random dot patterns requires correlation across time and space. It has been difficult to study the temporal requirements for the correlation step because motion detection also depends on temporal filtering preceding correlation and on integration at the next levels. To specifically study tuning for temporal interval in the correlation step, we performed an experiment in which prefiltering and postintegration were held constant and in which we used a motion stimulus containing coherent motion for a single interval value only. The stimulus consisted of a sparse random dot pattern in which each dot was presented in two frames only, separated by a specified interval. On each frame, half of the dots were refreshed and the other half was a displaced reincarnation of the pattern generated one or several frames earlier. Motion energy statistics in such a stimulus do not vary from frame to frame, and the directional bias in spatiotemporal correlations is similar for different interval settings. We measured coherence thresholds for left-right direction discrimination by varying motion coherence levels in a Quest staircase procedure, as a function of both step size and interval. Results show that highest sensitivity was found for an interval of 17-42 ms, irrespective of viewing distance. The falloff at longer intervals was much sharper than previously described. Tuning for temporal interval was largely, but not completely, independent of step size. The optimal temporal interval slightly decreased with increasing step size. Similarly, the optimal step size decreased with increasing temporal interval.

  8. Why do apparently healthy people use antacid tablets?

    PubMed

    Graham, D Y; Smith, J L; Patterson, D J

    1983-05-01

    Proprietary antacids represent a multimillion dollar business in this country. Marketing surveys have shown that approximately one-half of American adults have used antacids. Twenty-seven percent of adults take 2 or more doses per month. Seventy-five percent of total antacid consumption is by heavy users, defined as greater than 6 doses per week (less than 5% of adults). We investigated why apparently healthy people are heavy antacid users. Thirty-seven heavy users were evaluated. The median duration of antacid use was 20 years, and most took antacids 2-6 times per day, concentrated through the work week. The primary diagnosis was reflux esophagitis in 31 (84%), peptic ulcer disease in one, and nonulcer dyspepsia in five. Ninety-five percent had symptoms consistent with reflux esophagitis. Thirty-three completed a 1 month double-blind, randomized cross-over trial of antacid tablets (14 mEq neutralizing capacity per tablet) versus placebo. Twenty-nine correctly identified the antacid product (p less than 0.0001). Twenty-three subjects underwent Bernstein tests and endoscopy; 21 had positive Bernstein tests, 13 had definite esophagitis as determined endoscopically. We conclude 1) heavy proprietary antacid tablet use in the adult male is not an expression of functional disease but is due to reflux esophagitis, 2) tablet use can be effective symptomatic treatment, and 3) history is an adequate evaluation for most heavy antacid tablet users.

  9. Apparent diffusion profile estimation from high angular resolution diffusion images

    NASA Astrophysics Data System (ADS)

    Descoteaux, Maxime; Angelino, Elaine; Fitzgibbons, Shaun; Deriche, Rachid

    2006-03-01

    High angular resolution diffusion imaging (HARDI) has recently been of great interest to characterize non-Gaussian diffusion process. In the white matter of the brain, this occurs when fiber bundles cross, kiss or diverge within the same voxel. One of the important goal is to better describe the apparent diffusion process in these multiple fiber regions, thus overcoming the limitations of classical diffusion tensor imaging (DTI). In this paper, we design the appropriate mathematical tools to describe noisy HARDI data. Using a meaningful modified spherical harmonics basis to capture the physical constraints of the problem, we propose a new regularization algorithm to estimate a smoother and closer diffusivity profile to the true diffusivities without noise. We exploit properties of the spherical harmonics to define a smoothing term based on the Laplace-Beltrami for functions defined on the unit sphere. An additional contribution of the paper is the derivation of the general transformation taking the spherical harmonics coefficients to the high order tensor independent elements. This allows the careful study of the state of the art high order anisotropy measures computed from either spherical harmonics or tensor coefficients. We analyze their ability to characterize the underlying diffusion process. We are able to recover voxels with isotropic, single fiber anisotropic and multiple fiber anisotropic diffusion. We test and validate the approach on diffusion profiles from synthetic data and from a biological rat phantom.

  10. Immunohistochemical analysis of steroidogenic enzymes in ovarian-type stroma of pancreatic mucinous cystic neoplasms: Comparative study of subepithelial stromal cells in intraductal papillary mucinous neoplasms of the pancreas.

    PubMed

    Ishida, Kazuyuki; Sasano, Hironobu; Moriya, Takuya; Takahashi, Yayoi; Sugimoto, Ryo; Mue, Yoshiharu; Murakami, Keigo; Fujishima, Fumiyoshi; Nakamura, Yasuhiro; Morikawa, Takanori; Motoi, Fuyuhiko; Suzuki, Takashi; Unno, Michiaki; Sugai, Tamotsu

    2016-05-01

    Mucinous cystic neoplasms (MCNs) are generally defined as cyst-forming epithelial neoplasms that arise in the pancreas and harbor characteristic ovarian-type stroma beneath the epithelium. In this study, we compared the immunoreactivity of steroid-related factors in these subepithelial stromal cells in MCNs to those in intraductal papillary mucinous neoplasms (IPMNs) to further characterize this unique MCN ovarian-type stroma through evaluation of sex steroid biosynthesis. Twenty MCNs and twenty IPMNs were examined. Immunoreactivity of steroid hormone receptors, including estrogen receptor (ERα and ERβ), progesterone receptor (PR, PR-A, and PR-B), and androgen receptor (AR), was more frequently detected in MCN ovarian-type stromal cells than in IPMN stromal cells (P < 0.01). The H-scores (mean ± SD) of steroidogenic factor (SF)-1 were also significantly higher in MCNs (112.3 ± 33.1) than in IPMNs (0.9 ± 1.2) (P < 0.01). The steroidogenic enzymes cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), cytochrome P450 17 alpha-hydroxylase (P450c17) and 3β-hydroxysteroid dehydrogenase (3β-HSD) showed immunoreactivity in 9/20 (45.0 %), 15/20 (75.0 %) and 13/20 (65.0 %), respectively, of ovarian-type stroma from MCN cases. These results demonstrate that the ovarian-type stroma of MCNs can express steroidogenic enzymes. Thus, the ovarian-type stroma of MCNs can produce sex steroids that may also act on these cells.

  11. DISCOVERY OF AN APPARENT HIGH LATITUDE GALACTIC SUPERNOVA REMNANT

    SciTech Connect

    Fesen, Robert A.; Neustadt, Jack M. M.; Black, Christine S.; Koeppel, Ari H. D.

    2015-10-10

    Deep Hα images of a faint emission complex 4.°0 × 5.°5 in angular extent and located far off the Galactic plane at l = 70.°0, b = −21.°5 reveal numerous thin filaments suggestive of a supernova remnant’s (SNR’s) shock emission. Low dispersion optical spectra covering the wavelength range 4500–7500 Å show only Balmer line emissions for one filament while three others show a Balmer dominated spectrum along with weak [N i] 5198, 5200 Å, [O i] 6300, 6364 Å, [N ii] 6583 Å, [S ii] 6716, 6731 Å, and in one case [O iii] 5007 Å line emission. Many of the brighter Hα filaments are visible in near-UV GALEX images presumably due to C iii] 1909 Å line emission. ROSAT All Sky Survey images of this region show a faint crescent-shaped X-ray emission nebula coincident with the portion of the Hα nebulosity closest to the Galactic plane. The presence of long, thin Balmer dominated emission filaments with associated UV emission and coincident X-ray emission suggests this nebula is a high latitude Galactic SNR despite a lack of known associated nonthermal radio emission. Relative line intensities of the optical lines in some filaments differ from commonly observed [S ii]/Hα ≥ 0.4 radiative shocked filaments and typical Balmer filaments in SNRs. We discuss possible causes for the unusual optical SNR spectra.

  12. Apparent and Intrinsic Evolution of Active Region Upflows

    NASA Astrophysics Data System (ADS)

    Baker, Deborah; Janvier, Miho; Démoulin, Pascal; Mandrini, Cristina H.

    2017-04-01

    We analyze the evolution of Fe xii coronal plasma upflows from the edges of ten active regions (ARs) as they cross the solar disk using the Hinode Extreme Ultraviolet Imaging Spectrometer (EIS) to do this. Confirming the results of Démoulin et al. ( Sol. Phys. 283, 341, 2013), we find that for each AR there is an observed long-term evolution of the upflows. This evolution is largely due to the solar rotation that progressively changes the viewpoint of dominantly stationary upflows. From this projection effect, we estimate the unprojected upflow velocity and its inclination to the local vertical. AR upflows typically fan away from the AR core by 40° to nearly vertical for the following polarity. The span of inclination angles is more spread out for the leading polarity, with flows angled from -29° (inclined toward the AR center) to 28° (directed away from the AR). In addition to the limb-to-limb apparent evolution, we identify an intrinsic evolution of the upflows that is due to coronal activity, which is AR dependent. Furthermore, line widths are correlated with Doppler velocities only for the few ARs with the highest velocities. We conclude that for the line widths to be affected by the solar rotation, the spatial gradient of the upflow velocities must be large enough such that the line broadening exceeds the thermal line width of Fe xii. Finally, we find that upflows occurring in pairs or multiple pairs are a common feature of ARs observed by Hinode/EIS, with up to four pairs present in AR 11575. This is important for constraining the upflow-driving mechanism as it implies that the mechanism is not local and does not occur over a single polarity. AR upflows originating from reconnection along quasi-separatrix layers between overpressure AR loops and neighboring underpressure loops is consistent with upflows occurring in pairs, unlike other proposed mechanisms that act locally in one polarity.

  13. Normative Apparent Diffusion Coefficient Values in the Developing Fetal Brain

    PubMed Central

    Schneider, M.M.; Berman, J.I.; Baumer, F.M.; Glass, H.C.; Jeng, S.; Jeremy, R.J.; Esch, M.; Biran, V.; Barkovich, A.J.; Studholme, C.; Xu, D.; Glenn, O.A.

    2013-01-01

    BACKGROUND AND PURPOSE Previous studies of diffusion-weighted imaging (DWI) in fetuses are limited. Because of the need for normative data for comparison with young fetuses and preterm neonates with suspected brain abnormalities, we studied apparent diffusion coefficient (ADC) values in a population of singleton, nonsedated, healthy fetuses. MATERIALS AND METHODS DWI was performed in 28 singleton nonsedated fetuses with normal or questionably abnormal results on sonography and normal fetal MR imaging results; 10 fetuses also had a second fetal MR imaging, which included DWI. ADC values in the periatrial white matter (WM), frontal WM, thalamus, basal ganglia, cerebellum, and pons were plotted against gestational age and analyzed with linear regression. We compared mean ADC in different regions using the Tukey Honestly Significant Difference test. We also compared rates of decline in ADC with increasing gestational age across different areas by using the t test with multiple comparisons correction. Neurodevelopmental outcome was assessed. RESULTS Median gestational age was 24.28 weeks (range, 21–33.43 weeks). Results of all fetal MR imaging examinations were normal, including 1 fetus with a normal variant of a cavum velum interpositum. ADC values were highest in the frontal and periatrial WM and lowest in the thalamus and pons. ADC declined with increasing gestational age in periatrial WM (P = .0003), thalamus (P < .0001), basal ganglia (P = .0035), cerebellum (P < .0001), and pons (P = .024). Frontal WM ADC did not significantly change with gestational age. ADC declined fastest in the cerebellum, followed by the thalamus. CONCLUSIONS Regional differences in nonsedated fetal ADC values and their evolution with gestational age likely reflect differences in brain maturation and are similar to published data in premature neonates. PMID:19556350

  14. Deep depth undex simulator

    SciTech Connect

    Higginbotham, R. R.; Malakhoff, A.

    1985-01-29

    A deep depth underwater simulator is illustrated for determining the dual effects of nuclear type underwater explosion shockwaves and hydrostatic pressures on a test vessel while simulating, hydrostatically, that the test vessel is located at deep depths. The test vessel is positioned within a specially designed pressure vessel followed by pressurizing a fluid contained between the test and pressure vessels. The pressure vessel, with the test vessel suspended therein, is then placed in a body of water at a relatively shallow depth, and an explosive charge is detonated at a predetermined distance from the pressure vessel. The resulting shockwave is transmitted through the pressure vessel wall so that the shockwave impinging on the test vessel is representative of nuclear type explosive shockwaves transmitted to an underwater structure at great depths.

  15. Deep gluteal syndrome

    PubMed Central

    Martin, Hal David; Reddy, Manoj; Gómez-Hoyos, Juan

    2015-01-01

    Deep gluteal syndrome describes the presence of pain in the buttock caused from non-discogenic and extrapelvic entrapment of the sciatic nerve. Several structures can be involved in sciatic nerve entrapment within the gluteal space. A comprehensive history and physical examination can orientate the specific site where the sciatic nerve is entrapped, as well as several radiological signs that support the suspected diagnosis. Failure to identify the cause of pain in a timely manner can increase pain perception, and affect mental control, patient hope and consequently quality of life. This review presents a comprehensive approach to the patient with deep gluteal syndrome in order to improve the understanding of posterior hip anatomy, nerve kinematics, clinical manifestations, imaging findings, differential diagnosis and treatment considerations. PMID:27011826

  16. Project DEEP STEAM

    NASA Astrophysics Data System (ADS)

    Aeschliman, D. P.; Clay, R. G.; Donaldson, A. B.; Eisenhawer, S. W.; Fox, R. L.; Johnson, D. R.; Mulac, A. J.

    1982-01-01

    The objective of Project DEEP STEAM is to develop the technology to economically produce heavy oils from deep reservoirs. The tasks included in this project are the development of thermally efficient delivery systems and downhole steam generation systems. During the period January 1-March 31, 1981, effort has continued on a low pressure combustion downhole generator (Rocketdyne), and on two high pressure designs (Foster-Miller Associates, Sandia National Laboratories). The Sandia design was prepared for deployment in the Wilmington Field at Long Beach, California. Progress continued on the Min-Stress II packer concept at L'Garde, Inc., and on the extruded metal packer at Foster-Miller. Initial bare string field data are reported on the insulated tubular test at Lloydminster, Saskatchewan, Canada.

  17. Deep Water Ocean Acoustics

    DTIC Science & Technology

    2015-07-17

    under-ice scattering , bathymetric diffraction and the application of the ocean acoustic Parabolic Equation to infrasound. 2. Tasks a. Task 1...QSR-14C0172-Ocean Acoustics -063015 Figure 10. Estimated reflection coefficient as a function of frequency by taking the difference of downgoing and...OASIS, INC. 1 Report No. QSR-14C0172-Ocean Acoustics -063015 Quarterly Progress Report Technical and Financial Deep Water Ocean Acoustics

  18. Deep Brain Stimulation

    PubMed Central

    Chen, X.L.; Xiong, Y.Y.; Xu, G.L.; Liu, X.F.

    2013-01-01

    Deep brain stimulation (DBS) has provided remarkable therapeutic benefits for people with a variety of neurological disorders. Despite the uncertainty of the precise mechanisms underlying its efficacy, DBS is clinically effective in improving motor function of essential tremor, Parkinson's disease and primary dystonia and in relieving obsessive-compulsive disorder. Recently, this surgical technique has continued to expand to other numerous neurological diseases with encouraging results. This review highlighted the current and potential future clinical applications of DBS. PMID:25187779

  19. Deep Water Formation

    NASA Technical Reports Server (NTRS)

    Killworth, P. D.

    1984-01-01

    Some simple arguments on plumes of dense water and filling boxes were given. What determines the time for a large-scale environment to be modified by the injection of dense water at its edge is the mass flux, not the buoyancy flux. However, it is the denser buoyancy flux, when there are several competing plumes (e.g., the Mediterranean outflow versus the Denmark Strait outflow) that determines which plume will provide the bottom water for that ocean basin. It was noted that the obvious laboratory experiment (rotate a pie-shaped annulus, and heat/cool it on the surface) had never been performed. Thus, to some extent our belief that deep convection is somehow automatic at high latitudes to close off some ill-defined meridional circulation has never been tested. A summary of deep convection was given. The two fundamental formation mechanisms were shown. Of the two, it is open-ocean convection which forms the water which supplies the Denmark Strait overflow -- in all likelihood, as formation in the Greenland Sea remains stubbornly unobserved. But it is the slope convection which finally creates North Atlantic deep water, following the Denmark Strait overspill.

