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Sample records for islands revisited microenvironment

  1. Three Mile Island revisited

    International Nuclear Information System (INIS)

    MacLeod, G.K.

    1986-01-01

    The accident at Three Mile Island proved that the Pennsylvania Department of Health lacked the tools to deal with the serious health consequences that occurred during and after this emergency. Despite the relative safety of nuclear power generation, we must be better prepared for the health and medical consequences of serous radiation emergencies. The author reviews the Three Mile Island accident through the eyes of newspaper reporters

  2. Revisiting the Metaphor of the Island: Challenging "World Culture" from an Island Misunderstood

    Science.gov (United States)

    Rappleye, Jeremy

    2015-01-01

    This article revisits the newly "discovered" island that world culture theorists have repeatedly utilised to explain their theoretical stance, conceptual preferences and methodological approach. Yet, it seeks to (re)connect world culture with the real world by replacing their imagined atoll with a real one--the island-nation of Japan. In…

  3. Revisited Inventory of Glaciers on Axel Heiberg Island, Nunavut

    Science.gov (United States)

    Thomson, L.; Osinski, G.

    2009-05-01

    As documented in the IPCC's Climate Change 2007 report, the high latitude regions of the Northern Hemisphere are experiencing the highest rates of warming. Given that 35% of the global glacial ice exists within the Arctic Archipelago, this region provides an excellent laboratory for monitoring the anticipated degree of glacial recession [1]. Evidence of arctic warming through negative mass balance trends has been detected in several studies already [e.g., 2]. Here, we show the importance and value of historical records in the task of monitoring glacial retreat. A highly detailed inventory developed by S. Ommanney in 1969 [3], has been revisited and transformed into digital format for the purposes of integration with modern inventories. The Ommanney inventory covers the entirety of Axel Heiberg Island , NU, and includes details often lacking in present day inventories, including orientations (accumulation and ablation zones), elevations (highest, lowest, elevation of the snowline, and the mean elevations of both the accumulation and ablation areas), length (of the ablation area, exposed ice, and of the total glacier including debris cover), area (of the ablation area, exposed ice, and of the total glacier), accumulation area ratio (AAR), depth, volume, and a six digit code which gives qualitative details on glacier attributes. This report is one of the most thorough and comprehensive glacier inventory report ever published in Canada. More recent inventories used for comparison include the glacier extents created by the National Topographic System based on photography from 1980-1987, as well as extents developed by Dr. Luke Copland for the Global Land Ice Measurements from Space (GLIMS) database using 1999-2000 satellite imagery. Our preliminary results show that approximately 90% of ice bodies under 0.2km on Axel Heiberg Island have disappeared entirely in the 40 year period of interest. The issue of glacier definition will be discussed as a possible cause of these

  4. Microbial Mats on the Orkney Islands Revisited: Microenvironment and Microbial Community Composition

    DEFF Research Database (Denmark)

    Wieland, A.; Kühl, M.; McGowan, L.

    2003-01-01

    of these sediments. High amounts of algal lipids and slightly higher numbers (genera, abundances) of cyanobacteria were found in Waulkmill Bay mats. However, overall only a few genera and low numbers of unicellular and filamentous cyanobacteria were present in mats from Waulkmill and Swanbister beach, as deduced...... fragment length polymorphism) analysis in Swanbister beach mats, the depth distribution of different populations of purple and sulfate-reducing bacteria could be related to the microenvironmental conditions. Oxygen, but also sulfide and other (inorganic and organic) sulfur compounds, seems to play...

  5. Examining Relationships of Destination Image, Service Quality, e-WOM, and Revisit Intention to Sabang Island, Indonesia

    Directory of Open Access Journals (Sweden)

    Rangga Restu Prayogo

    2016-12-01

    Full Text Available The purpose of this research is to study the relationship among destination image, service quality, e-WOM, and revisit intentions in the tourism industry. A questionnaire given to tourists who visit one of the farrest island in western part of Indonesia, Sabang Island and using sampling through the convenience sampling. A structural equation model (SEM test with WarpPLS 3.0 was used to test the relationship between research variables. This research gathered from 150 respondents. The empirical results from PLS-SEM showed that; the destination image positive affect e-WOM and revisit intention; service quality affect e-WOM and revisit intention; e-WOM positive affect to revisit intention tourists. The implications and future research issues were discussed.

  6. Magmatic versus tectonic influence in the Eolian arc: the case of Vulcano and Lipari islands revisited

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    Ruch, Joel; Di Lorenzo, Riccardo; Vezzoli, Luigina Maria; De Rosa, Rosanna; Acocella, Valerio; Catalano, Stefano; Romagnoli, Gino

    2014-05-01

    The prevalent influence of magma versus tectonics for the edification and the evolution of volcanic zones is matter of debate. Here we focus on Vulcano and Lipari, two active volcanic islands located in the central sector of the Eolian arc (North of Sicily). Both systems are influenced by regional tectonics and affected by historical magmatic events taking place along a NS oriented structure, connecting both islands. We revisit and implement previous structural studies performed during the 1980's considering several new geophysical, geochemical and geodynamical findings. Four extensive structural campaigns have been performed on both islands and along the shorelines in 2012-2013 covering about 80% of the possible accessible outcrops. We collected ~500 measurements (e.g. faults, fractures and dikes) at 40 sites. Overall, most of the observed structures are oriented N-S and NNW-SSE, confirming previous studies, however, almost all features are strikingly dominated by an EW-oriented extensive regime, which is a novelty. These findings are supported by kinematic indicators and suggest a predominant dip-slip component (pitch from 80 and 130°) with alternating left and right kinematics. Marginal faulting in most recent formations have been observed, suggesting that the deformation may occur preferentially during transient deformation related to periods of magmatic activity, instead of resulting from continuous regional tectonic processes. Overall, fault and dike planes are characterized by a dominant eastward immersion, suggesting an asymmetric graben-like structure of the entire area. This may be explained by the presence of a topographic gradient connecting both islands to the deep Gioia basin to the East, leading to a preferential ample gravitational collapse. Finally, we propose a model in which the stress field rotates northward. It transits from a pure right lateral strike-slip regime along the Tindari fault zone (tectonic-dominant) to an extensive regime

  7. Revisited

    DEFF Research Database (Denmark)

    Tegtmeier, Silke; Meyer, Verena; Pakura, Stefanie

    2017-01-01

    were captured when they described entrepreneurs. Therefore, this paper aims to revisit gender role stereotypes among young adults. Design/methodology/approach: To measure stereotyping, participants were asked to describe entrepreneurs in general and either women or men in general. The Schein......Purpose: Entrepreneurship is shaped by a male norm, which has been widely demonstrated in qualitative studies. The authors strive to complement these methods by a quantitative approach. First, gender role stereotypes were measured in entrepreneurship. Second, the explicit notions of participants......: The images of men and entrepreneurs show a high and significant congruence (r = 0.803), mostly in those adjectives that are untypical for men and entrepreneurs. The congruence of women and entrepreneurs was low (r = 0.152) and insignificant. Contrary to the participants’ beliefs, their explicit notions did...

  8. The general dynamic model of island biogeography revisited on the level of major plant families

    DEFF Research Database (Denmark)

    Lenzner, Bernd; Beierkuhnlein, Carl; Patrick, Weigelt

    2017-01-01

    Aim: The general dynamic model (GDM) proposed by Whittaker et al. (2008) is a widely accepted theoretical framework in island biogeography. In this study, we explore whether GDM predictions hold when overall plant diversity is deconstructed into major plant families. Location: 101 islands from 14...... oceanic archipelagos worldwide. Methods: Occurrence data for all species of nine large, cosmopolitan flowering plant families were used to test predictions derived from the GDM. We analyzed the effects of island area and age on species richness as well as number and percentage of single-island endemic...... species per family using mixed-effect models. Results: Total species and endemic richness as well as the percentage of endemic species showed a hump-shaped relationship with island age. The overall pattern was mainly driven by few species-rich plant families. Varying patterns were found for individual...

  9. Moorean tree snail survival revisited: a multi-island genealogical perspective.

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    Lee, Taehwan; Burch, John B; Coote, Trevor; Pearce-Kelly, Paul; Hickman, Carole; Meyer, Jean-Yves; O Foighil, Diarmaid

    2009-08-18

    The mass extirpation of the island of Moorea's endemic partulid tree snail fauna, following the deliberate introduction of the alien predator Euglandina rosea, represents one of the highest profile conservation crises of the past thirty years. All of the island's partulids were thought to be extirpated by 1987, with five species persisting in zoos, but intensive field surveys have recently detected a number of surviving wild populations. We report here a mitochondrial (mt) phylogenetic estimate of Moorean partulid wild and captive lineage survival calibrated with a reference museum collection that pre-dates the predator's introduction and that also includes a parallel dataset from the neighboring island of Tahiti. Although severe winnowing of Moorea's mt lineage diversity has occurred, seven of eight (six Partula; two Samoana) partulid tip clades remain extant. The extinct mt clade occurred predominantly in the P. suturalis species complex and it represented a major component of Moorea's endemic partulid treespace. Extant Moorean mt clades exhibited a complex spectrum of persistence on Moorea, in captivity, and (in the form of five phylogenetically distinct sister lineages) on Tahiti. Most notably, three Partula taxa, bearing two multi-island mt lineages, have survived decades of E. rosea predation on Moorea (P. taeniata) and in the valleys of Tahiti (P. hyalina and P. clara). Their differential persistence was correlated with intrinsic attributes, such as taxonomy and mt lineages, rather than with their respective within-island distribution patterns. Conservation efforts directed toward Moorean and Tahitian partulids have typically operated within a single island frame of reference, but our discovery of robust genealogical ties among survivors on both islands implies that a multi-island perspective is required. Understanding what genetic and/or ecological factors have enabled Partula taeniata, P. hyalina and P. clara to differentially survive long-term direct

  10. Moorean tree snail survival revisited: a multi-island genealogical perspective

    Directory of Open Access Journals (Sweden)

    Meyer Jean-Yves

    2009-08-01

    Full Text Available Abstract Background The mass extirpation of the island of Moorea's endemic partulid tree snail fauna, following the deliberate introduction of the alien predator Euglandina rosea, represents one of the highest profile conservation crises of the past thirty years. All of the island's partulids were thought to be extirpated by 1987, with five species persisting in zoos, but intensive field surveys have recently detected a number of surviving wild populations. We report here a mitochondrial (mt phylogenetic estimate of Moorean partulid wild and captive lineage survival calibrated with a reference museum collection that pre-dates the predator's introduction and that also includes a parallel dataset from the neighboring island of Tahiti. Results Although severe winnowing of Moorea's mt lineage diversity has occurred, seven of eight (six Partula; two Samoana partulid tip clades remain extant. The extinct mt clade occurred predominantly in the P. suturalis species complex and it represented a major component of Moorea's endemic partulid treespace. Extant Moorean mt clades exhibited a complex spectrum of persistence on Moorea, in captivity, and (in the form of five phylogenetically distinct sister lineages on Tahiti. Most notably, three Partula taxa, bearing two multi-island mt lineages, have survived decades of E. rosea predation on Moorea (P. taeniata and in the valleys of Tahiti (P. hyalina and P. clara. Their differential persistence was correlated with intrinsic attributes, such as taxonomy and mt lineages, rather than with their respective within-island distribution patterns. Conclusion Conservation efforts directed toward Moorean and Tahitian partulids have typically operated within a single island frame of reference, but our discovery of robust genealogical ties among survivors on both islands implies that a multi-island perspective is required. Understanding what genetic and/or ecological factors have enabled Partula taeniata, P. hyalina and P

  11. MHD Equilibrium with Reversed Current Density and Magnetic Islands Revisited: the Vacuum Vector Potential Calculus

    Science.gov (United States)

    L. Braga, F.

    2013-10-01

    The solution of Grad-Shafranov equation determines the stationary behavior of fusion plasma inside a tokamak. To solve the equation it is necessary to know the toroidal current density profile. Recent works show that it is possible to determine a magnetohydrodynamic (MHD) equilibrium with reversed current density (RCD) profiles that presents magnetic islands. In this work we show analytical MHD equilibrium with a RCD profile and analyze the structure of the vacuum vector potential associated with these equilibria using the virtual casing principle.

