New avenues for improving pancreatic ductal adenocarcinoma (PDAC) treatment: Selective stroma depletion combined with nano drug delivery.

PubMed

Bhaw-Luximon, Archana; Jhurry, Dhanjay

2015-12-28

The effectiveness of chemotherapy in PDAC is hampered by the dynamic interaction between stroma and cancer cell. The two opposing schools of thought - non-depletion of the stroma vs its depletion - to better drug efficacy are here discussed. Disrupting stroma-cancer cell interaction to reduce tumor progression and promote apoptosis is identified as the new direction of treatment for PDAC. Clinical data have shown that elimination of fibrosis and blockade of the Hedgehog pathway in stroma effectively promote drug delivery to tumor site and apoptosis. Reduced stiffness of ECM, lower fibrosis, higher permeability and higher blood flow after stroma depletion increase drug delivery. Combination strategies involving selective stroma depletion coupled with chemotherapy is currently proving to be the most efficient at clinical level. Striking the right balance between fibrosis depletion and angiogenesis promotion resulting in enhanced drug delivery and apoptosis is a major challenge. The use of nano drug delivery devices coupled with stroma depletion is emerging as the next phase treatment for PDAC. The breakthrough to combat PDAC will likely be a combination of early diagnosis and the emerging chemotherapy strategies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

2017-06-01

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. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

RED CELL STROMA PROTEIN RICH IN VITAMIN B12 DURING ACTIVE REGENERATION

PubMed Central

Whipple, G. H.; Robscheit-Robbins, F. S.; Bale, W. F.

1955-01-01

During active blood regeneration in anemia in dogs an increase occurs in the stroma protein of the red cells. When vitamin B12 with radioactive cobalt is given at the start of this blood regeneration one finds concentration of labeled B 12 in the stroma protein but not in the hemoglobin. After the acute phase of red cell regeneration is ended the concentration of B12 in stroma protein falls rapidly to very low levels within 2 weeks. Subsequent episodes of red blood cell regeneration seems not to cause remobilization of radioactive cobalt into red cells from other body stores. It appears that the vitamin B12 is a factor of importance in the first steps of stroma protein formation in the first few days of the life of the red cell in the dog. This response in dogs and the response in pernicious anemia to vitamin B12 may have some points in common. Distribution of the B12-radioactive cobalt in the organs and tissues at autopsy has been recorded. Some very suggestive localizations were noted and some variation 1 week and 7 weeks after B12 injections. Radioactive cobalt escapes in the urine during the weeks following B12 injections. PMID:13271685

Donor cornea preparation in partial big bubble deep anterior lamellar keratoplasty.

PubMed

Lim, Li; Lim, Samuel Wen Yan

2014-01-01

The purpose of this paper is to describe a technique of donor cornea preparation to ensure good graft-host apposition in incomplete big bubble deep anterior lamellar keratoplasty. Following a partial-thickness trephination, manual dissection and excision of corneal stroma was performed. Anwar's big-bubble technique involving a deep stromal air injection was then initiated. However, the big bubble could not extend to the trephination edge and the peripheral residual corneal stroma could not be removed. Donor cornea preparation involving trimming of the posterior lip of the corneal button was then performed and good graft-host apposition was obtained without graft over-ride. We performed peripheral donor cornea trimming prior to allograft placement in order to ensure good graft-host apposition. Postoperatively, best-corrected visual acuity in both eyes was 6/7.5. Donor cornea preparation involving trimming of the posterior lip of the corneal button is a useful technique in instances where the big bubble does not extend to the trephination edge and ensures good graft-host apposition.

Stroma Breaking Theranostic Nanoparticles for Targeted Pancreatic Cancer Therapy

Cancer.gov

This project develops a dual-targeted and stroma breaking theranostic nanoparticle platform to address an unmet, clinical challenge of poor drug delivery efficiency in the application of nanomedicine to cancer therapy.

Tumor-stroma interactions a trademark for metastasis.

PubMed

Morales, Monica; Planet, Evarist; Arnal-Estape, Anna; Pavlovic, Milica; Tarragona, Maria; Gomis, Roger R

2011-10-01

We aimed to unravel genes that are significantly associated with metastasis in order to identify functions that support disseminated disease. We identify genes associated with metastasis and verify its clinical correlations using publicly available primary tumor expression profile data sets. We used facilities in R and Bioconductor (GSEA). Specific data structures and functions were imported. Our results show that genes associated with metastasis in primary tumor enriched for pathways associated with immune infiltration or cytokine-cytokine receptor interaction. As an example, we focus on the enrichment of TGFBR2 and TGF|X A set of communication tools capital for tumor-stroma interactions that define metastasis to the lung and support bone colonization. We showed that tumor-stroma communication through cytokine-cytokine receptor interaction pathway is selected in primary tumors with high risk of relapse. High levels of these factors support systemic instigation of the far metastatic nest as well as local metastatic-specific functions that provide solid ground for metastatic development. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reactive stroma in the prostate during late life: The role of microvasculature and antiangiogenic therapy influences.

PubMed

Montico, Fabio; Kido, Larissa Akemi; San Martin, Rebeca; Rowley, David R; Cagnon, Valéria H A

2015-10-01

Prostate cancer is associated to a reactive stroma microenvironment characterized by angiogenic processes that are favorable for tumor progression. Senescence has been identified as a predisposing factor for prostate malignancies. In turn, the relationships between aging, reactive stroma, and the mechanisms that induce this phenotype are largely unknown. Thus, we investigated the occurrence of reactive stroma in the mouse prostate during advanced age as well as the effects of antiangiogenic and androgen ablation therapies on reactive stroma recruitment. Male mice (52-week-old FVB) were treated with two classes of angiogenesis inhibitors: direct (TNP-470; 15 mg/kg; s.c.) and/or indirect (SU5416; 6 mg/kg; i.p.). Androgen ablation was carried out by finasteride administration (20 mg/kg; s.c.), alone or in association to both inhibitors. The Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model was used as a paradigm of cancer-associated reactive stroma. The dorsolateral prostate was collected for α-actin (αSMA), vimentin (VIM), and transforming growth factor-beta (TGF-β) immunohistochemical and Western blotting analyses as well as for CD34/αSMA and CD34/VIM colocalization. Senescence was associated with increased αSMA, VIM, and TGF-β expression as well as with the recruitment of CD34/αSMA and CD34/VIM dual-positive fibroblasts. These observations were similar to those verified in TRAMP mice. Antiangiogenic treatment promoted the recovery of senescence-associated stromal changes. Hormonal ablation, despite having led to impaired CD34/αSMA and CD34/VIM dual-positive cell recruitment, did not result in decreased stimulus to reactive stroma development, due to enhanced TGF-β expression in relation to the aged controls. Reactive stroma develops in the prostate of non-transgenic mice as a result of aging. The periacinar microvasculature is a candidate source for the recruitment of reactive stroma-associated cells, which may be derived either from

Big-bubble deep anterior lamellar keratoplasty using central vs peripheral air injection: a clinical trial.

PubMed

Feizi, Sepehr; Daryabari, Seyed-Hashem; Najdi, Danial; Javadi, Mohammad Ali; Karimian, Farid

2016-06-10

To compare 2 sites of air injection to achieve Descemet membrane (DM) detachment in big-bubble deep anterior lamellar keratoplasty (DALK). In this prospective, randomized study, 48 eyes of 48 keratoconus-affected patients who underwent DALK by cornea fellows were enrolled. Each patient was randomly assigned into one of 2 groups. After trephination to approximately 80% of the corneal thickness, a 27-G needle was inserted into the stroma from the trephination site. The needle was moved radially inside the trephination site and advanced to the central or paracentral cornea in group 1. In group 2, the needle was inserted into the deep stroma from the trephination site and advanced into the peripheral cornea to approximately 1.5 mm anterior to the limbus. Air was gently injected into the deep stroma until a big bubble was formed. The rates of DM separation and complications were compared between the 2 groups. Big-bubble formation was successful in 79.2% of the eyes in the study group. A bare DM was achieved by central injection in 68.0% of group 1 and by peripheral injection in 69.6% of group 2 (p = 0.68). This rate was increased to 80.0% and 78.3% in groups 1 and 2, respectively, after the injection site was shifted when injections failed. The study groups were comparable in terms of complications including DM perforation and bubble bursting. Both injection sites were equivalent in their rates of big-bubble formation and complications. Less experienced surgeons are advised to initially inject air outside the trephination.

Use of a "small-bubble technique" to increase the success of Anwar's "big-bubble technique" for deep lamellar keratoplasty with complete baring of Descemet's membrane.

PubMed

Parthasarathy, Anand; Por, Yong Ming; Tan, Donald T H

2007-10-01

To describe a quick and simple "small-bubble" technique to immediately determine the success of attaining complete Descemet's membrane (DM) separation from corneal stroma through Anwar's "big-bubble" technique of deep anterior lamellar keratoplasty (DALK) for complete stromal removal. A partial trephination was followed by a lamellar dissection of the anterior stroma. Deep stromal air injection was then attempted to achieve the big bubble to help separate the stroma from the DM. To confirm that a big bubble had been achieved, a small air bubble was injected into the anterior chamber (AC) through a limbal paracentesis. If the small bubble is then seen at the corneal periphery, it confirms that the big-bubble separation of DM was successful because the convex nature of the bubble will cause it to protrude posteriorly, forcing the small AC bubble to the periphery. If the small AC bubble is not seen in the corneal periphery, this means that it is present in the centre, beneath the opaque corneal stroma, and therefore the big bubble has not been achieved. We used the small-bubble technique to confirm the presence of the big bubble in three (one keratoconus, one interstitial keratitis and one dense corneal scar) out of 41 patients who underwent DALK. The small-bubble technique confirmed that the big bubble was achieved in the eye of all three patients. Complete stromal removal with baring of the DM was achieved, and postoperatively all three eyes achieved best corrected vision of 6/6. The small-bubble technique can be a useful surgical tool for corneal surgeons attempting lamellar keratoplasty using the big-bubble technique. It helps in confirming the separation of DM from the deep stroma, which is important in achieving total stromal replacement. It will help to make the transition to lamellar keratoplasty smoother, enhance corneal graft success and improve visual outcomes in patients.

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

Hyaluronan and hyaluronectin in the extracellular matrix of human brain tumour stroma.

PubMed

Delpech, B; Maingonnat, C; Girard, N; Chauzy, C; Maunoury, R; Olivier, A; Tayot, J; Creissard, P

1993-01-01

Hyaluronan (HA) and the hyaluronan-binding glycoprotein hyaluronectin (HN) were measured in 23 gliomas and 8 meningiomas and their location was revisited in 35 tumours. A clear-cut difference was found in the HN/HA ratio values of glioblastomas (below 0.5) and that of astrocytomas (above 0.5 P < 0.001). Besides their location in the intercellular part of gliomas, HA and HN displayed a perivascular location in 1/3 astrocytomas, 17/24 glioblastomas, and 3/7 meningiomas, suggesting they could be produced also by the vascular stroma of tumours and that they would characterise the neoangiogenesis. All cultivated glioma cells tested produced HA in vitro, whereas only 1/11 cell lines produced HN, at a low level. The results obtained suggest that glioma HA and HN are produced by both cancer cells and vascular stroma cells, which contribute to the edification of the extracellular matrix. In meningiomas only the stroma would be responsible for HA and HN production.

Large (9 mm) Deep Anterior Lamellar Keratoplasty with Clearance of a 6-mm Optical Zone Optimizes Outcomes of Keratoconus Surgery.

PubMed

Busin, Massimo; Leon, Pia; Nahum, Yoav; Scorcia, Vincenzo

2017-07-01

To evaluate the outcomes of a 9-mm deep anterior lamellar keratoplasty (DALK) with removal of the deep stroma limited to the central 6-mm optical zone. Prospective, noncomparative, interventional case series. A total of 80 consecutive keratoconic eyes without deep stromal scarring, with at least 1 postoperative examination 1 month after complete suture removal. A standardized DALK was performed, including (1) deep trephination of the recipient bed 450 to 550 μm in depth and 9 mm in diameter; (2) pneumatic dissection; (3) debulking of approximately 80% of the anterior stroma; (4) removal of the deep stroma (bubble roof) from a central 6-mm optical zone; and (5) transplantation of a 9-mm anterior corneal lamella cut by microkeratome-assisted dissection (400-μm head) and sutured with a double running 10-0 nylon suture. Success rate and type of pneumatic dissection obtained; best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), and topographic astigmatism (TA), central corneal thickness (CCT) and endothelial cell density 12 months postoperatively; and intraoperative and postoperative complications. Pneumatic dissection created a "big bubble" in 67 of 80 eyes (83.7%), all of them but 1 (1.5%) being of type 1 according to the classification by Dua et al. After complete suture removal, BSCVA averaged 0.09±0.72 logarithm of the minimum angle of resolution (logMAR) and was ≥20/20 in 28 eyes (35%), ≥20/25 in 54 eyes (67.5%), and ≥20/40 in 76 eyes (95%); RA averaged 3.10±1.30 diopters (D), with 73 eyes (91%) within 4.5 D and none above 6 D; regular TA was detected in 72 eyes (90%); mean CCT was 492±62.10 μm; postoperative endothelial cell density averaged 2026±397cells/mm 2 with a mean cell loss of 11.2%. Intraoperative complications included loss of suction (n = 1) and perforation (n = 4). No conversion to penetrating keratoplasty was necessary. After surgery, double anterior chamber was observed in 2 cases (2.5%), both managed

Changes in the Refractive Index of the Stroma and Its Extrafibrillar Matrix When the Cornea Swells

PubMed Central

Meek, Keith M.; Dennis, Sally; Khan, Shukria

2003-01-01

The transparency of the corneal stroma is critically dependent on the hydration of the tissue; if the cornea swells, light scattering increases. Although this scattering has been ascribed to the disruption caused to the arrangement of the collagen fibrils, theory predicts that light scattering could increase if there is an increased mismatch in the refractive indices of the collagen fibrils and the material between them. The purpose of this article is to use Gladstone and Dale's law of mixtures to calculate volume fractions for a number of different constituents in the stroma, and use these to show how the refractive indices of the stroma and its constituent extrafibrillar material would be expected to change as more solvent enters the tissue. Our calculations predict that solvent entering the extrafibrillar space causes a reduction in its refractive index, and hence a reduction in the overall refractive index of the bovine stroma according to the equation n′s = 1.335 + 0.04/(0.22 + 0.24 H′), where n′s is the refractive index and H′ is the hydration of the swollen stroma. This expression is in reasonable agreement with our experimental measurements of refractive index versus hydration in bovine corneas. When the hydration of the stroma increases from H = 3.2 to H = 8.0, we predict that the ratio of the refractive index of the collagen fibrils to that of the material between them increases from 1.041 to 1.052. This change would be expected to make only a small contribution to the large increase in light scattering observed when the cornea swells to H = 8. PMID:14507686

Structural alterations of the mucosa stroma in the Barrett's esophagus metaplasia-dysplasia-adenocarcinoma sequence.

PubMed

Bobryshev, Yuri V; Killingsworth, Murray C; Lord, Reginald V N

2012-09-01

Accumulating evidence suggests that the extracellular matrix play important roles in intercellular communications and contribute to the development of a number of diseases, including diseases of the gastrointestinal tract. The present study examined the structural characteristics and alterations of the extracellular matrix of the mucosa stroma in the Barrett's esophagus metaplasia-dysplasia-adenocarcinoma sequence. A total of 41 esophageal tissue specimens (15 esophageal adenocarcinoma, 10 Barrett's esophagus intestinal metaplasia, seven dysplasia and nine normal esophagus) were studied. The present study used transmission electron microscopy and computerized quantitative electron-microscopic analysis in order to investigate the characteristics of the extracellular matrix of the mucosa. The study revealed that marked structural alterations of the mucosa stroma, relating to changes in the distribution and appearance of collagen fibers as well as to changes in numbers of matrix microvesicles, occur in Barrett's esophagus and esophageal adenocarcinoma. It was found that there were 3.1 times more microvesicles in the stroma in Barrett's esophagus than in the stroma of the normal esophagus (P<0.0001) and that there were 5.8 times more microvesicles in esophageal adenocarcinoma than in the normal esophagus (P<0.0001). There were 1.9 times more microvesicles in esophageal adenocarcinoma than in Barrett's esophagus (P=0.0043). The study demonstrates distinctive alterations of the mucosa stroma extracellular matrix in the metaplasia-dysplasia-adenocarcinoma sequence. The findings suggest that the redistribution of collagen fibers and increases in numbers of matrix microvesicles may play roles in the formation of specialized intestinal metaplasia and the development of adenocarcinoma. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Assessing the temporal stability of spatial patterns of soil apparent electrical conductivity using geophysical methods

NASA Astrophysics Data System (ADS)

De Caires, Sunshine A.; Wuddivira, Mark N.; Bekele, Isaac

2014-10-01

Cocoa remains in the same field for decades, resulting in plantations dominated with aging trees growing on variable and depleted soils. We determined the spatio-temporal variability of key soil properties in a (5.81 ha) field from the International Cocoa Genebank, Trinidad using geophysical methods. Multi-year (2008-2009) measurements of apparent electrical conductivity at 0-0.75 m (shallow) and 0.75-1.5 m (deep) were conducted. Apparent electrical conductivity at deep and shallow gave the strongest linear correlation with clay-silt content (R = 0.67 and R = 0.78, respectively) and soil solution electrical conductivity (R = 0.76 and R = 0.60, respectively). Spearman rank correlation coefficients ranged between 0.89-0.97 and 0.81- 0.95 for apparent electrical conductivity at deep and shallow, respectively, signifying a strong linear dependence between measurement days. Thus, in the humid tropics, cocoa fields with thick organic litter layer and relatively dense understory cover, experience minimal fluctuations in transient properties of soil water and temperature at the topsoil resulting in similarly stable apparent electrical conductivity at shallow and deep. Therefore, apparent electrical conductivity at shallow, which covers the depth where cocoa feeder roots concentrate, can be used as a fertility indicator and to develop soil zones for efficient application of inputs and management of cocoa fields.

Inhibition of the hedgehog pathway targets the tumor-associated stroma in pancreatic cancer.

PubMed

Hwang, Rosa F; Moore, Todd T; Hattersley, Maureen Mertens; Scarpitti, Meghan; Yang, Bin; Devereaux, Erik; Ramachandran, Vijaya; Arumugam, Thiruvengadam; Ji, Baoan; Logsdon, Craig D; Brown, Jeffrey L; Godin, Robert

2012-09-01

The Hedgehog (Hh) pathway has emerged as an important pathway in multiple tumor types and is thought to be dependent on a paracrine signaling mechanism. The purpose of this study was to determine the role of pancreatic cancer-associated fibroblasts (human pancreatic stellate cells, HPSCs) in Hh signaling. In addition, we evaluated the efficacy of a novel Hh antagonist, AZD8542, on tumor progression with an emphasis on the role of the stroma compartment. Expression of Hh pathway members and activation of the Hh pathway were analyzed in both HPSCs and pancreatic cancer cells. We tested the effects of Smoothened (SMO) inhibition with AZD8542 on tumor growth in vivo using an orthotopic model of pancreatic cancer containing varying amounts of stroma. HPSCs expressed high levels of SMO receptor and low levels of Hh ligands, whereas cancer cells showed the converse expression pattern. HPSC proliferation was stimulated by Sonic Hedgehog with upregulation of downstream GLI1 mRNA. These effects were abrogated by AZD8542 treatment. In an orthotopic model of pancreatic cancer, AZD8542 inhibited tumor growth only when HPSCs were present, implicating a paracrine signaling mechanism dependent on stroma. Further evidence of paracrine signaling of the Hh pathway in prostate and colon cancer models is provided, demonstrating the broader applicability of our findings. Based on the use of our novel human-derived pancreatic cancer stellate cells, our results suggest that Hh-targeted therapies primarily affect the tumor-associated stroma, rather than the epithelial compartment.

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

Qualitative analysis of connective tissue stroma in different grades of oral squamous cell carcinoma: A histochemical study.

PubMed

Kullage, Smitha; Jose, Maji; Shanbhag, Vagish Kumar L; Abdulla, Riaz

2017-01-01

Detection of oral cancer at an early stage is of utmost importance to decrease morbidity and mortality. Tumor stroma plays a critical role during carcinogenesis. There is lack of information regarding the characteristics of the stroma in relation to the invading malignant epithelial cells and the interdependence between stroma and tumor cells in different grades of oral squamous cell carcinoma (OSCC). The present study was aimed to analyze and compare the nature of stroma in the vicinity of invading tumor islands in different grades of OSCC, using a histochemical technique picrosirius-polarization method. The present study also evaluated and correlated the possible role of inflammatory response in determining the nature of the stroma. The study included thirty cases of different grades of histologically diagnosed OSCC and ten sections of normal buccal mucosa as a control group. Nature of collagen was analyzed using picrosirius-polarization method, and intensity of inflammatory cell infiltrate was recorded using ImageJ software (1.42q, NIH, USA). The results were tabulated and analyzed statistically. Normal oral mucosa showed predominantly reddish birefringence. All cases of well-differentiated OSCC showed reddish-orange color. Nearly 70% moderately differentiated cases showed yellowish-orange (YO) and 60% of poorly differentiated cases, showed greenish-yellow (GY). The mean inflammatory cell count was highest in well-differentiated group. There was shift to YO and GY collagen when the cell differentiation and inflammatory cell count decreased in moderate and poorly differentiated cases. Both inflammatory cells and tumor cells have a role in determining the nature of the collagen fibers in tumor stroma of OSCC, probably with opposing effects on stromal behavior and hence both are significant in predicting prognosis.

Effects of the Loss of Conjunctival Muc16 on Corneal Epithelium and Stroma in Mice

PubMed Central

Shirai, Kumi; Okada, Yuka; Cheon, Dong-Joo; Miyajima, Masayasu; Behringer, Richard R.; Yamanaka, Osamu; Saika, Shizuya

2014-01-01

Purpose. To examine the role of conjunctival Muc16 in the homeostasis of the ocular surface epithelium and stroma using Muc16-null knockout (KO) mice. Methods. We used KO mice (n = 58) and C57/BL6 (WT) mice (n = 58). Histology and immunohistochemistry were employed to analyze the phenotypes in the ocular surface epithelium. The expression of phospho-Stat3, AP-1 components, interleukin 6 (IL-6), and tumor necrosis factor-α (TNFα) in the cornea and conjunctiva was examined. The shape of the nuclei of corneal epithelial cells was examined to evaluate intraepithelial cell differentiation. Epithelial cell proliferation was studied using bromo-deoxyuridine labeling. Finally, the wound healing of a round defect (2-mm diameter) in the corneal epithelium was measured. The keratocyte phenotype and macrophage invasion in the stroma were evaluated after epithelial repair. Results. The loss of Muc16 activated Stat3 signal, affected JunB signal, and upregulated the expression of IL-6 in the conjunctiva. Basal-like cells were observed in the suprabasal layer of the corneal epithelium with an increase in proliferation. The loss of Muc16 accelerated the wound healing of the corneal epithelium. The incidence of myofibroblast appearance and macrophage invasion were more marked in KO stroma than in WT stroma after epithelial repair. Conclusions. The loss of Muc16 in the conjunctiva affected the homeostasis of the corneal epithelium and stroma. The mechanism might include the upregulation of the inflammatory signaling cascade (i.e., Stat3 signal, and IL-6 expression in the KO conjunctiva). Current data provides insight into the research of the pathophysiology of dry eye syndrome. PMID:24812549

A tissue engineered human endometrial stroma that responds to cues for secretory differentiation, decidualization and menstruation

PubMed Central

Schutte, Stacey C.; Taylor, Robert N.

2012-01-01

Objective To show the responsiveness of a tissue engineered human endometrial stroma to combinations of hormones mimicking the secretory and menstrual phases of the cycle. Design In vitro experimental study Setting University uterine biology research laboratory Cells Telomerase immortalized human endometrial stromal cells Interventions The stromal cells were cultured in monolayers (2D) or encapsulated in a collagen I hydrogel (3D) to create a simplified tissue engineered stroma. The cells and tissues were exposed to hormone treatments mimicking early and late secretory phases, decidualization and steroid withdrawal conditions to recapitulate menstruation. Main Outcome Measure(s) Morphological and biochemical markers of decidualization and collagenase activity Result(s) The 3D tissue is capable of manifesting changes in morphology and biochemical markers of decidualization similar to 2D culture and characteristic of endometrial stroma in vivo. Unlike 2D culture, the 3D tissue responded to steroid withdrawal by increased collagenase activity and tissue breakdown. Conclusion(s) 3D tissue engineered endometrial stroma can mimic secretory and menstrual phases of the cycle and may be useful for studying uterine receptivity and menstruation in a physiological endocrine environment. PMID:22306710

Quantitative diffusion weighted imaging parameters in tumor and peritumoral stroma for prediction of molecular subtypes in breast cancer

NASA Astrophysics Data System (ADS)

He, Ting; Fan, Ming; Zhang, Peng; Li, Hui; Zhang, Juan; Shao, Guoliang; Li, Lihua

2018-03-01

Breast cancer can be classified into four molecular subtypes of Luminal A, Luminal B, HER2 and Basal-like, which have significant differences in treatment and survival outcomes. We in this study aim to predict immunohistochemistry (IHC) determined molecular subtypes of breast cancer using image features derived from tumor and peritumoral stroma region based on diffusion weighted imaging (DWI). A dataset of 126 breast cancer patients were collected who underwent preoperative breast MRI with a 3T scanner. The apparent diffusion coefficients (ADCs) were recorded from DWI, and breast image was segmented into regions comprising the tumor and the surrounding stromal. Statistical characteristics in various breast tumor and peritumoral regions were computed, including mean, minimum, maximum, variance, interquartile range, range, skewness, and kurtosis of ADC values. Additionally, the difference of features between each two regions were also calculated. The univariate logistic based classifier was performed for evaluating the performance of the individual features for discriminating subtypes. For multi-class classification, multivariate logistic regression model was trained and validated. The results showed that the tumor boundary and proximal peritumoral stroma region derived features have a higher performance in classification compared to that of the other regions. Furthermore, the prediction model using statistical features, difference features and all the features combined from these regions generated AUC values of 0.774, 0.796 and 0.811, respectively. The results in this study indicate that ADC feature in tumor and peritumoral stromal region would be valuable for estimating the molecular subtype in breast cancer.

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

CD34(+) fibrocytes in normal cervical stroma, cervical intraepithelial neoplasia III, and invasive squamous cell carcinoma of the cervix uteri.

PubMed

Barth, Peter J; Ramaswamy, Annette; Moll, Roland

2002-12-01

CD34(+) fibrocytes are widely distributed in normal connective tissues but have been reported to be absent within the stroma associated with invasive carcinomas. In the present study we investigated the presence and distribution of CD34(+) fibrocytes and alpha-smooth muscle actin (alpha-SMA) positive myofibroblasts in cervical intraepithelial neoplasia III (CIN III; n=8), invasive carcinoma of the cervix ( n=18) and adjacent normal cervical stroma. Normal cervical stroma and the stroma adjacent to CIN III disclosed a dense network of CD34(+) fibrocytes, whereas the stroma of invasive carcinoma was virtually free of this cell population. Early stromal invasion by squamous carcinoma was characterized by a focal loss of CD34(+) fibrocytes. alpha-SMA-positive myofibroblasts were not seen in the normal cervical stroma but occurred in six of eight cases of CIN III adjacent to the atypical epithelium. The stroma of invasive carcinoma was made up of large amounts of haphazardly arranged alpha-SMA-positive myofibroblasts. In the setting of the present study, a loss of CD34(+) fibrocytes was specific for stromal alterations associated with invasive carcinoma and proved to be a sensitive tool in detecting small foci of stromal invasion. Therefore, detection of a loss of CD34(+) fibrocytes may constitute an adjunctive tool in detecting (1) early stromal invasion and (2) invasive carcinoma in small biopsy specimens. Moreover, the present study shows that CD34(+) fibrocytes and myofibroblasts play an important role in stromal remodeling associated with invasive squamous cell carcinoma of the cervix.

Tumor stroma-containing 3D spheroid arrays: A tool to study nanoparticle penetration.

PubMed

Priwitaningrum, Dwi L; Blondé, Jean-Baptiste G; Sridhar, Adithya; van Baarlen, Joop; Hennink, Wim E; Storm, Gert; Le Gac, Séverine; Prakash, Jai

2016-12-28

Nanoparticle penetration through tumor tissue after extravasation is considered as a key issue for tumor distribution and therapeutic effects. Most tumors possess abundant stroma, a fibrotic tissue composed of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), which acts as a barrier for nanoparticle penetration. There is however a lack of suitable in vitro systems to study the tumor stroma penetration of nanoparticles. In the present study, we developed and thoroughly characterized a 3D co-culture spheroidal array to mimic tumor stroma and investigated the penetration of silica and PLGA nanoparticles in these spheroids. First, we examined human breast tumor patient biopsies to characterize the content and organization of stroma and found a high expression of alpha-smooth muscle actin (α-SMA; 40% positive area) and collagen-1 (50% positive area). Next, we prepared homospheroids of 4T1 mouse breast cancer cells or 3T3 mouse fibroblasts alone as well as heterospheroids combining 3T3 and 4T1 cells in different ratios (1:1 and 5:1) using a microwell array platform. Confocal live imaging revealed that fibroblasts distributed and reorganized within 48h in heterospheroids. Furthermore, immunohistochemical staining and gene expression analysis showed a proportional increase of α-SMA and collagen in heterospheroids with higher fibroblast ratios attaining 35% and 45% positive area at 5:1 (3T3:4T1) ratio, in a good match with the clinical breast tumor stroma. Subsequently, we studied the penetration of high and low negatively charged fluorescent silica nanoparticles (30nm; red and 100 or 70nm; green; zeta potential: -40mV and -20mV) and as well as Cy5-conjugated pegylated PLGA nanoparticles (200nm, -7mV) in both homo- and heterospheroid models. Fluorescent microscopy on spheroid cryosections after incubation with silica nanoparticles showed that 4T1 homospheroids allowed a high penetration of about 75-80% within 24h, with higher penetration in case of the

Role of Reactive Stroma in Prostate Cancer Progression

DTIC Science & Technology

2008-02-01

gel. Proteins were transferred onto nitrocellulose membrane (Bio-Rad Laboratories, Hercules, CA) and incubated in PBS buffer with 5% nonfat milk at...fusion protein, and incubated for 2 hours at room temperature. Secondary antibody was biotin-conjugated sheep anti-mouse IgG (Sigma), diluted at 1...stroma that forms at sites of wound repair, microbial invasion, or carcinoma as we have reported previously (1, 32, 35). Of these, CTGF is a known

Insulin/IGF-driven cancer cell-stroma crosstalk as a novel therapeutic target in pancreatic cancer.

PubMed

Mutgan, Ayse Ceren; Besikcioglu, H Erdinc; Wang, Shenghan; Friess, Helmut; Ceyhan, Güralp O; Demir, Ihsan Ekin

2018-02-23

Pancreatic ductal adenocarcinoma (PDAC) is unrivalled the deadliest gastrointestinal cancer in the western world. There is substantial evidence implying that insulin and insulin-like growth factor (IGF) signaling axis prompt PDAC into an advanced stage by enhancing tumor growth, metastasis and by driving therapy resistance. Numerous efforts have been made to block Insulin/IGF signaling pathway in cancer therapy. However, therapies that target the IGF1 receptor (IGF-1R) and IGF subtypes (IGF-1 and IGF-2) have been repeatedly unsuccessful. This failure may not only be due to the complexity and homology that is shared by Insulin and IGF receptors, but also due to the complex stroma-cancer interactions in the pancreas. Shedding light on the interactions between the endocrine/exocrine pancreas and the stroma in PDAC is likely to steer us toward the development of novel treatments. In this review, we highlight the stroma-derived IGF signaling and IGF-binding proteins as potential novel therapeutic targets in PDAC.

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

Role of Reactive Stroma in Prostate Cancer Progression

DTIC Science & Technology

2007-02-01

buffer with 5% nonfat milk at 4jC overnight. Mouse anti-V5 monoclonal antibody (Invitrogen), diluted at 1:5,000, was used as primary antibody to...detect the presence of CTGF-V5-His fusion protein, and incubated for 2 hours at room temperature. Secondary antibody was biotin-conjugated sheep anti-mouse...genes is associated with reactive stroma that forms at sites of wound repair, microbial invasion, or carcinoma as we have reported previously (1, 32, 35

Host-Derived Pericytes and Sca-1+ Cells Predominate in the MART-1− Stroma Fraction of Experimentally Induced Melanoma

PubMed Central

Treviño-Villarreal, J. Humberto; Cotanche, Douglas A.; Sepúlveda, Rosalinda; Bortoni, Magda E.; Manneberg, Otto; Udagawa, Taturo

2011-01-01

Identification of cell types in tumor-associated stroma that are involved in the development of melanoma is hampered by their heterogeneity. The authors used flow cytometry and immunohistochemistry to demonstrate that anti–MART-1 antibodies can discriminate between melanoma and stroma cells. They investigated the cellular composition of the MART-1−, non-hematopoietic melanoma-associated stroma, finding it consisted mainly of Sca-1+ and CD146+ cells. These cell types were also observed in the skin and muscle adjacent to developing melanomas. The Sca-1+ cell population was observed distributed in the epidermis, hair follicle bulges, and tumor capsule. The CD146+ population was found distributed within the tumor, mainly associated with blood vessels in a perivascular location. In addition to a perivascular distribution, CD146+ cells expressed α-smooth muscle actin, lacked expression of endothelial markers CD31 and CD34, and were therefore identified as pericytes. Pericytes were found to be associated with CD31+ endothelial cells; however, some pericytes were also observed associated with CD31−, MART-1+ B16 melanoma cells that appeared to form blood vessel structures. Furthermore, the authors observed extensive nuclear expression of HIF-1α in melanoma and stroma cells, suggesting hypoxia is an important factor associated with the melanoma microenvironment and vascularization. The results suggest that pericytes and Sca-1+ stroma cells are important contributors to melanoma development. PMID:22147606

New insights on stromules: stroma filled tubules extended by independent plastids.

PubMed

Schattat, Martin H; Klösgen, Ralf Bernd; Mathur, Jaideep

2012-09-01

The recognition of stromules as sporadically extended stroma filled tubules from all kinds of plastids constitutes one of the major insights that resulted from the direct application of green fluorescent protein aided imaging of living plant cells. Observations of dynamic green fluorescent stromules strongly suggested that plastids frequently interact with each other while photo-bleaching of interconnected plastids indicated that proteins can move within the stroma filled tubules. These observations readily fit into the prevailing concept of the endosymbiogenic origins of plastids and provided stromules the status of conduits for inter-plastid communication and macromolecule transfer. However, experimental evidence obtained recently through the use of photoconvertible protein labeled stromules strongly supports plastid independence rather than their interconnectivity. Additional information on stress conditions inducing stromules and observations on their alignment with other organelles suggests that the major role of stromules is to increase the interactive surface of a plastid with the rest of the cytoplasm.

Thymocyte emigration is mediated by active movement away from stroma-derived factors

PubMed Central

Poznansky, Mark C.; Olszak, Ivona T.; Evans, Richard H.; Wang, Zhengyu; Foxall, Russell B.; Olson, Douglas P.; Weibrecht, Kathryn; Luster, Andrew D.; Scadden, David T.

2002-01-01

T cells leave the thymus at a specific time during differentiation and do not return despite elaboration of known T cell chemoattractants by thymic stroma. We observed differentiation stage–restricted egress of thymocytes from an artificial thymus in which vascular structures or hemodynamics could not have been playing a role. Hypothesizing that active movement of cells away from a thymic product may be responsible, we demonstrated selective reduction in emigration from primary thymus by inhibitors of active movement down a concentration gradient (chemofugetaxis). Immature intrathymic precursors were insensitive to an emigration signal, whereas mature thymocytes and peripheral blood T cells were sensitive. Thymic stroma was noted to elaborate at least two proteins capable of inducing emigration, one of which was stromal cell–derived factor-1. Thymic emigration is mediated, at least in part, by specific fugetaxis-inducing factors to which only mature cells respond. PMID:11956248

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

Six stroma-based RNA markers diagnostic for prostate cancer in European-Americans validated at the RNA and protein levels in patients in China

PubMed Central

Zhu, Jianguo; Pan, Cong; Jiang, Jun; Deng, Mingsen; Gao, Hengjun; Men, Bozhao; McClelland, Michael; Mercola, Dan; Zhong, Wei-De; Jia, Zhenyu

2015-01-01

We previously analyzed human prostate tissue containing stroma near to tumor and from cancer-negative tissues of volunteers. Over 100 candidate gene expression differences were identified and used to develop a classifier that could detect nearby tumor with an accuracy of 97% (sensitivity = 98% and specificity = 88%) based on 364 independent test cases from primarily European American cases. These stroma-based gene signatures have the potential to identify cancer patients among those with negative biopsies. In this study, we used prostate tissues from Chinese cases to validate six of these markers (CAV1, COL4A2, HSPB1, ITGB3, MAP1A and MCAM). In validation by real-time PCR, four genes (COL4A2, HSPB1, ITGB3, and MAP1A) demonstrated significantly lower expression in tumor-adjacent stroma compared to normal stroma (p value ≤ 0.05). Next, we tested whether these expression differences could be extended to the protein level. In IHC assays, all six selected proteins showed lower expression in tumor-adjacent stroma compared to the normal stroma, of which COL4A2, HSPB1 and ITGB3 showed significant differences (p value ≤ 0.05). These results suggest that biomarkers for diagnosing prostate cancer based on tumor microenvironment may be applicable across multiple racial groups. PMID:26158290

MiR-21 Expression in the Tumor Stroma of Oral Squamous Cell Carcinoma: An Independent Biomarker of Disease Free Survival

PubMed Central

Specht, Lena; Fiehn, Anne-Marie K.; Therkildsen, Marianne H.; Friis-Hansen, Lennart; Dabelsteen, Erik; von Buchwald, Christian

2014-01-01

Oral squamous cell carcinoma (OSCC) patients have a high mortality rate; thus, new clinical biomarkers and therapeutic options are needed. MicroRNAs (miRNAs) are short noncoding RNAs that regulate posttranscriptional gene expression and are commonly deregulated in OSCC and other cancers. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in several types of cancer, and it might be a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in OSCC, paraffin-embedded tumor tissue samples from 86 patients with primary OSCC were analyzed by in situ hybridization. We found that miR-21 was primarily expressed in the tumor stroma and in some tumor-associated blood vessels with no expression in the adjacent normal epithelia or stroma. Using image analysis, we quantitatively estimated miR-21 expression levels specifically in the stroma of a cohort of OSCC samples. These miR-21 levels significantly correlated with disease free survival with the highest levels being located in the stroma. Stromal miR-21 expression was independently associated with a poorer prognosis, even after adjusting for clinical parameters (perineural invasion and N-stage) in a multivariate analysis. In summary, we have shown that miR-21 is located in the carcinoma cells, stroma and blood vessels of tumors, and its expression specifically in the stromal compartment has a negative prognostic value in OSCC. PMID:24755828

Association between tumor-stroma ratio and prognosis in solid tumor patients: a systematic review and meta-analysis.

PubMed

Wu, Jiayuan; Liang, Caixia; Chen, Manyu; Su, Wenmei

2016-10-18

Tumor-related stroma plays an active role in tumor invasion and metastasis. The tumor-stroma ratio (TSR) in the pathologic specimen has drawn increasing attention from the field of predicting tumor prognosis. However, the prognostic value of TSR in solid tumors necessitates further elucidation. We conducted a meta-analysis on 14 studies with 4238 patients through a comprehensive electronic search on databases updated on May 2016 to explore the relationship between TSR and prognosis of solid tumors. The overall hazard ratio showed that rich stroma in tumor tissue was associated with poor overall survival (OS) (14 studies, 4238 patients) and disease-free survival (DFS) (9 studies, 2235 patients) of patients with solid tumors. The effect of low TSR on poor OS was observed among various cancer types, but not in the early stage of cervical caner. A significant relationship between low TSR and poor OS was also observed in the subgroup analyses based on study region, blinding status, and Newcastle-Ottawa Scale (NOS) score. Subgroup analyses indicated that cancer type, clinical stage, study region, blinding status, and NOS score did not affect the prognostic value of TSR for DFS. Moreover, low TSR was significantly correlated with the serious clinical stage, advanced depth of invasion, and positive lymph node metastasis. These findings indicate that a high proportion of stroma in cancer tissue is associated with poor clinical outcomes in cancer patients, and TSR may serve as an independent prognostic factor for solid tumors.

Prognostic value of tumor-stroma ratio combined with the immune status of tumors in invasive breast carcinoma.

PubMed

Vangangelt, K M H; van Pelt, G W; Engels, C C; Putter, H; Liefers, G J; Smit, V T H B M; Tollenaar, R A E M; Kuppen, P J K; Mesker, W E

2018-04-01

Complex interactions occur between cancer cells and cells in the tumor microenvironment. In this study, the prognostic value of the interplay between tumor-stroma ratio (TSR) and the immune status of tumors in breast cancer patients was evaluated. A cohort of 574 breast cancer patients was analyzed. The percentage of tumor stroma was visually estimated on Hematoxylin and Eosin (H&E) stained histological tumor tissue sections. Immunohistochemical staining was performed for classical human leukocyte antigen (HLA) class I, HLA-E, HLA-G, markers for regulatory T (Treg) cells, natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs). TSR (P < .001) and immune status of tumors (P < .001) were both statistically significant for recurrence free period (RFP) and both independent prognosticators (P < .001) in which tumors with a high stromal content behave more aggressively as well as tumors with a low immune status. Ten years RFP for patients with a stroma-low tumor and high immune status profile was 87% compared to 17% of patients with a stroma-high tumor combined with low immune status profile (P < .001). Classical HLA class I is the most prominent immune marker in the immune status profiles. Determination of TSR is a simple, fast and cheap method. The effect on RFP of TSR when combined with immune status of tumors or expression of classical HLA class I is even stronger. Both are promising for further prediction and achievement of tailored treatment for breast cancer patients.

c-Jun N-terminal kinase in pancreatic tumor stroma augments tumor development in mice.

PubMed

Sato, Takeshi; Shibata, Wataru; Hikiba, Yohko; Kaneta, Yoshihiro; Suzuki, Nobumi; Ihara, Sozaburo; Ishii, Yasuaki; Sue, Soichiro; Kameta, Eri; Sugimori, Makoto; Yamada, Hiroaki; Kaneko, Hiroaki; Sasaki, Tomohiko; Ishii, Tomohiro; Tamura, Toshihide; Kondo, Masaaki; Maeda, Shin

2017-11-01

Pancreatic ductal adenocarcinoma (PDAC) is a life-threatening disease and there is an urgent need to develop improved therapeutic approaches. The role of c-Jun N-terminal kinase (JNK) in PDAC stroma is not well defined even though dense desmoplastic reactions are characteristic of PDAC histology. We aimed to explore the role of JNK in PDAC stroma in mice. We crossed Ptf1a Cre/+ ;Kras G12D/+ mice with JNK1 -/- mice to generate Ptf1a Cre/+ ;Kras G12D/+ ;JNK1 -/- (Kras;JNK1 -/- ) mice. Tumor weight was significantly lower in Kras;JNK1 -/- mice than in Kras;JNK1 +/- mice, whereas histopathological features were similar. We also transplanted a murine PDAC cell line (mPC) with intact JNK1 s.c. into WT and JNK1 -/- mice. Tumor diameters were significantly smaller in JNK1 -/- mice. Phosphorylated JNK (p-JNK) was activated in α-smooth muscle actin (SMA)-positive cells in tumor stroma, and mPC-conditioned medium activated p-JNK in tumor-associated fibroblasts (TAF) in vitro. Relative expression of Ccl20 was downregulated in stimulated TAF. Ccl20 is an important chemokine that promotes CD8 + T-cell infiltration by recruitment of dendritic cells, and the number of CD8 + T cells was decreased in Kras;JNK1 +/- mice compared with Kras;JNK1 -/- mice. These results suggest that the cancer secretome decreases Ccl20 secretion from TAF by activation of JNK, and downregulation of Ccl20 secretion might be correlated with reduction of infiltrating CD8 + T cells. Therefore, we concluded that inhibition of activated JNK in pancreatic tumor stroma could be a potential therapeutic target to increase Ccl20 secretion from TAF and induce accumulation of CD8 + T cells, which would be expected to enhance antitumor immunity. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Stars and stripes in pancreatic cancer: role of stellate cells and stroma in cancer progression

PubMed Central

Wilson, Jeremy S.; Pirola, Romano C.; Apte, Minoti V.

2014-01-01

Pancreatic cancer is a devastating disease with an unacceptably high mortality to incidence ratio. Traditional therapeutic approaches such as surgery in combination with chemo- or radiotherapy have had limited efficacy in improving the outcome of this disease. Up until just under a decade ago, the prominent desmoplastic reaction which is a characteristic of the majority of pancreatic ductal adenocarcinomas (PDAC) had been largely ignored. However, since the identification of the pancreatic stellate cell (PSC) as the key cell responsible for the production of the collagenous stroma in PDAC, increasing attention has been paid to the role of the stromal reaction in pancreatic cancer pathobiology. There is now compelling evidence that PSCs interact not only with cancer cells themselves, but with several other cell types in the stroma (endothelial cells, immune cells, and possibly neuronal cells) to promote cancer progression. This review summarizes current knowledge in the field about the influence of PSCs and the stromal microenvironment on cancer behavior and discusses novel therapeutic approaches which reflect an increasing awareness amongst clinicians and researchers that targeting cancer cells alone is no longer sufficient to improve patient outcome and that combinatorial treatments targeting the stroma as well as the cancer cells will be required to change the clinical course of this disease. PMID:24592240

Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

PubMed Central

Rafii, Shahin; Jaspers, Janneke E.; White, Ian A.; Hooper, Andrea T.; Doevendans, Pieter A.; Verhaar, Marianne C.

2013-01-01

Background Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired –at least partly– due to dysfunction of the bone marrow stromal compartment. Methods Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1+Flk-1+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34+ hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell–endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. Results In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. Conclusion EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients. PMID:23555959

Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

PubMed

Westerweel, Peter E; Teraa, Martin; Rafii, Shahin; Jaspers, Janneke E; White, Ian A; Hooper, Andrea T; Doevendans, Pieter A; Verhaar, Marianne C

2013-01-01

Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+) hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

[Maturation of Cordyceps sinensis associates with alterations of fungal expressions of multiple Ophiocordyceps sinensis mutants in stroma of Cordyceps sinensis].

PubMed

Gao, Ling; Li, Xiao-hong; Zhao, Jian-qing; Lu, Ji-hong; Zhao, Jia-gang; Zhu, Jia-shi

2012-06-18

To examine maturational changes in expressions of Ophiocordyceps sinensis (O.sinensis) transition and transversion mutation genotypes in Cordyceps sinensis (C.sinensis) stroma. MassARRAY single nucleotide polymorphism (SNP) matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrum genotyping was used, and 8 SNP extension primers were designed based on the scattered, multiple point mutations of known sequences for the O.sinensis mutants within their internal transcribed spacer (ITS) segments. Of the extension primers, 5 (not capable of distinguishing between the 2 AT-biased genotypes) located in rDNA ITS1 and ITS2 regions: 067721-211, 067721-240, 067721-477, 067721-531 and 067721-581. The other 3 extension primers located in 5.8S rDNA region: 067740-324, 067740-328 and 067740-360, to distinguish between the 2 AT-biased genotypes. MS chromatograms at the 8 SNP sites showed dynamic alterations of mutant alleles in C.sinensis stroma. The allele for the AT-biased genotypes at 067721-211 site showed higher peak height than its GC-biased counterpart in the premature C.sinensis stroma, but disappeared with C.sinensis maturation. Chromatograms displayed not only the transition mutation alleles, but also transversion mutants. Some of the transversion mutation alleles displayed higher peak heights than those for GC- and AT-biased alleles, but their peak heights and detection rates tended to be decreased with C.sinensis maturation. When distinguishing between the 2 AT-biases, AB067744 and AB067740 genotype alleles co-existed in the premature C.sinensis stroma. The allele peak height for AB067744 genotype was greatly decreased with C.sinensis maturation, while that for AB067740 genotype increased. Co-existence of at least 5 transition and transversion mutant genotypes of O.sinensis and the dynamic changes in their expressions in C.sinensis stroma along with C.sinensis maturation may be of extreme importance in C.sinensis stroma germination and

Primary Xenografts of Human Prostate Tissue as a Model to Study Angiogenesis Induced by Reactive Stroma

PubMed Central

Montecinos, Viviana P.; Godoy, Alejandro; Hinklin, Jennifer; Vethanayagam, R. Robert; Smith, Gary J.

2012-01-01

Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6–14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6–10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts. PMID:22303438

S100A8+ stroma cells predict a good prognosis and inhibit aggressiveness in colorectal carcinoma.

PubMed

Li, Si; Xu, Fangying; Li, Hui; Zhang, Jing; Zhong, Anjing; Huang, Bin; Lai, Maode

2017-01-01

Gene microarray and bioinformatic analysis showed that S100A8 was more abundant in the stroma surrounding tumor buddings (TBs) than in the stroma surrounding primary tumor cells in colorectal carcinomas. Here, S100A8 + cells in 419 colorectal carcinoma samples were stained by immunohistochemistry and counted using Image-pro plus 6.0. TBs were also counted and biomarkers associated with the epithelial-mesenchymal transition and apoptosis were assessed by immunohistochemistry. We evaluated the association between S100A8 + cells and clinico-pathological variables as well as survival. Migration and invasion as well as biomarkers of the epithelial-mesenchymal transition and apoptosis were tested in CRC cells, treated with graded concentrations of recombinant human S100A8 protein. We found that the density of S100A8 + cells in the tumor invasive front (S100A8 + TIF ) clearly distinguished patients with 5-y survival from those who did not survive ( p = 0.01). The S100A8 + -associated tumor budding (SATB) index determined by the S100A8 + TIF and TB was an independent predictor of overall survival ( p = 0.001) other than the S100A8 + TIF or TB alone. Migration and invasion properties of CRC cells were inhibited by recombinant human S100A8 treatment. The particular S100A8 + cells in the stroma were associated with important biomarkers of the epithelial-mesenchymal transition (E-cadherin and SNAIL) and apoptosis (BCL2). In conclusion, S100A8 + cells in the stroma predict a good prognosis in colorectal carcinoma. An index combining S100A8 + cells and TB independently predicts survival. Recombinant human S100A8 inhibited CRC cell migration and invasion, which was involved in epithelial-mesenchymal transition (E-cadherin and SNAIL) and apoptosis (BCL2).

S100A8+ stroma cells predict a good prognosis and inhibit aggressiveness in colorectal carcinoma

PubMed Central

Li, Si; Xu, Fangying; Li, Hui; Zhang, Jing; Zhong, Anjing; Huang, Bin; Lai, Maode

2017-01-01

ABSTRACT Gene microarray and bioinformatic analysis showed that S100A8 was more abundant in the stroma surrounding tumor buddings (TBs) than in the stroma surrounding primary tumor cells in colorectal carcinomas. Here, S100A8+ cells in 419 colorectal carcinoma samples were stained by immunohistochemistry and counted using Image-pro plus 6.0. TBs were also counted and biomarkers associated with the epithelial–mesenchymal transition and apoptosis were assessed by immunohistochemistry. We evaluated the association between S100A8+ cells and clinico-pathological variables as well as survival. Migration and invasion as well as biomarkers of the epithelial–mesenchymal transition and apoptosis were tested in CRC cells, treated with graded concentrations of recombinant human S100A8 protein. We found that the density of S100A8+ cells in the tumor invasive front (S100A8+TIF) clearly distinguished patients with 5-y survival from those who did not survive (p = 0.01). The S100A8+-associated tumor budding (SATB) index determined by the S100A8+TIF and TB was an independent predictor of overall survival (p = 0.001) other than the S100A8+TIF or TB alone. Migration and invasion properties of CRC cells were inhibited by recombinant human S100A8 treatment. The particular S100A8+ cells in the stroma were associated with important biomarkers of the epithelial–mesenchymal transition (E-cadherin and SNAIL) and apoptosis (BCL2). In conclusion, S100A8+ cells in the stroma predict a good prognosis in colorectal carcinoma. An index combining S100A8+ cells and TB independently predicts survival. Recombinant human S100A8 inhibited CRC cell migration and invasion, which was involved in epithelial–mesenchymal transition (E-cadherin and SNAIL) and apoptosis (BCL2). PMID:28197382

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

PubMed

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

2016-11-04

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.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Altered proteomic polymorphisms in the caterpillar body and stroma of natural Cordyceps sinensis during maturation.

PubMed

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

2014-01-01

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. 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). 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. 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 during maturation. In conjunction with

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

Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis

PubMed Central

Bohonyi, Noémi; Pohóczky, Krisztina; Szalontai, Bálint; Perkecz, Anikó; Kovács, Krisztina; Kajtár, Béla; Orbán, Lajos; Varga, Tamás; Szegedi, Sarolta; Bódis, József; Koppán, Miklós

2017-01-01

Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential Ankyrin 1 (TRPA1) expressed mainly by primary sensory neurons function as major nociceptive integrators. They are also present on the rat endometrium in an oestrogen-regulated manner. TRPV1 is upregulated in peritoneal and ovarian endometriosis patients, but there is no information about TRPA1 and their pathophysiological significances. In this study, patients undergoing laparoscopic surgery were investigated: severe dysmenorrhoea due to rectosigmoid deep infiltrating endometriosis (n = 15), uterine fibroid-induced moderate dysmenorrhoea (n = 7) and tubal infertility with no pain (n = 6). TRPA1 and TRPV1 mRNA and protein expressions were determined by quantitative polymerase chain reaction and semi-quantitative immunohistochemistry from the endometrium samples taken by curettage. Results were correlated with the clinical characteristics including pain intensity. TRPA1 and TRPV1 receptors were expressed in the healthy human endometrium at mRNA and protein levels. Sparse, scattered cytoplasmic TRPA1 and TRPV1 immunopositivities were found in the stroma and epithelial layers. We detected upregulated mRNA levels in deep infiltrating endometriosis lesions, and TRPV1 gene expression was also elevated in autocontrol endometrium of deep infiltrating endometriosis patients. Histological scoring revealed significant TRPA1 and TRPV1 difference between deep infiltrating endometriosis stroma and epithelium, and in deep infiltrating endometriosis epithelium compared to control samples. Besides, we measured elevated stromal TRPV1 immunopositivity in deep infiltrating endometriosis. Stromal TRPA1 and TRPV1 immunoreactivities strongly correlated with dysmenorrhoea severity, as well TRPV1 expression on ectopic epithelial cells and macrophages with dyspareunia. Epithelial TRPA1 and stromal TRPV1 immunopositivity also positively correlated with dyschezia severity. We provide the first

Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis.

PubMed

Bohonyi, Noémi; Pohóczky, Krisztina; Szalontai, Bálint; Perkecz, Anikó; Kovács, Krisztina; Kajtár, Béla; Orbán, Lajos; Varga, Tamás; Szegedi, Sarolta; Bódis, József; Helyes, Zsuzsanna; Koppán, Miklós

2017-01-01

Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential Ankyrin 1 (TRPA1) expressed mainly by primary sensory neurons function as major nociceptive integrators. They are also present on the rat endometrium in an oestrogen-regulated manner. TRPV1 is upregulated in peritoneal and ovarian endometriosis patients, but there is no information about TRPA1 and their pathophysiological significances. In this study, patients undergoing laparoscopic surgery were investigated: severe dysmenorrhoea due to rectosigmoid deep infiltrating endometriosis ( n = 15), uterine fibroid-induced moderate dysmenorrhoea ( n = 7) and tubal infertility with no pain ( n = 6). TRPA1 and TRPV1 mRNA and protein expressions were determined by quantitative polymerase chain reaction and semi-quantitative immunohistochemistry from the endometrium samples taken by curettage. Results were correlated with the clinical characteristics including pain intensity. TRPA1 and TRPV1 receptors were expressed in the healthy human endometrium at mRNA and protein levels. Sparse, scattered cytoplasmic TRPA1 and TRPV1 immunopositivities were found in the stroma and epithelial layers. We detected upregulated mRNA levels in deep infiltrating endometriosis lesions, and TRPV1 gene expression was also elevated in autocontrol endometrium of deep infiltrating endometriosis patients. Histological scoring revealed significant TRPA1 and TRPV1 difference between deep infiltrating endometriosis stroma and epithelium, and in deep infiltrating endometriosis epithelium compared to control samples. Besides, we measured elevated stromal TRPV1 immunopositivity in deep infiltrating endometriosis. Stromal TRPA1 and TRPV1 immunoreactivities strongly correlated with dysmenorrhoea severity, as well TRPV1 expression on ectopic epithelial cells and macrophages with dyspareunia. Epithelial TRPA1 and stromal TRPV1 immunopositivity also positively correlated with dyschezia severity. We provide the first

Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target.

PubMed

Farace, Paolo; D'Ambrosio, Daniela; Merigo, Flavia; Galiè, Mirco; Nanni, Cristina; Spinelli, Antonello; Fanti, Stefano; Degrassi, Anna; Sbarbati, Andrea; Rubello, Domenico; Marzola, Pasquina

2009-04-01

To analyse the influence of cancer-associated stroma on FDG-uptake in two carcinoma models characterized by different stromal degrees. Eight nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC-3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after implantation. After the mice were killed, histology, and CD31 and GLUT1 immunohistochemistry were performed. To further evaluate the highly stromalized carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two successive albumin-binding (MS-325) MRI scans during tumour growth. FDG uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours, histology confirmed the widespread presence of aberrant infiltrated stroma, embedded with numerous vessels marked by CD31. In both tumour types, the stromal matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was greater than in BXPC-3 tumour cells, but not homogeneously, since it was less evident in the tumour cells which were nearer to vessels and stroma. Finally, MS-325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours. Cancer-associated stroma has been reported to be capable of aerobic metabolism with low glucose consumption. Furthermore, it has been proposed that regions with high vascular perfusion exhibit a significantly lower FDG uptake, suggesting some vascular/metabolic reciprocity. Since our results are consistent with these recent findings, they signal a risk of tumour volume underestimation in radiotherapy if FDG uptake alone is used for target delineation of carcinomas, which suggests that additional evaluation should be performed using vasculature/perfusion-sensitive imaging.

IL-33 activates tumor stroma to promote intestinal polyposis.

PubMed

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

2015-05-12

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 Apc(Min/+) 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 Apc(Min/+) 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 Apc(Min/+) 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.

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.

Expression between African American and Caucasian Prostate Cancer Tissue Reveals that Stroma is the Site of Aggressive Changes

PubMed Central

Kinseth, Matthew A.; Jia, Zhenyu; Rahmatpanah, Farahnaz; Sawyers, Anne; Sutton, Manuel; Wang-Rodriguez, Jessica; Mercola, Dan; McGuire, Kathleen L.

2013-01-01

In prostate cancer, race/ethnicity is the highest risk factor after adjusting for age. African Americans have more aggressive tumors at every clinical stage of the disease, resulting in poorer prognosis and increased mortality. A major barrier to identifying crucial gene activity differences is heterogeneity, including tissue composition variation intrinsic to the histology of prostate cancer. We hypothesized differences in gene expression in specific tissue types would reveal mechanisms involved in the racial disparities of prostate cancer. We examined seventeen pairs of arrays for African Americans and Caucasians that were formed by closely matching the samples based on the known tissue type composition of the tumors. Using pair wise T-test we found significantly altered gene expression between African Americans and Caucasians. Independently, we performed multiple linear regression analyses to associate gene expression with race considering variation in percent tumor and stroma tissue. The majority of differentially expressed genes were associated with tumor-adjacent stroma rather than tumor tissue. Extracellular matrix, Integrin family and signaling mediators of the epithelial-to-mesenchymal transition pathways were all down regulated in stroma of African Americans. Using MetaCore (GeneGo Inc.) analysis, we observed that 35% of significant (p < 10-3) pathways identified EMT and 25% identified immune response pathways especially for Interleukins -2, -4, -5, -6, -7, -10, -13, -15 and -22 as the major changes. Our studies reveal that altered immune and EMT processes in tumor-adjacent stroma may be responsible for the aggressive nature of prostate cancer in African Americans. PMID:23754304

Columnar cell lesions and pseudoangiomatous hyperplasia like stroma: is there an epithelial-stromal interaction?

PubMed

Recavarren, Rosemary A; Chivukula, Mamatha; Carter, Gloria; Dabbs, David J

2009-10-10

The significance of association between cancer and its microenvironment has been increasingly recognized. It has been shown in animal models that interaction between neoplastic epithelial cells and adjacent stroma can modulate tumor behavior. Carcinoma associated stromal cells can transform normal epithelial cells into neoplastic cells. In breast, columnar cell lesions are non-obligate precursors of low grade ductal carcinoma in situ. Columnar cell lesions can be seen intimately associated with PASH-like-stroma, a lesion we termed as CCPLS. Our aim is to investigate epithelial-stromal interactions in CCPLS and compare them to PASH without columnar cell lesions in breast core needle biopsies. Normal terminal duct lobular unit (TDLU) epithelium was seen in association with columnar cell lesions as well as PASH. Eight (8) cases of each category were examined by a panel of immunostains: CD117 (C-kit), CD34, CD105, bFGF, AR, ER-beta, MIB-1. We observed a markedly decreased expression of c-kit in columnar cell lesions compared to TDLU-epithelium. CD105 showed a quantitative increase in activated vessels in CCPLS compared to PASH. A subset of CCPLS and PASH were androgen receptor positive. A strong nuclear positivity for ER-beta is observed in the epithelium and stroma of all CCPLS cases. We conclude that (1) activated blood vessels predominate in CCPLS; (2) A molecular alteration is signified by c-kit loss in columnar cell lesions; (3) ER-beta and androgen receptor positivity indicate CCPLS are hormonally responsive lesions. Our study suggests an intimate vascular and hormone dependent epithelial-stromal interaction exists in CCPLS lesions.

Ultrasound in polycystic ovary syndrome--the measuring of ovarian stroma and relationship with circulating androgens: results of a multicentric study.

PubMed

Fulghesu, A M; Angioni, S; Frau, E; Belosi, C; Apa, R; Mioni, R; Xamin, N; Capobianco, G P; Dessole, S; Fruzzetti, F; Lazzarini, V; Minerba, L; Melis, G B; Lanzone, A

2007-09-01

The introduction of transvaginal approach in ultrasound (US) has enabled the accurate evaluation of the structure of the ovary and stroma. Stroma represents an acknowledged US marker for polycystic ovary syndrome (PCOS). The proportion revealed between the stroma and the ovary surface in the median section (S/A ratio) had been indicated as a reliable marker for hyperandrogenism. In order to verify the feasibility of this determination in routine use and to confirm the efficacy of S/A ratio in predicting hyperandrogenism in PCOS, a multicentric study was performed in association with five Italian research groups. A total of 418 subjects of fertile age presenting oligomenorrhoea or secondary amenorrhoea, enlarged ovaries measuring >10 cm(3) and/or >12 follicles measuring 2-9 mm in diameter took part in the study. Clinical, US and hormonal evaluations were performed in the early follicular phase or on random days in amenorrhoeic subjects. US assessment included ovarian volume, follicle number, ovarian and stroma area in median section. The hormonal study included a baseline plasma determination of LH, FSH, estradiol (E(2)), androstenedione (A), testosterone (T), dehydroepiandrosteronesulphate, 17-hydroxy-progesterone, sex hormone-binding globulin and prolactin. Correlations and receiver operator curves were used in statistical analysis of data. S/A was found to be the best significant predictor of elevated A and T levels. In order to ascertain significant cut-off values in relation to A and T levels Youden indexes were calculated and indicated 0.32 as the best cut-off for the S/A ratio. This work underlines the importance of stroma measure in improving US diagnosis of PCOS and suggest that this parameter may be used in routine clinical practice. In fact, multicentre study demonstrated the easy feasibility of such procedure without need of sophisticated machines or intensive training for operators.

Cancer and Stroma-Targeted Immunotherapy with a Genetically Modified DC Vaccine

DTIC Science & Technology

2013-05-01

of Medicine One Baylor Plaza Houston, TX 77030 REPORT DATE: May 2013 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical...information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE May ...2013 2. REPORT TYPE Final report 3. DATES COVERED 01 May 2010 - 30 April 2013 4. TITLE AND SUBTITLE Cancer and Stroma-Targeted Immunotherapy

Retinoic acid signaling determines the fate of uterine stroma in the mouse Müllerian duct

PubMed Central

Nakajima, Tadaaki; Iguchi, Taisen; Sato, Tomomi

2016-01-01

The Müllerian duct develops into the oviduct, uterus, and vagina, all of which are quite distinct in their morphology and function. The epithelial fate of these female reproductive organs in developing mice is determined by factors secreted from the stroma; however, how stromal differentiation occurs in the female reproductive organs derived from the Müllerian duct is still unclear. In the present study, roles of retinoic acid (RA) signaling in developing female reproductive tracts were investigated. Retinol dehydrogenase 10 (RDH10) and aldehyde dehydrogenase family 1 subfamily A2 (ALDH1A2) mRNAs and proteins and transactivation activity of endogenous RA were found in the stroma of proximal Müllerian ducts and gradually decreased from the proximal to caudal regions in fetal mice. In organ-cultured Müllerian ducts, retinaldehyde or RA treatment induced uterine epithelial differentiation, defined as a layer of columnar epithelial cells negative for oviductal and vaginal epithelial markers. In contrast, inhibition of RA receptor (RAR) signaling induced vaginal epithelial differentiation, characterized as vaginal epithelial marker genes–positive stratified epithelium. Grafting experiments of the organ-cultured Müllerian duct revealed irreversible epithelial fate determination. Although RAR did not directly bind to the homeobox A10 (Hoxa10) promoter region, RA–RAR signaling stimulated Hoxa10 expression. Thus, RA–RAR signaling in the Müllerian duct determines the fate of stroma to form the future uterus and vagina. PMID:27911779

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

CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans

PubMed Central

Beatty, Gregory L.; Chiorean, Elena G.; Fishman, Matthew P.; Saboury, Babak; Teitelbaum, Ursina R.; Sun, Weijing; Huhn, Richard D.; Song, Wenru; Li, Dongguang; Sharp, Leslie L.; Torigian, Drew A.; O’Dwyer, Peter J.; Vonderheide, Robert H.