  20. The biodiversity of the deep Southern Ocean benthos.

    PubMed

    Brandt, A; De Broyer, C; De Mesel, I; Ellingsen, K E; Gooday, A J; Hilbig, B; Linse, K; Thomson, M R A; Tyler, P A

    2007-01-29

    Our knowledge of the biodiversity of the Southern Ocean (SO) deep benthos is scarce. In this review, we describe the general biodiversity patterns of meio-, macro- and megafaunal taxa, based on historical and recent expeditions, and against the background of the geological events and phylogenetic relationships that have influenced the biodiversity and evolution of the investigated taxa. The relationship of the fauna to environmental parameters, such as water depth, sediment type, food availability and carbonate solubility, as well as species interrelationships, probably have shaped present-day biodiversity patterns as much as evolution. However, different taxa exhibit different large-scale biodiversity and biogeographic patterns. Moreover, there is rarely any clear relationship of biodiversity pattern with depth, latitude or environmental parameters, such as sediment composition or grain size. Similarities and differences between the SO biodiversity and biodiversity of global oceans are outlined. The high percentage (often more than 90%) of new species in almost all taxa, as well as the high degree of endemism of many groups, may reflect undersampling of the area, and it is likely to decrease as more information is gathered about SO deep-sea biodiversity by future expeditions. Indeed, among certain taxa such as the Foraminifera, close links at the species level are already apparent between deep Weddell Sea faunas and those from similar depths in the North Atlantic and Arctic. With regard to the vertical zonation from the shelf edge into deep water, biodiversity patterns among some taxa in the SO might differ from those in other deep-sea areas, due to the deep Antarctic shelf and the evolution of eurybathy in many species, as well as to deep-water production that can fuel the SO deep sea with freshly produced organic matter derived not only from phytoplankton, but also from ice algae.

  1. The biodiversity of the deep Southern Ocean benthos

    PubMed Central

    Brandt, A; De Broyer, C; De Mesel, I; Ellingsen, K.E; Gooday, A.J; Hilbig, B; Linse, K; Thomson, M.R.A; Tyler, P.A

    2006-01-01

    Our knowledge of the biodiversity of the Southern Ocean (SO) deep benthos is scarce. In this review, we describe the general biodiversity patterns of meio-, macro- and megafaunal taxa, based on historical and recent expeditions, and against the background of the geological events and phylogenetic relationships that have influenced the biodiversity and evolution of the investigated taxa. The relationship of the fauna to environmental parameters, such as water depth, sediment type, food availability and carbonate solubility, as well as species interrelationships, probably have shaped present-day biodiversity patterns as much as evolution. However, different taxa exhibit different large-scale biodiversity and biogeographic patterns. Moreover, there is rarely any clear relationship of biodiversity pattern with depth, latitude or environmental parameters, such as sediment composition or grain size. Similarities and differences between the SO biodiversity and biodiversity of global oceans are outlined. The high percentage (often more than 90%) of new species in almost all taxa, as well as the high degree of endemism of many groups, may reflect undersampling of the area, and it is likely to decrease as more information is gathered about SO deep-sea biodiversity by future expeditions. Indeed, among certain taxa such as the Foraminifera, close links at the species level are already apparent between deep Weddell Sea faunas and those from similar depths in the North Atlantic and Arctic. With regard to the vertical zonation from the shelf edge into deep water, biodiversity patterns among some taxa in the SO might differ from those in other deep-sea areas, due to the deep Antarctic shelf and the evolution of eurybathy in many species, as well as to deep-water production that can fuel the SO deep sea with freshly produced organic matter derived not only from phytoplankton, but also from ice algae. PMID:17405207

  2. Hymenoscyphus fraxineus vs. Hymenoscyphus albidus – A comparative light microscopic study on the causal agent of European ash dieback and related foliicolous, stroma-forming species

    PubMed Central

    Baral, Hans-Otto; Bemmann, Martin

    2014-01-01

    Five species of Hymenoscyphus that fruit on black stromatized parts of dead leaves of deciduous trees are presented, giving details on their morphological and ecological characteristics. Several of these species have previously been misplaced in rutstroemiaceous genera because of the presence of a substratal stroma. However, the heteropolar, scutuloid ascospores with an often hook-like lateral protrusion at the rounded apex and the ascus apical ring of the Hymenoscyphus-type represent two reliable morphological characteristics that, together with molecular data, provide clear evidence for their placement in the genus Hymenoscyphus (Helotiaceae). Among the species treated is Hymenoscyphus fraxineus (=Hymenoscyphus pseudoalbidus), the causal agent of the European ash dieback disease. Since 1992 this species started within Europe to replace the rather uncommon Hymenoscyphus albidus, which is likewise confined to leaves of Fraxinus. Hy. fraxineus has been recorded already since 1990 in Eastern Asia (Japan, Korea, northeast of China), where it had been initially misidentified as Lambertella albida (≡Hy. albidus). In these regions, it occurs as a harmless saprotroph on Fraxinus mandshurica and Fraxinus rhynchophylla, suggesting that those populations are native while the European ash dieback disease has a recent Eastern Asiatic origin. The distinctly higher genetic diversity found in Japanese Hy. fraxineus in contrast to European Hy. fraxineus supports this view. Genetic similarities between Japanese Hy. fraxineus and European Hy. albidus suggest that also Hy. albidus might be a descendant of Asian Hy. fraxineus, though having invaded Europe much earlier. However, consistent genetic deviation between European and Asian Hy. fraxineus at two nucleotide positions of the ITS region indicates that the European ash disease originates from a region different from the presently known areas in Eastern Asia. Our results underline the importance of detailed morphological studies

  3. Hymenoscyphus fraxineus vs. Hymenoscyphus albidus - A comparative light microscopic study on the causal agent of European ash dieback and related foliicolous, stroma-forming species.

    PubMed

    Baral, Hans-Otto; Bemmann, Martin

    2014-10-02

    Five species of Hymenoscyphus that fruit on black stromatized parts of dead leaves of deciduous trees are presented, giving details on their morphological and ecological characteristics. Several of these species have previously been misplaced in rutstroemiaceous genera because of the presence of a substratal stroma. However, the heteropolar, scutuloid ascospores with an often hook-like lateral protrusion at the rounded apex and the ascus apical ring of the Hymenoscyphus-type represent two reliable morphological characteristics that, together with molecular data, provide clear evidence for their placement in the genus Hymenoscyphus (Helotiaceae). Among the species treated is Hymenoscyphus fraxineus (=Hymenoscyphus pseudoalbidus), the causal agent of the European ash dieback disease. Since 1992 this species started within Europe to replace the rather uncommon Hymenoscyphus albidus, which is likewise confined to leaves of Fraxinus. Hy. fraxineus has been recorded already since 1990 in Eastern Asia (Japan, Korea, northeast of China), where it had been initially misidentified as Lambertella albida (≡Hy. albidus). In these regions, it occurs as a harmless saprotroph on Fraxinus mandshurica and Fraxinus rhynchophylla, suggesting that those populations are native while the European ash dieback disease has a recent Eastern Asiatic origin. The distinctly higher genetic diversity found in Japanese Hy. fraxineus in contrast to European Hy. fraxineus supports this view. Genetic similarities between Japanese Hy. fraxineus and European Hy. albidus suggest that also Hy. albidus might be a descendant of Asian Hy. fraxineus, though having invaded Europe much earlier. However, consistent genetic deviation between European and Asian Hy. fraxineus at two nucleotide positions of the ITS region indicates that the European ash disease originates from a region different from the presently known areas in Eastern Asia. Our results underline the importance of detailed morphological studies

  4. Infrared microspectroscopy identifies biomolecular changes associated with chronic oxidative stress in mammary epithelium and stroma of breast tissues from healthy young women

    PubMed Central

    Patel, Imran I; Shearer, Debra A; Fogarty, Simon W; Fullwood, Nigel J; Quaroni, Luca; Martin, Francis L; Weisz, Judith

    2014-01-01

    Studies of the decades-long latent stages of breast carcinogenesis have been limited to when hyperplastic lesions are already present. Investigations of earlier stages of breast cancer (BC) latency have been stymied by the lack of fiducial biomarkers needed to identify where in histologically normal tissues progression toward a BC might be taking place. Recent evidence suggests that a marker of chronic oxidative stress (OxS), protein adducts of 4-hydroxy-2-nonenal (4HNE), can meet this need. Specifically: (1) 4HNE immunopositive (4HNE+) mammary epithelial (ME) cells were found to be prevalent in normal (reduction mammoplasty) tissues of most women (including many teenagers) studied, representative of those living in the United States’ high risk-posing environment and: (2) marked (>1.5-fold) differences were identified between tissues of healthy young women with many vs. few 4HNE+ ME cells in the relative levels of transcripts for 42 of the 84 OxS-associated genes represented in SABioscience Oxidative-Stress/Oxidative-Defense PCR array. Herein we used synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to identify molecular changes associated with 4HNE adducts in basal and luminal ME cells in terminal ductal units (TDLU), which are the cells of origin of BC, and associated intralobular and interlobular stroma, known contributors to carcinogenesis. Multivariate analysis-derived wavenumbers differentiated 4HNE+ and 4HNE− cells in each of the anatomical compartments. Specifically, principal component and linear discriminant analyses of mid-infrared spectra obtained from these cells revealed unambiguous, statistically highly significant differences in the “biochemical fingerprint” of 4HNE+ vs. 4HNE− luminal and basal ME cells, as well as between associated intralobular and interlobular stroma. These findings demonstrate further SR-FTIR microspectroscopy’s ability to identify molecular changes associated with altered

  5. Capacity of lung stroma to educate dendritic cells inhibiting mycobacteria-specific T-cell response depends upon genetic susceptibility to tuberculosis.

    PubMed

    Kapina, Marina A; Rubakova, Elvira I; Majorov, Konstantin B; Logunova, Nadezhda N; Apt, Alexander S

    2013-01-01

    The balance between activation and inhibition of local immune responses in affected tissues during prolonged chronic infections is important for host protection. There is ample evidence that regulatory, tolerogenic dendritic cells (DC) are developed and present in tissues and inhibit overwhelming inflammatory reactions. Also, it was firmly established that stromal microenvironment of many organs is able to induce development of immature regulatory DC (DCreg), an essential element of a general immune regulatory network. However, direct experimental data demonstrating inhibition of immune responses by stroma-instructed immature DCreg in infectious models are scarce, and virtually nothing is known about functioning of this axis of immunity during tuberculosis (TB) infection. In this study, we demonstrate that lung stromal cells are capable of supporting the development in culture of immature CD11b(+)CD11c(low)CD103(-) DCreg from lineage-negative (lin(-)) bone marrow precursors. DCreg developed on lung stroma isolated from mice of genetically TB-hyper-susceptible I/St and relatively resistant B6 inbred strains inhibited proliferative response of mycobacteria-specific CD4(+) T-cell lines a dose-dependent manner. Importantly, the inhibitory activity of B6 DCreg was substantially higher than that of I/St Dcreg. Moreover, when the donors of stromal cells were chronically infected with virulent mycobacteria, the capacity to instruct inhibitory DCreg was retained in B6, but further diminished in I/St stromal cells. DCreg-provided suppression was mediated by a few soluble mediators, including PGE2, NO and IL-10. The content of CD4(+)Foxp3(+) Treg cells in the mediastinal, lung-draining lymph nodes at the advanced stages of chronic infection did not change in I/St, but increased 2-fold in B6 mice, and lung pathology was much more pronounced in the former mice. Taken together, these data provide genetic evidence that the capacity to maintain populations of regulatory cells

  6. The deep subterranean biosphere

    NASA Astrophysics Data System (ADS)

    Pedersen, Karsten

    1993-08-01

    The main purpose with this review is to summarise present research on the microbiology of deep subterranean environments, deeper than 50-100 m. Included are mainly studies where drilling, excavation, core sampling and ground water sampling have been made for research. Studies done in environments penetrated for commercial purposes, such as water wells, mining, oil recovery etc., have been dismissed because of the obvious risk for contamination during the penetration. Different measures that can be applied to reduce the risk of microbial contamination of sampled specimens by the access operations are discussed. The requirement for reliable estimations of the present microbial biomass, its activity and diversity in subterranean ecosystems, is fundamental. An array of different methods to achieve this goal are presented. The depth limit for subterranean life is suggested to be set by temperature, provided there is energy available for microbial life. If so, it should be possible to enrich thermophilic bacteria from deep hot ground waters which also has been done. There are only a few sites where the subterranean microbiology has been studied in multidisiplinary programs including chemistry and geology. The two most extensively published sites are the sediments of the Atlantic coastal plain of South Carolina, USA, studied in a subsurface program, initiated and sponsored by the U.S. Department of Energy, and crystalline bed-rock in Sweden studied in a program concerning the safety of future underground repositories for nuclear waste. This review presents an array of independent reports suggesting that microbial life is widespread at depth in the crust of earth—the deep subterranean biosphere. The obvious consequences is that microbes may be involved in many subterranean geochemical processes, such as diagenesis, weathering, precipitation, and in oxidation or reduction reactions of metals, carbon, nitrogen and sulfur—just as they are in most terranean environments.

  7. Deep Space Positioning System

    NASA Technical Reports Server (NTRS)

    Vaughan, Andrew T. (Inventor); Riedel, Joseph E. (Inventor)

    2016-01-01

    A single, compact, lower power deep space positioning system (DPS) configured to determine a location of a spacecraft anywhere in the solar system, and provide state information relative to Earth, Sun, or any remote object. For example, the DPS includes a first camera and, possibly, a second camera configured to capture a plurality of navigation images to determine a state of a spacecraft in a solar system. The second camera is located behind, or adjacent to, a secondary reflector of a first camera in a body of a telescope.

  8. Deep shadow occulter

    NASA Technical Reports Server (NTRS)

    Cash, Webster (Inventor)

    2010-01-01

    Methods and apparatus are disclosed for occulting light. The occulter shape suppresses diffraction at any given size or angle and is practical to build because it can be made binary to avoid scatter. Binary structures may be fully opaque or fully transmitting at specific points. The diffraction suppression is spectrally broad so that it may be used with incoherent white light. An occulter may also include substantially opaque inner portion and an at least partially transparent outer portion. Such occulters may be used on the ground to create a deep shadow in a short distance, or may be used in space to suppress starlight and reveal exoplanets.

  9. Deep-sea Hexactinellida (Porifera) of the Weddell Sea

    NASA Astrophysics Data System (ADS)

    Janussen, Dorte; Tabachnick, Konstantin R.; Tendal, Ole S.

    2004-07-01

    New Hexactinellida from the deep Weddel Sea are described. This moderately diverse hexactinellid fauna includes 14 species belonging to 12 genera, of which five species and one subgenus are new to science: Periphragella antarctica n. sp., Holascus pseudostellatus n. sp., Caulophacus (Caulophacus) discohexactinus n. sp., C. ( Caulodiscus) brandti n. sp., C. ( Oxydiscus) weddelli n. sp., and C. ( Oxydiscus) n. subgen. So far, 20 hexactinellid species have been reported from the deep Weddell Sea, 15 are known from the northern part and 10 only from here, while 10 came from the southern area, and five of these only from there. However, this apparent high "endemism" of Antarctic hexactinellid sponges is most likely the result of severe undersampling of the deep-sea fauna. We find no reason to believe that a division between an oceanic and a more continental group of species exists. The current poor database indicates that a substantial part of the deep hexactinellid fauna of the Weddell Sea is shared with other deep-sea regions, but it does not indicate a special biogeographic relationship with any other ocean.

  10. A ubiquitous thermoacidophilic archaeon from deep-sea hydrothermal vents

    USGS Publications Warehouse

    Reysenbach, A.-L.; Liu, Yajing; Banta, A.B.; Beveridge, T.J.; Kirshtein, J.D.; Schouten, S.; Tivey, M.K.; Von Damm, Karen L.; Voytek, M.A.

    2006-01-01

    Deep-sea hydrothermal vents are important in global biogeochemical cycles, providing biological oases at the sea floor that are supported by the thermal and chemical flux from the Earth's interior. As hot, acidic and reduced hydrothermal fluids mix with cold, alkaline and oxygenated sea water, minerals precipitate to form porous sulphide-sulphate deposits. These structures provide microhabitats for a diversity of prokaryotes that exploit the geochemical and physical gradients in this dynamic ecosystem. It has been proposed that fluid pH in the actively venting sulphide structures is generally low (pH < 4.5), yet no extreme thermoacidophile has been isolated from vent deposits. Culture-independent surveys based on ribosomal RNA genes from deep-sea hydrothermal deposits have identified a widespread euryarchaeotal lineage, DHVE2 (deep-sea hydrothermal vent euryarchaeotic 2). Despite the ubiquity and apparent deep-sea endemism of DHVE2, cultivation of this group has been unsuccessful and thus its metabolism remains a mystery. Here we report the isolation and cultivation of a member of the DHVE2 group, which is an obligate thermoacidophilic sulphur- or iron-reducing heterotroph capable of growing from pH 3.3 to 5.8 and between 55 and 75??C. In addition, we demonstrate that this isolate constitutes up to 15% of the archaeal population, providing evidence that thermoacidophiles may be key players in the sulphur and iron cycling at deep-sea vents. ?? 2006 Nature Publishing Group.