  12. Three Mile Island epidemiologic radiation dose assessment revisited: 25 years after the accident.

    Science.gov (United States)

    Field, R William

    2005-01-01

    Over the past 25 years, public health concerns following the Three Mile Island (TMI) accident prompted several epidemiologic investigations in the vicinity of TMI. One of these studies is ongoing. This commentary suggests that the major source of radiation exposure to the population has been ignored as a potential confounding factor or effect modifying factor in previous and ongoing TMI epidemiologic studies that explore whether or not TMI accidental plant radiation releases caused an increase in lung cancer in the community around TMI. The commentary also documents the observation that the counties around TMI have the highest regional radon potential in the United States and concludes that radon progeny exposure should be included as part of the overall radiation dose assessment in future studies of radiation-induced lung cancer resulting from the TMI accident.

  13. Three Mile Island epidemiologic radiation dose assessment revisited: 25 years after the accident

    International Nuclear Information System (INIS)

    Field, R. W.

    2005-01-01

    Over the past 25 years, public health concerns following the Three Mile Island (TMI) accident prompted several epidemiologic investigations in the vicinity of TMI. One of these studies is ongoing. This commentary suggests that the major source of radiation exposure to the population has been ignored as a potential confounding factor or effect modifying factor in previous and ongoing TMI epidemiologic studies that explore whether or not TMI accidental plant radiation releases caused an increase in lung cancer in the community around TMI. The commentary also documents the observation that the counties around TMI have the highest regional radon potential in the United States and concludes that radon progeny exposure should be included as part of the overall radiation dose assessment in future studies of radiation-induced lung cancer resulting from the TMI accident. (authors)

  14. EMI – young HIMU rock association at the Cape Verde Islands revisited: on the role of oceanic carbonatites

    DEFF Research Database (Denmark)

    Holm, Paul Martin; Kokfelt, Thomas Find; Dyhr, Charlotte Thorup

    Isotopic compositions of the Cape Verde (Central) hotspot magmas indicate a predominant influence from young HIMU and EM-1 type sources. Detailed modelling based on high precision Sr, Nd and Pb (DS) isotope data suggests that seven local mantle end-members explain the isotopic variation within five...... HIMU. Carbonatites are widespread throughout Cape Verde Islands but volumetrically minor and are low in Ti, K, and Rb. In several silicate rocks from all three islands low Ti/Eu is evidence for a carbonatite component and is accompanied by LREE enrichment, and relatively low K and Rb. Other rocks have...

  15. Revisiting recent history: records of occurrence and expansion of the European green crab across Prince Edward Island, Atlantic Canada

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    Luke A. Poirier

    2017-11-01

    Full Text Available Abstract Background Late in the 1990s, the non-indigenous European green crab (Carcinus maenas colonized the shorelines of eastern Prince Edward Island, in Atlantic Canada. Due to concerns of further spread into productive shellfish habitats, an annual survey was conducted between 2000 and 2013 to detect a potential range expansion of this species. We compiled and analyzed that data and document green crab expansion using records of annual occurrence and relative density. Methods Surveys were conducted during the fall season of each year by deploying baited traps at 29 sites along the island’s two main shorelines (north and south shores. These sites were selected based on areas deemed more likely to be invaded by the green crab. Raw data per site and date was transformed to catch per unit effort (CPUE to estimate relative abundances. Results Populations of this species showed an uneven westward expansion along the north and south shores. Expansion rates changed among years but, overall, crab abundance was higher and changes in abundance were faster along the south shore than the north shore of the island. The westward expansion continues until this day. Conclusions Based on the information compiled we hypothesize that the dissimilarity in range expansion rate was related to the availability of suitable habitat to sustain large green crab populations along the south shore. We also discuss implications of this expansion for commercial shellfish and native coastal communities.

  16. St. Matthew Island reindeer crash revisited: Their demise was not nigh—but then, why did they die?

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    Frank L. Miller

    2005-05-01

    Full Text Available Twenty-nine yearling reindeer (Rangifer tarandus were released on St. Matthew Island in the Bering Sea Wildlife Refuge in 1944: 24 females and five males. They were reported to have increased to 1350 reindeer by summer 1957 and to 6000 by summer 1963. The 6000 reindeer on St. Matthew Island in summer 1963 were then reduced by 99% to 42 by summer 1966. The evidence suggests that after growing at a high average annual rate of lamda = 1.32 for 19 years, the entire die-off occurred in winter 1963—64, making it the largest single-year crash ever recorded in any R. tarandus population. Although a supposedly meaningful decline in successful reproduction and early survival of calves was originally reported for the population between 1957 and 1963, our reevaluation indicates this is an error resulting from the wrong sample being used in the between-year comparison. The quantitative data indicate no meaningful change occurred, and the calf:cow ratio was about 60 calves:100 cows in both 1957 and 1963. Calf production and survival were high up to the crash, and in the die-off population the age distribution (72%, 1—3 years old and the sex ratio (69 males:100 females reflected a still fast-growing R. tarandus population. All of these parameters do not support the hypothesis that the limited abundance of the absolute food supply was at a lethal level between 1957 and 1963 or in winter 1963—64. We now know from other studies that a high density of R. tarandus is not a prerequisite for a major single-year winter die-off. Existing population dynamics data do not support lack of lichens as a major causative factor in this single-year crash. If a decline had been caused by the limitation of the absolute food supply, it would have followed a multi-year pattern—it would not have been a single-year event. There was no evidence of a sudden, massive, island-wide loss of the absolute food supply, or that its nutritional value was inadequate for sustaining the

  17. Palaeo island-affinities revisited--biogeography and systematics of the Indo-Pacific genus Cethosia Fabricius (Lepidoptera: Nymphalidae).

    Science.gov (United States)

    Müller, C J; Beheregaray, L B

    2010-10-01

    The Indo-Pacific is a very complex region encompassing several micro-continents with unique tectonic and geomorphologic histories. Unsurprisingly, the biogeographic history of Indo-Pacific biota is generally poorly known, especially that of organisms found in the heart of the region, the biodiversity hotspot known as Wallacea. Here, we explore the biogeographic history of the Indo-Pacific butterfly genus Cethosia using all known species and many distinctive subspecies. Cethosia butterflies span the Indo-Pacific tropics, including several lineages with localized endemism that are critically important when reconstructing biogeographic history of the Indo-Pacific and, in particular, of Wallacea. A phylogenetic hypothesis is proposed, based on sequences of the mitochondrial genes cytochrome oxidase subunit I (COI) and NADH dehydrogenase 5 (ND5), and the nuclear wingless gene. Both Maximum Parsimony and Bayesian analyses showed that the genus is monophyletic and consistently recovered seven, generally very well supported, clades, namely the cydippe, leschenault, biblis, nietneri, hypsea, penthesilea and cyane clades. Species group relationships are largely concordant with general morphology (i.e., wing pattern and colouration) and, based on the phylogeny, we propose a revised systematic classification at the species level. The evolution of the genus appears associated with the inferred geological history of the region, in particular with respect to the expanding Wallacea theory, whereby ancient connected terranes were fragmented during the mid Miocene to early Pliocene, approximately 14-3 Mya. Recent diversification events in Cethosia were likely promoted by climatic fluctuations during the Pliocene and, to a lesser extent, the Pleistocene. Our results support the view that, while dispersal has been important for Cethosia throughout much of the region, the high levels of island endemism and the essentially allopatric radiations recovered in Cethosia in Wallacea are

  18. Volcanic evolution of central Basse-Terre Island revisited on the basis of new geochronology and geomorphology data

    Science.gov (United States)

    Ricci, J.; Quidelleur, X.; Lahitte, P.

    2015-10-01

    Twenty-six new and seven previous K-Ar ages obtained on groundmass separates for samples from the Axial Chain massif (Guadeloupe, F.W.I.), associated with geomorphological investigations, allow us to propose a new model of the volcanic evolution of the central part of Basse-Terre Island. The Axial Chain is composed of four edifices, Moustique, Matéliane, Capesterre, and Icaque mounts, showing coeval activity from 681 ± 12 to 509 ± 10 ka, which contradicts a previous hypothesis that flank collapse affected them successively. Our geomorphological reconstruction shows that the Axial Chain can be considered as a single large volcano, named the Southern Axial Chain volcano (SCA), rather than a succession of several smaller volcanoes. It raises questions regarding the formation of a large depression within the SCA volcano, prior to the construction of the Sans-Toucher volcano between 451 ± 13 and 412 ± 8 ka. Given presently available evidence, a slump affecting the western part of the SCA volcano is the most probable scenario to reconcile the complete age dataset and the present-day morphology of central Basse-Terre. Finally, our study shows that the SCA volcano had a post-activity volume of 90 km3, implying a construction rate of 0.5 km3/kyr. This value strongly constrains interpretations of magma generation processes throughout the Lesser Antilles arc.

  19. Targeting the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

    2006-11-07

    Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

  20. The PCa Tumor Microenvironment.

    Science.gov (United States)

    Sottnik, Joseph L; Zhang, Jian; Macoska, Jill A; Keller, Evan T

    2011-12-01

    The tumor microenvironment (TME) is a very complex niche that consists of multiple cell types, supportive matrix and soluble factors. Cells in the TME consist of both host cells that are present at tumor site at the onset of tumor growth and cells that are recruited in either response to tumor- or host-derived factors. PCa (PCa) thrives on crosstalk between tumor cells and the TME. Crosstalk results in an orchestrated evolution of both the tumor and microenvironment as the tumor progresses. The TME reacts to PCa-produced soluble factors as well as direct interaction with PCa cells. In return, the TME produces soluble factors, structural support and direct contact interactions that influence the establishment and progression of PCa. In this review, we focus on the host side of the equation to provide a foundation for understanding how different aspects of the TME contribute to PCa progression. We discuss immune effector cells, specialized niches, such as the vascular and bone marrow, and several key protein factors that mediate host effects on PCa. This discussion highlights the concept that the TME offers a potentially very fertile target for PCa therapy.

  1. Bioprinting the Cancer Microenvironment.

    Science.gov (United States)

    Zhang, Yu Shrike; Duchamp, Margaux; Oklu, Rahmi; Ellisen, Leif W; Langer, Robert; Khademhosseini, Ali

    2016-10-10

    Cancer is intrinsically complex, comprising both heterogeneous cellular compositions and microenvironmental cues. During the various stages of cancer initiation, development, and metastasis, cell-cell interactions (involving vascular and immune cells besides cancerous cells) as well as cell-extracellular matrix (ECM) interactions (e.g., alteration in stiffness and composition of the surrounding matrix) play major roles. Conventional cancer models both two- and three-dimensional (2D and 3D) present numerous limitations as they lack good vascularization and cannot mimic the complexity of tumors, thereby restricting their use as biomimetic models for applications such as drug screening and fundamental cancer biology studies. Bioprinting as an emerging biofabrication platform enables the creation of high-resolution 3D structures and has been extensively used in the past decade to model multiple organs and diseases. More recently, this versatile technique has further found its application in studying cancer genesis, growth, metastasis, and drug responses through creation of accurate models that recreate the complexity of the cancer microenvironment. In this review we will focus first on cancer biology and limitations with current cancer models. We then detail the current bioprinting strategies including the selection of bioinks for capturing the properties of the tumor matrices, after which we discuss bioprinting of vascular structures that are critical toward construction of complex 3D cancer organoids. We finally conclude with current literature on bioprinted cancer models and propose future perspectives.

  2. Tumor Biology and Microenvironment Research

    Science.gov (United States)

    Part of NCI's Division of Cancer Biology's research portfolio, research in this area seeks to understand the role of tumor cells and the tumor microenvironment (TME) in driving cancer initiation, progression, maintenance and recurrence.