2012-01-01

Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer. PMID:21436454

3D is not enough: Building up a cell instructive microenvironment for tumoral stroma microtissues.

PubMed

Brancato, Virginia; Garziano, Alessandro; Gioiella, Filomena; Urciuolo, Francesco; Imparato, Giorgia; Panzetta, Valeria; Fusco, Sabato; Netti, Paolo A

2017-01-01

We fabricated three-dimensional microtissues with the aim to replicate in vitro the composition and the functionalities of the tumor microenvironment. By arranging either normal fibroblasts (NF) or cancer-activated fibroblasts (CAF) in two different three dimensional (3D) configurations, two kinds of micromodules were produced: spheroids and microtissues. Spheroids were obtained by means of the traditional cell aggregation technique resulting in a 3D model characterized by high cell density and low amount of extracellular proteins. The microtissues were obtained by culturing cells into porous gelatin microscaffolds. In this latter configuration, cells assembled an intricate network of collagen, fibronectin and hyaluronic acid. We investigated the biophysical properties of both 3D models in terms of cell growth, metabolic activity, texture and composition of the extracellular matrix (via histological analysis and multiphoton imaging) and cell mechanical properties (via Particle Tracking Microrheology). In the spheroid models such biophysical properties remained unchanged regardless to the cell type used. In contrast, normal-microtissues and cancer-activated-microtissues displayed marked differences. CAF-microtissues possessed higher proliferation rate, superior contraction capability, different micro-rheological properties and an extracellular matrix richer in collagen fibronectin and hyaluronic acid. At last, multiphoton investigation revealed differences in the collagen network architecture. Taken together, these results suggested that despite to cell spheroids, microtissues better recapitulate the important differences existing in vivo between normal and cancer-activated stroma representing a more suitable system to mimic in vitro the stromal element of the tumor tissues. This work concerns the engineering of tumor tissue in vitro. Tumor models serve as biological equivalent to study pathologic progression and to screen or validate the drugs efficacy. Tumor

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

Compartmentalized Culture of Perivascular Stroma and Endothelial Cells in a Microfluidic Model of the Human Endometrium.

PubMed

Gnecco, Juan S; Pensabene, Virginia; Li, David J; Ding, Tianbing; Hui, Elliot E; Bruner-Tran, Kaylon L; Osteen, Kevin G

2017-07-01

The endometrium is the inner lining of the uterus. Following specific cyclic hormonal stimulation, endometrial stromal fibroblasts (stroma) and vascular endothelial cells exhibit morphological and biochemical changes to support embryo implantation and regulate vascular function, respectively. Herein, we integrated a resin-based porous membrane in a dual chamber microfluidic device in polydimethylsiloxane that allows long term in vitro co-culture of human endometrial stromal and endothelial cells. This transparent, 2-μm porous membrane separates the two chambers, allows for the diffusion of small molecules and enables high resolution bright field and fluorescent imaging. Within our primary human co-culture model of stromal and endothelial cells, we simulated the temporal hormone changes occurring during an idealized 28-day menstrual cycle. We observed the successful differentiation of stroma into functional decidual cells, determined by morphology as well as biochemically as measured by increased production of prolactin. By controlling the microfluidic properties of the device, we additionally found that shear stress forces promoted cytoskeleton alignment and tight junction formation in the endothelial layer. Finally, we demonstrated that the endometrial perivascular stroma model was sustainable for up to 4 weeks, remained sensitive to steroids and is suitable for quantitative biochemical analysis. Future utilization of this device will allow the direct evaluation of paracrine and endocrine crosstalk between these two cell types as well as studies of immunological events associated with normal vs. disease-related endometrial microenvironments.

Effect of Systemically Used Anti-Tumor Necrosis Factor-α Medication on the Corneal Epithelium and Stroma of Patients with Ankylosing Spondylitis.

PubMed

Arikan, Sedat; Gokmen, Ferhat; Ersan, Ismail; Akbal, Ayla; Resorlu, Hatice; Gencer, Baran; Ali Tufan, Hasan; Kara, Selcuk

2017-04-01

To evaluate the effect of systemically used anti-tumor necrosis factor alpha (TNF-α) medication on the thickness of corneal epithelium and stroma in patients with ankylosing spondylitis (AS). A total of 125 eyes of 69 participants were included in this retrospective study of three groups: healthy participants (Group 1), AS patients receiving anti-TNF-α medication (Group 2), and AS patients receiving a nonsteroidal anti-inflammatory medication (Group 3). According to anterior segment optical coherence tomography, the mean thickness of the corneal epithelium was significantly thicker in Group 2 than in Group 3 (51.6 ± 3.2 µm versus 50.4 ± 3 µm, p = 0.01), as was that of the stroma (475 ± 33 µm versus 443 ± 29 µm, p = 0.002). Anti-TNF-α medication and/or avoidance of nonsteroidal anti-inflammatory drugs could improve the thickness of both the corneal epithelium and stroma in AS patients.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Model System to Investigate the Effect of BRCA1 and/or p53 Inactivation in the Ovarian Stroma on Growth and Transformation Potential of the Ovarian Epithelium

DTIC Science & Technology

2009-10-01

Effect of BRCA1 and/or p53 Inactivation in the Ovarian Stroma on Growth and Transformation Potential of the Ovarian Epithelium PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER A Model System To Investigate the Effect of BRCA1 and/or p53 Inactivation in the Ovarian Stroma on Growth and... effects of loss of function of BRCA1 or BRCA1 and Trp53 in the stroma on the growth and neoplastic transformation of epithelial cells using 2D and 3D in

The prognostic value of reactive stroma on prostate needle biopsy: a population-based study.

PubMed

Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2015-05-01

Reactive tumor stroma has been shown to play an active role in prostatic carcinogenesis. A grading system for reactive stroma in prostate cancer (PC) has recently been established and found to predict biochemical recurrence and prostate cancer-specific mortality (PCSM) in prostatectomized patients. To the best of our knowledge, there has been no study investigating the prognostic value of reactive stromal grading (RSG) with regard to PCSM when evaluated in diagnostic prostate needle biopsies. A population-based study on 318 patients, encompassing all cases of PC diagnosed by needle biopsies and without evidence of systemic metastasis at the time of diagnosis in Aust-Agder County in the period 1991-1999. Patients were identified by cross-referencing the Cancer Registry of Norway. Clinical data were obtained by review of medical charts. The endpoint was PCSM. RSG was evaluated on haematoxylin and eosin stained sections according to previously described criteria; grade 0, 0-5% reactive stroma; grade 1, 6-15%; grade 2, 16-50%; grade 3, 51-100%. RSG could be evaluated in 278 patients. The median follow- up time was 110 months (interquartile range: 51-171). The 10-year PC - specific survival rate for RSGs of 0, 1, 2, and 3 was 96%, 81%, 69%, and 63%, respectively (P < 0.005). RSG remained independently associated with PCSM in a multivariate Cox regression analysis adjusting for prostate-specific antigen level, clinical stage, Gleason score, and mode of treatment. The concordance index of the multivariate model was 0.814 CONCLUSIONS: Our study demonstrates that RSG in diagnostic prostate needle biopsies predicts PCSM independently of other evaluable prognostic factors. Hence, RSG could be used in addition to traditional prognostic factors for prognostication and treatment stratification of PC patients. © 2015 Wiley Periodicals, Inc.

Local Lymphocytes and Nitric Oxide Synthase in the Uterine Cervical Stroma of Patients with Grade III Cervical Intraepithelial Neoplasia

PubMed Central

da Silva, Cléber Sergioda; Michelin, Marcia Antoniazi; Etchebehere, Renata Margarida; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

2010-01-01

OBJECTIVES: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS) in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III) or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma. METHODS: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas). The average ages in the control, CIN III and invasive groups were 43.9 (± 4.3), 35.5 (± 9.5), and 50 (± 11.2) years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3), cytotoxic lymphocytes (CD8), B lymphocytes (CD20), macrophages (CD68) and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control), at the intraepithelial lesion (CIN cases), and in the nfiltrating tumor. Two independent observers performed the immunohistochemical analysis. RESULTS: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05) in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05). CONCLUSION: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion. PMID:20613932

Squamous cell carcinoma of the lung with highly proliferating fibromatosis-like stroma: a rare phenomenon.

PubMed

Tajima, Shogo; Takanashi, Yusuke; Koda, Kenji

2015-01-01

Few cases of carcinoma with exuberant stromal proliferation have been documented, apart from scirrhous carcinoma. To the best of our knowledge, previous cases of carcinoma exhibiting exuberant stromal proliferation have exclusively been reported in the thyroid gland, specifically as papillary carcinoma. The exuberant stromal proliferation has been recognized to be similar to either fibromatosis or nodular fasciitis. Herein, we report a case of a 74-year-old Japanese man whose tumor in the upper lobe of his right lung displayed highly proliferating stroma with dispersed, poorly differentiated squamous cell carcinoma nests. The stromal spindle cells (fibroblasts/myofibroblasts) had similar molecular profiles to those typically observed in fibromatosis rather than nodular fasciitis, resulting in the designation of "fibromatosis-like" stroma. The presence of carcinoma cells, along with stromal cells, expressing TGF-β in this case likely fostered continuous stromal proliferation, presumably in conjunction with the unique microenvironment in which the carcinoma cells were present.

Distinct Roles of Cervical Epithelia and Stroma in Pregnancy and Parturition.

PubMed

Nallasamy, Shanmugasundaram; Mahendroo, Mala

2017-03-01

Through pregnancy the cervix must simultaneously remain competent for pregnancy maintenance and yet become progressively compliant to ensure on time parturition. Cervical changes precede not only term but also preterm birth. Thus, an understanding of the molecular mechanisms by which the cervix maintains the delicate balance between competence and compliance is required to prevent the potential for lifelong health complications that can result from a premature birth. Recent advances and accumulating evidence support distinct roles for the cervical epithelia and stroma in sustaining competence. Concurrently, structural reorganization of the stromal extracellular matrix allows for the gradual decline in tissue compliance. In recent years, advances in our understanding of the cervical remodeling process has resulted from the collective insights derived from biological, genomics, engineering, and mathematical modeling studies on clinical samples and animal models. This review will highlight recent literature that advances understanding of (1) the importance of barrier function in the lower female reproductive tract in protection against ascending infection, (2) cellular and extracellular matrix changes in the cervical stroma that influence the mechanical function of the cervix, (3) the potential translation of biological insights into clinical tools that impact preterm birth, and (4) the distinction between term and specific pathways of preterm birth. Finally, we present a discussion of future areas of investigation that are likely to advance understanding and lead to the development of clinical tools for accurate detection and prevention of premature birth. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

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

USDA-ARS?s Scientific Manuscript database

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...

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. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Non-coding RNAs, the Trojan horse in two-way communication between tumor and stroma in colorectal and hepatocellular carcinoma.

PubMed

Cătană, Cristina- Sorina; Pichler, Martin; Giannelli, Gianluigi; Mader, Robert M; Berindan-Neagoe, Ioana

2017-04-25

In a continuous and mutual exchange of information, cancer cells are invariably exposed to microenvironment transformation. This continuous alteration of the genetic, molecular and cellular peritumoral stroma background has become as critical as the management of primary tumor progression events in cancer cells. The communication between stroma and tumor cells within the extracellular matrix is one of the triggers in colon and liver carcinogenesis. All non- codingRNAs including long non-coding RNAs, microRNAs and ultraconserved genes play a critical role in almost all cancers and are responsible for the modulation of the tumor microenvironment in several malignant processes such as initiation, progression and dissemination. This review details the involvement of non codingRNAs in the evolution of human colorectal carcinoma and hepatocellular carcinoma in relationship with the microenvironment. Recent research has shown that a considerable number of dysregulated non- codingRNAs could be valuable diagnostic and prognostic biomarkers in cancer. Therefore, more in-depth knowledge of the role non- codingRNAs play in stroma-tumor communication and of the complex regulatory mechanisms between ultraconserved genes and microRNAs supports the validation of future effective therapeutic targets in patients suffering from hepatocellular and colorectal carcinoma, two distinctive entities which share quite a lot common non-coding RNAs.

Non-coding RNAs, the Trojan horse in two-way communication between tumor and stroma in colorectal and hepatocellular carcinoma

PubMed Central

Cătană, Cristina- Sorina; Pichler, Martin; Giannelli, Gianluigi; Mader, Robert M.; Berindan-Neagoe, Ioana

2017-01-01

In a continuous and mutual exchange of information, cancer cells are invariably exposed to microenvironment transformation. This continuous alteration of the genetic, molecular and cellular peritumoral stroma background has become as critical as the management of primary tumor progression events in cancer cells. The communication between stroma and tumor cells within the extracellular matrix is one of the triggers in colon and liver carcinogenesis. All non- codingRNAs including long non-coding RNAs, microRNAs and ultraconserved genes play a critical role in almost all cancers and are responsible for the modulation of the tumor microenvironment in several malignant processes such as initiation, progression and dissemination. This review details the involvement of non codingRNAs in the evolution of human colorectal carcinoma and hepatocellular carcinoma in relationship with the microenvironment. Recent research has shown that a considerable number of dysregulated non- codingRNAs could be valuable diagnostic and prognostic biomarkers in cancer. Therefore, more in-depth knowledge of the role non- codingRNAs play in stroma-tumor communication and of the complex regulatory mechanisms between ultraconserved genes and microRNAs supports the validation of future effective therapeutic targets in patients suffering from hepatocellular and colorectal carcinoma, two distinctive entities which share quite a lot common non-coding RNAs. PMID:28392501

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

Does the peritumoral stroma of basal cell carcinoma recapitulate the follicular connective tissue sheath?

PubMed

Sellheyer, Klaus; Krahl, Dieter

2011-07-01

There are compelling embryologic and anatomic relationships within adnexal tumors. However, these are mostly perceived within the epithelial component while the stromal component of the tumors is frequently overlooked. In postnatal skin, nestin is almost exclusively expressed in the perifollicular mesenchyme. This study examines the expression of this neuroepithelial stem cell protein in trichoblastoma/trichoepithelioma and in basal cell carcinoma (BCC), which is increasingly being viewed as follicular in nature. We employed standard immunohistochemical methods with three different antibodies to examine the expression of nestin in 25 BCCs and compared the staining pattern with that of 7 trichoblastomas and 11 trichoepitheliomas. Nestin is expressed in the peritumoral stroma of all tumors examined and is limited to the immediate layer of mesenchymal cells surrounding the tumor epithelium. In BCC, nestin-immunoreactive cells are found as a sheath of thin, spindled fibroblasts, while reactive cells are plump in trichoepitheliomas/trichoblastomas. We postulate that the peritumoral stroma of BCC imitates the perifollicular connective tissue sheath, while in contrast that of trichoepithelioma/trichoblastoma is similar to the papillary and immediate peripapillary follicular mesenchyme. Further functional and animal experimental studies are needed to test this hypothesis. Copyright © 2011 John Wiley & Sons A/S.

'Blue bubble' technique: an ab interno approach for Descemet separation in deep anterior lamellar keratoplasty using trypan blue stained viscoelastic device.

PubMed

Livny, Eitan; Bahar, Irit; Hammel, Naama; Nahum, Yoav

2018-04-01

In this study, we examined a novel variant of 'big-bubble' deep anterior lamellar keratoplasty using trypan-blue-stained viscoelastic device for the creation of a pre-descemetic bubble. Ten corneoscleral rims were mounted on an artificial anterior chamber (AC). The AC was filled with air through a limbal paracentesis. A Melles' triangulated spatula was inserted through the paracentesis, with its tip penetrating the AC, was then slightly retracted and pushed into the deep stroma above the roof of the paracentesis. A mixture of trypan blue and viscoelastic device (Healon, Abbott Medical Optics, Abbott Park, Illinois) was injected into this intra-stromal pocket using a 27-G cannula to create a pre-descemetic separation bubble. Bubble type and visualization of dyed viscoelastic device were noted. The method was later employed in three cases. In all 10 corneoscleral rims, the technique successfully created a visible pre-descemetic (type 1) bubble that could be expanded up to the predicted diameter of trephination. Subsequent trephination and the removal of corneal stroma were uneventful. In two out of four clinical cases, a type 1 bubble was created, while in two others, visco-dissection failed and dyed viscoelastic was seen in the AC. The presented technique holds promise of being a relatively easy to perform, predictable and well-controlled alternative for achieving a type 1 bubble during deep anterior lamellar keratoplasty surgery. The trypan-blue-stained viscoelastic device facilitates proper visualization and control of the separation bubble and assists in identifying the penetrance to the separation bubble prior to removal of the stromal cap. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Late onset of a persistent, deep stromal scarring after PRK and corneal cross-linking in a patient with forme fruste keratoconus.

PubMed

Güell, Jose L; Verdaguer, Paula; Elies, Daniel; Gris, Oscar; Manero, Felicidad

2014-04-01

To present a case of a late, deep stromal scar in a 22-year-old patient with forme fruste keratoconus who underwent combined corneal cross-linking and photorefractive keratectomy (PRK). Topography-guided corneal cross-linking combined with corneal PRK (without complications) was performed in both eyes with a delay of 2 weeks between each eye. At the 5-month postoperative examination of the right eye, a localized corneal haze was circumscribed to the posterior deep stroma, signifying a decrease of visual acuity. However, this improved partially and temporarily when treated with topical corticoids during 2 years of follow-up and then reoccurred, affecting the corrected distance visual acuity. To the authors' knowledge, this is the first documented, clinical case presenting a deep stromal affectation without endothelial decompensation and visual acuity affectation as a postoperative complication following topography-guided PRK and corneal cross-linking. Copyright 2014, SLACK Incorporated.

Depth-Dependent Transverse Shear Properties of the Human Corneal Stroma

PubMed Central

Petsche, Steven J.; Chernyak, Dimitri; Martiz, Jaime; Levenston, Marc E.

2012-01-01

Purpose. To measure the transverse shear modulus of the human corneal stroma and its profile through the depth by mechanical testing, and to assess the validity of the hypothesis that the shear modulus will be greater in the anterior third due to increased interweaving of lamellae. Methods. Torsional rheometry was used to measure the transverse shear properties of 6 mm diameter buttons of matched human cadaver cornea pairs. One cornea from each pair was cut into thirds through the thickness with a femtosecond laser and each stromal third was tested individually. The remaining intact corneas were tested to measure full stroma shear modulus. The shear modulus from a 1% shear strain oscillatory test was measured at various levels of axial compression for all samples. Results. After controlling for axial compression, the transverse shear moduli of isolated anterior layers were significantly higher than central and posterior layers. Mean modulus values at 0% axial strain were 7.71 ± 6.34 kPa in the anterior, 1.99 ± 0.45 kPa in the center, 1.31 ± 1.01 kPa in the posterior, and 9.48 ± 2.92 kPa for full thickness samples. A mean equilibrium compressive modulus of 38.7 ± 8.6 kPa at 0% axial strain was calculated from axial compression measured during the shear tests. Conclusions. Transverse shear moduli are two to three orders of magnitude lower than tensile moduli reported in the literature. The profile of shear moduli through the depth displayed a significant increase from posterior to anterior. This gradient supports the hypothesis and corresponds to the gradient of interwoven lamellae seen in imaging of stromal cross-sections. PMID:22205608

Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk.

PubMed

Orozco, Carlos A; Martinez-Bosch, Neus; Guerrero, Pedro E; Vinaixa, Judith; Dalotto-Moreno, Tomás; Iglesias, Mar; Moreno, Mireia; Djurec, Magdolna; Poirier, Françoise; Gabius, Hans-Joachim; Fernandez-Zapico, Martin E; Hwang, Rosa F; Guerra, Carmen; Rabinovich, Gabriel A; Navarro, Pilar

2018-04-17

Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a Kras -driven mouse model of PDA ( Ela-Kras G12V p53 -/- ) results in a significant increase in survival through mechanisms involving decreased stroma activation, attenuated vascularization, and enhanced T cell infiltration leading to diminished metastasis rates. In a human setting, human pancreatic stellate cells (HPSCs) promote cancer proliferation, migration, and invasion via Gal1-driven pathways. Moreover, in vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted HPSCs leads to impaired tumor formation and metastasis in mice. Gene-expression analyses of pancreatic tumor cells exposed to Gal1 reveal modulation of multiple regulatory pathways involved in tumor progression. Thus, Gal1 hierarchically regulates different events implicated in PDA biology including tumor cell proliferation, invasion, angiogenesis, inflammation, and metastasis, highlighting the broad therapeutic potential of Gal1-specific inhibitors, either alone or in combination with other therapeutic modalities.

Entropy of Vaidya Black Hole on Apparent Horizon with Minimal Length Revisited

NASA Astrophysics Data System (ADS)

Tang, Hao; Wu, Bin; Sun, Cheng-yi; Song, Yu; Yue, Rui-hong

2018-03-01

By considering the generalized uncertainty principle, the degrees of freedom near the apparent horizon of Vaidya black hole are calculated with the thin film model. The result shows that a cut-off can be introduced naturally rather than taking by hand. Furthermore, if the minimal length is chosen to be a specific value, the statistical entropy will satisfy the conventional area law at the horizon, which might reveal some deep things of the minimal length.

Entropy of Vaidya Black Hole on Apparent Horizon with Minimal Length Revisited

NASA Astrophysics Data System (ADS)

Tang, Hao; Wu, Bin; Sun, Cheng-yi; Song, Yu; Yue, Rui-hong

2018-07-01

By considering the generalized uncertainty principle, the degrees of freedom near the apparent horizon of Vaidya black hole are calculated with the thin film model. The result shows that a cut-off can be introduced naturally rather than taking by hand. Furthermore, if the minimal length is chosen to be a specific value, the statistical entropy will satisfy the conventional area law at the horizon, which might reveal some deep things of the minimal length.

Telomere Attrition in Isolated High-Grade Prostatic Intraepithelial Neoplasia and Surrounding Stroma Is Predictive of Prostate Cancer1

PubMed Central

Joshua, Anthony Michael; Vukovic, Bisera; Braudey, Ilan; Hussein, Sundus; Zielenska, Maria; Srigley, John; Evans, Andrew; Squire, Jeremy Andrew

2007-01-01

Abstract The causes of early genomic events underlying the development of prostate cancer (CaP) remain unclear. The onset of chromosomal instability is likely to facilitate the formation of crucial genomic aberrations both in the precursor lesion high-grade prostatic intraepithelial neoplasia (HPIN) and in CaP. Instability generated by telomere attrition is one potential mechanism that could initiate chromosomal rearrangements. In this study, normalized telomere length variation was examined in a cohort of 68 men without CaP who had HPIN only on prostatic biopsies. Multiple significant associations between telomere attrition and eventual diagnosis of CaP in the HPIN and in the surrounding stroma were found. Kaplan-Meier analysis of telomere length demonstrated a significantly increased risk for the development of cancer with short telomeres in the surrounding stroma [P = .035; hazard ratio (HR) = 2.12; 95% confidence interval (95% CI) = 0.231–0.956], and a trend for HPIN itself (P = .126; HR = 1.72; 95% CI = 0.287–1.168). Cox regression analysis also demonstrated significance between the time from the original biopsy to the diagnosis of cancer and telomere length in HPIN and in the surrounding stroma. These analyses showed significance, both alone and in combination with baseline prostate-specific antigen, and lend support to the hypothesis that telomere attrition in prostatic preneoplasia may be fundamental to the generation of chromosomal instability and to the emergence of CaP. PMID:17325746

Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts.

PubMed

Kabiri, Zahra; Greicius, Gediminas; Madan, Babita; Biechele, Steffen; Zhong, Zhendong; Zaribafzadeh, Hamed; Edison; Aliyev, Jamal; Wu, Yonghui; Bunte, Ralph; Williams, Bart O; Rossant, Janet; Virshup, David M

2014-06-01

Wnt/β-catenin signaling supports intestinal homeostasis by regulating proliferation in the crypt. Multiple Wnts are expressed in Paneth cells as well as other intestinal epithelial and stromal cells. Ex vivo, Wnts secreted by Paneth cells can support intestinal stem cells when Wnt signaling is enhanced with supplemental R-Spondin 1 (RSPO1). However, in vivo, the source of Wnts in the stem cell niche is less clear. Genetic ablation of Porcn, an endoplasmic reticulum resident O-acyltransferase that is essential for the secretion and activity of all vertebrate Wnts, confirmed the role of intestinal epithelial Wnts in ex vivo culture. Unexpectedly, mice lacking epithelial Wnt activity (Porcn(Del)/Villin-Cre mice) had normal intestinal proliferation and differentiation, as well as successful regeneration after radiation injury, indicating that epithelial Wnts are dispensable for these processes. Consistent with a key role for stroma in the crypt niche, intestinal stromal cells endogenously expressing Wnts and Rspo3 support the growth of Porcn(Del) organoids ex vivo without RSPO1 supplementation. Conversely, increasing pharmacologic PORCN inhibition, affecting both stroma and epithelium, reduced Lgr5 intestinal stem cells, inhibited recovery from radiation injury, and at the highest dose fully blocked intestinal proliferation. We conclude that epithelial Wnts are dispensable and that stromal production of Wnts can fully support normal murine intestinal homeostasis.

Complete Metabolome and Lipidome Analysis Reveals Novel Biomarkers in the Human Diabetic Corneal Stroma

PubMed Central

Priyadarsini, Shrestha; McKay, Tina B; Sarker-Nag, Akhee; Allegood, Jeremy; Chalfant, Charles; Ma, Jian-Xing; Karamichos, Dimitrios

2016-01-01

Prolonged hyperglycemia during diabetes mellitus can cause severe ophthalmic complications affecting both the anterior and posterior ocular segments leading to impaired vision or blindness. Diabetes-induced corneal pathologies are associated with decreased wound healing capacity, corneal edema, and altered epithelial basement membrane. The mechanism by which diabetes modulates structure and function within the corneal stroma are unknown. In our study, we characterized the effects of diabetes on extracellular matrix, lipid transport, and cellular metabolism by defining the entire metabolome and lipidome of Type 1 and Type 2 human diabetic corneal stroma. Significant increases in Collagen I and III were found in diabetic corneas suggesting that diabetes promotes defects in matrix structure leading to scarring. Furthermore, increased lipid content, including sphingosine-1-phosphate and dihydrosphingosine, in diabetic corneas compared to healthy controls were measured suggesting altered lipid retention. Metabolomics analysis identified elevated tryptophan metabolites, independent of glucose metabolism, which correlated with upregulation of the Kynurenine pathway in diabetic corneas. We also found significant upregulation of novel biomarkers aminoadipic acid, D,L-pipecolic acid, and dihydroorotate. Our study links aberrant tryptophan metabolism to end-stage pathologies associated with diabetes indicating the potential of the Kynurenine pathway as a therapeutic target for inhibiting diabetes-associated defects in the eye. PMID:27742548

Corneal stroma microfibrils.

PubMed

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

2015-03-01

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 (∼10 nm diameter). Immunogold evidence clearly

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

Automatic classification of cardioembolic and arteriosclerotic ischemic strokes from apparent diffusion coefficient datasets using texture analysis and deep learning

NASA Astrophysics Data System (ADS)

Villafruela, Javier; Crites, Sebastian; Cheng, Bastian; Knaack, Christian; Thomalla, Götz; Menon, Bijoy K.; Forkert, Nils D.

2017-03-01

Stroke is a leading cause of death and disability in the western hemisphere. Acute ischemic strokes can be broadly classified based on the underlying cause into atherosclerotic strokes, cardioembolic strokes, small vessels disease, and stroke with other causes. The ability to determine the exact origin of an acute ischemic stroke is highly relevant for optimal treatment decision and preventing recurrent events. However, the differentiation of atherosclerotic and cardioembolic phenotypes can be especially challenging due to similar appearance and symptoms. The aim of this study was to develop and evaluate the feasibility of an image-based machine learning approach for discriminating between arteriosclerotic and cardioembolic acute ischemic strokes using 56 apparent diffusion coefficient (ADC) datasets from acute stroke patients. For this purpose, acute infarct lesions were semi-atomically segmented and 30,981 geometric and texture image features were extracted for each stroke volume. To improve the performance and accuracy, categorical Pearson's χ2 test was used to select the most informative features while removing redundant attributes. As a result, only 289 features were finally included for training of a deep multilayer feed-forward neural network without bootstrapping. The proposed method was evaluated using a leave-one-out cross validation scheme. The proposed classification method achieved an average area under receiver operator characteristic curve value of 0.93 and a classification accuracy of 94.64%. These first results suggest that the proposed image-based classification framework can support neurologists in clinical routine differentiating between atherosclerotic and cardioembolic phenotypes.

Cytomegalovirus infection of the BS-1 human stroma cell line: effect on murine hemopoiesis.

PubMed

Steinberg, H N; Anderson, J; Lim, B; Chatis, P A

1993-10-01

BS-1, a stromal cell line derived from human bone marrow, can support the growth of murine erythroid (BFU-E), granulocyte-macrophage (CFU-GM), and megakaryocyte (CFU-M) progenitor cells in a short term in vitro coculture system. Exposure of BS-1 cells to cytomegalovirus (CMV) for 3 hr prior to coculture results in a marked reduction in the stroma cell's ability to support murine hemopoiesis. CMV's effect on the BS-1 cell's hematopoietic support function is dependent on the multiplicity of infection with total suppression of BFU-E observed at a 1:1 ratio of virus to bone marrow cells. A 50% loss in the ability of BS-1 cells to support BFU-E is observed at a 0.1:1 ratio. No effect of CMV is observed with further log dilutions of virus. CMV infection of BS-1 cells affects its support of erythroid progenitor cell growth to a greater extent than its influence on the development of granulocyte-macrophage colonies. Antibody to CMV or heat inactivation of the virus reverses the inhibitory affect on BS-1 cells. The results suggest that CMV can infect a cell that constitutes one of the cellular elements of the normal bone marrow microenvironment causing a decrease in the stroma's ability to support the growth and development of normal progenitor cells.

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

Organized metabolic crime in prostate cancer: The coexpression of MCT1 in tumor and MCT4 in stroma is an independent prognosticator for biochemical failure.

PubMed

Andersen, Sigve; Solstad, Ørjan; Moi, Line; Donnem, Tom; Eilertsen, Marte; Nordby, Yngve; Ness, Nora; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy M

2015-08-01

Lactate import or export over cell membranes is facilitated by monocarboxylate transporters (MCTs) 1 and 4. Expression profiles can be markers of an oxidative or glycolytic phenotype. Descriptive studies and functional studies in neoplastic cells and fibroblasts in prostate cancer (PC) have suggested a distinct phenotype. We aimed to explore expression of MCT1 and MCT4 in PC cells and surrounding stroma in a large cohort. Additionally, we wanted to find out if distinct expression profiles were associated with biochemical failure-free survival (BFFS). Tissue microarrays were constructed from 535 patients with radical prostatectomies between January 1, 1995, and December 31, 2005. Immunohistochemistry was used to detect expression, and degrees of expression were evaluated semiquantitatively by 2 pathologists using light microscopy. For MCT1, there was only epithelial expression, whereas there was a low level of expression of MCT4 in tumor and stroma. A total of 172 patients had a low expression of MCT1 in tumor and MCT4 in stroma. There were 232 patients who had a high expression of MCT1 and a low expression of MCT4 in stroma. Only 11 patients had a low tumoral MCT1 expression and a high stromal MCT4 expression, and 26 patients (5%) had a high expression of both. Patients with a high-high combination had a significantly reduced BFFS (P = 0.011), and when adjusting for other factors, its effect was significant and independent (HR = 1.99, CI 95%: 1.09-3.62; P = 0.024). This study adds to the current understanding of the reversed Warburg effect to be a significant phenotype in PC. High coexpression of MCT1 in tumor and MCT4 in stroma is independently associated to a worse BFFS, and the strength of this association is as strong as having a Gleason score of ≥9. Copyright © 2015 Elsevier Inc. All rights reserved.

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

In vitro study of air bubble dynamics following pneumodissection of donor corneas and relationship of air bubble pattern with a peripheral paracentesis incision.

PubMed

Chaurasia, Sunita; Ramappa, Muralidhar

2016-12-01

To study various types of morphological patterns of the air bubble and their relation to a peripheral paracentesis after air injection in corneal stroma in vitro experiment. Air was injected into the donor corneas from the endothelial side and pattern was noted. Four different scenarios were created, namely (a) air injection into the deep stroma (n=11), (b) air injection into the superficial stroma (n=3), (c) air injection into the deep stroma after making a peripheral incision internal to the trabecular meshwork region that simulated an anteriorly placed paracentesis incision, with the site of air injection within a clock hour of the peripheral incision (n=7) and (d) air injection into the deep stroma after making a peripheral incision, the site of air injection being 180° away from the peripheral incision site (n=3). Air injection at deep posterior stroma resulted in the formation of type-1 and type-2 bubbles, type 2 began from the periphery and followed the type-1 bubble pattern in majority of the donor corneas. The type-1 pattern was noted as a bubble in the central part of the donor disc that did not reach the peripheral extent of the cornea. The type-2 pattern was a bubble that started at the peripheral cornea and expanded but was limited by the limbus circumferentially. With a full-thickness peripheral incision and air injection in the same clock hour of the incision, only a type-1 bubble pattern was noted with air leakage from the site of the incision. The results of the study corroborate with the clinical observations made during deep lamellar keratoplasty (DLK). The placement of the paracentesis has a bearing on the pattern of the air bubble and can be used to an advantage during DLK surgery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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.

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).

Induction of hypoxia-inducible factor-1alpha and activation of caspase-3 in hypoxia-reoxygenated bone marrow stroma is negatively regulated by the delayed production of substance P.

PubMed

Qian, J; Ramroop, K; McLeod, A; Bandari, P; Livingston, D H; Harrison, J S; Rameshwar, P

2001-10-15

The bone marrow (BM), which is the major site of immune cell development in the adult, responds to different stimuli such as inflammation and hemorrhagic shock. Substance P (SP) is the major peptide encoded by the immune/hemopoietic modulator gene, preprotachykinin-1 (PPT-I). Differential gene expression using a microarray showed that SP reduced hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA levels in BM stroma. Because long-term hypoxia induced the expression of PPT-I in BM mononuclear cells, we used timeline studies to determine whether PPT-I is central to the biologic responses of BM stroma subjected to 30-min hypoxia (pO(2) = 35 mm Hg) followed by reoxygenation. HIF-1alpha mRNA and protein levels were increased up to 12 h. At this time, beta-PPT-I mRNA was detected with the release of SP at 16 h. SP release correlated with down-regulation of HIF-1alpha to baseline. A direct role for SP in HIF-1alpha expression was demonstrated as follows: 1) transient knockout of beta-PPT-I showed an increase in HIF-1alpha expression up to 48 h of reoxygenation; and 2) HIF-1alpha expression remained baseline during reoxygenation when stroma was subjected to hypoxia in the presence of SP. Reoxygenation activated the PPT-I promoter with concomitant nuclear translocation of HIF-1alpha that can bind to the respective consensus sequences within the PPT-I promoter. SP reversed active caspase-3, an indicator of apoptosis and erythropoiesis, to homeostasis level after reoxygenation of hypoxic stroma. The results show that during reoxgenation the PPT-I gene acts as a negative regulator on the expression of HIF-1alpha and active caspase-3 in BM stroma subjected to reoxygenation.

An unusual initial presentation of mantle cell lymphoma arising from the lymphoid stroma of warthin tumor.

PubMed

Arcega, Ramir S; Feinstein, Aaron J; Bhuta, Sunita; Blackwell, Keith E; Rao, Nagesh P; Pullarkat, Sheeja T

2015-12-03

Warthin tumors presenting concomitantly with a lymphoma is vanishingly rare with only 15 reported cases in English literature. Herein, we report an unusual initial presentation of a mantle cell lymphoma involving the lymphoid stroma of a Warthin tumor. A seventy-seven year old otherwise healthy gentleman with a 50-pack year smoking history presents with a slowly enlarging left cheek mass. CT scan of the neck demonstrated a left parotid gland tumor measuring 3.4 cm in greatest dimension. He underwent a left superficial parotidectomy, with subsequent histopathologic examination revealing a Warthin tumor with extensive expansion of the lymphoid stroma. Flow cytometric, immunohistochemical, and cytogenetic studies of the stromal component of the tumor confirmed the presence of a mantle cell lymphoma. Clinical staging demonstrated stage IVa disease, and was considered to be at low to intermediate risk due to the slow growth of the parotid lesion. The patient is undergoing close follow up with repeat PET-CT scans at six months. To the best of our knowledge, this is the first well documented collision tumor between mantle cell lymphoma and a Warthin tumor. This case also brings to light the significance of thorough evaluation of the lymphoid component of Warthin tumor.

Deep-Sea Microbes: Linking Biogeochemical Rates to -Omics Approaches

NASA Astrophysics Data System (ADS)

Herndl, G. J.; Sintes, E.; Bayer, B.; Bergauer, K.; Amano, C.; Hansman, R.; Garcia, J.; Reinthaler, T.

2016-02-01

Over the past decade substantial progress has been made in determining deep ocean microbial activity and resolving some of the enigmas in understanding the deep ocean carbon flux. Also, metagenomics approaches have shed light onto the dark ocean's microbes but linking -omics approaches to biogeochemical rate measurements are generally rare in microbial oceanography and even more so for the deep ocean. In this presentation, we will show by combining metagenomics, -proteomics and biogeochemical rate measurements on the bulk and single-cell level that deep-sea microbes exhibit characteristics of generalists with a large genome repertoire, versatile in utilizing substrate as revealed by metaproteomics. This is in striking contrast with the apparently rather uniform dissolved organic matter pool in the deep ocean. Combining the different -omics approaches with metabolic rate measurements, we will highlight some major inconsistencies and enigmas in our understanding of the carbon cycling and microbial food web structure in the dark ocean.

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.

Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

PubMed

Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

2007-04-01

Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

Biophysical interpretation and ex-vivo characterization of scattered light from tumor-associated breast stroma

NASA Astrophysics Data System (ADS)

Laughney, Ashley; Krishnaswamy, Venkat; Schwab, Mary; Wells, Wendy A.; Paulsen, Keith D.; Pogue, Brian W.

2009-02-01

The purpose of this study was to extract scatter parameters related to tissue ultra-structures from freshly excised breast tissue and to assess whether evident changes in scatter across diagnostic categories is primarily influenced by variation in the composition of each tissues subtypes or by physical remodeling of the extra-cellular environment. Pathologists easily distinguish between epithelium, stroma and adipose tissues, so this classification was adopted for macroscopic subtype classification. Micro-sampling reflectance spectroscopy was used to characterize single-backscattered photons from fresh, excised tumors and normal reduction specimens with sub-millimeter resolution. Phase contrast microscopy (sub-micron resolution) was used to characterize forward-scattered light through frozen tissue from the DHMC Tissue Bank, representing normal, benign and malignant breast tissue, sectioned at 10 microns. The packing density and orientation of collagen fibers in the extracellular matrix (ECM) associated with invasive, normal and benign epithelium was evaluated using transmission electron microscopy (TEM). Regions of interest (ROIs) in the H&E stained tissues were identified for analysis, as outlined by a pathologist as the gold standard. We conclude that the scatter parameters associated with tumor specimens (Npatients=6, Nspecimens=13) significantly differs from that of normal reductions (Npatients=6, Nspecimens=10). Further, tissue subtypes may be identified by their scatter spectra at sub-micron resolution. Stromal tissue scatters significantly more than the epithelial cells embedded in its ECM and adipose tissue scatters much less. However, the scatter signature of the stroma at the sub-micron level is not particularly differentiating in terms of a diagnosis.

Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.

Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were usedmore » to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in

Tumor-stroma ratio(TSR) as a potential novel predictor of prognosis in digestive system cancers: A meta-analysis.

PubMed

Zhang, Runjin; Song, Wei; Wang, Kai; Zou, Shubing

2017-09-01

The tumor-stroma ratio (TSR) has been reported as a prognosis predictor in multiple cancers. The aim of this meta-analysis was to investigate the potential value of TSR as a prognostic predictor of cancer in the digestive system. We searched PubMed, Embase, Elsevier and Web of Science. All studies exploring the association of TSR with overall survival (OS) or disease-free survival (DFS), and lymph node metastasis (LNM) were identified. In total, eight studies were eligible for analysis, and they included 1959 patients. Meta-analysis showed that the low TSR in the tumor could predict poor overall survival (OS) in multiple cancers (pooled Hazard Ratio [HR]: 2.15, 95%CI: 1.80-2.57, P<0.00001, fixed effects). For disease-free survival (DFS), low TSR was also a significant predictor (pooled Hazard Ratio [HR]: 2.31, 95%CI: 1.88-2.83, P<0.00001, fixed effects). In addition, low TSR was correlated with tumor stage. The tumor-stroma ratio (TSR) may potentially serve as a poor prognostic predictor for the metastasis and prognosis of cancer. Copyright © 2017. Published by Elsevier B.V.

CCL2/CCL5 secreted by the stroma induce IL-6/PYK2 dependent chemoresistance in ovarian cancer.

PubMed

Pasquier, Jennifer; Gosset, Marie; Geyl, Caroline; Hoarau-Véchot, Jessica; Chevrot, Audrey; Pocard, Marc; Mirshahi, Massoud; Lis, Raphael; Rafii, Arash; Touboul, Cyril

2018-02-19

Minimal residual disease is the main issue of advanced ovarian cancer treatment. According to the literature and previous results, we hypothesized that Mesenchymal Stromal Cells (MSC) could support this minimal residual disease by protecting ovarian cancer cells (OCC) from chemotherapy. In vitro study confirmed that MSC could induce OCC chemoresistance without contact using transwell setting. Further experiments showed that this induced chemoresistance was dependent on IL-6 OCC stimulation. We combined meticulous in vitro profiling and tumor xenograft models to study the role of IL-6 in MSC/OCC intereactions. We demonstrated that Tocilizumab® (anti-IL-6R therapy) in association with chemotherapy significantly reduced the peritoneal carcinosis index (PCI) than chemotherapy alone in mice xenografted with OCCs+MSCs. Further experiments showed that CCL2 and CCL5 are released by MSC in transwell co-culture and induce OCCs IL-6 secretion and chemoresistance. Finally, we found that IL-6 induced chemoresistance was dependent on PYK2 phosphorylation. These findings highlight the potential key role of the stroma in protecting minimal residual disease from chemotherapy, thus favoring recurrences. Future clinical trials targeting stroma could use anti-IL-6 therapy in association with chemotherapy.

Experience-based surgical approach to pancreatic mucinous cystic neoplasms with ovarian-type stroma

PubMed Central

Kang, Chang Moo; Matsushita, Akira; Hwang, Ho Kyoung; Matsuda, Yoko; Kim, Hyunki; Nakamura, Yoshiharu; Lee, Woo Jung

2018-01-01

The present study aimed to elucidate the clinicopathological characteristics of resected mucinous cystic neoplasm (MCN) with ovarian-type stroma and identify a surgical approach for MCN treatment, on the basis of Republic of Korean (Yonsei University College of Medicine, Seoul, South Korea) and Japanese (Nippon Medical School, Tokyo, Japan) bi-institutional collaboration. The present study retrospectively reviewed 55 MCNs with ovarian-type stroma using pathological re-examination. Clinicopathological features and preoperative clinical parameters were evaluated to predict malignant alterations in MCNs. The proportion of surgically treated MCNs has recently been increasing. All patients included in the present study were female, with a mean age of 47.9±13.3 years. Mural nodules were noted in 8 patients (14.5%) and the mean cyst size was 6.1±4.2 cm. A total of 9 patients (16.4%) were identified to exhibit non-invasive mucinous cystadenocarcinoma. The number of patients with small tumors (R2=−0.079, P=0.038) and asymptomatic pancreatic MCNs (P=0.022) was significantly increased (P<0.05), which resulted in the more frequent application of minimally invasive surgery (P<0.001). During the follow-up period (mean, 51.6 months; range, 1.1–242.8 months), no recurrence or tumor-associated mortality was identified. The presence of mural nodules (P=0.002) and a tumor size ≥4.5 cm (P=0.027) were identified as potential clinical parameters for predicting malignant transformation. The significance of mural nodules in predicting malignant transformation was increased in large MCNs (≥4.5 cm) of the pancreas compared with small MCNs (<4.5 cm) (P=0.002). Overall, non-invasive pancreatic MCNs are not aggressive, and minimally invasive pancreatectomy may be an effective approach for suitable patients. PMID:29434957

Study on a hydroxypropyl chitosan-gelatin based scaffold for corneal stroma tissue engineering

NASA Astrophysics Data System (ADS)

Wang, Shilu; Liu, Wanshun; Han, Baoqin; Yang, Lingling

2009-07-01

Hydroxypropyl chitosan (HPCTS) was crosslinked with gelatin (GEL) and chondroitin sulfate (CS) by 1,4-butanediol diglycidyl ether to synthesize a scaffold. In this study, this scaffold was tested in physical and biological characteristics as a bioactive corneal stroma surrogate. The results showed the scaffold exhibited 83-88% light transmission values at wavelengths of visible light. Besides that, the scaffold had 96% water content and allowed NaCl and glucose to permeate. Moreover, it was suitable for keratocytes growing on its surface. In the biological part, we compared the scaffold with CS-free ones to investigate the potential effect of CS and found out that CS notablely improved cell compatibility of the scaffold.

Pea chloroplast DnaJ-J8 and Toc12 are encoded by the same gene and localized in the stroma.

PubMed

Chiu, Chi-Chou; Chen, Lih-Jen; Li, Hsou-min

2010-11-01

Toc12 is a novel J domain-containing protein identified in pea (Pisum sativum) chloroplasts. It was shown to be an integral outer membrane protein localizing in the intermembrane space of the chloroplast envelope. Furthermore, Toc12 was shown to associate with an intermembrane space Hsp70, suggesting that Toc12 is important for protein translocation across the chloroplast envelope. Toc12 shares a high degree of sequence similarity with Arabidopsis (Arabidopsis thaliana) DnaJ-J8, which has been suggested to be a soluble protein of the chloroplast stroma. Here, we isolated genes encoding DnaJ-J8 from pea and found that Toc12 is a truncated clone of one of the pea DnaJ-J8s. Protein import analyses indicate that Toc12 and DnaJ-J8s possess a cleavable transit peptide and are localized in the stroma. Arabidopsis mutants with T-DNA insertions in the DnaJ-J8 gene show no defect in chloroplast protein import. Implications of these results in the energetics and mechanisms of chloroplast protein import are discussed.

Aberrant expression of epithelial leucine-rich repeat containing G protein-coupled receptor 5-positive cells in the eutopic endometrium in endometriosis and implications in deep-infiltrating endometriosis.

PubMed

Vallvé-Juanico, Júlia; Suárez-Salvador, Elena; Castellví, Josep; Ballesteros, Agustín; Taylor, Hugh S; Gil-Moreno, Antonio; Santamaria, Xavier

2017-11-01

To characterize leucine-rich repeat containing G protein-coupled receptor 5-positive (LGR5 + ) cells from the endometrium of women with endometriosis. Prospective experimental study. University hospital/fertility clinic. Twenty-seven women with endometriosis who underwent surgery and 12 healthy egg donors, together comprising 39 endometrial samples. Obtaining of uterine aspirates by using a Cornier Pipelle. Immunofluorescence in formalin-fixed paraffin-embedded tissue from mice and healthy and pathologic human endometrium using antibodies against LGR5, E-cadherin, and cytokeratin, and epithelial and stromal LGR5 + cells isolated from healthy and pathologic human eutopic endometrium by fluorescence-activated cell sorting and transcriptomic characterization by RNA high sequencing. Immunofluorescence showed that LGR5 + cells colocalized with epithelial markers in the stroma of the endometrium only in endometriotic patients. The results from RNA high sequencing of LGR5 + cells from epithelium and stroma did not show any statistically significant differences between them. The LGR5 + versus LGR5 - cells in pathologic endometrium showed 394 differentially expressed genes. The LGR5 + cells in deep-infiltrating endometriosis expressed inflammatory markers not present in the other types of the disease. Our results revealed the presence of aberrantly located LGR5 + cells coexpressing epithelial markers in the stromal compartment of women with endometriosis. These cells have a statistically significantly different expression profile in deep-infiltrating endometriosis in comparison with other types of endometriosis, independent of the menstrual cycle phase. Further studies are needed to elucidate their role and influence in reproductive outcomes. Copyright © 2017. Published by Elsevier Inc.

E-cadherin regulators are differentially expressed in the epithelium and stroma of keratocystic odontogenic tumors.

PubMed

Porto, Lia Pontes Arruda; dos Santos, Jean Nunes; Ramalho, Luciana Maria Pedreira; Figueiredo, Andreia Leal; Carneiro Júnior, Bráulio; Gurgel, Clarissa Araújo; Paiva, Katiúcia Batista Silva; Xavier, Flávia Caló Aquino

2016-04-01

The epithelial-mesenchymal transition (EMT) is the process where cells lose their epithelial features and acquire properties of typical mesenchymal cells. The dissociation of tumor cells due to changes in cell-cell adhesion is one of the key principles of tumor invasion and EMT. Thus, the knowledge of the molecular features of EMT in keratocyst odontogenic tumor (KOT) can provide useful markers to aid in the diagnosis and prognosis and perhaps contribute to an alternative therapeutic approach as it shows an aggressive clinical behavior and high recurrence rates. This study aimed to evaluate the EMT in KOT by the immunoexpression of E-cadherin, N-cadherin, Snail, and Slug and comparing to radicular cysts and dental follicles. Thirty-two KOTs, 15 radicular cysts, and 08 dental follicles were used for immunohistochemistry, evaluating the extent, intensity, labeling pattern, cellular compartment in the epithelium and stroma, and the presence of inflammation. E-cadherin was preserved in most cases of keratocystic odontogenic tumor. N-cadherin was increased in the tumor epithelium, a result that was positively correlated with the heterogeneous and nuclear immunoexpression of Slug in the epithelium; Slug also correlated with high Snail immunoexpression. N-cadherin was positively correlated with Slug in the stroma of keratocystic odontogenic tumors. The high immunoexpression of Snail and nuclear Slug in keratocystic odontogenic tumors suggests these proteins as transcription factors without necessarily participating in 'cadherin switching'. However, the knowledge of their induction of the epithelial-mesenchymal transition in odontogenic tumors is still limited. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Cosmopolitanism and Biogeography of the Genus Manganonema (Nematoda: Monhysterida) in the Deep Sea

PubMed Central

Zeppilli, Daniela; Vanreusel, Ann; Danovaro, Roberto

2011-01-01

Simple Summary The deep sea comprises more than 60% of the Earth surface, and likely represents the largest reservoir of as yet undiscovered biodiversity. Nematodes are the most abundant taxon on Earth and are particularly abundant and diverse in the deep sea. Nevertheless, knowledge of their biogeography especially in the deep sea is still at its infancy. This article explores the distribution of the genus Manganonema in the deep Atlantic Ocean and Mediterranean Sea providing new insights about this apparently rare deep-sea genus. Abstract Spatial patterns of species diversity provide information about the mechanisms that regulate biodiversity and are important for setting conservation priorities. Present knowledge of the biogeography of meiofauna in the deep sea is scarce. This investigation focuses on the distribution of the deep-sea nematode genus Manganonema, which is typically extremely rare in deep-sea sediment samples. Forty-four specimens of eight different species of this genus were recorded from different Atlantic and Mediterranean regions. Four out of the eight species encountered are new to science. We report here that this genus is widespread both in the Atlantic and in the Mediterranean Sea. These new findings together with literature information indicate that Manganonema is a cosmopolitan genus, inhabiting a variety of deep-sea habitats and oceans. Manganonema shows the highest diversity at water depths >4,000 m. Our data, therefore, indicate that this is preferentially an abyssal genus that is able, at the same time, to colonize specific habitats at depths shallower than 1,000 m. The analysis of the distribution of the genus Manganonema indicates the presence of large differences in dispersal strategies among different species, ranging from locally endemic to cosmopolitan. Lacking meroplanktonic larvae and having limited dispersal ability due to their small size, it has been hypothesized that nematodes have limited dispersal potential. However, the

Effect of culture medium on propagation and phenotype of corneal stroma-derived stem cells.

PubMed

Sidney, Laura E; Branch, Matthew J; Dua, Harminder S; Hopkinson, Andrew

2015-12-01

The limbal area of the corneal stroma has been identified as a source of mesenchymal-like stem cells, which have potential for exploitation as a cell therapy. However, the optimal culture conditions are disputed and few direct media comparisons have been performed. In this report, we evaluated several media types to identify the optimal for inducing an in vitro stem cell phenotype. Primary human corneal stroma-derived stem cells (CSSCs) were extracted from corneoscleral rims. Culture in seven different media types was compared: Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS); M199 with 20% FBS; DMEM-F12 with 20% serum replacement, basic fibroblast growth factor and leukemia inhibitory factor (SCM); endothelial growth medium (EGM); semi-solid MethoCult; serum-free keratinocyte medium (K-SFM); and StemPro-34. Effects on proliferation, morphology, protein and messenger RNA expression were evaluated. All media supported proliferation of CSSCs with the exception of K-SFM and StemPro-34. Morphology differed between media: DMEM produced large cells, whereas EGM produced very small cells. Culture in M199 produced a typical mesenchymal stromal cell phenotype with high expression of CD105, CD90 and CD73 but not CD34. Culture in SCM produced a phenotype more reminiscent of a progenitor cell type with expression of CD34, ABCG2, SSEA-4 and PAX6. Culture medium can significantly influence CSSC phenotype. SCM produced a cell phenotype closest to that of a pluripotent stem cell, and we consider it to be the most appropriate for development as a clinical-grade medium for the production of CSSC phenotypes suitable for cell therapy. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Arousal of cancer-associated stroma: overexpression of palladin activates fibroblasts to promote tumor invasion.

PubMed

Brentnall, Teresa A; Lai, Lisa A; Coleman, Joshua; Bronner, Mary P; Pan, Sheng; Chen, Ru

2012-01-01

Cancer-associated fibroblasts, comprised of activated fibroblasts or myofibroblasts, are found in the stroma surrounding solid tumors. These myofibroblasts promote invasion and metastasis of cancer cells. Mechanisms regulating the activation of the fibroblasts and the initiation of invasive tumorigenesis are of great interest. Upregulation of the cytoskeletal protein, palladin, has been detected in the stromal myofibroblasts surrounding many solid cancers and in expression screens for genes involved in invasion. Using a pancreatic cancer model, we investigated the functional consequence of overexpression of exogenous palladin in normal fibroblasts in vitro and its effect on the early stages of tumor invasion. Palladin expression in stromal fibroblasts occurs very early in tumorigenesis. In vivo, concordant expression of palladin and the myofibroblast marker, alpha smooth muscle actin (α-SMA), occurs early at the dysplastic stages in peri-tumoral stroma and progressively increases in pancreatic tumorigenesis. In vitro introduction of exogenous 90 kD palladin into normal human dermal fibroblasts (HDFs) induces activation of stromal fibroblasts into myofibroblasts as marked by induction of α-SMA and vimentin, and through the physical change of cell morphology. Moreover, palladin expression in the fibroblasts enhances cellular migration, invasion through the extracellular matrix, and creation of tunnels through which cancer cells can follow. The fibroblast invasion and creation of tunnels results from the development of invadopodia-like cellular protrusions which express invadopodia proteins and proteolytic enzymes. Palladin expression in fibroblasts is triggered by the co-culture of normal fibroblasts with k-ras-expressing epithelial cells. Overall, palladin expression can impart myofibroblast properties, in turn promoting the invasive potential of these peri-tumoral cells with invadopodia-driven degradation of extracellular matrix. Palladin expression in

Role of VLA-4 and VLA-5 in ex vivo maintenance of human and pig hematopoiesis in human stroma-supported long-term cultures.

PubMed

Giovino, Maria A; Wang, Hui; Sykes, Megan; Yang, Yong-Guang

2005-03-01

The advantage of recipient hematopoiesis over that of xenogeneic donors poses a fundamental obstacle to the induction of xenograft tolerance through mixed hematopoietic chimerism. Here we explore the role of beta1 integrins in maintenance of human vs porcine hematopoiesis within a human hematopoietic environment. Porcine and human c-kit+ bone marrow cells were purified and cultured on human bone marrow stroma for 6 weeks. The role of VLA-4 and VLA-5 in the maintenance of porcine vs human hematopoiesis in this human stroma-supported long-term bone marrow culture (LTBMC) system was evaluated by using blocking mAbs that bind to both species. Blocking VLA-4 with HP2/1 inhibited both human and porcine hematopoiesis, whereas anti-VLA-5 (SAM-1) suppressed the function of human, but not porcine, hematopoietic cells. In mixed LTBMC of porcine and human cells on a human stroma, porcine hematopoietic cells were at a competitive disadvantage, as seen by a rapid decline in cellularity, including clonogenic progenitors. This disadvantage was substantially overcome by the addition of SAM-1. Furthermore, human, but not porcine, cell adhesion to human fibronectin was inhibited by arginine-glycine-aspartic acid (RGD) peptides. Taken together, these results indicate that VLA-4 plays critical role for porcine hematopoiesis in a human hematopoietic environment, and raise the possibility that porcine VLA-5 might be unable to bind the respective human ligand and/or to initiate adequate post-ligand-binding signaling. Thus, VLA-5 may provide a potential target for developing approaches to improve porcine hematopoiesis in human recipients.

Distribution of Cd and other cations between the stroma and thylakoids: a quantitative approach to the search for Cd targets in chloroplasts.

PubMed

Lysenko, Eugene A; Klaus, Alexander A; Kartashov, Alexander V; Kusnetsov, Victor V

2018-06-21

Plant growth and photosynthetic activity are usually inhibited due to the overall action of Cd on a whole organism, though few cadmium cations can invade chloroplasts in vivo. We found that in vivo, the major portion of Cd in barley chloroplasts is located in the thylakoids (80%), and the minor portion is in the stroma (20%). Therefore, the electron-transport chain in the thylakoids would be the likely target for direct Cd action in vivo. In vitro, we found the distribution of Cd to be shifted to the stroma (40-60%). In barley chloroplasts, the major portions of Mg, Fe, Mn, and Cu were found to be located in the thylakoids, and most Ca, Zn, and K in the stroma. This finding was true for both control and Cu- or Fe-treated plants. Treatment with Cd affected the contents of all cations, and the largest portions of Ca and Zn were in the thylakoids. Alterations of the K and Mn contents were caused by Cd, Cu, or Fe treatment; the levels of other cations in chloroplasts were changed specifically by Cd treatment. The quantity of Cd in chloroplasts was small in comparison to that of Mg, Ca, and Fe. In thylakoids, the amount of Cd was similar to that of Cu and comparable to the levels of Zn and Mn. Accordingly, the possible targets for direct Cd action in thylakoids are the Mn cluster, plastocyanin, carbonic anhydrase, or FtsH protease. The quantity of Cd in thylakoids is sufficient to replace a cation nearly completely at one of these sites or partially (20-30%) at many of these sites.

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.

The Big-Bubble Full Femtosecond Laser-Assisted Technique in Deep Anterior Lamellar Keratoplasty.

PubMed

Buzzonetti, Luca; Petrocelli, Gianni; Valente, Paola; Iarossi, Giancarlo; Ardia, Roberta; Petroni, Sergio; Parrilla, Rosa

2015-12-01

To describe the big-bubble full femtosecond laser-assisted (BBFF) technique, which could be helpful in standardizing the big-bubble technique in deep anterior lamellar keratoplasty (DALK). Ten eyes of 10 consecutive patients affected by keratoconus underwent the BBFF technique using the 150-kHz IntraLase femtosecond laser (Intra-Lase FS Laser; Abbott Medical Optics, Inc., Santa Ana, CA). A 9-mm diameter metal mask with a single fissure 0.7 mm wide oriented at the 12-o'clock position was positioned into the cone, over the laser glass. The laser performed a ring lamellar cut (internal diameter = 3 mm; external diameter = 8 mm) 100 µm above the thinnest point, with the photodisruption effectively occurring only in the corneal stroma corresponding to the fissure to create a deep stromal channel; subsequently, an anterior side cut created an arcuate incision, from the corneal surface to the deep stromal channel on the mask's opening site. The mask was removed and the laser performed a full lamellar cut 200 µm above the thinnest point to create a lamella. After the removal of the lamella, the air needle was inserted into the stromal channel and air was injected to achieve a big bubble. The big bubble was achieved in 9 eyes (all type 1 bubbles) and all procedures were completed as DALK. Preliminary results suggest that the BBFF technique could help in standardizing the big-bubble technique in DALK, reducing the "learning curve" for surgeons who approach this technique and the risks of intraoperative complications. Copyright 2015, SLACK Incorporated.

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.

[Interdisciplinary Diagnosis and Treatment of Deep Infiltrating Endometriosis].

PubMed

Alkatout, I; Egberts, J-H; Mettler, L; Doniec, M; Wedel, T; Jünemann, K-P; Becker, T; Jonat, W; Schollmeyer, T

2016-12-01

Endometriosis is the second most common benign female genital disease after uterine myoma. This review discusses the interdisciplinary approach to the treatment of deep infiltrating endometriosis. Endometriosis has been defined as the presence of endometrial glands and stroma outside the internal epithelial lining of the cavum uteri. As a consequence, endometriosis can cause a wide range of symptoms such as chronic pelvic pain, subfertility, dysmenorrhea, deep dyspareunia, cyclical bowel or bladder symptoms (e.g., dyschezia, bloating, constipation, rectal bleeding, diarrhoea and hematuria), abnormal menstrual bleeding, chronic fatigue or low back pain. Approx. 50 % of teenagers and up to 32 % of women of reproductive age, operated for chronic pelvic pain or dysmenorrhoea, suffer from endometriosis. The time interval between the first unspecific symptoms and the medical diagnosis of endometriosis is about 7 years. This is caused not only by the non-specific nature of the symptoms but also by the frequent lack of awareness on the part of the cooperating disciplines with which the patients have first contact. As the pathogenesis of endometriosis is not clearly understood, a causal treatment is still impossible. Treatment options include expectant management, analgesia, hormonal medical therapy, surgical intervention and the combination of medical treatment before and/or after surgery. The correct treatment for each patient should take into account the severity of the disease and whether the patient desires to have children. The treatment should be as radical as necessary and as minimal as possible. The recurrence rate among treated patients lies between 5 and > 60 % and is very much dependent on the integrated management and surgical skills of the respective hospital. Consequently, to optimise the individual patient's treatment, a high degree of interdisciplinary cooperation in diagnosis and treatment is crucial and should, especially in the case of deep

[A Case Report of Gastric Carcinoma with Lymphoid Stroma Differentially Diagnosed from Malignant Lymphoma].

PubMed

Yamada, Kazuto; Kosuga, Toshiyuki; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Morimura, Ryo; Murayama, Yasutoshi; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Kuroda, Junya; Kishimoto, Mitsuo; Konishi, Eiichi; Otsuji, Eigo

2017-11-01

A 49-year-old man was referred to our hospital for close examination of a submucosal tumor with ulceration located in the upper gastric body. PET-CT showed FDG uptake both in the gastric tumor and an enlarged lymph node. Although routine biopsies and EUS-FNA of this tumor did not demonstrate any malignant findings, he underwent excisional biopsy of the enlarged lymph nodes to rule out malignant lymphoma. Histopathological examination revealed that the excised specimens were metastatic nodes of poorly differentiated carcinoma probably from the known gastric tumor. Subsequently, he underwent total gastrectomy with D2, and histopathological findings confirmed the final diagnosis of gastric carcinoma with lymphoid stroma(GCLS). We report a case of GCLS that was difficult to diagnose.