  11. The nature of thinking, shallow and deep

    PubMed Central

    Brase, Gary L.

    2014-01-01

    Because the criteria for success differ across various domains of life, no single normative standard will ever work for all types of thinking. One method for dealing with this apparent dilemma is to propose that the mind is made up of a large number of specialized modules. This review describes how this multi-modular framework for the mind overcomes several critical conceptual and theoretical challenges to our understanding of human thinking, and hopefully clarifies what are (and are not) some of the implications based on this framework. In particular, an evolutionarily informed “deep rationality” conception of human thinking can guide psychological research out of clusters of ad hoc models which currently occupy some fields. First, the idea of deep rationality helps theoretical frameworks in terms of orienting themselves with regard to time scale references, which can alter the nature of rationality assessments. Second, the functional domains of deep rationality can be hypothesized (non-exhaustively) to include the areas of self-protection, status, affiliation, mate acquisition, mate retention, kin care, and disease avoidance. Thus, although there is no single normative standard of rationality across all of human cognition, there are sensible and objective standards by which we can evaluate multiple, fundamental, domain-specific motives underlying human cognition and behavior. This review concludes with two examples to illustrate the implications of this framework. The first example, decisions about having a child, illustrates how competing models can be understood by realizing that different fundamental motives guiding people’s thinking can sometimes be in conflict. The second example is that of personifications within modern financial markets (e.g., in the form of corporations), which are entities specifically constructed to have just one fundamental motive. This single focus is the source of both the strengths and flaws in how such entities behave. PMID

  12. The nature of thinking, shallow and deep.

    PubMed

    Brase, Gary L

    2014-01-01

    Because the criteria for success differ across various domains of life, no single normative standard will ever work for all types of thinking. One method for dealing with this apparent dilemma is to propose that the mind is made up of a large number of specialized modules. This review describes how this multi-modular framework for the mind overcomes several critical conceptual and theoretical challenges to our understanding of human thinking, and hopefully clarifies what are (and are not) some of the implications based on this framework. In particular, an evolutionarily informed "deep rationality" conception of human thinking can guide psychological research out of clusters of ad hoc models which currently occupy some fields. First, the idea of deep rationality helps theoretical frameworks in terms of orienting themselves with regard to time scale references, which can alter the nature of rationality assessments. Second, the functional domains of deep rationality can be hypothesized (non-exhaustively) to include the areas of self-protection, status, affiliation, mate acquisition, mate retention, kin care, and disease avoidance. Thus, although there is no single normative standard of rationality across all of human cognition, there are sensible and objective standards by which we can evaluate multiple, fundamental, domain-specific motives underlying human cognition and behavior. This review concludes with two examples to illustrate the implications of this framework. The first example, decisions about having a child, illustrates how competing models can be understood by realizing that different fundamental motives guiding people's thinking can sometimes be in conflict. The second example is that of personifications within modern financial markets (e.g., in the form of corporations), which are entities specifically constructed to have just one fundamental motive. This single focus is the source of both the strengths and flaws in how such entities behave.

  13. Mechanoregulatory tumor-stroma crosstalk in pancreatic cancer: Measurements of the effects of extracellular matrix mechanics on tumor growth behavior, and vice-versa, to inform therapeutics

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan; Jones, Dustin; El-Hamidi, Hamid; Cramer, Gwendolyn; Hanna, William; Caide, Andrew; Jafari, Seyedehrojin

    The rheological properties of the extracellular matrix (ECM) have been shown to play key roles in regulating tumor growth behavior through mechanotranduction pathways. The role of the mechanical microenvironment may be particularly important tumors of the pancreas, noted for an abundance of rigid fibrotic stroma, implicated in therapeutic resistance. At the same time, cancer cells and their stromal partners (e.g. tumor associated fibroblasts) continually alter the mechanical microenvironment in response to extracellular physical and biochemical cues as part of a two-way mechanoregulatory dialog. Here, we describe experimental studies using 3D pancreatic cell cultures with customized mechanical properties, combined with optical microrheology to provide insight into tumor-driven matrix remodeling. Quantitative microscopy provides measurements of phenotypic changes accompanying systematic variation of ECM composition in collagen and laminin-rich basement membrane admixtures, while analysis of the trajectories of passive tracer particles embedded in ECM report dynamic changes in heterogeneity, microstructure and local shear modulus accompanying both ECM stiffening (fibrosis) processes, and ECM degradation near invading cells. We gratefully acknowledge funding from the National Cancer Institute, R00CA155045 (PI: Celli).

  14. Tumor stroma-derived Wnt5a induces differentiation of basal cell carcinoma of Ptch-mutant mice via CaMKII.

    PubMed

    Nitzki, Frauke; Zibat, Arne; König, Simone; Wijgerde, Mark; Rosenberger, Albert; Brembeck, Felix H; Carstens, Per-Ole; Frommhold, Anke; Uhmann, Anja; Klingler, Stefan; Reifenberger, Julia; Pukrop, Tobias; Aberger, Fritz; Schulz-Schaeffer, Walter; Hahn, Heidi

    2010-04-01

    Basal cell carcinoma (BCC) is the most common skin tumor in humans. Although BCCs rarely metastasize, they can cause significant morbidity due to local aggressiveness. Approximately 20% of BCCs show signs of spontaneous regression. The understanding of molecular events mediating spontaneous regression has the potential to reduce morbidity of BCC and, potentially, other tumors, if translated into tumor therapies. We show that BCCs induced in conditional Ptch(flox/flox)ERT2(+/-) knockout mice regress with time and show a more differentiated phenotype. Differentiation is accompanied by Wnt5a expression in the tumor stroma, which is first detectable at the fully developed tumor stage. Coculture experiments revealed that Wnt5a is upregulated in tumor-adjacent macrophages by soluble signals derived from BCC cells. In turn, Wnt5a induces the expression of the differentiation marker K10 in tumor cells, which is mediated by Wnt/Ca(2+) signaling in a CaMKII-dependent manner. These data support a role of stromal Wnt5a in BCC differentiation and regression, which may have important implications for development of new treatment strategies for this tumor. Taken together, our results establish BCC as an easily accessible model of tumor regression. The regression of BCC despite sustained Hedgehog signaling activity seems to be mediated by tumor-stromal interactions via Wnt5a signaling.

  15. Hepatoid carcinoma of the pancreas with lymphoid stroma: first description of the clinical, morphological, immunohistochemical, and molecular characteristics of an unusual pancreatic carcinoma.

    PubMed

    Vanoli, Alessandro; Argenti, Francesca; Vinci, Alessio; La Rosa, Stefano; Viglio, Alessandra; Riboni, Roberta; Necchi, Vittorio; Pugliese, Luigi; Sessa, Fausto; Pietrabissa, Andrea; Paulli, Marco

    2015-08-01

    We report a case of tumour in the head of the pancreas observed in a 57-year-old man with a history of worsening jaundice and elevated alpha-fetoprotein (AFP) serum level, who underwent Whipple pancreatoduodenectomy. Histologically, the tumour was predominantly composed of solid sheets of large eosinophilic cells with a prominent lymphoid infiltration without association neither with DNA microsatellite instability nor Epstein-Barr virus infection. The tumour was diffusely and strongly positive for hepatocyte paraffin-1 (Hep Par-1) and glypican-3 leading to the diagnosis of hepatoid carcinoma. Strong cytoplasmic staining for AFP was focally observed. Moreover, tumour cells showed countless cytoplasmic eosinophilic globules immunoreactive for the stress protein p62. A primary hepatocellular carcinoma of the liver was ruled out by careful clinical analysis. Hepatoid carcinoma is an extremely rare pancreatic neoplasm, and here, we describe the first case of such variant associated with lymphoid stroma. The characteristic histologic features and the immunophenotypic profile help in distinguishing this carcinoma from other pancreatic tumours, notably from medullary carcinoma.

  16. Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma.

    PubMed Central

    Teixidó, J; Hemler, M E; Greenberger, J S; Anklesaria, P

    1992-01-01

    Hematopoietic stem cell interaction with elements of the underlying stroma is essential for sustained normal hematopoiesis. Here we have determined that adhesion receptors in the integrin family play a role in promoting adhesion of human hematopoietic stem cells to cultured human marrow stromal cells. Enriched CD34hi progenitor cells expressed VLA-4, VLA-5, and at least one or more beta 2 integrins. Homogeneous marrow stromal cell monolayers capable of supporting proliferation of cocultivated CD34hi cells expressed VCAM-1 and fibronectin (ligands for VLA-4 and VLA-5) as well as ICAM-1 (ligand for LFA-1 and Mac-1). Adhesion-blocking experiments indicated that VLA-4/VCAM-1, VLA-5/fibronectin, and beta 2-integrin/ICAM-1 pathways all are important for CD34hi cell attachment to stromal cells. Consistent with this suggestion, IL-1 stimulation of stromal cells caused both increased VCAM-1 and ICAM-1 expression and increased attachment by CD34hi bone marrow cells. In addition, CD34hi cells utilized VLA-4 to adhere to purified VCAM-1 and employed VLA-5 (and to a lesser extent VLA-4) to adhere to purified fibronectin. Together these results suggest that CD34hi stem cells may utilize multiple integrin-mediated adhesion pathways to localize within specialized microenvironmental niches created by marrow stromal cells. Images PMID:1379610

  17. The hollow fiber bioreactor as a stroma-supported, serum-free ex vivo expansion platform for human umbilical cord blood cells.

    PubMed

    Xue, Cao; Kwek, Kenneth Y C; Chan, Jerry K Y; Chen, Qingfeng; Lim, Mayasari

    2014-07-01

    The bone marrow microenvironment plays an integral role in the regulation of hematopoiesis. Residing stromal cells and the extracellular matrix in the bone marrow microenvironment provide biological signals that control hematopoietic stem cell (HSC) function. In this study, we developed a bio-mimetic co-culture platform using the hollow fiber bioreactor (HFBR) for ex vivo expansion of HSCs. We evaluated the efficacy of such a platform in comparison to standard cultures performed on tissue culture polystyrene (TCP), using a human stromal cell line (HS-5) as stromal support, co-cultured with lineage-depleted human cord blood cells in serum-free medium supplemented with a cytokine cocktail. Our results showed that the performance of the HFBR in supporting total cell and CD34(+) progenitor cell expansion was comparable to that of cultures on TCP. Cells harvested from the HFBR had a higher clonogenic ability. The performance of ex vivo-expanded cells from the HFBR in hematopoietic reconstitution in humanized mice was comparable to that of the TCP control. Scanning electron microscopy revealed that stroma cell growth inside the HFBR created a three-dimensional cell matrix architecture. These findings demonstrate the feasibility of utilizing the HFBR for creating a complex cell matrix architecture, which may provide good in vitro mimicry of the bone marrow, supporting large-scale expansion of HSCs.

  18. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.

    PubMed

    Thomas, Sushma S; Makar, Karen W; Li, Lin; Zheng, Yingye; Yang, Peiying; Levy, Lisa; Rudolph, Rebecca Y; Lampe, Paul D; Yan, Min; Markowitz, Sanford D; Bigler, Jeannette; Lampe, Johanna W; Potter, John D

    2015-12-01

    Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) - accession number GSE71571 - was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9]).

  19. Image-guided modified deep anterior lamellar keratoplasty (DALK) corneal transplant using intraoperative optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Tao, Yuankai K.; LaBarbera, Michael; Ehlers, Justis P.; Srivastava, Sunil K.; Dupps, William J.

    2015-03-01

    Deep anterior lamellar keratoplasty (DALK) is an alternative to full-thickness corneal transplant and has advantages including the absence of allograft rejection; shortened duration of topical corticosteroid treatment and reduced associated risk of glaucoma, cataract, or infection; and enables use of grafts with poor endothelial quality. DALK begins by performing a trephination of approximately 80% stromal thickness, as measured by pachymetry. After removal of the anterior stoma, a needle is inserted into the residual stroma to inject air or viscoelastic to dissect Descemet's membrane. These procedures are inherently difficult and intraoperative rates of Descemet's membrane perforation between 4-39% have been reported. Optical coherence tomography (OCT) provides high-resolution images of tissue microstructures in the cornea, including Descemet's membrane, and allows quantitation of corneal layer thicknesses. Here, we use crosssectional intraoperative OCT (iOCT) measurements of corneal thickness during surgery and a novel micrometeradjustable biopsy punch to precision-cut the stroma down to Descemet's membrane. Our prototype cutting tool allows us to establish a dissection plane at the corneal endothelium interface, mitigates variability in cut-depths as a result of tremor, reduces procedure complexity, and reduces complication rates. iOCT-guided modified DALK procedures were performed on 47 cadaveric porcine eyes by non-experts and achieved a perforation rate of ~5% with a mean corneal dissection time <18 minutes. The procedure was also successful performed on a human donor eye without perforation. Our data shows the potential for iOCT-guided precision anterior segment surgery without variability as a result of tremor and improvements to standard clinical care.

  20. Fungi and macroaggregation in deep-sea sediments.

    PubMed

    Damare, Samir; Raghukumar, Chandralata

    2008-07-01

    Whereas fungi in terrestrial soils have been well studied, little is known of them in deep-sea sediments. Recent studies have demonstrated the presence of fungal hyphae in such sediments but in low abundance. We present evidence in this study that one of the apparent reasons for the poor detection of fungi in deep-sea sediments is their cryptic presence in macroaggregates. Fungal biomass carbon from different core sections of deep-sea sediments from approximately 5000 m depth in the Central Indian Ocean was estimated based on direct microscopic detection of fungal mycelia. Treatment of sediment samples with ethylenediamine tetra-acetic acid (EDTA) enabled more frequent detection and significantly higher biomass than in samples without such treatment. Treatment with EDTA resulted in detecting various stages of breakdown of aggregates in the sediments, gradually revealing the presence of fungal hyphae within them. Experimental studies of a deep-sea, as well as three terrestrial isolates of fungi, showed that all could grow at 200 bar and 5 degrees C in a nutrient medium and in deep-sea sediment extract. Hyphae of fungi grown in sediment extract under the above conditions showed various stages of accretion of particles around them, leading to the formation of aggregates. Such aggregates showed the presence of humic material, carbohydrate, and proteins. We suggest that fungi in deep-sea sediments may be involved in humic aggregate formation by processes very similar to those in terrestrial sediments. The importance of such a process in carbon sequestration and food web in the deep sea needs to be examined.

  1. Ecosystem function and services provided by the deep sea

    NASA Astrophysics Data System (ADS)

    Thurber, A. R.; Sweetman, A. K.; Narayanaswamy, B. E.; Jones, D. O. B.; Ingels, J.; Hansman, R. L.