  3. Lakatos Revisited.

    Science.gov (United States)

    Court, Deborah

    1999-01-01

    Revisits and reviews Imre Lakatos' ideas on "Falsification and the Methodology of Scientific Research Programmes." Suggests that Lakatos' framework offers an insightful way of looking at the relationship between theory and research that is relevant not only for evaluating research programs in theoretical physics, but in the social…

  4. The intestinal microenvironment in sepsis.

    Science.gov (United States)

    Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M

    2017-10-01

    The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.

  5. Dynamic microenvironments: the fourth dimension.

    Science.gov (United States)

    Tibbitt, Mark W; Anseth, Kristi S

    2012-11-14

    The extracellular space, or cell microenvironment, choreographs cell behavior through myriad controlled signals, and aberrant cues can result in dysfunction and disease. For functional studies of human cell biology or expansion and delivery of cells for therapeutic purposes, scientists must decipher this intricate map of microenvironment biology and develop ways to mimic these functions in vitro. In this Perspective, we describe technologies for four-dimensional (4D) biology: cell-laden matrices engineered to recapitulate tissue and organ function in 3D space and over time.

  6. Sensemaking Revisited

    DEFF Research Database (Denmark)

    Holt, Robin; Cornelissen, Joep

    2014-01-01

    We critique and extend theory on organizational sensemaking around three themes. First, we investigate sense arising non-productively and so beyond any instrumental relationship with things; second, we consider how sense is experienced through mood as well as our cognitive skills of manipulation ...... research by revisiting Weick’s seminal reading of Norman Maclean’s book surrounding the tragic events of a 1949 forest fire at Mann Gulch, USA....

  7. The external microenvironment of healing skin wounds

    DEFF Research Database (Denmark)

    Kruse, Carla R; Nuutila, Kristo; Lee, Cameron Cy

    2015-01-01

    The skin wound microenvironment can be divided into two main components that influence healing: the external wound microenvironment, which is outside the wound surface; and the internal wound microenvironment, underneath the surface, to which the cells within the wound are exposed. Treatment...

  8. Tumor microenvironment: Sanctuary of the devil.

    Science.gov (United States)

    Hui, Lanlan; Chen, Ye

    2015-11-01

    Tumor cells constantly interact with the surrounding microenvironment. Increasing evidence indicates that targeting the tumor microenvironment could complement traditional treatment and improve therapeutic outcomes for these malignancies. In this paper, we review new insights into the tumor microenvironment, and summarize selected examples of the cross-talk between tumor cells and their microenvironment, which have enhanced our understanding of pathophysiology of the microenvironment. We believe that this rapidly moving field promises many more to come, and they will guide the rational design of combinational therapies for success in cancer eradication. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Optical microassembly platform for constructing reconfigurable microenvironment for biomedical studies

    DEFF Research Database (Denmark)

    Rodrigo, Peter John; Kelemen, Lóránd; Palima, Darwin

    2009-01-01

    Cellular development is highly influenced by the surrounding microenvironment. We propose user-reconfigurable microenvironments and bio-compatible scaffolds as an approach for understanding cellular development processes. We demonstrate a model platform for constructing versatile microenvironment...

  10. The Importance of Being a Complement: CED Effects Revisited

    Science.gov (United States)

    Jurka, Johannes

    2010-01-01

    This dissertation revisits subject island effects (Ross 1967, Chomsky 1973) cross-linguistically. Controlled acceptability judgment studies in German, English, Japanese and Serbian show that extraction out of specifiers is consistently degraded compared to extraction out of complements, indicating that the Condition on Extraction domains (CED,…

  11. Microenvironment Determinants of Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Zhang Chenyu

    2011-02-01

    Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

  12. Immunological Dysregulation in Multiple Myeloma Microenvironment

    OpenAIRE

    Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

    2014-01-01

    Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extr...

  13. Commensal bacteria modulate the tumor microenvironment.

    Science.gov (United States)

    Poutahidis, Theofilos; Erdman, Susan E

    2016-09-28

    It has been recently shown that gut microbes modulate whole host immune and hormonal factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. This raises the possibility that the tumor microenvironment interacts with broader systemic microbial-immune networks. These accumulated findings suggest novel therapeutic opportunities for holobiont engineering in emerging tumor microenvironments. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Magnetic islands in tokamaks induced by thermal filamentation

    International Nuclear Information System (INIS)

    Dubois, M.A.; Mohamed-Benkadda, M.S.

    1991-11-01

    The thermal instability of filamentation is revisited in the fully nonlinear regime of a system of cool magnetic island chains, taking into account: the different transport processes inside and outside island cores, and a realistic temperature dependence of radiative losses. This mechanism is found to be a plausible candidate to explain the anomalous electron energy transport

  15. International Tourists’ Perceived Sustainability of Jeju Island, South Korea

    Directory of Open Access Journals (Sweden)

    Min-Seong Kim

    2017-12-01

    Full Text Available This study investigated the causal relationships between international tourists’ perceived sustainability of Jeju Island, South Korea and environmentally responsible behavior, revisit intention, and positive word-of-mouth communication. Perceived sustainability was employed as a multidimensional construct comprised of economic, cultural, and environmental aspects. Data were collected from international tourists that visited Jeju Island. The results indicated that environmentally responsible behavior was influenced positively by cultural sustainability, and negatively by environmental sustainability. Revisit intention and positive word-of-mouth communication were significantly affected by the three dimensions of sustainability. Based on the findings, associated implications were suggested for sustainable destination management of Jeju Island.

  16. Heat Islands

    Science.gov (United States)

    EPA's Heat Island Effect Site provides information on heat islands, their impacts, mitigation strategies, related research, a directory of heat island reduction initiatives in U.S. communities, and EPA's Heat Island Reduction Program.

  17. Island biogeography

    DEFF Research Database (Denmark)

    Whittaker, Robert James; Fernández-Palacios, José María; Matthews, Thomas J.

    2017-01-01

    Islands provide classic model biological systems. We review how growing appreciation of geoenvironmental dynamics of marine islands has led to advances in island biogeographic theory accommodating both evolutionary and ecological phenomena. Recognition of distinct island geodynamics permits gener...

  18. Oxidative phosphorylation revisited

    DEFF Research Database (Denmark)

    Nath, Sunil; Villadsen, John

    2015-01-01

    The fundamentals of oxidative phosphorylation and photophosphorylation are revisited. New experimental data on the involvement of succinate and malate anions respectively in oxidative phosphorylation and photophosphorylation are presented. These new data offer a novel molecular mechanistic...

  19. Enduring epigenetic landmarks define the cancer microenvironment

    Science.gov (United States)

    Pidsley, Ruth; Lawrence, Mitchell G.; Zotenko, Elena; Niranjan, Birunthi; Statham, Aaron; Song, Jenny; Chabanon, Roman M.; Qu, Wenjia; Wang, Hong; Richards, Michelle; Nair, Shalima S.; Armstrong, Nicola J.; Nim, Hieu T.; Papargiris, Melissa; Balanathan, Preetika; French, Hugh; Peters, Timothy; Norden, Sam; Ryan, Andrew; Pedersen, John; Kench, James; Daly, Roger J.; Horvath, Lisa G.; Stricker, Phillip; Frydenberg, Mark; Taylor, Renea A.; Stirzaker, Clare; Risbridger, Gail P.; Clark, Susan J.

    2018-01-01

    The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium and the surrounding microenvironment. To date, molecular profiling has largely been restricted to the epithelial component of tumors; therefore, features underpinning the persistent protumorigenic phenotype of the tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for the first time that cancer-associated fibroblasts (CAFs) from localized prostate cancer display remarkably distinct and enduring genome-wide changes in DNA methylation, significantly at enhancers and promoters, compared to nonmalignant prostate fibroblasts (NPFs). Differentially methylated regions associated with changes in gene expression have cancer-related functions and accurately distinguish CAFs from NPFs. Remarkably, a subset of changes is shared with prostate cancer epithelial cells, revealing the new concept of tumor-specific epigenome modifications in the tumor and its microenvironment. The distinct methylome of CAFs provides a novel epigenetic hallmark of the cancer microenvironment and promises new biomarkers to improve interpretation of diagnostic samples. PMID:29650553

  20. Dynamic Reciprocity in the Wound Microenvironment

    Science.gov (United States)

    Schultz, Gregory S.; Davidson, Jeffrey M.; Kirsner, Robert S.; Bornstein, Paul; Herman, Ira M.

    2011-01-01

    Here, we define dynamic reciprocity (DR) as an ongoing, bidirectional interaction amongst cells and their surrounding microenvironment. In the review, we posit that DR is especially meaningful during wound healing as the DR-driven biochemical, biophysical and cellular responses to injury play pivotal roles in regulating tissue regenerative responses. Such cell-extracellular matrix interactions not only guide and regulate cellular morphology, but cellular differentiation, migration, proliferation, and survival during tissue development, including e.g. embryogenesis, angiogenesis, as well as during pathologic processes including cancer diabetes, hypertension and chronic wound healing. Herein, we examine DR within the wound microenvironment while considering specific examples across acute and chronic wound healing. This review also considers how a number of hypotheses that attempt to explain chronic wound pathophysiology, which may be understood within the DR framework. The implications of applying the principles of dynamic reciprocity to optimize wound care practice and future development of innovative wound healing therapeutics are also briefly considered. PMID:21362080

  1. Immunological dysregulation in multiple myeloma microenvironment.

    Science.gov (United States)

    Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

    2014-01-01

    Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

  2. Immunological Dysregulation in Multiple Myeloma Microenvironment

    Directory of Open Access Journals (Sweden)

    Alessandra Romano

    2014-01-01

    Full Text Available Multiple Myeloma (MM is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC in bone marrow (BM. Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

  3. Bioinspired Hydrogels to Engineer Cancer Microenvironments.

    Science.gov (United States)

    Park, Kyung Min; Lewis, Daniel; Gerecht, Sharon

    2017-06-21

    Recent research has demonstrated that tumor microenvironments play pivotal roles in tumor development and metastasis through various physical, chemical, and biological factors, including extracellular matrix (ECM) composition, matrix remodeling, oxygen tension, pH, cytokines, and matrix stiffness. An emerging trend in cancer research involves the creation of engineered three-dimensional tumor models using bioinspired hydrogels that accurately recapitulate the native tumor microenvironment. With recent advances in materials engineering, many researchers are developing engineered tumor models, which are promising platforms for the study of cancer biology and for screening of therapeutic agents for better clinical outcomes. In this review, we discuss the development and use of polymeric hydrogel materials to engineer native tumor ECMs for cancer research, focusing on emerging technologies in cancer engineering that aim to accelerate clinical outcomes.

  4. Biomimetic strategies for the glioblastoma microenvironment

    Science.gov (United States)

    Cha, Junghwa; Kim, Pilnam

    2017-12-01

    Glioblastoma multiforme (GBM) is a devastating type of tumor with high mortality, caused by extensive infiltration into adjacent tissue and rapid recurrence. Most therapies for GBM have focused on the cytotoxicity, and have not targeted GBM spread. However, there have been numerous attempts to improve therapy by addressing GBM invasion, through understanding and mimicking its behavior using three-dimensional (3D) experimental models. Compared with two-dimensional models and in vivo animal models, 3D GBM models can capture the invasive motility of glioma cells within a 3D environment comprising many cellular and non-cellular components. Based on tissue engineering techniques, GBM invasion has been investigated within a biologically relevant environment, from biophysical and biochemical perspectives, to clarify the pro-invasive factors of GBM. This review discusses the recent progress in techniques for modeling the microenvironments of GBM tissue and suggests future directions with respect to recreating the GBM microenvironment and preclinical applications.