Human Embryonic Stem Cell-Derived Mesenchymal Stroma Cells (hES-MSCs) Engraft In Vivo and Support Hematopoiesis without Suppressing Immune Function: Implications for Off-The Shelf ES-MSC Therapies

PubMed Central

Li, Ou; Tormin, Ariane; Sundberg, Berit; Hyllner, Johan; Le Blanc, Katarina; Scheding, Stefan

2013-01-01

Mesenchymal stroma cells (MSCs) have a high potential for novel cell therapy approaches in clinical transplantation. Commonly used bone marrow-derived MSCs (BM-MSCs), however, have a restricted proliferative capacity and cultures are difficult to standardize. Recently developed human embryonic stem cell-derived mesenchymal stroma cells (hES-MSCs) might represent an alternative and unlimited source of hMSCs. We therefore compared human ES-cell-derived MSCs (hES-MP002.5 cells) to normal human bone marrow-derived MSCs (BM-MSCs). hES-MP002.5 cells had lower yet reasonable CFU-F capacity compared with BM-MSC (8±3 versus 29±13 CFU-F per 100 cells). Both cell types showed similar immunophenotypic properties, i.e. cells were positive for CD105, CD73, CD166, HLA-ABC, CD44, CD146, CD90, and negative for CD45, CD34, CD14, CD31, CD117, CD19, CD 271, SSEA-4 and HLA-DR. hES-MP002.5 cells, like BM-MSCs, could be differentiated into adipocytes, osteoblasts and chondrocytes in vitro. Neither hES-MP002.5 cells nor BM-MSCs homed to the bone marrow of immune-deficient NSG mice following intravenous transplantation, whereas intra-femoral transplantation into NSG mice resulted in engraftment for both cell types. In vitro long-term culture-initiating cell assays and in vivo co-transplantation experiments with cord blood CD34+ hematopoietic cells demonstrated furthermore that hES-MP002.5 cells, like BM-MSCs, possess potent stroma support function. In contrast to BM-MSCs, however, hES-MP002.5 cells showed no or only little activity in mixed lymphocyte cultures and phytohemagglutinin (PHA) lymphocyte stimulation assays. In summary, ES-cell derived MSCs might be an attractive unlimited source for stroma transplantation approaches without suppressing immune function. PMID:23383153

Megadalton Complexes in the Chloroplast Stroma of Arabidopsis thaliana Characterized by Size Exclusion Chromatography, Mass Spectrometry, and Hierarchical Clustering*

PubMed Central

Olinares, Paul Dominic B.; Ponnala, Lalit; van Wijk, Klaas J.

2010-01-01

To characterize MDa-sized macromolecular chloroplast stroma protein assemblies and to extend coverage of the chloroplast stroma proteome, we fractionated soluble chloroplast stroma in the non-denatured state by size exclusion chromatography with a size separation range up to ∼5 MDa. To maximize protein complex stability and resolution of megadalton complexes, ionic strength and composition were optimized. Subsequent high accuracy tandem mass spectrometry analysis (LTQ-Orbitrap) identified 1081 proteins across the complete native mass range. Protein complexes and assembly states above 0.8 MDa were resolved using hierarchical clustering, and protein heat maps were generated from normalized protein spectral counts for each of the size exclusion chromatography fractions; this complemented previous analysis of stromal complexes up to 0.8 MDa (Peltier, J. B., Cai, Y., Sun, Q., Zabrouskov, V., Giacomelli, L., Rudella, A., Ytterberg, A. J., Rutschow, H., and van Wijk, K. J. (2006) The oligomeric stromal proteome of Arabidopsis thaliana chloroplasts. Mol. Cell. Proteomics 5, 114–133). This combined experimental and bioinformatics analyses resolved chloroplast ribosomes in different assembly and functional states (e.g. 30, 50, and 70 S), which enabled the identification of plastid homologues of prokaryotic ribosome assembly factors as well as proteins involved in co-translational modifications, targeting, and folding. The roles of these ribosome-associating proteins will be discussed. Known RNA splice factors (e.g. CAF1/WTF1/RNC1) as well as uncharacterized proteins with RNA-binding domains (pentatricopeptide repeat, RNA recognition motif, and chloroplast ribosome maturation), RNases, and DEAD box helicases were found in various sized complexes. Chloroplast DNA (>3 MDa) was found in association with the complete heteromeric plastid-encoded DNA polymerase complex, and a dozen other DNA-binding proteins, e.g. DNA gyrase, topoisomerase, and various DNA repair enzymes. The

Evidence of iodine storage within thyroid stroma after iodine treatment: imaging by secondary ion mass spectometry (SIMS) microscopy in goitrous tissue.

PubMed

el May, M; Jeusset, J; el May, A; Mtimet, S; Fragu, P

1996-06-01

We measured the 127I distribution within tyroid tissue to find out where intrathyroid iodine was deposited during iodine treatment in eight Tunisian female patients (aged 33-58 yr) with endemic euthyroid goiter. Before surgery, five patients were treated during 6 months either by Lugol's solution (group 1: three patients) or by Lugol's and L-thyroxine (group 2: two patients). All patients remained euthyroid during the course of the treatment, which supplied 3.8 mg/day iodine. Three other patients did not receive Lugol's solution (control group). Secondary ion mass spectrometry microscopy was used to map 127-I quantitatively on thyroid sections. Specimens obtained at thyroid surgery were divided macroscopically into nodular and extranodular tissue and chemically fixed to preserve organified iodine. The iodine profile of patients in group 1 did not differ from that in group 2: large amounts of iodine were localized in thyroid follicles and stroma of both nodular and extranodular tissues. In the control group, iodine within stroma was found only in the extranodular tissue. Despite the limited number of patients studied, these data suggest that stromal iodine might represent a storage compartment in times of large iodine supply.

Infrared spectroscopic imaging: Label-free biochemical analysis of stroma and tissue fibrosis.

PubMed

Nazeer, Shaiju S; Sreedhar, Hari; Varma, Vishal K; Martinez-Marin, David; Massie, Christine; Walsh, Michael J

2017-11-01

Infrared spectroscopic tissue imaging is a potentially powerful adjunct tool to current histopathology techniques. By coupling the biochemical signature obtained through infrared spectroscopy to the spatial information offered by microscopy, this technique can selectively analyze the chemical composition of different features of unlabeled, unstained tissue sections. In the past, the tissue features that have received the most interest were parenchymal and epithelial cells, chiefly due to their involvement in dysplasia and progression to carcinoma; however, the field has recently turned its focus toward stroma and areas of fibrotic change. These components of tissue present an untapped source of biochemical information that can shed light on many diverse disease processes, and potentially hold useful predictive markers for these same pathologies. Here we review the recent applications of infrared spectroscopic imaging to stromal and fibrotic regions of diseased tissue, and explore the potential of this technique to advance current capabilities for tissue analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Apparent diffusion coefficient value as a biomarker reflecting morphological and biological features of prostate cancer.

PubMed

Bae, Hyeyeol; Yoshida, Soichiro; Matsuoka, Yoh; Nakajima, Hiroshi; Ito, Eisaku; Tanaka, Hiroshi; Oya, Miyako; Nakayama, Takayuki; Takeshita, Hideki; Kijima, Toshiki; Ishioka, Junichiro; Numao, Noboru; Koga, Fumitaka; Saito, Kazutaka; Akashi, Takumi; Fujii, Yasuhisa; Kihara, Kazunori

2014-03-01

To assess whether there is an association between the apparent diffusion coefficient (ADC) value and the pathological characteristics of prostate cancer. The study cohort consisted of 29 consecutive patients with prostate cancer treated with radical prostatectomy. All patients underwent diffusion-weighted MRI before the prostate biopsy. In 42 tumor foci, the associations of the ADC values with the clinicopathological characteristics and Ki-67 labeling index (LI) were analyzed. High-grade cancers (Gleason score [GS] ≥ 4 + 3), larger cancers (maximum diameter (MD) ≥ 16 mm), and highly proliferating cancers (Ki-67 LI ≥ 4.43 %) had significantly lower ADC values, respectively (P < .001, P = .008, and P = .044, respectively). There was no significant difference in ADC value according to age, prostate-specific antigen, presence of extra-prostatic extension, and intra-tumoral stroma proportion. Multivariate analysis showed that GS, Ki-67 LI, and MD had independent and significant correlations with ADC value (P < .001, P = .006, and P = .002, respectively). Low ADC tumors (<0.52 × 10(-3) mm(2)/s) are likely to be high-grade cancer foci compared with high ADC tumors (relative risk: 65.2). The sensitivity and specificity of the ADC value to predict high-grade cancer foci are 81.8 and 93.5 %, respectively. A low ADC value reflects the morphological and biological features of prostate cancer. Analyzing the ADC value may make it possible to more precisely predict the cancer aggressiveness of each focus before treatment.

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.

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

Apparent dietary intake in remote aboriginal communities.

PubMed

Lee, A J; O'Dea, K; Mathews, J D

1994-06-01

Apparent per capita food and nutrient intake in six remote Australian Aboriginal communities using the 'store-turnover' method is described. The method is based on the analysis of community-store food invoices. The face validity of the method supports the notion that, under the unique circumstances of remote Aboriginal communities, the turnover of foodstuffs from the community store is a useful measure of apparent dietary intake for the community as a whole. In all Aboriginal communities studied, the apparent intake of energy, sugars and fat was excessive, while the apparent intake of dietary fibre and several nutrients, including folic acid, was low. White sugar, flour, bread and meat provided in excess of 50 per cent of the apparent total energy intake. Of the apparent high fat intake, fatty meats contributed nearly 40 per cent in northern coastal communities and over 60 per cent in central desert communities. Sixty per cent of the apparent high intake of sugars was derived from sugar per se in both regions. Compared with national Australian apparent consumption data, intakes of sugar, white flour and sweetened carbonated beverages were much higher in Aboriginal communities, and intakes of wholemeal bread, fruit and vegetables were much lower. Results of the store-turnover method have important implications for community-based nutrition intervention programs.

Diagnostic value of inflammatory cell infiltrates, tumor stroma percentage and disease-free survival in patients with colorectal cancer

PubMed Central

Jakubowska, Katarzyna; Kisielewski, Wojciech; Kańczuga-Koda, Luiza; Koda, Mariusz; Famulski, Waldemar

2017-01-01

The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC). In addition, the correlation between cellular inflammatory infiltration, and anatomoclinical and histopathological features of patients was evaluated. The study involved 160 patients diagnosed with primary operable CRC. The local inflammatory infiltrate was assessed in the invasive front and center of the tumor using light microscopy with hematoxylin and eosin (H&E) staining, according to the Klintrup-Makinen criteria, tumor stroma percentage, and Glasgow microenvironment score. The inflammatory infiltrate in the invasive front of the tumor was correlated with gender (P=0.018), the invasion of blood vessels (P=0.020) and lymph vessels (P=0.038), the presence of tumor-infiltrating lymphocytes in the invasive front (P=0.033) and center (P<0.001) of the tumor, fibrosis (P<0.001), and the degree of desmoplasmic stroma (P=0.004). In contrast, inflammatory infiltration in the center of the tumor was associated with the tumor node metastasis stage (P=0.012), Dukes' stage (P=0.009), primary tumor stage (P=0.036), lymph node status (P=0.005), number of lymph nodes (P=0.006), invasion of lymph node pouches (P=0.021), size of lymph node metastasis (P=0.025) and the degree of desmoplasmic stroma (P=0.002). The low-group, who demonstrated an absent or weak inflammatory cell infiltrate in the invasive front of the tumor, had a statistically significant shorter

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

PubMed

Santamaria-Martínez, Albert; Barquinero, Jordi; Barbosa-Desongles, Anna; Hurtado, Antoni; Pinós, Tomàs; Seoane, Joan; Poupon, Marie-France; Morote, Joan; Reventós, 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(-), CD81(+) and Sca-1(+)). We also demonstrated that SP clonal cells secrete transforming growth factor beta1 (TGF-beta1) 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-beta1 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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santamaria-Martinez, Albert; Universitat de Barcelona, Barcelona; Barquinero, Jordi

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 andmore » 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.« less

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.

Adult-onset renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusion with smooth muscle stroma and abnormal vessels.

PubMed

Kuroda, Naoto; Tamura, Masato; Tanaka, Yukichi; Hes, Ondrej; Michal, Michal; Inoue, Kaori; Ohara, Masahiko; Mizuno, Keiko; Lee, Gang-Hong

2009-07-01

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion has been recently identified. Herein is presented a case of RCC with Xp11.2 translocations/TFE3 gene fusions with unusual histological findings. A 68-year-old Japanese woman was incidentally found to have a renal mass on CT. Histological examination showed clear cell neoplasm with alveolar and papillary growth patterns. The nuclear atypia corresponded to Fuhrman grade 3. Additionally, smooth muscle stroma was observed and abnormal vessels showing a heterogeniety in thickness were also identified. On immunohistochemistry, neoplastic cells were diffusely positive for transcription factor E3 (TFE3) and Melan A, and focally positive for CD10 and RCC marker. The smooth muscle stroma was positive for alpha-smooth muscle actin and h-caldesmon, but reverse transcription-polymerase chain reaction of the tumor using frozen material could not detect any previously reported chimeric transcripts including ASPL-TFE3, PRCC-TFE3, CLTC-TFE3, PSF-TFE3 or NoNo-TFE3. G-band karyotype was unsuccessful. Pathologists should pay attention to the afore-described unusual stromal reaction of adult-onset RCC associated with Xp11.2 translocations/TFE3 gene fusions.

Both the stroma and thylakoid lumen of tobacco chloroplasts are competent for the formation of disulphide bonds in recombinant proteins.

PubMed

Bally, Julia; Paget, Eric; Droux, Michel; Job, Claudette; Job, Dominique; Dubald, Manuel

2008-01-01

Plant chloroplasts are promising vehicles for recombinant protein production, but the process of protein folding in these organelles is not well understood in comparison with that in prokaryotic systems, such as Escherichia coli. This is particularly true for disulphide bond formation which is crucial for the biological activity of many therapeutic proteins. We have investigated the capacity of tobacco (Nicotiana tabacum) chloroplasts to efficiently form disulphide bonds in proteins by expressing in this plant cell organelle a well-known bacterial enzyme, alkaline phosphatase, whose activity and stability strictly depend on the correct formation of two intramolecular disulphide bonds. Plastid transformants have been generated that express either the mature enzyme, localized in the stroma, or the full-length coding region, including its signal peptide. The latter has the potential to direct the recombinant alkaline phosphatase into the lumen of thylakoids, giving access to this even less well-characterized organellar compartment. We show that the chloroplast stroma supports the formation of an active enzyme, unlike a normal bacterial cytosol. Sorting of alkaline phosphatase to the thylakoid lumen occurs in the plastid transformants translating the full-length coding region, and leads to larger amounts and more active enzyme. These results are compared with those obtained in bacteria. The implications of these findings on protein folding properties and competency of chloroplasts for disulphide bond formation are discussed.

Fronts and intrusions in the upper Deep Polar Water of the Eurasian and Makarov basins

NASA Astrophysics Data System (ADS)

Kuzmina, Natalia; Rudels, Bert; Zhurbas, Natalia; Lyzhkov, Dmitry

2013-04-01

CTD data obtained in the Arctic Basin are analyzed to describe structural features of intrusive layers and fronts encountered in the upper Deep Polar Water. This work is an extension of Arctic intrusions studies by Rudels et al. (1999) and Kuzmina et al. (2011). Numerous examples of fronts and intrusions observed in a deep layer (depth range of 600-1300 m) in the Eurasian and Makarov basins where salinity is increasing, and temperature is decreasing with depth (stable-stable thermohaline stratification), are described. The data are used to estimate hydrological parameters capable of determining different types of fronts and characterizing intrusive layers depending on the front structure. Coherence of intrusive layers is shown to get broken with the change of front structure. An evidence is found that enhanced turbulent mixing above local bottom elevations can prevent from intrusive layering. A linear stability model description of the observed intrusions is developed based on the Merryfield's (2000) assumption that interleaving is caused by differential mixing. Theoretical analysis is focused on prediction of the slopes of unstable modes at baroclinic and thermohaline fronts. Apparent vertical diffusivity due to turbulent mixing at baroclinic and thermohaline fronts is estimated on the basis of comparison of observed intrusion slopes with modeled slopes of the most unstable modes. Apparent lateral diffusivity is estimated too, based on Joyce (1980) approach. These estimates show that intrusive instability of fronts caused by differential mixing can result in sizable values of apparent lateral heat diffusivity in the deep Arctic layer that are quite comparable with those of the upper and intermediate Arctic layers (Walsh, Carmack, 2003; Kuzmina et al., 2011).

Subterranean gravity and other deep hole geophysics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stacey, F.D.

1983-01-01

The early history of the determination of the Newtonian gravitational constant, G, was closely linked with the developments of geodesy and gravity surveying. The current search for non-Newtonian effects that may provide an experimental guide to unification theories has led to our retracting some of this history. Modern geophysical techniques and facilities, using especially mines and deep ocean probes, permit absolute measurements of G for distance scales up to a few kilometers. Although the accuracy of the very long range determinations cannot equal that of the best laboratory measurements, they are crucial to assessment of the possibility of a scalemore » dependence of G. Preliminary data give values of G on a scale 100-1000 m biased about 1% higher than the laboratory value. Possibilities of systematic error compel us to question this apparently significant bias but it provides the incentive for better controlled large scale experiments. Several are in progress or under development. A particular difficulty concerns the measurement of in situ density. Even for hard rock, release from overburden pressure causes microcracks and pores to open. Natural pore closure is effective only with deep burial and for this reason there are advantages in deep instrument placement for several geophysical studies.« less

Fabrication of a corneal model composed of corneal epithelial and endothelial cells via a collagen vitrigel membrane functioned as an acellular stroma and its application to the corneal permeability test of chemicals.

PubMed

Yamaguchi, Hiroyuki; Takezawa, Toshiaki

2018-05-29

A collagen vitrigel membrane (CVM) we developed can function as both a scaffold for cells and a pathway for chemicals. To extrapolate the corneal permeability of chemicals in vivo, we proposed six corneal models using the CVM. Thin and thick CVMs were utilized as models for Bowman's membrane (BM) and an acellular-stroma (AS), respectively. Models for a corneal epithelium (CEpi), a corneal epithelium-acellular stroma (CEpi-AS), a corneal epithelium-endothelium (CEpi-Endo) and a corneal epithelium-acellular stroma-endothelium (CEpi-AS-Endo) were fabricated by culturing corneal epithelial cells and/or corneal endothelial cells on the surface of CVMs. Subsequently, the permeability coefficient (P app ) value of each model was calculated using five chemicals with different molecular radii; cyanocobalamin and four FITC-dextrans (FD-4, FD-10, FD-20 and FD-40). The slopes of P app versus molecular radii of those chemicals in the both BM and AS models were almost similar to data using an excised rabbit corneal stroma. The ratios of P app values in models for BM, CEpi and CEpi-Endo against those in data using an excised rabbit cornea were calculated as 75.4, 6.4 and 4.5-folds for FD-4 and 38.7, 10.0 and 4.2-folds for FD-10, respectively. Similarly, those in models for AS, CEpi-AS and CEpi-AS-Endo were calculated as 26.1, 2.5 and 0.6-folds for FD-4 and 26.1, 1.5 and 0.6-folds for FD-10, respectively. These results suggest that the CEpi-AS-Endo model with both the barrier function of corneal cell layers and the diffusion capacity of chemicals in thick CVM is most appropriate for extrapolating the corneal permeability of chemicals in vivo . The American Society for Pharmacology and Experimental Therapeutics.

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.

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

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

Malignant Mesothelioma in the Thoracic Cavity of a Crj:CD(SD) Rat Characterized by Round Hyalinous Stroma.

PubMed

Doi, Takuya; Kotani, Yuri; Takahashi, Kazuaki; Hashimoto, Satomi; Yamada, Naoaki; Kokoshima, Hiroko; Tomonari, Yuki; Wako, Yumi; Tsuchitani, Minoru

2010-06-01

Spontaneous malignant mesothelioma was found in a 104-week-old male Crj:CD(SD) rat. The tumor was scattered on the surface of the lung, heart, mediastinal pleura and thoracic wall and metastasized to the alveolar septa. Histopathologically, small flattened or cuboidal tumor cells proliferated with stroma, formed almost normal papillary structures and reacted positively to colloidal iron stain and immunohistochemical staining for mesothelin. Round hyalinous stromata were pronounced, which is a characteristic feature, and the possible reason for this is as follows; at first, a small amount of collagen fibers was formed in the center of the clusters of several tumor cells, and then the cell clusters expanded like balloons with an increase in the collagen fibers.

Deep trees: Woodfall biodiversity dynamics in present and past oceans

NASA Astrophysics Data System (ADS)

Sigwart, Julia D.

2017-03-01

Marine deposits of sunken wood provide an important habitat for deep-sea biota, including an extensive wood-endemic invertebrate fauna. These habitats are important in their own right; many species on organic falls are not able to survive in other deep sea ecosystems. Evolutionary transitions of species among various chemosynthesis-based ecosystems does not proceed deliberately from organic falls toward hydrothermal vents. Polyplacophoran molluscs (chitons) are generally rare in deep-sea systems but are found in comparatively high diversity and abundance on tropical sunken wood. A new time-calibrated phylogeny for the predominantly deep-sea order Lepidopleurida shows the chiton lineages found in sunken wood habitats do not comprise a single clade or radiation, but represents a minimum of three independent radiations in the Pacific alone. Most marine invertebrate groups diversified in the deep sea following the end Cretaceous extinction event; by contrast, sunken-wood chitons may have persisted in these habitats for longer than other animals. Fossil chitons from the early Carboniferous (ca. 350 Mya) have strong similarities to modern wood-endemic taxa, yet the common ancestor of living Lepidopleurida occurred much later in the Triassic and did not apparently rely on woodfall. Clades within Lepidopleurida that occupy wood habitats in the tropical Pacific probably arose in the Jurassic, which corresponds to evidence from the fossil record, but with an additional separate colonisation more recently in the early Paleogene. Wood-endemic chiton species encompass multiple independent evolutionary origins of co-occurring wood species, and these separate lineages correspond to differences in micohabitat and feeding strategies. These patterns demonstrate the ongoing evolutionary linkages between terrestrial and deep marine environments, and the opportunistic adaptations of deep-sea organisms.

Interference figures of polarimetric interferometry analysis of the human corneal stroma

PubMed Central

Mastropasqua, Rodolfo; Nubile, Mario; Salgari, Niccolò; Lanzini, Manuela; Calienno, Roberta; Mattei, Peter A.; Sborgia, Alessandra; Agnifili, Luca

2017-01-01

A rotating polarimetric 90°-cross linear-filter interferometry system was used to detect the morphological characteristics and features of interference patterns produced in in-vivo corneal stroma in healthy human corneas of 23 subjects. The characteristic corneal isogyres presenting with an evident cross-shaped pattern, grossly aligned with the fixation axis, were observed in all patients with centers within the pupillary dark area, impeding the exact determination of the center point. During the rotational scan in 78.3% of the eyes the cross-shaped pattern of the isogyre gradually separated to form two distinct hyperbolic arcs in opposite quadrants, reaching their maximal separation at 45 degrees with respect to angle of cross-shaped pattern formation. The corneal cross and hyperbolic-pattern repeated every 90° throughout the 360° rotational scan. While the interpretation of the isogyres presents particular difficulties, two summary parameters can be extracted for each cornea: the presence/orientation of a single or two dark areas in post-processed images and isochromes. However, the development of dedicated software for semi-quantitative analysis of these parameters and enantiomorphism may become available in the near future. The possible application of polarimetric interferometry in the field of both corneal pathologies and corneal surgery may be of great interest for clinical purposes. PMID:28570631

Interference figures of polarimetric interferometry analysis of the human corneal stroma.

PubMed

Mastropasqua, Rodolfo; Nubile, Mario; Salgari, Niccolò; Lanzini, Manuela; Calienno, Roberta; Mattei, Peter A; Sborgia, Alessandra; Agnifili, Luca

2017-01-01

A rotating polarimetric 90°-cross linear-filter interferometry system was used to detect the morphological characteristics and features of interference patterns produced in in-vivo corneal stroma in healthy human corneas of 23 subjects. The characteristic corneal isogyres presenting with an evident cross-shaped pattern, grossly aligned with the fixation axis, were observed in all patients with centers within the pupillary dark area, impeding the exact determination of the center point. During the rotational scan in 78.3% of the eyes the cross-shaped pattern of the isogyre gradually separated to form two distinct hyperbolic arcs in opposite quadrants, reaching their maximal separation at 45 degrees with respect to angle of cross-shaped pattern formation. The corneal cross and hyperbolic-pattern repeated every 90° throughout the 360° rotational scan. While the interpretation of the isogyres presents particular difficulties, two summary parameters can be extracted for each cornea: the presence/orientation of a single or two dark areas in post-processed images and isochromes. However, the development of dedicated software for semi-quantitative analysis of these parameters and enantiomorphism may become available in the near future. The possible application of polarimetric interferometry in the field of both corneal pathologies and corneal surgery may be of great interest for clinical purposes.

Correlation between apparent diffusion coefficient and histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy.

PubMed

Wang, Jifei; Sun, Meili; Liu, Dawei; Hu, Xiaoshu; Pui, Margaret H; Meng, Quanfei; Gao, Zhenhua

2017-08-01

Background Neoadjuvant chemotherapy has made limb-salvage surgery possible for the patients with osteosarcoma. Diffusion-weighted magnetic resonance imaging (DWI) has been used to monitor chemotherapy response. Purpose To correlate the apparent diffusion coefficient (ADC) values with histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy. Material and Methods Twelve patients with osteoblastic (n = 7), chondroblastic (n = 4), and fibroblastic (n = 1) osteosarcomas underwent post-chemotherapy DWI before limb-salvage surgery. ADCs corresponding to 127 histological tissue samples from the 12 resected specimens were compared to histological features. Results The mean ADC value of non-cartilaginous viable tumor (38/91, ADC = 1.22 ± 0.03 × 10 -3  mm 2 /s) was significantly ( P < 0.001) lower than that of non-cartilaginous tumor cell necrosis without stroma disintegration (25/91, ADC =1.77 ± 0.03 × 10 -3  mm 2 /s), cartilaginous viable tumor (14/91, ADC = 2.19 ± 0.04 × 10 -3  mm 2 /s), and cystic areas including liquefied necrosis, blood space, and secondary aneurysmal bone cyst (14/91, ADC = 2.29 ± 0.05 × 10 -3  mm 2 /s). The mean ADC value of non-cartilaginous tumor cell necrosis was also significantly ( P < 0.001) smaller than those of viable cartilaginous tumor and cystic/hemorrhagic necrosis whereas the mean ADC values were not significantly ( P > 0.05) different between viable cartilaginous tumor and cystic/hemorrhagic necrosis. Conclusion DWI allows assessment of tumor necrosis after neoadjuvant chemotherapy by ADC differences between viable tumor and necrosis in fibroblastic and osteoblastic osteosarcomas whereas viable chondroblastic osteosarcoma has high ADC and cannot be distinguished reliably from necrosis.

Apparent diffusion coefficient as it relates to histopathology findings in post-chemotherapy nephroblastoma: a feasibility study.

PubMed

Littooij, Annemieke S; Nikkels, Peter G; Hulsbergen-van de Kaa, Christina A; van de Ven, Cees P; van den Heuvel-Eibrink, Marry M; Olsen, Øystein E

2017-11-01

Nephroblastomas represent a group of heterogeneous tumours with variable proportions of distinct histopathological components. The purpose of this study was to investigate whether direct comparison of apparent diffusion coefficient (ADC) measurements with post-resection histopathology subtypes is feasible and whether ADC metrics are related to histopathological components. Twenty-three children were eligible for inclusion in this retrospective study. All children had MRI including diffusion-weighted imaging (DWI) after preoperative chemotherapy, just before tumour resection. A pathologist and radiologist identified corresponding slices at MRI and postoperative specimens using tumour morphology, the upper/lower calyx and hilar vessels as reference points. An experienced reader performed ADC measurements, excluding non-enhancing areas. A pathologist reviewed the corresponding postoperative slides according to the international standard guidelines. We tested potential associations with the Spearman rank test. Side-by-side comparison of MRI-DWI with corresponding histopathology slides was feasible in 15 transverse slices in 9 lesions in 8 patients. Most exclusions were related to extensive areas of necrosis/haemorrhage. In one lesion correlation was not possible because of the different orientation of sectioning of the specimen and MRI slices. The 25% ADC showed a strong relationship with percentage of blastema (Spearman rho=-0.71, P=0.003), whereas median ADC was strongly related to the percentage stroma (Spearman rho=0.74, P=0.002) at histopathology. Side-by-side comparison of MRI-DWI and histopathology is feasible in the majority of patients who do not have massive necrosis and hemorrhage. Blastemal and stromal components have a strong linear relationship with ADC markers.

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.

The deep, hot biosphere: Twenty-five years of retrospection.

PubMed

Colman, Daniel R; Poudel, Saroj; Stamps, Blake W; Boyd, Eric S; Spear, John R

2017-07-03

Twenty-five years ago this month, Thomas Gold published a seminal manuscript suggesting the presence of a "deep, hot biosphere" in the Earth's crust. Since this publication, a considerable amount of attention has been given to the study of deep biospheres, their role in geochemical cycles, and their potential to inform on the origin of life and its potential outside of Earth. Overwhelming evidence now supports the presence of a deep biosphere ubiquitously distributed on Earth in both terrestrial and marine settings. Furthermore, it has become apparent that much of this life is dependent on lithogenically sourced high-energy compounds to sustain productivity. A vast diversity of uncultivated microorganisms has been detected in subsurface environments, and we show that H 2 , CH 4 , and CO feature prominently in many of their predicted metabolisms. Despite 25 years of intense study, key questions remain on life in the deep subsurface, including whether it is endemic and the extent of its involvement in the anaerobic formation and degradation of hydrocarbons. Emergent data from cultivation and next-generation sequencing approaches continue to provide promising new hints to answer these questions. As Gold suggested, and as has become increasingly evident, to better understand the subsurface is critical to further understanding the Earth, life, the evolution of life, and the potential for life elsewhere. To this end, we suggest the need to develop a robust network of interdisciplinary scientists and accessible field sites for long-term monitoring of the Earth's subsurface in the form of a deep subsurface microbiome initiative.

The deep, hot biosphere: Twenty-five years of retrospection

PubMed Central

Colman, Daniel R.; Poudel, Saroj; Stamps, Blake W.; Boyd, Eric S.; Spear, John R.

2017-01-01

Twenty-five years ago this month, Thomas Gold published a seminal manuscript suggesting the presence of a “deep, hot biosphere” in the Earth’s crust. Since this publication, a considerable amount of attention has been given to the study of deep biospheres, their role in geochemical cycles, and their potential to inform on the origin of life and its potential outside of Earth. Overwhelming evidence now supports the presence of a deep biosphere ubiquitously distributed on Earth in both terrestrial and marine settings. Furthermore, it has become apparent that much of this life is dependent on lithogenically sourced high-energy compounds to sustain productivity. A vast diversity of uncultivated microorganisms has been detected in subsurface environments, and we show that H2, CH4, and CO feature prominently in many of their predicted metabolisms. Despite 25 years of intense study, key questions remain on life in the deep subsurface, including whether it is endemic and the extent of its involvement in the anaerobic formation and degradation of hydrocarbons. Emergent data from cultivation and next-generation sequencing approaches continue to provide promising new hints to answer these questions. As Gold suggested, and as has become increasingly evident, to better understand the subsurface is critical to further understanding the Earth, life, the evolution of life, and the potential for life elsewhere. To this end, we suggest the need to develop a robust network of interdisciplinary scientists and accessible field sites for long-term monitoring of the Earth’s subsurface in the form of a deep subsurface microbiome initiative. PMID:28674200

Ab initio calculations of deep-level carrier nonradiative recombination rates in bulk semiconductors.

PubMed

Shi, Lin; Wang, Lin-Wang

2012-12-14

Nonradiative carrier recombination is of both applied and fundamental interest. Here a novel algorithm is introduced to calculate such a deep level nonradiative recombination rate using the ab initio density functional theory. This algorithm can calculate the electron-phonon coupling constants all at once. An approximation is presented to calculate the phonon modes for one impurity in a large supercell. The neutral Zn impurity site together with a N vacancy is considered as the carrier-capturing deep impurity level in bulk GaN. Its capture coefficient is calculated as 5.57 × 10(-10)cm(3)/s at 300 K. We found that there is no apparent onset of such a nonradiative process as a function of temperature.

Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth.

PubMed

Mathivet, Thomas; Bouleti, Claire; Van Woensel, Matthias; Stanchi, Fabio; Verschuere, Tina; Phng, Li-Kun; Dejaegher, Joost; Balcer, Marly; Matsumoto, Ken; Georgieva, Petya B; Belmans, Jochen; Sciot, Raf; Stockmann, Christian; Mazzone, Massimiliano; De Vleeschouwer, Steven; Gerhardt, Holger

2017-12-01

Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages. This vascular phenotype transition was accompanied by recruitment of predominantly pro-inflammatory M1-like macrophages in the early stages, followed by in situ repolarization to M2-like macrophages, which produced VEGF-A and relocate to perivascular areas. A similar enrichment and perivascular accumulation of M2 versus M1 macrophages correlated with vessel dilation and malignancy in human glioma samples of different WHO malignancy grade. Targeting macrophages using anti-CSF1 treatment restored normal blood vessel patterning and function. Combination treatment with chemotherapy showed survival benefit, suggesting that targeting macrophages as the key driver of blood vessel dysmorphia in glioma progression presents opportunities to improve efficacy of chemotherapeutic agents. We propose that vessel dysfunction is not simply a general feature of tumor vessel formation, but rather an emergent property resulting from a dynamic and functional reorganization of the tumor stroma and its angiogenic influences. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Multimodel analysis of anisotropic diffusive tracer-gas transport in a deep arid unsaturated zone

USGS Publications Warehouse

Green, Christopher T.; Walvoord, Michelle Ann; Andraski, Brian J.; Striegl, Robert G.; Stonestrom, David A.

2015-01-01

Gas transport in the unsaturated zone affects contaminant flux and remediation, interpretation of groundwater travel times from atmospheric tracers, and mass budgets of environmentally important gases. Although unsaturated zone transport of gases is commonly treated as dominated by diffusion, the characteristics of transport in deep layered sediments remain uncertain. In this study, we use a multimodel approach to analyze results of a gas-tracer (SF6) test to clarify characteristics of gas transport in deep unsaturated alluvium. Thirty-five separate models with distinct diffusivity structures were calibrated to the tracer-test data and were compared on the basis of Akaike Information Criteria estimates of posterior model probability. Models included analytical and numerical solutions. Analytical models provided estimates of bulk-scale apparent diffusivities at the scale of tens of meters. Numerical models provided information on local-scale diffusivities and feasible lithological features producing the observed tracer breakthrough curves. The combined approaches indicate significant anisotropy of bulk-scale diffusivity, likely associated with high-diffusivity layers. Both approaches indicated that diffusivities in some intervals were greater than expected from standard models relating porosity to diffusivity. High apparent diffusivities and anisotropic diffusivity structures were consistent with previous observations at the study site of rapid lateral transport and limited vertical spreading of gas-phase contaminants. Additional processes such as advective oscillations may be involved. These results indicate that gases in deep, layered unsaturated zone sediments can spread laterally more quickly, and produce higher peak concentrations, than predicted by homogeneous, isotropic diffusion models.

Intensity and Pattern of Enhancement on CESM: Prognostic Significance and its Relation to Expression of Podoplanin in Tumor Stroma - A Preliminary Report.

PubMed

Luczynska, Elzbieta; Niemiec, Joanna; Heinze, Sylwia; Adamczyk, Agnieszka; Ambicka, Aleksandra; Marcyniuk, Paulina; Rudnicki, Wojciech; Mitus, Jerzy W; Dyczek, Sonia; Rys, Janusz; Sas-Korczynska, Beata

2018-02-01

It is possible that the degree of enhancement on contrast-enhanced spectral mammography (CESM), a new diagnostic method, might provide prognostic information for breast cancer patients. Therefore, in a group of 82 breast cancer patients, we analyzed the prognostic significance of degree and pattern of enhancement on CESM as well as its relation to: (a) breast cancer immunophenotype (based on ER/PR/HER2 status) (b) podoplanin expression in cancer stroma (lymphatic vessel density plus podoplanin-positivity of cancer-associated fibroblasts), and (c) other histological parameters. For each tumor the intensity of enhancement on CESM was qualitatively assessed as strong or weak/medium, while the pattern - as homogenous and heterogenous. Herein we report, for the first time, that strong and heterogenous enhancement on CESM was related to unfavorable disease-free survival of breast cancer patients (p=0.005). Moreover, the strong enhancement was more frequent in large and node-positive tumors (pT>1, pN>0) (p=0.002), as well as in carcinomas with podoplanin-sparse stroma (p=0.008). Intensity and pattern of enhancement on CESM might provide (together with the results of other diagnostic imaging methods) not only the confirmation of presence or absence of tumor, but also prognostic information. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Observations that Constrain the Scaling of Apparent Stress

NASA Astrophysics Data System (ADS)

McGarr, A.; Fletcher, J. B.

2002-12-01

Slip models developed for major earthquakes are composed of distributions of fault slip, rupture time, and slip velocity time function over the rupture surface, as divided into many smaller subfaults. Using a recently-developed technique, the seismic energy radiated from each subfault can be estimated from the time history of slip there and the average rupture velocity. Total seismic energies, calculated by summing contributions from all of the subfaults, agree reasonably well with independent estimates based on seismic energy flux in the far-field at regional or teleseismic distances. Two recent examples are the 1999 Izmit, Turkey and the 1999 Hector Mine, California earthquakes for which the NEIS teleseismic measurements of radiated energy agree fairly closely with seismic energy estimates from several different slip models, developed by others, for each of these events. Similar remarks apply to the 1989 Loma Prieta, 1992 Landers, and 1995 Kobe earthquakes. Apparent stresses calculated from these energy and moment results do not indicate any moment or magnitude dependence. The distributions of both fault slip and seismic energy radiation over the rupture surfaces of earthquakes are highly inhomogeneous. These results from slip models, combined with underground and seismic observations of slip for much smaller mining-induced earthquakes, can provide stronger constraint on the possible scaling of apparent stress with moment magnitude M or seismic moment. Slip models for major earthquakes in the range M6.2 to M7.4 show maximum slips ranging from 1.6 to 8 m. Mining-induced earthquakes at depths near 2000 m in South Africa are associated with peak slips of 0.2 to 0.37 m for events of M4.4 to M4.6. These maximum slips, whether derived from a slip model or directly observed underground in a deep gold mine, scale quite definitively as the cube root of the seismic moment. In contrast, peak slip rates (maximum subfault slip/rise time) appear to be scale invariant. A 1.25 m

Attention and apparent motion.

PubMed

Horowitz, T; Treisman, A

1994-01-01

Two dissociations between short- and long-range motion in visual search are reported. Previous research has shown parallel processing for short-range motion and apparently serial processing for long-range motion. This finding has been replicated and it has also been found that search for short-range targets can be impaired both by using bicontrast stimuli, and by prior adaptation to the target direction of motion. Neither factor impaired search in long-range motion displays. Adaptation actually facilitated search with long-range displays, which is attributed to response-level effects. A feature-integration account of apparent motion is proposed. In this theory, short-range motion depends on specialized motion feature detectors operating in parallel across the display, but subject to selective adaptation, whereas attention is needed to link successive elements when they appear at greater separations, or across opposite contrasts.

Relationship between Epstein-Barr virus-encoded RNA expression, apoptosis and lymphocytic infiltration in gastric carcinoma with lymphoid-rich stroma.

PubMed

Cho, Mee-Yon; Kim, Tae Heon; Yi, Sang Yeop; Jung, Woo Hee; Park, Kwang Hwa

2004-01-01

To investigate the association of apoptosis with apoptotic proteins and Epstein-Barr virus (EBV) expression in gastric carcinoma with lymphoid-rich stroma (GCLRS) in order to clarify the relationship between lymphocytic infiltration, EBV expression and apoptosis in gastric carcinoma. We performed immunohistochemical stains for bcl-2, bax and in situ hybridization for EBV-encoded RNA and the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling technique using the 24 cases of GCLRS and 23 cases of gastric carcinoma with lymphoid-poor stroma (GCLPS) out of 1,635 cases of gastric carcinoma. The prevalence of GCLRS was 1.47% (24/1,635). The prevalence of EBV involvement in GCLRS (79%, 19/24) was significantly higher than in GCLPS (8.7%, 2/23). Apoptosis was revealed in all cases and there was no statistical difference between GCLRS and GCLPS. Immunohistochemical expression for bcl-2 was revealed only in the cytoplasm of lymphocytes in all cases, but bax showed distinct expression in the cytoplasm of neoplastic cells in all cases. There was a significant correlation between bax expression and the apoptotic index (p <0.05). Lymphocytic infiltration was significantly correlated with the expression of EBV (p <0.05) but not with survival rate and apoptosis. Most of the GCLRS cases were rated as low clinical stage (stage IA or B) and seemed to have a good prognosis. These results support the hypothesis that EBV infection plays an important role in the tumorigenesis of GCLRS, which has a better prognosis than usual gastric adenocarcinoma although there was no significant difference in the apoptotic index between GCLRS and GCLPS.

Differences in uterine immunoexpression of PR, ERα and OTR when comparing prostaglandin- to progestagen-based protocols for ovine estrus synchronization.

PubMed

Ruiz-González, I; Sánchez, M A; García-Palencia, P; Sánchez, B; García-Fernández, R A; González-Bulnes, A; Flores, J M

2012-07-01

The aim of this work was to compare PR, ERα and OTR uterine expression between days 9 and 21 of pregnancy in ewes whose estrus had been synchronized with two different protocols. Sixty-four adult Manchega ewes were synchronized with either conventional progestagens (P) or prostaglandin analogues (PG), and mated. Uterine samples were obtained from pregnant animals (group P, n=24; group PG, n=25) on days 9 post coitus (pc), 13pc, 15pc, 17pc and 21pc. Immunohistochemical detection of progesterone receptor (PR), estrogen receptor-α (ERα) and oxytocin receptor (OTR) was assessed in different uterine cell compartments including luminal and glandular epithelium, stroma and myometrium. Interaction day × treatment was obtained when assessing PR expression in the caruncular stroma (P=0.027) and myometrium (P=0.000), as well as for ERα in the superficial stroma (P=0.05). Significant "day post coitus" effect was found regarding to PR (P<0.01, with the exception of the superficial stroma, deep stroma and myometrium), ERα (P<0.01), and OTR (P<0.05, except in the deep compartments). No significant "treatment" effect was found for PR, ERα or OTR protein immunoexpression. This study supports the implication of PR, ERα and OTR within days 9-21 of the ovine pregnancy. Moreover, different expression pattern of PR and ERα proteins has been found between treatments in various compartments studied. Collectively, these results indicate that PR, ERα and OTR expression during early pregnancy is similar between ewes treated with either progestagens or prostaglandin analogues-based protocols for estrus synchronization. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of deep moonquake source parameters: Implication for fault characteristics and thermal state

NASA Astrophysics Data System (ADS)

Kawamura, Taichi; Lognonné, Philippe; Nishikawa, Yasuhiro; Tanaka, Satoshi

2017-07-01

While deep moonquakes are seismic events commonly observed on the Moon, their source mechanism is still unexplained. The two main issues are poorly constrained source parameters and incompatibilities between the thermal profiles suggested by many studies and the apparent need for brittle properties at these depths. In this study, we reinvestigated the deep moonquake data to reestimate its source parameters and uncover the characteristics of deep moonquake faults that differ from those on Earth. We first improve the estimation of source parameters through spectral analysis using "new" broadband seismic records made by combining those of the Apollo long- and short-period seismometers. We use the broader frequency band of the combined spectra to estimate corner frequencies and DC values of spectra, which are important parameters to constrain the source parameters. We further use the spectral features to estimate seismic moments and stress drops for more than 100 deep moonquake events from three different source regions. This study revealed that deep moonquake faults are extremely smooth compared to terrestrial faults. Second, we reevaluate the brittle-ductile transition temperature that is consistent with the obtained source parameters. We show that the source parameters imply that the tidal stress is the main source of the stress glut causing deep moonquakes and the large strain rate from tides makes the brittle-ductile transition temperature higher. Higher transition temperatures open a new possibility to construct a thermal model that is consistent with deep moonquake occurrence and pressure condition and thereby improve our understandings of the deep moonquake source mechanism.

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

Infections and apparent life-threatening events.

PubMed

Altman, Robin L; Li, Karl I; Brand, Donald A

2008-05-01

The need for routine sepsis evaluation in patients who have experienced an apparent life-threatening event but lack signs of infection remains controversial. To assess their risk of a serious occult bacterial infection, records were reviewed of 95 infants in whom infections were discovered during their inpatient evaluation after an apparent life-threatening event. Noted for each patient was the presence of any suggestive findings that would have prompted a physician to consider the given type of infection in the differential diagnosis. Thirty patients had bacterial infections; all but 5 had suggestive findings. The exceptions included 1 patient with pneumonia and 4 with urinary tract infections. None of the remaining 25 patients had occult bacterial infections. In patients with an apparent life-threatening event who appear well and lack signs suggestive of a serious bacterial infection, it may be possible to forego routine sepsis evaluation beyond a chest radiograph and urine culture without risking a serious missed diagnosis.

Figure-ground segregation modulates apparent motion.

PubMed

Ramachandran, V S; Anstis, S

1986-01-01

We explored the relationship between figure-ground segmentation and apparent motion. Results suggest that: static elements in the surround can eliminate apparent motion of a cluster of dots in the centre, but only if the cluster and surround have similar "grain" or texture; outlines that define occluding surfaces are taken into account by the motion mechanism; the brain uses a hierarchy of precedence rules in attributing motion to different segments of the visual scene. Being designated as "figure" confers a high rank in this scheme of priorities.

Surgical outcome of deep anterior lamellar keratoplasty with air-assisted manual dissection for corneas with previous inflammation or fibrosis

PubMed Central

Ho, Yi-Ju; Wu, Cheng-Hsiu; Chen, Hung-Chi; Hsiao, Chin-Shi; Hsueh, Yi-Jen; Ma, David Hui-Kang

2017-01-01

PURPOSE: To report our experience in air-assisted manual dissection deep anterior lamellar keratoplasty (DALK) for the treatment of corneal scar with previous inflammation and fibrosis. MATERIALS AND METHODS: We retrospectively reviewed the medical history of 21 patients (male:female = 13:8 mean age 41.9 years old) with corneal pathology from previous infection and inflammation. Trephination diameter ranged from 7.0 to 8.0 mm, and the graft was oversized by 0.25–0.50 mm. Debulking technique was performed to expose Descemet's membrane after filling stroma with air. Starting from postoperative 3 months, selective suture removal was performed to reduce corneal astigmatism. RESULTS: The mean follow-up period was 59.9 ± 19.8 (20–96) months. Intraoperative microperforation occurred in 2 eyes (9.5%); however, there was no shift to penetrating keratoplasty. Air-bubble tamponade was performed in 7 eyes (33.3%) for postoperative gapping of the graft. There were 2 failed grafts (9.5%) due to corneal ulcer while all the other grafts remained clear throughout follow-up. The mean preoperative best-corrected visual acuity (BCVA) was 1.84 ± 0.66 logMAR, which improved to 0.74 ± 0.63 (P < 0.01). The average sphere power was − 0.88 ± 3.88 diopter (D), average cylinder power 3.03 ± 1.46D, and average endothelial count 1877 ± 375 cells/mm2. CONCLUSION: In severe ocular surface diseases, big-bubble technique frequently failed to separate predescemtic plane; however, it effectively created air-filled stroma which was easier to remove. Although BCVA was suboptimal due to ocular surface disorders, graft survival and clarity rate is high, justifying the application of DALK in these cases. PMID:29296551

Selective Akt Inhibitors Synergize with Tyrosine Kinase Inhibitors and Effectively Override Stroma-Associated Cytoprotection of Mutant FLT3-Positive AML Cells

PubMed Central

Zhang, Xin; Nelson, Erik; Sattler, Martin; Liu, Feiyang; Nicolais, Maria; Zhang, Jianming; Mitsiades, Constantine; Smith, Robert W.; Stone, Richard; Galinsky, Ilene; Nonami, Atsushi; Griffin, James D.; Gray, Nathanael

2013-01-01

Objectives Tyrosine kinase inhibitor (TKI)-treated acute myeloid leukemia (AML) patients commonly show rapid and significant peripheral blood blast cell reduction, however a marginal decrease in bone marrow blasts. This suggests a protective environment and highlights the demand for a better understanding of stromal:leukemia cell communication. As a strategy to improve clinical efficacy, we searched for novel agents capable of potentiating the stroma-diminished effects of TKI treatment of mutant FLT3-expressing cells. Methods We designed a combinatorial high throughput drug screen using well-characterized kinase inhibitor-focused libraries to identify novel kinase inhibitors capable of overriding stromal-mediated resistance to TKIs, such as PKC412 and AC220. Standard liquid culture proliferation assays, cell cycle and apoptosis analysis, and immunoblotting were carried out with cell lines or primary AML to validate putative candidates from the screen and characterize the mechanism(s) underlying observed synergy. Results and Conclusions Our study led to the observation of synergy between selective Akt inhibitors and FLT3 inhibitors against mutant FLT3-positive AML in either the absence or presence of stroma. Our findings are consistent with evidence that Akt activation is characteristic of mutant FLT3-transformed cells, as well as observed residual Akt activity following FLT3 inhibitor treatment. In conclusion, our study highlights the potential importance of Akt as a signaling factor in leukemia survival, and supports the use of the co-culture chemical screen to identify agents able to potentiate TKI anti-leukemia activity in a cytoprotective microenvironment. PMID:23437141

Salvaging deep anterior lamellar keratoplasty with microbubble incision technique in failed "big bubble" cases: an update study.

PubMed

Banerjee, Sanjib; Li, He J; Tsaousis, Konstantinos T; Tabin, Geoffrey C

2016-11-04

To report the achievement rate of bare Descemet membrane (DM) dissection with the help of microbubble incision technique in eyes with failed big bubble formation and to investigate the mechanism of the microbubble rescue technique through ex vivo imaging of human cadaver corneas. This retrospective clinical study included 80 eyes of 80 patients that underwent deep anterior lamellar keratoplasty (DALK). In 22/80 (27.5%) cases, big bubble dissection failed. After puncturing the microbubbles, viscodissection helped to achieve separation of DM from the remaining stroma. In addition, an ex vivo study with human cadaver cornea specimens, gross photography, and anterior segment optical coherence tomography imaging was accomplished ex vivo to explore the mechanism of this method. Microbubble dissection technique led to successful DALK in 19 of 22 cases of failed big bubble. Microperforation occurred in 3 eyes. Deep anterior lamellar keratoplasty was completed without any complications in 2 out of the 3 eyes with microperforation. In 1 eye, conversion to penetrating keratoplasty was required. Microbubble-guided viscodissection achieved 95.4% (21/22) success in exposing bare DM in failed big-bubble cases of DALK. Anterior segment optical coherence tomography imaging results of cadaver eyes showed where these microbubbles were concentrated and their related size. Microbubble-guided DALK should be considered an effective rescue technique in achieving bare DM in eyes with failed big bubble. Our ex vivo experiment illustrated the possible alterations in cornea anatomy during this technique.

Refuge-mediated apparent competition in plant-consumer interactions.

PubMed

Orrock, John L; Holt, Robert D; Baskett, Marissa L

2010-01-01

At the intersection of consumer behaviour and plant competition is the concept of refuge-mediated apparent competition: an indirect interaction whereby plants provide a refuge for a shared consumer, subsequently increasing consumer pressure on another plant species. Here, we use a simple model and empirical examples to develop and illustrate the concept of refuge-mediated apparent competition. We find that the likelihood that an inferior competitor will succeed via refuge-mediated apparent competition is greater when competitors have similar resource requirements and when consumers exhibit a strong response to the refuge and high attack rates on the superior competitor. Refuge-mediated apparent competition may create an emergent Allee effect, such that a species invades only if it is sufficiently abundant to alter consumer impact on resident species. This indirect interaction may help explain unresolved patterns observed in biological invasion, such as the different physical structure of invasive exotic plants, the lag phase, and the failure of restoration efforts. Given the ubiquity of refuge-seeking behaviour by consumers and the ability of consumers to alter the outcome of direct competition among plants, refuge-mediated apparent competition may be an underappreciated mechanism affecting the composition and diversity of plant communities.

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

Apparent Brightness and Topography Images of Vibidia Crater

NASA Image and Video Library

2012-03-09

The left-hand image from NASA Dawn spacecraft shows the apparent brightness of asteroid Vesta surface. The right-hand image is based on this apparent brightness image, with a color-coded height representation of the topography overlain onto it.

Paratesticular dedifferentiated liposarcoma with prominent myxoid stroma: report of a case and review of the literature.

PubMed

Tajima, Shogo; Koda, Kenji

2017-06-01

Paratesticular sarcoma is rare, but liposarcoma is its most common type. Paratesticular liposarcoma sometimes presents as dedifferentiated liposarcoma. Both high-grade and low-grade dedifferentiation have been reported. Herein, we presented a unique case of a 64-year-old man with low-grade dedifferentiated liposarcoma with prominent myxoid stroma. Well-differentiated liposarcoma components extended along the spermatic cord. The constituent cells of the dedifferentiated component were peculiar in that, they were relatively uniform cells with atypia and did not have pleomorphism to such an extent that it mimicked myxofibrosarcoma. This myxoid component was confidently differentiated from myxoid liposarcoma with the help of immunohistochemical analysis using CDK4 and MDM2. These two markers were also expressed in the well-differentiated component. It could therefore be confirmed that this sarcoma is dedifferentiated liposarcoma but is not mixed-type liposarcoma comprising well-differentiated liposarcoma and myxoid liposarcoma.

Apparent directional selection by biased pleiotropic mutation.

PubMed

Tanaka, Yoshinari

2010-07-01

Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.

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.

Preoperative tumor size at MRI predicts deep myometrial invasion, lymph node metastases, and patient outcome in endometrial carcinomas.

PubMed

Ytre-Hauge, Sigmund; Husby, Jenny A; Magnussen, Inger J; Werner, Henrica M J; Salvesen, Øyvind O; Bjørge, Line; Trovik, Jone; Stefansson, Ingunn M; Salvesen, Helga B; Haldorsen, Ingfrid S

2015-03-01

The aim of this study was to explore the relation between preoperative tumor size based on magnetic resonance imaging (MRI) and the surgical pathologic staging parameters (deep myometrial invasion, cervical stroma invasion, and metastatic lymph nodes) and to assess the prognostic impact of tumor size in endometrial carcinomas. Interobserver variability for the different tumor size measurements was also assessed. Preoperative pelvic MRI of 212 patients with histologically confirmed endometrial carcinomas was read independently by 3 radiologists. Maximum tumor diameters were measured in 3 orthogonal planes (anteroposterior, transverse, and craniocaudal planes [CC]), and tumor volumes were estimated. Tumor size was analyzed in relation to surgical staging results and patient survival. The multivariate analyses were adjusted for preoperative risk status based on endometrial biopsy. Intraclass correlation coefficients and receiver operating characteristics curves for the different tumor measurements were also calculated. Anteroposterior tumor diameter independently predicted deep myometrial invasion (P < 0.001), whereas CC tumor diameter tended to independently predict lymph node metastases (P = 0.06). Based on receiver operating characteristic curves, the following tumor size cutoff values were identified: anteroposterior diameter greater than 2 cm predicted deep myometrial invasion (unadjusted odds ratio [OR], 12.4; P < 0.001; adjusted OR, 6.7; P < 0.001) and CC diameter greater than 4 cm predicted lymph node metastases (unadjusted OR, 6.2; P < 0.001; adjusted OR, 4.9; P = 0.009). Large tumor size was associated with reduced progression/recurrence-free survival (P ≤ 0.005 for all size parameters), and CC diameter had an independent impact on survival (adjusted hazards ratio, 1.04; P = 0.009). The interobserver variability for the different size measurements was very low (intraclass correlation coefficient, 0.78-0.85). Anteroposterior tumor diameter greater than 2 cm

Syllidae (Annelida: Phyllodocida) from the deep Mediterranean Sea, with the description of three new species.

PubMed

Langeneck, Joachim; Musco, Luigi; Busoni, Giulio; Conese, Ilaria; Aliani, Stefano; Castelli, Alberto

2018-01-03

Despite almost two centuries of research, the diversity of Mediterranean deep-sea environments remain still largely unexplored. This is particularly true for the polychaete family Syllidae. We report herein 14 species; among them, we describe Erinaceusyllis barbarae n. sp., Exogone sophiae n. sp. and Prosphaerosyllis danovaroi n. sp. and report Parexogone wolfi San Martín, 1991, Exogone lopezi San Martín, Ceberio Aguirrezabalaga, 1996 and Anguillosyllis Day, 1963 for the first time from the Western Mediterranean, the latter based on a single individual likely belonging to an undescribed species. Moreover, we re-establish Syllis profunda Cognetti, 1955 based on type and new material. Present data, along with a critical analysis of available literature, show that Syllidae are highly diverse in deep Mediterranean environments, even though they are rarely reported, probably due to the scarce number of studies devoted to the size-fraction of benthos including deep-sea syllids. Most deep-sea Syllidae have wide distributions, which do not include shallow-waters. 100 m depth apparently represents the boundary between the assemblages dominated by generalist shallow water syllids like Exogone naidina Ørsted, 1843 and Syllis parapari San Martín López, 2000, and those deep-water assemblages characterised by strictly deep-water species like Parexogone campoyi San Martín, Ceberio Aguirrezabalaga, 1996, Parexogone wolfi San Martín, 1991 and Syllis sp. 1 (= Langerhansia caeca Katzmann, 1973).

Effect of increasing levels of apparent metabolizable energy on laying hens in barn system.

PubMed

Kang, Hwan Ku; Park, Seong Bok; Jeon, Jin Joo; Kim, Hyun Soo; Park, Ki Tae; Kim, Sang Ho; Hong, Eui Chul; Kim, Chan Ho

2018-04-12

This experiment was to investigate the effect of increasing levels of apparent metabolizable energy (AMEn) on the laying performance, egg quality, blood parameter, blood biochemistry, intestinal morphology, and apparent total tract digestibility (ATTD) of energy and nutrients in diets fed to laying hens. A total of three-hundred twenty 33-week-old Hy-Line Brown laying hens (Gallus domesticus) were evenly assigned to four experimental diets of 2,750, 2,850, 2,950, and 3,050 kcal AMEn/kg in floor with deep litter of rice hulls. There were four replicates of each treatment, each consisting of 20 birds in a pen. AMEn intake was increased (linear, p < 0.05) with inclusion level of AMEn in diets increased. Feed intake and feed conversion ratio were improved (linear, p < 0.01), but hen-day egg production tended to be increased as increasing level of AMEn in diets increased. During the experiment, leukocyte concentration and blood biochemistry (total cholesterol, triglyceride, glucose, total protein, calcium, asparate aminotransferase (AST), and alanine transferase (ALT) were not influenced by increasing level of AMEn in diets. Gross energy and ether extract were increased (linear, p < 0.01) with inclusion level of AMEn in diets increased. Laying hens fed high AMEn diet (i.e., 3,050 kcal/kg in the current experiment) tended to overconsume energy with a positive effect on feed intake, feed conversion ratio, nutrient digestibility, and intestinal morphology but not in egg production and egg mass.

49 CFR 98.3 - Reports of apparent violations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Reports of apparent violations. 98.3 Section 98.3 Transportation Office of the Secretary of Transportation ENFORCEMENT OF RESTRICTIONS ON POST-EMPLOYMENT ACTIVITIES Administration of Enforcement Proceedings § 98.3 Reports of apparent violations. Any person may...

[CD4 and CD8 T lymphocytes and NK cells in the stroma of the uterine cervix of women infected with human papillomavirus].

PubMed

Alves, Daniella Borges; Tozetti, Inês Aparecida; Gatto, Flávia Almeida; Cassandri, Fernanda; Ferreira, Alda Maria Teixeira; Carlos Eurico Dos Santos, Fernandes; Falcão, Gustavo Ribeiro; Scapulatempo, Ilzia Doraci Lins; Padovani, Cacilda Tezelli Junqueira; Abdo, Maria Auxiliadora Gomes Sandim

2010-01-01

Immune response might be a key element regarding the progression or regression of human papillomavirus (HPV) infection in the stroma of the uterine cervix. This study aimed to quantify the presence of CD4 and CD8 T lymphocytes and NK cells in the cervical stroma, by means of immunohistochemistry, in high and low grade lesions in patients infected by HPV METHODS: Fifty-six biopsy samples from the uterine cervix were used. Forty-three samples were positive for oncogenic high-risk HPV DNA and had a histopathological diagnosis of high and low-grade cervical intraepithelial neoplasia (CIN) or negative for intraepithelial lesion and malignancy (NILM); while the other 13 samples were negative for HPV DNA with a histopathological diagnosis of NILM RESULTS: Higher quantities of CD4 T lymphocytes were observed in CIN II/III, carcinoma and NILM samples (p = 0.04) and in those in which the viral load was between 10 and 1.000 RLU/PCB. CD8 T lymphocytes were predominant in CIN II/III samples (p = 0.02) and also in samples with viral loads between 100 and 1,000 RLU/PCB. NK cells predominated in samples with low-grade lesions and low viral load This study proved that in the initial stages of the infection, in which no high-grade cell abnormalities have yet occurred, no cells that might trigger the effector phase of the immune response.

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

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

PubMed

Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Endolithic Boring Enhance the Deep-sea Carbonate Lithification on the Southwest Indian Ridge

NASA Astrophysics Data System (ADS)

Peng, X.; Xu, H.

2017-12-01

Deep-sea carbonates represent an important type of sedimentary rock due to their effect on the composition of upper oceanic crust and their contribution to deep-sea geochemical cycles. However, the lithification of deep-sea carbonates at the seafloor has remained a mystery for many years. A large lithified carbonate area, characterized by thriving benthic faunas and tremendous amount of endolithic borings, was discovered in 2008, blanketed on the seafloor of ultraslow spreading Southwest Indian Ridge (SWIR). Macrofaunal inhabitants including echinoids, polychaetes, gastropods as well as crustaceans, are abundant in the sample. The most readily apparent feature of the sample is the localized enhancement of density around the borings. The boring features of these carbonate rocks and factors that may enhance deep-sea carbonate lithification are reported. The δ13CPDB values of 46 bulk samples are -0.37 to 1.86‰, while these samples have a relatively narrow δ18OPDB range of 1.35 to 3.79‰. The bulk δ13CPDB values of chalk and gray excrements are positively correlated with bulk δ18OPDB values (r = 0.91) (Fig. 8), which reflects that endolithic boring is possibly a critical factor influence the lithification. We suggest that active boring may trigger the dissolution of the original calcite and thus accelerate deep-sea carbonate lithification on mid-ocean ridges. Our study reports an unfamiliar phenomenon of non-burial carbonate lithification and interested by the observation that it is often associated with boring feature. These carbonate rocks may provide a novel mechanism for deep-sea carbonate lithification at the deep-sea seafloor and also illuminate the geological and biological importance of deep-sea carbonate rocks on mid-ocean ridges.

Deserts on the sea floor: Edward Forbes and his azoic hypothesis for a lifeless deep ocean.

PubMed

Anderson, Thomas R; Rice, Tony

2006-12-01

While dredging in the Aegean Sea during the mid-19th century, Manxman Edward Forbes noticed that plants and animals became progressively more impoverished the greater the depth they were from the surface of the water. By extrapolation Forbes proposed his now infamous azoic hypothesis, namely that life would be extinguished altogether in the murky depths of the deep ocean. The whole idea seemed so entirely logical given the enormous pressure, cold and eternal darkness of this apparently uninhabitable environment. Yet we now know that the sea floor is teeming with life. Curiously, it took 25 years for the azoic hypothesis to fall from grace. This was despite the presence of ample contrary evidence, including starfishes, worms and other organisms that seemingly originated from the deep seabed. This is a tale of scientists ignoring observations that ran counter to their deep-seated, yet entirely erroneous, beliefs.

Apparent Solar Tornado-Like Prominences

NASA Astrophysics Data System (ADS)

Panasenco, Olga; Martin, Sara F.; Velli, Marco

2014-02-01

Recent high-resolution observations from the Solar Dynamics Observatory (SDO) have reawakened interest in the old and fascinating phenomenon of solar tornado-like prominences. This class of prominences was first introduced by Pettit ( Astrophys. J. 76, 9, 1932), who studied them over many years. Observations of tornado prominences similar to the ones seen by SDO had already been documented by Secchi ( Le Soleil, 1877). High-resolution and high-cadence multiwavelength data obtained by SDO reveal that the tornado-like appearance of these prominences is mainly an illusion due to projection effects. We discuss two different cases where prominences on the limb might appear to have a tornado-like behavior. One case of apparent vortical motions in prominence spines and barbs arises from the (mostly) 2D counterstreaming plasma motion along the prominence spine and barbs together with oscillations along individual threads. The other case of apparent rotational motion is observed in a prominence cavity and results from the 3D plasma motion along the writhed magnetic fields inside and along the prominence cavity as seen projected on the limb. Thus, the "tornado" impression results either from counterstreaming and oscillations or from the projection on the plane of the sky of plasma motion along magnetic-field lines, rather than from a true vortical motion around an (apparent) vertical or horizontal axis. We discuss the link between tornado-like prominences, filament barbs, and photospheric vortices at their base.

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

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

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... contracting officer before award. The contracting officer first shall obtain from the bidder a verification of 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, 2011 CFR

2011-10-01

... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.407-2 Apparent... contracting officer before award. The contracting officer first shall obtain from the bidder a verification of the bid intended. Examples of apparent mistakes are— (1) Obvious misplacement of a decimal point; (2...