    2014-07-01

    The deep sea is often viewed as a vast, dark, remote, and inhospitable environment, yet the deep ocean and seafloor are crucial to our lives through the services that they provide. Our understanding of how the deep sea functions remains limited, but when treated synoptically, a diversity of supporting, provisioning, regulating and cultural services becomes apparent. The biological pump transports carbon from the atmosphere into deep-ocean water masses that are separated over prolonged periods, reducing the impact of anthropogenic carbon release. Microbial oxidation of methane keeps another potent greenhouse gas out of the atmosphere while trapping carbon in authigenic carbonates. Nutrient regeneration by all faunal size classes provides the elements necessary for fueling surface productivity and fisheries, and microbial processes detoxify a diversity of compounds. Each of these processes occur on a very small scale, yet considering the vast area over which they occur they become important for the global functioning of the ocean. The deep sea also provides a wealth of resources, including fish stocks, enormous bioprospecting potential, and elements and energy reserves that are currently being extracted and will be increasingly important in the near future. Society benefits from the intrigue and mystery, the strange life forms, and the great unknown that has acted as a muse for inspiration and imagination since near the beginning of civilization. While many functions occur on the scale of microns to meters and timescales up to years, the derived services that result are only useful after centuries of integrated activity. This vast dark habitat, which covers the majority of the globe, harbors processes that directly impact humans in a variety of ways; however, the same traits that differentiate it from terrestrial or shallow marine systems also result in a greater need for integrated spatial and temporal understanding as it experiences increased use by society. In

  2. Distributed Episodic Exploratory Planning (DEEP)

    DTIC Science & Technology

    2012-04-01

    and numbers representing case identifiers, it showed the memory usage to be extremely minimal. 3.2.2.2. Latent Semantic Analysis (LSA) The DEEP team...faced a challenge in preparing historical StarCraft log files for storage in a DEEP-friendly case-base. Latent semantic analysis (LSA) is a...the document. (Using Latent Semantic Analysis to Improve Information Retrieval, 1988) The challenge for DEEP was to convert a continuous APPROVED FOR

  3. Understanding the "lethal" drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment.

    PubMed

    Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E; Chiavarina, Barbara; Pavlides, Stephanos; Whitaker-Menezes, Diana; Tsirigos, Aristotelis; Witkiewicz, Agnieszka; Lin, Zhao; Balliet, Renee; Howell, Anthony; Sotgia, Federica

    2010-09-15

    We have recently proposed a new model for understanding how tumors evolve. To achieve successful "Tumor-Stroma Co-Evolution", cancer cells induce oxidative stress in adjacent fibroblasts and possibly other stromal cells. Oxidative stress in the tumor stroma mimics the effects of hypoxia, under aerobic conditions, resulting in an excess production of reactive oxygen species (ROS). Excess stromal production of ROS drives the onset of an anti-oxidant defense in adjacent cancer cells, protecting them from apoptosis. Moreover, excess stromal ROS production has a "Bystander-Effect", leading to DNA damage and aneuploidy in adjacent cancer cells, both hallmarks of genomic instability. Finally, ROS-driven oxidative stress induces autophagy and mitophagy in the tumor micro-environment, leading to the stromal over-production of recycled nutrients (including energy-rich metabolites, such as ketones and L-lactate). These recycled nutrients or chemical building blocks then help drive mitochondrial biogenesis in cancer cells, thereby promoting the anabolic growth of cancer cells (via an energy imbalance). We also show that ketones and lactate help "fuel" tumor growth and cancer cell metastasis and can act as chemo-attractants for cancer cells. We have termed this new paradigm for accelerating tumor-stroma co-evolution, "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism". Heterotypic signaling in cancer-associated fibroblasts activates the transcription factors HIF1alpha and NFκB, potentiating the onset of hypoxic and inflammatory response(s), which further upregulates the autophagic program in the stromal compartment. Via stromal autophagy, this hypoxic/inflammatory response may provide a new escape mechanism for cancer cells during anti-angiogenic therapy, further exacerbating tumor recurrence and metastasis.

  4. Deep drawing of uranium metal

    SciTech Connect

    Jackson, R J; Lundberg, M R

    1987-01-19

    A procedure was developed to fabricate uranium forming blanks with high ''draw-ability'' so that cup shapes could be easily and uniformly deep drawn. The overall procedure involved a posttreatment to develop optimum mechanical and structural properties in the deep-drawn cups. The fabrication sequence is casting high-purity logs, pucking cast logs, cross-rolling pucks to forming blanks, annealing and outgassing forming blanks, cold deep drawing to hemispherical shapes, and stress relieving, outgassing, and annealing deep-drawn parts to restore ductility and impart dimensional stability. The fabrication development and the resulting fabrication procedure are discussed in detail. The mechanical properties and microstructural properties are discussed.

  5. Deep learning for image classification

    NASA Astrophysics Data System (ADS)

    McCoppin, Ryan; Rizki, Mateen

    2014-06-01

    This paper provides an overview of deep learning and introduces the several subfields of deep learning including a specific tutorial of convolutional neural networks. Traditional methods for learning image features are compared to deep learning techniques. In addition, we present our preliminary classification results, our basic implementation of a convolutional restricted Boltzmann machine on the Mixed National Institute of Standards and Technology database (MNIST), and we explain how to use deep learning networks to assist in our development of a robust gender classification system.

  6. Deep earthquakes beneath the Fiji Basin, SW Pacific: Earth's most intense deep seismicity in stagnant slabs

    USGS Publications Warehouse

    Okal, E.A.; Kirby, S.H.

    1998-01-01

    Previous work has suggested that many of the deep earthquakes beneath the Fiji Basin occur in slab material that has been detached and foundered to the bottom of the transition zone or has been laid down by trench migration in a similar recumbent position. Since nowhere else in the Earth do so many earthquakes occur in slabs stagnated in the transition zone, these earthquakes merit closer study. Accordingly, we have assembled from historical and modern data a comprehensive catalogue of the relocated hypocenters and focal mechanisms of well-located deep events in the geographic area between the bottoms of the main Vanuatu and Tonga Wadati-Benioff zones. Two regions of deep seismogenesis are recognized there: (i) 163 deep shocks have occurred north of 15??S in the Vityaz Group from 1949 to 1996. These seismological observations and the absence of other features characteristic of active subduction suggest that the Vityaz group represents deep failure in a detached slab that has foundered to a horizontal orientation near the bottom of the transition zone. (ii) Another group of nearly 50 'outboard' deep shocks occur between about 450 and 660 km depth, west of the complexly buckled and offset western edge of the Tonga Wadati-Benioff zone. Their geometry is in the form of two or possibly three small-circle arcs that roughly parallel the inferred motion of Tonga trench migration. Earthquakes in the southernmost of these arcs occur in a recumbent high-seismic-wavespeed slab anomaly that connects both to the main inclined Tonga anomaly to the east and a lower mantle anomaly to the west [Van der Hilst, R., 1995. Complex morphology of subducted lithosphere in the mantle beneath the Tonga trench. Nature, Vol. 374, pp. 154-157.]. Both groups show complexity in their focal mechanisms. The major question raised by these observations is the cause of this apparent temporary arrest in the descent of the Tonga slab into the lower mantle. We approach these questions by considering the

  7. Deep frequency modulation interferometry.

    PubMed

    Gerberding, Oliver

    2015-06-01

    Laser interferometry with pm/Hz precision and multi-fringe dynamic range at low frequencies is a core technology to measure the motion of various objects (test masses) in space and ground based experiments for gravitational wave detection and geodesy. Even though available interferometer schemes are well understood, their construction remains complex, often involving, for example, the need to build quasi-monolithic optical benches with dozens of components. In recent years techniques have been investigated that aim to reduce this complexity by combining phase modulation techniques with sophisticated digital readout algorithms. This article presents a new scheme that uses strong laser frequency modulations in combination with the deep phase modulation readout algorithm to construct simpler and easily scalable interferometers.

  8. Neptune's deep atmosphere revealed

    SciTech Connect

    de Pater, I. ); Atreya, S.K. ); Romani, P.N.

    1989-08-01

    The brightness temperature of Uranus at 20 cm is 260 {plus minus} 10K, while for Neptune it is 318 {plus minus} 16K. Since NH{sub 3} is the dominant absorber at this wavelength the authors have modeled the microwave spectra of Neptune based upon an assumed deep gaseous mixing ratio of NH{sub 3} and subsequent loss into clouds. The difference between the two brightness temperatures implies that the NH{sub 3} mixing ratio below the level of cloud formation on Neptune compared to Uranus is lower by nearly 2 order of magnitude. An alternative explanation is that the 20 cm radiation from Neptune is a combination of thermal plus synchrotron emission as proposed by de Pater and Goertz (1989).

  9. Deep, zonal subequatorial currents.

    PubMed

    Talley, L D; Johnson, G C

    1994-02-25

    Large-scale, westward-extending tongues of warm (Pacific) and cold (Atlantic) water are found between 2000 and 3000 meters both north and south of the equator in the Pacific and Atlantic oceans. They are centered at 5 degrees to 8 degrees north and 10 degrees to 15 degrees south (Pacific) and 5 degrees to 8 degrees north and 15 degrees to 20 degrees south (Atlantic). They are separated in both oceans by a contrasting eastward-extending tongue, centered at about 1 degrees to 2 degrees south, in agreement with previous helium isotope observations (Pacific). Thus, the indicated deep tropical westward flows north and south of the equator and eastward flow near the equator may result from more general forcing than the hydrothermal forcing previously hypothesized.

  10. Method of deep drilling

    DOEpatents

    Colgate, Stirling A.

    1984-01-01

    Deep drilling is facilitated by the following steps practiced separately or in any combination: (1) Periodically and sequentially fracturing zones adjacent the bottom of the bore hole with a thixotropic fastsetting fluid that is accepted into the fracture to overstress the zone, such fracturing and injection being periodic as a function of the progression of the drill. (2) Casing the bore hole with ductile, pre-annealed casing sections, each of which is run down through the previously set casing and swaged in situ to a diameter large enough to allow the next section to run down through it. (3) Drilling the bore hole using a drill string of a low density alloy and a high density drilling mud so that the drill string is partially floated.

  11. Deep anterior lamellar keratoplasty for pellucid marginal degeneration***

    PubMed Central

    Al-Torbak, Abdullah A.

    2012-01-01

    Purpose To present the surgical outcomes of deep anterior lamellar keratoplasty (DALK) for pellucid marginal degeneration (PMD). Methods A retrospective review was performed in 16 eyes of 16 patients who underwent DALK at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia between January 1, 2006 and December 30, 2009. Baring of Descemet’s membrane (DM) during DALK was achieved in 8 (50%) eyes; residual stroma was left intraoperatively in the remaining 8 (50%) eyes. The big bubble technique was performed in 10 (62.5%) eyes and manual dissection was performed in the remaining 6 (37.5%) eyes. Visual acuity (LogMAR notation), intraocular pressure, intraoperative complications and postoperative graft status were assessed. Results The mean follow up was 14.6 ± 8.2 months (range 6–35 months). The mean overall age was 31.4 ± 9.6 years (range, 19–50 years). Visual acuity increased statistically significantly from 0.9 ± 0.3 (range 0.5–1.6) preoperatively to 0.4 ± 0.2 (range 0.0–0.7) at last follow-up (p < 0.0001). There was a statistically significant improvement in postoperative sphere, cylinder, and spherical equivalent (p < 0.035, p < 0.001, and p < 0.02, respectively) compared to preoperative. Postoperative visual acuity was not statistically significantly related to gender, type of surgical technique, and baring or perforation of DM. The main graft-related complication was graft–host vascularization (2/16 eyes). Conclusion DALK reduces severe corneal astigmatism and results in good visual and refractive outcomes and is an effective alternative for patients with PMD. PMID:23964180

  12. Modeling ocean deep convection

    NASA Astrophysics Data System (ADS)

    Canuto, V. M.; Howard, A.; Hogan, P.; Cheng, Y.; Dubovikov, M. S.; Montenegro, L. M.

    The goal of this study is to assess models for Deep Convection with special emphasis on their use in coarse resolution ocean general circulation models. A model for deep convection must contain both vertical transport and lateral advection by mesoscale eddies generated by baroclinic instabilities. The first process operates mostly in the initial phases while the second dominates the final stages. Here, the emphasis is on models for vertical mixing. When mesoscales are not resolved, they are treated with the Gent and McWilliams parameterization. The model results are tested against the measurements of Lavender, Davis and Owens, 2002 (LDO) in the Labrador Sea. Specifically, we shall inquire whether the models are able to reproduce the region of " deepest convection," which we shall refer to as DC (mixed layer depths 800-1300 m). The region where it was measured by Lavender et al. (2002) will be referred to as the LDO region. The main results of this study can be summarized as follows. 3° × 3° resolution. A GFDL-type OGCM with the GISS vertical mixing model predicts DC in the LDO region where the vertical heat diffusivity is found to be 10 m 2 s -1, a value that is quite close to the one suggested by heuristic studies. No parameter was changed from the original GISS model. However, the GISS model also predicts some DC in a region to the east of the LDO region. 3° × 3° resolution. A GFDL-type OGCM with the KPP model (everything else being the same) does not predict DC in the LDO region where the vertical heat diffusivity is found to be 0.5 × 10 -4 m 2 s -1 which is the background value. The KPP model yields DC only to the east of the LDO region. 1° × 1° resolution. In this case, a MY2.5 mixing scheme predicts DC in the LDO region. However, it also predicts DC to the west, north and south of it, where it is not observed. The behavior of the KPP and MY models are somewhat anti-symmetric. The MY models yield too low a mixing in stably stratified flows since they

  13. Repetitive transcranial magnetic stimulation of human MT+ reduces apparent motion perception.

    PubMed

    Matsuyoshi, Daisuke; Hirose, Nobuyuki; Mima, Tatsuya; Fukuyama, Hidenao; Osaka, Naoyuki

    2007-12-18

    We investigated the effects of repetitive transcranial magnetic stimulation (rTMS) over the human cerebral cortex on apparent motion perception. Previous studies have shown that human extrastriate visual area MT+ (V5) processes not only real but also apparent motion. However, the functional relevance of MT+ on long-range apparent motion perception remains unclear. Here, we show direct evidence for the involvement of MT+ in apparent motion perception using rTMS, which is known to temporarily inhibit a localized region in the cerebral cortex. The results showed that apparent motion perception decreased after applying rTMS over MT+, but not after applying rTMS over the control region (inferior temporal gyrus). The decrease in performance caused by applying rTMS to MT+ suggests that MT+ is a causally responsible region for apparent motion perception, and thus, further supports the idea that MT+ plays a major role in the perception of motion.

  14. Apparent size contrasts of retinal images and size constancy as determinants of the moon illusion.

    PubMed

    Smith, O W; Smith, P C; Geist, C C; Zimmermann, R R

    1978-06-01

    Kaufman and Rock (1962) and Rock and Kaufman (1962) concluded that the moon illusion is a function of and attributable to apparent distance. They also reported a large framing effect as an exception. Analysis of the effect suggests two components which can account for the illusion independently of apparent distance. These are apparent size contrasts of visual images of discriminable features or objects of the earth with the moon's image and size constancy of the features or objects plus the interactions of the two. Apparent distances to horizons are always a consequence of the necessary conditions for the illusion. They are related to the illusion but are not a determinant of it.

  15. The Capodimonte Deep Field

    NASA Astrophysics Data System (ADS)

    2001-04-01

    A Window towards the Distant Universe Summary The Osservatorio Astronomico Capodimonte Deep Field (OACDF) is a multi-colour imaging survey project that is opening a new window towards the distant universe. It is conducted with the ESO Wide Field Imager (WFI) , a 67-million pixel advanced camera attached to the MPG/ESO 2.2-m telescope at the La Silla Observatory (Chile). As a pilot project at the Osservatorio Astronomico di Capodimonte (OAC) [1], the OACDF aims at providing a large photometric database for deep extragalactic studies, with important by-products for galactic and planetary research. Moreover, it also serves to gather experience in the proper and efficient handling of very large data sets, preparing for the arrival of the VLT Survey Telescope (VST) with the 1 x 1 degree 2 OmegaCam facility. PR Photo 15a/01 : Colour composite of the OACDF2 field . PR Photo 15b/01 : Interacting galaxies in the OACDF2 field. PR Photo 15c/01 : Spiral galaxy and nebulous object in the OACDF2 field. PR Photo 15d/01 : A galaxy cluster in the OACDF2 field. PR Photo 15e/01 : Another galaxy cluster in the OACDF2 field. PR Photo 15f/01 : An elliptical galaxy in the OACDF2 field. The Capodimonte Deep Field ESO PR Photo 15a/01 ESO PR Photo 15a/01 [Preview - JPEG: 400 x 426 pix - 73k] [Normal - JPEG: 800 x 851 pix - 736k] [Hi-Res - JPEG: 3000 x 3190 pix - 7.3M] Caption : This three-colour image of about 1/4 of the Capodimonte Deep Field (OACDF) was obtained with the Wide-Field Imager (WFI) on the MPG/ESO 2.2-m telescope at the la Silla Observatory. It covers "OACDF Subfield no. 2 (OACDF2)" with an area of about 35 x 32 arcmin 2 (about the size of the full moon), and it is one of the "deepest" wide-field images ever obtained. Technical information about this photo is available below. With the comparatively few large telescopes available in the world, it is not possible to study the Universe to its outmost limits in all directions. Instead, astronomers try to obtain the most detailed

  16. Deep space network energy program

    NASA Technical Reports Server (NTRS)

    Friesema, S. E.

    1980-01-01

    If the Deep Space Network is to exist in a cost effective and reliable manner in the next decade, the problems presented by international energy cost increases and energy availability must be addressed. The Deep Space Network Energy Program was established to implement solutions compatible with the ongoing development of the total network.

  17. Context and Deep Learning Design

    ERIC Educational Resources Information Center

    Boyle, Tom; Ravenscroft, Andrew

    2012-01-01

    Conceptual clarification is essential if we are to establish a stable and deep discipline of technology enhanced learning. The technology is alluring; this can distract from deep design in a surface rush to exploit the affordances of the new technology. We need a basis for design, and a conceptual unit of organization, that are applicable across…

  18. Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: implications for preventing chemotherapy resistance.