  5. Biological stoichiometry in tumor micro-environments.

    Directory of Open Access Journals (Sweden)

    Irina Kareva

    Full Text Available Tumors can be viewed as evolving ecological systems, in which heterogeneous populations of cancer cells compete with each other and somatic cells for space and nutrients within the ecosystem of the human body. According to the growth rate hypothesis (GRH, increased phosphorus availability in an ecosystem, such as the tumor micro-environment, may promote selection within the tumor for a more proliferative and thus potentially more malignant phenotype. The applicability of the GRH to tumor growth is evaluated using a mathematical model, which suggests that limiting phosphorus availability might promote intercellular competition within a tumor, and thereby delay disease progression. It is also shown that a tumor can respond differently to changes in its micro-environment depending on the initial distribution of clones within the tumor, regardless of its initial size. This suggests that composition of the tumor as a whole needs to be evaluated in order to maximize the efficacy of therapy.

  6. Interaction of tumor cells with the microenvironment

    Directory of Open Access Journals (Sweden)

    Lehnert Hendrik

    2011-09-01

    Full Text Available Abstract Recent advances in tumor biology have revealed that a detailed analysis of the complex interactions of tumor cells with their adjacent microenvironment (tumor stroma is mandatory in order to understand the various mechanisms involved in tumor growth and the development of metastasis. The mutual interactions between tumor cells and cellular and non-cellular components (extracellular matrix = ECM of the tumor microenvironment will eventually lead to a loss of tissue homeostasis and promote tumor development and progression. Thus, interactions of genetically altered tumor cells and the ECM on the one hand and reactive non-neoplastic cells on the other hand essentially control most aspects of tumorigenesis such as epithelial-mesenchymal-transition (EMT, migration, invasion (i.e. migration through connective tissue, metastasis formation, neovascularisation, apoptosis and chemotherapeutic drug resistance. In this mini-review we will focus on these issues that were recently raised by two review articles in CCS.

  7. Lysyl Oxidase and the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Tong-Hong Wang

    2016-12-01

    Full Text Available The lysyl oxidase (LOX family of oxidases contains a group of extracellular copper-dependent enzymes that catalyze the cross-linking of collagen and elastin by oxidation, thus maintaining the rigidity and structural stability of the extracellular matrix (ECM. Aberrant expression or activation of LOX alters the cellular microenvironment, leading to many diseases, including atherosclerosis, tissue fibrosis, and cancer. Recently, a number of studies have shown that LOX is overexpressed in most cancers and that it is involved in the regulation of tumor progression and metastasis. In contrast, a few reports have also indicated the tumor-suppressing role of LOX. In this short review, we discuss recent research on the correlations between LOX and cancer. Further, the role of LOX in tumor microenvironment remodeling, tumorigenesis, and metastasis and the underlying mechanisms have also been elucidated.

  8. Probing the tumor microenvironment: collection and induction

    Science.gov (United States)

    Williams, James K.; Padgen, Michael R.; Wang, Yarong; Entenberg, David; Gertler, Frank; Condeelis, John S.; Castracane, James

    2012-03-01

    The Nano Intravital Device, or NANIVID, is under development as an optically transparent, implantable tool to study the tumor microenvironment. Two etched glass substrates are sealed using a thin polymer membrane to create a reservoir with a single outlet. This reservoir is loaded with a hydrogel blend that contains growth factors or other chemicals to be delivered to the tumor microenvironment. When the device is implanted in the tumor, the hydrogel will swell and release these entrapped molecules, forming a gradient. Validation of the device has been performed in vitro using epidermal growth factor (EGF) and MenaINV, a highly invasive, rat mammary adenocarcinoma cell line. In both 2-D and 3-D environments, cells migrated toward the gradient of EGF released from the device. The chorioallantoic membrane (CAM) of White Leghorn chicken eggs is being utilized to grow xenograft tumors that will be used for ex vivo cell collection. Device optimization is being performed for in vivo use as a tool to collect the invasive cell population. Preliminary cell collection experiments in vivo were performed using a mouse model of breast cancer. As a second application, the device is being explored as a delivery vehicle for chemicals that induce controlled changes in the tumor microenvironment. H2O2 was loaded in the device and generated intracellular reactive oxygen species (ROS) in cells near the device outlet. In the future, other induction targets will be explored, including hypoglycemia and the manipulation of extracellular matrix stiffness.

  9. Revisiting Okun's Relationship

    NARCIS (Netherlands)

    Dixon, R.; Lim, G.C.; van Ours, Jan

    2016-01-01

    Our paper revisits Okun's relationship between observed unemployment rates and output gaps. We include in the relationship the effect of labour market institutions as well as age and gender effects. Our empirical analysis is based on 20 OECD countries over the period 1985-2013. We find that the

  10. Revisiting the Okun relationship

    NARCIS (Netherlands)

    Dixon, R. (Robert); Lim, G.C.; J.C. van Ours (Jan)

    2017-01-01

    textabstractOur article revisits the Okun relationship between observed unemployment rates and output gaps. We include in the relationship the effect of labour market institutions as well as age and gender effects. Our empirical analysis is based on 20 OECD countries over the period 1985–2013. We

  11. Bounded Intention Planning Revisited

    OpenAIRE

    Sievers Silvan; Wehrle Martin; Helmert Malte

    2014-01-01

    Bounded intention planning provides a pruning technique for optimal planning that has been proposed several years ago. In addition partial order reduction techniques based on stubborn sets have recently been investigated for this purpose. In this paper we revisit bounded intention planning in the view of stubborn sets.

  12. A Hydrostatic Paradox Revisited

    Science.gov (United States)

    Ganci, Salvatore

    2012-01-01

    This paper revisits a well-known hydrostatic paradox, observed when turning upside down a glass partially filled with water and covered with a sheet of light material. The phenomenon is studied in its most general form by including the mass of the cover. A historical survey of this experiment shows that a common misunderstanding of the phenomenon…

  13. The Faraday effect revisited

    DEFF Research Database (Denmark)

    Cornean, Horia; Nenciu, Gheorghe

    2009-01-01

    This paper is the second in a series revisiting the (effect of) Faraday rotation. We formulate and prove the thermodynamic limit for the transverse electric conductivity of Bloch electrons, as well as for the Verdet constant. The main mathematical tool is a regularized magnetic and geometric...

  14. Canary Islands

    Science.gov (United States)

    1992-01-01

    This easterly looking view shows the seven major volcanic islands of the Canary Island chain (28.0N, 16.5W) and offers a unique view of the islands that have become a frequent vacation spot for Europeans. The northwest coastline of Africa, (Morocco and Western Sahara), is visible in the background. Frequently, these islands create an impact on local weather (cloud formations) and ocean currents (island wakes) as seen in this photo.

  15. The Microenvironment in Gliomas: Phenotypic Expressions

    Directory of Open Access Journals (Sweden)

    Davide Schiffer

    2015-12-01

    Full Text Available The microenvironment of malignant gliomas is described according to its definition in the literature. Beside tumor cells, a series of stromal cells (microglia/macrophages, pericytes, fibroblasts, endothelial cells, normal and reactive astrocytes represents the cell component, whereas a complex network of molecular signaling represents the functional component. Its most evident expressions are perivascular and perinecrotic niches that are believed to be the site of tumor stem cells or progenitors in the tumor. Phenotypically, both niches are not easily recognizable; here, they are described together with a critical revision of their concept. As for perinecrotic niches, an alternative interpretation is given about their origin that regards the tumor stem cells as the residue of those that populated hyperproliferating areas in which necroses develop. This is based on the concept that the stem-like is a status and not a cell type, depending on the microenvironment that regulates a conversion of tumor non-stem cells and tumor stem cells through a cell reprogramming.

  16. 'Felson Signs' revisited

    International Nuclear Information System (INIS)

    George, Phiji P.; Irodi, Aparna; Keshava, Shyamkumar N.; Lamont, Anthony C.

    2014-01-01

    In this article we revisit, with the help of images, those classic signs in chest radiography described by Dr Benjamin Felson himself, or other illustrious radiologists of his time, cited and discussed in 'Chest Roentgenology'. We briefly describe the causes of the signs, their utility and the differential diagnosis to be considered when each sign is seen. Wherever possible, we use CT images to illustrate the basis of some of these classic radiographic signs.

  17. Time functions revisited

    Science.gov (United States)

    Fathi, Albert

    2015-07-01

    In this paper we revisit our joint work with Antonio Siconolfi on time functions. We will give a brief introduction to the subject. We will then show how to construct a Lipschitz time function in a simplified setting. We will end with a new result showing that the Aubry set is not an artifact of our proof of existence of time functions for stably causal manifolds.

  18. Seven Issues, Revisited

    OpenAIRE

    Whitehead, Jim; De Bra, Paul; Grønbæk, Kaj; Larsen, Deena; Legget, John; schraefel, monica m.c.

    2002-01-01

    It has been 15 years since the original presentation by Frank Halasz at Hypertext'87 on seven issues for the next generation of hypertext systems. These issues are: Search and Query Composites Virtual Structures Computation in/over hypertext network Versioning Collaborative Work Extensibility and Tailorability Since that time, these issues have formed the nucleus of multiple research agendas within the Hypertext community. Befitting this direction-setting role, the issues have been revisited ...

  19. Deterministic Graphical Games Revisited

    DEFF Research Database (Denmark)

    Andersson, Daniel; Hansen, Kristoffer Arnsfelt; Miltersen, Peter Bro

    2008-01-01

    We revisit the deterministic graphical games of Washburn. A deterministic graphical game can be described as a simple stochastic game (a notion due to Anne Condon), except that we allow arbitrary real payoffs but disallow moves of chance. We study the complexity of solving deterministic graphical...... games and obtain an almost-linear time comparison-based algorithm for computing an equilibrium of such a game. The existence of a linear time comparison-based algorithm remains an open problem....

  20. Vestindien Revisited: I kølvandet på kuldampere og cruiseturister

    DEFF Research Database (Denmark)

    Brichet, Nathalia Sofie; Hastrup, Frida; Ørstedholm, Maroe

    2017-01-01

    What traces did Denmark officially leave behind when the West Indies were sold to the United States in 1917? And how are the islands still affected today by Denmark’s presence on the islands? The M/S Maritime Museum tries to answer these questions in its special new exhibition, ‘U.S. VIRGIN ISLAN...... special exhibition “U.S. VIRGIN ISLANDS REVISITED – in the wake of colliers and cruise tourists,” to commemorate the centennial anniversary of selling the West Indies to the United States of America....

  1. Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

    Science.gov (United States)

    Cruz-Monserrate, Zobeida; Roland, Christina L.; Deng, Defeng; Arumugam, Thiruvengadam; Moshnikova, Anna; Andreev, Oleg A.; Reshetnyak, Yana K.; Logsdon, Craig D.

    2014-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.

  2. Decreased decorin expression in the tumor microenvironment

    International Nuclear Information System (INIS)

    Bozoky, Benedek; Savchenko, Andrii; Guven, Hayrettin; Ponten, Fredrik; Klein, George; Szekely, Laszlo

    2014-01-01

    Decorin is a small leucine-rich proteoglycan, synthesized and deposited by fibroblasts in the stroma where it binds to collagen I. It sequesters several growth factors and antagonizes numerous members of the receptor tyrosine kinase family. In experimental murine systems, it acted as a potent tumor suppressor. Examining the Human Protein Atlas online database of immunostained tissue samples we have surveyed decorin expression in silico in several different tumor types, comparing them with corresponding normal tissues. We found that decorin is abundantly secreted and deposited in normal connective tissue but its expression is consistently decreased in the tumor microenvironment. We developed a software to quantitate the difference in expression. The presence of two closely related proteoglycans in the newly formed tumor stroma indicated that the decreased decorin expression was not caused by the delay in proteoglycan deposition in the newly formed connective tissue surrounding the tumor

  3. Of Microenvironments and Mammary Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  4. Plasticity of the Muscle Stem Cell Microenvironment.