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.

49 CFR 98.3 - Reports of apparent violations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Reports of apparent violations. 98.3 Section 98.3 Transportation Office of the Secretary of Transportation ENFORCEMENT OF RESTRICTIONS ON POST-EMPLOYMENT ACTIVITIES Administration of Enforcement Proceedings § 98.3 Reports of apparent violations. Any person may report, to the Assistant General...

Attenuation of Slab determined from T-wave generation by deep earthquakes

NASA Astrophysics Data System (ADS)

Huang, J.; Ni, S.

2006-05-01

T-wave are seismically generated acoustic waves that propagate over great distance in the ocean sound channel (SOFAR). Because of the high attenuation in both the upper mantle and the ocean crust, T wave is rarely observed for earthquakes deeper than 80 km. However some deep earthquakes deeper than 80km indeed generate apparent T-waves if the subducted slab is continuous Okal et al. (1997) . We studied the deep earthquakes in the Fiji/Tonga region, where the subducted lithosphere is old and thus with small attenuation. After analyzing 33 earthquakes with the depth from 10 Km to 650 Km in Fiji/Tonga, we observed and modeled obvious T-phases from these earthquakes observed at station RAR. We used the T-wave generated by deep earthquakes to compute the quality factor of the Fiji/Tonga slab. The method used in this study is followed the equation (1) by [Groot-Hedlin et al,2001][1]. A=A0/(1+(Ω0/Ω)2)×exp(-LΩ/Qv)×Ωn where the A is the amplitude computed by the practicable data, amplitude depending on the earthquakes, and A0 is the inherent frequency related with the earthquake's half duration, L is the length of ray path that P wave or S travel in the slab, and the V is the velocity of P-wave. In this study, we fix the n=2, by assuming the T- wave scattering points in the Fiji/Tonga island arc having the same attribution as the continental shelf. After some computing and careful analysis, we determined the quality factor of the Fiji/Tonga to be around 1000, Such result is consistent with results from the traditional P,S-wave data[Roth & Wiens,1999][2] . Okal et al. (1997) pointed out that the slab in the part of central South America was also a continuous slab, by modeling apparent T-waves from the great 1994 Bolivian deep earthquake in relation to channeling of S wave energy propagating upward through the slab[3]. [1]Catherine D. de Groot-Hedlin, John A. Orcutt, excitation of T-phases by seafloor scattering, J. Acoust. Soc, 109,1944-1954,2001. [2]Erich G.Roth and

In Vivo Adipogenesis in Rats Measured by Cell Kinetics in Adipocytes and Plastic-Adherent Stroma-Vascular Cells in Response to High-Fat Diet and Thiazolidinedione

PubMed Central

Tchoukalova, Yourka D.; Fitch, Mark; Rogers, Pamela M.; Covington, Jeffrey D.; Henagan, Tara M.; Ye, Jianping; Hellerstein, Marc K.; Ravussin, Eric

2012-01-01

Impairment of adipogenesis contributes to the development of obesity-related insulin resistance. The current in vitro approaches for its assessment represent crude estimates of the adipogenic potential because of the disruption of the in vivo microenvironment. A novel assessment of in vivo adipogenesis using the incorporation of the stable isotope deuterium (2H) into the DNA of isolated adipocytes and stroma-vascular fraction from adipose tissue has been developed. In the current study, we have refined this technique by purifying the adipocytes via a negative immune selection and sorting the plastic adherent stroma-vascular (aSV) subfraction (using 3 h culture) that contains mostly adipocyte progenitor cells and ∼10% of small adipocytes. Using a 3-week 8% 2H2O ingestion with a high-fat diet (HFD) or HFD plus pioglitazone (HFD-P), we demonstrate that the fractions of new aSV cells (faSV) and immunopurified adipocytes (fAD) (the ratio of their 2H-enrichment of DNA to the maximal 2H-enrichment of DNA of bone marrow reference cells) recapitulate the known hyperplastic mechanism of weight gain with pioglitazone treatment. We conclude that faSV and fAD are reliable indices of in vivo adipogenesis. The proposed method represents a valuable tool for studying the effect of interventions (drugs, diets, and exercise) on in vivo adipogenesis. PMID:22124466

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

USGS Publications Warehouse

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

2015-01-01

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

39 CFR 946.2 - Disposition of property of apparent owners.

Code of Federal Regulations, 2010 CFR

2010-07-01

... DISPOSITION OF STOLEN MAIL MATTER AND PROPERTY ACQUIRED BY THE POSTAL INSPECTION SERVICE FOR USE AS EVIDENCE § 946.2 Disposition of property of apparent owners. Where an apparent owner of property subject to this... 39 Postal Service 1 2010-07-01 2010-07-01 false Disposition of property of apparent owners. 946.2...

39 CFR 946.2 - Disposition of property of apparent owners.

Code of Federal Regulations, 2011 CFR

2011-07-01

... DISPOSITION OF STOLEN MAIL MATTER AND PROPERTY ACQUIRED BY THE POSTAL INSPECTION SERVICE FOR USE AS EVIDENCE § 946.2 Disposition of property of apparent owners. Where an apparent owner of property subject to this... 39 Postal Service 1 2011-07-01 2011-07-01 false Disposition of property of apparent owners. 946.2...

Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis.

PubMed

Meijer, Kim A; Eijlers, Anand J C; Geurts, Jeroen J G; Schoonheim, Menno M

2018-02-01

Functional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages. A cohort of 121 patients with early relapsing-remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes. Patients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability. Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Analysis of tumor- and stroma-supplied proteolytic networks reveals a brain metastasis-promoting role for cathepsin S

PubMed Central

Sevenich, Lisa; Bowman, Robert L.; Mason, Steven D.; Quail, Daniela F.; Rapaport, Franck; Elie, Benelita T.; Brogi, Edi; Brastianos, Priscilla K.; Hahn, William C.; Holsinger, Leslie J.; Massagué, Joan; Leslie, Christina S.; Joyce, Johanna A.

2014-01-01

Metastasis remains the most common cause of death in most cancers, with limited therapies for combating disseminated disease. While the primary tumor microenvironment is an important regulator of cancer progression, it is less well understood how different tissue environments influence metastasis. We analyzed tumor-stroma interactions that modulate organ tropism of brain, bone and lung metastasis in xenograft models. We identified a number of potential modulators of site-specific metastasis, including cathepsin S as a regulator of breast-to-brain metastasis. High cathepsin S expression at the primary site correlated with decreased brain metastasis-free survival in breast cancer patients. Both macrophages and tumor cells produce cathepsin S, and only the combined depletion significantly reduced brain metastasis in vivo. Cathepsin S specifically mediates blood-brain barrier transmigration via proteolytic processing of the junctional adhesion molecule (JAM)-B. Pharmacological inhibition of cathepsin S significantly reduced experimental brain metastasis, supporting its consideration as a therapeutic target for this disease. PMID:25086747

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment.

PubMed

Obonai, Toshifumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Kozuka, Naoyuki; Yasunaga, Masahiro; Matsumura, Yasuhiro

2016-03-24

The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma.

Picocyanobacteria and deep-ocean fluorescent dissolved organic matter share similar optical properties

NASA Astrophysics Data System (ADS)

Zhao, Zhao; Gonsior, Michael; Luek, Jenna; Timko, Stephen; Ianiri, Hope; Hertkorn, Norbert; Schmitt-Kopplin, Philippe; Fang, Xiaoting; Zeng, Qinglu; Jiao, Nianzhi; Chen, Feng

2017-05-01

Marine chromophoric dissolved organic matter (CDOM) and its related fluorescent components (FDOM), which are widely distributed but highly photobleached in the surface ocean, are critical in regulating light attenuation in the ocean. However, the origins of marine FDOM are still under investigation. Here we show that cultured picocyanobacteria, Synechococcus and Prochlorococcus, release FDOM that closely match the typical fluorescent signals found in oceanic environments. Picocyanobacterial FDOM also shows comparable apparent fluorescent quantum yields and undergoes similar photo-degradation behaviour when compared with deep-ocean FDOM, further strengthening the similarity between them. Ultrahigh-resolution mass spectrometry (MS) and nuclear magnetic resonance spectroscopy reveal abundant nitrogen-containing compounds in Synechococcus DOM, which may originate from degradation products of the fluorescent phycobilin pigments. Given the importance of picocyanobacteria in the global carbon cycle, our results indicate that picocyanobacteria are likely to be important sources of marine autochthonous FDOM, which may accumulate in the deep ocean.

Picocyanobacteria and deep-ocean fluorescent dissolved organic matter share similar optical properties

PubMed Central

Zhao, Zhao; Gonsior, Michael; Luek, Jenna; Timko, Stephen; Ianiri, Hope; Hertkorn, Norbert; Schmitt-Kopplin, Philippe; Fang, Xiaoting; Zeng, Qinglu; Jiao, Nianzhi; Chen, Feng

2017-01-01

Marine chromophoric dissolved organic matter (CDOM) and its related fluorescent components (FDOM), which are widely distributed but highly photobleached in the surface ocean, are critical in regulating light attenuation in the ocean. However, the origins of marine FDOM are still under investigation. Here we show that cultured picocyanobacteria, Synechococcus and Prochlorococcus, release FDOM that closely match the typical fluorescent signals found in oceanic environments. Picocyanobacterial FDOM also shows comparable apparent fluorescent quantum yields and undergoes similar photo-degradation behaviour when compared with deep-ocean FDOM, further strengthening the similarity between them. Ultrahigh-resolution mass spectrometry (MS) and nuclear magnetic resonance spectroscopy reveal abundant nitrogen-containing compounds in Synechococcus DOM, which may originate from degradation products of the fluorescent phycobilin pigments. Given the importance of picocyanobacteria in the global carbon cycle, our results indicate that picocyanobacteria are likely to be important sources of marine autochthonous FDOM, which may accumulate in the deep ocean. PMID:28513605

Holocene Deep Ocean Variability Detected with Individual Benthic Foraminifera

NASA Astrophysics Data System (ADS)

Bova, S. C.; Herbert, T.; Fox-Kemper, B.

2015-12-01

Historical observations of deep ocean temperatures (>700 m water depth) show apparently unprecedented rates of warming over the past half century that parallel observed surface warming, on the order of 0.1°C/decade (Purkey and Johnson 2010). Most water masses below 700 m depth, however, have not been at the sea surface where they exchange heat and carbon with the atmosphere since well before industrialization (Gebbie and Huybers 2012). How then has the heat content of isolated deep water masses responded to climate change over the last century? In models, wave mechanisms propagate thermocline anomalies quickly (Masuda et al. 2010), but these dynamics are not fully understood. We therefore turn to the sedimentary record to constrain the bounds of earlier variability from Holocene anomalies. The oxygen isotopic composition (δ18O) of individual benthic foraminifera provide approximately month-long snapshots of the temperature and salinity of ambient deep water during calcification. We exploit the short lifespan of these organisms to reconstruct variability in δ18Oshell, and thus the variability in deep water temperature and salinity, during five 200-yr Holocene intervals at 1000 m water depth in the Eastern Equatorial Pacific (EEP). Modern variability in benthic foraminifer δ18O was too weak to detect but variability at 1000 m water depth in the EEP exceeded our detection limit during two Holocene intervals at high confidence (p<0.01), with δ18O anomalies up to ~0.6 ± 0.15‰ that persist for a month or longer. Although the source of these anomalies remains speculative, rapid communication between the surface and deep ocean that operates on human timescales, faster than previously recognized, or intrinsic variability that has not been active during the history of ocean observations are potential explanations. Further work combining models and high-resolution proxy data is needed to identify the mechanism and global extent of this type of subsurface variability

Deep UV Native Fluorescence Imaging of Antarctic Cryptoendolithic Communities

NASA Technical Reports Server (NTRS)

Storrie-Lombardi, M. C.; Douglas, S.; Sun, H.; McDonald, G. D.; Bhartia, R.; Nealson, K. H.; Hug, W. F.

2001-01-01

An interdisciplinary team at the Jet Propulsion Laboratory Center for Life Detection has embarked on a project to provide in situ chemical and morphological characterization of Antarctic cryptoendolithic microbial communities. We present here in situ deep ultraviolet (UV) native fluorescence and environmental scanning electron microscopy images transiting 8.5 mm into a sandstone sample from the Antarctic Dry Valleys. The deep ultraviolet imaging system employs 224.3, 248.6, and 325 nm lasers to elicit differential fluorescence and resonance Raman responses from biomolecules and minerals. The 224.3 and 248.6 nm lasers elicit a fluorescence response from the aromatic amino and nucleic acids. Excitation at 325 nm may elicit activity from a variety of biomolecules, but is more likely to elicit mineral fluorescence. The resultant fluorescence images provide in situ chemical and morphological maps of microorganisms and the associated organic matrix. Visible broadband reflectance images provide orientation against the mineral background. Environmental scanning electron micrographs provided detailed morphological information. The technique has made possible the construction of detailed fluorescent maps extending from the surface of an Antarctic sandstone sample to a depth of 8.5 mm. The images detect no evidence of microbial life in the superficial 0.2 mm crustal layer. The black lichen component between 0.3 and 0.5 mm deep absorbs all wavelengths of both laser and broadband illumination. Filamentous deep ultraviolet native fluorescent activity dominates in the white layer between 0.6 mm and 5.0 mm from the surface. These filamentous forms are fungi that continue into the red (iron-rich) region of the sample extending from 5.0 to 8.5 mm. Using differential image subtraction techniques it is possible to identify fungal nuclei. The ultraviolet response is markedly attenuated in this region, apparently from the absorption of ultraviolet light by iron-rich particles coating

Rollover of Apparent Wave Attenuation in Ice Covered Seas

NASA Astrophysics Data System (ADS)

Li, Jingkai; Kohout, Alison L.; Doble, Martin J.; Wadhams, Peter; Guan, Changlong; Shen, Hayley H.

2017-11-01

Wave attenuation from two field experiments in the ice-covered Southern Ocean is examined. Instead of monotonically increasing with shorter waves, the measured apparent attenuation rate peaks at an intermediate wave period. This "rollover" phenomenon has been postulated as the result of wind input and nonlinear energy transfer between wave frequencies. Using WAVEWATCH III®, we first validate the model results with available buoy data, then use the model data to analyze the apparent wave attenuation. With the choice of source parameterizations used in this study, it is shown that rollover of the apparent attenuation exists when wind input and nonlinear transfer are present, independent of the different wave attenuation models used. The period of rollover increases with increasing distance between buoys. Furthermore, the apparent attenuation for shorter waves drops with increasing separation between buoys or increasing wind input. These phenomena are direct consequences of the wind input and nonlinear energy transfer, which offset the damping caused by the intervening ice.

Observations of apparent superslow wave propagation in solar prominences

NASA Astrophysics Data System (ADS)

Raes, J. O.; Van Doorsselaere, T.; Baes, M.; Wright, A. N.

2017-06-01

Context. Phase mixing of standing continuum Alfvén waves and/or continuum slow waves in atmospheric magnetic structures such as coronal arcades can create the apparent effect of a wave propagating across the magnetic field. Aims: We observe a prominence with SDO/AIA on 2015 March 15 and find the presence of oscillatory motion. We aim to demonstrate that interpreting this motion as a magneto hydrodynamic (MHD) wave is faulty. We also connect the decrease of the apparent velocity over time with the phase mixing process, which depends on the curvature of the magnetic field lines. Methods: By measuring the displacement of the prominence at different heights to calculate the apparent velocity, we show that the propagation slows down over time, in accordance with the theoretical work of Kaneko et al. We also show that this propagation speed drops below what is to be expected for even slow MHD waves for those circumstances. We use a modified Kippenhahn-Schlüter prominence model to calculate the curvature of the magnetic field and fit our observations accordingly. Results: Measuring three of the apparent waves, we get apparent velocities of 14, 8, and 4 km s-1. Fitting a simple model for the magnetic field configuration, we obtain that the filament is located 103 Mm below the magnetic centre. We also obtain that the scale of the magnetic field strength in the vertical direction plays no role in the concept of apparent superslow waves and that the moment of excitation of the waves happened roughly one oscillation period before the end of the eruption that excited the oscillation. Conclusions: Some of the observed phase velocities are lower than expected for slow modes for the circumstances, showing that they rather fit with the concept of apparent superslow propagation. A fit with our magnetic field model allows for inferring the magnetic geometry of the prominence. The movie attached to Fig. 1 is available at http://www.aanda.org

Stroma-induced Jagged1 expression drives PC3 prostate cancer cell migration; disparate effects of RIP-generated proteolytic fragments on cell behaviour and Notch signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delury, Craig, E-mail: c.delury@lancaster.ac.uk; Hart, Claire, E-mail: claire.hart@manchester.ac.uk; Brown, Mick, E-mail: michael.brown@ics.manchester.ac.uk

The Notch ligand Jagged1 is subject to regulated intramembrane proteolysis (RIP) which yields a soluble ectodomain (sJag) and a soluble Jagged1 intracellular domain (JICD). The full-length Jagged1 protein enhances prostate cancer (PCa) cell proliferation and is highly expressed in metastatic cells. However, little is known regarding the mechanisms by which Jagged1 or its RIP-generated fragments might promote PCa bone metastasis. In the current study we show that bone marrow stroma (BMS) induces Jagged1 expression in bone metastatic prostate cancer PC3 cells and that this enhanced expression is mechanistically linked to the promotion of cell migration. We also show that RIP-generatedmore » Jagged1 fragments exert disparate effects on PC3 cell behaviour and Notch signaling. In conclusion, the expression of both the full-length ligand and its RIP-generated fragments must be considered in tandem when attempting to regulate Jagged1 as a possible PCa therapy. - Highlights: • Bone marrow stroma induces Jagged1 expression in prostate cancer (PCa) PC3 cells. • This enhanced expression of full-length Jagged1 is required for PC3 cell migration. • Proteolytic fragments of Jagged1 exert disparate effects on PC3 cell behaviour. • Effects of fragments on cell behaviour do not correlate with Notch signaling. • Effects of Jagged1 and its fragments on PCa metastasis likely to be complex.« less

Fertility and apparent genetic anticipation in Lynch syndrome.

PubMed

Stupart, Douglas; Win, Aung Ko; Jenkins, Mark; Winship, Ingrid M; Goldberg, Paul; Ramesar, Rajkumar

2014-09-01

Genetic anticipation is the phenomenon in which age of onset of an inherited disorder decreases in successive generations. Inconsistent evidence suggests that this occurs in Lynch syndrome. A possible cause for apparent anticipation is fecundity bias, which occurs if the disease adversely affects fertility. The purpose of this study was to determine the effect of age of diagnosis of colorectal cancer (CRC) on lifetime fertility in Lynch syndrome, and whether this can falsely create the appearance of genetic anticipation. A computer model simulated age of diagnosis of CRC in hypothetical Lynch syndrome carriers and their offspring. The model assumed similar age distribution of CRC across generations (i.e. that there was no true anticipation). Age distribution of CRC diagnosis, and lifetime fertility rates (grouped by age of diagnosis of CRC) were determined from the Australasian Colorectal Cancer Family Registry (ACCFR). Apparent anticipation was calculated by comparing ages of diagnosis of CRC in affected parent-child pairs. A total of 1,088 patients with CRC were identified from the ACCFR. Total lifetime (cohort) fertility was related to age of diagnosis of CRC (correlation coefficient 0.13, P = 0.0001). In the simulation, apparent anticipation was 1.8 ± 0.54 years (P = 0.0044). Observed apparent anticipation in the ACCFR cohort was 4.8 ± 1.73 years (P = 0.0064). There was no difference in apparent anticipation between the simulate d and observed parent-child pairs (P = 0.89). The appearance of genetic anticipation in Lynch syndrome can be falsely created due to changes in fertility.

Stakeholder perspectives on the importance of rare-species research for deep-sea environmental management

NASA Astrophysics Data System (ADS)

Turner, Phillip J.; Campbell, Lisa M.; Van Dover, Cindy L.

2017-07-01

The apparent prevalence of rare species (rarity) in the deep sea is a concern for environmental management and conservation of biodiversity. Rare species are often considered at risk of extinction and, in terrestrial and shallow water environments, have been shown to play key roles within an ecosystem. In the deep-sea environment, current research focuses primarily on abundant species and deep-sea stakeholders are questioning the importance of rare species in ecosystem functioning. This study asks whether deep-sea stakeholders (primarily scientists) view rare-species research as a priority in guiding environmental management. Delphi methodology (i.e., an iterative survey approach) was used to understand views about whether or not 'deep-sea scientists should allocate more resources to research on rare species in the deep sea, even if this means less resources might be available for abundant-species research.' Results suggest little consensus regarding the prioritization of resources for rare-species research. From Survey 1 to Survey 3, the average participant response shifted toward a view that rare-species research is not a priority if it comes at a cost to research on abundant species. Participants pointed to the need for a balanced approach and highlighted knowledge gaps about even the most fundamental questions, including whether rare species are truly 'rare' or simply under-sampled. Participants emphasized the lack of basic biological knowledge for rare and abundant species, particularly abundant meio- and microscopic species, as well as uncertainty in the roles rare and abundant species play in ecosystem processes. Approaches that jointly consider the role of rare and abundant species in ecosystem functioning (e.g., biological trait analysis) may help to clarify the extent to which rare species need to be incorporated into deep-sea environment management in order to maintain ecosystem functioning.

Modeling apparent color for visual evaluation of camouflage fabrics

NASA Astrophysics Data System (ADS)

Ramsey, S.; Mayo, T.; Shabaev, A.; Lambrakos, S. G.

2017-08-01

As the U.S. Navy, Army, and Special Operations Forces progress towards fielding more advanced uniforms with multi-colored and highly detailed camouflage patterning, additional test methodologies are necessary in evaluating color in these types of camouflage textiles. The apparent color is the combination of all visible wavelengths (380-760 nm) of light reflected from large (>=1m2 ) fabric sample sizes for a given standoff distance (10-25ft). Camouflage patterns lose resolution with increasing standoff distance, and eventually all colors within the pattern appear monotone (the "apparent color" of the pattern). This paper presents an apparent color prediction model that can be used for evaluation of camouflage fabrics.

Gravitational pressure, apparent horizon and thermodynamics of FLRW universe in the teleparallel gravity

NASA Astrophysics Data System (ADS)

da Rocha-Neto, J. F.; Morais, B. R.

2018-04-01

In the context of the teleparallel equivalent of general relativity the concept of gravitational pressure and gravitational energy-momentum arisen in a natural way. In the case of a Friedmann-Lemaitre-Robertson-Walker space FLRW we obtain the total energy contained inside the apparent horizon and the radial pressure over the apparent horizon area. We use these definitions to written a thermodynamics relation TAdSA = dEA+PAdVA at the apparent horizon, where EA is the total energy inside the apparent horizon, VA is the areal volume of the apparent horizon, PA is the radial pressure over the apparent horizon area, SA is the entropy which can be assumed as one quarter of the apparent horizon area only for a non stationary apparent horizon. We identify TA as the temperature at the surface of the apparent horizon. We shown that for all expanding accelerated FLRW model of universe the radial pressure is positive.

Capacity of Lung Stroma to Educate Dendritic Cells Inhibiting Mycobacteria-Specific T-Cell Response Depends upon Genetic Susceptibility to Tuberculosis

PubMed Central

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+CD11clowCD103- 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 during M

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

Hydrothermal systems are a sink for dissolved black carbon in the deep ocean

NASA Astrophysics Data System (ADS)

Niggemann, J.; Hawkes, J. A.; Rossel, P. E.; Stubbins, A.; Dittmar, T.

2016-02-01

Exposure to heat during fires on land or geothermal processes in Earth's crust induces modifications in the molecular structure of organic matter. The products of this thermogenesis are collectively termed black carbon. Dissolved black carbon (DBC) is a significant component of the oceanic dissolved organic carbon (DOC) pool. In the deep ocean, DBC accounts for 2% of DOC and has an apparent radiocarbon age of 18,000 years. Thus, DBC is much older than the bulk DOC pool, suggesting that DBC is highly refractory. Recently, it has been shown that recalcitrant deep-ocean DOC is efficiently removed during hydrothermal circulation. Here, we hypothesize that hydrothermal circulation is also a net sink for deep ocean DBC. We analyzed DBC in samples collected at different vent sites in the Atlantic, Pacific and Southern oceans. DBC was quantified in solid-phase extracts as benzenepolycarboxylic acids (BPCAs) following nitric acid digestion. Concentrations of DBC were much lower in hydrothermal fluids than in surrounding deep ocean seawater, confirming that hydrothermal circulation acts as a net sink for oceanic DBC. The relative contribution of DBC to bulk DOC did not change during hydrothermal circulation, indicating that DBC is removed at similar rates as bulk DOC. The ratio of the oxidation products benzenehexacarboxylic acid (B6CA) to benzenepentacarboxylic acid (B5CA) was significantly higher in hydrothermally altered samples compared to ratios typically found in the deep ocean, reflecting a higher degree of condensation of DBC molecules after hydrothermal circulation. Our study identified hydrothermal circulation as a quantitatively important sink for refractory DBC in the deep ocean. In contrast to photodegradation of DBC at the sea surface, which is more efficient for more condensed DBC, i.e. decreasing the B6CA/B5CA ratio, hydrothermal processing increases the B6CA/B5CA ratio, introducing a characteristic hydrothermal DBC signature.

Reflection imaging of the Moon's interior using deep-moonquake seismic interferometry

NASA Astrophysics Data System (ADS)

Nishitsuji, Yohei; Rowe, C. A.; Wapenaar, Kees; Draganov, Deyan

2016-04-01

The internal structure of the Moon has been investigated over many years using a variety of seismic methods, such as travel time analysis, receiver functions, and tomography. Here we propose to apply body-wave seismic interferometry to deep moonquakes in order to retrieve zero-offset reflection responses (and thus images) beneath the Apollo stations on the nearside of the Moon from virtual sources colocated with the stations. This method is called deep-moonquake seismic interferometry (DMSI). Our results show a laterally coherent acoustic boundary around 50 km depth beneath all four Apollo stations. We interpret this boundary as the lunar seismic Moho. This depth agrees with Japan Aerospace Exploration Agency's (JAXA) SELenological and Engineering Explorer (SELENE) result and previous travel time analysis at the Apollo 12/14 sites. The deeper part of the image we obtain from DMSI shows laterally incoherent structures. Such lateral inhomogeneity we interpret as representing a zone characterized by strong scattering and constant apparent seismic velocity at our resolution scale (0.2-2.0 Hz).

Prediction of apparent extinction for optical transmission through rain

NASA Astrophysics Data System (ADS)

Vasseur, H.; Gibbins, C. J.

1996-12-01

At optical wavelengths, geometrical optics holds that the extinction efficiency of raindrops is equal to two. This approximation yields a wavelength-independent extinction coefficient that, however, can hardly be used to predict accurately rain extinction measured in optical transmissions. Actually, in addition to the extinct direct incoming light, a significant part of the power scattered by the rain particles reaches the receiver. This leads to a reduced apparent extinction that depends on both rain characteristics and link parameters. A simple method is proposed to evaluate this apparent extinction. It accounts for the additional scattered power that enters the receiver when one considers the forward-scattering pattern of the raindrops as well as the multiple-scattering effects using, respectively, the Fraunhofer diffraction and Twersky theory. It results in a direct analytical formula that enables a quick and accurate estimation of the rain apparent extinction and highlights the influence of the link parameters. Predictions of apparent extinction through rain are found in excellent agreement with measurements in the visible and IR regions.

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

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.

Current Status of The Romanian National Deep Geological Repository Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radu, M.; Nicolae, R.; Nicolae, D.

2008-07-01

Construction of a deep geological repository is a very demanding and costly task. By now, countries that have Candu reactors, have not processed the spent fuel passing to the interim storage as a preliminary step of final disposal within the nuclear fuel cycle back-end. Romania, in comparison to other nations, represents a rather small territory, with high population density, wherein the geological formation areas with radioactive waste storage potential are limited and restricted not only from the point of view of the selection criteria due to the rocks natural characteristics, but also from the point of view of their involvementmore » in social and economical activities. In the framework of the national R and D Programs, series of 'Map investigations' have been made regarding the selection and preliminary characterization of the host geological formation for the nation's spent fuel deep geological repository. The fact that Romania has many deposits of natural gas, oil, ore and geothermal water, and intensively utilizes soil and also is very forested, cause some of the apparent acceptable sites to be rejected in the subsequent analysis. Currently, according to the Law on the spent fuel and radioactive waste management, including disposal, The National Agency of Radioactive Waste is responsible and coordinates the national strategy in the field and, subsequently, further actions will be decided. The Romanian National Strategy, approved in 2004, projects the operation of a deep geological repository to begin in 2055. (authors)« less

Down-regulation of connective tissue growth factor by inhibition of transforming growth factor beta blocks the tumor-stroma cross-talk and tumor progression in hepatocellular carcinoma.

PubMed

Mazzocca, Antonio; Fransvea, Emilia; Dituri, Francesco; Lupo, Luigi; Antonaci, Salvatore; Giannelli, Gianluigi

2010-02-01

Tumor-stroma interactions in hepatocellular carcinoma (HCC) are of key importance to tumor progression. In this study, we show that HCC invasive cells produce high levels of connective tissue growth factor (CTGF) and generate tumors with a high stromal component in a xenograft model. A transforming growth factor beta (TGF-beta) receptor inhibitor, LY2109761, inhibited the synthesis and release of CTGF, as well as reducing the stromal component of the tumors. In addition, the TGF-beta-dependent down-regulation of CTGF diminished tumor growth, intravasation, and metastatic dissemination of HCC cells by inhibiting cancer-associated fibroblast proliferation. By contrast, noninvasive HCC cells were found to produce low levels of CTGF. Upon TGF-beta1 stimulation, noninvasive HCC cells form tumors with a high stromal content and CTGF expression, which is inhibited by treatment with LY2109761. In addition, the acquired intravasation and metastatic spread of noninvasive HCC cells after TGF-beta1 stimulation was blocked by LY2109761. LY2109761 interrupts the cross-talk between cancer cells and cancer-associated fibroblasts, leading to a significant reduction of HCC growth and dissemination. Interestingly, patients with high CTGF expression had poor prognosis, suggesting that treatment aimed at reducing TGF-beta-dependent CTGF expression may offer clinical benefits. Taken together, our preclinical results indicate that LY2109761 targets the cross-talk between HCC and the stroma and provide a rationale for future clinical trials.

Nearly extremal apparent horizons in simulations of merging black holes

NASA Astrophysics Data System (ADS)

Lovelace, Geoffrey; Scheel, Mark; Owen, Robert; Giesler, Matthew; Katebi, Reza; Szilagyi, Bela; Chu, Tony; Demos, Nicholas; Hemberger, Daniel; Kidder, Lawrence; Pfeiffer, Harald; Afshari, Nousha; SXS Collaboration

2015-04-01

The spin S of a Kerr black hole is bounded by the surface area A of its apparent horizon: 8 πS <= A . We present recent results (arXiv:1411.7297) for the extremality of apparent horizons for merging, rapidly rotating black holes with equal masses and equal spins aligned with the orbital angular momentum. Measuring the area and (using approximate Killing vectors) the spin on the individual and common apparent horizons, we find that the inequality 8 πS < A is satisfied but is very close to equality on the common apparent horizon at the instant it first appears--even for initial spins as large as S /M2 = 0 . 994 . We compute the smallest value e0 that Booth and Fairhurst's extremality parameter can take for any scaling of the horizon's null normal vectors, concluding that the common horizons are at least moderately close to extremal just after they appear. We construct binary-black-hole initial data with marginally trapped surfaces with 8 πS > A and e0 > 1 , but these surfaces are always surrounded by apparent horizons with 8 πS < A and e0 < 1 .

Evidence of two distinct functionally specialized fibroblast lineages in breast stroma.

PubMed

Morsing, Mikkel; Klitgaard, Marie Christine; Jafari, Abbas; Villadsen, René; Kassem, Moustapha; Petersen, Ole William; Rønnov-Jessen, Lone

2016-11-03

The terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma. The two lineages are prospectively isolated by fluorescence activated cell sorting (FACS) based on different expression levels of CD105 and CD26. The characteristics of the two fibroblast lineages are assessed by immunocytochemical staining and gene expression analysis. The differentiation capacity of the two fibroblast populations is determined by exposure to specific differentiating conditions followed by analysis of adipogenic and osteogenic differentiation. To test whether the two fibroblast lineages are functionally imprinted by their site of origin, single cell sorted CD271 low /MUC1 high normal breast luminal epithelial cells are plated on fibroblast feeders for the observation of morphological development. Epithelial structure formation and polarization is shown by immunofluorescence and digitalized quantification of immunoperoxidase-stained cultures. Lobular fibroblasts are CD105 high /CD26 low while interlobular fibroblasts are CD105 low /CD26 high . Once isolated the two lineages remain phenotypically stable and functionally distinct in culture. Lobular fibroblasts have properties in common with bone marrow derived mesenchymal stem cells and they specifically convey growth and branching morphogenesis of epithelial progenitors. Two distinct functionally specialized fibroblast lineages exist in the normal human breast, of which the lobular fibroblasts have properties in common with mesenchymal stem cells and support epithelial growth and morphogenesis. We propose that

Invasion in breast lesions: the role of the epithelial-stroma barrier.

PubMed

Rakha, Emad A; Miligy, Islam M; Gorringe, Kylie L; Toss, Michael S; Green, Andrew R; Fox, Stephen B; Schmitt, Fernando C; Tan, Puay-Hoon; Tse, Gary M; Badve, Sunil; Decker, Thomas; Vincent-Salomon, Anne; Dabbs, David J; Foschini, Maria P; Moreno, Filipa; Wentao, Yang; Geyer, Felipe C; Reis-Filho, Jorge S; Pinder, Sarah E; Lakhani, Sunil R; Ellis, Ian O

2018-06-01

Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different lesions in breast pathological diagnosis is based typically on the presence of an intact barrier between the malignant epithelial cells and stroma; namely, the myoepithelial cell (MEC) layer and surrounding basement membrane (BM). Despite being robust diagnostic criteria, the identification of MECs and BM to differentiate in-situ from invasive carcinoma is not always straightforward. The MEC layer around DCIS may be interrupted and/or show an altered immunoprofile. MECs may be absent in some benign locally infiltrative lesions such as microglandular adenosis and infiltrating epitheliosis, and occasionally in non-infiltrative conditions such as apocrine lesions, and in these contexts this does not denote malignancy or invasive disease with metastatic potential. MECs may also be absent around some malignant lesions such as some forms of papillary carcinoma, yet these behave in an indolent fashion akin to some DCIS. In Paget's disease, malignant mammary epithelial cells extend anteriorly from the ducts to infiltrate the epidermis of the nipple but do not typically infiltrate through the BM into the dermis. Conversely, BM-like material can be seen around invasive carcinoma cells and around metastatic tumour cell deposits. Here, we review the role of MECs and BM in breast pathology and highlight potential clinical implications. We advise caution in interpretation of MEC features in breast pathology and mindfulness of the substantive evidence base in the literature associated with behaviour and clinical outcome of lesions classified as benign on conventional morphological examination before changing classification to an invasive lesion on the sole basis of MEC characteristics. © 2017 John Wiley & Sons Ltd.

Electrolytic removal of recurrence of granular corneal dystrophy.

PubMed

Mashima, Y; Kawashima, M; Yamada, M

2003-11-01

To report the efficacy of corneal electrolysis for the treatment of recurrent corneal opacities at the subepithelial region or at the host-graft interface of the stroma in granular corneal dystrophy (GCD). In patients with recurrences of opacities at the host-graft interface of the stroma after lamellar keratoplasty, the deep aspect of the graft was partially separated from host tissue to expose the deposits. The graft was everted, and electrolysis was applied directly to remove the deposits attached to both surfaces of the host and the graft. Then the graft was returned to its place and sutured. In patients with diffuse subepithelial opacities following penetrating keratoplasty, electrolysis was applied directly to the corneal surface. Deposits in the subepithelial region or at the host-graft interface of the stroma disappeared following treatment, and vision recovered. However, GCD recurred 2-3 years after the treatment. Corneal electrolysis is a simple, easy, and inexpensive way to remove deposits that recur after lamellar or penetrating keratoplasty for GCD.

Apparent dispersion in transient groundwater flow

USGS Publications Warehouse

Goode, Daniel J.; Konikow, Leonard F.

1990-01-01

This paper investigates the effects of large-scale temporal velocity fluctuations, particularly changes in the direction of flow, on solute spreading in a two-dimensional aquifer. Relations for apparent longitudinal and transverse dispersivity are developed through an analytical solution for dispersion in a fluctuating, quasi-steady uniform flow field, in which storativity is zero. For transient flow, spatial moments are evaluated from numerical solutions. Ignored or unknown transients in the direction of flow primarily act to increase the apparent transverse dispersivity because the longitudinal dispersivity is acting in a direction that is not the assumed flow direction. This increase is a function of the angle between the transient flow vector and the assumed steady state flow direction and the ratio of transverse to longitudinal dispersivity. The maximum effect on transverse dispersivity occurs if storativity is assumed to be zero, such that the flow field responds instantly to boundary condition changes.

Does the Deep Layer of the Deep Temporalis Fascia Really Exist?

PubMed

Li, Hui; Li, Kaide; Jia, Wenhao; Han, Chaoying; Chen, Jinlong; Liu, Lei

2018-04-14

It has been widely accepted that a split of the deep temporal fascia occurs approximately 2 to 3 cm above the zygomatic arch and extends into the superficial and deep layers. The deep layer of the deep temporal fascia is between the superficial temporal fat pad and the temporal muscle. However, during procedures, the authors noted the absence of the deep layer of the deep temporal fascia between the superficial temporal fat pad and the temporal muscle. This prospective study was conducted to clarify the presence or absence of a deep layer of the deep temporal fascia. Anatomic layers of the soft tissues of the temporal region, with reference to the deep temporal fascia, were investigated in 130 cases operated on for zygomaticofacial fractures using the supratemporal approach from June 2013 to June 2017. Of 130 surgeries, the authors found the absence of a thick, obviously identifiable, fascial layer between the superficial temporal fat pad and the temporal muscle. In fact, the authors found nothing above the temporal muscle in most cases. In a few cases, the authors observed only a small amount of scattered loose connective tissue between the superficial temporal fat pad and the temporal muscle. This clinical study showed the absence of a thick, obviously identifiable, fascial layer between the superficial temporal fat pad and the temporal muscle, which suggests that a "deep layer of the deep temporal fascia" might not exist. Copyright © 2018. Published by Elsevier Inc.

Potential impacts of leakage from deep CO2 geosequestration on overlying freshwater aquifers.

PubMed

Little, Mark G; Jackson, Robert B

2010-12-01

Carbon Capture and Storage may use deep saline aquifers for CO(2) sequestration, but small CO(2) leakage could pose a risk to overlying fresh groundwater. We performed laboratory incubations of CO(2) infiltration under oxidizing conditions for >300 days on samples from four freshwater aquifers to 1) understand how CO(2) leakage affects freshwater quality; 2) develop selection criteria for deep sequestration sites based on inorganic metal contamination caused by CO(2) leaks to shallow aquifers; and 3) identify geochemical signatures for early detection criteria. After exposure to CO(2), water pH declines of 1-2 units were apparent in all aquifer samples. CO(2) caused concentrations of the alkali and alkaline earths and manganese, cobalt, nickel, and iron to increase by more than 2 orders of magnitude. Potentially dangerous uranium and barium increased throughout the entire experiment in some samples. Solid-phase metal mobility, carbonate buffering capacity, and redox state in the shallow overlying aquifers influence the impact of CO(2) leakage and should be considered when selecting deep geosequestration sites. Manganese, iron, calcium, and pH could be used as geochemical markers of a CO(2) leak, as their concentrations increase within 2 weeks of exposure to CO(2).

Bias of apparent tracer ages in heterogeneous environments.

PubMed

McCallum, James L; Cook, Peter G; Simmons, Craig T; Werner, Adrian D

2014-01-01

The interpretation of apparent ages often assumes that a water sample is composed of a single age. In heterogeneous aquifers, apparent ages estimated with environmental tracer methods do not reflect mean water ages because of the mixing of waters from many flow paths with different ages. This is due to nonlinear variations in atmospheric concentrations of the tracer with time resulting in biases of mixed concentrations used to determine apparent ages. The bias of these methods is rarely reported and has not been systematically evaluated in heterogeneous settings. We simulate residence time distributions (RTDs) and environmental tracers CFCs, SF6 , (85) Kr, and (39) Ar in synthetic heterogeneous confined aquifers and compare apparent ages to mean ages. Heterogeneity was simulated as both K-field variance (σ(2) ) and structure. We demonstrate that an increase in heterogeneity (increase in σ(2) or structure) results in an increase in the width of the RTD. In low heterogeneity cases, widths were generally on the order of 10 years and biases generally less than 10%. In high heterogeneity cases, widths can reach 100 s of years and biases can reach up to 100%. In cases where the temporal variations of atmospheric concentration of individual tracers vary, different patterns of bias are observed for the same mean age. We show that CFC-12 and CFC-113 ages may be used to correct for the mean age if analytical errors are small. © 2013, National Ground Water Association.

Execution of deep dipole geoelectrical soundings in areas of geothermal interest. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patella, D.

It is suggested that deep geoelectrical problems may be resolved by carrying out dipole soundings in the field and applying a quantitative interpretation in the Schlumberger domain. The 'transformation' of original field dipole sounding curves into equivalent Schlumberger curves is outlined for the cases of layered structures and arbitrary underground structures. Theoretical apparent resistivity curves are derived for soundings over bidimensional structures. Following a summary of the geological features of the Travale-Radicondoli geothermal area of Italy, the dipole sounding method employed for this field study and the means of collecting and analyzing the data, are outlined.

Surgical treatment for apparent early stage endometrial cancer

PubMed Central

2014-01-01

Most experts would agree that the standard surgical treatment for endometrial cancer includes a hysterectomy and bilateral salpingo-oophorectomy; however, the benefit of full surgical staging with lymph node dissection in patients with apparent early stage disease remains a topic of debate. Recent prospective data and advances in laparoscopic techniques have transformed this disease into one that can be successfully managed with minimally invasive surgery. This review will discuss the current surgical management of apparent early stage endometrial cancer and some of the new techniques that are being incorporated. PMID:24596812

Gene expression profiling of rat spermatogonia and Sertoli cells reveals signaling pathways from stem cells to niche and testicular cancer cells to surrounding stroma

PubMed Central

2011-01-01

Background Stem cells and their niches are studied in many systems, but mammalian germ stem cells (GSC) and their niches are still poorly understood. In rat testis, spermatogonia and undifferentiated Sertoli cells proliferate before puberty, but at puberty most spermatogonia enter spermatogenesis, and Sertoli cells differentiate to support this program. Thus, pre-pubertal spermatogonia might possess GSC potential and pre-pubertal Sertoli cells niche functions. We hypothesized that the different stem cell pools at pre-puberty and maturity provide a model for the identification of stem cell and niche-specific genes. We compared the transcript profiles of spermatogonia and Sertoli cells from pre-pubertal and pubertal rats and examined how these related to genes expressed in testicular cancers, which might originate from inappropriate communication between GSCs and Sertoli cells. Results The pre-pubertal spermatogonia-specific gene set comprised known stem cell and spermatogonial stem cell (SSC) markers. Similarly, the pre-pubertal Sertoli cell-specific gene set comprised known niche gene transcripts. A large fraction of these specifically enriched transcripts encoded trans-membrane, extra-cellular, and secreted proteins highlighting stem cell to niche communication. Comparing selective gene sets established in this study with published gene expression data of testicular cancers and their stroma, we identified sets expressed genes shared between testicular tumors and pre-pubertal spermatogonia, and tumor stroma and pre-pubertal Sertoli cells with statistic significance. Conclusions Our data suggest that SSC and their niche specifically express complementary factors for cell communication and that the same factors might be implicated in the communication between tumor cells and their micro-enviroment in testicular cancer. PMID:21232125

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

PubMed Central

Obonai, Toshifumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Kozuka, Naoyuki; Yasunaga, Masahiro; Matsumura, Yasuhiro

2016-01-01

The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma. PMID:27009516

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.

Targeting PI3K in cancer: impact on tumor cells, their protective stroma, angiogenesis and immunotherapy

PubMed Central

Okkenhaug, Klaus; Graupera, Mariona; Vanhaesebroeck, Bart

2017-01-01

The PI3K pathway is hyperactivated in most cancers, yet the capacity of PI3K inhibitors to induce tumor cell death is limited. The efficacy of PI3K inhibition can also derive from interference with the cancer cells’ ability to respond to stromal signals, as illustrated by the approved PI3Kδ inhibitor Idelalisib in B-cell malignancies. Inhibition of the leukocyte-enriched PI3Kδ or PI3Kγ may unleash more potent anti-tumor T-cell responses, by inhibiting regulatory T-cells and immune-suppressive myeloid cells. Moreover, tumor angiogenesis may be targeted by PI3K inhibitors to enhance cancer therapy. Future work should therefore focus on the effects of PI3K inhibitors on the stroma, in addition to their direct effects on tumors. Significance The PI3K pathway extends beyond the direct regulation of cancer cell proliferation and survival. In B-cell malignancies, targeting PI3K purges the tumor cells from their protective microenvironment. Moreover, we propose that PI3K isoform-selective inhibitors may be exploited in the context of cancer immunotherapy and by targeting angiogenesis to improve drug and immune cell delivery. PMID:27655435

Human brain metastatic stroma attracts breast cancer cells via chemokines CXCL16 and CXCL12.

PubMed

Chung, Brile; Esmaeili, Ali A; Gopalakrishna-Pillai, Sailesh; Murad, John P; Andersen, Emily S; Kumar Reddy, Naveen; Srinivasan, Gayathri; Armstrong, Brian; Chu, Caleb; Kim, Young; Tong, Tommy; Waisman, James; Yim, John H; Badie, Behnam; Lee, Peter P

2017-01-01

The tumor microenvironment is composed of heterogeneous populations of cells, including cancer, immune, and stromal cells. Progression of tumor growth and initiation of metastasis is critically dependent on the reciprocal interactions between cancer cells and stroma. Through RNA-Seq and protein analyses, we found that cancer-associated fibroblasts derived from human breast cancer brain metastasis express significantly higher levels of chemokines CXCL12 and CXCL16 than fibroblasts from primary breast tumors or normal breast. To further understand the interplay between cancer cells and cancer-associated fibroblasts from each site, we developed three-dimensional organoids composed of patient-derived primary or brain metastasis cancer cells with matching cancer-associated fibroblasts. Three-dimensional CAF aggregates generated from brain metastasis promote migration of cancer cells more effectively than cancer-associated fibroblast aggregates derived from primary tumor or normal breast stromal cells. Treatment with a CXCR4 antagonist and/or CXCL16 neutralizing antibody, alone or in combination, significantly inhibited migration of cancer cells to brain metastatic cancer-associated fibroblast aggregates. These results demonstrate that human brain metastasis cancer-associated fibroblasts potently attract breast cancer cells via chemokines CXCL12 and CXCL16, and blocking CXCR6-CXCL16/CXCR4-CXCL12 receptor-ligand interactions may be an effective therapy for preventing breast cancer brain metastasis.

DeepSynergy: predicting anti-cancer drug synergy with Deep Learning

PubMed Central

Preuer, Kristina; Lewis, Richard P I; Hochreiter, Sepp; Bender, Andreas; Bulusu, Krishna C; Klambauer, Günter

2018-01-01

Abstract Motivation While drug combination therapies are a well-established concept in cancer treatment, identifying novel synergistic combinations is challenging due to the size of combinatorial space. However, computational approaches have emerged as a time- and cost-efficient way to prioritize combinations to test, based on recently available large-scale combination screening data. Recently, Deep Learning has had an impact in many research areas by achieving new state-of-the-art model performance. However, Deep Learning has not yet been applied to drug synergy prediction, which is the approach we present here, termed DeepSynergy. DeepSynergy uses chemical and genomic information as input information, a normalization strategy to account for input data heterogeneity, and conical layers to model drug synergies. Results DeepSynergy was compared to other machine learning methods such as Gradient Boosting Machines, Random Forests, Support Vector Machines and Elastic Nets on the largest publicly available synergy dataset with respect to mean squared error. DeepSynergy significantly outperformed the other methods with an improvement of 7.2% over the second best method at the prediction of novel drug combinations within the space of explored drugs and cell lines. At this task, the mean Pearson correlation coefficient between the measured and the predicted values of DeepSynergy was 0.73. Applying DeepSynergy for classification of these novel drug combinations resulted in a high predictive performance of an AUC of 0.90. Furthermore, we found that all compared methods exhibit low predictive performance when extrapolating to unexplored drugs or cell lines, which we suggest is due to limitations in the size and diversity of the dataset. We envision that DeepSynergy could be a valuable tool for selecting novel synergistic drug combinations. Availability and implementation DeepSynergy is available via www.bioinf.jku.at/software/DeepSynergy. Contact klambauer

Nearly extremal apparent horizons in simulations of merging black holes

NASA Astrophysics Data System (ADS)

Lovelace, Geoffrey; Scheel, Mark A.; Owen, Robert; Giesler, Matthew; Katebi, Reza; Szilágyi, Béla; Chu, Tony; Demos, Nicholas; Hemberger, Daniel A.; Kidder, Lawrence E.; Pfeiffer, Harald P.; Afshari, Nousha

2015-03-01

The spin angular momentum S of an isolated Kerr black hole is bounded by the surface area A of its apparent horizon: 8π S≤slant A, with equality for extremal black holes. In this paper, we explore the extremality of individual and common apparent horizons for merging, rapidly spinning binary black holes. We consider simulations of merging black holes with equal masses M and initial spin angular momenta aligned with the orbital angular momentum, including new simulations with spin magnitudes up to S/{{M}2}=0.994. We measure the area and (using approximate Killing vectors) the spin on the individual and common apparent horizons, finding that the inequality 8π S\\lt A is satisfied in all cases but is very close to equality on the common apparent horizon at the instant it first appears. We also evaluate the Booth-Fairhurst extremality, whose value for a given apparent horizon depends on the scaling of the horizon’s null normal vectors. In particular, we introduce a gauge-invariant lower bound on the extremality by computing the smallest value that Booth and Fairhurst’s extremality parameter can take for any scaling. Using this lower bound, we conclude that the common horizons are at least moderately close to extremal just after they appear. Finally, following Lovelace et al (2008 Phys. Rev. D 78 084017), we construct quasiequilibrium binary-black hole initial data with ‘overspun’ marginally trapped surfaces with 8π S\\gt A. We show that the overspun surfaces are indeed superextremal: our lower bound on their Booth-Fairhurst extremality exceeds unity. However, we confirm that these superextremal surfaces are always surrounded by marginally outer trapped surfaces (i.e., by apparent horizons) with 8π S\\lt A. The extremality lower bound on the enclosing apparent horizon is always less than unity but can exceed the value for an extremal Kerr black hole.

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.

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

True and apparent inhibition of amyloid fibril formation.

PubMed

Martins, Pedro M

2013-01-01

A possible therapeutic strategy for amyloid diseases involves the use of small molecule compounds to inhibit protein assembly into insoluble aggregates. According to the recently proposed Crystallization-Like Model, the kinetics of amyloid fibrillization can be retarded by decreasing the frequency of new fibril formation or by decreasing the elongation rate of existing fibrils. To the compounds that affect the nucleation and/or the growth steps we call true inhibitors. An apparent inhibition mechanism may however result from the alteration of thermodynamic properties such as the solubility of the amyloidogenic protein. Apparent inhibitors markedly influence protein aggregation kinetics measured in vitro, yet they are likely to lead to disappointing results when tested in vivo. This is because cells and tissues media are in general much more buffered against small variations in composition than the solutions prepared in lab. Here we show how to discriminate between true and apparent inhibition mechanisms from experimental data on protein aggregation kinetics. The goal is to be able to identify false positives much earlier during the drug development process.

Dendrites, deep learning, and sequences in the hippocampus.

PubMed

Bhalla, Upinder S

2017-10-12

The hippocampus places us both in time and space. It does so over remarkably large spans: milliseconds to years, and centimeters to kilometers. This works for sensory representations, for memory, and for behavioral context. How does it fit in such wide ranges of time and space scales, and keep order among the many dimensions of stimulus context? A key organizing principle for a wide sweep of scales and stimulus dimensions is that of order in time, or sequences. Sequences of neuronal activity are ubiquitous in sensory processing, in motor control, in planning actions, and in memory. Against this strong evidence for the phenomenon, there are currently more models than definite experiments about how the brain generates ordered activity. The flip side of sequence generation is discrimination. Discrimination of sequences has been extensively studied at the behavioral, systems, and modeling level, but again physiological mechanisms are fewer. It is against this backdrop that I discuss two recent developments in neural sequence computation, that at face value share little beyond the label "neural." These are dendritic sequence discrimination, and deep learning. One derives from channel physiology and molecular signaling, the other from applied neural network theory - apparently extreme ends of the spectrum of neural circuit detail. I suggest that each of these topics has deep lessons about the possible mechanisms, scales, and capabilities of hippocampal sequence computation. © 2017 Wiley Periodicals, Inc.

A Theoretical Model to Predict Both Horizontal Displacement and Vertical Displacement for Electromagnetic Induction-Based Deep Displacement Sensors

PubMed Central

Shentu, Nanying; Zhang, Hongjian; Li, Qing; Zhou, Hongliang; Tong, Renyuan; Li, Xiong

2012-01-01

Deep displacement observation is one basic means of landslide dynamic study and early warning monitoring and a key part of engineering geological investigation. In our previous work, we proposed a novel electromagnetic induction-based deep displacement sensor (I-type) to predict deep horizontal displacement and a theoretical model called equation-based equivalent loop approach (EELA) to describe its sensing characters. However in many landslide and related geological engineering cases, both horizontal displacement and vertical displacement vary apparently and dynamically so both may require monitoring. In this study, a II-type deep displacement sensor is designed by revising our I-type sensor to simultaneously monitor the deep horizontal displacement and vertical displacement variations at different depths within a sliding mass. Meanwhile, a new theoretical modeling called the numerical integration-based equivalent loop approach (NIELA) has been proposed to quantitatively depict II-type sensors’ mutual inductance properties with respect to predicted horizontal displacements and vertical displacements. After detailed examinations and comparative studies between measured mutual inductance voltage, NIELA-based mutual inductance and EELA-based mutual inductance, NIELA has verified to be an effective and quite accurate analytic model for characterization of II-type sensors. The NIELA model is widely applicable for II-type sensors’ monitoring on all kinds of landslides and other related geohazards with satisfactory estimation accuracy and calculation efficiency. PMID:22368467

A theoretical model to predict both horizontal displacement and vertical displacement for electromagnetic induction-based deep displacement sensors.

PubMed

Shentu, Nanying; Zhang, Hongjian; Li, Qing; Zhou, Hongliang; Tong, Renyuan; Li, Xiong

2012-01-01

Deep displacement observation is one basic means of landslide dynamic study and early warning monitoring and a key part of engineering geological investigation. In our previous work, we proposed a novel electromagnetic induction-based deep displacement sensor (I-type) to predict deep horizontal displacement and a theoretical model called equation-based equivalent loop approach (EELA) to describe its sensing characters. However in many landslide and related geological engineering cases, both horizontal displacement and vertical displacement vary apparently and dynamically so both may require monitoring. In this study, a II-type deep displacement sensor is designed by revising our I-type sensor to simultaneously monitor the deep horizontal displacement and vertical displacement variations at different depths within a sliding mass. Meanwhile, a new theoretical modeling called the numerical integration-based equivalent loop approach (NIELA) has been proposed to quantitatively depict II-type sensors' mutual inductance properties with respect to predicted horizontal displacements and vertical displacements. After detailed examinations and comparative studies between measured mutual inductance voltage, NIELA-based mutual inductance and EELA-based mutual inductance, NIELA has verified to be an effective and quite accurate analytic model for characterization of II-type sensors. The NIELA model is widely applicable for II-type sensors' monitoring on all kinds of landslides and other related geohazards with satisfactory estimation accuracy and calculation efficiency.

Endometrial expression of the insulin-like growth factor system during uterine involution in the postpartum dairy cow.

PubMed

Llewellyn, S; Fitzpatrick, R; Kenny, D A; Patton, J; Wathes, D C

2008-05-01

Rapid uterine involution in the postpartum period of dairy cows is important to achieve a short interval to conception. Expression patterns for members of the insulin-like growth factor (IGF) family were determined by in situ hybridisation at day 14+/-0.4 postpartum (n=12 cows) to investigate a potential role for IGFs in modulating uterine involution. Expression in each uterine tissue region was measured as optical density units and data were analysed according to region and horn. IGF-I mRNA was localized to the sub-epithelial stroma (SES) of inter-caruncular and caruncular endometrium. Both IGF-II and IGF-1R expression was detected in the deep endometrial stroma (DES), the caruncular stroma and myometrium. IGFBP-2, IGFBP-4 and IGFBP-6 mRNAs were all localised to the SES of inter-caruncular and caruncular uterine tissue, and in the DES and caruncular stroma, with IGFBP-4 mRNA additionally expressed in myometrium. IGFBP-3 mRNA was only detectable in luminal epithelium. IGFBP-5 mRNA was found in myometrium, inter-caruncular and caruncular SES and caruncular stroma. These data support a role for IGF-I and IGF-II in the extensive tissue remodelling and repair which the postpartum uterus undergoes to return to its non-pregnant state. The differential expression of binding proteins between tissues (IGFBP-3 in epithelium, IGFBP-2, -4, -5 and -6 in stroma and IGFBP-4 and -5 in myometrium) suggest tight control of IGF activity within each compartment. Differential expression of many members of the IGF family between the significantly larger previously gravid horn and the previously non-gravid horn may relate to differences in their rate of tissue remodelling.

Deep Logic Networks: Inserting and Extracting Knowledge From Deep Belief Networks.

PubMed

Tran, Son N; d'Avila Garcez, Artur S

2018-02-01

Developments in deep learning have seen the use of layerwise unsupervised learning combined with supervised learning for fine-tuning. With this layerwise approach, a deep network can be seen as a more modular system that lends itself well to learning representations. In this paper, we investigate whether such modularity can be useful to the insertion of background knowledge into deep networks, whether it can improve learning performance when it is available, and to the extraction of knowledge from trained deep networks, and whether it can offer a better understanding of the representations learned by such networks. To this end, we use a simple symbolic language-a set of logical rules that we call confidence rules-and show that it is suitable for the representation of quantitative reasoning in deep networks. We show by knowledge extraction that confidence rules can offer a low-cost representation for layerwise networks (or restricted Boltzmann machines). We also show that layerwise extraction can produce an improvement in the accuracy of deep belief networks. Furthermore, the proposed symbolic characterization of deep networks provides a novel method for the insertion of prior knowledge and training of deep networks. With the use of this method, a deep neural-symbolic system is proposed and evaluated, with the experimental results indicating that modularity through the use of confidence rules and knowledge insertion can be beneficial to network performance.

Reservoir compartmentalization of deep-water Intra Qua Iboe sand (Pliocene), Edop field, offshore Nigeria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hermance, W.E.; Olaifa, J.O.; Shanmugam, G.

An integration of 3-D seismic and sedimentological information provides a basis for recognizing and mapping individual flow units within the Intra Qua Iboe (IQI) reservoir (Pliocene), Edop Field, offshore Nigeria. Core examination show the following depositional facies: A-Sandy slump/mass flow, B-Muddy slump/mass flow, C. Bottom current reworking. D-Non-channelized turbidity currents, E. Channelized (coalesced) turbidity currents. F-Channelized (isolated) turbidity currents, G-Pelagic/hemipelagic, H-Levee, I-Reworked slope, J-Wave dominated, and K-Tide dominated facies. With the exception of facies J and K, all these facies are of deep-water affinity. The IQI was deposited on an upper slope environment in close proximity to the shelf edge.more » Through time, as the shelf edge migrated scaward, deposition began with a channel dominated deep-water system (IQI 1 and 2) and progressed through a slump/debris flow dominated deep-water system (IQI 3, the principle reservoir) to a tide and wave dominated shallow-water system (IQI 4). Compositional and textural similarities between the deep-water facies result in similar log motifs. Furthermore, these depositional facies are not readily apparent as distinct seismic facies. Deep-water facies A, D, E, and F are reservoir facies, whereas facies B, C, G, H, and I are non-reservoir facies. However, Facies G is useful as a seismically mappable event throughout the study area. Mapping of these non-reservoir events provides the framework for understanding gross reservoir architecture. This study has resulted in seven defined reservoir units within the IQI, which serves as the architectural framework for ongoing reservoir characterization.« less

Deep Vein Thrombosis

MedlinePlus

Deep vein thrombosis, or DVT, is a blood clot that forms in a vein deep in the body. Most ... vein swells, the condition is called thrombophlebitis. A deep vein thrombosis can break loose and cause a serious problem ...

Constraining the source location of the 30 May 2015 (Mw 7.9) Bonin deep-focus earthquake using seismogram envelopes of high-frequency P waveforms: Occurrence of deep-focus earthquake at the bottom of a subducting slab

NASA Astrophysics Data System (ADS)

Takemura, Shunsuke; Maeda, Takuto; Furumura, Takashi; Obara, Kazushige

2016-05-01

In this study, the source location of the 30 May 2015 (Mw 7.9) deep-focus Bonin earthquake was constrained using P wave seismograms recorded across Japan. We focus on propagation characteristics of high-frequency P wave. Deep-focus intraslab earthquakes typically show spindle-shaped seismogram envelopes with peak delays of several seconds and subsequent long-duration coda waves; however, both the main shock and aftershock of the 2015 Bonin event exhibited pulse-like P wave propagations with high apparent velocities (~12.2 km/s). Such P wave propagation features were reproduced by finite-difference method simulations of seismic wave propagation in the case of slab-bottom source. The pulse-like P wave seismogram envelopes observed from the 2015 Bonin earthquake show that its source was located at the bottom of the Pacific slab at a depth of ~680 km, rather than within its middle or upper regions.

Deep centers in AlGaN-based light emitting diode structures

NASA Astrophysics Data System (ADS)

Polyakov, A. Y.; Smirnov, N. B.; Govorkov, A. V.; Mil'vidskii, M. G.; Usikov, A. S.; Pushnyi, B. V.; Lundin, W. V.

1999-10-01

Deep traps were studied in GaN homojunction and AlGaN/GaN heterojunction light emitting diode (LED) p-i-n structures by means of deep levels transient spectroscopy (DLTS), admittance and electroluminescence (EL) spectra measurements. It is shown that, in homojunction LED structures, the EL spectra comes from recombination involving Mg acceptors in-diffusing into the active i-layer. This Mg in-diffusion is strongly suppressed in heterostructures with the upper p-type layer containing about 5% of Al. As a result the main peak in the EL spectra of heterostructures is shifted toward higher energy compared to homojunctions. Joint doping of the i-layer with Zn and Si allows to shift the main EL peak to longer wavelength. The dominant electron traps observed in the studied LED structures had ionization energies of 0.55 and 0.85 eV. The dominant hole traps had apparent ionization energies of 0.85 and 0.4 eV. The latter traps were shown to be metastable and it is argued that they could be at least in part responsible for the persistent photoconductivity observed in p-GaN.

Out of Their Depth? Isolated Deep Populations of the Cosmopolitan Coral Desmophyllum dianthus May Be Highly Vulnerable to Environmental Change

PubMed Central

Miller, Karen J.; Rowden, Ashley A.; Williams, Alan; Häussermann, Vreni

2011-01-01

Deep sea scleractinian corals will be particularly vulnerable to the effects of climate change, facing loss of up to 70% of their habitat as the Aragonite Saturation Horizon (below which corals are unable to form calcium carbonate skeletons) rises. Persistence of deep sea scleractinian corals will therefore rely on the ability of larvae to disperse to, and colonise, suitable shallow-water habitat. We used DNA sequence data of the internal transcribed spacer (ITS), the mitochondrial ribosomal subunit (16S) and mitochondrial control region (MtC) to determine levels of gene flow both within and among populations of the deep sea coral Desmophyllum dianthus in SE Australia, New Zealand and Chile to assess the ability of corals to disperse into different regions and habitats. We found significant genetic subdivision among the three widely separated geographic regions consistent with isolation and limited contemporary gene flow. Furthermore, corals from different depth strata (shallow <600 m, mid 1000–1500 m, deep >1500 m) even on the same or nearby seamounts were strongly differentiated, indicating limited vertical larval dispersal. Genetic differentiation with depth is consistent with the stratification of the Subantarctic Mode Water, Antarctic Intermediate Water, the Circumpolar Deep and North Pacific Deep Waters in the Southern Ocean, and we propose that coral larvae will be retained within, and rarely migrate among, these water masses. The apparent absence of vertical larval dispersal suggests deep populations of D. dianthus are unlikely to colonise shallow water as the aragonite saturation horizon rises and deep waters become uninhabitable. Similarly, assumptions that deep populations will act as refuges for shallow populations that are impacted by activities such as fishing or mining are also unlikely to hold true. Clearly future environmental management strategies must consider both regional and depth-related isolation of deep-sea coral populations. PMID

Corrosion casts of big bubbles formed during deep anterior lamellar keratoplasty.