    PubMed

    Ko, Ying-Hui; Lin, Zhao; Flomenberg, Neal; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E

    2011-12-15

    activity, driving a vicious cycle of catabolism in the tumor stroma and anabolic tumor cell expansion.

  19. Interferon regulatory factor-two restricts expression of interferon-stimulated genes to the endometrial stroma and glandular epithelium of the ovine uterus.

    PubMed

    Choi, Y; Johnson, G A; Burghardt, R C; Berghman, L R; Joyce, M M; Taylor, K M; Stewart, M D; Bazer, F W; Spencer, T E

    2001-10-01

    Interferon tau (IFNtau) is the signal for maternal recognition of pregnancy in ruminants. The positive effects of IFNtau on IFN-stimulated gene (ISG) expression are mediated by ISG factor 3 (ISGF3), which is composed of signal transducer and activator of transcription (Stat) 1, Stat 2, and IFN regulatory factor-9 (IRF-9), and by gamma-activated factor (GAF), which is a Stat 1 homodimer. Induction of ISGs, such as ISG17 and 2',5'-oligoadenylate synthetase, by IFNtau during pregnancy is limited to the endometrial stroma (S) and glandular epithelium (GE) of the ovine uterus. The IRF-2, a potent transcriptional repressor of ISG expression, is expressed in the luminal epithelium (LE). This study determined effects of the estrous cycle, pregnancy, and IFNtau on expression of Stat 1, Stat 2, IRF-9, IRF-1, and IRF-2 genes in the ovine endometrium. In cyclic ewes, Stat 1, Stat 2, IRF-1, and IRF-9 mRNA and protein were detected at low levels in the S and GE. During pregnancy, expression of these genes increased only in the S and GE. Expression of IRF-2 was detected only in the LE and superficial GE (sGE) of both cyclic and pregnant ewes. In cyclic ewes, intrauterine administration of IFNtau stimulated Stat 1, Stat 2, IRF-9, and IRF-1 expression in the endometrium. Ovine IRF-2 repressed transcriptional activity driven by IFN-stimulated response elements that bind ISGF3, but not by gamma-activation sequences that bind GAF. These results suggest that IRF-2 in the LE and sGE restricts IFNtau induction of ISGs to the S and GE. In the S and GE, IFNtau hyperactivation of ISG expression likely involves formation and actions of the transcription factors ISGF3 and, perhaps, IRF-1.

  20. Long-lasting morphofunctional remodelling of liver parenchyma and stroma after a single exposure to low and moderate doses of cadmium in rats

    PubMed Central

    Cupertino, Marli C; Costa, Kyvia L C; Santos, Daiane C M; Novaes, Rômulo D; Condessa, Suellen S; Neves, Ana C; Oliveira, Juraci A; Matta, Sérgio L P

    2013-01-01

    Frequent exposure to cadmium (Cd) in low doses is common; however, the long-lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long-lasting hepatic morphofunctional adaptations in rats exposed to low and moderate doses of Cd. Five experimental groups were tested: control (0.9% saline) and other four receiving single intraperitoneal doses of 0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks and the following parameters were analysed: biometrics, oedema, Cd bio-accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and catalase (CAT), serum transaminases, liver histopathology and stereology. In all groups exposed to Cd there was significant increase in SOD and CAT activities, ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio, macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen accumulation by hepatocytes and the proportion of sinusoidal capillaries were significantly reduced compared with controls. The liver somatic index was increased, and liver oedema was evident in animals exposed to higher dose of Cd. Areas of necrosis were found in animals exposed to the three highest doses. These results indicate that Cd is an extremely toxic bioactive heavy metal, which even at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd exposure induces morphofunctional pathological remodelling of the hepatic stroma and parenchyma, which remain active after eight weeks. In response to injury, the liver tissue triggers a reactive process by enhancing activation of antioxidant enzymes and collagenogenesis. PMID:24020407

  1. Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter–Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth

    PubMed Central

    Sung, Shian-Ying; Chang, Junn-Liang; Chen, Kuan-Chou; Yeh, Shauh-Der; Liu, Yun-Ru; Su, Yen-Hao; Hsueh, Chia-Yen; Chung, Leland W. K.; Hsieh, Chia-Ling

    2016-01-01

    Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E) containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor–promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc) into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter–driven herpes simplex virus thymidine kinase gene (Ad-522E-TK) was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers. PMID:27054343

  2. The assessment of cryopreservation conditions for human umbilical cord stroma-derived mesenchymal stem cells towards a potential use for stem cell banking.

    PubMed

    Balci, Deniz; Can, Alp

    2013-01-01

    Human umbilical cord stroma-derived mesenchymal stem cells (hUCS-MSCs) are considered as a remarkable and promising stem cell source to be potentially used in cellular therapies. While no graft rejection has been reported in the recipient organism even in xeno-transplantation studies, attenuate tumor cell growth and gene transfers have been experimentally shown. In this study, we have demonstrated a reliable, reproducible and efficient cryopreservation method of hUCS-MSCs resulting in one of the highest cell survival rates reported so far. Conventional, computer-controlled multistep slow freezing (MSSF), and vitrification methods were comparatively tested using cell permeable [dimethylsulfoxide (DMSO), ethylene glycol] and impermeable [trehalose, sucrose, hydroxyethyl starch (HES), human serum albumin] cryoprotectant agents (CPAs). After determining the ice nucleation point for each solution, latent heat evolution was suppressed during freezing, followed by a cooling process to -40°C at 1°C/min or 0.3°C/min. The efficiency of the cryopreservation techniques used was determined by cell viability and proliferation assays, the expression of cell surface markers, cytoskeletal proteins and chromosome alignments. The cell survival rate was found to be highest (87 ± 5%) by MSSF with sucrose (0.1 M) +DMSO (10%) at 1°C/min freezing rate. In this group, no significant difference was noted before and after the cryopreservation in cell morphology, cytokeratin, vimentin, and α-smooth muscle actin profiles and the expressions of CD105, CD90, CD73, CD29 and HLA-DR. Second highest cell survival ratio (85 ± 6%) was obtained in DMSO (10%) alone at 1°C/min freezing rate. Interestingly, poor (18 ± 15%) cell survival rates were obtained after vitrification. Cumulatively, results indicated that MSSF favors the other freezing protocols with an addition of sucrose or DMSO alone depending on the freezing rate used.

  3. Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

    PubMed

    Sung, Shian-Ying; Chang, Junn-Liang; Chen, Kuan-Chou; Yeh, Shauh-Der; Liu, Yun-Ru; Su, Yen-Hao; Hsueh, Chia-Yen; Chung, Leland W K; Hsieh, Chia-Ling

    2016-01-01

    Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E) containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc) into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK) was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

  4. Macrophage migration inhibitory factor produced by the tumour stroma but not by tumour cells regulates angiogenesis in the B16-F10 melanoma model

    PubMed Central

    Girard, E; Strathdee, C; Trueblood, E; Quéva, C

    2012-01-01

    Background: Macrophage migration inhibitory factor (MIF) has been proposed as a link between inflammation and tumorigenesis. Despite its potentially broad influence in tumour biology and prevalent expression, the value of MIF as a therapeutic target in cancer remains unclear. We sought to validate MIF in tumour models by achieving a complete inhibition of its expression in tumour cells and in the tumour stroma. Methods: We used MIF shRNA-transduced B16-F10 melanoma cells implanted in wild-type and MIF−/− C57Bl6 mice to investigate the effect of loss of MIF on tumour growth. Cytokine detection and immunohistochemistry (IHC) were used to evaluate tumours ex vivo. Results: Macrophage migration inhibitory factor shRNA inhibited expression of MIF protein by B16-F10 melanoma cells in vitro and in vivo. In vitro, the loss of MIF in this cell line resulted in a decreased response to hypoxia as indicated by reduced expression of VEGF. In vivo the growth of B16-F10 tumours was inhibited by an average of 47% in the MIF−/− mice compared with wild-type but was unaffected by loss of MIF expression by the tumour cells. Immunohistochemistry analysis revealed that microvessel density was decreased in tumours implanted in the MIF−/− mice. Profiling of serum cytokines showed a decrease in pro-angiogenic cytokines in MIF−/− mice. Conclusion: We report that the absence of MIF in the host resulted in slower tumour growth, which was associated with reduced vascularity. While the major contribution of MIF appeared to be in the regulation of angiogenesis, tumour cell-derived MIF played a negligible role in this process. PMID:22955855

  5. Deep sulfur cycle

    NASA Astrophysics Data System (ADS)

    Shimizu, N.; Mandeville, C. W.

    2009-12-01

    Geochemical cycle of sulfur in near-surface reservoirs has been a subject of intense studies for decades. It has been shown that sulfur isotopic compositions of sedimentary sulfides and sulfates record interactions of the atmosphere, hydrosphere, biosphere and lithosphere, with δ34S of sedimentary sulfides continuously decreasing from 0‰ toward present-day values of ~-30 to -40‰ over the Phanerozoic (e.g., Canfield, 2004). It has also been shown that microbial reduction of the present-day seawater sulfate (δ34S=+21‰) results in large shifts in isotopic compositions of secondary pyrites in altered oceanic crust (to δ34S=-70‰: Rouxel et al., 2009). How much of these near surface isotopic variations survive during deep geochemical cycle of sulfur interacting with the mantle infinite reservoir with δ34S=0‰? Could extent of their survival be used as a tracer of processes and dynamics involved in deep geochemical cycle? As a first step toward answering these questions, δ34S was determined in-situ using a Cameca IMS 1280 ion microprobe at Woods Hole Oceanographic Institution in materials representing various domains of deep geochemical cycle. They include pyrites in altered MORB as potential subducting materials and pyrites in UHP eclogites as samples that have experienced subduction zone processes, and mantle-derived melts are represented by olivine-hosted melt inclusions in MORB and those in IAB, and undegassed submarine OIB glasses. Salient features of the results include: (1) pyrites in altered MORB (with O. Rouxel; from ODP site 801 and ODP Hole 1301B) range from -70 to +19‰, (2) pyrites in UHP eclogites from the Western Gneiss Region, Norway (with B. Hacker and A. Kylander-Clark) show a limited overall range from -3.4 to + 2.8‰ among five samples, with one of them covering almost the entire range, indicating limited scale lengths of isotopic equilibration during subduction, (3) olivine-hosted melt inclusions in arc basalts from Galunggung (-2

  6. Deep Learning the Universe

    NASA Astrophysics Data System (ADS)

    Singh, Shiwangi; Bard, Deborah

    2017-01-01

    Weak gravitational lensing is an effective tool to map the structure of matter in the universe, and has been used for more than ten years as a probe of the nature of dark energy. Beyond the well-established two-point summary statistics, attention is now turning to methods that use the full statistical information available in the lensing observables, through analysis of the reconstructed shear field. This offers an opportunity to take advantage of powerful deep learning methods for image analysis. We present two early studies that demonstrate that deep learning can be used to characterise features in weak lensing convergence maps, and to identify the underlying cosmological model that produced them.We developed an unsupervised Denoising Convolutional Autoencoder model in order to learn an abstract representation directly from our data. This model uses a convolution-deconvolution architecture, which is fed with input data (corrupted with binomial noise to prevent over-fitting). Our model effectively trains itself to minimize the mean-squared error between the input and the output using gradient descent, resulting in a model which, theoretically, is broad enough to tackle other similarly structured problems. Using this model we were able to successfully reconstruct simulated convergence maps and identify the structures in them. We also determined which structures had the highest “importance” - i.e. which structures were most typical of the data. We note that the structures that had the highest importance in our reconstruction were around high mass concentrations, but were highly non-Gaussian.We also developed a supervised Convolutional Neural Network (CNN) for classification of weak lensing convergence maps from two different simulated theoretical models. The CNN uses a softmax classifier which minimizes a binary cross-entropy loss between the estimated distribution and true distribution. In other words, given an unseen convergence map the trained CNN determines

  7. Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options

    PubMed Central

    Trovato, Maria Antonietta; Palmara, Vittorio Italo; Rapisarda, Agnese Maria Chiara; Sturlese, Emanuele; De Dominici, Rosanna; Alecci, Stefano; D'Amico, Paolo; Triolo, Onofrio

    2016-01-01

    Endometriosis is defined as the presence of endometrial mucosa (glands and stroma) abnormally implanted in locations other than the uterine cavity. Deep infiltrating endometriosis (DIE) is considered the most aggressive presentation of the disease, penetrating more than 5 mm in affected tissues, and it is reported in approximately 20% of all women with endometriosis. DIE can cause a complete distortion of the pelvic anatomy and it mainly involves uterosacral ligaments, bladder, rectovaginal septum, rectum, and rectosigmoid colon. This review describes the state of the art in laparoscopic approach for DIE with a special interest in intestinal involvement, according to recent literature findings. Our attention has been focused particularly on full-thickness excision versus shaving technique in deep endometriosis intestinal involvement. Particularly, the aim of this paper is clarifying from the clinical and methodological points of view the best surgical treatment of deep intestinal endometriosis, since there is no standard of care in the literature and in different surgical settings. Indeed, this review tries to suggest when it is advisable to manage the full-thickness excision or the shaving technique, also analyzing perioperative management, main complications, and surgical outcomes. PMID:27579309

  8. Deep tectonic influence on shallow structures of Allegheny plateau

    SciTech Connect

    Reeves, T.K. Jr.; Morris, J.

    1988-08-01

    The lower plateau area of western Pennsylvania and western West Virginia is underlain by numerous salt-cored anticlinal structures. The locations of these anticlines have been controlled by disturbances in the salt and discontinuities on detachment horizons. These discontinuities were produced by deep-seated faults with ongoing movements that persisted into or through the time of Salina deposition. Tilting of the basin during post-Salina sedimentation caused the salts to mobilize. These highly ductile units began to sag into the deep basin at a very early stage and moved by sliding until they reached the zones where faulting had disrupted the glide surfaces. Seismic examples show how the pileup of salts along these fault-disturbed zones has produced the cores of the modern anticlines. Characteristic movements within these salt pillows have led to such familiar Appalachian features as anticlines that are steeper on the southeastern flank, fracturing and faulting with apparent thrusting in the Onondaga-Oriskany-Helderberg section, and zones of fracture porosity and enhanced producibility in the Devonian shales and shallow reservoirs. An understanding of deep structures and salt deformation features in a shallow prospect area can lead to the discovery of zones of fracture porosity and can improve production in tight formations or permit the avoidance of areas where fracturing is so intense that no effective cap rock remains. Deep structure and salt tectonics can be relevant to shallow development work.

  9. Deep atomic force microscopy

    SciTech Connect

    Barnard, H.; Drake, B.; Randall, C.; Hansma, P. K.

    2013-12-15

    The Atomic Force Microscope (AFM) possesses several desirable imaging features including the ability to produce height profiles as well as two-dimensional images, in fluid or air, at high resolution. AFM has been used to study a vast selection of samples on the scale of angstroms to micrometers. However, current AFMs cannot access samples with vertical topography of the order of 100 μm or greater. Research efforts have produced AFM scanners capable of vertical motion greater than 100 μm, but commercially available probe tip lengths are still typically less than 10 μm high. Even the longest probe tips are below 100 μm and even at this range are problematic. In this paper, we present a method to hand-fabricate “Deep AFM” probes with tips of the order of 100 μm and longer so that AFM can be used to image samples with large scale vertical topography, such as fractured bone samples.

  10. Operation Deep Sweep

    NASA Astrophysics Data System (ADS)

    Bell, Peter M.

    Fifty scientists and a crew of 18 have embarked on a 64,000 km odyssey to explore the Pacific from pole to pole—the most ambitious program in the history of the marine geology branch of the U.S. Geological Survey (USGS). Called Operation Deep Sweep, the 1-year cruise will search areas above the Arctic Circle, off of Alaska, to McMurdo Sound in Antarctica. The 63-m, 1,300-tonne research vessel Samuel P. Lee sailed from its home port of Redwood City, Calif., to San Francisco to begin the first leg of the lengthy journey.According to USGS officials and the cosponsoring Circum-Pacific Council for Energy and Mineral Resources of the American Association of Petroleum Geologists, the cruise will ultimately involve 150 scientists, some of them representing Germany, France, Australia, and New Zealand. David Howell, branch chief of Pacific Marine Geology for the USGS, said the voyage of the Lee was “the most far reaching and of the longest duration” ever attempted by his unit. He said the cruise would string together a large number of scientific experiments spanning the Pacific. Howell likened the voyage to the Lewis and Clark Expedition of 1803-1806 (which explored Louisiana and the western United States) because “we're going into unknown territory and into regions not studied except in the most cursory manner.”