    Science.gov (United States)

    Dinulovic, Ivana; Furrer, Regula; Handschin, Christoph

    2017-01-01

    Satellite cells (SCs) are adult muscle stem cells capable of repairing damaged and creating new muscle tissue throughout life. Their functionality is tightly controlled by a microenvironment composed of a wide variety of factors, such as numerous secreted molecules and different cell types, including blood vessels, oxygen, hormones, motor neurons, immune cells, cytokines, fibroblasts, growth factors, myofibers, myofiber metabolism, the extracellular matrix and tissue stiffness. This complex niche controls SC biology-quiescence, activation, proliferation, differentiation or renewal and return to quiescence. In this review, we attempt to give a brief overview of the most important players in the niche and their mutual interaction with SCs. We address the importance of the niche to SC behavior under physiological and pathological conditions, and finally survey the significance of an artificial niche both for basic and translational research purposes.

  5. Sensitivity of Dendritic Cells to Microenvironment Signals

    Directory of Open Access Journals (Sweden)

    Juliana Maria Motta

    2016-01-01

    Full Text Available Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies.

  6. Mounting Pressure in the Microenvironment: Fluids, Solids, and Cells in Pancreatic Ductal Adenocarcinoma.

    Science.gov (United States)

    DuFort, Christopher C; DelGiorno, Kathleen E; Hingorani, Sunil R

    2016-06-01

    The microenvironment influences the pathogenesis of solid tumors and plays an outsized role in some. Our understanding of the stromal response to cancers, particularly pancreatic ductal adenocarcinoma, has evolved from that of host defense to tumor offense. We know that most, although not all, of the factors and processes in the microenvironment support tumor epithelial cells. This reappraisal of the roles of stromal elements has also revealed potential vulnerabilities and therapeutic opportunities to exploit. The high concentration in the stroma of the glycosaminoglycan hyaluronan, together with the large gel-fluid phase and pressures it generates, were recently identified as primary sources of treatment resistance in pancreas cancer. Whereas the relatively minor role of free interstitial fluid in the fluid mechanics and perfusion of tumors has been long appreciated, the less mobile, gel-fluid phase has been largely ignored for historical and technical reasons. The inability of classic methods of fluid pressure measurement to capture the gel-fluid phase, together with a dependence on xenograft and allograft systems that inaccurately model tumor vascular biology, has led to an undue emphasis on the role of free fluid in impeding perfusion and drug delivery and an almost complete oversight of the predominant role of the gel-fluid phase. We propose that a hyaluronan-rich, relatively immobile gel-fluid phase induces vascular collapse and hypoperfusion as a primary mechanism of treatment resistance in pancreas cancers. Similar properties may be operant in other solid tumors as well, so revisiting and characterizing fluid mechanics with modern techniques in other autochthonous cancers may be warranted. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. [Prostate cancer microenvironment: Its structure, functions and therapeutic applications].

    Science.gov (United States)

    Lorion, R; Bladou, F; Spatz, A; van Kempen, L; Irani, J

    2016-06-01

    In the field of prostate cancer there is a growing tendency for more and more studies to emphasise the predominant role of the zone situated between the tumour and the host: the tumour microenvironment. The aim of this article is to describe the structure and the functions of the prostate cancer microenvironment as well as the principal treatments that are being applied to it. PubMed and ScienceDirect databases have been interrogated using the association of keywords "tumour microenvironment" and "neoplasm therapy" along with "microenvironnement tumoral" and "traitements". Of the 593 articles initially found, 50 were finally included. The tumour microenvironment principally includes host elements that are diverted from their primary functions and encourage the development of the tumour. In it we find immunity cells, support tissue as well as vascular and lymphatic neovascularization. Highlighting the major role played by this microenvironment has led to the development of specific treatments, notably antiangiogenic therapy and immunotherapy. The tumour microenvironment, the tumour and the host influence themselves mutually and create a variable situation over time. Improvement of the knowledge of the prostate cancer microenvironment gradually enables us to pass from an approach centred on the tumour to a broader approach to the whole tumoral ecosystem. This enabled the emergence of new treatments whose place in the therapeutic arsenal still need to be found. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Deterministic Graphical Games Revisited

    DEFF Research Database (Denmark)

    Andersson, Klas Olof Daniel; Hansen, Kristoffer Arnsfelt; Miltersen, Peter Bro

    2012-01-01

    Starting from Zermelo’s classical formal treatment of chess, we trace through history the analysis of two-player win/lose/draw games with perfect information and potentially infinite play. Such chess-like games have appeared in many different research communities, and methods for solving them......, such as retrograde analysis, have been rediscovered independently. We then revisit Washburn’s deterministic graphical games (DGGs), a natural generalization of chess-like games to arbitrary zero-sum payoffs. We study the complexity of solving DGGs and obtain an almost-linear time comparison-based algorithm...

  9. Bottomonium spectrum revisited

    CERN Document Server

    Segovia, Jorge; Entem, David R.; Fernández, Francisco

    2016-01-01

    We revisit the bottomonium spectrum motivated by the recently exciting experimental progress in the observation of new bottomonium states, both conventional and unconventional. Our framework is a nonrelativistic constituent quark model which has been applied to a wide range of hadronic observables from the light to the heavy quark sector and thus the model parameters are completely constrained. Beyond the spectrum, we provide a large number of electromagnetic, strong and hadronic decays in order to discuss the quark content of the bottomonium states and give more insights about the better way to determine their properties experimentally.

  10. Metamorphosis in Craniiformea revisited

    DEFF Research Database (Denmark)

    Altenburger, Andreas; Wanninger, Andreas; Holmer, Lars E.

    2013-01-01

    We revisited the brachiopod fold hypothesis and investigated metamorphosis in the craniiform brachiopod Novocrania anomala. Larval development is lecithotrophic and the dorsal (brachial) valve is secreted by dorsal epithelia. We found that the juvenile ventral valve, which consists only of a thin...... brachiopods during metamorphosis to cement their pedicle to the substrate. N. anomala is therefore not initially attached by a valve but by material corresponding to pedicle cuticle. This is different to previous descriptions, which had led to speculations about a folding event in the evolution of Brachiopoda...

  11. Saint Lucia revisited.

    Science.gov (United States)

    Bos, R; Février, M; Knudsen, A B

    1988-10-01

    The eastern Caribbean island of Saint Lucia is now famous in parasitological history as the setting for a major programme of schistosomiasis control'. Perhaps less well-known are the island's effective control of many intestinal parasites, and elimination of malaria, such that the current patterns of mortality and other demographic indicators now resemble those of industrialized countries. More recently, the island has become the focus for another community-based health programme as the Caribbean region again comes to grips with Aedes aegypti and its recently imported relative, Aedes albopictus, important vectors of yellow fever and dengue viruses (see Box 1).

  12. Innate lymphoid cells and their stromal microenvironments.

    Science.gov (United States)

    Kellermayer, Zoltán; Vojkovics, Dóra; Balogh, Péter

    2017-09-01

    In addition to the interaction between antigen presenting cells, T and B lymphocytes, recent studies have revealed important roles for a diverse set of auxiliary cells that profoundly influence the induction and regulation of immune responses against pathogens. Of these the stromal cells composed of various non-hematopoietic constituents are crucial for the creation and maintenance of specialized semi-static three-dimensional lymphoid tissue microenvironment, whereas the more recently described innate lymphoid cells are generated by the diversification of committed lymphoid precursor cells independently from clonally rearranged antigen receptor genes. Recent findings have revealed important contributions by innate lymphoid cells in inflammation and protection against pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also influence the onset of immune responses in tissue-specific fashion, raising the possibility of tissue-specific stromal - innate lymphoid cell collaboration. In this review we summarize the main features and interactions between these two cells types, with particular emphasis on ILC type 3 cells and their microenvironmental partners. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  13. Revisiting Nursing Research in Nigeria

    African Journals Online (AJOL)

    2016-08-18

    Aug 18, 2016 ... health care research, it is therefore pertinent to revisit the state of nursing research in the country. .... platforms, updated libraries with electronic resource ... benchmarks for developing countries of 26%, [17] the amount is still ...

  14. Microenvironment-Centred Dynamics in Aggressive B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Matilde Cacciatore

    2012-01-01

    Full Text Available Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas.

  15. Dry Eye Management: Targeting the Ocular Surface Microenvironment.

    Science.gov (United States)

    Zhang, Xiaobo; M, Vimalin Jeyalatha; Qu, Yangluowa; He, Xin; Ou, Shangkun; Bu, Jinghua; Jia, Changkai; Wang, Junqi; Wu, Han; Liu, Zuguo; Li, Wei

    2017-06-29

    Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment.

  16. Dry Eye Management: Targeting the Ocular Surface Microenvironment

    Science.gov (United States)

    Zhang, Xiaobo; Jeyalatha M, Vimalin; Qu, Yangluowa; He, Xin; Ou, Shangkun; Bu, Jinghua; Jia, Changkai; Wang, Junqi; Wu, Han; Liu, Zuguo

    2017-01-01

    Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment. PMID:28661456

  17. Tumor microenvironment indoctrination: an emerging hallmark of cancer.

    Science.gov (United States)

    Goetz, Jacky G

    2012-01-01

    Nastiness of cancer does not only reside in the corruption of cancer cells by genetic aberrations that drive their sustained proliferative power--the roots of malignancy--but also in its aptitude to reciprocally sculpt its surrounding environment and cellular stromal ecosystem, in such a way that the corrupted tumor microenvironment becomes a full pro-tumorigenic entity. Such a contribution had been appreciated three decades ago already, with the discovery of tumor angiogenesis and extracellular matrix remodeling. Nevertheless, the recent emergence of the tumor microenvironment as the critical determinant in cancer biology is paralleled by the promising therapeutic potential it carries, opening alternate routes to fight cancer. The study of the tumor microenvironment recruited numerous lead-scientists over the years, with distinct perspectives, and some of them have kindly accepted to contribute to the elaboration of this special issue entitled Tumor microenvironment indoctrination: An emerging hallmark of cancer.

  18. Impact of the ovarian microenvironment on serous cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-14-1-0182 TITLE: Impact of the ovarian microenvironment on serous cancer PRINCIPAL INVESTIGATOR: Joanna E. Burdette...Impact of the ovarian microenvironment on serous cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0182 5c. PROGRAM ELEMENT NUMBER 6...for intervention that would block serous cancer while still confined to the fallopian tubes. Using a series of normal, modified, and tumorigenic tubal

  19. Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

    Science.gov (United States)

    2016-09-01

    regulators of branching morphogenesis during mammary gland development 17,18, arguing that normal mammary epithelial cells cooperate with these innate ...CD45+CD11b+F4/80+ cells lacking lymphoid and granulocytic markers (Supplementary Fig.3B). viSNE plots 30 of myelo- monocytic cells (Fig.5A) showed that...cancer cells and how the microenvironment in these primary sites named P-TMEM (Primary Tumor Microenvironment of Metastases) contribute to early

  20. Marshall Islands

    OpenAIRE

    World Bank

    2015-01-01

    This note aims to build understanding of the existing disaster risk financing and insurance (DRFI) tools in use in The Marshall Islands and to identify gaps where potential engagement could further develop financial resilience. The likelihood that a hazardous event will have a significant impact on the Marshall Islands has risen with the increasing levels of population and assets in the urban ...

  1. The inflammatory microenvironment in colorectal neoplasia.

    Science.gov (United States)

    McLean, Mairi H; Murray, Graeme I; Stewart, Keith N; Norrie, Gillian; Mayer, Claus; Hold, Georgina L; Thomson, John; Fyfe, Nicky; Hope, Mairi; Mowat, N Ashley G; Drew, Janice E; El-Omar, Emad M

    2011-01-07

    Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. Inflammatory activity within the stroma of invasive colorectal tumours is known to be a key predictor of disease activity with type, density and location of immune cells impacting on patient prognosis. To date, there has been no report of inflammatory phenotype within pre-malignant human colonic adenomas. Assessing the stromal microenvironment and particularly, inflammatory activity within colorectal neoplastic lesions is central to understanding early colorectal carcinogenesis. Inflammatory cell infiltrate was assessed by immunohistochemistry in paired colonic adenoma and adjacent normal colonic mucosa samples, and adenomas exhibiting increasing degrees of epithelial cell dysplasia. Macrophage phenotype was assessed using double stain immunohistochemistry incorporating expression of an intracellular enzyme of function. A targeted array of inflammatory cytokine and receptor genes, validated by RT-PCR, was used to assess inflammatory gene expression. Inflammatory cell infiltrates are a key feature of sporadic adenomatous colonic polyps with increased macrophage, neutrophil and T cell (specifically helper and activated subsets) infiltration in adenomatous colonic polyps, that increases in association with characteristics of high malignant potential, namely, increasing degree of cell dysplasia and adenoma size. Macrophages within adenomas express iNOS, suggestive of a pro-inflammatory phenotype. Several inflammatory cytokine genes (CXCL1, CXCL2, CXCL3, CCL20, IL8, CCL23, CCL19, CCL21, CCL5) are dysregulated in adenomas. This study has provided evidence of increased inflammation within pre-malignant colonic adenomas. This may allow potential mechanistic pathways in the initiation and promotion of early colorectal carcinogenesis to be identified.