PubMed

Feizi, Sepehr; Kanavi, Mozhgan Rezaei; Kharaghani, Davood; Balagholi, Sahar; Meskinfam, Masoumeh; Javadi, Mohammad Ali

2016-11-01

To characterize the walls of big bubbles formed during deep anterior lamellar keratoplasty (DALK) using the corrosion casting technique. Fresh corneoscleral buttons with normal transparency and without any known eye diseases (n = 11) were obtained from 11 human donors. A 20-gauge needle was used to inject a solution of 20 % polyvinyl alcohol (PVA) immediately beneath the corneal endothelium to form big bubbles in eight corneoscleral buttons. In the second experiment on three corneoscleral buttons, a big bubble was first formed by air injection beneath the endothelium. Thereafter, 20 % PVA was injected into the bubble space. Scanning electron microscopy was used to characterize the surfaces of the casts, which replicated the walls of the big bubbles. A type-1 bubble was formed in all corneas. In one cornea, one type-1 bubble was initially formed centrally, and while it was enlarged, an eccentric type-2 bubble appeared. Scanning electron microscopy showed that the casts of type-1 bubbles had two distinct surfaces. The anterior surface demonstrated several holes or pits, depending on the material used for the bubble formation, whereas the posterior surface exhibited an uneven surface. The anterior and posterior surfaces of the type-2 cast were more or less similar. A communication measuring 531.9 µm in length and 171.4 µm in diameter was found between the two bubbles. The corrosion casting technique provides a permanent three-dimensional record of the potential spaces and barriers in the posterior corneal stroma, which explains several features associated with big-bubble DALK.

PET Imaging of Macrophage Mannose Receptor-Expressing Macrophages in Tumor Stroma Using 18F-Radiolabeled Camelid Single-Domain Antibody Fragments.

PubMed

Blykers, Anneleen; Schoonooghe, Steve; Xavier, Catarina; D'hoe, Kevin; Laoui, Damya; D'Huyvetter, Matthias; Vaneycken, Ilse; Cleeren, Frederik; Bormans, Guy; Heemskerk, Johannes; Raes, Geert; De Baetselier, Patrick; Lahoutte, Tony; Devoogdt, Nick; Van Ginderachter, Jo A; Caveliers, Vicky

2015-08-01

Tumor-associated macrophages constitute a major component of the stroma of solid tumors, encompassing distinct subpopulations with different characteristics and functions. We aimed to identify M2-oriented tumor-supporting macrophages within the tumor microenvironment as indicators of cancer progression and prognosis, using PET imaging. This can be realized by designing (18)F-labeled camelid single-domain antibody fragments (sdAbs) specifically targeting the macrophage mannose receptor (MMR), which has been identified as an important biomarker on this cell population. Cross-reactive anti-MMR sdAbs were generated after immunization of an alpaca with the extracellular domains of both human and mouse MMR. The lead binder was chosen on the basis of comparisons of binding affinity and in vivo pharmacokinetics. The PET tracer (18)F-fluorobenzoate (FB)-anti-MMR sdAb was developed using the prosthetic group N-succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB), and its biodistribution, tumor-targeting potential, and specificity in terms of macrophage and MMR targeting were evaluated in mouse tumor models. Four sdAbs were selected after affinity screening, but only 2 were found to be cross-reactive for human and mouse MMR. The lead anti-MMR 3.49 sdAb, bearing an affinity of 12 and 1.8 nM for mouse and human MMR, respectively, was chosen for its favorable in vivo biodistribution profile and tumor-targeting capacity. (18)F-FB-anti-MMR 3.49 sdAb was synthesized with a 5%-10% radiochemical yield using an automated and optimized protocol. In vivo biodistribution analyses showed fast clearance via the kidneys and retention in MMR-expressing organs and tumor. The kidney retention of the fluorinated sdAb was 20-fold lower than a (99m)Tc-labeled counterpart. Compared with MMR- and C-C chemokine receptor 2-deficient mice, significantly higher uptake was observed in tumors grown in wild-type mice, demonstrating the specificity of the (18)F tracer for MMR and macrophages, respectively. Anti

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

2017-10-01

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 3rd passage was made in the same manner. Five UPS tumors from each passage in both RFP and non-colored mouse models were harvested. The FV1,000 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. J. Cell. Biochem. 118: 3367-3371, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

RIA fractions contain mesenchymal stroma cells with high osteogenic potency.

PubMed

Kuehlfluck, Pamela; Moghaddam, Arash; Helbig, Lars; Child, Christopher; Wildemann, Britt; Schmidmaier, Gerhard

2015-12-01

The gold standard for treatment of non-union is the transplantation of autologous bone from iliac crest. As an alternative, material can be harvested by femoral reaming with the Reamer-Irrigator-Aspirator(®) (RIA)-System. This material might be a source for human mesenchymal stroma cells (MSCs) with osteogenic potency. The aim of this study was the characterisation of cells harvested with the RIA system and the comparison of their properties with cells isolated from bone marrow ("BM") and fat tissue ("adipose"). The RIA material was separated into the liquid aspiration fraction ("liquid") and the solid RIA fraction. From the solid RIA fraction the cells were cultured either directly ("native") or after collagenase digestion and filtration ("filtrate"). Stem cell characteristics were analysed and the osteogenic potential was investigated in vitro and in vivo. Fat tissue and bone marrow were harvested from nine patients (three women, six males, with a mean of 48.1 years) with atrophic non-union RIA material. The cells were isolated and characterised by flow cytometry, three lineage differentiation capacities and colony-forming unit fibroblast assay. Gene expression profiles were performed and osteogenic differentiation in vivo was analysed. All three RIA fractions contained mesenchymal stromal cells (MSCs) as demonstrated by CFU-F assay, three linage differentiation and surface marker analysis. The RIA-MSCs exhibited a significantly higher osteogenic potential in vitro compared to adipose-MSCs, whereas no difference was seen compared to BM-MSCs. Quantitative RT-PCR analysis revealed an expression of osteogenic markers in all isolated cells. The implantation of MSCs with β-TCP scaffolds into the mice muscle showed significantly higher bone formation for the filtrate RIA-MSC, native RIA-MSC and BM-MSC groups compared to the adipose-MSC group. The filtrate RIA-MSCs formed twice as much new bone in vivo compared to BM-MSCs. The present study showed high potency of

Geographic variation in apparent competition between native and invasive Phragmites australis.

PubMed

Bhattarai, Ganesh P; Meyerson, Laura A; Cronin, James T

2017-02-01

Apparent competition, the negative interaction between species mediated by shared natural enemies, is thought to play an important role in shaping the structure and dynamics of natural communities. However, its importance in driving species invasions, and whether the strength of this indirect interaction varies across the latitudinal range of the invasion, has not been fully explored. We performed replicated field experiments at four sites spanning 900 km along the Atlantic Coast of the United States to assess the presence and strength of apparent competition between sympatric native and invasive lineages of Phragmites australis. Four herbivore guilds were considered: stem-feeders, leaf-miners, leaf-chewers and aphids. We also tested the hypothesis that the strength of this interaction declines with increasing latitude. Within each site, native and invasive plants of P. australis were cross-transplanted between co-occurring native and invasive patches in the same marsh habitat and herbivore damage was evaluated at the end of the growing season. Apparent competition was evident for both lineages and involved all but the leaf-chewer guild. For native plants, total aphids per plant was 296% higher and the incidence of stem-feeding and leaf-mining herbivores was 34% and 221% higher, respectively, when transplanted into invasive than native patches. These data suggest that invasive P. australis has a negative effect on native P. australis via apparent competition. Averaged among herbivore types, the indirect effects of the invasive lineage on the native lineage was 57% higher than the reverse situation, suggesting that apparent competition was asymmetric. We also found that the strength of apparent competition acting against the native lineage was comparable to the benefits to the invasive lineage from enemy release (i.e., proportionately lower mean herbivory of the invasive relative to the native taxa). Finally, we found the first evidence that the strength of

Hydrogen peroxide in deep waters from the Mediterranean Sea, South Atlantic and South Pacific Oceans

NASA Astrophysics Data System (ADS)

Hopwood, Mark J.; Rapp, Insa; Schlosser, Christian; Achterberg, Eric P.

2017-03-01

Hydrogen peroxide (H2O2) is present ubiquitously in marine surface waters where it is a reactive intermediate in the cycling of many trace elements. Photochemical processes are considered the dominant natural H2O2 source, yet cannot explain nanomolar H2O2 concentrations below the photic zone. Here, we determined the concentration of H2O2 in full depth profiles across three ocean basins (Mediterranean Sea, South Atlantic and South Pacific Oceans). To determine the accuracy of H2O2 measurements in the deep ocean we also re-assessed the contribution of interfering species to ‘apparent H2O2’, as analysed by the luminol based chemiluminescence technique. Within the vicinity of coastal oxygen minimum zones, accurate measurement of H2O2 was not possible due to interference from Fe(II). Offshore, in deep (>1000 m) waters H2O2 concentrations ranged from 0.25 ± 0.27 nM (Mediterranean, Balearics-Algeria) to 2.9 ± 2.2 nM (Mediterranean, Corsica-France). Our results indicate that a dark, pelagic H2O2 production mechanism must occur throughout the deep ocean. A bacterial source of H2O2 is the most likely origin and we show that this source is likely sufficient to account for all of the observed H2O2 in the deep ocean.

Hydrogen peroxide in deep waters from the Mediterranean Sea, South Atlantic and South Pacific Oceans

PubMed Central

Hopwood, Mark J.; Rapp, Insa; Schlosser, Christian; Achterberg, Eric P.

2017-01-01

Hydrogen peroxide (H2O2) is present ubiquitously in marine surface waters where it is a reactive intermediate in the cycling of many trace elements. Photochemical processes are considered the dominant natural H2O2 source, yet cannot explain nanomolar H2O2 concentrations below the photic zone. Here, we determined the concentration of H2O2 in full depth profiles across three ocean basins (Mediterranean Sea, South Atlantic and South Pacific Oceans). To determine the accuracy of H2O2 measurements in the deep ocean we also re-assessed the contribution of interfering species to ‘apparent H2O2’, as analysed by the luminol based chemiluminescence technique. Within the vicinity of coastal oxygen minimum zones, accurate measurement of H2O2 was not possible due to interference from Fe(II). Offshore, in deep (>1000 m) waters H2O2 concentrations ranged from 0.25 ± 0.27 nM (Mediterranean, Balearics-Algeria) to 2.9 ± 2.2 nM (Mediterranean, Corsica-France). Our results indicate that a dark, pelagic H2O2 production mechanism must occur throughout the deep ocean. A bacterial source of H2O2 is the most likely origin and we show that this source is likely sufficient to account for all of the observed H2O2 in the deep ocean. PMID:28266529

The 'Appar' flax release: Origin, distinguishing characteristics, and use; and a native alternative

Treesearch

Rosemary L. Pendleton; Stanley G. Kitchen; E. Durant McArthur; Joann E. Mudge

2008-01-01

This article summarizes information on the taxonomy of 'Appar', a perennial blue flax cultivar (Linum perenne L. [Linaceae]), and characteristics that distinguish it from native Lewis flax (Linum lewisii Pursh [Linaceae]). 'Appar' apparently originated as a European flax that escaped from garden cultivation. Randomly amplified polymorphic DNA (RAPD...

The instantaneous apparent resistivity tensor: a visualization scheme for LOTEM electric field measurements

NASA Astrophysics Data System (ADS)

Caldwell, T. Grant; Bibby, Hugh M.

1998-12-01

Long-offset transient electromagnetic (LOTEM) data have traditionally been represented as early- and late-time apparent resistivities. Time-varying electric field data recorded in a LOTEM survey made with multiple sources can be represented by an `instantaneous apparent resistivity tensor'. Three independent, coordinate-invariant, time-varying apparent resistivities can be derived from this tensor. For dipolar sources, the invariants are also independent of source orientation. In a uniform-resistivity half-space, the invariant given by the square root of the tensor determinant remains almost constant with time, deviating from the half-space resistivity by a maximum of 6 per cent. For a layered half-space, a distance-time pseudo-section of the determinant apparent resistivity produces an image of the layering beneath the measurement profile. As time increases, the instantaneous apparent resistivity tensor approaches the direct current apparent resistivity tensor. An approximate time-to-depth conversion can be achieved by integrating the diffusion depth formula with time, using the determinant apparent resistivity at each instant to represent the resistivity of the conductive medium. Localized near-surface inhomogeneities produce shifts in the time-domain apparent resistivity sounding curves that preserve the gradient, analogous to static shifts seen in magnetotelluric soundings. Instantaneous apparent resistivity tensors calculated for 3-D resistivity models suggest that profiles of LOTEM measurements across a simple 3-D structure can be used to create an image that reproduces the main features of the subsurface resistivity. Where measurements are distributed over an area, maps of the tensor invariants can be made into a sequence of images, which provides a way of `time slicing' down through the target structure.

Deep-sea pennatulaceans (sea pens) - recent discoveries, morphological adaptations, and responses to benthic oceanographic parameters

NASA Astrophysics Data System (ADS)

Williams, G. C.

2015-12-01

Pennatulaceans are sessile, benthic marine organisms that are bathymetrically wide-ranging, from the intertidal to approximately 6300 m in depth, and are conspicuous constituents of deep-sea environments. The vast majority of species are adapted for anchoring in soft sediments by the cylindrical peduncle - a muscular hydrostatic skeleton. However, in the past decade a few species ("Rockpens") have been discovered and described that can attach to hard substratum such as exposed rocky outcrops at depths between 669 and 1969 m, by a plunger-like adaptation of the base of the peduncle. Of the thirty-six known genera, eleven (or 30%) have been recorded from depths greater than 1000 m. The pennatulacean depth record holders are an unidentified species of Umbellula from 6260 m in the Peru-Chile Trench and a recently-discovered and described genus and species, Porcupinella profunda, from 5300 m the Porcupine Abyssal Plain of the northeastern Atlantic. A morphologically-differentiated type of polyp (acrozooid) have recently been discovered and described in two genera of shallow-water coral reef sea pens. Acrozooids apparently represent asexual buds and presumably can detach from the adult to start clonal colonies through asexual budding. Acrozooids are to be expected in deep-sea pennatulaceans, but so far have not been observed below 24 m in depth. Morphological responses at depths greater than 1000 m in deep-sea pennatulaceas include: fewer polyps, larger polyps, elongated stalks, and clustering of polyps along the rachis. Responses to deep-ocean physical parameters and anthropogenic changes that could affect the abundance and distribution of deep-sea pennatulaceans include changes in bottom current flow and food availability, changes in seawater temperature and pH, habitat destruction by fish trawling, and sunken refuse pollution. No evidence of the effects of ocean acidification or other effects of anthropogenic climate change in sea pens of the deep-sea has been

Differential expression and regulation of vitamin D hydroxylases and inflammatory genes in prostate stroma and epithelium by 1,25-dihydroxyvitamin D in men with prostate cancer and an in vitro model.

PubMed

Giangreco, Angeline A; Dambal, Shweta; Wagner, Dennis; Van der Kwast, Theodorus; Vieth, Reinhold; Prins, Gail S; Nonn, Larisa

2015-04-01

Previous work on vitamin D in the prostate has focused on the prostatic epithelium, from which prostate cancer arises. Prostatic epithelial cells are surrounded by stroma, which has well-established regulatory control over epithelial proliferation, differentiation, and the inflammatory response. Here we examined the regulation of vitamin D-related genes and inflammatory genes by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D) in laser-capture microdissected prostate tissue from a vitamin D3 clinical trial and in an in vitro model that facilitates stromal-epithelial crosstalk. Analysis of the trial tissues showed that VDR was present in both cell types, whereas expression of the hydroxylases was the highest in the epithelium. Examination of gene expression by prostatic (1,25(OH)2D) concentrations showed that VDR was significantly lower in prostate tissues with the highest concentration of 1,25(OH)2D, and down-regulation of VDR by 1,25(OH) 2D was confirmed in the primary cell cultures. Analysis of inflammatory genes in the patient tissues revealed that IL-6 expression was the highest in the prostate stroma while PTGS2 (COX2) levels were lowest in the prostate cancer tissues from men in the highest tertile of prostatic 1,25(OH)2D. In vitro, TNF-α, IL-6 and IL-8 were suppressed by 1,25 (OH)2D in the primary epithelial cells, whereas TNF-α and PTGS2 were suppressed by 1,25(OH) 2D in the stromal cells. Importantly, the ability of 1,25(OH)2D to alter pro-inflammatory-induced changes in epithelial cell growth were dependent on the presence of the stromal cells. In summary, whereas both stromal and epithelial cells of the prostate express VDR and can presumably respond to 1,25(OH)2D, the prostatic epithelium appears to be the main producer of 1,25(OH)2D. Further, while the prostate epithelium was more responsive to the anti-inflammatory activity of 1,25 (OH)2D than stromal cells, stroma-epithelial crosstalk enhanced the phenotypic effects of 1,25(OH)2D and the inflammatory

Variation of the apparent viscosity of thickened drinks.

PubMed

O'Leary, Mark; Hanson, Ben; Smith, Christina H

2011-01-01

In dysphagia care, thickening powders are widely added to drinks to slow their flow speed by increasing their viscosity. Current practice relies on subjective evaluation of viscosity using verbal descriptors. Several brands of thickener are available, with differences in constituent ingredients and instructions for use. Some thickened fluids have previously been shown to exhibit time-varying non-Newtonian flow behaviour, which may complicate attempts at subjective viscosity judgement. The aims were to quantify the apparent viscosity over time produced by thickeners having a range of constituent ingredients, and to relate the results to clinical practice. A comparative evaluation of currently available thickener products, including two which have recently been reformulated, was performed. Their subjective compliance to the National Descriptors standards was assessed, and their apparent viscosity was measured using a rheometer at shear rates representative of situations from slow tipping in a beaker (0.1 s⁻¹) to a fast swallow (100 s⁻¹). Testing was performed repeatedly up to 3 h from mixing. When mixed with water, it was found that most products compared well with subjective National Descriptors at three thickness levels. The fluids were all highly non-Newtonian; their apparent viscosity was strongly dependent on the rate of testing, typically decreasing by a factor of almost 100 as shear rate increased. All fluids showed some change in viscosity with time from mixing; this varied between products from -34% to 37% in the tests. This magnitude was less than the difference between thickness levels specified by the National Descriptors. The apparent viscosity of thickened fluids depends strongly on the shear rate at which it is examined. This inherent behaviour is likely to hinder subjective evaluation of viscosity. If quantitative measures of viscosity are required (for example, for standardization purposes), they must therefore be qualified with information of

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

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.

Msx homeobox genes critically regulate embryo implantation by controlling paracrine signaling between uterine stroma and epithelium.

PubMed

Nallasamy, Shanmugasundaram; Li, Quanxi; Bagchi, Milan K; Bagchi, Indrani C

2012-01-01

The mammalian Msx homeobox genes, Msx1 and Msx2, encode transcription factors that control organogenesis and tissue interactions during embryonic development. We observed overlapping expression of these factors in uterine epithelial and stromal compartments of pregnant mice prior to embryo implantation. Conditional ablation of both Msx1 and Msx2 in the uterus resulted in female infertility due to a failure in implantation. In these mutant mice (Msx1/2(d/d)), the uterine epithelium exhibited persistent proliferative activity and failed to attach to the embryos. Gene expression profiling of uterine epithelium and stroma of Msx1/2(d/d) mice revealed an elevated expression of several members of the Wnt gene family in the preimplantation uterus. Increased canonical Wnt signaling in the stromal cells activated β-catenin, stimulating the production of a subset of fibroblast growth factors (FGFs) in these cells. The secreted FGFs acted in a paracrine manner via the FGF receptors in the epithelium to promote epithelial proliferation, thereby preventing differentiation of this tissue and creating a non-receptive uterus refractory to implantation. Collectively, these findings delineate a unique signaling network, involving Msx1/2, Wnts, and FGFs, which operate in the uterus at the time of implantation to control the mesenchymal-epithelial dialogue critical for successful establishment of pregnancy.

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

Absolute plate motions relative to deep mantle plumes

NASA Astrophysics Data System (ADS)

Wang, Shimin; Yu, Hongzheng; Zhang, Qiong; Zhao, Yonghong

2018-05-01

Advances in whole waveform seismic tomography have revealed the presence of broad mantle plumes rooted at the base of the Earth's mantle beneath major hotspots. Hotspot tracks associated with these deep mantle plumes provide ideal constraints for inverting absolute plate motions as well as testing the fixed hotspot hypothesis. In this paper, 27 observed hotspot trends associated with 24 deep mantle plumes are used together with the MORVEL model for relative plate motions to determine an absolute plate motion model, in terms of a maximum likelihood optimization for angular data fitting, combined with an outlier data detection procedure based on statistical tests. The obtained T25M model fits 25 observed trends of globally distributed hotspot tracks to the statistically required level, while the other two hotspot trend data (Comores on Somalia and Iceland on Eurasia) are identified as outliers, which are significantly incompatible with other data. For most hotspots with rate data available, T25M predicts plate velocities significantly lower than the observed rates of hotspot volcanic migration, which cannot be fully explained by biased errors in observed rate data. Instead, the apparent hotspot motions derived by subtracting the observed hotspot migration velocities from the T25M plate velocities exhibit a combined pattern of being opposite to plate velocities and moving towards mid-ocean ridges. The newly estimated net rotation of the lithosphere is statistically compatible with three recent estimates, but differs significantly from 30 of 33 prior estimates.

Quantum Tunneling from Apparent Horizon of Rainbow-FRW Universe

NASA Astrophysics Data System (ADS)

Lin, Kai; Yang, Shuzheng

2009-07-01

The quantum tunneling from the apparent horizon of rainbow-FRW universe is studied in this paper. We apply the semi-classical approximation, which is put forward by Parikh and Wilczek et al., to research on the scalar field particles tunneling from the apparent horizon of the rainbow-FRW universe, and then use the spin 1/2 Fermions tunneling theory, which brought forward by Kerner and Mann firstly, to research on the Fermions Hawking radiation via semi-classical approximation. Finally, we discuss the meanings of the quantum effect via Finsler geometry.

Apparent resistivity for transient electromagnetic induction logging and its correction in radial layer identification

NASA Astrophysics Data System (ADS)

Meng, Qingxin; Hu, Xiangyun; Pan, Heping; Xi, Yufei

2018-04-01

We propose an algorithm for calculating all-time apparent resistivity from transient electromagnetic induction logging. The algorithm is based on the whole-space transient electric field expression of the uniform model and Halley's optimisation. In trial calculations for uniform models, the all-time algorithm is shown to have high accuracy. We use the finite-difference time-domain method to simulate the transient electromagnetic field in radial two-layer models without wall rock and convert the simulation results to apparent resistivity using the all-time algorithm. The time-varying apparent resistivity reflects the radially layered geoelectrical structure of the models and the apparent resistivity of the earliest time channel follows the true resistivity of the inner layer; however, the apparent resistivity at larger times reflects the comprehensive electrical characteristics of the inner and outer layers. To accurately identify the outer layer resistivity based on the series relationship model of the layered resistance, the apparent resistivity and diffusion depth of the different time channels are approximately replaced by related model parameters; that is, we propose an apparent resistivity correction algorithm. By correcting the time-varying apparent resistivity of radial two-layer models, we show that the correction results reflect the radially layered electrical structure and the corrected resistivities of the larger time channels follow the outer layer resistivity. The transient electromagnetic fields of radially layered models with wall rock are simulated to obtain the 2D time-varying profiles of the apparent resistivity and corrections. The results suggest that the time-varying apparent resistivity and correction results reflect the vertical and radial geoelectrical structures. For models with small wall-rock effect, the correction removes the effect of the low-resistance inner layer on the apparent resistivity of the larger time channels.

Deep Web video

ScienceCinema

None Available

2018-02-06

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.

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…

Footprint of Deepwater Horizon blowout impact to deep-water coral communities

PubMed Central

Fisher, Charles R.; Hsing, Pen-Yuan; Kaiser, Carl L.; Yoerger, Dana R.; Roberts, Harry H.; Shedd, William W.; Cordes, Erik E.; Shank, Timothy M.; Berlet, Samantha P.; Saunders, Miles G.; Larcom, Elizabeth A.; Brooks, James M.

2014-01-01

On April 20, 2010, the Deepwater Horizon (DWH) blowout occurred, releasing more oil than any accidental spill in history. Oil release continued for 87 d and much of the oil and gas remained in, or returned to, the deep sea. A coral community significantly impacted by the spill was discovered in late 2010 at 1,370 m depth. Here we describe the discovery of five previously unknown coral communities near the Macondo wellhead and show that at least two additional coral communities were impacted by the spill. Although the oil-containing flocullent material that was present on corals when the first impacted community was discovered was largely gone, a characteristic patchy covering of hydrozoans on dead portions of the skeleton allowed recognition of impacted colonies at the more recently discovered sites. One of these communities was 6 km south of the Macondo wellhead and over 90% of the corals present showed the characteristic signs of recent impact. The other community, 22 km southeast of the wellhead between 1,850 and 1,950 m depth, was more lightly impacted. However, the discovery of this site considerably extends the distance from Macondo and depth range of significant impact to benthic macrofaunal communities. We also show that most known deep-water coral communities in the Gulf of Mexico do not appear to have been acutely impacted by the spill, although two of the newly discovered communities near the wellhead apparently not impacted by the spill have been impacted by deep-sea fishing operations. PMID:25071200

DeepInfer: open-source deep learning deployment toolkit for image-guided therapy

NASA Astrophysics Data System (ADS)

Mehrtash, Alireza; Pesteie, Mehran; Hetherington, Jorden; Behringer, Peter A.; Kapur, Tina; Wells, William M.; Rohling, Robert; Fedorov, Andriy; Abolmaesumi, Purang

2017-03-01

Deep learning models have outperformed some of the previous state-of-the-art approaches in medical image analysis. Instead of using hand-engineered features, deep models attempt to automatically extract hierarchical representations at multiple levels of abstraction from the data. Therefore, deep models are usually considered to be more flexible and robust solutions for image analysis problems compared to conventional computer vision models. They have demonstrated significant improvements in computer-aided diagnosis and automatic medical image analysis applied to such tasks as image segmentation, classification and registration. However, deploying deep learning models often has a steep learning curve and requires detailed knowledge of various software packages. Thus, many deep models have not been integrated into the clinical research work ows causing a gap between the state-of-the-art machine learning in medical applications and evaluation in clinical research procedures. In this paper, we propose "DeepInfer" - an open-source toolkit for developing and deploying deep learning models within the 3D Slicer medical image analysis platform. Utilizing a repository of task-specific models, DeepInfer allows clinical researchers and biomedical engineers to deploy a trained model selected from the public registry, and apply it to new data without the need for software development or configuration. As two practical use cases, we demonstrate the application of DeepInfer in prostate segmentation for targeted MRI-guided biopsy and identification of the target plane in 3D ultrasound for spinal injections.

DeepInfer: Open-Source Deep Learning Deployment Toolkit for Image-Guided Therapy.

PubMed

Mehrtash, Alireza; Pesteie, Mehran; Hetherington, Jorden; Behringer, Peter A; Kapur, Tina; Wells, William M; Rohling, Robert; Fedorov, Andriy; Abolmaesumi, Purang

2017-02-11

Deep learning models have outperformed some of the previous state-of-the-art approaches in medical image analysis. Instead of using hand-engineered features, deep models attempt to automatically extract hierarchical representations at multiple levels of abstraction from the data. Therefore, deep models are usually considered to be more flexible and robust solutions for image analysis problems compared to conventional computer vision models. They have demonstrated significant improvements in computer-aided diagnosis and automatic medical image analysis applied to such tasks as image segmentation, classification and registration. However, deploying deep learning models often has a steep learning curve and requires detailed knowledge of various software packages. Thus, many deep models have not been integrated into the clinical research workflows causing a gap between the state-of-the-art machine learning in medical applications and evaluation in clinical research procedures. In this paper, we propose "DeepInfer" - an open-source toolkit for developing and deploying deep learning models within the 3D Slicer medical image analysis platform. Utilizing a repository of task-specific models, DeepInfer allows clinical researchers and biomedical engineers to deploy a trained model selected from the public registry, and apply it to new data without the need for software development or configuration. As two practical use cases, we demonstrate the application of DeepInfer in prostate segmentation for targeted MRI-guided biopsy and identification of the target plane in 3D ultrasound for spinal injections.

DeepInfer: Open-Source Deep Learning Deployment Toolkit for Image-Guided Therapy

PubMed Central

Mehrtash, Alireza; Pesteie, Mehran; Hetherington, Jorden; Behringer, Peter A.; Kapur, Tina; Wells, William M.; Rohling, Robert; Fedorov, Andriy; Abolmaesumi, Purang

2017-01-01

Deep learning models have outperformed some of the previous state-of-the-art approaches in medical image analysis. Instead of using hand-engineered features, deep models attempt to automatically extract hierarchical representations at multiple levels of abstraction from the data. Therefore, deep models are usually considered to be more flexible and robust solutions for image analysis problems compared to conventional computer vision models. They have demonstrated significant improvements in computer-aided diagnosis and automatic medical image analysis applied to such tasks as image segmentation, classification and registration. However, deploying deep learning models often has a steep learning curve and requires detailed knowledge of various software packages. Thus, many deep models have not been integrated into the clinical research workflows causing a gap between the state-of-the-art machine learning in medical applications and evaluation in clinical research procedures. In this paper, we propose “DeepInfer” – an open-source toolkit for developing and deploying deep learning models within the 3D Slicer medical image analysis platform. Utilizing a repository of task-specific models, DeepInfer allows clinical researchers and biomedical engineers to deploy a trained model selected from the public registry, and apply it to new data without the need for software development or configuration. As two practical use cases, we demonstrate the application of DeepInfer in prostate segmentation for targeted MRI-guided biopsy and identification of the target plane in 3D ultrasound for spinal injections. PMID:28615794

Endometrial expression of the insulin-like growth factor system during uterine involution in the postpartum dairy cow☆

PubMed Central

Llewellyn, S.; Fitzpatrick, R.; Kenny, D.A.; Patton, J.; Wathes, D.C.

2008-01-01

Rapid uterine involution in the postpartum period of dairy cows is important to achieve a short interval to conception. Expression patterns for members of the insulin-like growth factor (IGF) family were determined by in situ hybridisation at day 14 ± 0.4 postpartum (n = 12 cows) to investigate a potential role for IGFs in modulating uterine involution. Expression in each uterine tissue region was measured as optical density units and data were analysed according to region and horn. IGF-I mRNA was localized to the sub-epithelial stroma (SES) of inter-caruncular and caruncular endometrium. Both IGF-II and IGF-1R expression was detected in the deep endometrial stroma (DES), the caruncular stroma and myometrium. IGFBP-2, IGFBP-4 and IGFBP-6 mRNAs were all localised to the SES of inter-caruncular and caruncular uterine tissue, and in the DES and caruncular stroma, with IGFBP-4 mRNA additionally expressed in myometrium. IGFBP-3 mRNA was only detectable in luminal epithelium. IGFBP-5 mRNA was found in myometrium, inter-caruncular and caruncular SES and caruncular stroma. These data support a role for IGF-I and IGF-II in the extensive tissue remodelling and repair which the postpartum uterus undergoes to return to its non-pregnant state. The differential expression of binding proteins between tissues (IGFBP-3 in epithelium, IGFBP-2, -4, -5 and -6 in stroma and IGFBP-4 and -5 in myometrium) suggest tight control of IGF activity within each compartment. Differential expression of many members of the IGF family between the significantly larger previously gravid horn and the previously non-gravid horn may relate to differences in their rate of tissue remodelling. PMID:18258405

DeepNeuron: an open deep learning toolbox for neuron tracing.

PubMed

Zhou, Zhi; Kuo, Hsien-Chi; Peng, Hanchuan; Long, Fuhui

2018-06-06

Reconstructing three-dimensional (3D) morphology of neurons is essential for understanding brain structures and functions. Over the past decades, a number of neuron tracing tools including manual, semiautomatic, and fully automatic approaches have been developed to extract and analyze 3D neuronal structures. Nevertheless, most of them were developed based on coding certain rules to extract and connect structural components of a neuron, showing limited performance on complicated neuron morphology. Recently, deep learning outperforms many other machine learning methods in a wide range of image analysis and computer vision tasks. Here we developed a new Open Source toolbox, DeepNeuron, which uses deep learning networks to learn features and rules from data and trace neuron morphology in light microscopy images. DeepNeuron provides a family of modules to solve basic yet challenging problems in neuron tracing. These problems include but not limited to: (1) detecting neuron signal under different image conditions, (2) connecting neuronal signals into tree(s), (3) pruning and refining tree morphology, (4) quantifying the quality of morphology, and (5) classifying dendrites and axons in real time. We have tested DeepNeuron using light microscopy images including bright-field and confocal images of human and mouse brain, on which DeepNeuron demonstrates robustness and accuracy in neuron tracing.

Gliosarcoma developing from an irradiated ependymoma.

PubMed

Kepes, J J; Bastian, F O; Weber, E D

1996-11-01

A 17-year-old girl was operated for a cystic mass located deep within the left parieto-occipital white matter. Histologically the tumor was an ependymoma with a vascular stroma. In spite of irradiation the tumor recurred locally twice, 1 and 2 years respectively after the original operation. The ependymoma portion of the tumor remained unchanged, but the stroma showed increased vascular hyperplasia at the time of the second operation and transformation into a fibrosarcoma in the third operative specimen. Proliferating cell markers (MIB-1) were positive only in the ependymoma cell nuclei in the first two specimens, but were also extensively present in the nuclei of the fibrosarcoma in the third specimen. In the latter, the fibrosarcoma portion greatly overwhelmed the residual ependymoma islands, but remained sharply delineated from them. This is the first observed case of a gliosarcoma originating from an ependymoma. The histological pattern of this mixed tumor clearly indicates that the source of the sarcomatous portions was the neoplastically transformed fibrovascular stroma of the original tumor, rather than "desmoplastic" alterations of the neoplastic ependymal cells themselves.

Thymic B Cell-Mediated Attack of Thymic Stroma Precedes Type 1 Diabetes Development

PubMed Central

Pinto, Ana Isabel; Smith, Jennifer; Kissack, Miriam R.; Hogg, Karen G.; Green, E. Allison

2018-01-01

Type 1 diabetes (T1D) results from a coordinated autoimmune attack of insulin producing beta cells in the pancreas by the innate and adaptive immune systems, beta cell death being predominantly T cell-mediated. In addition to T cells, peripheral B cells are important in T1D progression. The thymus of mice and man also contains B cells, and lately they have been linked to central tolerance of T cells. The role of thymic B cells in T1D is undefined. Here, we show there are abnormalities in the thymic B cell compartment before beta cell destruction and T1D manifestation. Using non-obese diabetic (NOD) mice, we document that preceding T1D development, there is significant accumulation of thymic B cells-partly through in situ development- and the putative formation of ectopic germinal centers. In addition, in NOD mice we quantify thymic plasma cells and observe in situ binding of immunoglobulins to undefined antigens on a proportion of medullary thymic epithelial cells (mTECs). By contrast, no ectopic germinal centers or pronounced intrathymic autoantibodies are detectable in animals not genetically predisposed to developing T1D. Binding of autoantibodies to thymic stroma correlates with apoptosis of mTECs, including insulin-expressing cells. By contrast, apoptosis of mTECs was decreased by 50% in B cell-deficient NOD mice suggesting intrathymic autoantibodies may selectively target certain mTECs for destruction. Furthermore, we observe that these thymic B cell-associated events correlated with an increased prevalence of premature thymic emigration of T cells. Together, our data suggest that the thymus may be a principal autoimmune target in T1D and contributes to disease progression.

Bone marrow-derived cells contribute to regeneration of injured prostate epithelium and stroma.

PubMed

Nakata, Wataru; Nakai, Yasutomo; Yoshida, Takahiro; Sato, Mototaka; Hatano, Koji; Nagahara, Akira; Fujita, Kazutoshi; Uemura, Motohide; Nonomura, Norio

2015-06-01

Recent studies have reported that bone marrow-derived cells (BMDCs), which are recruited to sites of tissue injury and inflammation, can differentiate into epithelial cells, such as liver, lung, gastrointestinal tract, and skin cells. We investigated the role of BMDCs in contributing to regeneration of injured prostate epithelium. Using chimera rats that received allogenic bone marrow grafts from green fluorescent protein (GFP) transgenic rats after lethal whole-body irradiation, we investigated the existence of epithelial marker-positive BMDCs in injured prostate tissue caused by transurethral injection of lipopolysaccharide. Prostate tissues were harvested 2 weeks after transurethral lipopolysaccharide injection. Immunofluorescence staining showed that some cells in the stroma co-expressed GFP and pan-cytokeratin, which suggested the existence of epithelial marker-positive BMDCs. To confirm the existence of such cells, we collected bone marrow-derived non-hematopoietic cells (GFP+/CD45- cells) from the prostate by fluorescence-activated cell sorter analysis and analyzed the characteristics of the GFP+/CD45- cells. The number of cells in this population significantly increased from 0.042% to 0.492% compared with normal prostate tissue. We found by immunofluorescent analysis and RT-PCR that GFP+/CD45- cells expressed cytokeratin, which suggested that these cells have some features of epithelial cells. In the prostate obtained from the chimera rats 34 weeks after lipopolysaccharide injection, GFP- and cytokeratin-positive cells were observed in the prostate gland, which suggested that some of the cells in the prostate gland regenerated after prostate inflammation derived from bone marrow. BMDCs might be able to differentiate into prostate epithelial cells after prostatic injury. © 2015 Wiley Periodicals, Inc.

Hydrologic processes in deep vadose zones in interdrainage arid environments

USGS Publications Warehouse

Walvoord, Michelle Ann; Scanlon, Bridget R.; Hogan, James F.; Phillips, Fred M.; Scanlon, Bridget R.

2004-01-01

A unifying theory for the hydrology of desert vadose zones is particularly timely considering the rising population and water stresses in arid and semiarid regions. Conventional models cannot reconcile the apparent discrepancy between upward flow indicated by hydraulic gradient data and downward flow suggested by environmental tracer data in deep vadose zone profiles. A conceptual model described here explains both hydraulic and tracer data remarkably well by incorporating the hydrologic role of desert plants that encroached former juniper woodland 10 to 15 thousand years ago in the southwestern United States. Vapor transport also plays an important role in redistributing moisture through deep soils, particularly in coarse-grained sediments. Application of the conceptual model to several interdrainage arid settings reproduces measured matric potentials and chloride accumulation by simulating the transition from downward flow to upward flow just below the root zone initiated by climate and vegetation change. Model results indicate a slow hydraulic drying response in deep vadose zones that enables matric potential profiles to be used to distinguish whether precipitation episodically percolated below the root zone or was completely removed via evapotranspiration during the majority of the Holocene. Recharge declined dramatically during the Holocene in interdrainage basin floor settings of arid and semiarid basins. Current flux estimates across the water table in these environmental settings, are on the order of 0.01 to 0.1 mm yr-1 and may be recharge (downward) or discharge (upward) depending on vadose zone characteristics, such as soil texture, geothermal gradient, and water table depth. In summary, diffuse recharge through the basin floor probably contributes only minimally to the total recharge in arid and semiarid basins.

Two-photon optical microscopy imaging of endothelial keratoplasty grafts.

PubMed

Lombardo, Marco; Parekh, Mohit; Serrao, Sebastiano; Ruzza, Alessandro; Ferrari, Stefano; Lombardo, Giuseppe

2017-03-01

To investigate the microstructure of endothelial keratoplasty grafts using two-photon optical microscopy. Six endothelial keratoplasty grafts obtained from human donor corneoscleral tissues and prepared by submerged hydrodissection technique were imaged by two-photon optical microscopy. In each graft, two liquid bubbles were created in order to investigate the presence of a conserved cleavage plane regardless of the volume of posterior stroma that remained attached to Descemet's membrane (DM); the first bubble (bubble A) was generated under DM and the second bubble (bubble B) injection was done in order to obtain a layer of deep stroma that kept the two bubbles separated. Six human donor corneoscleral tissues were used as controls. Second harmonic generation and two-photon emitted fluorescence signals were collected from each specimen. Dissection of stroma occurred along the posterior collagen lamellae at variable distance from DM, which ranged between 3 and 16 μm in bubble A and between 23 and 41 μm in bubble B. The residual stroma included, anteriorly, bands of collagen lamellae, and thin bundles of stromal collagen fibrils, posteriorly, which were tightly intertwining with the underlying DM. There was no anatomically distinct plane of separation between these pre-Descemetic stromal collagen bundles and the overlying collagen lamellae with this hydrodissection technique. Two-photon optical microscopy provided label-free high-resolution imaging of endothelial keratoplasty grafts, showing that the most posterior stroma changes organization at approximately 10 μm above the DM. The pre-Descemetic stromal collagen fibrils form an intertwined complex with DM, which cannot be separated using hydrodissection.

DeepSig: deep learning improves signal peptide detection in proteins.

PubMed

Savojardo, Castrense; Martelli, Pier Luigi; Fariselli, Piero; Casadio, Rita

2018-05-15

The identification of signal peptides in protein sequences is an important step toward protein localization and function characterization. Here, we present DeepSig, an improved approach for signal peptide detection and cleavage-site prediction based on deep learning methods. Comparative benchmarks performed on an updated independent dataset of proteins show that DeepSig is the current best performing method, scoring better than other available state-of-the-art approaches on both signal peptide detection and precise cleavage-site identification. DeepSig is available as both standalone program and web server at https://deepsig.biocomp.unibo.it. All datasets used in this study can be obtained from the same website. pierluigi.martelli@unibo.it. Supplementary data are available at Bioinformatics online.

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, 8×10 10 N·m for free-field data versus 9×10 10 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

Apparent Explosion Moments from Rg Waves Recorded on SPE

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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, 8×10 10 N·m for free-field data versus 9×10 10 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

The spatial-temporal evolution law of microseismic activities in the failure process of deep rock masses

NASA Astrophysics Data System (ADS)

Yuan-hui, Li; Gang, Lei; Shi-da, Xu; Da-wei, Wu

2018-07-01

Under high stress and blasting disturbance, the failure of deep rock masses is a complex, dynamic evolutionary process. To reveal the relation between macroscopic failure of deep rock masses and spatial-temporal evolution law of micro-cracking within, the initiation, extension, and connection of micro-cracks under blasting disturbance and the deformation and failure mechanism of deep rock masses were studied. The investigation was carried out using the microseismic (MS) monitoring system established in the deep mining area of Ashele Copper Mine (Xinjiang Uygur Autonomous Region, China). The results showed that the failure of the deep rock masses is a dynamic process accompanied with stress release and stress adjustment. It is not only related to the blasting-based mining, but also associated with zones of stress concentration formed due to the mining. In that space, the concentrated area in the cloud chart for the distribution of MS event density before failure of the rocks shows the basically same pattern with the damaged rocks obtained through scanning of mined-out areas, which indicates that the cloud chart can be used to determine potential risk areas of rocks in the spatial domain. In the time domain, relevant parameters of MS events presented different changes before the failure of the rocks: the energy index decreased while the cumulative apparent volume gradually increased, the magnitude distribution of microseismic events decreased rapidly, and the fractal dimension decreased at first and then remained stable. This demonstrates that the different changes in relevant MS parameters allow researchers to predict the failure time of the rocks. By analysing the dynamic evolution process of the failure of the deep rock masses, areas at potential risk can be predicted spatially and temporally. The result provides guidance for those involved in the safe production and management of underground engineering and establishes a theoretical basis for the study on the

Morphology and growth pattern of Amazon deep-sea fan: a computer-processed GLORIA side-scan mosaic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flood, R.D.; Damuth, J.E.

1984-04-01

Deep-sea fans have become increasingly important targets for exploration because of their favorable facies associations. A better understanding of deep-sea fans is needed to successfully exploit these complex sediment bodies. Recent studies of the Amazon fan, using long-range side-scan sonar (GLORIA) and single-channel seismic data, provide an overall view of channel patterns of this fan and demonstrate the relationship between successive channel/levee systems. The digitally collected GLORIA data have been computer processed to produce a mosaic of the fan. Computer processing has corrected the records for slant range and ship navigation, and targets have been enhanced. Many features of themore » modern fan system are readily apparent on the sonar mosaic. The 1.5 to 0.5-km (5000 to 1600-ft) wide channels meander intensely across the fan with sinuosities up to 2.5. Because of these meanders, the channel gradients decrease regularly across the fan despite changes in regional slope. Other channel-related targets include cutoff meanders, overbank deposits (especially small debris flows), and channel branchings. Other debris flows cover large areas of the fan and override channel/levee systems. Air-gun records show that this fan is built of a series of channel/levee systems that overlay one another. Channels from at least 6 of these systems are visible at the surface now, but apparently only one channel at a time has been active. The length of time needed to build a single channel/levee system is not known, but it appears to be rapid.« less

Apparent elastic modulus and hysteresis of skeletal muscle cells throughout differentiation

NASA Technical Reports Server (NTRS)

Collinsworth, Amy M.; Zhang, Sarah; Kraus, William E.; Truskey, George A.

2002-01-01

The effect of differentiation on the transverse mechanical properties of mammalian myocytes was determined by using atomic force microscopy. The apparent elastic modulus increased from 11.5 +/- 1.3 kPa for undifferentiated myoblasts to 45.3 +/- 4.0 kPa after 8 days of differentiation (P < 0.05). The relative contribution of viscosity, as determined from the normalized hysteresis area, ranged from 0.13 +/- 0.02 to 0.21 +/- 0.03 and did not change throughout differentiation. Myosin expression correlated with the apparent elastic modulus, but neither myosin nor beta-tubulin were associated with hysteresis. Microtubules did not affect mechanical properties because treatment with colchicine did not alter the apparent elastic modulus or hysteresis. Treatment with cytochalasin D or 2,3-butanedione 2-monoxime led to a significant reduction in the apparent elastic modulus but no change in hysteresis. In summary, skeletal muscle cells exhibited viscoelastic behavior that changed during differentiation, yielding an increase in the transverse elastic modulus. Major contributors to changes in the transverse elastic modulus during differentiation were actin and myosin.

Loss of caveolin-1 and gain of MCT4 expression in the tumor stroma

PubMed Central

Martins, Diana; Beça, Francisco F; Sousa, Bárbara; Baltazar, Fátima; Paredes, Joana; Schmitt, Fernando

2013-01-01

The progression from in situ to invasive breast carcinoma is still an event poorly understood. However, it has been suggested that interactions between the neoplastic cells and the tumor microenvironment may play an important role in this process. Thus, the determination of differential tumor-stromal metabolic interactions could be an important step in invasiveness. The expression of stromal Caveolin-1 (Cav-1) has already been implicated in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Additionally, stromal Cav-1 expression has been associated with the expression of stromal monocarboxylate transporter 4 (MCT4) in invasive breast cancer. However, the role of stromal MCT4 in invasiveness has never been explored, neither the association between Cav-1 and MCT4 in the transition from breast DCIS to IDC. Therefore, our aim was to investigate in a series of breast cancer samples including matched in situ and invasive components, if there was a relationship between stromal Cav-1 and MCT4 in the progression from in situ to invasive carcinoma. We found loss of stromal Cav-1 in the progression to IDC in 75% of the cases. In contrast, MCT4 stromal expression was acquired in 87% of the IDCs. Interestingly, a concomitant loss of Cav-1 and gain of MCT4 was observed in the stroma of 75% of the cases, when matched in situ and invasive carcinomas were compared. These results suggest that alterations in Cav-1 and MCT4 may thus mark a critical point in the progression from in situ to invasive breast cancer. PMID:23907124

Multi-epoch VLBA Imaging of 20 New TeV Blazars: Apparent Jet Speeds

NASA Astrophysics Data System (ADS)

Piner, B. Glenn; Edwards, Philip G.

2018-01-01

We present 88 multi-epoch Very Long Baseline Array (VLBA) images (most at an observing frequency of 8 GHz) of 20 TeV blazars, all of the high-frequency-peaked BL Lac (HBL) class, that have not been previously studied at multiple epochs on the parsec scale. From these 20 sources, we analyze the apparent speeds of 43 jet components that are all detected at four or more epochs. As has been found for other TeV HBLs, the apparent speeds of these components are relatively slow. About two-thirds of the components have an apparent speed that is consistent (within 2σ) with no motion, and some of these components may be stationary patterns whose apparent speed does not relate to the underlying bulk flow speed. In addition, a superluminal tail to the apparent speed distribution of the TeV HBLs is detected for the first time, with eight components in seven sources having a 2σ lower limit on the apparent speed exceeding 1c. We combine the data from these 20 sources with an additional 18 sources from the literature to analyze the complete apparent speed distribution of all 38 TeV HBLs that have been studied with very long baseline interferometry at multiple epochs. The highest 2σ apparent speed lower limit considering all sources is 3.6c. This suggests that bulk Lorentz factors of up to about 4, but probably not much higher, exist in the parsec-scale radio-emitting regions of these sources, consistent with estimates obtained in the radio by other means such as brightness temperatures. This can be reconciled with the high Lorentz factors estimated from the high-energy data if the jet has velocity structures consisting of different emission regions with different Lorentz factors. In particular, we analyze the current apparent speed data for the TeV HBLs in the context of a model with a fast central spine and a slower outer layer.

Nitrate Contamination of Deep Aquifers in the Salinas Valley, California

NASA Astrophysics Data System (ADS)

Moran, J. E.; Esser, B. K.; Hillegonds, D. J.; Holtz, M.; Roberts, S. K.; Singleton, M. J.; Visser, A.; Kulongoski, J. T.; Belitz, K.

2011-12-01

The Salinas Valley, known as 'the salad bowl of the world', has been an agricultural center for more than 100 years. Irrigated row crops such as lettuce and strawberries dominate both land use and water use. Groundwater is the exclusive supply for both irrigation and drinking water. Some irrigation wells and most public water supply wells in the Salinas Valley are constructed to draw water from deep portions of the aquifer system, where contamination by nitrate is less likely than in the shallow portions of the aquifer system. However, a number of wells with top perforations greater than 75 m deep, screened below confining or semi-confining units, have nitrate concentrations greater than the Maximum Contaminant Limit (MCL) of 45 mg/L as NO3-. This study uses nitrate concentrations from several hundred irrigation, drinking water, and monitoring wells (Monterey County Water Resources Agency, 1997), along with tritium-helium groundwater ages acquired at Lawrence Livermore National Laboratory through the State of California Groundwater Monitoring and Assessment (GAMA) program (reported in Kulongoski et al., 2007 and in Moran et al., in press), to identify nitrate 'hot spots' in the deep aquifer and to examine possible modes of nitrate transport to the deep aquifer. In addition, observed apparent groundwater ages are compared with the results of transport simulations that use particle tracking and a stochastic-geostatistical framework to incorporate aquifer heterogeneity to determine the distribution of travel times from the water table to each well (Fogg et al., 1999). The combined evidence from nitrate, tritium, tritiogenic 3He, and radiogenic 4He concentrations, reveals complex recharge and flow to the capture zone of the deep drinking water wells. Widespread groundwater pumping for irrigation accelerates vertical groundwater flow such that high nitrate groundwater reaches some deep drinking water wells. Deeper portions of the wells often draw in water that recharged

Palynofacies reveal fresh terrestrial organic matter inputs in the terminal lobes of the Congo deep-sea fan

NASA Astrophysics Data System (ADS)

Schnyder, Johann; Stetten, Elsa; Baudin, François; Pruski, Audrey M.; Martinez, Philippe

2017-08-01

The Congo deep-sea fan is directly connected to the Congo River by a unique submarine canyon. The Congo River delivers up to 2×1012gPOC/yr, a part of which is funnelled by the submarine canyon and feeds the deep-sea environments. The more distal part of the Congo deep-sea fan, the terminal lobe area, has a surface of 2500 km2 and is situated up to 800 km offshore at depths of 4750-5000 m. It is a remarkable place to study the fate and distribution of the organic matter transferred from the continent to the deep ocean via turbidity currents. Forty-two samples were analyzed from the terminal lobes, including sites from the active channel, one of its levees and an abandoned distal channel. Samples were collected using multitube cores and push-cores using a Victor 6000 ROV, which surveyed the dense chemosynthetic habitats that locally characterize the terminal lobes. Palynofacies reveal a remarkably well-preserved, dominantly terrestrial particulate organic matter assemblage, that has been transferred from the continent into the deep-sea by turbidity currents. Delicate plant structures, cuticle fragments and plant cellular material is often preserved, highlighting the efficiency of turbidity currents to transfer terrestrial organic matter to the sea-floor, where it is preserved. Moreover, the palynofacies data reveal a general sorting by density or buoyancy of the organic particles, as the turbulent currents escaped the active channel, feeding the levees and the more distal, abandoned channel area. Finally, in addition to aforementioned hydrodynamic factors controlling the organic matter accumulation, a secondary influence of chemosynthetic habitats on organic matter preservation is also apparent. Palynofacies is therefore a useful tool to record the distribution of organic matter in recent and ancient deep-sea fan environments, an important topic for both academic and petroleum studies.

DeepMitosis: Mitosis detection via deep detection, verification and segmentation networks.

PubMed

Li, Chao; Wang, Xinggang; Liu, Wenyu; Latecki, Longin Jan

2018-04-01

Mitotic count is a critical predictor of tumor aggressiveness in the breast cancer diagnosis. Nowadays mitosis counting is mainly performed by pathologists manually, which is extremely arduous and time-consuming. In this paper, we propose an accurate method for detecting the mitotic cells from histopathological slides using a novel multi-stage deep learning framework. Our method consists of a deep segmentation network for generating mitosis region when only a weak label is given (i.e., only the centroid pixel of mitosis is annotated), an elaborately designed deep detection network for localizing mitosis by using contextual region information, and a deep verification network for improving detection accuracy by removing false positives. We validate the proposed deep learning method on two widely used Mitosis Detection in Breast Cancer Histological Images (MITOSIS) datasets. Experimental results show that we can achieve the highest F-score on the MITOSIS dataset from ICPR 2012 grand challenge merely using the deep detection network. For the ICPR 2014 MITOSIS dataset that only provides the centroid location of mitosis, we employ the segmentation model to estimate the bounding box annotation for training the deep detection network. We also apply the verification model to eliminate some false positives produced from the detection model. By fusing scores of the detection and verification models, we achieve the state-of-the-art results. Moreover, our method is very fast with GPU computing, which makes it feasible for clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Use of a minimally invasive tubular retraction system for deep-seated tumors in pediatric patients.

PubMed

Recinos, Pablo F; Raza, Shaan M; Jallo, George I; Recinos, Violette Renard

2011-05-01

Microsurgical removal is the preferred treatment for most deep-seated, intraaxial tumors in the pediatric population. The feasibility of surgery as an option has improved with advances in surgical technology and technique. Tubular retractors disperse retraction forces over a greater surface area than do conventional retractors, which can lower the risk of ischemic complications. The authors describe their experience utilizing a new tubular retractor system specifically designed for cranial applications in conjunction with frameless neuronavigation. The Vycor ViewSite retractor was used in 4 pediatric patients (ages 15 months and 9, 10, and 16 years) with deep-seated intraaxial tumors. The lesions included a papillary tumor of the pineal region, a low-grade astrocytoma in the occipital lobe, a dysembryoplastic neuroepithelial tumor arising from the basal ganglia, and an intraventricular low-grade glioma. The extent of white matter damage along the surgical trajectory (based on T2 or FLAIR and diffusion restriction/apparent diffusion coefficient signals) and the extent of resection were assessed on postoperative imaging. Satisfactory resection or biopsy was achieved in all patients. A comparison of pre- and postoperative MR imaging studies revealed evidence of white matter damage along the surgical trajectory in 1 patient. None of the patients demonstrated new neurological deficits postoperatively. Obtaining surgical access to deep-seated, intraaxial tumors is challenging. In this small series of pediatric patients, the combination of the ViewSite tubular retractor and frameless neuronavigation facilitated the surgical approach. The combination of these technologies adds to the armamentarium to safely approach tumors in deep locations.

Structure of gamma-ray burst jets: intrinsic versus apparent properties

NASA Astrophysics Data System (ADS)

Salafia, O. S.; Ghisellini, G.; Pescalli, A.; Ghirlanda, G.; Nappo, F.

2015-07-01

With this paper we introduce the concept of apparent structure of a gamma-ray burst (GRB) jet, as opposed to its intrinsic structure. The latter is customarily defined specifying the functions ɛ(θ) (the energy emitted per jet unit solid angle) and Γ(θ) (the Lorentz factor of the emitting material); the apparent structure is instead defined by us as the isotropic equivalent energy Eiso(θv) as a function of the viewing angle θv. We show how to predict the apparent structure of a jet given its intrinsic structure. We find that a Gaussian intrinsic structure yields a power-law apparent structure: this opens a new viewpoint on the Gaussian (which can be understood as a proxy for a realistic narrow, well-collimated jet structure) as a possible candidate for a quasi-universal GRB jet structure. We show that such a model (a) is consistent with recent constraints on the observed luminosity function of GRBs; (b) implies fewer orphan afterglows with respect to the standard uniform model; (c) can break out the progenitor star (in the collapsar scenario) without wasting an unreasonable amount of energy; (d) is compatible with the explanation of the Amati correlation as a viewing angle effect; (e) can be very standard in energy content, and still yield a very wide range of observed isotropic equivalent energies.

Apparent consumption of refined sugar in Australia (1938-2011).

PubMed

McNeill, T J; Shrapnel, W S

2015-11-01

In Australia, the Australian Bureau of Statistics discontinued collection of apparent consumption data for refined sugars in 1998/1999. The objectives of this study were to update this data series to determine whether it is a reliable data series that reflects consumption of refined sugars, defined as sucrose in the forms of refined or raw sugar or liquified sugars manufactured for human consumption. The study used the same methodology as that used by the Australian Bureau of Statistics to derive a refined sugars consumption estimate each year until the collection was discontinued. Sales by Australian refiners, refined sugars imports and the net balance of refined sugars contained in foods imported into, and exported from, Australia were used to calculate total refined sugars use for each year up to 2011. Per capita consumption figures were then derived. During the period 1938-2011, apparent consumption of refined sugars in Australia fell 13.1% from 48.3 to 42.0 kg per head (R(2)=0.74). Between the 1950s and the 1970s, apparent consumption was relatively stable at about 50 kg per person. In the shorter period 1970-2011, refined sugars consumption fell 16.5% from 50.3 to 42.0 kg per head, though greater variability was evident (R(2)=0.53). An alternative data set showed greater volatility with no trend up or down. The limited variability of the extended apparent consumption series and its consistency with recent national dietary survey data and sugar-sweetened beverage sales data indicate that it is a reliable data set that reflects declining intake of refined sugars in Australia.

Dissolved inorganic carbon isotopic composition of the Gulf of Mexico deep-water masses.

NASA Astrophysics Data System (ADS)

Quintanilla-Terminel, J. G.; Herguera, J. C.; Ferreira-Bartrina, V.; Hernández-Ayón, J. M.; Camacho-Ibar, V.

2014-12-01

This study provides new data for the establishment of a carbon biogeochemical dynamics baseline in the deep Gulf of Mexico (GM) based on carbon isotopes in dissolved inorganic carbon. Water samples from 40 deep-water stations south of 25˚N were collected during XIXIMI-2 cruise, July 2011, aboard BO/Justo Sierra. Vertical profiles of temperature, salinity and dissolved oxygen (DO) were further measured in each station. In the Stable Isotopes Laboratory at CICESE we determined the carbon isotopic composition of the dissolved inorganic carbon (DIC) (δ13CDIC). Remarkably, density, DO and δ13CCID profiles showed a clear difference between the Loop current and the deep-waters of the GM south of 25˚N. We found the following average δ13CCID values in the Loop current and in the deep-waters of the Gulf: subtropical underwater (SUW): 0.73±0.06‰ and 0.86±0.04‰; 18 degree water (18W): 0.76 ± 0.08‰ and 0.58± 0.06‰; North Atlantic central water (NACW): 0.77 ± 0.05‰ and 0.71 ± 0.09‰; South Atlantic central water (SACW): 0.80 ± 0.08‰ and 0.77 ± 0.07‰; Antartic intermediate water (AAIW): 1.00 ± 0.06‰ and 0.90 ± 0.08‰; North Atlantic deep water (NADW): 1.03 ± 0.06‰ and 1.01 ± 0.10‰. We will discuss how the biological component, δ13CCID-BIO, of subsurface water masses match very closely the apparent oxygen utilization relation described by Kroopnick, 1985, with the exception of SUW, and as a consequence the 18W is probably the water mass most affected by organic carbon remineralization processes in the GM south of 25˚N. We further show how these waters seem to store a larger proportion of anthropogenic carbon than the deeper water masses.

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.

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…

deepTools: a flexible platform for exploring deep-sequencing data.

PubMed

Ramírez, Fidel; Dündar, Friederike; Diehl, Sarah; Grüning, Björn A; Manke, Thomas

2014-07-01

We present a Galaxy based web server for processing and visualizing deeply sequenced data. The web server's core functionality consists of a suite of newly developed tools, called deepTools, that enable users with little bioinformatic background to explore the results of their sequencing experiments in a standardized setting. Users can upload pre-processed files with continuous data in standard formats and generate heatmaps and summary plots in a straight-forward, yet highly customizable manner. In addition, we offer several tools for the analysis of files containing aligned reads and enable efficient and reproducible generation of normalized coverage files. As a modular and open-source platform, deepTools can easily be expanded and customized to future demands and developments. The deepTools webserver is freely available at http://deeptools.ie-freiburg.mpg.de and is accompanied by extensive documentation and tutorials aimed at conveying the principles of deep-sequencing data analysis. The web server can be used without registration. deepTools can be installed locally either stand-alone or as part of Galaxy. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

A Multistage Fluidized Bed for the Deep Removal of Sour Gases: Proof of Concept and Tray Efficiencies

PubMed Central

2018-01-01

Currently there are significant amounts of natural gas that cannot be produced and treated to meet pipeline specifications, because that would not be economically viable. This work investigates a bench scale multistage fluidized bed (MSFB) with shallow beds for sour gas removal from natural gas using a commercially available supported amine sorbent. A MSFB is regarded as a promising adsorber type for deep sour gas removal to parts per million concentrations. A series of experiments was conducted using carbon dioxide as sour gas and nitrogen to mimic natural gas. Removal below 3 mol ppm was successfully demonstrated. This indicates that gas bypassing is minor (that is, good gas–solid contacting) and that apparent adsorption kinetics are fast for the amine sorbent applied. Tray efficiencies for a chemisorption/adsorption system were reported for one of the first times. Current experiments performed at atmospheric pressure strongly indicate that deep removal is possible at higher pressures in a multistage fluidized bed. PMID:29606794

A Multistage Fluidized Bed for the Deep Removal of Sour Gases: Proof of Concept and Tray Efficiencies.

PubMed

Driessen, Rick T; Bos, Martin J; Brilman, Derk W F

2018-03-21

Currently there are significant amounts of natural gas that cannot be produced and treated to meet pipeline specifications, because that would not be economically viable. This work investigates a bench scale multistage fluidized bed (MSFB) with shallow beds for sour gas removal from natural gas using a commercially available supported amine sorbent. A MSFB is regarded as a promising adsorber type for deep sour gas removal to parts per million concentrations. A series of experiments was conducted using carbon dioxide as sour gas and nitrogen to mimic natural gas. Removal below 3 mol ppm was successfully demonstrated. This indicates that gas bypassing is minor (that is, good gas-solid contacting) and that apparent adsorption kinetics are fast for the amine sorbent applied. Tray efficiencies for a chemisorption/adsorption system were reported for one of the first times. Current experiments performed at atmospheric pressure strongly indicate that deep removal is possible at higher pressures in a multistage fluidized bed.

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.

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.

Prediction of Tissue Outcome and Assessment of Treatment Effect in Acute Ischemic Stroke Using Deep Learning.

PubMed

Nielsen, Anne; Hansen, Mikkel Bo; Tietze, Anna; Mouridsen, Kim

2018-06-01

Treatment options for patients with acute ischemic stroke depend on the volume of salvageable tissue. This volume assessment is currently based on fixed thresholds and single imagine modalities, limiting accuracy. We wish to develop and validate a predictive model capable of automatically identifying and combining acute imaging features to accurately predict final lesion volume. Using acute magnetic resonance imaging, we developed and trained a deep convolutional neural network (CNN deep ) to predict final imaging outcome. A total of 222 patients were included, of which 187 were treated with rtPA (recombinant tissue-type plasminogen activator). The performance of CNN deep was compared with a shallow CNN based on the perfusion-weighted imaging biomarker Tmax (CNN Tmax ), a shallow CNN based on a combination of 9 different biomarkers (CNN shallow ), a generalized linear model, and thresholding of the diffusion-weighted imaging biomarker apparent diffusion coefficient (ADC) at 600×10 -6 mm 2 /s (ADC thres ). To assess whether CNN deep is capable of differentiating outcomes of ±intravenous rtPA, patients not receiving intravenous rtPA were included to train CNN deep, -rtpa to access a treatment effect. The networks' performances were evaluated using visual inspection, area under the receiver operating characteristic curve (AUC), and contrast. CNN deep yields significantly better performance in predicting final outcome (AUC=0.88±0.12) than generalized linear model (AUC=0.78±0.12; P =0.005), CNN Tmax (AUC=0.72±0.14; P <0.003), and ADC thres (AUC=0.66±0.13; P <0.0001) and a substantially better performance than CNN shallow (AUC=0.85±0.11; P =0.063). Measured by contrast, CNN deep improves the predictions significantly, showing superiority to all other methods ( P ≤0.003). CNN deep also seems to be able to differentiate outcomes based on treatment strategy with the volume of final infarct being significantly different ( P =0.048). The considerable prediction

Deep crustal electromagnetic structure of central India tectonic zone and its implications

NASA Astrophysics Data System (ADS)

Naganjaneyulu, K.; Naidu, G. Dhanunjaya; Rao, M. Someswara; Shankar, K. Ravi; Kishore, S. R. K.; Murthy, D. N.; Veeraswamy, K.; Harinarayana, T.