  11. Large-scale variability of atmospheric deep convection in relation to sea surface temperature in the tropics

    SciTech Connect

    Zhang, C. )

    1993-10-01

    Empirical relationships between tropical sea surface temperature (SST) and atmospheric deep convection are examined. The relationships are addressed from two aspects: how deep convection varies with changing SST and how it varies at constant SST. Deep convection remains weak and rarely observed for SST < 26[degrees]C; the frequency and mean intensity of deep convection substantially increase with SST from 26[degrees]C up to about 29.5[degrees]-30[degrees]C, and then decay for further increasing SST. Meanwhile, in the warm pool region with SST > 27[degrees]C, situations of no deep convection and vigorous deep convection can both be observed; the areal coverage of convectively related high clouds is always dominated by that of clear sky and low clouds. The variability of deep convection, thus becomes larger for higher SST. The large variability of deep convection at constant high SST is attributable to the differences in mean spatial distributions and in the annual variations of SST and deep convection. In general, the relationship is less apparent for the intertropical convergence zone than the other regions of the tropical oceans. The empirical relationship varies in space and time. In the warm pool region, the absence of deep convection at particular locations and times and the large variability of deep convection do not imply changes in high SST have little effect on deep convection. Rather, they reflect other factors can sometimes be dominantly unfavorable to deep convection. As SST increases, deep convection becomes more frequent and tends to be more intense on average, regardless of other factors. This increase in deep convection with SST is smooth and continuous. 52 refs., 26 figs., 1 tab.

  12. College Student Disclosure of Non-Apparent Disabilities to Receive Classroom Accommodations

    ERIC Educational Resources Information Center

    Kranke, Derrick; Jackson, Sarah E.; Taylor, Debbie A.; Anderson-Fye, Eileen; Floersch, Jerry

    2013-01-01

    College students with psychiatric (non-apparent) disabilities have a much higher dropout rate and tend to underperform academically when compared with peers who do not have non-apparent disabilities. These students are also vulnerable because their disability could delay the development of milestones critical to adulthood. Limited research…

  13. Generation and removal of apparent singularities in linear ordinary differential equations with polynomial coefficients

    NASA Astrophysics Data System (ADS)

    Slavyanov, S. Yu.; Satco, D. A.; Ishkhanyan, A. M.; Rotinyan, T. A.

    2016-12-01

    We discuss several examples of generating apparent singular points as a result of differentiating particular homogeneous linear ordinary differential equations with polynomial coefficients and formulate two general conjectures on the generation and removal of apparent singularities in arbitrary Fuchsian differential equations with polynomial coefficients. We consider a model problem in polymer physics.

  14. Financial Barriers for Students with Non-Apparent Disabilities within Canadian Postsecondary Education

    ERIC Educational Resources Information Center

    Chambers, Tony; Bolton, Melissa; Sukhai, Mahadeo A.

    2013-01-01

    This study examined the education-related debt, sources of debt, and the process of acquiring accommodations for students with non-apparent (such as learning disabilities and mental health disabilities) and apparent disabilities in Canadian postsecondary education. A third group emerged during analyses, students with medical disabilities, which…

  15. Taking a Hands-On Approach: Apparent Grasping Ability Scales the Perception of Object Size

    ERIC Educational Resources Information Center

    Linkenauger, Sally A.; Witt, Jessica K.; Proffitt, Dennis R.

    2011-01-01

    We examined whether the apparent size of an object is scaled to the morphology of the relevant body part with which one intends to act on it. To be specific, we tested if the visually perceived size of graspable objects is scaled to the extent of apparent grasping ability for the individual. Previous research has shown that right-handed…

  16. Deep learning for computational chemistry.

    PubMed

    Goh, Garrett B; Hodas, Nathan O; Vishnu, Abhinav

    2017-03-08

    The rise and fall of artificial neural networks is well documented in the scientific literature of both computer science and computational chemistry. Yet almost two decades later, we are now seeing a resurgence of interest in deep learning, a machine learning algorithm based on multilayer neural networks. Within the last few years, we have seen the transformative impact of deep learning in many domains, particularly in speech recognition and computer vision, to the extent that the majority of expert practitioners in those field are now regularly eschewing prior established models in favor of deep learning models. In this review, we provide an introductory overview into the theory of deep neural networks and their unique properties that distinguish them from traditional machine learning algorithms used in cheminformatics. By providing an overview of the variety of emerging applications of deep neural networks, we highlight its ubiquity and broad applicability to a wide range of challenges in the field, including quantitative structure activity relationship, virtual screening, protein structure prediction, quantum chemistry, materials design, and property prediction. In reviewing the performance of deep neural networks, we observed a consistent outperformance against non-neural networks state-of-the-art models across disparate research topics, and deep neural network-based models often exceeded the "glass ceiling" expectations of their respective tasks. Coupled with the maturity of GPU-accelerated computing for training deep neural networks and the exponential growth of chemical data on which to train these networks on, we anticipate that deep learning algorithms will be a valuable tool for computational chemistry. © 2017 Wiley Periodicals, Inc.

  17. Microbial Life in the Deep Subsurface: Deep, Hot and Radioactive

    NASA Technical Reports Server (NTRS)

    DeStefano, Andrea L.; Ford, Jill C.; Winsor, Seana K.; Allen, Carlton C.; Miller, Judith; McNamara, Karen M.; Gibson, Everett K., Jr.

    2000-01-01

    Recent studies, motivated in part by the search for extraterrestrial life, continue to expand the recognized limits of Earth's biosphere. This work explored evidence for life a high-temperature, radioactive environment in the deep subsurface.

  18. Deep Learning in Drug Discovery.

    PubMed

    Gawehn, Erik; Hiss, Jan A; Schneider, Gisbert

    2016-01-01

    Artificial neural networks had their first heyday in molecular informatics and drug discovery approximately two decades ago. Currently, we are witnessing renewed interest in adapting advanced neural network architectures for pharmaceutical research by borrowing from the field of "deep learning". Compared with some of the other life sciences, their application in drug discovery is still limited. Here, we provide an overview of this emerging field of molecular informatics, present the basic concepts of prominent deep learning methods and offer motivation to explore these techniques for their usefulness in computer-assisted drug discovery and design. We specifically emphasize deep neural networks, restricted Boltzmann machine networks and convolutional networks.

  19. Deep UV LEDs

    NASA Astrophysics Data System (ADS)

    Han, Jung; Amano, Hiroshi; Schowalter, Leo

    2014-06-01

    Deep ultraviolet (DUV) photons interact strongly with a broad range of chemical and biological molecules; compact DUV light sources could enable a wide range of applications in chemi/bio-sensing, sterilization, agriculture, and industrial curing. The much shorter wavelength also results in useful characteristics related to optical diffraction (for lithography) and scattering (non-line-of-sight communication). The family of III-N (AlGaInN) compound semiconductors offers a tunable energy gap from infrared to DUV. While InGaN-based blue light emitters have been the primary focus for the obvious application of solid state lighting, there is a growing interest in the development of efficient UV and DUV light-emitting devices. In the past few years we have witnessed an increasing investment from both government and industry sectors to further the state of DUV light-emitting devices. The contributions in Semiconductor Science and Technology 's special issue on DUV devices provide an up-to-date snapshot covering many relevant topics in this field. Given the expected importance of bulk AlN substrate in DUV technology, we are pleased to include a review article by Hartmann et al on the growth of AlN bulk crystal by physical vapour transport. The issue of polarization field within the deep ultraviolet LEDs is examined in the article by Braut et al. Several commercial companies provide useful updates in their development of DUV emitters, including Nichia (Fujioka et al ), Nitride Semiconductors (Muramoto et al ) and Sensor Electronic Technology (Shatalov et al ). We believe these articles will provide an excellent overview of the state of technology. The growth of AlGaN heterostructures by molecular beam epitaxy, in contrast to the common organo-metallic vapour phase epitaxy, is discussed by Ivanov et al. Since hexagonal boron nitride (BN) has received much attention as both a UV and a two-dimensional electronic material, we believe it serves readers well to include the

  20. Air Apparent.

    ERIC Educational Resources Information Center

    Harbster, David A.

    1988-01-01

    Explains the principle upon which a barometer operates. Describes how to construct two barometric devices for use in the classroom that show air's changing pressure. Cites some conditions for predicting weather. (RT)

  1. Morphology of deep gland of the third eyelid in pig foetuses.

    PubMed

    Klećkowska-Nawrot, J; Dziegiel, P

    2008-02-01

    The morphological and histological examinations of the deep gland of the third eyelid were carried out on pig foetuses coming from the 35th, 50th, 63rd, 94th and 112th day of gestation. The morphological examinations were conducted using the method of macroscopic preparation with a forehead magnifying glass and binocular (magnification 1.5-5.0x). In order to make anatomical elements more visible, 60-80% absolute alcohol and 0.5-4% acetic acid solution were used for the examinations. For the histological examinations, the whole eyeball with developing accessory organs was collected from the pig foetuses on the 35th day of gestation. On the 50th, 63rd, 94th and 112th day of gestation only the deep gland of the third eyelid was collected. Staining with haematoxylin-eosin and Azan method was performed. It was found during the examinations that the process of the formation of the deep gland of the third eyelid starts on the 35th day of gestation. On the 50th day of gestation, the gland cells are evenly distributed in the connective tissue stroma. On the 63rd day of gestation, the connective tissue divides the gland parenchyma into indistinct lobes composed of 6-15 lobules. On the 94th day of gestation, the gland lobes become visible; the efferent ducts are situated in the central part of the lobe. On the 112th day of gestation, the lobes are composed of a high number of lobules composed of two kinds of excretory ducts. The first type of the excretory ducts is lined with the simple cuboid epithelium whose nuclei are situated at the base of the cell. The other type of the excretory ducts is lined with the simple cuboid epithelium whose nuclei are round and arranged less or more peripherally.

  2. Deep Space Telecommunications Systems Engineering

    NASA Technical Reports Server (NTRS)

    Yuen, J. H. (Editor)

    1982-01-01

    Descriptive and analytical information useful for the optimal design, specification, and performance evaluation of deep space telecommunications systems is presented. Telemetry, tracking, and command systems, receiver design, spacecraft antennas, frequency selection, interference, and modulation techniques are addressed.

  3. NEW APPROACHES: Deep inelastic scattering

    NASA Astrophysics Data System (ADS)

    Allday, J.

    1998-01-01

    Feynman diagrams can be used to explain deep inelastic scattering, but it must be remembered that the emission and absorption of a photon are not independent events - the underlying field is important.

  4. What Is Deep Vein Thrombosis?

    MedlinePlus

    ... deep vein of the leg can break off, travel to the lungs, and block blood flow. Rate This Content: NEXT >> Updated: October 28, 2011 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA NO FEAR ACT ...

  5. Goldstone Deep Space Communication Complex

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Three 34m (110 ft.) diameter Beam Waveguide antennas located at the Goldstone Deep Space Communications Complex, situated in the Mojave Desert in California. This is one of three complexes which comprise NASA's Deep Space Network (DSN). The DSN provides radio communications for all of NASA's interplanetary spacecraft and is also utilized for radio astronomy and radar observations of the solar system and the universe.

  6. Mimicking Metastases Including Tumor Stroma: A New Technique to Generate a Three-Dimensional Colorectal Cancer Model Based on a Biological Decellularized Intestinal Scaffold

    PubMed Central

    Nietzer, Sarah; Baur, Florentin; Sieber, Stefan; Hansmann, Jan; Schwarz, Thomas; Stoffer, Carolin; Häfner, Heide; Gasser, Martin; Waaga-Gasser, Ana Maria; Walles, Heike

    2016-01-01

    generation, a bioreactor was constructed for dynamic culture approaches. This induced a close tissue-like association of cultured tumor cells with fibroblasts reflecting tumor biopsies. Therapy with 5-fluorouracil (5-FU) was effective only in 3D coculture. In conclusion, our 3D tumor model reflects human tissue-related tumor characteristics, including lower tumor cell proliferation. It is now available for drug testing in metastatic context—especially for substances targeting tumor–stroma interactions. PMID:27137941

  7. Hot, deep origin of petroleum: deep basin evidence and application

    USGS Publications Warehouse

    Price, Leigh C.

    1978-01-01

    Use of the model of a hot deep origin of oil places rigid constraints on the migration and entrapment of crude oil. Specifically, oil originating from depth migrates vertically up faults and is emplaced in traps at shallower depths. Review of petroleum-producing basins worldwide shows oil occurrence in these basins conforms to the restraints of and therefore supports the hypothesis. Most of the world's oil is found in the very deepest sedimentary basins, and production over or adjacent to the deep basin is cut by or directly updip from faults dipping into the basin deep. Generally the greater the fault throw the greater the reserves. Fault-block highs next to deep sedimentary troughs are the best target areas by the present concept. Traps along major basin-forming faults are quite prospective. The structural style of a basin governs the distribution, types, and amounts of hydrocarbons expected and hence the exploration strategy. Production in delta depocenters (Niger) is in structures cut by or updip from major growth faults, and structures not associated with such faults are barren. Production in block fault basins is on horsts next to deep sedimentary troughs (Sirte, North Sea). In basins whose sediment thickness, structure and geologic history are known to a moderate degree, the main oil occurrences can be specifically predicted by analysis of fault systems and possible hydrocarbon migration routes. Use of the concept permits the identification of significant targets which have either been downgraded or ignored in the past, such as production in or just updip from thrust belts, stratigraphic traps over the deep basin associated with major faulting, production over the basin deep, and regional stratigraphic trapping updip from established production along major fault zones.

  8. Marine deep seismic reflection profiles off central California

    SciTech Connect

    Ewing, J. Houston Advanced Research Center, The Woodlands, TX ); Talwani, M. Houston Advanced Research Center, The Woodlands, TX )

    1991-04-10

    A strong reflection horizon at two-way travel time of approximately 6 s is observed in a deep seismic profile across the outer continental shelf of central California. It is interpreted as the seismic image of subducted oceanic crust emplaced prior to the change from principally convergent to principally transcurrent motion between the Pacific and North American plates during the late Paleogene. The reflector dips landward at a very shallow angle and is at a depth of 14-15 km under Santa Lucia Bank. The reflection is not observed, or at best is very discontinuous, under the inner shelf (Santa Maria Basin). This suggests that tectonic or other processes have produced significantly different structural styles or compositions on the two sides of the Santa Lucia Bank fault. Under the outer shelf a prominent, apparently deeper (later arrival time) horizon dips more steeply and diverges from the 6-s reflector. The deep horizon is at least partially composed of diffracted energy but is nearly linear after migration. Possible interpretations are that the horizon indicates crustal imbrication or out-of-plane diffractions. Alternatively, it is a relict feature imparted to the crust at the now inactive Pacific-Farallon spreading ridge. Reflective zones at intermediate depths are observed in apparently accreted sediments in parts of the Santa Lucia and Santa Maria basins. These features could represent tectonically induced fabrics within the accretionary complex, or they could be coherent depositional sequences.

  9. Tritium/Helium-3 Apparent Ages of Shallow Ground Water, Portland Basin, Oregon, 1997-98

    USGS Publications Warehouse

    Hinkle, Stephen R.

    2009-01-01

    Water samples for tritium/helium-3 age dating were collected from 12 shallow monitoring wells in the Portland basin, Oregon, in 1997, and again in 1998. Robust tritium/helium-3 apparent (piston-flow) ages were obtained for water samples from 10 of the 12 wells; apparent ages ranged from 1.1 to 21.2 years. Method precision was demonstrated by close agreement between data collected in 1997 and 1998. Tritium/helium-3 apparent ages generally increase with increasing depth below the water table, and agree well with age/depth relations based on assumptions of effects of recharge rate on vertical ground-water movement.

  10. Comparison of skin and muscle biopsies before and after pentoxifylline treatment in patients with leg ulcers due to deep venous incompetence.