  2. The Inflammatory Microenvironment in Colorectal Neoplasia

    Science.gov (United States)

    McLean, Mairi H.; Murray, Graeme I.; Stewart, Keith N.; Norrie, Gillian; Mayer, Claus; Hold, Georgina L.; Thomson, John; Fyfe, Nicky; Hope, Mairi; Mowat, N. Ashley G.; Drew, Janice E.; El-Omar, Emad M.

    2011-01-01

    Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. Inflammatory activity within the stroma of invasive colorectal tumours is known to be a key predictor of disease activity with type, density and location of immune cells impacting on patient prognosis. To date, there has been no report of inflammatory phenotype within pre-malignant human colonic adenomas. Assessing the stromal microenvironment and particularly, inflammatory activity within colorectal neoplastic lesions is central to understanding early colorectal carcinogenesis. Inflammatory cell infiltrate was assessed by immunohistochemistry in paired colonic adenoma and adjacent normal colonic mucosa samples, and adenomas exhibiting increasing degrees of epithelial cell dysplasia. Macrophage phenotype was assessed using double stain immunohistochemistry incorporating expression of an intracellular enzyme of function. A targeted array of inflammatory cytokine and receptor genes, validated by RT-PCR, was used to assess inflammatory gene expression. Inflammatory cell infiltrates are a key feature of sporadic adenomatous colonic polyps with increased macrophage, neutrophil and T cell (specifically helper and activated subsets) infiltration in adenomatous colonic polyps, that increases in association with characteristics of high malignant potential, namely, increasing degree of cell dysplasia and adenoma size. Macrophages within adenomas express iNOS, suggestive of a pro-inflammatory phenotype. Several inflammatory cytokine genes (CXCL1, CXCL2, CXCL3, CCL20, IL8, CCL23, CCL19, CCL21, CCL5) are dysregulated in adenomas. This study has provided evidence of increased inflammation within pre-malignant colonic adenomas. This may allow potential mechanistic pathways in the initiation and promotion of early colorectal carcinogenesis to be identified. PMID:21249124

  3. The inflammatory microenvironment in colorectal neoplasia.

    Directory of Open Access Journals (Sweden)

    Mairi H McLean

    Full Text Available Colorectal cancer (CRC is a major cause of mortality and morbidity worldwide. Inflammatory activity within the stroma of invasive colorectal tumours is known to be a key predictor of disease activity with type, density and location of immune cells impacting on patient prognosis. To date, there has been no report of inflammatory phenotype within pre-malignant human colonic adenomas. Assessing the stromal microenvironment and particularly, inflammatory activity within colorectal neoplastic lesions is central to understanding early colorectal carcinogenesis. Inflammatory cell infiltrate was assessed by immunohistochemistry in paired colonic adenoma and adjacent normal colonic mucosa samples, and adenomas exhibiting increasing degrees of epithelial cell dysplasia. Macrophage phenotype was assessed using double stain immunohistochemistry incorporating expression of an intracellular enzyme of function. A targeted array of inflammatory cytokine and receptor genes, validated by RT-PCR, was used to assess inflammatory gene expression. Inflammatory cell infiltrates are a key feature of sporadic adenomatous colonic polyps with increased macrophage, neutrophil and T cell (specifically helper and activated subsets infiltration in adenomatous colonic polyps, that increases in association with characteristics of high malignant potential, namely, increasing degree of cell dysplasia and adenoma size. Macrophages within adenomas express iNOS, suggestive of a pro-inflammatory phenotype. Several inflammatory cytokine genes (CXCL1, CXCL2, CXCL3, CCL20, IL8, CCL23, CCL19, CCL21, CCL5 are dysregulated in adenomas. This study has provided evidence of increased inflammation within pre-malignant colonic adenomas. This may allow potential mechanistic pathways in the initiation and promotion of early colorectal carcinogenesis to be identified.

  4. Life quality index revisited

    DEFF Research Database (Denmark)

    Ditlevsen, Ove Dalager

    2004-01-01

    The derivation of the life quality index (LQI) is revisited for a revision. This revision takes into account the unpaid but necessary work time needed to stay alive in clean and healthy conditions to be fit for effective wealth producing work and to enjoyable free time. Dimension analysis...... at birth should not vary between countries. Finally the distributional assumptions are relaxed as compared to the assumptions made in an earlier work by the author. These assumptions concern the calculation of the life expectancy change due to the removal of an accident source. Moreover a simple public...... consistency problems with the standard power function expression of the LQI are pointed out. It is emphasized that the combination coefficient in the convex differential combination between the relative differential of the gross domestic product per capita and the relative differential of the expected life...

  5. Quantum duel revisited

    International Nuclear Information System (INIS)

    Schmidt, Alexandre G M; Paiva, Milena M

    2012-01-01

    We revisit the quantum two-person duel. In this problem, both Alice and Bob each possess a spin-1/2 particle which models dead and alive states for each player. We review the Abbott and Flitney result—now considering non-zero α 1 and α 2 in order to decide if it is better for Alice to shoot or not the second time—and we also consider a duel where players do not necessarily start alive. This simple assumption allows us to explore several interesting special cases, namely how a dead player can win the duel shooting just once, or how can Bob revive Alice after one shot, and the better strategy for Alice—being either alive or in a superposition of alive and dead states—fighting a dead opponent. (paper)

  6. Satellite failures revisited

    Science.gov (United States)

    Balcerak, Ernie

    2012-12-01

    In January 1994, the two geostationary satellites known as Anik-E1 and Anik-E2, operated by Telesat Canada, failed one after the other within 9 hours, leaving many northern Canadian communities without television and data services. The outage, which shut down much of the country's broadcast television for hours and cost Telesat Canada more than $15 million, generated significant media attention. Lam et al. used publicly available records to revisit the event; they looked at failure details, media coverage, recovery effort, and cost. They also used satellite and ground data to determine the precise causes of those satellite failures. The researchers traced the entire space weather event from conditions on the Sun through the interplanetary medium to the particle environment in geostationary orbit.

  7. Logistics Innovation Process Revisited

    DEFF Research Database (Denmark)

    Gammelgaard, Britta; Su, Shong-Iee Ivan; Yang, Su-Lan

    2011-01-01

    Purpose – The purpose of this paper is to learn more about logistics innovation processes and their implications for the focal organization as well as the supply chain, especially suppliers. Design/methodology/approach – The empirical basis of the study is a longitudinal action research project...... that was triggered by the practical needs of new ways of handling material flows of a hospital. This approach made it possible to revisit theory on logistics innovation process. Findings – Apart from the tangible benefits reported to the case hospital, five findings can be extracted from this study: the logistics...... innovation process model may include not just customers but also suppliers; logistics innovation in buyer-supplier relations may serve as an alternative to outsourcing; logistics innovation processes are dynamic and may improve supplier partnerships; logistics innovations in the supply chain are as dependent...

  8. Klein's double discontinuity revisited

    DEFF Research Database (Denmark)

    Winsløw, Carl; Grønbæk, Niels

    2014-01-01

    Much effort and research has been invested into understanding and bridging the ‘gaps’ which many students experience in terms of contents and expectations as they begin university studies with a heavy component of mathematics, typically in the form of calculus courses. We have several studies...... of bridging measures, success rates and many other aspects of these “entrance transition” problems. In this paper, we consider the inverse transition, experienced by university students as they revisit core parts of high school mathematics (in particular, calculus) after completing the undergraduate...... mathematics courses which are mandatory to become a high school teacher of mathematics. To what extent does the “advanced” experience enable them to approach the high school calculus in a deeper and more autonomous way ? To what extent can “capstone” courses support such an approach ? How could it be hindered...

  9. Reframing in dentistry: Revisited

    Directory of Open Access Journals (Sweden)

    Sivakumar Nuvvula

    2013-01-01

    Full Text Available The successful practice of dentistry involves a good combination of technical skills and soft skills. Soft skills or communication skills are not taught extensively in dental schools and it can be challenging to learn and at times in treating dental patients. Guiding the child′s behavior in the dental operatory is one of the preliminary steps to be taken by the pediatric dentist and one who can successfully modify the behavior can definitely pave the way for a life time comprehensive oral care. This article is an attempt to revisit a simple behavior guidance technique, reframing and explain the possible psychological perspectives behind it for better use in the clinical practice.

  10. Multiparametric classification links tumor microenvironments with tumor cell phenotype.

    Directory of Open Access Journals (Sweden)

    Bojana Gligorijevic

    2014-11-01

    Full Text Available While it has been established that a number of microenvironment components can affect the likelihood of metastasis, the link between microenvironment and tumor cell phenotypes is poorly understood. Here we have examined microenvironment control over two different tumor cell motility phenotypes required for metastasis. By high-resolution multiphoton microscopy of mammary carcinoma in mice, we detected two phenotypes of motile tumor cells, different in locomotion speed. Only slower tumor cells exhibited protrusions with molecular, morphological, and functional characteristics associated with invadopodia. Each region in the primary tumor exhibited either fast- or slow-locomotion. To understand how the tumor microenvironment controls invadopodium formation and tumor cell locomotion, we systematically analyzed components of the microenvironment previously associated with cell invasion and migration. No single microenvironmental property was able to predict the locations of tumor cell phenotypes in the tumor if used in isolation or combined linearly. To solve this, we utilized the support vector machine (SVM algorithm to classify phenotypes in a nonlinear fashion. This approach identified conditions that promoted either motility phenotype. We then demonstrated that varying one of the conditions may change tumor cell behavior only in a context-dependent manner. In addition, to establish the link between phenotypes and cell fates, we photoconverted and monitored the fate of tumor cells in different microenvironments, finding that only tumor cells in the invadopodium-rich microenvironments degraded extracellular matrix (ECM and disseminated. The number of invadopodia positively correlated with degradation, while the inhibiting metalloproteases eliminated degradation and lung metastasis, consistent with a direct link among invadopodia, ECM degradation, and metastasis. We have detected and characterized two phenotypes of motile tumor cells in vivo, which

  11. Royal Society Scientific Meeting: Extracellular vesicles in the tumour microenvironment.

    Science.gov (United States)

    Pink, Ryan Charles; Elmusrati, Areeg A; Lambert, Daniel; Carter, David Raul Francisco

    2018-01-05

    Cancer cells do not grow as an isolated homogeneous mass; tumours are, in fact, complex and heterogeneous collections of cancer and surrounding stromal cells, collectively termed the tumour microenvironment. The interaction between cancer cells and stromal cells in the tumour microenvironment has emerged as a key concept in the regulation of cancer progression. Understanding the intercellular dialogue in the tumour microenvironment is therefore an important goal. One aspect of this dialogue that has not been appreciated until recently is the role of extracellular vesicles (EVs). EVs are small vesicles released by cells under both normal and pathological conditions; they can transfer biological molecules between cells leading to changes in phenotype. EVs have emerged as important regulators of biological processes and can be dysregulated in diseases such as cancer; rapidly growing interest in their biology and therapeutic potential led to the Royal Society hosting a Scientific Meeting to explore the roles of EVs in the tumour microenvironment. This cross-disciplinary meeting explored examples of how aberrant crosstalk between tumour and stromal cells can promote cancer progression, and how such signalling can be targeted for diagnostic, prognostic and therapeutic benefit. In this review, and the special edition of Philosophical Transactions of the Royal Society B that follows, we will provide an overview of the content and outcomes of this exciting meeting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'. © 2017 The Author(s).