2010-07-01

Magnetotelluric data at 45 locations along the Mahan-Khajuria Kalan profile in the central India tectonic zone are analysed. This 290 km long profile yields data in the period range 0.001-1000 s across the tectonic elements of the study region bounded by Purna fault, Gavligarh fault, Tapti fault, Narmada South fault and Narmada North fault. Multi-site, multi-frequency analysis suggests N70°E as the geo-electric strike direction. Data rotated into the N70°E strike direction are modelled using a non-linear conjugate gradient scheme with error floors of 10% for both apparent resistivity and phase components. Two-dimensional magnetotelluric model yields conductors that correlate with known faults in the study region and regional seismicity. Presence of a -30 mgal gravity high together with the observed conductive bodies (less than 20 ohm m) in the deep crust beneath the Purna graben and Tapti valley is explained by the process of magmatic underplating. The conductive bodies beneath the Mahakoshal rift belt and Vindhyans accompanied by regional gravity lows of the order -70 mgal are attributed to the presence of deep crustal fluids. Following the re-activation model proposed for the entire region, the conductors (20 ohm m) at various depth levels correspond to mafic magmatic and/or fluid intrusions controlled by deep-seated faults that seem to tap reservoirs beyond the crust-mantle boundary. The shallow depth localized faults also seem to have facilitated further upward movement of these underplated material and fluids release during this process.

Msx Homeobox Genes Critically Regulate Embryo Implantation by Controlling Paracrine Signaling between Uterine Stroma and Epithelium

PubMed Central

Nallasamy, Shanmugasundaram; Li, Quanxi; Bagchi, Milan K.; Bagchi, Indrani C.

2012-01-01

The mammalian Msx homeobox genes, Msx1 and Msx2, encode transcription factors that control organogenesis and tissue interactions during embryonic development. We observed overlapping expression of these factors in uterine epithelial and stromal compartments of pregnant mice prior to embryo implantation. Conditional ablation of both Msx1 and Msx2 in the uterus resulted in female infertility due to a failure in implantation. In these mutant mice (Msx1/2 d/d), the uterine epithelium exhibited persistent proliferative activity and failed to attach to the embryos. Gene expression profiling of uterine epithelium and stroma of Msx1/2 d/d mice revealed an elevated expression of several members of the Wnt gene family in the preimplantation uterus. Increased canonical Wnt signaling in the stromal cells activated β-catenin, stimulating the production of a subset of fibroblast growth factors (FGFs) in these cells. The secreted FGFs acted in a paracrine manner via the FGF receptors in the epithelium to promote epithelial proliferation, thereby preventing differentiation of this tissue and creating a non-receptive uterus refractory to implantation. Collectively, these findings delineate a unique signaling network, involving Msx1/2, Wnts, and FGFs, which operate in the uterus at the time of implantation to control the mesenchymal-epithelial dialogue critical for successful establishment of pregnancy. PMID:22383889

The deep structure of Venusian plateau highlands

NASA Technical Reports Server (NTRS)

Grimm, Robert E.

1994-01-01

Magellan gravity data confirm that several of the large, tectonically deformed, plateau-like highlands on venus are shallowly compensated, most likely by crustal thickness variations. Apparent depths of isostatic compensation, computed in the spatial domain, range from 30 to 50 km for Alpha, Tellus, Ovda, and Thetis Regiones. Using a two-layer model for isostatic compensation, Alpha, Tellus, and Ovda are best represented as nearly completely compensated in crust that is regionally 20-40 km thick around these highlands, with little contribution from deeper mantle sources. In contrast to these three areas, a stronger regional gravity high associated with Thetis requires a significant upper mantle component to compensation. This is evident in the spectral admittance as a pronounced deep, long-wavelength anomaly. In the two-layer isostatic model, a broad, deeply compensated upland underlies a shallowly compensated central block of Thetis. If this deep component is interpreted as a thermal anomaly, the loci of maximum upwelling agree well with sites of recent extension. The plateau highlands are thus physiographically and isostatically equivalent to terrestrial continents, though probably not compositionally. They also share the record of a long tectonic history. The large regional gravity anomaly of Thetis indicates that active mantle proceses continue even beneath some areas (tessera) thought to be a relic of a former geological regime. The excellent agreement of modeled crustal thicknesses around Alpha, Tellus, and Ovda Regiones suggests that 20-40 km is a representative global value for the plains. Such a crust is thicker than previously estimated and about twice as thick as the expected thickness of crust produced at venusian spreading centers

Deep learning in bioinformatics.

PubMed

Min, Seonwoo; Lee, Byunghan; Yoon, Sungroh

2017-09-01

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. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Tertiary work-up of apparent treatment-resistant hypertension.

PubMed

Heimark, Sondre; Eskås, Per Anders; Mariampillai, Julian Eek; Larstorp, Anne Cecilie K; Høieggen, Aud; Fadl Elmula, Fadl Elmula M

2016-10-01

Treatment-resistant hypertension (TRH) has regained attention with development of new methods for treatment. However, the prevalence of TRH varies considerably from primary to secondary and tertiary care. We aimed to assess the prevalence of true TRH in a population of patients with apparent TRH in a university hospital setting of tertiary work-up and also investigate reasons for poor BP control and evaluate how work-up can be performed in general practice and secondary care. In this cohort study, we characterize a study population from Oslo Renal Denervation (RDN) Study. Patients (n = 83) were referred for RDN from secondary care. All patients underwent thorough medical investigation and 24-h ambulatory blood pressure measurements (24ABPM) after directly observed therapy (DOT). We then assessed reasons for lack of BP control. Fifty-three of 83 patients did not have true TRH. Main reasons for non-TRH were poor drug adherence (32%), secondary hypertension (30%) and white coat hypertension (15%). Forty-seven percent achieved blood pressure control after DOT with subsequent 24ABPM. There were otherwise no statistically significant differences in patient characteristics between the true TRH and the non-TRH group. Despite being a highly selected cohort referred for tertiary work-up of apparent TRH, BP control was achieved or secondary causes were identified in almost two thirds of the patients. Thorough investigation according to guidelines and DOT with subsequent 24ABPM is needed in work-up of apparent TRH.

The Deepwater Horizon Oil Spill: Ecogenomics of the Deep-Sea Plume

NASA Astrophysics Data System (ADS)

Hazen, T. C.

2012-12-01

The explosion on April 20, 2010 at the BP-leased Deepwater Horizon drilling rig in the Gulf of Mexico off the coast of Louisiana, resulted in oil and gas rising to the surface and the oil coming ashore in many parts of the Gulf, it also resulted in the dispersment of an immense oil plume 4,000 feet below the surface of the water. Despite spanning more than 600 feet in the water column and extending more than 10 miles from the wellhead, the dispersed oil plume was gone within weeks after the wellhead was capped - degraded and diluted to undetectable levels. Furthermore, this degradation took place without significant oxygen depletion. Ecogenomics enabled discovery of new and unclassified species of oil-eating bacteria that apparently lives in the deep Gulf where oil seeps are common. Using 16s microarrays, functional gene arrays, clone libraries, lipid analysis and a variety of hydrocarbon and micronutrient analyses we were able to characterize the oil degraders. Metagenomic sequence data was obtained for the deep-water samples using the Illumina platform. In addition, single cells were sorted and sequenced for the some of the most dominant bacteria that were represented in the oil plume; namely uncultivated representatives of Colwellia and Oceanospirillum. In addition, we performed laboratory microcosm experiments using uncontaminated water collected from The Gulf at the depth of the oil plume to which we added oil and COREXIT. These samples were characterized by 454 pyrotag. The results provide information about the key players and processes involved in degradation of oil, with and without COREXIT, in different impacted environments in The Gulf of Mexico. We are also extending these studies to explore dozens of deep sediment samples that were also collected after the oil spill around the wellhead. This data suggests that a great potential for intrinsic bioremediation of oil plumes exists in the deep-sea and other environs in the Gulf of Mexico.

Apparent Ionic Charge in Electrolyte and Polyelectrolyte Solutions

ERIC Educational Resources Information Center

Magdelenat, H.; And Others

1978-01-01

Compares average displacements of charged particles under thermal motion alone with those obtained by the action of an external electric field to develop a concept of "apparent charge" to approximate actual structural charge in an electrolyte solution. (SL)

Evaluating apparent competition in limiting the recovery of an endangered ungulate.

PubMed

Johnson, Heather E; Hebblewhite, Mark; Stephenson, Thomas R; German, David W; Pierce, Becky M; Bleich, Vernon C

2013-01-01

Predation can disproportionately affect endangered prey populations when generalist predators are numerically linked to more abundant primary prey. Apparent competition, the term for this phenomenon, has been increasingly implicated in the declines of endangered prey populations. We examined the potential for apparent competition to limit the recovery of Sierra Nevada bighorn sheep (Ovis canadensis sierrae), an endangered subspecies under the US Endangered Species Act. Using a combination of location, demographic, and habitat data, we assessed whether cougar (Puma concolor) predation on endangered bighorn sheep was a consequence of their winter range overlap with abundant mule deer (Odocoileus hemionus). Consistent with the apparent competition hypothesis, bighorn sheep populations with higher spatial overlap with deer exhibited higher rates of cougar predation which had additive effects on adult survival. Bighorn sheep killed by cougars were primarily located within deer winter ranges, even though those areas constituted only a portion of the bighorn sheep winter ranges. We suspect that variation in sympatry between bighorn sheep and deer populations was largely driven by differences in habitat selection among bighorn sheep herds. Indeed, bighorn sheep herds that experienced the highest rates of predation and the greatest spatial overlap with deer also exhibited the strongest selection for low elevation habitat. Although predator-mediated apparent competition may limit some populations of bighorn sheep, it is not the primary factor limiting all populations, suggesting that the dynamics of different herds are highly idiosyncratic. Management plans for endangered species should consider the spatial distributions of key competitors and predators to reduce the potential for apparent competition to hijack conservation success.

Unintentional Changes in the Apparent Stiffness of the Multi-Joint Limb

PubMed Central

Zhou, Tao; Zatsiorsky, Vladimir M.; Latash, Mark L.

2015-01-01

We explored the phenomenon of unintentional changes in the apparent stiffness of the human arm produced by transient changes in the external force. The subjects performed a positional task against a constant baseline force and were instructed not to react to changes in the force. A HapticMaster robot produced a smooth force increase (a perturbation) leading to a hand movement, followed by a dwell time. No visible hand drift was observed during the dwell time. After the robot force dropped to its initial baseline value, the hand moved towards the initial position but stopped short of it. Small perturbations were applied at different time intervals along different directions during the dwell time. Arm apparent stiffness distribution in a horizontal plane was approximated with an ellipse. The apparent stiffness magnitude along the main axis of the ellipse showed a non-monotonic increase with dwell time while the apparent stiffness along the minor axis did not change significantly. We interpreted the early part of the changes in the apparent stiffness as due to peripheral muscle properties. The later part is interpreted as caused by a combination of two processes, a drift in the referent hand coordinate due to the hypothesized back-coupling between the referent and actual hand coordinates and an implicit instruction to keep the hand steady when no changes in robot-generated force took place. The data provide support for the idea of back-coupling between the referent and actual body configurations, which may be an important contributor to stability of motor actions. PMID:26169103

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…

[Deep needling and shallow needling at three acupoints around ear for subjective tinnitus: a randomized controlled trial].

PubMed

Yin, Tao; Ni, Jinxia; Zhu, Wenzeng

2015-10-01

To compare the effective differences between deep needling and shallow needling at three acupoints around ear for subjective tinnitus. Fifty patients with subjective tinnitus were randomized divided into a deep needling group and a shallow needling group, 25 cases in each group. Twenty-two patients in the deep needling group and 20 patients in the shallow needling group were brought into statistic in the end. In the two groups, the three acupoints around ear and distal acupoints were both selected. The acupoints of the affected side such as Yifeng (TE 17), Tinghui (GB 2), Ermen (TE 21), Zhigou (TE 6), Zhongzhu (TE 3) and Hegu (LI 4) were adopted. Yifeng (TE 17), Tinghui (GB 2) and Ermen (TE 21) were acupunctured 30-38 mm in the deep needling group and 15-20 mm in the shallow needling group. The other acupoints were conventionally acupunctured in the two groups. The needles were retained for 30 min,once a day and five times a week for all patients. The treatment was continuously for 4 weeks in the two groups. Tinnitus handicap inventory (THI) scores, tinnitus grades and visual analogue scale (VAS) for tinnitus sound levels were observed before and after treatment, and the effects of the two groups were compared. The total effective rate in the deep needling group was 59.1% (13/22), and it was better than 20.0% (4/20) in the shallow needling group (P < 0.05). In the deep needling, group, the THI score, tinnitus grade and the VAS score were improved than those before treatment (all P < 0.05). In the shallow needling group, the three above indices before and after treatment were not different in statistical significance (all P > 0.05). After treatment, all the three indices in the deep needling group were superior to those in the shallow needling group (all P < 0.05). Acupuncture at the three acupoints around ear deeply could apparently improve tinnitus, and reduce tinnitus sound levels for subjective tinnitus. The effect is better than that by shallow needling at the

Event and Apparent Horizon Finders for 3 + 1 Numerical Relativity.

PubMed

Thornburg, Jonathan

2007-01-01

Event and apparent horizons are key diagnostics for the presence and properties of black holes. In this article I review numerical algorithms and codes for finding event and apparent horizons in numerically-computed spacetimes, focusing on calculations done using the 3 + 1 ADM formalism. The event horizon of an asymptotically-flat spacetime is the boundary between those events from which a future-pointing null geodesic can reach future null infinity and those events from which no such geodesic exists. The event horizon is a (continuous) null surface in spacetime. The event horizon is defined nonlocally in time : it is a global property of the entire spacetime and must be found in a separate post-processing phase after all (or at least the nonstationary part) of spacetime has been numerically computed. There are three basic algorithms for finding event horizons, based on integrating null geodesics forwards in time, integrating null geodesics backwards in time, and integrating null surfaces backwards in time. The last of these is generally the most efficient and accurate. In contrast to an event horizon, an apparent horizon is defined locally in time in a spacelike slice and depends only on data in that slice, so it can be (and usually is) found during the numerical computation of a spacetime. A marginally outer trapped surface (MOTS) in a slice is a smooth closed 2-surface whose future-pointing outgoing null geodesics have zero expansion Θ. An apparent horizon is then defined as a MOTS not contained in any other MOTS. The MOTS condition is a nonlinear elliptic partial differential equation (PDE) for the surface shape, containing the ADM 3-metric, its spatial derivatives, and the extrinsic curvature as coefficients. Most "apparent horizon" finders actually find MOTSs. There are a large number of apparent horizon finding algorithms, with differing trade-offs between speed, robustness, accuracy, and ease of programming. In axisymmetry, shooting algorithms work well

Discovery of an Apparent Nova in M81

NASA Astrophysics Data System (ADS)

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

2017-12-01

The M81 nova monitoring collaboration reports the discovery of an apparent nova in M81 on a co-added 3150-s unfiltered CCD frame taken on 2017 Dec. 2.127 UT with the 0.65-m telescope at Ondrejov (OND).

Corneal subbasal nerve fiber regeneration in myopic patients after laser in situ keratomileusis★

PubMed Central

Deng, Shijing; Wang, Mengmeng; Zhang, Fengju; Sun, Xuguang; Hou, Wenbo; Guo, Ning

2012-01-01

A total of 26 myopic patients (52 eyes) underwent laser in situ keratomileusis. In vivo confocal microscopy revealed that most of the regenerated corneal subbasal nerve fibers in the corneal flap originated from the stump of corneal subbasal nerve fibers outside the ablation zone and extended towards the center of the cornea in all patients. Meanwhile, new fibers were also found to directly regenerate from deep in the stroma in some cases. Approximately 94% of regenerated corneal subbasal nerve fibers (73/78 eyes) regrew vertically into the peripheral central 6-mm circle area 1 month after surgery, 78% (28/36 eyes) grew into the central 3–6 mm area at 2 months, and 23% into the central 3-mm circle area at 3 months. In addition, there was no significant difference in corneal subbasal nerve fiber regenerative capacity between the basic fibroblast growth factor group and the 20% (v/v) deproteinized extract of calf blood group. The majority of corneal subbasal nerve fiber regeneration occurred from the stump of corneal subbasal nerve fibers outside the corneal flap, and the remaining growth occurred deep within the stroma. PMID:25657693

Depth reversals in stereoscopic displays driven by apparent size

NASA Astrophysics Data System (ADS)

Sacher, Gunnar; Hayes, Amy; Thornton, Ian M.; Sereno, Margaret E.; Malony, Allen D.

1998-04-01

In visual scenes, depth information is derived from a variety of monocular and binocular cues. When in conflict, a monocular cue is sometimes able to override the binocular information. We examined the accuracy of relative depth judgments in orthographic, stereoscopic displays and found that perceived relative size can override binocular disparity as a depth cue in a situation where the relative size information is itself generated from disparity information, not from retinal size difference. A size discrimination task confirmed the assumption that disparity information was perceived and used to generate apparent size differences. The tendency for the apparent size cue to override disparity information can be modulated by varying the strength of the apparent size cue. In addition, an analysis of reaction times provides supporting evidence for this novel depth reversal effect. We believe that human perception must be regarded as an important component of stereoscopic applications. Hence, if applications are to be effective and accurate, it is necessary to take into account the richness and complexity of the human visual perceptual system that interacts with them. We discuss implications of this and similar research for human performance in virtual environments, the design of visual presentations for virtual worlds, and the design of visualization tools.

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. Copyright © 2010 Elsevier Ltd and The Ergonomics Society. All rights reserved.

The formation of Greenland Sea Deep Water: double diffusion or deep convection?

NASA Astrophysics Data System (ADS)

Clarke, R. Allyn; Swift, James H.; Reid, Joseph L.; Koltermann, K. Peter

1990-09-01

An examination of the extensive hydrographic data sets collected by C.S.S. Hudson and F.S. Meteor in the Norwegian and Greenland Seas during February-June 1982 reveals property distributions and circulation patterns broadly similar to those seen in earlier data sets. These data sets, however, reveal the even stronger role played by topography, with evidence of separate circulation patterns and separate water masses in each of the deep basins. The high precision temperature, salinity and oxygen data obtained reveals significant differences in the deep and bottom waters found in the various basins of the Norwegian and Greenland Seas. A comparison of the 1982 data set with earlier sets shows that the renewal of Greenland Sea Deep Water must have taken place sometime over the last decade; however there is no evidence that deep convective renewal of any of the deep and bottom waters in this region was taking place at the time of the observations. The large-scale density fields, however, do suggest that deep convection to the bottom is most likely to occure in the Greenland Basin due to its deep cyclonic circulation. The hypothesis that Greenland Sea Deep Water (GSDW) is formed through dipycnal mixing processes acting on the warm salty core of Atlantic Water entering the Greenland Sea is examined. θ-S correlations and oxygen concentrations suggest that the salinity maxima in the Greenland Sea are the product of at least two separate mixing processes, not the hypothesized single mixing process leading to GSDW. A simple one-dimensional mixed layer model with ice growth and decay demonstrates that convective renewal of GSDW would have occurred within the Greenland Sea had the winter been a little more severe. The new GSDW produced would have only 0.003 less salt and less than 0.04 ml 1 -1 greater oxygen concentration than that already in the basin. Consequently, detection of whether new deep water has been produced following a winter cooling season could be difficult even

In vivo magnetization transfer and diffusion-weighted magnetic resonance imaging detects thrombus composition in a mouse model of deep vein thrombosis.

PubMed

Phinikaridou, Alkystis; Andia, Marcelo E; Saha, Prakash; Modarai, Bijan; Smith, Alberto; Botnar, René M

2013-05-01

Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis. Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; PANOVA<0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus (r=0.70; P<0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10(-3) mm(2)/s]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10(-3) mm(2)/s]). MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention.

Observation of oxygen ventilation into deep waters through targeted deployment of multiple Argo-O2 floats in the north-western Mediterranean Sea in 2013

NASA Astrophysics Data System (ADS)

Coppola, L.; Prieur, L.; Taupier-Letage, I.; Estournel, C.; Testor, P.; Lefevre, D.; Belamari, S.; LeReste, S.; Taillandier, V.

2017-08-01

During the winter 2013, an intense observation and monitoring was performed in the north-western Mediterranean Sea to study deep water formation process that drives thermohaline circulation and biogeochemical processes (HYMEX SOP2 and DEWEX projects). To observe intensively and continuously the impact of deep convection on oxygen (O2) ventilation, an observation strategy was based on the enhancement of the Argo-O2 floats to monitor the offshore dense water formation area (DWF) in the Gulf of Lion prior to and at the end of the convective period (December 2012 to April 2013). The intense O2 measurements performed through shipborne CTD casts and Argo-O2 floats deployment revealed an O2 inventory rapidly impacted by mixed layer (ML) deepening on the month scale. The open-sea convection in winter 2013 ventilated the deep waters from mid-February to the end of May 2013. The newly ventilated dense water volume, based on an Apparent Oxygen Utilization (AOU) threshold, was estimated to be about 1.5 × 1013 m3 during the DWF episode, increasing the deep O2 concentrations from 196 to 205 µmol kg-1 in the north-western basin.

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

Stromal Androgen Receptor in Prostate Cancer Development and Progression

PubMed Central

Leach, Damien A.; Buchanan, Grant

2017-01-01

Prostate cancer development and progression is the result of complex interactions between epithelia cells and fibroblasts/myofibroblasts, in a series of dynamic process amenable to regulation by hormones. Whilst androgen action through the androgen receptor (AR) is a well-established component of prostate cancer biology, it has been becoming increasingly apparent that changes in AR signalling in the surrounding stroma can dramatically influence tumour cell behavior. This is reflected in the consistent finding of a strong association between stromal AR expression and patient outcomes. In this review, we explore the relationship between AR signalling in fibroblasts/myofibroblasts and prostate cancer cells in the primary site, and detail the known functions, actions, and mechanisms of fibroblast AR signaling. We conclude with an evidence-based summary of how androgen action in stroma dramatically influences disease progression. PMID:28117763

Assessing the intersection/remagnetization puzzle with synthetic apparent polar wander paths

NASA Astrophysics Data System (ADS)

Pivarunas, Anthony F.; Meert, Joseph G.; Miller, Scott R.

2018-05-01

Paleomagnetic data are of variable quality. To assist in a systematic assessment of data, a set of seven quality criteria (VQ1 - VQ7) were introduced by Van der Voo (1990). The last of those criteria `VQ7' concerns the possibility of remagnetization when a particular paleomagnetic pole resembles a younger paleopole from the same stable region. While remagnetizations are often the culprit, the mere resemblance of an older pole to a younger pole does not a priori require that the rocks under investigation are remagnetized. Given that the Earth has a finite surface area; that apparent polar wander paths are represented as wide swathes rather than points, and that continental motion has taken place over several billion years, we ask the question `How likely is it for an apparent polar wander path to loop back on itself?' To answer this question, we constructed synthetic apparent polar wander paths (APWPs) in an effort to evaluate the likelihood of self-intersection. We find that given 500 Myr of apparent polar wander, ˜60 per cent of the synthetic APWPs show self-intersection. Given 1000 Myr of apparent polar wander, ˜95 per cent of the synthetic APWPs show self-intersection. These results show that resemblance to younger paleopoles, over the long term, may be governed by simple probability rather than only remagnetization. We recognize that remagnetization does occur, sometimes pervasively, and must be reckoned with in the assessment of paleomagnetic data. Perhaps VQ7 should be amended to the first sentence in the original discussion (Van der Voo, 1990), and focus on satisfying `No suspicion of remagnetization' via other means rather than solely a resemblance to younger poles.

Do deep convolutional neural networks really need to be deep when applied for remote scene classification?

NASA Astrophysics Data System (ADS)

Luo, Chang; Wang, Jie; Feng, Gang; Xu, Suhui; Wang, Shiqiang

2017-10-01

Deep convolutional neural networks (CNNs) have been widely used to obtain high-level representation in various computer vision tasks. However, for remote scene classification, there are not sufficient images to train a very deep CNN from scratch. From two viewpoints of generalization power, we propose two promising kinds of deep CNNs for remote scenes and try to find whether deep CNNs need to be deep for remote scene classification. First, we transfer successful pretrained deep CNNs to remote scenes based on the theory that depth of CNNs brings the generalization power by learning available hypothesis for finite data samples. Second, according to the opposite viewpoint that generalization power of deep CNNs comes from massive memorization and shallow CNNs with enough neural nodes have perfect finite sample expressivity, we design a lightweight deep CNN (LDCNN) for remote scene classification. With five well-known pretrained deep CNNs, experimental results on two independent remote-sensing datasets demonstrate that transferred deep CNNs can achieve state-of-the-art results in an unsupervised setting. However, because of its shallow architecture, LDCNN cannot obtain satisfactory performance, regardless of whether in an unsupervised, semisupervised, or supervised setting. CNNs really need depth to obtain general features for remote scenes. This paper also provides baseline for applying deep CNNs to other remote sensing tasks.

APPARENT CROSS-FIELD SUPERSLOW PROPAGATION OF MAGNETOHYDRODYNAMIC WAVES IN SOLAR PLASMAS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaneko, T.; Yokoyama, T.; Goossens, M.

2015-10-20

In this paper we show that the phase-mixing of continuum Alfvén waves and/or continuum slow waves in the magnetic structures of the solar atmosphere as, e.g., coronal arcades, can create the illusion of wave propagation across the magnetic field. This phenomenon could be erroneously interpreted as fast magnetosonic waves. The cross-field propagation due to the phase-mixing of continuum waves is apparent because there is no real propagation of energy across the magnetic surfaces. We investigate the continuous Alfvén and slow spectra in two-dimensional (2D) Cartesian equilibrium models with a purely poloidal magnetic field. We show that apparent superslow propagation acrossmore » the magnetic surfaces in solar coronal structures is a consequence of the existence of continuum Alfvén waves and continuum slow waves that naturally live on those structures and phase-mix as time evolves. The apparent cross-field phase velocity is related to the spatial variation of the local Alfvén/slow frequency across the magnetic surfaces and is slower than the Alfvén/sound velocities for typical coronal conditions. Understanding the nature of the apparent cross-field propagation is important for the correct analysis of numerical simulations and the correct interpretation of observations.« less

The DEEP2 Galaxy Redshift Survey: Design, Observations, Data Reduction, and Redshifts

NASA Technical Reports Server (NTRS)

Newman, Jeffrey A.; Cooper, Michael C.; Davis, Marc; Faber, S. M.; Coil, Alison L; Guhathakurta, Puraga; Koo, David C.; Phillips, Andrew C.; Conroy, Charlie; Dutton, Aaron A.;

DeepSurv: personalized treatment recommender system using a Cox proportional hazards deep neural network.

PubMed

Katzman, Jared L; Shaham, Uri; Cloninger, Alexander; Bates, Jonathan; Jiang, Tingting; Kluger, Yuval

2018-02-26

Medical practitioners use survival models to explore and understand the relationships between patients' covariates (e.g. clinical and genetic features) and the effectiveness of various treatment options. Standard survival models like the linear Cox proportional hazards model require extensive feature engineering or prior medical knowledge to model treatment interaction at an individual level. While nonlinear survival methods, such as neural networks and survival forests, can inherently model these high-level interaction terms, they have yet to be shown as effective treatment recommender systems. We introduce DeepSurv, a Cox proportional hazards deep neural network and state-of-the-art survival method for modeling interactions between a patient's covariates and treatment effectiveness in order to provide personalized treatment recommendations. We perform a number of experiments training DeepSurv on simulated and real survival data. We demonstrate that DeepSurv performs as well as or better than other state-of-the-art survival models and validate that DeepSurv successfully models increasingly complex relationships between a patient's covariates and their risk of failure. We then show how DeepSurv models the relationship between a patient's features and effectiveness of different treatment options to show how DeepSurv can be used to provide individual treatment recommendations. Finally, we train DeepSurv on real clinical studies to demonstrate how it's personalized treatment recommendations would increase the survival time of a set of patients. The predictive and modeling capabilities of DeepSurv will enable medical researchers to use deep neural networks as a tool in their exploration, understanding, and prediction of the effects of a patient's characteristics on their risk of failure.

Pathogenesis of deep endometriosis.

PubMed

Gordts, Stephan; Koninckx, Philippe; Brosens, Ivo

2017-12-01

The pathophysiology of (deep) endometriosis is still unclear. As originally suggested by Cullen, change the definition "deeper than 5 mm" to "adenomyosis externa." With the discovery of the old European literature on uterine bleeding in 5%-10% of the neonates and histologic evidence that the bleeding represents decidual shedding, it is postulated/hypothesized that endometrial stem/progenitor cells, implanted in the pelvic cavity after birth, may be at the origin of adolescent and even the occasionally premenarcheal pelvic endometriosis. Endometriosis in the adolescent is characterized by angiogenic and hemorrhagic peritoneal and ovarian lesions. The development of deep endometriosis at a later age suggests that deep infiltrating endometriosis is a delayed stage of endometriosis. Another hypothesis is that the endometriotic cell has undergone genetic or epigenetic changes and those specific changes determine the development into deep endometriosis. This is compatible with the hereditary aspects, and with the clonality of deep and cystic ovarian endometriosis. It explains the predisposition and an eventual causal effect by dioxin or radiation. Specific genetic/epigenetic changes could explain the various expressions and thus typical, cystic, and deep endometriosis become three different diseases. Subtle lesions are not a disease until epi(genetic) changes occur. A classification should reflect that deep endometriosis is a specific disease. In conclusion the pathophysiology of deep endometriosis remains debated and the mechanisms of disease progression, as well as the role of genetics and epigenetics in the process, still needs to be unraveled. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Pre-Hawking radiation cannot prevent the formation of apparent horizon

NASA Astrophysics Data System (ADS)

Chen, Pisin; Unruh, William G.; Wu, Chih-Hung; Yeom, Dong-Han

2018-03-01

As an attempt to solve the black hole information loss paradox, recently there has been the suggestion that, due to semiclassical effects, a pre-Hawking radiation must exist during the gravitational collapse of matter, which in turn prevents the apparent horizon from forming. Assuming the pre-Hawking radiation does exist, here we argue the opposite. First we note that the stress energy tensor near the horizon for the pre-Hawking radiation is far too small to do anything to the motion of a collapsing shell. Thus the shell will always cross the apparent horizon within a finite proper time. Moreover, the amount of energy that can be radiated must be less than half of the total initial energy (if the particle starts at rest at infinity) before the shell becomes a null shell and cannot radiate any more without becoming tachyonic. We conclude that for any gravitational collapsing process within Einstein gravity and semiclassical quantum field theory, the formation of the apparent horizon is inevitable. Pre-Hawking radiation is therefore not a valid solution to the information paradox.

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.

Dining in the Deep: The Feeding Ecology of Deep-Sea Fishes

NASA Astrophysics Data System (ADS)

Drazen, Jeffrey C.; Sutton, Tracey T.

2017-01-01

Deep-sea fishes inhabit ˜75% of the biosphere and are a critical part of deep-sea food webs. Diet analysis and more recent trophic biomarker approaches, such as stable isotopes and fatty-acid profiles, have enabled the description of feeding guilds and an increased recognition of the vertical connectivity in food webs in a whole-water-column sense, including benthic-pelagic coupling. Ecosystem modeling requires data on feeding rates; the available estimates indicate that deep-sea fishes have lower per-individual feeding rates than coastal and epipelagic fishes, but the overall predation impact may be high. A limited number of studies have measured the vertical flux of carbon by mesopelagic fishes, which appears to be substantial. Anthropogenic activities are altering deep-sea ecosystems and their services, which are mediated by trophic interactions. We also summarize outstanding data gaps.

Successful nucleofection of rat adipose-derived stroma cells with Ambystoma mexicanum epidermal lipoxygenase (AmbLOXe).

PubMed

Fülbier, Angela; Schnabel, Reinhild; Michael, Stefanie; Vogt, Peter M; Strauß, Sarah; Reimers, Kerstin; Radtke, Christine

2014-10-09

Adipose-derived stroma cells (ASCs) are attractive cells for cell-based gene therapy but are generally difficult to transfect. Nucleofection has proven to be an efficient method for transfection of primary cells. Therefore, we used this technique to transfect ASCs with a vector encoding for Ambystoma mexicanum epidermal lipoxygenase (AmbLOXe) which is a promising bioactive enzyme in regenerative processes. Thereby, we thought to even further increase the large regenerative potential of the ASCs. ASCs were isolated from the inguinal fat pad of Lewis rats and were subsequently transfected in passage 1 using Nucleofector® 2b and the hMSC Nucleofector kit. Transfection efficiency was determined measuring co-transfected green fluorescent protein (GFP) in a flow cytometer and gene expression in transfected cells was detected by reverse transcription polymerase chain reaction (RT-PCR). Moreover, cell migration was assessed using a scratch assay and results were tested for statistical significance with ANOVA followed by Bonferroni's post hoc test. High initial transfection rates were achieved with an average of 79.8 ± 2.82% of GFP positive cells although longer cultivation periods reduced the number of positive cells to below 5% after four passages. Although successful production of AmbLOXe transcript could be proven the gene product had no measureable effect on cell migration. Our study demonstrates the feasibility of ASCs to serve as a vehicle of AmbLOXe transport for gene therapeutic purposes in regenerative medicine. One potential field of applications could be peripheral nerve injuries.

Pathogenesis of the dry eye syndrome observed by optical coherence tomography in vitro

NASA Astrophysics Data System (ADS)

Kray, Oya; Lenz, Markus; Spöler, Felix; Kray, Stefan; Kurz, Heinrich

2011-06-01

Three dimensional optical coherence tomography (OCT) is introduced as a valuable tool to analyze the pathogenesis of corneal diseases. Here, OCT in combination with a novel in vitro model for the dry eye syndrome enables an improved understanding of the underlying damaging process of the ocular surface. En-face OCT projections indicate a deep structural damage of the epithelium and anterior stroma by osmotic forces.

Metazoan meiofauna in deep-sea canyons and adjacent open slopes: A large-scale comparison with focus on the rare taxa

NASA Astrophysics Data System (ADS)

Bianchelli, S.; Gambi, C.; Zeppilli, D.; Danovaro, R.

2010-03-01

Metazoan meiofaunal abundance, total biomass, nematode size and the richness of taxa were investigated along bathymetric gradients (from the shelf break down to ca. 5000-m depth) in six submarine canyons and on five adjacent open slopes of three deep-sea regions. The investigated areas were distributed along >2500 km, on the Portuguese to the Catalan and South Adriatic margins. The Portuguese and Catalan margins displayed the highest abundances, biomass and richness of taxa, while the lowest values were observed in the Central Mediterranean Sea. The comparison between canyons and the nearby open slopes showed the lack of significant differences in terms of meiofaunal abundance and biomass at any sampling depth. In most canyons and on most slopes, meiofaunal variables did not display consistent bathymetric patterns. Conversely, we found that the different topographic features were apparently responsible for significant differences in the abundance and distribution of the rare meiofaunal taxa (i.e. taxa accounting for <1% of total meiofaunal abundance). Several taxa belonging to the temporary meiofauna, such as larvae/juveniles of Priapulida, Holothuroidea, Ascidiacea and Cnidaria, were encountered exclusively on open slopes, while others (including the Tanaidacea and Echinodea larvae) were found exclusively in canyons sediments. Results reported here indicate that, at large spatial scales, differences in deep-sea meiofaunal abundance and biomass are not only controlled by the available food sources, but also by the region or habitat specific topographic features, which apparently play a key role in the distribution of rare benthic taxa.

Deep neural networks for direct, featureless learning through observation: The case of two-dimensional spin models

NASA Astrophysics Data System (ADS)

Mills, Kyle; Tamblyn, Isaac

2018-03-01

We demonstrate the capability of a convolutional deep neural network in predicting the nearest-neighbor energy of the 4 ×4 Ising model. Using its success at this task, we motivate the study of the larger 8 ×8 Ising model, showing that the deep neural network can learn the nearest-neighbor Ising Hamiltonian after only seeing a vanishingly small fraction of configuration space. Additionally, we show that the neural network has learned both the energy and magnetization operators with sufficient accuracy to replicate the low-temperature Ising phase transition. We then demonstrate the ability of the neural network to learn other spin models, teaching the convolutional deep neural network to accurately predict the long-range interaction of a screened Coulomb Hamiltonian, a sinusoidally attenuated screened Coulomb Hamiltonian, and a modified Potts model Hamiltonian. In the case of the long-range interaction, we demonstrate the ability of the neural network to recover the phase transition with equivalent accuracy to the numerically exact method. Furthermore, in the case of the long-range interaction, the benefits of the neural network become apparent; it is able to make predictions with a high degree of accuracy, and do so 1600 times faster than a CUDA-optimized exact calculation. Additionally, we demonstrate how the neural network succeeds at these tasks by looking at the weights learned in a simplified demonstration.

DeepARG: a deep learning approach for predicting antibiotic resistance genes from metagenomic data.

PubMed

Arango-Argoty, Gustavo; Garner, Emily; Pruden, Amy; Heath, Lenwood S; Vikesland, Peter; Zhang, Liqing

2018-02-01

Growing concerns about increasing rates of antibiotic resistance call for expanded and comprehensive global monitoring. Advancing methods for monitoring of environmental media (e.g., wastewater, agricultural waste, food, and water) is especially needed for identifying potential resources of novel antibiotic resistance genes (ARGs), hot spots for gene exchange, and as pathways for the spread of ARGs and human exposure. Next-generation sequencing now enables direct access and profiling of the total metagenomic DNA pool, where ARGs are typically identified or predicted based on the "best hits" of sequence searches against existing databases. Unfortunately, this approach produces a high rate of false negatives. To address such limitations, we propose here a deep learning approach, taking into account a dissimilarity matrix created using all known categories of ARGs. Two deep learning models, DeepARG-SS and DeepARG-LS, were constructed for short read sequences and full gene length sequences, respectively. Evaluation of the deep learning models over 30 antibiotic resistance categories demonstrates that the DeepARG models can predict ARGs with both high precision (> 0.97) and recall (> 0.90). The models displayed an advantage over the typical best hit approach, yielding consistently lower false negative rates and thus higher overall recall (> 0.9). As more data become available for under-represented ARG categories, the DeepARG models' performance can be expected to be further enhanced due to the nature of the underlying neural networks. Our newly developed ARG database, DeepARG-DB, encompasses ARGs predicted with a high degree of confidence and extensive manual inspection, greatly expanding current ARG repositories. The deep learning models developed here offer more accurate antimicrobial resistance annotation relative to current bioinformatics practice. DeepARG does not require strict cutoffs, which enables identification of a much broader diversity of ARGs. The

Deep South Atlantic carbonate chemistry and increased interocean deep water exchange during last deglaciation

NASA Astrophysics Data System (ADS)

Yu, Jimin; Anderson, Robert F.; Jin, Zhangdong; Menviel, Laurie; Zhang, Fei; Ryerson, Fredrick J.; Rohling, Eelco J.

2014-04-01

Carbon release from the deep ocean at glacial terminations is a critical component of past climate change, but the underlying mechanisms remain poorly understood. We present a 28,000-year high-resolution record of carbonate ion concentration, a key parameter of the global carbon cycle, at 5-km water depth in the South Atlantic. We observe similar carbonate ion concentrations between the Last Glacial Maximum and the late Holocene, despite elevated concentrations in the glacial surface ocean. This strongly supports the importance of respiratory carbon accumulation in a stratified deep ocean for atmospheric CO2 reduction during the last ice age. After ˜9 μmol/kg decline during Heinrich Stadial 1, deep South Atlantic carbonate ion concentration rose by ˜24 μmol/kg from the onset of Bølling to Pre-boreal, likely caused by strengthening North Atlantic Deep Water formation (Bølling) or increased ventilation in the Southern Ocean (Younger Drays) or both (Pre-boreal). The ˜15 μmol/kg decline in deep water carbonate ion since ˜10 ka is consistent with extraction of alkalinity from seawater by deep-sea CaCO3 compensation and coral reef growth on continental shelves during the Holocene. Between 16,600 and 15,000 years ago, deep South Atlantic carbonate ion values converged with those at 3.4-km water depth in the western equatorial Pacific, as did carbon isotope and radiocarbon values. These observations suggest a period of enhanced lateral exchange of carbon between the deep South Atlantic and Pacific Oceans, probably due to an increased transfer of momentum from southern westerlies to the Southern Ocean. By spreading carbon-rich deep Pacific waters around Antarctica for upwelling, invigorated interocean deep water exchange would lead to more efficient CO2 degassing from the Southern Ocean, and thus to an atmospheric CO2 rise, during the early deglaciation.

Deleterious Mutations, Apparent Stabilizing Selection and the Maintenance of Quantitative Variation

PubMed Central

Kondrashov, A. S.; Turelli, M.

1992-01-01

Apparent stabilizing selection on a quantitative trait that is not causally connected to fitness can result from the pleiotropic effects of unconditionally deleterious mutations, because as N. Barton noted, ``... individuals with extreme values of the trait will tend to carry more deleterious alleles ....'' We use a simple model to investigate the dependence of this apparent selection on the genomic deleterious mutation rate, U; the equilibrium distribution of K, the number of deleterious mutations per genome; and the parameters describing directional selection against deleterious mutations. Unlike previous analyses, we allow for epistatic selection against deleterious alleles. For various selection functions and realistic parameter values, the distribution of K, the distribution of breeding values for a pleiotropically affected trait, and the apparent stabilizing selection function are all nearly Gaussian. The additive genetic variance for the quantitative trait is kQa(2), where k is the average number of deleterious mutations per genome, Q is the proportion of deleterious mutations that affect the trait, and a(2) is the variance of pleiotropic effects for individual mutations that do affect the trait. In contrast, when the trait is measured in units of its additive standard deviation, the apparent fitness function is essentially independent of Q and a(2); and β, the intensity of selection, measured as the ratio of additive genetic variance to the ``variance'' of the fitness curve, is very close to s = U/k, the selection coefficient against individual deleterious mutations at equilibrium. Therefore, this model predicts appreciable apparent stabilizing selection if s exceeds about 0.03, which is consistent with various data. However, the model also predicts that β must equal V(m)/V(G), the ratio of new additive variance for the trait introduced each generation by mutation to the standing additive variance. Most, although not all, estimates of this ratio imply

Corneal electrolysis for recurrence of corneal stromal dystrophy after keratoplasty

PubMed Central

Mashima, Y; Kawai, M; Yamada, M

2002-01-01

Aims: To evaluate corneal electrolysis as a treatment for recurrent diffuse corneal opacities at the host-graft interface of the stroma or at the subepithelial region in two types of granular corneal dystrophy (GCD). Methods: Recurrence developed at the host-graft interface of the stroma after lamellar keratoplasty in a patient with Avellino corneal dystrophy (ACD). At surgery, the deep aspect of the graft in this patient was partially separated from host tissue to expose the deposits, with one third of the host-graft junction left intact. The graft was everted, and electrolysis was applied directly to remove the deposits attached to both surfaces of the host and the graft. Then the graft was returned to its place and sutured. In two patients with homozygous ACD and one patient with the superficial variant of GCD, diffuse subepithelial opacities developed following penetrating keratoplasty. Electrolysis was applied directly to the corneal surface. Results: Deposits at the host-graft interface of the stroma and in the subepithelial region disappeared following treatment, and vision recovered in all patients. Conclusions: This method is a simple, easy, and inexpensive way to remove deposits that recur after lamellar or penetrating keratoplasty. PMID:11864880

Corneal electrolysis for recurrence of corneal stromal dystrophy after keratoplasty.

PubMed

Mashima, Y; Kawai, M; Yamada, M

2002-03-01

To evaluate corneal electrolysis as a treatment for recurrent diffuse corneal opacities at the host-graft interface of the stroma or at the subepithelial region in two types of granular corneal dystrophy (GCD). Recurrence developed at the host-graft interface of the stroma after lamellar keratoplasty in a patient with Avellino corneal dystrophy (ACD). At surgery, the deep aspect of the graft in this patient was partially separated from host tissue to expose the deposits, with one third of the host-graft junction left intact. The graft was everted, and electrolysis was applied directly to remove the deposits attached to both surfaces of the host and the graft. Then the graft was returned to its place and sutured. In two patients with homozygous ACD and one patient with the superficial variant of GCD, diffuse subepithelial opacities developed following penetrating keratoplasty. Electrolysis was applied directly to the corneal surface. Deposits at the host-graft interface of the stroma and in the subepithelial region disappeared following treatment, and vision recovered in all patients. This method is a simple, easy, and inexpensive way to remove deposits that recur after lamellar or penetrating keratoplasty.

DeepQA: improving the estimation of single protein model quality with deep belief networks.

PubMed

Cao, Renzhi; Bhattacharya, Debswapna; Hou, Jie; Cheng, Jianlin

2016-12-05

Protein quality assessment (QA) useful for ranking and selecting protein models has long been viewed as one of the major challenges for protein tertiary structure prediction. Especially, estimating the quality of a single protein model, which is important for selecting a few good models out of a large model pool consisting of mostly low-quality models, is still a largely unsolved problem. We introduce a novel single-model quality assessment method DeepQA based on deep belief network that utilizes a number of selected features describing the quality of a model from different perspectives, such as energy, physio-chemical characteristics, and structural information. The deep belief network is trained on several large datasets consisting of models from the Critical Assessment of Protein Structure Prediction (CASP) experiments, several publicly available datasets, and models generated by our in-house ab initio method. Our experiments demonstrate that deep belief network has better performance compared to Support Vector Machines and Neural Networks on the protein model quality assessment problem, and our method DeepQA achieves the state-of-the-art performance on CASP11 dataset. It also outperformed two well-established methods in selecting good outlier models from a large set of models of mostly low quality generated by ab initio modeling methods. DeepQA is a useful deep learning tool for protein single model quality assessment and protein structure prediction. The source code, executable, document and training/test datasets of DeepQA for Linux is freely available to non-commercial users at http://cactus.rnet.missouri.edu/DeepQA/ .

The ‘apparent clearance’ of free phenytoin in elderly vs. younger adults

PubMed Central

Wright, Daniel F B; Begg, Evan J

2010-01-01

AIMS To test the hypothesis that the ‘apparent clearance’ of free phenytoin is reduced in elderly patients. METHODS Two separate studies were conducted comparing free phenytoin ‘apparent clearance’ in elderly vs. younger adults. The first study was a retrospective analysis of free phenytoin concentrations measured at Christchurch Hospital from 1997 to 2006. In the second study free phenytoin concentrations were measured prospectively in ambulatory subjects who were taking phenytoin regularly. RESULTS In the retrospective study (n = 29), free phenytoin ‘apparent clearance’ was 0.27 ± 0.04 l kg−1 day−1 (95% CI 0.19, 0.34) in the elderly cohort vs. 0.37 ± 0.06 l kg−1 day−1 (95% CI 0.22, 0.52) in younger adults, but the difference was not statistically significant. In the prospective study, free phenytoin ‘apparent clearance’ showed a non-significant trend to being reduced in the elderly patients (0.12 ± 0.02 l kg−1 day−1, 95% CI 0.07, 0.17) compared with the younger cohort (0.18 ± 0.07 l kg−1 day−1, 95% CI 0.09, 0.26) in those not taking interacting drugs (n = 21). CONCLUSIONS This research does not prove the hypothesis that the ‘apparent clearance’ of free phenytoin is reduced in the elderly. However, the trends found in these two studies are supported by trends in the same direction in other published studies, suggesting an age effect. PMID:20642556

Apparent Yield Strength of Hot-Pressed SiCs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daloz, William L; Wereszczak, Andrew A; Jadaan, Osama M.

2008-01-01

Apparent yield strengths (YApp) of four hot-pressed silicon carbides (SiC-B, SiC-N,SiC-HPN, and SiC-SC-1RN) were estimated using diamond spherical or Hertzian indentation. The von Mises and Tresca criteria were considered. The developed test method was robust, simple and quick to execute, and thusly enabled the acquisition of confident sampling statistics. The choice of indenter size, test method, and method of analysis are described. The compressive force necessary to initiate apparent yielding was identified postmortem using differential interference contrast (or Nomarski) imaging with an optical microscope. It was found that the YApp of SiC-HPN (14.0 GPa) was approximately 10% higher than themore » equivalently valued YApp of SiC-B, SiC-N, and SiC-SC-1RN. This discrimination in YApp shows that the use of this test method could be insightful because there were no differences among the average Knoop hardnesses of the four SiC grades.« less

The apparent solubility of aluminum (III) in Hanford high-level waste.

PubMed

Reynolds, Jacob G

2012-01-01

The solubility of aluminum in Hanford nuclear waste impacts on the processability of the waste by a number of proposed treatment options. For many years, Hanford staff has anecdotally noted that aluminum appears to be considerably more soluble in Hanford waste than the simpler electrolyte solutions used as analogues. There has been minimal scientific study to confirm these anecdotal observations, however. The present study determines the apparent solubility product for gibbsite in 50 tank samples. The ratio of hydroxide to aluminum in the liquid phase for the samples is calculated and plotted as a function of total sodium molarity. Total sodium molarity is used as a surrogate for ionic strength, because the relative ratios of mono-, di- and trivalent anions are not available for all of the samples. These results were compared to the simple NaOH-NaAl(OH)(4)-H(2)O system, and the NaOH-NaAl(OH)(4)-NaCl-H(2)O system data retrieved from the literature. The results show that gibbsite is apparently more soluble in the samples than in the simple systems whenever the sodium molarity is greater than 2M. This apparent enhanced solubility cannot be explained solely by differences in ionic strength. The change in solubility with ionic strength in simple systems is small compared to the difference between aluminum solubility in Hanford waste and the simple systems. The reason for the apparent enhanced solubility is unknown, but could include kinetic or thermodynamic factors that are not present in the simple electrolyte systems. Any kinetic explanation would have to explain why the samples are always supersaturated whenever the sodium molarity is above 2M. Real waste characterization data should not be used to validate thermodynamic solubility models until it can be confirmed that the apparent enhanced gibbsite solubility is a thermodynamic effect and not a kinetic effect.

Effect of air gap on apparent temperature of body wearing various sizes of T-shirt

NASA Astrophysics Data System (ADS)

Takatera, M.; Uchiyama, E.; Zhu, C.; Kim, KO; Ishizawa, H.

2017-10-01

We investigated the effect of air gap on the apparent temperature. Using the developed thermocouple fabric and a thermal manikin, we measured temperature distribution of the measuring garments due to the change of T-shirt sizes. We were able to measure the apparent temperature distribution at points near a body while wearing different sizes of T-shirts. It was observed that the temperature distribution depending on different air gap between clothing and body. The apparent temperature depends on garment size and place. The effect of air gap on apparent temperature of body was experimentally confirmed.

DeepPicker: A deep learning approach for fully automated particle picking in cryo-EM.

PubMed

Wang, Feng; Gong, Huichao; Liu, Gaochao; Li, Meijing; Yan, Chuangye; Xia, Tian; Li, Xueming; Zeng, Jianyang

2016-09-01

Particle picking is a time-consuming step in single-particle analysis and often requires significant interventions from users, which has become a bottleneck for future automated electron cryo-microscopy (cryo-EM). Here we report a deep learning framework, called DeepPicker, to address this problem and fill the current gaps toward a fully automated cryo-EM pipeline. DeepPicker employs a novel cross-molecule training strategy to capture common features of particles from previously-analyzed micrographs, and thus does not require any human intervention during particle picking. Tests on the recently-published cryo-EM data of three complexes have demonstrated that our deep learning based scheme can successfully accomplish the human-level particle picking process and identify a sufficient number of particles that are comparable to those picked manually by human experts. These results indicate that DeepPicker can provide a practically useful tool to significantly reduce the time and manual effort spent in single-particle analysis and thus greatly facilitate high-resolution cryo-EM structure determination. DeepPicker is released as an open-source program, which can be downloaded from https://github.com/nejyeah/DeepPicker-python. Copyright © 2016 Elsevier Inc. All rights reserved.

DeepBase: annotation and discovery of microRNAs and other noncoding RNAs from deep-sequencing data.

PubMed

Yang, Jian-Hua; Qu, Liang-Hu

2012-01-01

Recent advances in high-throughput deep-sequencing technology have produced large numbers of short and long RNA sequences and enabled the detection and profiling of known and novel microRNAs (miRNAs) and other noncoding RNAs (ncRNAs) at unprecedented sensitivity and depth. In this chapter, we describe the use of deepBase, a database that we have developed to integrate all public deep-sequencing data and to facilitate the comprehensive annotation and discovery of miRNAs and other ncRNAs from these data. deepBase provides an integrative, interactive, and versatile web graphical interface to evaluate miRBase-annotated miRNA genes and other known ncRNAs, explores the expression patterns of miRNAs and other ncRNAs, and discovers novel miRNAs and other ncRNAs from deep-sequencing data. deepBase also provides a deepView genome browser to comparatively analyze these data at multiple levels. deepBase is available at http://deepbase.sysu.edu.cn/.

Automated tracking of tumor-stroma morphology in microtissues identifies functional targets within the tumor microenvironment for therapeutic intervention

PubMed Central

Åkerfelt, Malin; Bayramoglu, Neslihan; Robinson, Sean; Toriseva, Mervi; Schukov, Hannu-Pekka; Härmä, Ville; Virtanen, Johannes; Sormunen, Raija; Kaakinen, Mika; Kannala, Juho; Eklund, Lauri; Heikkilä, Janne; Nees, Matthias

2015-01-01

Cancer-associated fibroblasts (CAFs) constitute an important part of the tumor microenvironment and promote invasion via paracrine functions and physical impact on the tumor. Although the importance of including CAFs into three-dimensional (3D) cell cultures has been acknowledged, computational support for quantitative live-cell measurements of complex cell cultures has been lacking. Here, we have developed a novel automated pipeline to model tumor-stroma interplay, track motility and quantify morphological changes of 3D co-cultures, in real-time live-cell settings. The platform consists of microtissues from prostate cancer cells, combined with CAFs in extracellular matrix that allows biochemical perturbation. Tracking of fibroblast dynamics revealed that CAFs guided the way for tumor cells to invade and increased the growth and invasiveness of tumor organoids. We utilized the platform to determine the efficacy of inhibitors in prostate cancer and the associated tumor microenvironment as a functional unit. Interestingly, certain inhibitors selectively disrupted tumor-CAF interactions, e.g. focal adhesion kinase (FAK) inhibitors specifically blocked tumor growth and invasion concurrently with fibroblast spreading and motility. This complex phenotype was not detected in other standard in vitro models. These results highlight the advantage of our approach, which recapitulates tumor histology and can significantly improve cancer target validation in vitro. PMID:26375443

Radioimmunoassay determinations of p-hydroxyphenformin and of apparent phenformin in human plasma or serum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alkalay, D.; Khemani, L.; Bartlett, M.F.

1978-01-01

Sensitive radioimmunoassay procedures are described for measuring p-hydroxyphenformin and apparent phenformin in human plasma or serum. The p-hydroxyphenformin procedure, which requires advance phenformin analysis, offers excellent accuracy. The determinations of apparent phenformin are influenced by the phenformin and p-hydroxyphenformin contents of the samples. Over a period of four months, the methods showed a precision associated with relative standard deviations of 12% for apparent phenformin and 13% for p-hydroxyphenformin.

Spatio-temporal evolution of apparent resistivity during coal-seam hydraulic flushing

NASA Astrophysics Data System (ADS)

Li, Dexing; Wang, Enyuan; Song, Dazhao; Qiu, Liming; Kong, Xiangguo

2018-06-01

Hydraulic flushing in gas predrainage is widely used, but the hydraulic-flushing effect is evaluated in a traditional way, by determining the desorption volume, moisture content, gas drainage rate and other conventional indices. To verify the rationality and feasibility of the multielectrode resistivity method in the evaluation of coal-seam hydraulic flushing and to research the spatio-temporal evolution of apparent resistivity during hydraulic flushing, a field test was conducted in 17# coal seam at Nuodong Mine, Guizhou. During hydraulic flushing, four stages were defined according to the variation in coal rock resistivity with time, namely, the preparation stage, the sharply decreasing stage, the rapidly increasing stage and the steady stage. The apparent resistivity of the coal rock mass is affected mainly by its own degree of fragmentation and flushing volume. A more serious rupture and a greater flushing volume yield a smaller apparent resistivity during the sharply decreasing stage and a higher resistivity during the stable stage. After three months of gas predrainage, the residual gas content and the gas pressure at different points in the expected affected area decrease below the critical value. Changes in the residual gas content and gas pressure at these points are consistent with the apparent resistivity, which validates the rationality and feasibility of the multielectrode resistivity method in evaluating coal-seam hydraulic flushing.

Hidden cycle of dissolved organic carbon in the deep ocean.

PubMed

Follett, Christopher L; Repeta, Daniel J; Rothman, Daniel H; Xu, Li; Santinelli, Chiara

2014-11-25

Marine dissolved organic carbon (DOC) is a large (660 Pg C) reactive carbon reservoir that mediates the oceanic microbial food web and interacts with climate on both short and long timescales. Carbon isotopic content provides information on the DOC source via δ(13)C and age via Δ(14)C. Bulk isotope measurements suggest a microbially sourced DOC reservoir with two distinct components of differing radiocarbon age. However, such measurements cannot determine internal dynamics and fluxes. Here we analyze serial oxidation experiments to quantify the isotopic diversity of DOC at an oligotrophic site in the central Pacific Ocean. Our results show diversity in both stable and radio isotopes at all depths, confirming DOC cycling hidden within bulk analyses. We confirm the presence of isotopically enriched, modern DOC cocycling with an isotopically depleted older fraction in the upper ocean. However, our results show that up to 30% of the deep DOC reservoir is modern and supported by a 1 Pg/y carbon flux, which is 10 times higher than inferred from bulk isotope measurements. Isotopically depleted material turns over at an apparent time scale of 30,000 y, which is far slower than indicated by bulk isotope measurements. These results are consistent with global DOC measurements and explain both the fluctuations in deep DOC concentration and the anomalous radiocarbon values of DOC in the Southern Ocean. Collectively these results provide an unprecedented view of the ways in which DOC moves through the marine carbon cycle.

Hidden cycle of dissolved organic carbon in the deep ocean

PubMed Central

Follett, Christopher L.; Repeta, Daniel J.; Rothman, Daniel H.; Xu, Li; Santinelli, Chiara

2014-01-01

Marine dissolved organic carbon (DOC) is a large (660 Pg C) reactive carbon reservoir that mediates the oceanic microbial food web and interacts with climate on both short and long timescales. Carbon isotopic content provides information on the DOC source via δ13C and age via Δ14C. Bulk isotope measurements suggest a microbially sourced DOC reservoir with two distinct components of differing radiocarbon age. However, such measurements cannot determine internal dynamics and fluxes. Here we analyze serial oxidation experiments to quantify the isotopic diversity of DOC at an oligotrophic site in the central Pacific Ocean. Our results show diversity in both stable and radio isotopes at all depths, confirming DOC cycling hidden within bulk analyses. We confirm the presence of isotopically enriched, modern DOC cocycling with an isotopically depleted older fraction in the upper ocean. However, our results show that up to 30% of the deep DOC reservoir is modern and supported by a 1 Pg/y carbon flux, which is 10 times higher than inferred from bulk isotope measurements. Isotopically depleted material turns over at an apparent time scale of 30,000 y, which is far slower than indicated by bulk isotope measurements. These results are consistent with global DOC measurements and explain both the fluctuations in deep DOC concentration and the anomalous radiocarbon values of DOC in the Southern Ocean. Collectively these results provide an unprecedented view of the ways in which DOC moves through the marine carbon cycle. PMID:25385632

Spatial Attention and Audiovisual Interactions in Apparent Motion

ERIC Educational Resources Information Center

Sanabria, Daniel; Soto-Faraco, Salvador; Spence, Charles

2007-01-01

In this study, the authors combined the cross-modal dynamic capture task (involving the horizontal apparent movement of visual and auditory stimuli) with spatial cuing in the vertical dimension to investigate the role of spatial attention in cross-modal interactions during motion perception. Spatial attention was manipulated endogenously, either…

Superficial ovarian cortex vascularization is inversely related to the follicle reserve in normal cycling ovaries and is increased in polycystic ovary syndrome.

PubMed

Delgado-Rosas, F; Gaytán, M; Morales, C; Gómez, R; Gaytán, F

2009-05-01

The superficial ovarian cortex constitutes the micro-environment where resting and early growing follicles reside. As small follicles do not possess an independent capillary network, both their survival and early growth depend on their proximity to the cortical vessels. Little is known about the possible changes in superficial ovarian cortex vascularization in normal women throughout reproductive life or in pathological conditions such as polycystic ovary syndrome (PCOS) involving abnormal early follicle growth. We studied the vascularization of the superficial and deep cortical stroma (DCS) in normal cycling ovaries from 21 to 50 years of age and in infertile women with PCOS. We used archival ovarian samples and specific CD34 immunostaining to determine blood vessel density and to analyse correlation with age and with the ovarian follicle reserve. Normal cycling ovaries showed an age-related increase in the superficial cortical stroma vascularization that was inversely correlated with the density of small (primordial and primary) follicles. In contrast, blood vessel density in the DCS significantly decreased in women aged >or=40 years. Ovaries from PCOS showed a 2-fold increase in blood vessel density in both superficial cortical stroma and DCS with respect to age-matched controls. The increased vascularization of the superficial cortical stroma in normal ovaries in relation to age and in ovaries from PCOS could have profound effects on cortical metabolic rate, primordial follicle survival/activation and early follicle growth, and may underline changes in follicle dynamics in mid-aged women and in PCOS.

Organic matter assimilation and selective feeding by holothurians in the deep sea: some observations and comments

NASA Astrophysics Data System (ADS)

Ginger, Michael L.; Billett, David S. M.; Mackenzie, Karen L.; Konstandinos Kiriakoulakis; Neto, Renato R.; K. Boardman, Daniel; Santos, Vera L. C. S.; Horsfall, Ian M.; A. Wolff, George

The selective feeding behaviour and assimilation efficiencies of deep-sea holothurians were investigated in order to assess their impact on carbon and nitrogen remineralisation on the Porcupine Abyssal Plain (PAP; ˜ 49°N 16°W, ˜ 4850 m water depth). Unfortunately, reliable determination of organic matter in the gut contents of the organisms proved to be difficult, because of the lysis of cells associated with the death of the animals on recovery. This was expressed in high levels of free fatty acids in the gut contents of Oneirophanta mutabilis, which we ascribe to unregulated lipolysis of phospholipids and triacylglycerides. It was not possible to estimate accurately the contribution that such material made to the gut contents, but based on the distributions of sterols in the gut sediments, it is likely to have been substantial. Therefore, all assimilation efficiencies calculated for holothurians in the deep sea should be treated with caution. Fortuitously, a bloom of holothurians that feed on the sediment surface (namely Amperima rosea and Ellipinion molle) during the period of study provided an opportunity indirectly to assess the impact of megafauna on organic matter cycling at the PAP. Observations suggest that the depletion of phytosterols from the surficial sediments between July and October 1997 resulted from the selective uptake of fresh phytodetritus by the blooming species. Deep-sea holothurians do not biosynthesise sterols de novo and an estimate of the sterol required by the increased population of A. rosea and E. molle is equivalent to the sterol flux to the seafloor during the spring/summer of 1997. The implications are dramatic. Firstly, these and other megafauna apparently turned over and selectively removed phytosterols from the freshly arrived phytodetritus and the surficial sediment (0-5 mm) at the PAP in less than four months. Secondly, their action impacted the food resource available to other organisms. Finally, as phytosterols are

Quantifying apparent anisotropy in a chemically heterogeneous Earth's mantle

NASA Astrophysics Data System (ADS)

Faccenda, M.; Ferreira, A. M.; Lithgow-Bertelloni, C. R.; Stixrude, L. P.; Pennacchioni, G.