    PubMed

    Angelides, N S; von der Ahe, C W; Themistocleus, P

    1991-01-01

    The aim of this study was to understand the possible mechanisms by which deep venous insufficiency and venous hypertension are associated with trophic skin changes and ulceration and to explain the therapeutic effect of Pentoxifylline in patients with leg ulcers due to deep venous incompetence. Twenty patients were included in this pilot study. They were graded into two groups: group 1, included 10 patients (5 F and 5 M) with deep venous incompetence and normal arteries; group 2, included 10 patients (1 F and 9 M) with deep venous incompetence and moderate arterial disease. Skin and muscle biopsies were carried out before and after the oral administration of 1,200 mg of Pentoxifylline daily (400 mg t.d.s). The following parameters were investigated by means of light microscopy and immunofluorescence tests: engorgement of venous stroma; decrease of intimal elastica; hyaline degeneration; floccular degeneration; pericapillary fibrin deposits and fibrin degradation products; inflammation and fat necrosis; myofibril degeneration; fibrous scar; regeneration and reconstitution of muscle fibres. The results indicated that local inflammation at the ulcer's area cause accumulation of white blood cells in the capillaries and the interstitial fluid, where there is also accumulation of fibrinogen. These changes may lead to chronic tissue ischaemia and ulceration. The known favourable effect of Pentoxifylline on red cells and leucocyte function as well as its lowering effect on plasma fibrinogen level, may be responsible for the observed therapeutic effect of Pentoxifylline on venous leg ulcers.

  11. Ecosystem function and services provided by the deep sea

    NASA Astrophysics Data System (ADS)

    Thurber, A. R.; Sweetman, A. K.; Narayanaswamy, B. E.; Jones, D. O. B.; Ingels, J.; Hansman, R. L.

    2013-11-01

    The deep sea is often viewed as a vast, dark, remote, and inhospitable environment, yet the deep ocean and seafloor are crucial to our lives through the services and provisions that they provide. Our understanding of how the deep sea functions remains limited, but when treated synoptically, a diversity of provisioning, regulating and cultural services become apparent. The biological pump transports carbon from the atmosphere into deep-ocean water masses which are separated over prolonged periods, reducing the impact of anthropogenic carbon release. Microbial oxidation of methane keeps another potent greenhouse gas out of the atmosphere while trapping carbon in authigenic carbonates. Nutrient regeneration by all faunal size classes provides the elements necessary to fuel surface productivity and fisheries, and microbial processes detoxify a diversity of compounds. Each of these processes occur on a very small scale, yet considering the vast area over which they occur they become important for the global functioning of the ocean. The deep sea also provides a diversity of resources, including fish stocks, enormous bioprospecting potential, and elements and energy reserves that are currently being extracted and will be increasingly important in the near future. Society benefits from the intrigue and mystery, the strange life forms, and the great unknown which has acted as a muse for inspiration and imagination since near the beginning of civilization. While many functions occur on the scale of microns to meters and time scales up to years, the derived services that result are only useful after centuries of integrated activity. This vast dark habitat, that covers the majority of the globe, harbors processes that directly impact humans in a diversity of ways, however the same traits that differentiate it from terrestrial or shallow marine systems also result in a greater need for integrated spatial and temporal understanding as it experiences increased use by society.

  12. Influence of topography and human activity on apparent in situ 10Be-derived erosion rates in Yunnan, SW China

    NASA Astrophysics Data System (ADS)

    Schmidt, Amanda H.; Neilson, Thomas B.; Bierman, Paul R.; Rood, Dylan H.; Ouimet, William B.; Sosa Gonzalez, Veronica

    2016-11-01

    In order to understand better if and where erosion rates calculated using in situ 10Be are affected by contemporary changes in land use and attendant deep regolith erosion, we calculated erosion rates using measurements of in situ 10Be in quartz from 52 samples of river sediment collected from three tributaries of the Mekong River (median basin area = 46.5 km2). Erosion rates range from 12 to 209 mm kyr-1 with an area-weighted mean of 117 ± 49 mm kyr-1 (1 standard deviation) and median of 74 mm kyr-1. We observed a decrease in the relative influence of human activity from our steepest and least altered watershed in the north to the most heavily altered landscapes in the south. In the areas of the landscape least disturbed by humans, erosion rates correlate best with measures of topographic steepness. In the most heavily altered landscapes, measures of modern land use correlate with 10Be-estimated erosion rates but topographic steepness parameters cease to correlate with erosion rates. We conclude that, in some small watersheds with high rates and intensity of agricultural land use that we sampled, tillage and resultant erosion has excavated deeply enough into the regolith to deliver subsurface sediment to streams and thus raise apparent in situ 10Be-derived erosion rates by as much as 2.5 times over background rates had the watersheds not been disturbed.

  13. Near Infrared Imaging of the Hubble Deep Field with Keck Telescope

    NASA Technical Reports Server (NTRS)

    Hogg, David W.; Neugebauer, G.; Armus, Lee; Matthews, K.; Pahre, Michael A.; Soifer, B. T.; Weinberger, A. J.

    1997-01-01

    Two deep K-band (2.2 micrometer) images, with point-source detection limits of K=25.2 mag (one sigma), taken with the Keck Telescope in subfields of the Hubble Deep Field, are presented and analyzed. A sample of objects to K=24 mag is constructed and V(sub 606)- I(sub 814) and I(sub 814)-K colors are measured. By stacking visually selected objects, mean I(sub 814)-K colors can be measured to very faint levels, the mean I(sub 814)-K color is constant with apparent magnitude down to V(sub 606)=28 mag.

  14. Response of Swimming Paramecia to in situ changes in their apparent weight

    NASA Astrophysics Data System (ADS)

    Jung, Ilyong; Mickalide, Harry; Valles, James M., Jr.

    2012-02-01

    There is a class of marine micro-organisms that are small enough that low Reynold's number hydrodynamics dictates their swimming mechanics and large enough that the force of gravity exerts a noticeable influence on their motion. Experiments on populations of paramecia suggest that they exert a greater propulsion when swimming against gravity. This negative gravi-kinesis is surprising because it suggests that they sense their tiny apparent weight of about 80 pN. To understand this response in more detail, we are investigating how individual paramecia caudatum change their swimming speed and helical trajectories in response to changes in their apparent weight. We vary the apparent weight with the technique of Magnetic Force Buoyancy Variation employing a high field resistive magnet at the National High Magnetic Field Laboratory. We will present analysis of the swimming for apparent weight changes as large as a factor of 8.

  15. Apparent phosphorus availabilities of selected traditional and alternative feedstuffs for channel catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A digestibility trial with channel catfish Ictalurus punctatus was conducted to determine apparent availability coefficients (AACs) of phosphorus for selected common feedstuffs: soybean meal, cottonseed meal, wheat middlings, corn gluten feed (CGF), and corn distillers dried grains with solubles (DD...

  16. Multiple myeloma: Development of plasma cell sarcoma during apparently successful chemotherapy

    PubMed Central

    Holt, J. M.; Robb-Smith, A. H. T.

    1973-01-01

    Three patients with multiple myeloma who developed a plasma cell sarcoma during apparently successful chemothapy are described. It is postulated that the chemotherapy induced the sarcomatous change. Images PMID:4584727

  17. Stimulus Orientation and the Apparent Developmental Lag Between Perception and Performance

    ERIC Educational Resources Information Center

    Strayer, Janet; Ames, Elinor W.

    1972-01-01

    Aim of the present study was to clarify the processes involved in the apparent lag in copying a diamond by reducing the lag experimentally with perceptual training of discrimination of orientation. (Authors)

  18. [TO CURE THE APPARENTLY DEAD. NOSOLOGY AND MEDICAL RESUSCITATION IN ITALY(XVIII CENT.)].

    PubMed

    Marinozzi, Silvia

    2015-01-01

    The first specific techniques and triages for medical resuscitation developed in the XVIII century, specifically to rescue the drowned persons. The topic of resuscitation in strictly connected to the theme of the apparent death, to the dread of the "buried alive", to the progress of forensic medicine and to the administrative and legislative policies. The contribute aims to focus on the contribution of the medical and pathologic nosology about the conception of the apparent death, read as asphyxia.

  19. Desmotomy for treatment of chronic desmitis of the accessory ligament of the deep digital flexor tendon in a horse.

    PubMed Central

    Todhunter, P G; Schumacher, J; Finn-Bodner, S T

    1997-01-01

    Chronic lameness was determined to be caused by desmitis of the accessory ligament of the deep digital flexor tendon and adhesions associated with these 2 structures. Desmotomy of the accessory ligament, resection of adhesions, and controlled exercise during convalescence resulted in return to normal use without apparent lameness. Images Figure 1. Figure 2. PMID:9332748

  20. A Deep ALMA Image of the Hubble Ultra Deep Field

    NASA Astrophysics Data System (ADS)

    Dunlop, J. S.

    2016-12-01

    Although primarily designed as a high-resolution imaging spectrometer at submillimetre/millimetre wavelengths, the Atacama Large Millimeter/submillimeter Array (ALMA) has a vital role to play in producing the key deep, unconfused, submillimetre/millimetre continuum surveys required to bridge the current gap in our understanding of visible and dust-obscured star formation in the young Universe. The first such survey has now been completed, comprising a mosaic of 45 ALMA pointings at a wavelength of 1.3 mm, covering the Hubble Ultra Deep Field (HUDF). This deep, homogeneous ALMA survey, combined with the wealth of existing data in the HUDF, has already provided new clarity on the nature of dusty star-forming galaxies, and the relative evolution of dust-obscured and unobscured star formation over cosmic time.

  1. Apparent competition with an invasive plant hastens the extinction of an endangered lupine.

    PubMed

    Dangremond, Emily M; Pardini, Eleanor A; Knight, Tiffany M

    2010-08-01

    Invasive plants may compete with native plants by increasing the pressure of native consumers, a mechanism known as "apparent competition." Apparent competition can be as strong as or stronger than direct competition, but the role of apparent competition has rarely been examined in biological invasions. We used four years of demographic data and seed-removal experiments to determine if introduced grasses caused elevated levels of seed consumption on native plant species in a coastal dune system in California, USA. We show that the endangered, coastal dune plant Lupinus tidestromii experiences high levels of pre-dispersal seed consumption by the native rodent Peromyscus maniculatus due to its proximity to the invasive grass, Ammophila arenaria. We use stage-structured, stochastic population models to project that two of three study populations will decline toward extinction under ambient levels of consumption. For one of these declining populations, a relatively small decrease in consumption pressure should allow for persistence. We show that apparent competition with an invasive species significantly decreases the population growth rate and persistence of a native species. We expect that apparent competition is an important mechanism in other ecosystems because invasive plants often change habitat structure and plant-consumer interactions. Possible implications of the apparent-competition mechanism include selective extinction of species preferred by seed consumers in the presence of an invasive species and biological homogenization of communities toward non-preferred native plant species.

  2. Deep RNNs for video denoising

    NASA Astrophysics Data System (ADS)

    Chen, Xinyuan; Song, Li; Yang, Xiaokang

    2016-09-01

    Video denoising can be described as the problem of mapping from a specific length of noisy frames to clean one. We propose a deep architecture based on Recurrent Neural Network (RNN) for video denoising. The model learns a patch-based end-to-end mapping between the clean and noisy video sequences. It takes the corrupted video sequences as the input and outputs the clean one. Our deep network, which we refer to as deep Recurrent Neural Networks (deep RNNs or DRNNs), stacks RNN layers where each layer receives the hidden state of the previous layer as input. Experiment shows (i) the recurrent architecture through temporal domain extracts motion information and does favor to video denoising, and (ii) deep architecture have large enough capacity for expressing mapping relation between corrupted videos as input and clean videos as output, furthermore, (iii) the model has generality to learned different mappings from videos corrupted by different types of noise (e.g., Poisson-Gaussian noise). By training on large video databases, we are able to compete with some existing video denoising methods.

  3. Hyaluronic acid content of deep and subcutaneous bursae of man.

    PubMed Central

    Canoso, J J; Stack, M T; Brandt, K D

    1983-01-01

    To provide a comparison of the contents of subcutaneous and deep bursae we dissected these structures from unfixed cadavers without apparent joint disease. No free fluid was found within any olecranon or prepatellar bursae (examples of subcutaneous bursae), while viscous fluid was invariably present in the (deep) retrocalcaneal bursae. The hyaluronic acid content of the washings of 5 rectrocalcaneal bursae ranged from 142 to 591 nmol hexosamine (mean = 281 nmol hexosamine). In contrast, the hyaluronic acid content of 4 olecranon bursae was much lower (range 35-72 nmol, mean 53 nmol hexosamine), and hyaluronate was not detected in washings from either of 2 prepatellar bursae. The greater hyaluronate content of the retrocalcaneal bursae did not appear to be due to a greater surface area, since on the basis of calculations made from plaster casts the surface areas of the olecranon and prepatellar bursae were approximately 3 times and 2 times, respectively, greater than that of the retrocalcaneal bursae. The data suggest that, although hyaluronic acid may lubricate deep bursae, other factors may be more important in reducing friction within superficial bursae. Images PMID:6847262

  4. Deep Learning and Bayesian Methods

    NASA Astrophysics Data System (ADS)

    Prosper, Harrison B.

    2017-03-01

    A revolution is underway in which deep neural networks are routinely used to solve diffcult problems such as face recognition and natural language understanding. Particle physicists have taken notice and have started to deploy these methods, achieving results that suggest a potentially significant shift in how data might be analyzed in the not too distant future. We discuss a few recent developments in the application of deep neural networks and then indulge in speculation about how such methods might be used to automate certain aspects of data analysis in particle physics. Next, the connection to Bayesian methods is discussed and the paper ends with thoughts on a significant practical issue, namely, how, from a Bayesian perspective, one might optimize the construction of deep neural networks.

  5. Endometrial Endometrioid Carcinoma With Large Cystic Growth Configuration and Deceptive Pattern of Invasion Associated With Abundant Nodular Fasciitis-like Stroma: A Unique Hitherto Unreported Histology in Endometrioid Carcinoma.

    PubMed

    Švajdler, Marián; Michal, Michael; Dubinský, Pavol; Švajdler, Peter; Ondič, Ondrej; Michal, Michal

    2016-11-01

    We describe a case of an unusual endometrial endometrioid carcinoma occurring in a 67-year-old woman. The tumor involved uterine corpus as well as lower uterine segment and presented as polypoid tumor protruding through the cervical orifice. Microscopically, the tumor was characterized by broad zones of cytologically bland fibromyxoid stroma resembling nodular fasciitis, showing vaguely nodular architecture. Neoplastic glands were characterized by interconnected elongated slit-like and large cystic profiles, mostly lined by flattened epithelium with variable squamous differentiation, whereas typical columnar endometrioid cells were only focally present. Voluminous nodules of the stroma produced phyllodes-like appearance of the tumor. The tumor showed some resemblance to the microcystic, elongated, and fragmented (MELF) glands growth pattern, but in contrast with MELF pattern, where fibromyxoid change occurs focally, in the presented case abundant myofibroblastic proliferation was present throughout the tumor and the neoplastic glands showed anastomosing "large cystic" rather than "small cystic" profiles. Some of the neoplastic glands presented almost complete or complete squamous differentiation, with relatively bland-looking squamous cells and no hint of endometrioid differentiation, which resulted in initial misdiagnosis of Müllerian adenofibroma. We believe that nodular fasciitis-like pattern represents yet undescribed, and diagnostically challenging pattern of invasion in endometrial endometrioid carcinoma.

  6. Impaired tumor growth in colony-stimulating factor 1 (CSF-1)-deficient, macrophage-deficient op/op mouse: evidence for a role of CSF-1-dependent macrophages in formation of tumor stroma.

    PubMed

    Nowicki, A; Szenajch, J; Ostrowska, G; Wojtowicz, A; Wojtowicz, K; Kruszewski, A A; Maruszynski, M; Aukerman, S L; Wiktor-Jedrzejczak, W

    1996-01-03

    Macrophages have been suggested to play a major role in the immune response to cancer. They have also been suggested to stimulate the formation of tumor stroma and to promote tumor vascularization. The availability of the op/op mouse, which has no endogenous colony-stimulating factor 1 (CSF-1) and which possesses a profound macrophage deficiency, provides a new model to verify these notions. Subcutaneous growth of transplantable Lewis lung cancer (LLC) is markedly impaired in the op/op mice compared with normal littermates. Treatment of tumor-bearing op/op mice with human recombinant CSF-1 corrects this impairment. Histological analysis of tumors grown in op/op and normal mice revealed marked differences. Tumors grown in op/op mice display a decreased mitotic index and pronounced necrosis, particularly hemorrhagic. Moreover, particularly in the op/op tumors, peculiar sinusoid-like abortive vessels (not filled with blood) have been observed. These tumors, in contrast to tumors grown in normal mice, are almost deprived of regular arteries and veins. In contrast to tumors grown in normal mice, they exhibit almost no Sirius red-stained collagenous fibers and Gomori silver-stained reticular fibers. Our data suggest that the CSF-1-dependent macrophage subpopulation missing in op/op mice plays a primary role in supporting tumor stroma formation and tumor vascularization in murine LLC tumors.