  12. Multimodal imaging of lung cancer and its microenvironment (Conference Presentation)

    Science.gov (United States)

    Hariri, Lida P.; Niederst, Matthew J.; Mulvey, Hillary; Adams, David C.; Hu, Haichuan; Chico Calero, Isabel; Szabari, Margit V.; Vakoc, Benjamin J.; Hasan, Tayyaba; Bouma, Brett E.; Engelman, Jeffrey A.; Suter, Melissa J.

    2016-03-01

    Despite significant advances in targeted therapies for lung cancer, nearly all patients develop drug resistance within 6-12 months and prognosis remains poor. Developing drug resistance is a progressive process that involves tumor cells and their microenvironment. We hypothesize that microenvironment factors alter tumor growth and response to targeted therapy. We conducted in vitro studies in human EGFR-mutant lung carcinoma cells, and demonstrated that factors secreted from lung fibroblasts results in increased tumor cell survival during targeted therapy with EGFR inhibitor, gefitinib. We also demonstrated that increased environment stiffness results in increased tumor survival during gefitinib therapy. In order to test our hypothesis in vivo, we developed a multimodal optical imaging protocol for preclinical intravital imaging in mouse models to assess tumor and its microenvironment over time. We have successfully conducted multimodal imaging of dorsal skinfold chamber (DSC) window mice implanted with GFP-labeled human EGFR mutant lung carcinoma cells and visualized changes in tumor development and microenvironment facets over time. Multimodal imaging included structural OCT to assess tumor viability and necrosis, polarization-sensitive OCT to measure tissue birefringence for collagen/fibroblast detection, and Doppler OCT to assess tumor vasculature. Confocal imaging was also performed for high-resolution visualization of EGFR-mutant lung cancer cells labeled with GFP, and was coregistered with OCT. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging is a useful tool to assess tumor and its microenvironment over time.

  13. Cellular immobilization within microfluidic microenvironments: dielectrophoresis with polyelectrolyte multilayers.

    Science.gov (United States)

    Forry, Samuel P; Reyes, Darwin R; Gaitan, Michael; Locascio, Laurie E

    2006-10-25

    The development of biomimetic microenvironments will improve cell culture techniques by enabling in vitro cell cultures that mimic in vivo behavior; however, experimental control over attachment, cellular position, or intercellular distances within such microenvironments remains challenging. We report here the rapid and controllable immobilization of suspended mammalian cells within microfabricated environments using a combination of electronic (dielectrophoresis, DEP) and chemical (polyelectrolyte multilayers, PEMS) forces. While cellular position within the microsystem is rapidly patterned via intermittent DEP trapping, persistent adhesion after removal of electronic forces is enabled by surface treatment with PEMS that are amenable to cellular attachment. In contrast to DEP trapping alone, persistent adhesion enables the soluble microenvironment to be systematically varied, facilitating the use of soluble probes of cell state and enabling cellular characterization in response to various soluble stimuli.

  14. Engineering Breast Cancer Microenvironments and 3D Bioprinting

    Directory of Open Access Journals (Sweden)

    Jorge A. Belgodere

    2018-05-01

    Full Text Available The extracellular matrix (ECM is a critical cue to direct tumorigenesis and metastasis. Although two-dimensional (2D culture models have been widely employed to understand breast cancer microenvironments over the past several decades, the 2D models still exhibit limited success. Overwhelming evidence supports that three dimensional (3D, physiologically relevant culture models are required to better understand cancer progression and develop more effective treatment. Such platforms should include cancer-specific architectures, relevant physicochemical signals, stromal–cancer cell interactions, immune components, vascular components, and cell-ECM interactions found in patient tumors. This review briefly summarizes how cancer microenvironments (stromal component, cell-ECM interactions, and molecular modulators are defined and what emerging technologies (perfusable scaffold, tumor stiffness, supporting cells within tumors and complex patterning can be utilized to better mimic native-like breast cancer microenvironments. Furthermore, this review emphasizes biophysical properties that differ between primary tumor ECM and tissue sites of metastatic lesions with a focus on matrix modulation of cancer stem cells, providing a rationale for investigation of underexplored ECM proteins that could alter patient prognosis. To engineer breast cancer microenvironments, we categorized technologies into two groups: (1 biochemical factors modulating breast cancer cell-ECM interactions and (2 3D bioprinting methods and its applications to model breast cancer microenvironments. Biochemical factors include matrix-associated proteins, soluble factors, ECMs, and synthetic biomaterials. For the application of 3D bioprinting, we discuss the transition of 2D patterning to 3D scaffolding with various bioprinting technologies to implement biophysical cues to model breast cancer microenvironments.

  15. Roles of stromal microenvironment in colon cancer progression.

    Science.gov (United States)

    Taketo, Makoto Mark

    2012-05-01

    Although our understanding of epithelial cancer cells has advanced significantly, our understanding of the cancer microenvironment is still fragmentary. In contrast to our intuitive impression that our body always suppresses cancer growth, recent pieces of evidence show that cancer often exploits our body reactions to expand, invade local tissues and metastasize to distant organs. Accordingly, investigations of such body reactions in the tumour microenvironment should help us to design novel therapeutic strategies that can be combined with the traditional therapeutics targeted at the cancer cells themselves. In this article, I am going to review our recent efforts in search of novel therapeutic strategies against colon cancer using mouse models.

  16. The critical catastrophe revisited

    International Nuclear Information System (INIS)

    De Mulatier, Clélia; Rosso, Alberto; Dumonteil, Eric; Zoia, Andrea

    2015-01-01

    The neutron population in a prototype model of nuclear reactor can be described in terms of a collection of particles confined in a box and undergoing three key random mechanisms: diffusion, reproduction due to fissions, and death due to absorption events. When the reactor is operated at the critical point, and fissions are exactly compensated by absorptions, the whole neutron population might in principle go to extinction because of the wild fluctuations induced by births and deaths. This phenomenon, which has been named critical catastrophe, is nonetheless never observed in practice: feedback mechanisms acting on the total population, such as human intervention, have a stabilizing effect. In this work, we revisit the critical catastrophe by investigating the spatial behaviour of the fluctuations in a confined geometry. When the system is free to evolve, the neutrons may display a wild patchiness (clustering). On the contrary, imposing a population control on the total population acts also against the local fluctuations, and may thus inhibit the spatial clustering. The effectiveness of population control in quenching spatial fluctuations will be shown to depend on the competition between the mixing time of the neutrons (i.e. the average time taken for a particle to explore the finite viable space) and the extinction time

  17. Magnetic moments revisited

    International Nuclear Information System (INIS)

    Towner, I.S.; Khanna, F.C.

    1984-01-01

    Consideration of core polarization, isobar currents and meson-exchange processes gives a satisfactory understanding of the ground-state magnetic moments in closed-shell-plus (or minus)-one nuclei, A = 3, 15, 17, 39 and 41. Ever since the earliest days of the nuclear shell model the understanding of magnetic moments of nuclear states of supposedly simple configurations, such as doubly closed LS shells +-1 nucleon, has been a challenge for theorists. The experimental moments, which in most cases are known with extraordinary precision, show a small yet significant departure from the single-particle Schmidt values. The departure, however, is difficult to evaluate precisely since, as will be seen, it results from a sensitive cancellation between several competing corrections each of which can be as large as the observed discrepancy. This, then, is the continuing fascination of magnetic moments. In this contribution, we revisit the subjet principally to identify the role played by isobar currents, which are of much concern at this conference. But in so doing we warn quite strongly of the dangers of considering just isobar currents in isolation; equal consideration must be given to competing processes which in this context are the mundane nuclear structure effects, such as core polarization, and the more popular meson-exchange currents

  18. Lorentz violation naturalness revisited

    Energy Technology Data Exchange (ETDEWEB)

    Belenchia, Alessio; Gambassi, Andrea; Liberati, Stefano [SISSA - International School for Advanced Studies, via Bonomea 265, 34136 Trieste (Italy); INFN, Sezione di Trieste, via Valerio 2, 34127 Trieste (Italy)

    2016-06-08

    We revisit here the naturalness problem of Lorentz invariance violations on a simple toy model of a scalar field coupled to a fermion field via a Yukawa interaction. We first review some well-known results concerning the low-energy percolation of Lorentz violation from high energies, presenting some details of the analysis not explicitly discussed in the literature and discussing some previously unnoticed subtleties. We then show how a separation between the scale of validity of the effective field theory and that one of Lorentz invariance violations can hinder this low-energy percolation. While such protection mechanism was previously considered in the literature, we provide here a simple illustration of how it works and of its general features. Finally, we consider a case in which dissipation is present, showing that the dissipative behaviour does not percolate generically to lower mass dimension operators albeit dispersion does. Moreover, we show that a scale separation can protect from unsuppressed low-energy percolation also in this case.

  19. Leadership and Management Theories Revisited

    DEFF Research Database (Denmark)

    Madsen, Mona Toft

    2001-01-01

    The goal of the paper is to revisit and analyze key contributions to the understanding of leadership and management. As a part of the discussion a role perspective that allows for additional and/or integrated leader dimensions, including a change-centered, will be outlined. Seemingly, a major...

  20. Revisiting Inter-Genre Similarity

    DEFF Research Database (Denmark)

    Sturm, Bob L.; Gouyon, Fabien

    2013-01-01

    We revisit the idea of ``inter-genre similarity'' (IGS) for machine learning in general, and music genre recognition in particular. We show analytically that the probability of error for IGS is higher than naive Bayes classification with zero-one loss (NB). We show empirically that IGS does...... not perform well, even for data that satisfies all its assumptions....

  1. POETIC AND PICTORIAL REVISITS OF THE MOZAMBIQUE ISLAND

    Directory of Open Access Journals (Sweden)

    Carmen Lucia Tindó Secco

    2012-11-01

    Full Text Available The rewriting of Mozambique with the pen of poetry and the ink of affections. Landscapes: poetry, painting and history. The intercrossing of people, cultures and different knowledges in the Mozambican ground of multiple inheritances.

  2. Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jaehong Kim

    2016-01-01

    Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

  3. Impact of Microenvironment and Stem-Like Plasticity in Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Raggi, Chiara; Invernizzi, Pietro; Andersen, Jesper Bøje

    2014-01-01

    or tumor microenvironment (TME) likely promotes initiation and progression of this malignancy contributing to its heterogeneity. This review will emphasize the dynamic interplay between stem-like intrinsic and TME-extrinsic pathways, which may represent novel options for multi-targeted therapies in CCA....

  4. Microenvironments and microscale productivity of cyanobacterial desert crusts

    Science.gov (United States)

    Garcia-Pichel, F.; Belnap, Jayne

    1996-01-01

    We used microsensors to characterize physicochemical microenvironments and photosynthesis occurring immediately after water saturation in two desert soil crusts from southeastern Utah, which were formed by the cyanobacteria Microcoleus vaginatus Gomont, Nostoc spp., and Scytonema sp. The light fields within the crusts presented steep vertical gradients in magnitude and spectral composition. Near-surface light-trapping zones were formed due to the scattering nature of the sand particles, but strong light attenuation resulted in euphotic zones only ca. 1 mm deep, which were progressively enriched in longer wavelengths with depth. Rates of gross photosynthesis (3.4a??9.4 mmol O2A?ma??2A?ha??1) and dark respiration (0.81a??3.1 mmol Oa??2A?ma??2A?ha??1) occurring within 1 to several mm from the surface were high enough to drive the formation of marked oxygen microenvironments that ranged from oxygen supersaturation to anoxia. The photosynthetic activity also resulted in localized pH values in excess of 10, 2a??3 units above the soil pH. Differences in metabolic parameters and community structure between two types of crusts were consistent with a successional pattern, which could be partially explained on the basis of the microenvironments. We discuss the significance of high metabolic rates and the formation of microenvironments for the ecology of desert crusts, as well as the advantages and limitations of microsensor-based methods for crust investigation.