2017-12-01

The interpretation of seismic observations of anisotropy is not straightforward. For example, it is well established that a finely layered, purely isotropic medium is equivalent at large scale to a homogeneous anisotropic medium (Backus, 1962) and there is seismological evidence for fine layered media, such as quasi-laminated structures constrained from high-frequency scattered waves (e.g., Furumura and Kennett, 2005; Kennett and Furumura, 2008). Thus, when imaging fine layering with seismic wave data with wavelength larger than the layer's thickness may result in artificial (also called apparent) anisotropy. Recent studies identified families of stable fine scale models that are equivalent to long-wavelength, vertically transversely isotropic (VTI) models (Fichtner et al., 2013; Wang et al., 2013; Bodin et al., 2015), and efforts to consider more general media are currently under way (e.g., Capdeville et al., 2010a,b). However, it is not clear whether the equivalent fine scale models are compatible with the properties of Earth's mantle materials. In this contribution, we quantify apparent anisotropy arising from fine layering by considering a range of realistic Earth's compositions both at grain and rock scale. We show that significant apparent anisotropy can be formed in ideal conditions only in very narrow regions, while in most of the Earth's mantle apparent anisotropy will hardly be detectable. ReferencesBackus, G.E., 1962. J. Geophys. Res. 67, 4427-4440. Bodin, T., Capdeville, Y., Romanowicz, B. & Montagner, J.-P., 2015. In The Earth's Heterogeneous Mantle, pp. 105-144, eds Khan, A. & Deschamps, F., Springer. Capdeville, Y., Guillot, L., Marigo, J.J., 2010a. Geophys. J. Int. 182, 903-922. Capdeville, Y., Guillot, L., Marigo, J.J., 2010b. Geophys. J. Int. 181, 897-910. Fichtner, A., B. Kennett, and J. Trampert, 2013. Phys. Earth Planet. Inter., 219, 11-20. Furumura, T., Kennett, B.L.N., 2005. J. Geophys. Res. 110, 10.129/2004JB003486. Kennett, B.L.N., Furumura

Effect of temperature and heating rate on apparent lethal concentrations of pyrolysis products

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Solis, A. N.; Marcussen, W. H.; Furst, A.

1976-01-01

The apparent lethal concentrations for 50 percent of the test animals of the pyrolysis products from twelve polymeric materials were studied as a function of temperature and heating rate. The materials were polyethylene, nylon 6, ABS, polycarbonate, polyether sulfone, polyaryl sulfone, wool fabric, aromatic polyamide fabric, polychloroprene foam, polyvinyl fluoride film, Douglas fir, and red oak. The apparent lethal concentration values of most materials vary significantly with temperature and heating rate. The apparent lethal concentration values, based on weight of sample charged, appears to effectively integrate the thermophysical, thermochemical, and physiological responses from a known quantity of material under specified imposed conditions.

Pre-Hawking radiation cannot prevent the formation of apparent horizon

DOE PAGES

Chen, Pisin; Unruh, William G.; Wu, Chih-Hung; ...

2018-03-30

As an attempt to solve the black hole information loss paradox, recently there has been the suggestion that, due to semiclassical effects, a pre-Hawking radiation must exist during the gravitational collapse of matter, which in turn prevents the apparent horizon from forming. Assuming the pre-Hawking radiation does exist, here we argue the opposite. First we note that the stress energy tensor near the horizon for the pre-Hawking radiation is far too small to do anything to the motion of a collapsing shell. Thus the shell will always cross the apparent horizon within a finite proper time. Moreover, the amount ofmore » energy that can be radiated must be less than half of the total initial energy (if the particle starts at rest at infinity) before the shell becomes a null shell and cannot radiate any more without becoming tachyonic. Here, we conclude that for any gravitational collapsing process within Einstein gravity and semiclassical quantum field theory, the formation of the apparent horizon is inevitable. Pre-Hawking radiation is therefore not a valid solution to the information paradox.« less

Pre-Hawking radiation cannot prevent the formation of apparent horizon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Pisin; Unruh, William G.; Wu, Chih-Hung

As an attempt to solve the black hole information loss paradox, recently there has been the suggestion that, due to semiclassical effects, a pre-Hawking radiation must exist during the gravitational collapse of matter, which in turn prevents the apparent horizon from forming. Assuming the pre-Hawking radiation does exist, here we argue the opposite. First we note that the stress energy tensor near the horizon for the pre-Hawking radiation is far too small to do anything to the motion of a collapsing shell. Thus the shell will always cross the apparent horizon within a finite proper time. Moreover, the amount ofmore » energy that can be radiated must be less than half of the total initial energy (if the particle starts at rest at infinity) before the shell becomes a null shell and cannot radiate any more without becoming tachyonic. Here, we conclude that for any gravitational collapsing process within Einstein gravity and semiclassical quantum field theory, the formation of the apparent horizon is inevitable. Pre-Hawking radiation is therefore not a valid solution to the information paradox.« less

Elastic properties and apparent density of human edentulous maxilla and mandible

PubMed Central

Seong, Wook-Jin; Kim, Uk-Kyu; Swift, James Q.; Heo, Young-Cheul; Hodges, James S.; Ko, Ching-Chang

2009-01-01

The aim of this study aim was to determine whether elastic properties and apparent density of bone differ in different anatomical regions of the maxilla and mandible. Additional analyses assessed how elastic properties and apparent density were related. Four pairs of edentulous maxilla and mandibles were retrieved from fresh human cadavers. Bone samples from four anatomical regions (maxillary anterior, maxillary posterior, mandibular anterior, mandibular posterior) were obtained. Elastic modulus (EM) and hardness (H) were measured using the nano-indentation technique. Bone samples containing cortical and trabecular bone were used to measure composite apparent density (cAD) using Archimedes’ principle. Statistical analyses used repeated measures ANOVA and Pearson correlations. Bone physical properties differed between regions of the maxilla and mandible. Generally, mandible had higher physical property measurements than maxilla. EM and H were higher in posterior than in anterior regions; the reverse was true for cAD. Posterior maxillary cAD was significantly lower than that in the three other regions. PMID:19647417

Elastic properties and apparent density of human edentulous maxilla and mandible.

PubMed

Seong, W-J; Kim, U-K; Swift, J Q; Heo, Y-C; Hodges, J S; Ko, C-C

2009-10-01

The aim of this study was to determine whether elastic properties and apparent density of bone differ in different anatomical regions of the maxilla and mandible. Additional analyses assessed how elastic properties and apparent density were related. Four pairs of edentulous maxilla and mandibles were retrieved from fresh human cadavers. Bone samples from four anatomical regions (maxillary anterior, maxillary posterior, mandibular anterior, mandibular posterior) were obtained. Elastic modulus (EM) and hardness (H) were measured using the nano-indentation technique. Bone samples containing cortical and trabecular bone were used to measure composite apparent density (cAD) using Archimedes' principle. Statistical analyses used repeated measures ANOVA and Pearson correlations. Bone physical properties differed between regions of the maxilla and mandible. Generally, mandible had higher physical property measurements than maxilla. EM and H were higher in posterior than in anterior regions; the reverse was true for cAD. Posterior maxillary cAD was significantly lower than that in the three other regions.

Apparent contact angle and contact angle hysteresis on liquid infused surfaces.

PubMed

Semprebon, Ciro; McHale, Glen; Kusumaatmaja, Halim

2016-12-21

We theoretically investigate the apparent contact angle and contact angle hysteresis of a droplet placed on a liquid infused surface. We show that the apparent contact angle is not uniquely defined by material parameters, but also has a dependence on the relative size between the droplet and its surrounding wetting ridge formed by the infusing liquid. We derive a closed form expression for the contact angle in the limit of vanishing wetting ridge, and compute the correction for small but finite ridge, which corresponds to an effective line tension term. We also predict contact angle hysteresis on liquid infused surfaces generated by the pinning of the contact lines by the surface corrugations. Our analytical expressions for both the apparent contact angle and contact angle hysteresis can be interpreted as 'weighted sums' between the contact angles of the infusing liquid relative to the droplet and surrounding gas phases, where the weighting coefficients are given by ratios of the fluid surface tensions.

pDeep: Predicting MS/MS Spectra of Peptides with Deep Learning.

PubMed

Zhou, Xie-Xuan; Zeng, Wen-Feng; Chi, Hao; Luo, Chunjie; Liu, Chao; Zhan, Jianfeng; He, Si-Min; Zhang, Zhifei

2017-12-05

In tandem mass spectrometry (MS/MS)-based proteomics, search engines rely on comparison between an experimental MS/MS spectrum and the theoretical spectra of the candidate peptides. Hence, accurate prediction of the theoretical spectra of peptides appears to be particularly important. Here, we present pDeep, a deep neural network-based model for the spectrum prediction of peptides. Using the bidirectional long short-term memory (BiLSTM), pDeep can predict higher-energy collisional dissociation, electron-transfer dissociation, and electron-transfer and higher-energy collision dissociation MS/MS spectra of peptides with >0.9 median Pearson correlation coefficients. Further, we showed that intermediate layer of the neural network could reveal physicochemical properties of amino acids, for example the similarities of fragmentation behaviors between amino acids. We also showed the potential of pDeep to distinguish extremely similar peptides (peptides that contain isobaric amino acids, for example, GG = N, AG = Q, or even I = L), which were very difficult to distinguish using traditional search engines.

Thermal Dependence of the Apparent Km of Glutathione Reductases from Three Plant Species

PubMed Central

Mahan, James R.; Burke, John J.; Orzech, Karen A.

1990-01-01

The thermal dependencies of the apparent Km of the glutathione reductases from spinach (Spinacia oleracea L.) corn (Zea mays L.), and cucumber (Cucumis sativus L.) were determined. The apparent Km of the enzymes were found to vary up to 9-fold between 12.5 and 45°C. Values of the apparent Km in excess of 200% of the observed minimum are suggested to be detrimental to the normal function of the enzyme. We propose the term “thermal kinetic window” to describe to the range of temperatures over which the apparent Km of the glutathione reductase is within 200% of its minimum and suggest that it may be a useful indicator of the limits of thermal stress for a given species. The thermal kinetic windows determined in this study are: <16°C for spinach, 23 to 32°C for corn, and 35 to 41°C for cucumber. PMID:16667543

The apparency hypothesis applied to a local pharmacopoeia in the Brazilian northeast

PubMed Central

2014-01-01

Background Data from an ethnobotanical study were analyzed to see if they were in agreement with the biochemical basis of the apparency hypothesis based on an analysis of a pharmacopeia in a rural community adjacent to the Araripe National Forest (Floresta Nacional do Araripe - FLONA) in northeastern Brazil. The apparency hypothesis considers two groups of plants, apparent and non-apparent, that are characterized by conspicuity for herbivores (humans) and their chemical defenses. Methods This study involved 153 interviewees and used semi-structured interviews. The plants were grouped by habit and lignification to evaluate the behavior of these categories in terms of ethnospecies richness, use value and practical and commercial importance. Information about sites for collecting medicinal plants was also obtained. The salience of the ethnospecies was calculated. G-tests were used to test for differences in ethnospecies richness among collection sites and the Kruskal-Wallis test to identify differences in the use values of plants depending on habit and lignifications (e.g. plants were classes as woody or non-woody, the first group comprising trees, shrubs, and lignified climbers (vines) and the latter group comprising herbs and non-lignified climbers). Spearman’s correlation test was performed to relate salience to use value and these two factors with the commercial value of the plants. Results A total of 222 medicinal plants were cited. Herbaceous and woody plants exhibited the highest ethnospecies richness, the non-woody and herbaceous plants had the most practical value (current use), and anthropogenic areas were the main sources of woody and non-woody medicinal plants; herbs and trees were equally versatile in treating diseases and did not differ with regard to use value. Trees were highlighted as the most commercially important growth habit. Conclusions From the perspective of its biochemical fundamentals, the apparency hypothesis does not have predictive

An analytical model for subsurface irradiance and remote sensing reflectance in deep and shallow case-2 waters.

PubMed

Albert, A; Mobley, C

2003-11-03

Subsurface remote sensing signals, represented by the irradiance re fl ectance and the remote sensing re fl ectance, were investigated. The present study is based on simulations with the radiative transfer program Hydrolight using optical properties of Lake Constance (German: Bodensee) based on in-situ measurements of the water constituents and the bottom characteristics. Analytical equations are derived for the irradiance re fl ectance and remote sensing re fl ectance for deep and shallow water applications. The input of the parameterization are the inherent optical properties of the water - absorption a(lambda) and backscattering bb(lambda). Additionally, the solar zenith angle thetas, the viewing angle thetav , and the surface wind speed u are considered. For shallow water applications the bottom albedo RB and the bottom depth zB are included into the parameterizations. The result is a complete set of analytical equations for the remote sensing signals R and Rrs in deep and shallow waters with an accuracy better than 4%. In addition, parameterizations of apparent optical properties were derived for the upward and downward diffuse attenuation coefficients Ku and Kd.

Mapping apparent stress and energy radiation over fault zones of major earthquakes

USGS Publications Warehouse

McGarr, A.; Fletcher, Joe B.

2002-01-01

Using published slip models for five major earthquakes, 1979 Imperial Valley, 1989 Loma Prieta, 1992 Landers, 1994 Northridge, and 1995 Kobe, we produce maps of apparent stress and radiated seismic energy over their fault surfaces. The slip models, obtained by inverting seismic and geodetic data, entail the division of the fault surfaces into many subfaults for which the time histories of seismic slip are determined. To estimate the seismic energy radiated by each subfault, we measure the near-fault seismic-energy flux from the time-dependent slip there and then multiply by a function of rupture velocity to obtain the corresponding energy that propagates into the far-field. This function, the ratio of far-field to near-fault energy, is typically less than 1/3, inasmuch as most of the near-fault energy remains near the fault and is associated with permanent earthquake deformation. Adding the energy contributions from all of the subfaults yields an estimate of the total seismic energy, which can be compared with independent energy estimates based on seismic-energy flux measured in the far-field, often at teleseismic distances. Estimates of seismic energy based on slip models are robust, in that different models, for a given earthquake, yield energy estimates that are in close agreement. Moreover, the slip-model estimates of energy are generally in good accord with independent estimates by others, based on regional or teleseismic data. Apparent stress is estimated for each subfault by dividing the corresponding seismic moment into the radiated energy. Distributions of apparent stress over an earthquake fault zone show considerable heterogeneity, with peak values that are typically about double the whole-earthquake values (based on the ratio of seismic energy to seismic moment). The range of apparent stresses estimated for subfaults of the events studied here is similar to the range of apparent stresses for earthquakes in continental settings, with peak values of about

True versus apparent shapes of bow shocks

NASA Astrophysics Data System (ADS)

Tarango-Yong, Jorge A.; Henney, William J.

2018-06-01

Astrophysical bow shocks are a common result of the interaction between two supersonic plasma flows, such as winds or jets from stars or active galaxies, or streams due to the relative motion between a star and the interstellar medium. For cylindrically symmetric bow shocks, we develop a general theory for the effects of inclination angle on the apparent shape. We propose a new two-dimensional classification scheme for bow shapes, which is based on dimensionless geometric ratios that can be estimated from observational images. The two ratios are related to the flatness of the bow's apex, which we term planitude, and the openness of its wings, which we term alatude. We calculate the expected distribution in the planitude-alatude plane for a variety of simple geometrical and physical models: quadrics of revolution, wilkinoids, cantoids, and ancantoids. We further test our methods against numerical magnetohydrodynamical simulations of stellar bow shocks and find that the apparent planitude and alatude measured from infrared dust continuum maps serve as accurate diagnostics of the shape of the contact discontinuity, which can be used to discriminate between different physical models. We present an algorithm that can determine the planitude and alatude from observed bow shock emission maps with a precision of 10 to 20 per cent.

Apparent Mass Nonlinearity for Paired Oscillating Plates

NASA Astrophysics Data System (ADS)

Granlund, Kenneth; Ol, Michael

2014-11-01

The classical potential-flow problem of a plate oscillating sinusoidally at small amplitude, in a direction normal to its plane, has a well-known analytical solution of a fluid ``mass,'' multiplied by plate acceleration, being equal to the force on the plate. This so-called apparent-mass is analytically equal to that of a cylinder of fluid, with diameter equal to plate chord. The force is directly proportional to frequency squared. Here we consider experimentally a generalization, where two coplanar plates of equal chord are placed at some lateral distance apart. For spacing of ~0.5 chord and larger between the two plates, the analytical solution for a single plate can simply be doubled. Zero spacing means a plate of twice the chord and therefore a heuristic cylinder of fluid of twice the cross-sectional area. This limit is approached for plate spacing <0.5c. For a spacing of 0.1-0.2c, the force due to apparent mass was found to increase with frequency, when normalized by frequency squared; this is a nonlinearity and a departure from the classical theory. Flow visualization in a water-tank suggests that such departure can be imputed to vortex shedding from the plates' edges inside the inter-plate gap.

Automated Video Quality Assessment for Deep-Sea Video

NASA Astrophysics Data System (ADS)

Pirenne, B.; Hoeberechts, M.; Kalmbach, A.; Sadhu, T.; Branzan Albu, A.; Glotin, H.; Jeffries, M. A.; Bui, A. O. V.

2015-12-01

Video provides a rich source of data for geophysical analysis, often supplying detailed information about the environment when other instruments may not. This is especially true of deep-sea environments, where direct visual observations cannot be made. As computer vision techniques improve and volumes of video data increase, automated video analysis is emerging as a practical alternative to labor-intensive manual analysis. Automated techniques can be much more sensitive to video quality than their manual counterparts, so performing quality assessment before doing full analysis is critical to producing valid results.Ocean Networks Canada (ONC), an initiative of the University of Victoria, operates cabled ocean observatories that supply continuous power and Internet connectivity to a broad suite of subsea instruments from the coast to the deep sea, including video and still cameras. This network of ocean observatories has produced almost 20,000 hours of video (about 38 hours are recorded each day) and an additional 8,000 hours of logs from remotely operated vehicle (ROV) dives. We begin by surveying some ways in which deep-sea video poses challenges for automated analysis, including: 1. Non-uniform lighting: Single, directional, light sources produce uneven luminance distributions and shadows; remotely operated lighting equipment are also susceptible to technical failures. 2. Particulate noise: Turbidity and marine snow are often present in underwater video; particles in the water column can have sharper focus and higher contrast than the objects of interest due to their proximity to the light source and can also influence the camera's autofocus and auto white-balance routines. 3. Color distortion (low contrast): The rate of absorption of light in water varies by wavelength, and is higher overall than in air, altering apparent colors and lowering the contrast of objects at a distance.We also describe measures under development at ONC for detecting and mitigating

Mitogenomics does not resolve deep molluscan relationships (yet?).

PubMed

Stöger, I; Schrödl, M

2013-11-01

The origin of molluscs among lophotrochozoan metazoans is unresolved and interclass relationships are contradictory between morphology-based, multi-locus, and recent phylogenomic analyses. Within the "Deep Metazoan Phylogeny" framework, all available molluscan mitochondrial genomes were compiled, covering 6 of 8 classes. Genomes were reannotated, and 13 protein coding genes (PCGs) were analyzed in various taxon settings, under multiple masking and coding regimes. Maximum Likelihood based methods were used for phylogenetic reconstructions. In all cases, molluscs result mixed up with lophotrochozoan outgroups, and most molluscan classes with more than single representatives available are non-monophyletic. We discuss systematic errors such as long branch attraction to cause aberrant, basal positions of fast evolving ingroups such as scaphopods, patellogastropods and, in particular, the gastropod subgroup Heterobranchia. Mitochondrial sequences analyzed either as amino acids or nucleotides may perform well in some (Cephalopoda) but not in other palaeozoic molluscan groups; they are not suitable to reconstruct deep (Cambrian) molluscan evolution. Supposedly "rare" mitochondrial genome level features have long been promoted as phylogenetically informative. In our newly annotated data set, features such as genome size, transcription on one or both strands, and certain coupled pairs of PCGs show a homoplastic, but obviously non-random distribution. Apparently congruent (but not unambiguous) signal for non-trivial subclades, e.g. for a clade composed of pteriomorph and heterodont bivalves, needs confirmation from a more comprehensive bivalve sampling. We found that larger clusters not only of PCGs but also of rRNAs and even tRNAs can bear local phylogenetic signal; adding trnG-trnE to the end of the ancestral cluster trnM-trnC-trnY-trnW-trnQ might be synapomorphic for Mollusca. Mitochondrial gene arrangement and other genome level features explored and reviewed herein thus

Combined Diffusion Tensor Imaging and Apparent Transverse Relaxation Rate Differentiate Parkinson Disease and Atypical Parkinsonism.

PubMed

Du, G; Lewis, M M; Kanekar, S; Sterling, N W; He, L; Kong, L; Li, R; Huang, X

2017-05-01

Both diffusion tensor imaging and the apparent transverse relaxation rate have shown promise in differentiating Parkinson disease from atypical parkinsonism (particularly multiple system atrophy and progressive supranuclear palsy). The objective of the study was to assess the ability of DTI, the apparent transverse relaxation rate, and their combination for differentiating Parkinson disease, multiple system atrophy, progressive supranuclear palsy, and controls. A total of 106 subjects (36 controls, 35 patients with Parkinson disease, 16 with multiple system atrophy, and 19 with progressive supranuclear palsy) were included. DTI and the apparent transverse relaxation rate measures from the striatal, midbrain, limbic, and cerebellar regions were obtained and compared among groups. The discrimination performance of DTI and the apparent transverse relaxation rate among groups was assessed by using Elastic-Net machine learning and receiver operating characteristic curve analysis. Compared with controls, patients with Parkinson disease showed significant apparent transverse relaxation rate differences in the red nucleus. Compared to those with Parkinson disease, patients with both multiple system atrophy and progressive supranuclear palsy showed more widespread changes, extending from the midbrain to striatal and cerebellar structures. The pattern of changes, however, was different between the 2 groups. For instance, patients with multiple system atrophy showed decreased fractional anisotropy and an increased apparent transverse relaxation rate in the subthalamic nucleus, whereas patients with progressive supranuclear palsy showed an increased mean diffusivity in the hippocampus. Combined, DTI and the apparent transverse relaxation rate were significantly better than DTI or the apparent transverse relaxation rate alone in separating controls from those with Parkinson disease/multiple system atrophy/progressive supranuclear palsy; controls from those with Parkinson

Prognostic and functional role of subtype-specific tumor-stroma interaction in breast cancer.

PubMed

Merlino, Giuseppe; Miodini, Patrizia; Callari, Maurizio; D'Aiuto, Francesca; Cappelletti, Vera; Daidone, Maria Grazia

2017-10-01

None of the clinically relevant gene expression signatures available for breast cancer were specifically developed to capture the influence of the microenvironment on tumor cells. Here, we attempted to build subtype-specific signatures derived from an in vitro model reproducing tumor cell modifications after interaction with activated or normal stromal cells. Gene expression signatures derived from HER2+, luminal, and basal breast cancer cell lines (treated by normal fibroblasts or cancer-associated fibroblasts conditioned media) were evaluated in clinical tumors by in silico analysis on published gene expression profiles (GEPs). Patients were classified as microenvironment-positive (μENV+ve), that is, with tumors showing molecular profiles suggesting activation by the stroma, or microenvironment-negative (μENV-ve) based on correlation of their tumors' GEP with the respective subtype-specific signature. Patients with estrogen receptor alpha (ER)+/HER2-/μENV+ve tumors were characterized by 2.5-fold higher risk of developing distant metastases (HR = 2.546; 95% CI: 1.751-3.701, P = 9.84E-07), while μENV status did not affect, or only suggested the risk of distant metastases, in women with HER2+ (HR = 1.541; 95% CI: 0.788-3.012, P = 0.206) or ER-/HER2- tumors (HR = 1.894; 95% CI: 0.938-3.824; P = 0.0747), respectively. In ER+/HER2- tumors, the μENV status remained significantly associated with metastatic progression (HR = 2.098; CI: 1.214-3.624; P = 0.00791) in multivariable analysis including size, age, and Genomic Grade Index. Validity of our in vitro model was also supported by in vitro biological endpoints such as cell growth (MTT assay) and migration/invasion (Transwell assay). In vitro-derived gene signatures tracing the bidirectional interaction with cancer activated fibroblasts are subtype-specific and add independent prognostic information to classical prognostic variables in women with ER+/HER2- tumors. © 2017 The Authors. Published

Keratocyte density 3 months, 15 months, and 3 years after corneal surface ablation with mitomycin C.

PubMed

de Benito-Llopis, Laura; Cañadas, Pilar; Drake, Pilar; Hernández-Verdejo, José Luis; Teus, Miguel A

2012-01-01

To study the effects of surface ablation with mitomycin C (MMC) on keratocyte population. Prospective, nonrandomized, interventional, comparative case series. Thirty two eyes treated with surface ablation with 0.02% MMC were compared with nontreated eyes at Vissum Santa Hortensia, Madrid, Spain. Keratocyte density was measured with the Heidelberg Retina Tomograph II (Rostock Cornea Module) 3, 15, and 36 to 42 months after the surgery in the anterior, mid, and posterior stroma, and compared with control eyes. Three months postoperatively, we found a lower stromal bed density compared to controls (16 993 ± 8001 vs 29 660 ± 5904 cells/mm(3), P = .0001), while there was a significantly higher cell density in the mid (30 783 ± 9300 vs 18 505 ± 1996 cells/mm(3), P = .0001) and deep stroma (30 268 ± 8321 vs 18 438 ± 2139 cells/mm(3), P = .0001). Three years after the surgery, the cellularity in the stromal bed had not significantly changed from the 3-month follow-up, but the density in the mid (18 889 ± 3474 cells/mm(3)) and posterior stroma (18 992 ± 3402 cells/mm(3)) had decreased to show no difference from controls. The mean cell density between the anterior, mid, and posterior stroma was not significantly different from controls 15 months and 3 years after the surgery. Our study suggests that there is a reorganization of the stromal cell population soon after surface ablation with MMC, with a decrease in the stromal bed compensated initially with an increase in the mid and posterior stroma. Corneal cellularity tends to normalize over time, and 3 years postoperatively the mean cell density throughout the cornea seems to maintain normal values. Copyright © 2012 Elsevier Inc. All rights reserved.

Oxygen minimum zone: An important oceanographic habitat for deep-diving northern elephant seals, Mirounga angustirostris.

PubMed

Naito, Yasuhiko; Costa, Daniel P; Adachi, Taiki; Robinson, Patrick W; Peterson, Sarah H; Mitani, Yoko; Takahashi, Akinori

2017-08-01

Little is known about the foraging behavior of top predators in the deep mesopelagic ocean. Elephant seals dive to the deep biota-poor oxygen minimum zone (OMZ) (>800 m depth) despite high diving costs in terms of energy and time, but how they successfully forage in the OMZ remains largely unknown. Assessment of their feeding rate is the key to understanding their foraging behavior, but this has been challenging. Here, we assessed the feeding rate of 14 female northern elephant seals determined by jaw motion events (JME) and dive cycle time to examine how feeding rates varied with dive depth, particularly in the OMZ. We also obtained video footage from seal-mounted videos to understand their feeding in the OMZ. While the diel vertical migration pattern was apparent for most depths of the JME, some very deep dives, beyond the normal diel depth ranges, occurred episodically during daylight hours. The midmesopelagic zone was the main foraging zone for all seals. Larger seals tended to show smaller numbers of JME and lower feeding rates than smaller seals during migration, suggesting that larger seals tended to feed on larger prey to satisfy their metabolic needs. Larger seals also dived frequently to the deep OMZ, possibly because of a greater diving ability than smaller seals, suggesting their dependency on food in the deeper depth zones. Video observations showed that seals encountered the rarely reported ragfish ( Icosteus aenigmaticus ) in the depths of the OMZ, which failed to show an escape response from the seals, suggesting that low oxygen concentrations might reduce prey mobility. Less mobile prey in OMZ would enhance the efficiency of foraging in this zone, especially for large seals that can dive deeper and longer. We suggest that the OMZ plays an important role in structuring the mesopelagic ecosystem and for the survival and evolution of elephant seals.

The frequency-domain approach for apparent density mapping

NASA Astrophysics Data System (ADS)

Tong, T.; Guo, L.

2017-12-01

Apparent density mapping is a technique to estimate density distribution in the subsurface layer from the observed gravity data. It has been widely applied for geologic mapping, tectonic study and mineral exploration for decades. Apparent density mapping usually models the density layer as a collection of vertical, juxtaposed prisms in both horizontal directions, whose top and bottom surfaces are assumed to be horizontal or variable-depth, and then inverts or deconvolves the gravity anomalies to determine the density of each prism. Conventionally, the frequency-domain approach, which assumes that both top and bottom surfaces of the layer are horizontal, is usually utilized for fast density mapping. However, such assumption is not always valid in the real world, since either the top surface or the bottom surface may be variable-depth. Here, we presented a frequency-domain approach for apparent density mapping, which permits both the top and bottom surfaces of the layer to be variable-depth. We first derived the formula for forward calculation of gravity anomalies caused by the density layer, whose top and bottom surfaces are variable-depth, and the formula for inversion of gravity anomalies for the density distribution. Then we proposed the procedure for density mapping based on both the formulas of inversion and forward calculation. We tested the approach on the synthetic data, which verified its effectiveness. We also tested the approach on the real Bouguer gravity anomalies data from the central South China. The top surface was assumed to be flat and was on the sea level, and the bottom surface was considered as the Moho surface. The result presented the crustal density distribution, which was coinciding well with the basic tectonic features in the study area.

Deep learning for computational chemistry.

PubMed

Goh, Garrett B; Hodas, Nathan O; Vishnu, Abhinav

2017-06-15

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. © 2017 Wiley Periodicals, Inc.

Deep learning for computational chemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goh, Garrett B.; Hodas, Nathan O.; Vishnu, Abhinav

The rise and fall of artificial neural networks is well documented in the scientific literature of both the fields of 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 “deep” neural networks. Within the last few years, we have seen the transformative impact of deep learning the computer science domain, notably in speech recognition and computer vision, to the extent that the majority of practitioners in those field are now regularly eschewing prior established models in favor of deep learning models. Inmore » this review, we provide an introductory overview into the theory of deep neural networks and their unique properties as compared to 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 QSAR, virtual screening, protein structure modeling, QM calculations, materials synthesis 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 useful tool and may grow into a pivotal role for various challenges in the computational chemistry field.« less

Pb-isotopic Features of Primitive Rocks from Hess Deep: Distinguishing between EPR and Cocos-Nazca Mantle Source(s)

NASA Astrophysics Data System (ADS)

Jean, M. M.; Falloon, T.; Gillis, K. M.

2014-12-01

We have acquired high-precision Pb-isotopic signatures of primitive lithologies (basalts/gabbros) recovered from IODP Expedition 345.The Hess Deep Rift, located in the vicinity of the Galapagos triple junction (Cocos, Nazca, and Pacific), is viewed as one the best-studied tectonic windows into fast-spreading crust because a relatively young (<1.5 Ma) cross section of oceanic crust. This allows for (1) characterization of the mantle source(s) at Hess Deep, (2) insight into the extent of isotopic homogeneity or heterogeneity in the area, and (3) constrain the relative contributions from the intruding Cocos-Nazca spreading center. The observed Pb-isotopic variation at Hess Deep covers almost the entire range of EPR MORB (10°N to -5°S). Hess Deep samples range from 208Pb (37.3-38.25), 207Pb (15.47-15.58), 206Pb (17.69-18.91). These compositions suggest that this part of Hess Deep mantle is no more isotopically homogeneous than EPR mantle. Two distinct arrays are also observed: 208Pb-enriched (r2=0.985; n=30) and 208Pb-depleted (r2=0.988; n=6). The 208Pb/204Pb isotopes indicates that the Pb-source for some of the samples at Hess Deep had very low Th/U ratios, whereas other areas around the Galapagos microplate seem to have more "normal" ratios. These trends are less apparent when viewed with 207Pb-isotopes. Instead, the majority of basalts and gabbros follow the NHRL, however, at the depleted-end of this array a negative excursion to more enriched compositions is observed. This negative but linear trend could signify an alteration trend or mixing with an EMI-type mantle source, yet this mixing is not observed with 208Pb. This trend is also observed at Pito Deep, which has similar origins to Hess Deep (Barker et al., 2008; Pollack et al., 2009). The Galapagos region has been considered a testing ground for mixing of HIMU, Enriched Mantle, and Depleted Mantle reservoirs (e.g., Schilling et al., 2002). According to our data, however, an EPR-component must also be

The apparent solubility of aluminum (III) in Hanford high-level waste

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reynolds, Jacob G.

2012-12-01

The solubility of aluminum in Hanford nuclear waste impacts on the process ability of the waste by a number of proposed treatment options. For many years, Hanford staff has anecdotally noted that aluminum appears to be considerably more soluble in Hanford waste than the simpler electrolyte solutions used as analogues. There has been minimal scientific study to confirm these anecdotal observations, however. The present study determines the apparent solubility product for gibbsite in 50 tank samples. The ratio of hydroxide to aluminum in the liquid phase for the samples is calculated and plotted as a function of total sodium molarity.more » Total sodium molarity is used as a surrogate for ionic strength, because the relative ratios of mono, di and trivalent anions are not available for all of the samples. These results were compared to the simple NaOH-NaAl(OH{sub 4})H{sub 2}O system, and the NaOH-NaAl(OH{sub 4})NaCl-H{sub 2}O system data retrieved from the literature. The results show that gibbsite is apparently more soluble in the samples than in the simple systems whenever the sodium molarity is greater than two. This apparent enhanced solubility cannot be explained solely by differences in ionic strength. The change in solubility with ionic strength in simple systems is small compared to the difference between aluminum solubility in Hanford waste and the simple systems. The reason for the apparent enhanced solubility is unknown, but could include. kinetic or thermodynamic factors that are not present in the simple electrolyte systems. Any kinetic explanation would have to explain why the samples are always supersaturated whenever the sodium molarity is above two. Real waste characterization data should not be used to validate thermodynamic solubility models until it can be confirmed that the apparent enhanced gibbsite solubility is a thermodynamic effect and not a kinetic effect.« less

Effect of reactivity loss on apparent reaction order of burning char particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, Jeffrey J.; Shaddix, Christopher R.

Considerable debate still exists in the char combustion community over the expected and observed reaction orders of carbon reacting with oxygen. In particular, very low values of the reaction order (approaching zero) are commonly observed in char combustion experiments. These observations appear to conflict with porous catalyst theory as first expressed by Thiele, which suggests that the apparent reaction order must be greater than 0.5. In this work, we propose that this conflict may be resolved by considering the decrease in char reactivity with burnout due to ash effects, thermal annealing, or other phenomena. Specifically, the influence of ash dilutionmore » of the available surface area on the apparent reaction order is explored. Equations describing the ash dilution effect are combined with a model for particle burnout based on single-film nth-order Arrhenius char combustion and yield an analytical expression for the effective reaction order. When this expression is applied for experimental conditions reflecting combustion of individual pulverized coal particles in an entrained flow reactor, the apparent reaction order is shown to be lower than the inherent char matrix reaction order, even for negligible extents of char conversion. As char conversion proceeds and approaches completion, the apparent reaction order drops precipitously past zero to negative values. Conversely, the inclusion of the ash dilution model has little effect on the char conversion profile or char particle temperature until significant burnout has occurred. Taken together, these results suggest that the common experimental observation of low apparent reaction orders during char combustion is a consequence of the lack of explicit modeling of the decrease in char reactivity with burnout. (author)« less

Application of mixture experimental design to simvastatin apparent solubility predictions in the microemulsifion formed by self-microemulsifying.

PubMed

Meng, Jian; Zheng, Liangyuan

2007-09-01

Self-microemulsifying drug delivery systems (SMEDDS) are useful to improve the bioavailability of poorly water-soluble drugs by increasing their apparent solubility through solubilization. However, very few studies, to date, have systematically examined the level of drug apparent solubility in o/w microemulsion formed by self-microemulsifying. In this study, a mixture experimental design was used to simulate the influence of the compositions on simvastatin apparent solubility quantitatively through an empirical model. The reduced cubic polynomial equation successfully modeled the evolution of simvastatin apparent solubility. The results were presented using an analysis of response surface showing a scale of possible simvastatin apparent solubility between 0.0024 ~ 29.0 mg/mL. Moreover, this technique showed that simvastatin apparent solubility was mainly influenced by microemulsion concentration and, suggested that the drug would precipitate in the gastrointestinal tract due to dilution by gastrointestinal fluids. Furthermore, the model would help us design the formulation to maximize the drug apparent solubility and avoid precipitation of the drug.

Crude oil treatment leads to shift of bacterial communities in soils from the deep active layer and upper permafrost along the China-Russia Crude Oil Pipeline route.

PubMed

Yang, Sizhong; Wen, Xi; Zhao, Liang; Shi, Yulan; Jin, Huijun

2014-01-01

The buried China-Russia Crude Oil Pipeline (CRCOP) across the permafrost-associated cold ecosystem in northeastern China carries a risk of contamination to the deep active layers and upper permafrost in case of accidental rupture of the embedded pipeline or migration of oil spills. As many soil microbes are capable of degrading petroleum, knowledge about the intrinsic degraders and the microbial dynamics in the deep subsurface could extend our understanding of the application of in-situ bioremediation. In this study, an experiment was conducted to investigate the bacterial communities in response to simulated contamination to deep soil samples by using 454 pyrosequencing amplicons. The result showed that bacterial diversity was reduced after 8-weeks contamination. A shift in bacterial community composition was apparent in crude oil-amended soils with Proteobacteria (esp. α-subdivision) being the dominant phylum, together with Actinobacteria and Firmicutes. The contamination led to enrichment of indigenous bacterial taxa like Novosphingobium, Sphingobium, Caulobacter, Phenylobacterium, Alicylobacillus and Arthrobacter, which are generally capable of degrading polycyclic aromatic hydrocarbons (PAHs). The community shift highlighted the resilience of PAH degraders and their potential for in-situ degradation of crude oil under favorable conditions in the deep soils.

Crude Oil Treatment Leads to Shift of Bacterial Communities in Soils from the Deep Active Layer and Upper Permafrost along the China-Russia Crude Oil Pipeline Route

PubMed Central

Yang, Sizhong; Wen, Xi; Zhao, Liang; Shi, Yulan; Jin, Huijun

2014-01-01

The buried China-Russia Crude Oil Pipeline (CRCOP) across the permafrost-associated cold ecosystem in northeastern China carries a risk of contamination to the deep active layers and upper permafrost in case of accidental rupture of the embedded pipeline or migration of oil spills. As many soil microbes are capable of degrading petroleum, knowledge about the intrinsic degraders and the microbial dynamics in the deep subsurface could extend our understanding of the application of in-situ bioremediation. In this study, an experiment was conducted to investigate the bacterial communities in response to simulated contamination to deep soil samples by using 454 pyrosequencing amplicons. The result showed that bacterial diversity was reduced after 8-weeks contamination. A shift in bacterial community composition was apparent in crude oil-amended soils with Proteobacteria (esp. α-subdivision) being the dominant phylum, together with Actinobacteria and Firmicutes. The contamination led to enrichment of indigenous bacterial taxa like Novosphingobium, Sphingobium, Caulobacter, Phenylobacterium, Alicylobacillus and Arthrobacter, which are generally capable of degrading polycyclic aromatic hydrocarbons (PAHs). The community shift highlighted the resilience of PAH degraders and their potential for in-situ degradation of crude oil under favorable conditions in the deep soils. PMID:24794099

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)

DeepID-Net: Deformable Deep Convolutional Neural Networks for Object Detection.

PubMed

Ouyang, Wanli; Zeng, Xingyu; Wang, Xiaogang; Qiu, Shi; Luo, Ping; Tian, Yonglong; Li, Hongsheng; Yang, Shuo; Wang, Zhe; Li, Hongyang; Loy, Chen Change; Wang, Kun; Yan, Junjie; Tang, Xiaoou

2016-07-07

In this paper, we propose deformable deep convolutional neural networks for generic object detection. This new deep learning object detection framework has innovations in multiple aspects. In the proposed new deep architecture, a new deformation constrained pooling (def-pooling) layer models the deformation of object parts with geometric constraint and penalty. A new pre-training strategy is proposed to learn feature representations more suitable for the object detection task and with good generalization capability. By changing the net structures, training strategies, adding and removing some key components in the detection pipeline, a set of models with large diversity are obtained, which significantly improves the effectiveness of model averaging. The proposed approach improves the mean averaged precision obtained by RCNN [16], which was the state-of-the-art, from 31% to 50.3% on the ILSVRC2014 detection test set. It also outperforms the winner of ILSVRC2014, GoogLeNet, by 6.1%. Detailed component-wise analysis is also provided through extensive experimental evaluation, which provides a global view for people to understand the deep learning object detection pipeline.

Visual adaptation alters the apparent speed of real-world actions.

PubMed

Mather, George; Sharman, Rebecca J; Parsons, Todd

2017-07-27

The apparent physical speed of an object in the field of view remains constant despite variations in retinal velocity due to viewing conditions (velocity constancy). For example, people and cars appear to move across the field of view at the same objective speed regardless of distance. In this study a series of experiments investigated the visual processes underpinning judgements of objective speed using an adaptation paradigm and video recordings of natural human locomotion. Viewing a video played in slow-motion for 30 seconds caused participants to perceive subsequently viewed clips played at standard speed as too fast, so playback had to be slowed down in order for it to appear natural; conversely after viewing fast-forward videos for 30 seconds, playback had to be speeded up in order to appear natural. The perceived speed of locomotion shifted towards the speed depicted in the adapting video ('re-normalisation'). Results were qualitatively different from those obtained in previously reported studies of retinal velocity adaptation. Adapting videos that were scrambled to remove recognizable human figures or coherent motion caused significant, though smaller shifts in apparent locomotion speed, indicating that both low-level and high-level visual properties of the adapting stimulus contributed to the changes in apparent speed.

deepTools2: a next generation web server for deep-sequencing data analysis.

PubMed

Ramírez, Fidel; Ryan, Devon P; Grüning, Björn; Bhardwaj, Vivek; Kilpert, Fabian; Richter, Andreas S; Heyne, Steffen; Dündar, Friederike; Manke, Thomas

2016-07-08

We present an update to our Galaxy-based web server for processing and visualizing deeply sequenced data. Its core tool set, deepTools, allows users to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches. Since we first described our deepTools Galaxy server in 2014, we have implemented new solutions for many requests from the community and our users. Here, we introduce significant enhancements and new tools to further improve data visualization and interpretation. deepTools continue to be open to all users and freely available as a web service at deeptools.ie-freiburg.mpg.de The new deepTools2 suite can be easily deployed within any Galaxy framework via the toolshed repository, and we also provide source code for command line usage under Linux and Mac OS X. A public and documented API for access to deepTools functionality is also available. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Apparent-contact-angle model at partial wetting and evaporation: Impact of surface forces

NASA Astrophysics Data System (ADS)

Janeček, V.; Nikolayev, V. S.

2013-01-01

This theoretical and numerical study deals with evaporation of a fluid wedge in contact with its pure vapor. The model describes a regime where the continuous wetting film is absent and the actual line of the triple gas-liquid-solid contact appears. A constant temperature higher than the saturation temperature is imposed at the solid substrate. The fluid flow is solved in the lubrication approximation. The introduction of the surface forces in the case of the partial wetting is discussed. The apparent contact angle (the gas-liquid interface slope far from the contact line) is studied numerically as a function of the substrate superheating, contact line velocity, and parameters related to the solid-fluid interaction (Young and microscopic contact angles, Hamaker constant, etc.). The dependence of the apparent contact angle on the substrate temperature is in agreement with existing approaches. For water, the apparent contact angle may be 20∘ larger than the Young contact angle for 1 K superheating. The effect of the surface forces on the apparent contact angle is found to be weak.

Apparent-contact-angle model at partial wetting and evaporation: impact of surface forces.

PubMed

Janeček, V; Nikolayev, V S

2013-01-01

This theoretical and numerical study deals with evaporation of a fluid wedge in contact with its pure vapor. The model describes a regime where the continuous wetting film is absent and the actual line of the triple gas-liquid-solid contact appears. A constant temperature higher than the saturation temperature is imposed at the solid substrate. The fluid flow is solved in the lubrication approximation. The introduction of the surface forces in the case of the partial wetting is discussed. The apparent contact angle (the gas-liquid interface slope far from the contact line) is studied numerically as a function of the substrate superheating, contact line velocity, and parameters related to the solid-fluid interaction (Young and microscopic contact angles, Hamaker constant, etc.). The dependence of the apparent contact angle on the substrate temperature is in agreement with existing approaches. For water, the apparent contact angle may be 20° larger than the Young contact angle for 1 K superheating. The effect of the surface forces on the apparent contact angle is found to be weak.

MusiteDeep: a deep-learning framework for general and kinase-specific phosphorylation site prediction.

PubMed

Wang, Duolin; Zeng, Shuai; Xu, Chunhui; Qiu, Wangren; Liang, Yanchun; Joshi, Trupti; Xu, Dong

2017-12-15

Computational methods for phosphorylation site prediction play important roles in protein function studies and experimental design. Most existing methods are based on feature extraction, which may result in incomplete or biased features. Deep learning as the cutting-edge machine learning method has the ability to automatically discover complex representations of phosphorylation patterns from the raw sequences, and hence it provides a powerful tool for improvement of phosphorylation site prediction. We present MusiteDeep, the first deep-learning framework for predicting general and kinase-specific phosphorylation sites. MusiteDeep takes raw sequence data as input and uses convolutional neural networks with a novel two-dimensional attention mechanism. It achieves over a 50% relative improvement in the area under the precision-recall curve in general phosphorylation site prediction and obtains competitive results in kinase-specific prediction compared to other well-known tools on the benchmark data. MusiteDeep is provided as an open-source tool available at https://github.com/duolinwang/MusiteDeep. xudong@missouri.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Searching for prostate cancer by fully automated magnetic resonance imaging classification: deep learning versus non-deep learning.

PubMed

Wang, Xinggang; Yang, Wei; Weinreb, Jeffrey; Han, Juan; Li, Qiubai; Kong, Xiangchuang; Yan, Yongluan; Ke, Zan; Luo, Bo; Liu, Tao; Wang, Liang

2017-11-13

Prostate cancer (PCa) is a major cause of death since ancient time documented in Egyptian Ptolemaic mummy imaging. PCa detection is critical to personalized medicine and varies considerably under an MRI scan. 172 patients with 2,602 morphologic images (axial 2D T2-weighted imaging) of the prostate were obtained. A deep learning with deep convolutional neural network (DCNN) and a non-deep learning with SIFT image feature and bag-of-word (BoW), a representative method for image recognition and analysis, were used to distinguish pathologically confirmed PCa patients from prostate benign conditions (BCs) patients with prostatitis or prostate benign hyperplasia (BPH). In fully automated detection of PCa patients, deep learning had a statistically higher area under the receiver operating characteristics curve (AUC) than non-deep learning (P = 0.0007 < 0.001). The AUCs were 0.84 (95% CI 0.78-0.89) for deep learning method and 0.70 (95% CI 0.63-0.77) for non-deep learning method, respectively. Our results suggest that deep learning with DCNN is superior to non-deep learning with SIFT image feature and BoW model for fully automated PCa patients differentiation from prostate BCs patients. Our deep learning method is extensible to image modalities such as MR imaging, CT and PET of other organs.

Deep breathing after surgery

MedlinePlus

... and taking big breaths can be uncomfortable. A device called an incentive spirometer can help you take deep breaths correctly. If you do not have this device, you can still practice deep breathing on your ...

Lattice-like collagen fiber meshwork in the iris stroma of the cat: a possible mechanism to generate the tension directed towards the iris root which is required for pupillary dilatation in the sympathectomized eye.

PubMed

Sakuraba, M; Yun, S; Ichinohe, N; Yonekura, H; Shoumura, K

1999-10-01

NaOH digestion technique for collagen fiber dissection and scanning electron microscopy demonstrated a lattice-like meshwork in the anterior surface of the iris stroma of the cat. The mesh threads were made of collagen fibril bundles. In the constricted pupil, the meshes were square to rhomboid with the diagonals in the direction of the radius or circumference of the iris. In the dilated pupil, however, the meshes were strongly flattened rhomboid or ellipse with a longer diagnoal or axis in the circumferential direction. At the mesh corners facing the pupillary margin or the iris root, the collagen fibril bundles were strongly bent in the iris of the constricted pupil, while they were almost straight or slightly wavy in the iris of the dilated pupil. Accumulation of elasticity tension generated by this small distortion of the iris-mesh threads in the constricted pupil was considered to generate a tension directed towards the iris root, which is required for pupillary dilatation in the sympathectomized eye. On the posterior surface of the iris stroma, numerous thin pleats tightly woven with collagen fibrils traversed straightway through the radial length of the ciliary zone of the iris in both constricted and dilated pupils. The structural changes of these pleats in miosis and mydriasis were very small compared with the meshwork of the anterior aspect of the iris. Therefore, they were considered to work mainly as an iris skeleton.

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.

Statistical Features of Deep-ocean Tsunamis Based on 30 Years of Bottom Pressure Observations in the Northeast Pacific

NASA Astrophysics Data System (ADS)

Fine, I.; Thomson, R.; Chadwick, W. W., Jr.; Davis, E. E.; Fox, C. G.

2016-12-01

We have used a set of high-resolution bottom pressure recorder (BPR) time series collected at Axial Seamount on the Juan de Fuca Ridge beginning in 1986 to examine tsunami waves of seismological origin in the northeast Pacific. These data are a combination of autonomous, internally-recording battery-powered instruments and cabled instruments on the OOI Cabled Array. Of the total of 120 tsunami events catalogued for the coasts of Japan, Alaska, western North America and Hawaii, we found evidence for 38 events in the Axial Seamount BPR records. Many of these tsunamis were not observed along the adjacent west coast of the USA and Canada because of the much higher noise level of coastal locations and the lack of digital tide gauge data prior to 2000. We have also identified several tsunamis of apparent seismological origin that were observed at coastal stations but not at the deep ocean site. Careful analysis of these observations suggests that they were likely of meteorological origin. Analysis of the pressure measurements from Axial Seamount, along with BPR measurements from a nearby ODP CORK (Ocean Drilling Program Circulation Obviation Retrofit Kit) borehole and DART (Deep-ocean Assessment and Reporting of Tsunamis) locations, reveals features of deep-ocean tsunamis that are markedly different from features observed at coastal locations. Results also show that the energy of deep-ocean tsunamis can differ significantly among the three sets of stations despite their close spatial spacing and that this difference is strongly dependent on the direction of the incoming tsunami waves. These deep-ocean observations provide the most comprehensive statistics possible for tsunamis in the Pacific Ocean over the past 30 years. New insight into the distribution of tsunami amplitudes and wave energy derived from the deep-ocean sites should prove useful for long-term tsunami prediction and mitigation for coastal communities along the west coast of the USA and Canada.

Is Multitask Deep Learning Practical for Pharma?

PubMed

Ramsundar, Bharath; Liu, Bowen; Wu, Zhenqin; Verras, Andreas; Tudor, Matthew; Sheridan, Robert P; Pande, Vijay

2017-08-28

Multitask deep learning has emerged as a powerful tool for computational drug discovery. However, despite a number of preliminary studies, multitask deep networks have yet to be widely deployed in the pharmaceutical and biotech industries. This lack of acceptance stems from both software difficulties and lack of understanding of the robustness of multitask deep networks. Our work aims to resolve both of these barriers to adoption. We introduce a high-quality open-source implementation of multitask deep networks as part of the DeepChem open-source platform. Our implementation enables simple python scripts to construct, fit, and evaluate sophisticated deep models. We use our implementation to analyze the performance of multitask deep networks and related deep models on four collections of pharmaceutical data (three of which have not previously been analyzed in the literature). We split these data sets into train/valid/test using time and neighbor splits to test multitask deep learning performance under challenging conditions. Our results demonstrate that multitask deep networks are surprisingly robust and can offer strong improvement over random forests. Our analysis and open-source implementation in DeepChem provide an argument that multitask deep networks are ready for widespread use in commercial drug discovery.

Deep Space Quantum Link

NASA Astrophysics Data System (ADS)

Mohageg, M.; Strekalov, D.; Dolinar, S.; Shaw, M.; Yu, N.

2018-02-01

The Deep Space Quantum Link will test the effects of gravity on quantum systems, test the non-locality of quantum states at deep space distances, and perform long distance quantum teleportation to an Earth-based receiver.

Independent Discovery of an Apparent Nova in M81

NASA Astrophysics Data System (ADS)

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

2018-02-01

The M81 nova monitoring collaboration reports the independent discovery of an apparent nova in M81 on a co-added 2700-s unfiltered CCD frame taken on 2018 Feb. 19.039 UT with the 0.65-m telescope at Ondrejov (OND).

Marker associations with starch paste viscosity profiles in rice independent of apparent amylose content

USDA-ARS?s Scientific Manuscript database

Apparent amylose is considered the most important factor in determining rice cooking quality. However, certain varieties with similar apparent amylose contents have different cooking quality responses. A mapping population was developed from a cross of Cocodrie (CCDR) and Dixiebelle (DXBL) which hav...

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.

Apparent cosmic acceleration from Type Ia supernovae

NASA Astrophysics Data System (ADS)

Dam, Lawrence H.; Heinesen, Asta; Wiltshire, David L.

2017-11-01

Parameters that quantify the acceleration of cosmic expansion are conventionally determined within the standard Friedmann-Lemaître-Robertson-Walker (FLRW) model, which fixes spatial curvature to be homogeneous. Generic averages of Einstein's equations in inhomogeneous cosmology lead to models with non-rigidly evolving average spatial curvature, and different parametrizations of apparent cosmic acceleration. The timescape cosmology is a viable example of such a model without dark energy. Using the largest available supernova data set, the JLA catalogue, we find that the timescape model fits the luminosity distance-redshift data with a likelihood that is statistically indistinguishable from the standard spatially flat Λ cold dark matter cosmology by Bayesian comparison. In the timescape case cosmic acceleration is non-zero but has a marginal amplitude, with best-fitting apparent deceleration parameter, q_{0}=-0.043^{+0.004}_{-0.000}. Systematic issues regarding standardization of supernova light curves are analysed. Cuts of data at the statistical homogeneity scale affect light-curve parameter fits independent of cosmology. A cosmological model dependence of empirical changes to the mean colour parameter is also found. Irrespective of which model ultimately fits better, we argue that as a competitive model with a non-FLRW expansion history, the timescape model may prove a useful diagnostic tool for disentangling selection effects and astrophysical systematics from the underlying expansion history.

DeepGene: an advanced cancer type classifier based on deep learning and somatic point mutations.

PubMed

Yuan, Yuchen; Shi, Yi; Li, Changyang; Kim, Jinman; Cai, Weidong; Han, Zeguang; Feng, David Dagan

2016-12-23

With the developments of DNA sequencing technology, large amounts of sequencing data have become available in recent years and provide unprecedented opportunities for advanced association studies between somatic point mutations and cancer types/subtypes, which may contribute to more accurate somatic point mutation based cancer classification (SMCC). However in existing SMCC methods, issues like high data sparsity, small volume of sample size, and the application of simple linear classifiers, are major obstacles in improving the classification performance. To address the obstacles in existing SMCC studies, we propose DeepGene, an advanced deep neural network (DNN) based classifier, that consists of three steps: firstly, the clustered gene filtering (CGF) concentrates the gene data by mutation occurrence frequency, filtering out the majority of irrelevant genes; secondly, the indexed sparsity reduction (ISR) converts the gene data into indexes of its non-zero elements, thereby significantly suppressing the impact of data sparsity; finally, the data after CGF and ISR is fed into a DNN classifier, which extracts high-level features for accurate classification. Experimental results on our curated TCGA-DeepGene dataset, which is a reformulated subset of the TCGA dataset containing 12 selected types of cancer, show that CGF, ISR and DNN all contribute in improving the overall classification performance. We further compare DeepGene with three widely adopted classifiers and demonstrate that DeepGene has at least 24% performance improvement in terms of testing accuracy. Based on deep learning and somatic point mutation data, we devise DeepGene, an advanced cancer type classifier, which addresses the obstacles in existing SMCC studies. Experiments indicate that DeepGene outperforms three widely adopted existing classifiers, which is mainly attributed to its deep learning module that is able to extract the high level features between combinatorial somatic point mutations and

Deep Water Ocean Acoustics

DTIC Science & Technology

2015-04-15

0 A S S PROGRESS REPORT NO. QSR-14C0172-0CEAN ACOUSTICS-033115 Contract No. N00014-14-C-0172 Office of Naval Research Task Reporting: Deep ...AND SUBTITLE Deep Water Ocean Acoustics 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e...298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Cost Summary OASIS, INC. JOB STATUS RB’ORT 1172 DEEP WATER ACOUSTICS FOP. 9/27f13-316/16

Stable architectures for deep neural networks

NASA Astrophysics Data System (ADS)

Haber, Eldad; Ruthotto, Lars

2018-01-01

Deep neural networks have become invaluable tools for supervised machine learning, e.g. classification of text or images. While often offering superior results over traditional techniques and successfully expressing complicated patterns in data, deep architectures are known to be challenging to design and train such that they generalize well to new data. Critical issues with deep architectures are numerical instabilities in derivative-based learning algorithms commonly called exploding or vanishing gradients. In this paper, we propose new forward propagation techniques inspired by systems of ordinary differential equations (ODE) that overcome this challenge and lead to well-posed learning problems for arbitrarily deep networks. The backbone of our approach is our interpretation of deep learning as a parameter estimation problem of nonlinear dynamical systems. Given this formulation, we analyze stability and well-posedness of deep learning and use this new understanding to develop new network architectures. We relate the exploding and vanishing gradient phenomenon to the stability of the discrete ODE and present several strategies for stabilizing deep learning for very deep networks. While our new architectures restrict the solution space, several numerical experiments show their competitiveness with state-of-the-art networks.

Deep-sea in situ observations of gonatid squid and their prey reveal high occurrence of cannibalism

NASA Astrophysics Data System (ADS)

Hoving, H. J. T.; Robison, B. H.

2016-10-01

In situ observations are rarely applied in food web studies of deep-sea organisms. Using deep-sea observations obtained by remotely operated vehicles in the Monterey Submarine Canyon, we examined the prey choices of more than 100 individual squids of the genus Gonatus. Off the California coast, these squids are abundant, semelparous (one reproductive cycle) oceanic predators but their diet has remained virtually unknown. Gonatus onyx and Gonatus berryi were observed to feed on mesopelagic fishes (in particular the myctophid Stenobrachius leucopsarus) as often as on squids but inter-specific differences in feeding were apparent. Gonatids were the most common squid prey and while cannibalism occurred in both species it was particularly high in Gonatus onyx (42% of all prey items). Typically, the size of prey was similar to the size of the predator but the squids were also seen to take much larger prey. Postjuvenile gonatids are opportunistic predators that consume nektonic members of the meso-and bathypelagic communities, including their own species. Such voracious feeding is likely necessary to support the high energetic demands associated with the single reproductive event; and for females the long brooding period during which they must depend on stored resources.

The deep-sea under global change.

PubMed

Danovaro, Roberto; Corinaldesi, Cinzia; Dell'Anno, Antonio; Snelgrove, Paul V R

2017-06-05

The deep ocean encompasses 95% of the oceans' volume and is the largest and least explored biome of Earth's Biosphere. New life forms are continuously being discovered. The physiological mechanisms allowing organisms to adapt to extreme conditions of the deep ocean (high pressures, from very low to very high temperatures, food shortage, lack of solar light) are still largely unknown. Some deep-sea species have very long life-spans, whereas others can tolerate toxic compounds at high concentrations; these characteristics offer an opportunity to explore the specialized biochemical and physiological mechanisms associated with these responses. Widespread symbiotic relationships play fundamental roles in driving host functions, nutrition, health, and evolution. Deep-sea organisms communicate and interact through sound emissions, chemical signals and bioluminescence. Several giants of the oceans hunt exclusively at depth, and new studies reveal a tight connection between processes in the shallow water and some deep-sea species. Limited biological knowledge of the deep-sea limits our capacity to predict future response of deep-sea organisms subject to increasing human pressure and changing global environmental conditions. Molecular tools, sensor-tagged animals, in situ and laboratory experiments, and new technologies can enable unprecedented advancement of deep-sea biology, and facilitate the sustainable management of deep ocean use under global change. Copyright © 2017. Published by Elsevier Ltd.

Conservation of deep pelagic biodiversity.

PubMed

Robison, Bruce H

2009-08-01

The deep ocean is home to the largest ecosystems on our planet. This vast realm contains what may be the greatest number of animal species, the greatest biomass, and the greatest number of individual organisms in the living world. Humans have explored the deep ocean for about 150 years, and most of what is known is based on studies of the deep seafloor. In contrast, the water column above the deep seabed comprises more than 90% of the living space, yet less than 1% of this biome has been explored. The deep pelagic biota is the largest and least-known major faunal group on Earth despite its obvious importance at the global scale. Pelagic species represent an incomparable reservoir of biodiversity. Although we have yet to discover and describe the majority of these species, the threats to their continued existence are numerous and growing. Conserving deep pelagic biodiversity is a problem of global proportions that has never been addressed comprehensively. The potential effects of these threats include the extensive restructuring of entire ecosystems, changes in the geographical ranges of many species, large-scale elimination of taxa, and a decline in biodiversity at all scales. This review provides an initial framework of threat assessment for confronting the challenge of conserving deep pelagic biodiversity; and it outlines the need for baseline surveys and protected areas as preliminary policy goals.

The Hubble Space Telescope Medium Deep Survey with the Wide Field and Planetary Camera. 1: Methodology and results on the field near 3C 273

NASA Technical Reports Server (NTRS)

Griffiths, R. E.; Ratnatunga, K. U.; Neuschaefer, L. W.; Casertano, S.; Im, M.; Wyckoff, E. W.; Ellis, R. S.; Gilmore, G. F.; Elson, R. A. W.; Glazebrook, K.

1994-01-01

We present results from the Medium Deep Survey (MDS), a Key Project using the Hubble Space Telescope (HST). Wide Field Camera (WFC) images of random fields have been taken in 'parallel mode' with an effective resolution of 0.2 sec full width at half maximum (FWHM) in the V(F555W) and I(F785LP) filters. The exposures presented here were targeted on a field away from 3C 273, and resulted in approximately 5 hr integration time in each filter. Detailed morphological structure is seen in galaxy images with total integrated magnitudes down to V approximately = 22.5 and I approximately = 21.5. Parameters are estimated that best fit the observed galaxy images, and 143 objects are identified (including 23 stars) in the field to a fainter limiting magnitude of I approximately = 23.5. We outline the extragalactic goals of the HST Medium Deep Survey, summarize our basic data reduction procedures, and present number (magnitude) counts, a color-magnitude diagram for the field, surface brightness profiles for the brighter galaxies, and best-fit half-light radii for the fainter galaxies as a function of apparent magnitude. A median galaxy half-light radius of 0.4 sec is measured, and the distribution of galaxy sizes versus magnitude is presented. We observe an apparent deficit of galaxies with half-light radii between approximately 0.6 sec and 1.5 sec, with respect to standard no-evolution or mild evolution cosmological models. An apparent excess of compact objects (half-light radii approximately 0.1 sec) is also observed with respect to those models. Finally, we find a small excess in the number of faint galaxy pairs and groups with respect to a random low-redshift field sample.

Reproductive traits of tropical deep-water pandalid shrimps ( Heterocarpus ensifer) from the SW Gulf of Mexico

NASA Astrophysics Data System (ADS)

Briones-Fourzán, Patricia; Barradas-Ortíz, Cecilia; Negrete-Soto, Fernando; Lozano-Álvarez, Enrique

2010-08-01

Heterocarpus ensifer is a tropical deep-water pandalid shrimp whose reproductive features are poorly known. We examined reproductive traits of a population of H. ensifer inhabiting the continental slope (311-715 m in depth) off the Yucatan Peninsula, Mexico (SW Gulf of Mexico). Size range of the total sample ( n=816) was 10.4-38.9 mm carapace length. Females grow larger than males, but both sexes mature at 57% of their maximum theoretical size and at ˜30% of their total lifespan. Among adult females, the proportion of ovigerous females was high in all seasons, indicating year-round reproduction. Most females carrying embryos in advanced stages of development had ovaries in advanced stages of maturation, indicating production of successive spawns. In the autumn, however, the proportion of ovigerous females and the condition index of these females were lower compared to other seasons. This pattern potentially reflects a reduction in food resources following the summer minimum in particulate organic carbon flux to the deep benthos, as reported in previous studies. Spawns consisting of large numbers (16024±5644, mean±SD) of small eggs (0.045±0.009 mm 3) are consistent with extended planktotrophic larval development, an uncommon feature in deep-water carideans. Egg number increased as a power function of female size but with substantial variability, and egg size varied widely within and between females. There was no apparent trade-off between egg number and egg size and neither of these two variables was influenced by female condition. These results indicate iteroparity and a high and variable reproductive effort, reflecting a reproductive strategy developed to compensate for high larval mortality. The present study provides a baseline to compare reproductive traits between Atlantic populations of this tropical deep-water pandalid.

Deep Seawater Intrusion Enhanced by Geothermal Through Deep Faults in Xinzhou Geothermal Field in Guangdong, China

NASA Astrophysics Data System (ADS)

Lu, G.; Ou, H.; Hu, B. X.; Wang, X.

2017-12-01

This study investigates abnormal sea water intrusion from deep depth, riding an inland-ward deep groundwater flow, which is enhanced by deep faults and geothermal processes. The study site Xinzhou geothermal field is 20 km from the coast line. It is in southern China's Guangdong coast, a part of China's long coastal geothermal belt. The geothermal water is salty, having fueled an speculation that it was ancient sea water retained. However, the perpetual "pumping" of the self-flowing outflow of geothermal waters might alter the deep underground flow to favor large-scale or long distant sea water intrusion. We studied geochemical characteristics of the geothermal water and found it as a mixture of the sea water with rain water or pore water, with no indication of dilution involved. And we conducted numerical studies of the buoyancy-driven geothermal flow in the deep ground and find that deep down in thousand meters there is favorable hydraulic gradient favoring inland-ward groundwater flow, allowing seawater intrude inland for an unusually long tens of kilometers in a granitic groundwater flow system. This work formed the first in understanding geo-environment for deep ground water flow.