  7. Clinical evaluation of Deep Anterior Lamellar Keratoplasty (DALK) for stromal corneal opacities

    PubMed Central

    Mathur, Vijay; Parihar, J.K.S.; Srivastava, V.K.; Avasthi, A.

    2012-01-01

    Background Corneal scars are commonly formed following many diseases of the eye like trauma, inflammation and infections. They lead to permanent diminution of vision which can be managed by Penetrating Keratoplasty (PK). PK is removing diseased as well as healthy tissues and is associated with many post-operative complications. Deep Anterior Lamellar Keratoplasty (DALK) is a relatively newer procedure which replaces only the diseased stroma, leaving the original corneal endothelium intact. This procedure is associated with lesser incidence of post-operative complications. Methods The study was conducted at a large tertiary care centre. 10 patients with stromal corneal scars were subjected to DALK and results were analysed after 06 months. Poor quality donor corneal tissue of B− and C grade was used in all cases. Results 7 out of 10 patients (70%) undergoing DALK had post-operative visual acuity of 6/24 or better. 03 patients who did not have adequate recovery of visual acuity were due to over-riding of the graft in 01 case (10%), fungal keratitis in 01 case (10%) and interface haze in 01 case (10%). Conclusion DALK is a promising new technique for management of superficial corneal stromal scars using poor quality donor corneal tissue. Initial results are encouraging with minimal complications. PMID:24532929

  8. Apparent ruminal synthesis and intestinal disappearance of vitamin B12 and its analogs in dairy cows.

    PubMed

    Girard, C L; Santschi, D E; Stabler, S P; Allen, R H

    2009-09-01

    The aim of the project was to calculate the apparent synthesis or destruction of cobalamin (vitamin B(12)) and its analogs in the rumen as well as their apparent intestinal disappearance in dairy cows. Four lactating cows were fed a diet supplemented with cobalt alone (0.76 mg/kg of DM; control) or with cobalt and vitamin B(12) (cyanocobalamin, 500 mg/d; treated). In addition to cobalamin, the only biologically active molecule for the cow, 7 analogs were identified in duodenal and ileal digesta: cobinamide, which lacks the base, ribose, and phosphate groups; and 6 other molecules in which the base, 5,6-dimethylbenzimidazole, is replaced by cresol, 2-CH(3)-adenine, adenine, 2-CH(3)-S-adenine, or 5-OH-benzimidazole, or an unidentified cobamine. Small amounts of cobalamin and cobinamide were detected in the total mixed ration, but apparent synthesis of all forms took place in rumen. During the control period, cobalamin represented 38% of the total amounts of corrinoids produced in rumen. Approximately 11% of the average daily intake of cobalt was used for apparent ruminal synthesis of corrinoids, of which only 4% was incorporated into cobalamin. Only 20% of the supplement of cyanocobalamin was recovered at the duodenal level; cobinamide appeared to be the major product of degradation of supplementary cyanocobalamin in the rumen. During the control and treatment periods, there was an apparent intestinal disappearance of cobalamin and 5-OH-benzimidazole cobamide only; only the apparent intestinal disappearance of cobalamin differed between the 2 periods. Although cobalamin was not the major form synthesized by ruminal microflora and, even if supplementary cyanocobalamin was extensively destroyed by ruminal microflora, based on calculations of apparent intestinal disappearance, cobalamin seems to be the major form absorbed in the small intestine.

  9. Deep Impact Network Experiment (DINET)

    NASA Technical Reports Server (NTRS)

    Burleigh, Scott

    2008-01-01

    DINET is a technology development experiment intended to increase the technical readiness of JPL s implementation of DTN protocols - "ION". The objective is to advance ION in flight and ground SW to TRL 8, with code of sufficient quality that future flight projects can easily use it at low risk. DINET is to be implemented on the Deep Impact flyby spacecraft. DINET operations will be performed in late 2008 during the Deep Impact spacecraft team "stand down" after EPOCH operations and before the start of development for DIXI operations.

  10. Relationships between deep-sea tunicate populations west and east of the Straits of Gibraltar

    NASA Astrophysics Data System (ADS)

    Monniot, Claude; Monniot, Françoise

    Twenty-four species of tunicates were collected from deep bottoms on each side of the Gibraltar sill, in the adjacent Mediterranean Sea and Atlantic Ocean. In the Atlantic, stations bathed by Atlantic and Mediterranean waters were both sampled. No transport of ascidian taxa by the outflow of Mediterranean water into the Atlantic is apparent. The alternative hypothesis of an Atlantic origin of bathyal ascidian species in the Mediterranean Sea is proposed.

  11. Stimulation Technologies for Deep Well Completions

    SciTech Connect

    2003-09-30

    The Department of Energy (DOE) is sponsoring the Deep Trek Program targeted at improving the economics of drilling and completing deep gas wells. Under the DOE program, Pinnacle Technologies is conducting a study to evaluate the stimulation of deep wells. The objective of the project is to assess U.S. deep well drilling & stimulation activity, review rock mechanics & fracture growth in deep, high pressure/temperature wells and evaluate stimulation technology in several key deep plays. An assessment of historical deep gas well drilling activity and forecast of future trends was completed during the first six months of the project; this segment of the project was covered in Technical Project Report No. 1. The second progress report covers the next six months of the project during which efforts were primarily split between summarizing rock mechanics and fracture growth in deep reservoirs and contacting operators about case studies of deep gas well stimulation.

  12. Flicker adaptation or superimposition raises the apparent spatial frequency of coarse test gratings.

    PubMed

    Kaneko, Sae; Giaschi, Deborah; Anstis, Stuart

    2015-03-01

    Independent channels respond to both the spatial and temporal characteristics of visual stimuli. Gratings <3 cycles per degree (cpd) are sensed by transient channels that prefer intermittent stimulation, while gratings >3 cpd are sensed by sustained channels that prefer steady stimulation. From this we predict that adaptation to a spatially uniform flickering field will selectively adapt the transient channels and raise the apparent spatial frequency of coarse sinusoidal gratings. Observers adapted to a spatially uniform field whose upper or lower half was steady and whose other half was flickering. They then adjusted the spatial frequency of a stationary test (matching) grating on the previously unmodulated half field until it matched the apparent spatial frequency of a grating falling on the previously flickering half field. The adapting field flickered at 8 Hz and the spatial frequency of the gratings was varied in octave steps from 0.25 to 16 cpd. As predicted, adapting to flicker raised the apparent spatial frequency of the test gratings. The aftereffect reached a peak of 11% between 0.5 and 1 cpd and disappeared above 4 cpd. We also observed that superimposed 10 Hz luminance flicker raised the apparent spatial frequency of 0.5 cpd test gratings. The effect was not seen with slower flicker or finer test gratings. Altogether, our study suggests that apparent spatial frequency is determined by the balance between transient and sustained channels and that an imbalance between the channels caused by flicker can alter spatial frequency perception.

  13. Amorphous solid dispersion enhances permeation of poorly soluble ABT-102: true supersaturation vs. apparent solubility enhancement.

    PubMed

    Frank, Kerstin J; Rosenblatt, Karin M; Westedt, Ulrich; Hölig, Peter; Rosenberg, Jörg; Mägerlein, Markus; Fricker, Gert; Brandl, Martin

    2012-11-01

    Amorphous solid dispersions (ASDs) represent a promising formulation approach for poorly soluble drugs. We explored the formulation-related impact of ASDs on permeation rate, apparent solubility and molecular solubility of the poorly soluble drug ABT-102. The influence of fasted state simulated intestinal fluid (FaSSIF) as dispersion medium was also studied. ASDs were prepared by hot-melt extrusion. Permeation rate was assessed by the Caco-2 transwell assay. Cell viability and barrier integrity were assured by AlamarBlue©, TEER and permeability of the hydrophilic marker carboxyfluorescein. Apparent solubility and molecular solubility were evaluated by using centrifugation and inverse dialysis, respectively. The in vitro permeation rate of ABT-102 from aqueous dispersions of the ASD was found 4 times faster than that from the dispersions of the crystals, while apparent solubility and molecular solubility of ABT-102 were increased. Yet, a further increase in apparent solubility due to micellar solubilization as observed when dispersing the ASD in FaSSIF, did not affect molecular solubility or permeation rate. Overall, a good correlation between permeation rate and molecular solubility but not apparent solubility was seen.

  14. Depth representation of moving 3-D objects in apparent-motion path.

    PubMed

    Hidaka, Souta; Kawachi, Yousuke; Gyoba, Jiro

    2008-01-01

    Apparent motion is perceived when two objects are presented alternately at different positions. The internal representations of apparently moving objects are formed in an apparent-motion path which lacks physical inputs. We investigated the depth information contained in the representation of 3-D moving objects in an apparent-motion path. We examined how probe objects-briefly placed in the motion path-affected the perceived smoothness of apparent motion. The probe objects comprised 3-D objects which were defined by being shaded or by disparity (convex/concave) or 2-D (flat) objects, while the moving objects were convex/concave objects. We found that flat probe objects induced a significantly smoother motion perception than concave probe objects only in the case of the convex moving objects. However, convex probe objects did not lead to smoother motion as the flat objects did, although the convex probe objects contained the same depth information for the moving objects. Moreover, the difference between probe objects was reduced when the moving objects were concave. These counterintuitive results were consistent in conditions when both depth cues were used. The results suggest that internal representations contain incomplete depth information that is intermediate between that of 2-D and 3-D objects.

  15. Apparent plasticity in functional traits determining competitive ability and spatial distribution: a case from desert

    PubMed Central

    Xie, Jiang-Bo; Xu, Gui-Qing; Jenerette, G. Darrel; Bai, Yong-fei; Wang, Zhong-Yuan; Li, Yan

    2015-01-01

    Species competitive abilities and their distributions are closely related to functional traits such as biomass allocation patterns. When we consider how nutrient supply affects competitive abilities, quantifying the apparent and true plasticity in functional traits is important because the allometric relationships among traits are universal in plants. We propose to integrate the notion of allometry and the classical reaction norm into a composite theoretical framework that quantifies the apparent and true plasticity. Combining the framework with a meta-analysis, a series of field surveys and a competition experiment, we aimed to determine the causes of the dune/interdune distribution patterns of two Haloxylon species in the Gurbantonggut Desert. We found that (1) the biomass allocation patterns of both Haloxylon species in responses to environmental conditions were apparent rather than true plasticity and (2) the allometric allocation patterns affected the plants’ competition for soil nutrient supply. A key implication of our results is that the apparent plasticity in functional traits of plants determines their response to environmental change. Without identifying the apparent and true plasticity, we would substantially overestimate the magnitude, duration and even the direction of plant responses in functional traits to climate change. PMID:26190745

  16. The apparent strain stability and repeatability of a BCL3 resistance strain gage

    NASA Technical Reports Server (NTRS)

    Lei, Jih-Fen

    1991-01-01

    Experiments were conducted at NASA-Lewis to study the effect of microstructural instability on the apparent strain stability and reproducibility of a BCL3 resistance strain gage. The resistance drift of the gage at various temperatures in the phase transition temperature range (PTTR) was measured. The effects of the heating and cooling rates with which the gage passed through the PTTR on the apparent strain characteristics of the gage were also studied. BCL3 gage, like other Fe-Cr-Al based gages, exhibited apparent strain instability in the temperature range of 700 to 1100 F due to the reversible microstructural transition the gage materials experienced in this temperature range. The BCL3 gage had a maximum apparent strain drift in the neighborhood of 770 F with an average drift rate of approx. -440 microstrain/hr in 2 hrs. The use of the BCL3 gage as well as other Fe-Cl-Al based gages for static strain measurements within the PTTR should be avoided unless the time durations in the PTTR are small enough to introduce a neglible drift. The microstructure transition that the BCL3 gage underwent occurred in the temperature range of 750 to 1050 F during heating and around 1000 to 800 F during cooling. The heating rate, and, in particular, the cooling rate with which the gage passed through the PTTR affected the shape and the repeatability of the apparent strain curve of the gage.

  17. Apparent density patterns in subchondral bone of the sloth and anteater forelimb.

    PubMed

    Patel, Biren A; Carlson, Kristian J

    2008-10-23

    Vertebrate morphologists often are interested in inferring limb-loading patterns in animals characterized by different locomotor repertoires. Because bone apparent density (i.e. mass per unit volume of bone inclusive of porosities) is a determinant of compressive strength, and thus indicative of compressive loading, recent comparative studies in primates have proposed a structure-function relationship between apparent density of subchondral bone and locomotor behaviours that vary in compressive loading. If such patterns are found in other mammals, then these relationships would be strengthened further. Here, we examine the distal radius of suspensory sloths that generally load their forelimbs (FLs) in tension and of quadrupedal anteaters that generally load their FLs in compression. Computed tomography osteoabsorptiometry was used to visualize the patterns in subchondral apparent density. Suspensory sloths exhibit relatively smaller areas of high apparent density than quadrupedal anteaters. This locomotor-based pattern is analogous to the pattern observed in suspensory and quadrupedal primates. Similarity between xenarthran and primate trends suggests broad-scale applicability for analysing subchondral bone apparent density and supports the idea that bone functionally alters its material properties in response to locomotor behaviours.

  18. STIMULATION TECHNOLOGIES FOR DEEP WELL COMPLETIONS

    SciTech Connect

    Stephen Wolhart

    2003-06-01

    The Department of Energy (DOE) is sponsoring a Deep Trek Program targeted at improving the economics of drilling and completing deep gas wells. Under the DOE program, Pinnacle Technologies is conducting a project to evaluate the stimulation of deep wells. The objective of the project is to assess U.S. deep well drilling & stimulation activity, review rock mechanics & fracture growth in deep, high pressure/temperature wells and evaluate stimulation technology in several key deep plays. Phase 1 was recently completed and consisted of assessing deep gas well drilling activity (1995-2007) and an industry survey on deep gas well stimulation practices by region. Of the 29,000 oil, gas and dry holes drilled in 2002, about 300 were drilled in the deep well; 25% were dry, 50% were high temperature/high pressure completions and 25% were simply deep completions. South Texas has about 30% of these wells, Oklahoma 20%, Gulf of Mexico Shelf 15% and the Gulf Coast about 15%. The Rockies represent only 2% of deep drilling. Of the 60 operators who drill deep and HTHP wells, the top 20 drill almost 80% of the wells. Six operators drill half the U.S. deep wells. Deep drilling peaked at 425 wells in 1998 and fell to 250 in 1999. Drilling is expected to rise through 2004 after which drilling should cycle down as overall drilling declines.

  19. Deep water exchanges between the South China Sea and the Pacific since the last glacial period

    NASA Astrophysics Data System (ADS)

    Wan, Sui; Jian, Zhimin

    2014-12-01

    Deep ocean circulation is widely considered as one of the important factors for increasing CO2 concentration and decreasing radiocarbon activity (Δ14C) of the atmosphere during the last deglaciation. The AMS 14C ages of benthic and planktonic foraminifers from 18 samples of Core MD05-2904 (water depth of 2066 m) in the northern South China Sea (SCS) and 15 samples of Core MD05-2896 (water depth of 1657 m) in the southern SCS were analyzed in this study for reconstructing the intrabasin deep oceanic processes and hence exploring the deep water exchanges between the SCS and the Pacific since the last glacial period. The results show that during the Holocene the average apparent ventilation age of deep water was younger in the southern SCS (~1350 years) than in the northern SCS (~1850 years) due to relatively strong vertical mixing and advection, consistent with modern observations. However, during the last glacial period and deglaciation the deep water was older in the southern SCS (~2050 years and ~1800 to 1200 years, respectively) than in the northern SCS (~1600 years and ~670 years, respectively), indicating reduced deep mixing and advection. Moreover, the northern SCS deep water was significantly younger during the last deglaciation than during the Holocene and the last glacial period, implying the existence of northern sourced newly formed and relatively young North Pacific deep water. Our records do not support the intrusion of anomalously 14C-depleted deep water to the middepth of the low-latitude western Pacific and the SCS during the "Mystery Interval" (17.5-14.5 kyr B.P.).

  20. Electrochemical Machining Removes Deep Obstructions

    NASA Technical Reports Server (NTRS)

    Catania, Mark J.

    1987-01-01

    Electrochemical machining (ECM) is effective way of removing obstructing material between two deep holes supposed to intersect but do not because of misalignment of drilling tools. ECM makes it possible to rework costly castings otherwise scrapped. Method fast even for tough or hard alloys and complicated three-dimensional shapes.