In Vivo Magnetization Transfer and Diffusion-Weighted Magnetic Resonance Imaging Detects Thrombus Composition in a Mouse Model of Deep Vein Thrombosis

PubMed Central

Saha, Prakash; Modarai, Bijan; Smith, Alberto; Botnar, René M.

2014-01-01

Background Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis. Methods and Results Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; Panova<0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus (r=0.70; P<0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10−3 mm2/s]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10−3 mm2/s]). Conclusions MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention. PMID:23564561

76 FR 66078 - Notice of Industry Workshop on Technical and Regulatory Challenges in Deep and Ultra-Deep Outer...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

...-0087] Notice of Industry Workshop on Technical and Regulatory Challenges in Deep and Ultra-Deep Outer... and gas exploration and production in deep and ultra-deep OCS waters. Through this workshop, BSEE will... structured venue for consultation among offshore deepwater oil and gas industry and regulatory experts in...

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.

DeepSurveyCam--A Deep Ocean Optical Mapping System.

PubMed

Kwasnitschka, Tom; Köser, Kevin; Sticklus, Jan; Rothenbeck, Marcel; Weiß, Tim; Wenzlaff, Emanuel; Schoening, Timm; Triebe, Lars; Steinführer, Anja; Devey, Colin; Greinert, Jens

2016-01-28

Underwater photogrammetry and in particular systematic visual surveys of the deep sea are by far less developed than similar techniques on land or in space. The main challenges are the rough conditions with extremely high pressure, the accessibility of target areas (container and ship deployment of robust sensors, then diving for hours to the ocean floor), and the limitations of localization technologies (no GPS). The absence of natural light complicates energy budget considerations for deep diving flash-equipped drones. Refraction effects influence geometric image formation considerations with respect to field of view and focus, while attenuation and scattering degrade the radiometric image quality and limit the effective visibility. As an improvement on the stated issues, we present an AUV-based optical system intended for autonomous visual mapping of large areas of the seafloor (square kilometers) in up to 6000 m water depth. We compare it to existing systems and discuss tradeoffs such as resolution vs. mapped area and show results from a recent deployment with 90,000 mapped square meters of deep ocean floor.

DeepSurveyCam—A Deep Ocean Optical Mapping System

PubMed Central

Kwasnitschka, Tom; Köser, Kevin; Sticklus, Jan; Rothenbeck, Marcel; Weiß, Tim; Wenzlaff, Emanuel; Schoening, Timm; Triebe, Lars; Steinführer, Anja; Devey, Colin; Greinert, Jens

2016-01-01

Underwater photogrammetry and in particular systematic visual surveys of the deep sea are by far less developed than similar techniques on land or in space. The main challenges are the rough conditions with extremely high pressure, the accessibility of target areas (container and ship deployment of robust sensors, then diving for hours to the ocean floor), and the limitations of localization technologies (no GPS). The absence of natural light complicates energy budget considerations for deep diving flash-equipped drones. Refraction effects influence geometric image formation considerations with respect to field of view and focus, while attenuation and scattering degrade the radiometric image quality and limit the effective visibility. As an improvement on the stated issues, we present an AUV-based optical system intended for autonomous visual mapping of large areas of the seafloor (square kilometers) in up to 6000 m water depth. We compare it to existing systems and discuss tradeoffs such as resolution vs. mapped area and show results from a recent deployment with 90,000 mapped square meters of deep ocean floor. PMID:26828495

Effects of atmospheric composition on apparent activation energy of silicate weathering: I. Model formulation

NASA Astrophysics Data System (ADS)

Kanzaki, Yoshiki; Murakami, Takashi

2018-07-01

We have developed a weathering model to comprehensively understand the determining factors of the apparent activation energy of silicate weathering in order to better estimate the silicate-weathering flux in the Precambrian. The model formulates the reaction rate of a mineral as a basis, then the elemental loss by summing the reaction rates of whole minerals, and finally the weathering flux from a given weathering profile by integrating the elemental losses along the depth of the profile. The rate expressions are formulated with physicochemical parameters relevant to weathering, including solution and atmospheric compositions. The apparent activation energies of silicate weathering are then represented by the temperature dependences of the physicochemical parameters based on the rate expressions. It was found that the interactions between individual mineral-reactions and the compositions of solution and atmosphere are necessarily accompanied by those of temperature-dependence counterparts. Indeed, the model calculates the apparent activation energy of silicate weathering as a function of the temperature dependence of atmospheric CO2 (Δ HCO2‧) . The dependence of the apparent activation energy of silicate weathering on Δ HCO2‧ may explain the empirical dependence of silicate weathering on the atmospheric composition. We further introduce a compensation law between the apparent activation energy and the pre-exponential factor to obtain the relationship between the silicate-weathering flux (FCO2), temperature and the apparent activation energy. The model calculation and the compensation law enable us to predict FCO2 as a function of temperature, once Δ HCO2‧ is given. The validity of the model is supported by agreements between the model prediction and observations of the apparent activation energy and FCO2 in the modern weathering systems. The present weathering model will be useful for the estimation of FCO2 in the Precambrian, for which Δ HCO2‧ can be

Effect of deep-fat frying on sensory and textural attributes of pellet snacks.

PubMed

BahramParvar, Maryam; Mohammadi Moghaddam, Toktam; Razavi, Seyed M A

2014-12-01

In this paper, the effects of several frying parameters on the quality of indirect expanded snacks were studied. Pellets, in two colors of yellow and green, were deep-fat fried at 150, 170, and 190 °C for 0.5, 1.5, 2.5, 3.5, and 4.5 min; then, subjected to uniaxial compression test and sensory analysis. The results showed that hardness, fracture force and apparent modulus of elasticity reduced with increase in frying time and temperature due to puffing samples and decrease in crust thickness. In contrast, higher frying temperature improved the crispness of samples. Panelists preferred the flavor, color, and total acceptance of yellow samples to the green ones. Moreover, principal component analysis (PCA) of instrumental and sensory data provided important information for the correlation of objective and sensory properties.

Deep-convection events foster carbonate ion reduction in deep coral reefs

NASA Astrophysics Data System (ADS)

Perez, Fiz F.; Fontela, Marcos; Garcia-Ibañez, Maribel I.; Lherminier, Pascale; Zunino, Patricia; de la Paz, Mercedes; Padín, Xose A.; Alonso-Pérez, Fernando; Velo, Anton; Guallart, Elisa F.; Mercier, Herle

2017-04-01

Since millennial times, water mass circulation and deep-convection events have been transforming warm upper waters at high latitudes into cold and well-oxygenated deep waters. These processes have filled the deep North Atlantic Ocean with waters moderately saturated in calcium carbonate, thus promoting the growth of stony corals, which are hotspots of biodiversity. During the Anthropocene, the meridional circulation has been conveying cumulative amounts of more acidified waters with lower calcium carbonate saturation levels due to the incorporation of anthropogenic carbon dioxide, with very harsh conditions for deep cold-water corals projected by 2100. We evaluate the diminution of calcium carbonate saturation levels (aragonite form) due to the increase in anthropogenic carbon dioxide during the last two decades (2002-2016). We observe a strong decrease in the aragonite saturation levels concomitant with the reduction in the volume transport of aragonite-saturated waters. We estimate a 30-35% reduction in the transport of ion carbonate excess over the saturation levels with respect to the natural carbon cycle for the period 2002-2016. This reduction is associated with an increase in the downward transport of hydrogen ions. We also observe a heaving of the aragonite saturation horizons during the last 25 years, which is estimated at 6 m year-1 for the deep waters and 12-14 m year-1 for the intermediated waters. The harsh winters of 2015 and 2016 have fostered the fast addition of more acidified water into the lower layers of the North Atlantic through deep-convection events. In the future scenario of 2oC warming, the anthropogenic carbon dioxide in the water column would be double than today and the associated transport of hydrogen ions towards the bottom water would reduce the aragonite saturation levels to 60-80% with respect to preindustrial levels. This reduction in the aragonite saturation levels would suppose a strong diminution of the North Atlantic habitats

Origin of the flax cultivar 'Appar' and its position within the Linum perenne complex

Treesearch

Rosemary L. Pendleton; Stanley G. Kitchen; Joann Mudge; E. Durant McArthur

2008-01-01

The 'Appar' flax germplasm was originally released by the USDA Soil Conservation Service as a cultivar of Linum lewisii. The observation that 'Appar' is heterostylic, a key taxonomic character distinguishing Lewis flax from other members of the Linum perenne complex, created a need for further study in order to...

Temperature impacts on deep-sea biodiversity.

PubMed

Yasuhara, Moriaki; Danovaro, Roberto

2016-05-01

Temperature is considered to be a fundamental factor controlling biodiversity in marine ecosystems, but precisely what role temperature plays in modulating diversity is still not clear. The deep ocean, lacking light and in situ photosynthetic primary production, is an ideal model system to test the effects of temperature changes on biodiversity. Here we synthesize current knowledge on temperature-diversity relationships in the deep sea. Our results from both present and past deep-sea assemblages suggest that, when a wide range of deep-sea bottom-water temperatures is considered, a unimodal relationship exists between temperature and diversity (that may be right skewed). It is possible that temperature is important only when at relatively high and low levels but does not play a major role in the intermediate temperature range. Possible mechanisms explaining the temperature-biodiversity relationship include the physiological-tolerance hypothesis, the metabolic hypothesis, island biogeography theory, or some combination of these. The possible unimodal relationship discussed here may allow us to identify tipping points at which on-going global change and deep-water warming may increase or decrease deep-sea biodiversity. Predicted changes in deep-sea temperatures due to human-induced climate change may have more adverse consequences than expected considering the sensitivity of deep-sea ecosystems to temperature changes. © 2014 Cambridge Philosophical Society.

[Search for life in deep biospheres].

PubMed

Naganuma, Takeshi

2003-12-01

The life in deep biospheres bridges conventional biology and future exobiology. This review focuses the microbiological studies from the selected deep biospheres, i.e., deep-sea hydrothermal vents, sub-hydrothermal vents, terrestrial subsurface and a sub-glacier lake. The dark biospheres facilitate the emergence of organisms and communities dependent on chemolithoautotrophy, which are overwhelmed by photoautotrophy (photosynthesis) in the surface biospheres. The life at deep-sea hydrothermal vents owes much to chemolithoautotrophy based on the oxidation of sulfide emitted from the vents. It is likely that similarly active bodies such as the Jovian satellite Europa may have hydrothermal vents and associated biological communities. Anoxic or anaerobic condition is characteristic of deep subsurface biospheres. Subsurface microorganisms exploit available oxidants, or terminal electron acceptors (TEA), for anaerobic respiration. Sulfate, nitrate, iron (III) and CO2 are the representative TEAs in the deep subsurface. Below the 3000-4000 m-thick glacier on Antarctica, there have been >70 lakes with liquid water located. One of such sub-glacial lakes, Lake Vostok, is about to be drill-penetrated for microbiological studies. These deep biosphere "platforms" provide new knowledge about the diversity and potential of the Earth's life. The expertise obtained from the deep biosphere expeditions will facilitate the capability of exobiologial exploration.

deepNF: Deep network fusion for protein function prediction.

PubMed

Gligorijevic, Vladimir; Barot, Meet; Bonneau, Richard

2018-06-01

The prevalence of high-throughput experimental methods has resulted in an abundance of large-scale molecular and functional interaction networks. The connectivity of these networks provides a rich source of information for inferring functional annotations for genes and proteins. An important challenge has been to develop methods for combining these heterogeneous networks to extract useful protein feature representations for function prediction. Most of the existing approaches for network integration use shallow models that encounter difficulty in capturing complex and highly-nonlinear network structures. Thus, we propose deepNF, a network fusion method based on Multimodal Deep Autoencoders to extract high-level features of proteins from multiple heterogeneous interaction networks. We apply this method to combine STRING networks to construct a common low-dimensional representation containing high-level protein features. We use separate layers for different network types in the early stages of the multimodal autoencoder, later connecting all the layers into a single bottleneck layer from which we extract features to predict protein function. We compare the cross-validation and temporal holdout predictive performance of our method with state-of-the-art methods, including the recently proposed method Mashup. Our results show that our method outperforms previous methods for both human and yeast STRING networks. We also show substantial improvement in the performance of our method in predicting GO terms of varying type and specificity. deepNF is freely available at: https://github.com/VGligorijevic/deepNF. vgligorijevic@flatironinstitute.org, rb133@nyu.edu. Supplementary data are available at Bioinformatics online.

Apparent Viscosity of Active Nematics in Poiseuille Flow

NASA Astrophysics Data System (ADS)

Cui, Zhenlu; Su, Jianbing; Zeng, Xiaoming

2015-09-01

A Leslie-Erickson continuum hydrodynamic for flowing active nematics has been used to characterize active particle systems such as bacterial suspensions. The behavior of such a system under a plane pressure-driven Poiseuille flow is analyzed. When plate anchoring is tangential and normal, we find the apparent viscosity formula indicating a significant difference between tangential anchoring and normal anchoring conditions for both active rodlike and discoid nematics.

Cancer/stroma interplay via cyclooxygenase-2 and indoleamine 2,3-dioxygenase promotes breast cancer progression.

PubMed

Chen, Jing-Yi; Li, Chien-Feng; Kuo, Cheng-Chin; Tsai, Kelvin K; Hou, Ming-Feng; Hung, Wen-Chun

2014-07-25

Expression of indoleamine 2,3-dioxygenase (IDO) in primary breast cancer increases tumor growth and metastasis. However, the clinical significance of stromal IDO and the regulation of stromal IDO are unclear. Metabolomics and enzyme-linked immunosorbent assay (ELISA) were used to study the effect of cyclooxygenase-2 (COX-2)-overexpressing breast cancer cells on IDO expression in co-cultured human breast fibroblasts. Biochemical inhibitors and short-hairpin RNA (shRNA) were used to clarify how prostaglandin E2 (PGE2) upregulates IDO expression. Associations of stromal IDO with clinicopathologic parameters were tested in tumor specimens. An orthotopic animal model was used to examine the effect of COX-2 and IDO inhibitors on tumor growth. Kynurenine, the metabolite generated by IDO, increases in the supernatant of fibroblasts co-cultured with COX-2-overexpressing breast cancer cells. PGE2 released by cancer cells upregulates IDO expression in fibroblasts through an EP4/signal transducer and activator of transcription 3 (STAT3)-dependent pathway. Conversely, fibroblast-secreted kynurenine promotes the formation of the E-cadherin/Aryl hydrocarbon receptor (AhR)/S-phase kinase-associated protein 2 (Skp2) complex, resulting in degradation of E-cadherin to increase breast cancer invasiveness. The enhancement of motility of breast cancer cells induced by co-culture with fibroblasts is suppressed by the IDO inhibitor 1-methyl-tryptophan. Pathological analysis demonstrates that upregulation of stromal IDO is a poor prognosis factor and is associated with of COX-2 overexpression. Co-expression of cancer COX-2 and stromal IDO predicts a worse disease-free and metastasis-free survival. Finally, COX-2 and IDO inhibitors inhibit tumor growth in vivo. Integration of metabolomics and molecular and pathological approaches reveals the interplay between cancer and stroma via COX-2, and IDO promotes tumor progression and predicts poor patient survival.

Noncommutative FRW Apparent Horizon and Hawking Radiation

NASA Astrophysics Data System (ADS)

Bouhallouf, H.; Mebarki, N.; Aissaoui, H.

2017-11-01

In the context of noncommutative (NCG) gauge gravity, and using a cosmic time power law formula for the scale factor, a Friedman-Robertson-Walker (FRW) like metric is obtained. Within the fermions tunneling effect approach and depending on the various intervals of the power parameter, expressions of the apparent horizon are also derived. It is shown that in some regions of the parameter space, a pure NCG trapped horizon does exist leading to new interpretation of the role played by the noncommutativity of the space-time.

The Deep Space Network: A Radio Communications Instrument for Deep Space Exploration

NASA Technical Reports Server (NTRS)

Renzetti, N. A.; Stelzried, C. T.; Noreen, G. K.; Slobin, S. D.; Petty, S. M.; Trowbridge, D. L.; Donnelly, H.; Kinman, P. W.; Armstrong, J. W.; Burow, N. A.

1983-01-01

The primary purpose of the Deep Space Network (DSN) is to serve as a communications instrument for deep space exploration, providing communications between the spacecraft and the ground facilities. The uplink communications channel provides instructions or commands to the spacecraft. The downlink communications channel provides command verification and spacecraft engineering and science instrument payload data.

Crystalloids in apparent autophagic plastids: remnants of plastids or peroxisomes?

PubMed

Papini, Alessio; van Doorn, Wouter G

2015-02-01

Plant macroautophagy is carried out by autophagosome-type organelles. Recent evidence suggests that plastids also can carry out macroautophagy. The double membrane at the surface of plastids apparently invaginates, forming an intraplastidial space. This space contains a portion of cytoplasm that apparently becomes degraded. Here we report, in Tillandsia sp. and Aechmaea sp., the presence of almost square or diamond-shaped crystalloids inside what seems the intraplastidial space of autophagous plastids. The same type of crystalloids were observed in chloroplasts and other plastids, but were not found in the cytoplasm or the vacuole. Peroxisomes contained smaller and more irregularly shaped crystalloids compared to the ones observed in 'autophagous' plastids. It is hypothesized that plastids are able to sequester chloroplasts and other plastids. Copyright © 2014 Elsevier GmbH. All rights reserved.

Cancer-Associated Mutations in Endometriosis without Cancer

PubMed Central

Anglesio, M.S.; Papadopoulos, N.; Ayhan, A.; Nazeran, T.M.; Noë, M.; Horlings, H.M.; Lum, A.; Jones, S.; Senz, J.; Seckin, T.; Ho, J.; Wu, R.-C.; Lac, V.; Ogawa, H.; Tessier-Cloutier, B.; Alhassan, R.; Wang, A.; Wang, Y.; Cohen, J.D.; Wong, F.; Hasanovic, A.; Orr, N.; Zhang, M.; Popoli, M.; McMahon, W.; Wood, L.D.; Mattox, A.; Allaire, C.; Segars, J.; Williams, C.; Tomasetti, C.; Boyd, N.; Kinzler, K.W.; Gilks, C.B.; Diaz, L.; Wang, T.-L.; Vogelstein, B.; Yong, P.J.; Huntsman, D.G.; Shih, I.-M.

2017-01-01

BACKGROUND Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis. METHODS We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients). Mutations were validated with the use of digital genomic methods in micro-dissected epithelium and stroma. Epithelial and stromal components of lesions from an additional 12 patients were analyzed by means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent activating KRAS mutations. RESULTS Exome sequencing revealed somatic mutations in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe-Sequencing System or immunohistochemical analysis. The likelihood of driver genes being affected at this rate in the absence of selection was estimated at P = 0.001 (binomial test). Targeted sequencing and a droplet digital PCR assay identified KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with mutations in the epithelium but not the stroma. One patient harbored two different KRAS mutations, c.35G→T and c.35G→C, and another carried identical KRAS c.35G→A mutations in three distinct lesions. CONCLUSIONS We found that lesions in deep infiltrating endometriosis, which are associated with virtually no risk of malignant transformation, harbor somatic cancer driver mutations. Ten of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions. PMID:28489996

Determination of apparent coupling factors for adhesive bonded acrylic plates using SEAL approach

NASA Astrophysics Data System (ADS)

Pankaj, Achuthan. C.; Shivaprasad, M. V.; Murigendrappa, S. M.

2018-04-01

Apparent coupling loss factors (CLF) and velocity responses has been computed for two lap joined adhesive bonded plates using finite element and experimental statistical energy analysis like approach. A finite element model of the plates has been created using ANSYS software. The statistical energy parameters have been computed using the velocity responses obtained from a harmonic forced excitation analysis. Experiments have been carried out for two different cases of adhesive bonded joints and the results have been compared with the apparent coupling factors and velocity responses obtained from finite element analysis. The results obtained from the studies signify the importance of modeling of adhesive bonded joints in computation of the apparent coupling factors and its further use in computation of energies and velocity responses using statistical energy analysis like approach.

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.

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

DeepMirTar: a deep-learning approach for predicting human miRNA targets.

PubMed

Wen, Ming; Cong, Peisheng; Zhang, Zhimin; Lu, Hongmei; Li, Tonghua

2018-06-01

MicroRNAs (miRNAs) are small noncoding RNAs that function in RNA silencing and post-transcriptional regulation of gene expression by targeting messenger RNAs (mRNAs). Because the underlying mechanisms associated with miRNA binding to mRNA are not fully understood, a major challenge of miRNA studies involves the identification of miRNA-target sites on mRNA. In silico prediction of miRNA-target sites can expedite costly and time-consuming experimental work by providing the most promising miRNA-target-site candidates. In this study, we reported the design and implementation of DeepMirTar, a deep-learning-based approach for accurately predicting human miRNA targets at the site level. The predicted miRNA-target sites are those having canonical or non-canonical seed, and features, including high-level expert-designed, low-level expert-designed, and raw-data-level, were used to represent the miRNA-target site. Comparison with other state-of-the-art machine-learning methods and existing miRNA-target-prediction tools indicated that DeepMirTar improved overall predictive performance. DeepMirTar is freely available at https://github.com/Bjoux2/DeepMirTar_SdA. lith@tongji.edu.cn, hongmeilu@csu.edu.cn. Supplementary data are available at Bioinformatics online.

Unguioblastoma and unguioblastic fibroma--an expanded spectrum of onychomatricoma.

PubMed

Ko, Christine J; Shi, Linda; Barr, Ronald J; Mölne, Lena; Ternesten-Bratel, Annika; Headington, John T

2004-04-01

Onychomatricoma is a rare tumor that appears to originate from cells of the nail matrix. Three cases of onychomatricoma that met Perrin et al.'s1 histologic criteria of onychomatricoma are described. However, using a single term to classify all three tumors ignores the apparent microscopic differences that exist among them. To demonstrate better the spectrum of so-called onychomatricoma and properly acknowledge the noticeable disparity among our cases, a series of terms is proposed. This terminology is based on the histologic spectrum of epithelial-stromal ratio of stromal cellularity and of extent nuclear pleomorphism. Use of such criteria has a precedent in the classification of follicular and odontogenic fibroepithelial neoplasms. This new nomenclature includes "unguioblastoma" for tumors with a predominant epithelial component and "unguioblastic fibroma" for tumors where a cellular stroma is more prominent and characteristic. The term "atypical unguioblastic fibroma" is used to describe a third rare neoplasm, in which the cellular stroma shows nuclear pleomorphism and atypia with an increase of mitotic activity.

Effects of fat reserves on annual apparent survival of blackbirds Turdus merula

USGS Publications Warehouse

Miller, M.W.; Aradis, A.; Landucci, G.

2003-01-01

1. Fat reserves are stored energy that may help birds survive periods of harsh winter weather. This hypothesis predicts that annual apparent survival is higher for birds with large fat reserves than for birds with few or no fat reserves in winter. 2. Blackbirds (Turdus merula Linnaeus) were ringed in central Italy from 16 November to 20 February during 1990-2001. Fat scores were recorded for each bird. We used these capture-mark-recapture data for 1703 blackbirds to estimate the effect of large fat reserves on annual apparent survival, while controlling for transients, using computer programs surviv and mark. Probability of birds retaining large fat reserves, or retaining few fat reserves, over 2 successive years was also estimated. 3. Birds with large fat reserves did not have higher estimated annual apparent survival than birds with few fat reserves, inconsistent with our prediction. No effects of age, sex or year were detected on annual apparent survival. Birds with few fat reserves in any given year tended to have few fat reserves the following year. Birds with large fat reserves in any given year were unlikely to have large fat reserves the next year. 4. Large fat reserves may not increase annual survival of blackbirds wintering in central Italy. Winter weather in our study area may be too mild to effect survival. Alternatively, increased predation risk associated with large fat reserves may counteract any benefits of reduced starvation risk.

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.

Extreme Longevity in Proteinaceous Deep-Sea Corals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roark, E B; Guilderson, T P; Dunbar, R B

2009-02-09

Deep-sea corals are found on hard substrates on seamounts and continental margins world-wide at depths of 300 to {approx}3000 meters. Deep-sea coral communities are hotspots of deep ocean biomass and biodiversity, providing critical habitat for fish and invertebrates. Newly applied radiocarbon age date from the deep water proteinaceous corals Gerardia sp. and Leiopathes glaberrima show that radial growth rates are as low as 4 to 35 {micro}m yr{sup -1} and that individual colony longevities are on the order of thousands of years. The management and conservation of deep sea coral communities is challenged by their commercial harvest for the jewelrymore » trade and damage caused by deep water fishing practices. In light of their unusual longevity, a better understanding of deep sea coral ecology and their interrelationships with associated benthic communities is needed to inform coherent international conservation strategies for these important deep-sea ecosystems.« less

Deep Unfolding for Topic Models.

PubMed

Chien, Jen-Tzung; Lee, Chao-Hsi

2018-02-01

Deep unfolding provides an approach to integrate the probabilistic generative models and the deterministic neural networks. Such an approach is benefited by deep representation, easy interpretation, flexible learning and stochastic modeling. This study develops the unsupervised and supervised learning of deep unfolded topic models for document representation and classification. Conventionally, the unsupervised and supervised topic models are inferred via the variational inference algorithm where the model parameters are estimated by maximizing the lower bound of logarithm of marginal likelihood using input documents without and with class labels, respectively. The representation capability or classification accuracy is constrained by the variational lower bound and the tied model parameters across inference procedure. This paper aims to relax these constraints by directly maximizing the end performance criterion and continuously untying the parameters in learning process via deep unfolding inference (DUI). The inference procedure is treated as the layer-wise learning in a deep neural network. The end performance is iteratively improved by using the estimated topic parameters according to the exponentiated updates. Deep learning of topic models is therefore implemented through a back-propagation procedure. Experimental results show the merits of DUI with increasing number of layers compared with variational inference in unsupervised as well as supervised topic models.

Apparent plasticity in functional traits determining competitive ability and spatial distribution: a case from desert.

PubMed

Xie, Jiang-Bo; Xu, Gui-Qing; Jenerette, G Darrel; Bai, Yong-fei; Wang, Zhong-Yuan; Li, Yan

2015-07-20

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.

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

Crop response to deep tillage - a meta-analysis

NASA Astrophysics Data System (ADS)

Schneider, Florian; Don, Axel; Hennings, Inga; Schmittmann, Oliver; Seidel, Sabine J.

2017-04-01

Subsoil, i.e. the soil layer below the topsoil, stores tremendous stocks of nutrients and can keep water even under drought conditions. Deep tillage may be a method to enhance the plant-availability of subsoil resources. However, in field trials, deep tillage effects on crop yields were inconsistent. Therefore, we conducted a meta-analysis of crop yield response to subsoiling, deep ploughing and deep mixing of soil profiles. Our search resulted in 1530 yield comparisons following deep and conventional control tillage on 67 experimental cropping sites. The vast majority of the data derived from temperate latitudes, from trials conducted in the USA (679 observations) and Germany (630 observations). On average, crop yield response to deep tillage was slightly positive (6% increase). However, individual deep tillage effects were highly scattered including about 40% yield depressions after deep tillage. Deep tillage on soils with root restrictive layers increased crop yields about 20%, while soils containing >70% silt increased the risk of yield depressions following deep tillage. Generally, deep tillage effects increased with drought intensity indicating deep tillage as climate adaptation measure at certain sites. Our results suggest that deep tillage can facilitate the plant-availability of subsoil nutrients, which increases crop yields if (i) nutrients in the topsoil are growth limiting, and (ii) deep tillage does not come at the cost of impairing topsoil fertility. On sites with root restrictive soil layers, deep tillage can be an effective measure to mitigate drought stress and improve the resilience of crops. However, deep tillage should only be performed on soils with a stable structure, i.e. <70% silt content. We will discuss the contribution of deep tillage options to enhance the sustainability of agricultural production by facilitating the uptake of nutrients and water from the subsoil.

Patient age, refractive index of the corneal stroma, and outcomes of uneventful laser in situ keratomileusis.

PubMed

Patel, Sudi; Alió, Jorge L; Walewska, Anna; Amparo, Francisco; Artola, Alberto

2013-03-01

To determine the influence of age and the corneal stromal refractive index on the difference between the predicted and actual postoperative refractive error after laser in situ keratomileusis (LASIK) and whether the precision of outcomes could be improved by considering age and the refractive index. Vissum Instituto Oftalmologico de Alicante, Alicante, Spain. Case series. Flaps were created using a mechanical microkeratome. The stromal refractive index was measured using a VCH-1 refractometer after flap lifting. Refractive data were obtained 1, 3, and 6 months postoperatively. Uneventful LASIK was performed in 133 eyes. The mean age, refractive index, and applied corrections were 33.4 years ± 9.49 (SD), 1.368 ± 0.006, and -2.43 ± 3.36 diopters (D), respectively. The difference between the predicted and actual postoperative refractive error = 2.315-0.021 age-1.106 refractive index (F = 3.647, r = 0.254, P=.029; n = 109) at 1 month and = 11.820-0.023 age-7.976 refractive index (F = 3.392, r = 0.261, P=.022, n = 106) at 3 months. A correlation between the actual and calculated postoperative refraction improved from r = -0.178 (P=.064; n = 75) to r = -0.418 (P<.001) after considering the true refractive index 6 months postoperatively. The predicted outcomes of LASIK can be improved by inputting the refractive index of the individual corneal stroma. Unexpected outcomes (>0.50 D) of LASIK could be avoided by considering patient age and the refractive index and by adjusting the applied correction accordingly. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Effect of surfactants on apparent oxygen consumption of photosystem I isolated from Arthrospira platensis.

PubMed

Yu, Daoyong; Huang, Guihong; Xu, Fengxi; Ge, Baosheng; Liu, Shuang; Xu, Hai; Huang, Fang

2014-11-01

Surfactants play a significant role in solubilization of photosystem I (PSI) in vitro. Triton X-100 (TX), n-Dodecyl-β-D-maltoside (DDM), and sodium dodecyl sulfate (SDS) were employed to solubilize PSI particles in MES buffer to compare the effect of surfactant and its dosage on the apparent oxygen consumption rate of PSI. Through a combined assessment of sucrose density gradient centrifugation, Native PAGE and 77 K fluorescence with the apparent oxygen consumption, the nature of the enhancement of the apparent oxygen consumption activity of PSI by surfactants has been analyzed. Aggregated PSI particles can be dispersed by surfactant molecules into micelles, and the apparent oxygen consumption rate is higher for surfactant-solubilized PSI than for integral PSI particles. For DDM, PSI particles are solubilized mostly as the integral trimeric form. For TX, PSI particles are solubilized as incomplete trimeric and some monomeric forms. For the much harsher surfactant, SDS, PSI particles are completely solubilized as monomeric and its subunit forms. The enhancement of the oxygen consumption rate cannot be explained only by the effects of surfactant on the equilibrium between monomeric and trimeric forms of solubililized PSI. Care must be taken when the electron transfer activity of PSI is evaluated by methods based on oxygen consumption because the apparent oxygen consumption rate is influenced by uncoupled chlorophyll (Chl) from PSI, i.e., the larger the amount of uncoupled Chl, the higher the rate of apparent oxygen consumption. 77 K fluorescence spectra can be used to ensure that there is no uncoupled Chl present in the system. In order to eliminate the effect of trace uncoupled Chl, an efficient physical quencher of (1)O2, such as 1 mM NaN3, may be added into the mixture.

Simultaneous control of apparent extract and volatile compounds concentrations in low-malt beer fermentation.

PubMed

Kobayashi, Michiko; Nagahisa, Keisuke; Shimizu, Hiroshi; Shioya, Suteaki

2006-12-01

Volatile compounds cause undesirable flavor when their concentrations exceed threshold values in beer fermentation. The objective of this study is to develop a system for controlling apparent extract concentration, which indicates the fermentation degree and which should be decreased below a targeted value at a fixed time under a constraint of tolerable amounts of volatile compounds. In beer fermentation, even though the production of volatile compounds is suppressed by maintaining a low fermentation temperature, a low temperature causes a delay in the control of apparent extract concentration. Volatile compound concentration was estimated on-line, and the simulation of apparent extract consumption and volatile compound production was performed. To formulate various beer tastes and conserve energy for attemperation, optimal temperature profiles were determined using a genetic algorithm (GA). The developed feedback control of the brewing temperature profile was successfully applied, and apparent extract and volatile compound concentrations at a fixed time reached their target concentrations. Additionally, the control technique developed in this study enables us to brew a wide variety of beers with different tastes.

Interaction of Perceptual Grouping and Crossmodal Temporal Capture in Tactile Apparent-Motion

PubMed Central

Chen, Lihan; Shi, Zhuanghua; Müller, Hermann J.

2011-01-01

Previous studies have shown that in tasks requiring participants to report the direction of apparent motion, task-irrelevant mono-beeps can “capture” visual motion perception when the beeps occur temporally close to the visual stimuli. However, the contributions of the relative timing of multimodal events and the event structure, modulating uni- and/or crossmodal perceptual grouping, remain unclear. To examine this question and extend the investigation to the tactile modality, the current experiments presented tactile two-tap apparent-motion streams, with an SOA of 400 ms between successive, left-/right-hand middle-finger taps, accompanied by task-irrelevant, non-spatial auditory stimuli. The streams were shown for 90 seconds, and participants' task was to continuously report the perceived (left- or rightward) direction of tactile motion. In Experiment 1, each tactile stimulus was paired with an auditory beep, though odd-numbered taps were paired with an asynchronous beep, with audiotactile SOAs ranging from −75 ms to 75 ms. Perceived direction of tactile motion varied systematically with audiotactile SOA, indicative of a temporal-capture effect. In Experiment 2, two audiotactile SOAs—one short (75 ms), one long (325 ms)—were compared. The long-SOA condition preserved the crossmodal event structure (so the temporal-capture dynamics should have been similar to that in Experiment 1), but both beeps now occurred temporally close to the taps on one side (even-numbered taps). The two SOAs were found to produce opposite modulations of apparent motion, indicative of an influence of crossmodal grouping. In Experiment 3, only odd-numbered, but not even-numbered, taps were paired with auditory beeps. This abolished the temporal-capture effect and, instead, a dominant percept of apparent motion from the audiotactile side to the tactile-only side was observed independently of the SOA variation. These findings suggest that asymmetric crossmodal grouping leads to an

The Making of Deep Impact

NASA Image and Video Library

2006-10-19

This image shows NASA Deep Impact spacecraft being built at Ball Aerospace & Technologies Corporation, Boulder, Colo. on July 2, 2005. The spacecraft impactor was released from Deep Impact flyby spacecraft.

Summer School in Deep Ecology.

ERIC Educational Resources Information Center

Macmillan, Catherine Hume

1995-01-01

Describes one teacher's experiences at the Institute for Deep Ecology Education (IDEE) Summer School in Applied Deep Ecology. Reviews the program offered and the focus on interactive, experiential activities. (LZ)

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.

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…

Dust attenuation in 2 < z < 3 star-forming galaxies from deep ALMA observations of the Hubble Ultra Deep Field

NASA Astrophysics Data System (ADS)

McLure, R. J.; Dunlop, J. S.; Cullen, F.; Bourne, N.; Best, P. N.; Khochfar, S.; Bowler, R. A. A.; Biggs, A. D.; Geach, J. E.; Scott, D.; Michałowski, M. J.; Rujopakarn, W.; van Kampen, E.; Kirkpatrick, A.; Pope, A.

2018-05-01

We present the results of a new study of the relationship between infrared excess (IRX ≡ LIR/LUV), ultraviolet (UV) spectral slope (β) and stellar mass at redshifts 2 < z < 3, based on a deep Atacama Large Millimeter Array (ALMA) 1.3-mm continuum mosaic of the Hubble Ultra Deep Field. Excluding the most heavily obscured sources, we use a stacking analysis to show that z ≃ 2.5 star-forming galaxies in the mass range 9.25≤ log (M_{\\ast }/M_{⊙}) ≤ 10.75 are fully consistent with the IRX-β relation expected for a relatively grey attenuation curve, similar to the commonly adopted Calzetti law. Based on a large, mass-complete sample of 2 ≤ z ≤ 3 star-forming galaxies drawn from multiple surveys, we proceed to derive a new empirical relationship between β and stellar mass, making it possible to predict UV attenuation (A1600) and IRX as a function of stellar mass, for any assumed attenuation law. Once again, we find that z ≃ 2.5 star-forming galaxies follow A1600-M* and IRX-M* relations consistent with a relatively grey attenuation law, and find no compelling evidence that star-forming galaxies at this epoch follow a reddening law as steep as the Small Magellanic Cloud (SMC) extinction curve. In fact, we use a simple simulation to demonstrate that previous determinations of the IRX-β relation may have been biased towards low values of IRX at red values of β, mimicking the signature expected for an SMC-like dust law. We show that this provides a plausible mechanism for reconciling apparently contradictory results in the literature and that, based on typical measurement uncertainties, stellar mass provides a cleaner prediction of UV attenuation than β. Although the situation at lower stellar masses remains uncertain, we conclude that for 2 < z < 3 star-forming galaxies with log (M_{\\ast }/M_{⊙}) ≥ 9.75, both the IRX-β and IRX-M* relations are well described by a Calzetti-like attenuation law.

Towards apparent convergence in asymptotically safe quantum gravity

NASA Astrophysics Data System (ADS)

Denz, T.; Pawlowski, J. M.; Reichert, M.

2018-04-01

The asymptotic safety scenario in gravity is accessed within the systematic vertex expansion scheme for functional renormalisation group flows put forward in Christiansen et al. (Phys Lett B 728:114, 2014), Christiansen et al. (Phy Rev D 93:044036, 2016), and implemented in Christiansen et al. (Phys Rev D 92:121501, 2015) for propagators and three-point functions. In the present work this expansion scheme is extended to the dynamical graviton four-point function. For the first time, this provides us with a closed flow equation for the graviton propagator: all vertices and propagators involved are computed from their own flows. In terms of a covariant operator expansion the current approximation gives access to Λ , R, R^2 as well as R_{μ ν }^2 and higher derivative operators. We find a UV fixed point with three attractive and two repulsive directions, thus confirming previous studies on the relevance of the first three operators. In the infrared we find trajectories that correspond to classical general relativity and further show non-classical behaviour in some fluctuation couplings. We also find signatures for the apparent convergence of the systematic vertex expansion. This opens a promising path towards establishing asymptotically safe gravity in terms of apparent convergence.

Anisotropy beneath the Southern Pacific - real or apparent?

NASA Astrophysics Data System (ADS)

Prasse, Philipp; Thomas, Christine

2016-04-01

Anisotropy of the lowermost mantle beneath the South- to Central Pacific is investigated using US-Array receivers and events located near the Tonga-Fiji subduction zones. Differential splitting in three different distance ranges (65° -85° , 90° -110° and >110°) of S-ScS, SKS-S, SKS-Sdiff phases is used. By utilizing differential splitting technique, it was possible to correct for upper mantle, as well as source- and receiver side anisotropy and effectively quantify shear wave splitting originating in the lowermost mantle. Delay times of horizontal (SH) and vertical polarized (SV) shear waves show that predominantly the SH wave is delayed relative to the SV wave. Motivated by the discrepancy in previous Pacific studies investigating the lowermost mantle beneath the Pacific the possibility of isotropic structure producing the observed splitting is tested. Synthetic seismograms are computed, based on various isotropic models and the resulting synthetics are analysed in the same way as the real data. While simple layered models do not produce splitting and therefore apparent anisotropy, models in which the lowermost mantle is represented as a negative gradient in P- and S-wave velocity, produce clear apparent anisotropy. Thus, this study presents a possible alternative way of explaining the structure of the D" region.

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.

Apparent thermal inertia and the surface heterogeneity of Mars

NASA Astrophysics Data System (ADS)

Putzig, Nathaniel E.; Mellon, Michael T.

2007-11-01

Thermal inertia derivation techniques generally assume that surface properties are uniform at horizontal scales below the footprint of the observing instrument and to depths of several decimeters. Consequently, surfaces with horizontal or vertical heterogeneity may yield apparent thermal inertia which varies with time of day and season. To investigate these temporal variations, we processed three Mars years of Mars Global Surveyor Thermal Emission Spectrometer observations and produced global nightside and dayside seasonal maps of apparent thermal inertia. These maps show broad regions with diurnal and seasonal differences up to 200 J m -2 K -1s -1/2 at mid-latitudes (60° S to 60° N) and 600 J m -2 K -1s -1/2 or greater in the polar regions. We compared the seasonal mapping results with modeled apparent thermal inertia and created new maps of surface heterogeneity at 5° resolution, delineating regions that have thermal characteristics consistent with horizontal mixtures or layers of two materials. The thermal behavior of most regions on Mars appears to be dominated by layering, with upper layers of higher thermal inertia (e.g., duricrusts or desert pavements over fines) prevailing in mid-latitudes and upper layers of lower thermal inertia (e.g., dust-covered rock, soils with an ice table at shallow depths) prevailing in polar regions. Less common are regions dominated by horizontal mixtures, such as those containing differing proportions of rocks, sand, dust, and duricrust or surfaces with divergent local slopes. Other regions show thermal behavior that is more complex and not well-represented by two-component surface models. These results have important implications for Mars surface geology, climate modeling, landing-site selection, and other endeavors that employ thermal inertia as a tool for characterizing surface properties.

Accidental deep field bias in CMB T and SNe z correlation

NASA Astrophysics Data System (ADS)

Friday, Tracey; Clowes, Roger G.; Raghunathan, Srinivasan; Williger, Gerard M.

2018-05-01

Evidence presented by Yershov, Orlov and Raikov apparently showed that the WMAP/Planck cosmic microwave background (CMB) pixel-temperatures (T) at supernovae (SNe) locations tend to increase with increasing redshift (z). They suggest this correlation could be caused by the Integrated Sachs-Wolfe effect and/or by some unrelated foreground emission. Here, we assess this correlation independently using Planck 2015 SMICA R2.01 data and, following Yershov et al., a sample of 2783 SNe from the Sternberg Astronomical Institute. Our analysis supports the prima facie existence of the correlation but attributes it to a composite selection bias (high CMB T × high SNe z) caused by the accidental alignment of seven deep survey fields with CMB hotspots. These seven fields contain 9.2 per cent of the SNe sample (256 SNe). Spearman's rank-order correlation coefficient indicates the correlation present in the whole sample (ρs = 0.5, p-value =6.7 × 10-9) is insignificant for a sub-sample of the seven fields together (ρs = 0.2, p-value =0.2) and entirely absent for the remainder of the SNe (ρs = 0.1, p-value =0.6). We demonstrate the temperature and redshift biases of these seven deep fields, and estimate the likelihood of their falling on CMB hotspots by chance is at least ˜ 6.8 per cent (approximately 1 in 15). We show that a sample of 7880 SNe from the Open Supernova Catalogue exhibits the same effect and we conclude that the correlation is an accidental but not unlikely selection bias.

Deep Water Cooling | Climate Neutral Research Campuses | NREL

Science.gov Websites

the Cornell website. Additional examples of research campus geothermal cooling projects include Deep Water Cooling Deep Water Cooling Research campuses that are located near a deep lake or deep plan for your research campus. Considerations Sample Project Related Links Deep water cooling involves

Transforming growth factor beta mediates the progesterone suppression of an epithelial metalloproteinase by adjacent stroma in the human endometrium.

PubMed Central

Bruner, K L; Rodgers, W H; Gold, L I; Korc, M; Hargrove, J T; Matrisian, L M; Osteen, K G

1995-01-01

Unlike most normal adult tissues, cyclic growth and tissue remodeling occur within the uterine endometrium throughout the reproductive years. The matrix metalloproteinases (MMPs), a family of structurally related enzymes that degrade specific components of the extracellular matrix are thought to be the physiologically relevant mediators of extracellular matrix composition and turnover. Our laboratory has identified MMPs of the stromelysin family in the cycling human endometrium, implicating these enzymes in mediating the extensive remodeling that occurs in this tissue. While the stromelysins are expressed in vivo during proliferation-associated remodeling and menstruation-associated endometrial breakdown, none of the stromelysins are expressed during the progesterone-dominated secretory phase of the cycle. Our in vitro studies of isolated cell types have confirmed progesterone suppression of stromal MMPs, but a stromal-derived paracrine factor was found necessary for suppression of the epithelial-specific MMP matrilysin. In this report, we demonstrate that transforming growth factor beta (TGF-beta) is produced by endometrial stroma in response to progesterone and can suppress expression of epithelial matrilysin independent of progesterone. Additionally, we find that an antibody directed against the mammalian isoforms of TGF-beta abolishes progesterone suppression of matrilysin in stromal-epithelial cocultures, implicating TGF-beta as the principal mediator of matrilysin suppression in the human endometrium. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7638197

Fractional time-dependent apparent viscosity model for semisolid foodstuffs

NASA Astrophysics Data System (ADS)

Yang, Xu; Chen, Wen; Sun, HongGuang

2017-10-01

The difficulty in the description of thixotropic behaviors in semisolid foodstuffs is the time dependent nature of apparent viscosity under constant shear rate. In this study, we propose a novel theoretical model via fractional derivative to address the high demand by industries. The present model adopts the critical parameter of fractional derivative order α to describe the corresponding time-dependent thixotropic behavior. More interestingly, the parameter α provides a quantitative insight into discriminating foodstuffs. With the re-exploration of three groups of experimental data (tehineh, balangu, and natillas), the proposed methodology is validated in good applicability and efficiency. The results show that the present fractional apparent viscosity model performs successfully for tested foodstuffs in the shear rate range of 50-150 s^{ - 1}. The fractional order α decreases with the increase of temperature at low temperature, below 50 °C, but increases with growing shear rate. While the ideal initial viscosity k decreases with the increase of temperature, shear rate, and ingredient content. It is observed that the magnitude of α is capable of characterizing the thixotropy of semisolid foodstuffs.

Enhanced metastatic capacity of breast cancer cells after interaction and hybrid formation with mesenchymal stroma/stem cells (MSC).

PubMed

Melzer, Catharina; von der Ohe, Juliane; Hass, Ralf

2018-01-05

Fusion of breast cancer cells with tumor-associated populations of the microenvironment including mesenchymal stroma/stem-like cells (MSC) represents a rare event in cell communication whereby the metastatic capacity of those hybrid cells remains unclear. Functional changes were investigated in vitro and in vivo following spontaneous fusion and hybrid cell formation between primary human MSC and human MDA-MB-231 breast cancer cells. Thus, lentiviral eGFP-labeled MSC and breast cancer cells labeled with mcherry resulted in dual-fluorescing hybrid cells after co-culture. Double FACS sorting and single cell cloning revealed two different aneuploid male hybrid populations (MDA-hyb1 and MDA-hyb2) with different STR profiles, pronounced telomerase activities, and enhanced proliferative capacities as compared to the parental cells. Microarray-based mRNA profiling demonstrated marked regulation of genes involved in epithelial-mesenchymal transition and increased expression of metastasis-associated genes including S100A4. In vivo studies following subcutaneous injection of the breast cancer and the two hybrid populations substantiated the in vitro findings by a significantly elevated tumor growth of the hybrid cells. Moreover, both hybrid populations developed various distant organ metastases in a much shorter period of time than the parental breast cancer cells. Together, these data demonstrate spontaneous development of new tumor cell populations exhibiting different parental properties after close interaction and subsequent fusion of MSC with breast cancer cells. This formation of tumor hybrids contributes to continuously increasing tumor heterogeneity and elevated metastatic capacities.

Expression and Function of the Progesterone Receptor in Human Prostate Stroma Provide Novel Insights to Cell Proliferation Control

PubMed Central

Yu, Yue; Liu, Liangliang; Xie, Ning; Xue, Hui; Fazli, Ladan; Buttyan, Ralph; Wang, Yuzhuo; Gleave, Martin

2013-01-01

Context: Like other tissues, the prostate is an admixture of many different cell types that can be segregated into components of the epithelium or stroma. Reciprocal interactions between these 2 types of cells are critical for maintaining prostate homeostasis, whereas aberrant stromal cell proliferation can disrupt this balance and result in diseases such as benign prostatic hyperplasia. Although the androgen and estrogen receptors are relatively well studied for their functions in controlling stromal cell proliferation and differentiation, the role of the progesterone receptor (PR) remains unclear. Objective: The aim of the study was to investigate the expression and function of the PR in the prostate. Design and Setting: Human prostate biopsies, renal capsule xenografts, and prostate stromal cells were used. Immunohistochemistry, Western blotting, real-time quantitative PCR, cell proliferation, flow cytometry, and gene microarray analyses were performed. Results: Two PR isoforms, PRA and PRB, are expressed in prostate stromal fibroblasts and smooth muscle cells, but not in epithelial cells. Both PR isoforms suppress prostate stromal cell proliferation through inhibition of the expression of cyclinA, cyclinB, and cdc25c, thus delaying cell cycling through S and M phases. Gene microarray analyses further demonstrated that PRA and PRB regulated different transcriptomes. However, one of the major gene groups commonly regulated by both PR isoforms was the one associated with regulation of cell proliferation. Conclusion: PR plays an inhibitory role in prostate stromal cell proliferation. PMID:23666965

How Stressful Is "Deep Bubbling"?

PubMed

Tyrmi, Jaana; Laukkanen, Anne-Maria

2017-03-01

Water resistance therapy by phonating through a tube into the water is used to treat dysphonia. Deep submersion (≥10 cm in water, "deep bubbling") is used for hypofunctional voice disorders. Using it with caution is recommended to avoid vocal overloading. This experimental study aimed to investigate how strenuous "deep bubbling" is. Fourteen subjects, half of them with voice training, repeated the syllable [pa:] in comfortable speaking pitch and loudness, loudly, and in strained voice. Thereafter, they phonated a vowel-like sound both in comfortable loudness and loudly into a glass resonance tube immersed 10 cm into the water. Oral pressure, contact quotient (CQ, calculated from electroglottographic signal), and sound pressure level were studied. The peak oral pressure P(oral) during [p] and shuttering of the outer end of the tube was measured to estimate the subglottic pressure P(sub) and the mean P(oral) during vowel portions to enable calculation of transglottic pressure P(trans). Sensations during phonation were reported with an open-ended interview. P(sub) and P(oral) were higher in "deep bubbling" and P(trans) lower than in loud syllable phonation, but the CQ did not differ significantly. Similar results were obtained for the comparison between loud "deep bubbling" and strained phonation, although P(sub) did not differ significantly. Most of the subjects reported "deep bubbling" to be stressful only for respiratory and lip muscles. No big differences were found between trained and untrained subjects. The CQ values suggest that "deep bubbling" may increase vocal fold loading. Further studies should address impact stress during water resistance exercises. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Simulator Studies of the Deep Stall

NASA Technical Reports Server (NTRS)

White, Maurice D.; Cooper, George E.

1965-01-01

Simulator studies of the deep-stall problem encountered with modern airplanes are discussed. The results indicate that the basic deep-stall tendencies produced by aerodynamic characteristics are augmented by operational considerations. Because of control difficulties to be anticipated in the deep stall, it is desirable that adequate safeguards be provided against inadvertent penetrations.

Identifying apparent local stable isotope equilibrium in a complex non-equilibrium system.

PubMed

He, Yuyang; Cao, Xiaobin; Wang, Jianwei; Bao, Huiming

2018-02-28

Although being out of equilibrium, biomolecules in organisms have the potential to approach isotope equilibrium locally because enzymatic reactions are intrinsically reversible. A rigorous approach that can describe isotope distribution among biomolecules and their apparent deviation from equilibrium state is lacking, however. Applying the concept of distance matrix in graph theory, we propose that apparent local isotope equilibrium among a subset of biomolecules can be assessed using an apparent fractionation difference (|Δα|) matrix, in which the differences between the observed isotope composition (δ') and the calculated equilibrium fractionation factor (1000lnβ) can be more rigorously evaluated than by using a previous approach for multiple biomolecules. We tested our |Δα| matrix approach by re-analyzing published data of different amino acids (AAs) in potato and in green alga. Our re-analysis shows that biosynthesis pathways could be the reason for an apparently close-to-equilibrium relationship inside AA families in potato leaves. Different biosynthesis/degradation pathways in tubers may have led to the observed isotope distribution difference between potato leaves and tubers. The analysis of data from green algae does not support the conclusion that AAs are further from equilibrium in glucose-cultured green algae than in the autotrophic ones. Application of the |Δα| matrix can help us to locate potential reversible reactions or reaction networks in a complex system such as a metabolic system. The same approach can be broadly applied to all complex systems that have multiple components, e.g. geochemical or atmospheric systems of early Earth or other planets. Copyright © 2017 John Wiley & Sons, Ltd.

Mathematical Models for the Apparent Mass of the Seated Human Body Exposed to Vertical Vibration

NASA Astrophysics Data System (ADS)

Wei, L.; Griffin, M. J.

1998-05-01

Alternative mathematical models of the vertical apparent mass of the seated human body are developed. The optimum parameters of four models (two single-degree-of-freedom models and two two-degree-of-freedom models) are derived from the mean measured apparent masses of 60 subjects (24 men, 24 women, 12 children) previously reported. The best fits were obtained by fitting the phase data with single-degree-of-freedom and two-degree-of-freedom models having rigid support structures. For these two models, curve fitting was performed on each of the 60 subjects (so as to obtain optimum model parameters for each subject), for the averages of each of the three groups of subjects, and for the entire group of subjects. The values obtained are tabulated. Use of a two-degree-of-freedom model provided a better fit to the phase of the apparent mass at frequencies greater than about 8 Hz and an improved fit to the modulus of the apparent mass at frequencies around 5 Hz. It is concluded that the two-degree-of-freedom model provides an apparent mass similar to that of the human body, but this does not imply that the body moves in the same manner as the masses in this optimized two-degree-of-freedom model.

Electrical characterization of deep levels created by bombarding nitrogen-doped 4H-SiC with alpha-particle irradiation

NASA Astrophysics Data System (ADS)

Omotoso, Ezekiel; Meyer, Walter E.; Auret, F. Danie; Paradzah, Alexander T.; Legodi, Matshisa J.

2016-03-01

Deep-level transient spectroscopy (DLTS) and Laplace-DLTS were used to investigate the effect of alpha-particle irradiation on the electrical properties of nitrogen-doped 4H-SiC. The samples were bombarded with alpha-particles at room temperature (300 K) using an americium-241 (241Am) radionuclide source. DLTS revealed the presence of four deep levels in the as-grown samples, E0.09, E0.11, E0.16 and E0.65. After irradiation with a fluence of 4.1 × 1010 alpha-particles-cm-2, DLTS measurements indicated the presence of two new deep levels, E0.39 and E0.62 with energy levels, EC - 0.39 eV and EC - 0.62 eV, with an apparent capture cross sections of 2 × 10-16 and 2 × 10-14 cm2, respectively. Furthermore, irradiation with fluence of 8.9 × 1010 alpha-particles-cm-2 resulted in the disappearance of shallow defects due to a lowering of the Fermi level. These defects re-appeared after annealing at 300 °C for 20 min. Defects, E0.39 and E0.42 with close emission rates were attributed to silicon or carbon vacancy and could only be separated by using high resolution Laplace-DLTS. The DLTS peaks at EC - (0.55-0.70) eV (known as Z1/Z2) were attributed to an isolated carbon vacancy (VC).

Corneal confocal microscopy following conventional, transepithelial, and accelerated corneal collagen cross-linking procedures for keratoconus.

PubMed

Touboul, David; Efron, Nathan; Smadja, David; Praud, Delphine; Malet, Florence; Colin, Joseph

2012-11-01

To compare early corneal healing following conventional, transepithelial, and accelerated corneal collagen cross-linking (CXL) protocols. Twenty-four patients with progressive keratoconus were divided into three groups to receive conventional, transepithelial, or accelerated CXL. In vivo corneal confocal microscopy was performed on each patient preoperatively and at 1, 3, and 6 months postoperatively. Closure of the epithelial wound was complete 3 days following conventional and accelerated CXL. The subbasal nerve plexus was essentially obliterated immediately following conventional and accelerated CXL, and virtually no nerve fibers had regenerated by 6 months. The anterior stroma showed significant changes 1 month following conventional CXL; these changes were similar but more pronounced following accelerated CXL. Observed stromal changes included complete obliteration of keratocytes, increased tissue reflectivity, a honeycomb-like appearance, and circular lacunae. Some recovery of keratocyte density was noted after 6 months. These changes were less pronounced in the mid-stroma, and there were no apparent changes to the posterior stroma or endothelium. The cornea appeared to be unaltered following transepithelial CXL. In vivo corneal confocal microscopy analysis of the postoperative impact of CXL on the cornea revealed clear differences among conventional, accelerated, and transepithelial CXL protocols. Accelerated CXL had a greater impact than conventional CXL on the anterior cornea, whereas transepithelial CXL did not appear to alter corneal morphology. Copyright 2012, SLACK Incorporated.

Deep Extragalactic X-Ray Surveys

NASA Astrophysics Data System (ADS)

Brandt, W. N.; Hasinger, G.

2005-09-01

Deep surveys of the cosmic X-ray background are reviewed in the context of observational progress enabled by the Chandra X-Ray Observatory and the X-Ray Multi-Mirror Mission-Newton. The sources found by deep surveys are described along with their redshift and luminosity distributions, and the effectiveness of such surveys at selecting active galactic nuclei (AGN) is assessed. Some key results from deep surveys are highlighted, including (a) measurements of AGN evolution and the growth of supermassive black holes, (b) constraints on the demography and physics of high-redshift AGN, (c) the X-ray AGN content of infrared and submillimeter galaxies, and (d) X-ray emission from distant starburst and normal galaxies. We also describe some outstanding problems and future prospects for deep extragalactic X-ray surveys.

75 FR 51869 - CAFTA-DR Consultation Request Regarding Guatemala's Apparent Failure to Effectively Enforce its...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

... Request Regarding Guatemala's Apparent Failure to Effectively Enforce its Labor Laws AGENCY: Office of the... (CAFTA-DR), the United States requested consultations with the Government of Guatemala to discuss Guatemala's apparent failure to meet its obligation under Article 16.2.1(a) to effectively enforce its labor...

LONG-TERM STARVATION-INDUCED LOSS OF APPARENT ANTIBIOTIC RESISTANCE IN CELLS CONTAINING THE PLASMID PSA

EPA Science Inventory

Escherichia coli, Pseudomonas fluorescens, and a Pseudomonas sp. strain 133B containing the pSa plasmid were starved in well water for up to 523 days. There were two patterns of apparent antibiotic resistance loss observed. In Pseudomonas sp. strain 133B, there was no apparent lo...

MR Anatomy of Deep Brain Nuclei with Special Reference to Specific Diseases and Deep Brain Stimulation Localization

PubMed Central

Telford, Ryan; Vattoth, Surjith

2014-01-01

Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832

DeepNAT: Deep convolutional neural network for segmenting neuroanatomy.

PubMed

Wachinger, Christian; Reuter, Martin; Klein, Tassilo

2018-04-15

We introduce DeepNAT, a 3D Deep convolutional neural network for the automatic segmentation of NeuroAnaTomy in T1-weighted magnetic resonance images. DeepNAT is an end-to-end learning-based approach to brain segmentation that jointly learns an abstract feature representation and a multi-class classification. We propose a 3D patch-based approach, where we do not only predict the center voxel of the patch but also neighbors, which is formulated as multi-task learning. To address a class imbalance problem, we arrange two networks hierarchically, where the first one separates foreground from background, and the second one identifies 25 brain structures on the foreground. Since patches lack spatial context, we augment them with coordinates. To this end, we introduce a novel intrinsic parameterization of the brain volume, formed by eigenfunctions of the Laplace-Beltrami operator. As network architecture, we use three convolutional layers with pooling, batch normalization, and non-linearities, followed by fully connected layers with dropout. The final segmentation is inferred from the probabilistic output of the network with a 3D fully connected conditional random field, which ensures label agreement between close voxels. The roughly 2.7million parameters in the network are learned with stochastic gradient descent. Our results show that DeepNAT compares favorably to state-of-the-art methods. Finally, the purely learning-based method may have a high potential for the adaptation to young, old, or diseased brains by fine-tuning the pre-trained network with a small training sample on the target application, where the availability of larger datasets with manual annotations may boost the overall segmentation accuracy in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress on the seismogenic and deep creep plate interface during the earthquake cycle in subduction zones

NASA Astrophysics Data System (ADS)

Ruff, Larry J.

2001-04-01

the earthquake cycle ranges from 0.1 MPa (Nankai) to 1.7 MPa (Chile). These absolute stress values for the deep creep zone are slightly smaller than the great earthquake stress drops. Since the great earthquake recurrence time ( T recur) is much larger than τ for Nankai, Alaska, and Chile, the model predicts that rapid post-seismic creep should re-load the seismogenic zone to about (1/3) of the co-seismic change; geodetically observed values range from about (1/10) to more than (1/2). Also, for the case of (Trecur/τ) ≫1, the model predicts that the slip velocity across the deep creep interface during the inter-seismic phase should be about (2/3) the plate tectonic velocity (R). Thus the deep creep velocity used in Savage-type models should be less than R. Even complex 3-D models with non-linear creep laws should make a similar prediction for inter-seismic deep creep rates. At present, it seems that geodetic observations at Nankai and other subduction zones are more consistent with a deep creep rate of R rather than (2/3) R. This discrepancy is quite puzzling and is difficult to explain in the context of a 2-D steady-state earthquake cycle model. Future observational and modeling studies should examine this apparent discrepancy to gain more understanding of the earthquake cycle in subduction zones.

Deep Learning and Its Applications in Biomedicine.

PubMed

Cao, Chensi; Liu, Feng; Tan, Hai; Song, Deshou; Shu, Wenjie; Li, Weizhong; Zhou, Yiming; Bo, Xiaochen; Xie, Zhi

2018-02-01

Advances in biological and medical technologies have been providing us explosive volumes of biological and physiological data, such as medical images, electroencephalography, genomic and protein sequences. Learning from these data facilitates the understanding of human health and disease. Developed from artificial neural networks, deep learning-based algorithms show great promise in extracting features and learning patterns from complex data. The aim of this paper is to provide an overview of deep learning techniques and some of the state-of-the-art applications in the biomedical field. We first introduce the development of artificial neural network and deep learning. We then describe two main components of deep learning, i.e., deep learning architectures and model optimization. Subsequently, some examples are demonstrated for deep learning applications, including medical image classification, genomic sequence analysis, as well as protein structure classification and prediction. Finally, we offer our perspectives for the future directions in the field of deep learning. Copyright © 2018. Production and hosting by Elsevier B.V.

Deep learning applications in ophthalmology.

PubMed

Rahimy, Ehsan

2018-05-01

To describe the emerging applications of deep learning in ophthalmology. Recent studies have shown that various deep learning models are capable of detecting and diagnosing various diseases afflicting the posterior segment of the eye with high accuracy. Most of the initial studies have centered around detection of referable diabetic retinopathy, age-related macular degeneration, and glaucoma. Deep learning has shown promising results in automated image analysis of fundus photographs and optical coherence tomography images. Additional testing and research is required to clinically validate this technology.

Spatial interpolation of soil organic carbon using apparent electrical conductivity as secondary information

NASA Astrophysics Data System (ADS)

Martinez, G.; Vanderlinden, K.; Ordóñez, R.; Muriel, J. L.

2009-04-01

Soil organic carbon (SOC) spatial characterization is necessary to evaluate under what circumstances soil acts as a source or sink of carbon dioxide. However, at the field or catchment scale it is hard to accurately characterize its spatial distribution since large numbers of soil samples are necessary. As an alternative, near-surface geophysical sensor-based information can improve the spatial estimation of soil properties at these scales. Electromagnetic induction (EMI) sensors provide non-invasive and non-destructive measurements of the soil apparent electrical conductivity (ECa), which depends under non-saline conditions on clay content, water content or SOC, among other properties that determine the electromagnetic behavior of the soil. This study deals with the possible use of ECa-derived maps to improve SOC spatial estimation by Simple Kriging with varying local means (SKlm). Field work was carried out in a vertisol in SW Spain. The field is part of a long-term tillage experiment set up in 1982 with three replicates of conventional tillage (CT) and Direct Drilling (DD) plots with unitary dimensions of 15x65m. Shallow and deep (up to 0.8m depth) apparent electrical conductivity (ECas and ECad, respectively) was measured using the EM38-DD EMI sensor. Soil samples were taken from the upper horizont and analyzed for their SOC content. Correlation coefficients of ECas and ECad with SOC were low (0.331 and 0.175) due to the small range of SOC values and possibly also to the different support of the ECa and SOC data. Especially the ECas values were higher in the DD plots. The normalized ECa difference (ΔECa), calculated as the difference between the normalized ECas and ECad values, distinguished clearly the CT and DD plots, with the DD plots showing positive ΔECa values and CT plots ΔECa negative values. The field was stratified using fuzzy k-means (FKM) classification of ΔECa (FKM1), and ECas and ECad (FKM2). The FKM1 map mainly showed the difference between