  5. Effects of ground insulation and greenhouse microenvironment on ...

    African Journals Online (AJOL)

    A study was conducted at Egerton University, Njoro, Kenya to establish the potential of plastic digester to produce biogas under natural and greenhouse microenvironment. The specific objectives were to evaluate the effects of greenhouse and ground insulation on the rate and quality of biogas generation. A greenhouse ...

  6. Influence of the Tumor Microenvironment on Cancer Cells Metabolic Reprogramming

    Directory of Open Access Journals (Sweden)

    Victoire Gouirand

    2018-04-01

    Full Text Available As with castles, tumor cells are fortified by surrounding non-malignant cells, such as cancer-associated fibroblasts, immune cells, but also nerve fibers and extracellular matrix. In most cancers, this fortification creates a considerable solid pressure which limits oxygen and nutrient delivery to the tumor cells and causes a hypoxic and nutritional stress. Consequently, tumor cells have to adapt their metabolism to survive and proliferate in this harsh microenvironment. To satisfy their need in energy and biomass, tumor cells develop new capacities to benefit from metabolites of the microenvironment, either by their uptake through the macropinocytosis process or through metabolite transporters, or by a cross-talk with stromal cells and capture of extracellular vesicles that are released by the neighboring cells. However, the microenvironments of primary tumor and metastatic niches differ tremendously in their cellular/acellular components and available nutrients. Therefore, cancer cells must develop a metabolic flexibility conferring on them the ability to satisfy their biomass and energetic demands at both primary and metastasis sites. In this review, we propose a brief overview of how proliferating cancer cells take advantage of their surrounding microenvironment to satisfy their high metabolic demand at both primary and metastasis sites.

  7. Functional live cell imaging of the pulmonary neuroepithelial body microenvironment

    NARCIS (Netherlands)

    De Proost, Ian; Pintelon, Isabel; Brouns, Inge; Kroese, A; Riccardi, Daniela; Kemp, Paul J.; Timmermans, Jean-Pierre; Adriaensen, Dirk

    Pulmonary neuroepithelial bodies (NEBs) are densely innervated groups of neuroendocrine cells invariably accompanied by Clara-like cells. Together with NEBs, Clara-like cells form the so-called "NEB microenvironment," which recently has been assigned a potential pulmonary stem cell niche. Conclusive

  8. Class renormalization: islands around islands

    International Nuclear Information System (INIS)

    Meiss, J.D.

    1986-01-01

    An orbit of 'class' is one that rotates about a periodic orbit of one lower class with definite frequency. This contrasts to the 'level' of a periodic orbit which is the number of elements in its continued fraction expansion. Level renormalization is conventionally used to study the structure of quasi-periodic orbits. The scaling structure of periodic orbits encircling other periodic orbits in area preserving maps is discussed here. Fixed points corresponding to the accumulation of p/q bifurcations are found and scaling exponents determined. Fixed points for q > 2 correspond to self-similar islands around islands. Frequencies of the island boundary circles at the fixed points are obtained. Importance of this scaling for the motion of particles in stochastic regions is emphasized. (author)

  9. 'Counterfeit deviance' revisited.

    Science.gov (United States)

    Griffiths, Dorothy; Hingsburger, Dave; Hoath, Jordan; Ioannou, Stephanie

    2013-09-01

    The field has seen a renewed interest in exploring the theory of 'counterfeit deviance' for persons with intellectual disability who sexually offend. The term was first presented in 1991 by Hingsburger, Griffiths and Quinsey as a means to differentiate in clinical assessment a subgroup of persons with intellectual disability whose behaviours appeared like paraphilia but served a function that was not related to paraphilia sexual urges or fantasies. Case observations were put forward to provide differential diagnosis of paraphilia in persons with intellectual disabilities compared to those with counterfeit deviance. The brief paper was published in a journal that is no longer available and as such much of what is currently written on the topic is based on secondary sources. The current paper presents a theoretical piece to revisit the original counterfeit deviance theory to clarify the myths and misconceptions that have arisen and evaluate the theory based on additional research and clinical findings. The authors also propose areas where there may be a basis for expansion of the theory. The theory of counterfeit deviance still has relevance as a consideration for clinicians when assessing the nature of a sexual offence committed by a person with an intellectual disability. Clinical differentiation of paraphilia from counterfeit deviance provides a foundation for intervention that is designed to specifically treat the underlying factors that contributed to the offence for a given individual. Counterfeit deviance is a concept that continues to provide areas for consideration for clinicians regarding the assessment and treatment of an individual with an intellectual disability who has sexually offended. It is not and never was an explanation for all sexually offending behavior among persons with intellectual disabilities. © 2013 John Wiley & Sons Ltd.

  10. Gaussian entanglement revisited

    Science.gov (United States)

    Lami, Ludovico; Serafini, Alessio; Adesso, Gerardo

    2018-02-01

    We present a novel approach to the separability problem for Gaussian quantum states of bosonic continuous variable systems. We derive a simplified necessary and sufficient separability criterion for arbitrary Gaussian states of m versus n modes, which relies on convex optimisation over marginal covariance matrices on one subsystem only. We further revisit the currently known results stating the equivalence between separability and positive partial transposition (PPT) for specific classes of Gaussian states. Using techniques based on matrix analysis, such as Schur complements and matrix means, we then provide a unified treatment and compact proofs of all these results. In particular, we recover the PPT-separability equivalence for: (i) Gaussian states of 1 versus n modes; and (ii) isotropic Gaussian states. In passing, we also retrieve (iii) the recently established equivalence between separability of a Gaussian state and and its complete Gaussian extendability. Our techniques are then applied to progress beyond the state of the art. We prove that: (iv) Gaussian states that are invariant under partial transposition are necessarily separable; (v) the PPT criterion is necessary and sufficient for separability for Gaussian states of m versus n modes that are symmetric under the exchange of any two modes belonging to one of the parties; and (vi) Gaussian states which remain PPT under passive optical operations can not be entangled by them either. This is not a foregone conclusion per se (since Gaussian bound entangled states do exist) and settles a question that had been left unanswered in the existing literature on the subject. This paper, enjoyable by both the quantum optics and the matrix analysis communities, overall delivers technical and conceptual advances which are likely to be useful for further applications in continuous variable quantum information theory, beyond the separability problem.

  11. Izmit Foreshocks Revisited

    Science.gov (United States)

    Ellsworth, W. L.; Bulut, F.

    2016-12-01

    Much of what we know about the initiation of earthquakes comes from the temporal and spatial relationship of foreshocks to the initiation point of the mainshock. The 1999 Mw 7.6 Izmit, Turkey, earthquake was preceded by a 44 minute-long foreshock sequence. Bouchon et al. (Science, 2011) analyzed the foreshocks using a single seismic station, UCG, located to the north of the east-west fault, and concluded on the basis of waveform similarity that the foreshocks repeatedly re-ruptured the same fault patch, driven by slow slip at the base of the crust. We revisit the foreshock sequence using seismograms from 9 additional stations that recorded the four largest foreshocks (Mw 2.0 to 2.8) to better characterize spatial and temporal evolution of the foreshock sequence and their relationship to the mainshock hypocenter. Cross-correlation timing and hypocentroid location with hypoDD reveals a systematic west-to-east propagation of the four largest foreshocks toward the mainshock hypocenter. Foreshock rupture dimensions estimated using spectral ratios imply no major overlap for the first three foreshocks. The centroid of 4th and largest foreshock continues the eastward migration, but lies within the circular source area of the 3rd. The 3rd, however, has a low stress drop and strong directivity to the west . The mainshock hypocenter locates on the eastern edge of foreshock 4. We also re-analyzed waveform similarity of all 18 foreshocks recorded at UCG by removing the common mode signal and clustering the residual seismogram using the correlation coefficient as the distance metric. The smaller foreshocks cluster with the larger events in time order, sometimes as foreshocks and more commonly as aftershocks. These observations show that the Izmit foreshock sequence is consistent with a stress-transfer driven cascade, moving systematically to the east along the fault and that there is no observational requirement for creep as a driving mechanism.

  12. Making microenvironments: A look into incorporating macromolecular crowding into in vitro experiments, to generate biomimetic microenvironments which are capable of directing cell function for tissue engineering applications.

    Science.gov (United States)

    Benny, Paula; Raghunath, Michael

    2017-01-01

    Biomimetic microenvironments are key components to successful cell culture and tissue engineering in vitro. One of the most accurate biomimetic microenvironments is that made by the cells themselves. Cell-made microenvironments are most similar to the in vivo state as they are cell-specific and produced by the actual cells which reside in that specific microenvironment. However, cell-made microenvironments have been challenging to re-create in vitro due to the lack of extracellular matrix composition, volume and complexity which are required. By applying macromolecular crowding to current cell culture protocols, cell-made microenvironments, or cell-derived matrices, can be generated at significant rates in vitro. In this review, we will examine the causes and effects of macromolecular crowding and how it has been applied in several in vitro systems including tissue engineering.

  13. Dynamic Topography Revisited

    Science.gov (United States)

    Moresi, Louis

    2015-04-01

    Dynamic Topography Revisited Dynamic topography is usually considered to be one of the trinity of contributing causes to the Earth's non-hydrostatic topography along with the long-term elastic strength of the lithosphere and isostatic responses to density anomalies within the lithosphere. Dynamic topography, thought of this way, is what is left over when other sources of support have been eliminated. An alternate and explicit definition of dynamic topography is that deflection of the surface which is attributable to creeping viscous flow. The problem with the first definition of dynamic topography is 1) that the lithosphere is almost certainly a visco-elastic / brittle layer with no absolute boundary between flowing and static regions, and 2) the lithosphere is, a thermal / compositional boundary layer in which some buoyancy is attributable to immutable, intrinsic density variations and some is due to thermal anomalies which are coupled to the flow. In each case, it is difficult to draw a sharp line between each contribution to the overall topography. The second definition of dynamic topography does seem cleaner / more precise but it suffers from the problem that it is not measurable in practice. On the other hand, this approach has resulted in a rich literature concerning the analysis of large scale geoid and topography and the relation to buoyancy and mechanical properties of the Earth [e.g. refs 1,2,3] In convection models with viscous, elastic, brittle rheology and compositional buoyancy, however, it is possible to examine how the surface topography (and geoid) are supported and how different ways of interpreting the "observable" fields introduce different biases. This is what we will do. References (a.k.a. homework) [1] Hager, B. H., R. W. Clayton, M. A. Richards, R. P. Comer, and A. M. Dziewonski (1985), Lower mantle heterogeneity, dynamic topography and the geoid, Nature, 313(6003), 541-545, doi:10.1038/313541a0. [2] Parsons, B., and S. Daly (1983), The

  14. Radiation risks revisited

    International Nuclear Information System (INIS)

    Ackland, L.

    1993-01-01

    The Stewart team's findings are based on previously restricted Hanford data that the U.S. Dept. of Energy began releasing in 1990 to settle a lawsuit filed by the Three Mile Island Public Health Fund. The records include those of the 7,342 workers who died before 1987 and were employed at the plant between 1944 and 1978. These workers were among more than 35,000 men and women whose radiation doses were measured by film-badge monitoring during this period. According to contemporary radiation standards, these recorded exposures were safe. But Stewart and Kneale, using a new technique to more effectively isolate occupational doses from other causes of cancer, have calculated that approximately 3 percent of the 1,732 cancer deaths in the group resulted from work-place radiation exposure

  15. Remembered Experiences and Revisit Intentions

    DEFF Research Database (Denmark)

    Barnes, Stuart; Mattsson, Jan; Sørensen, Flemming

    2016-01-01

    Tourism is an experience-intensive sector in which customers seek and pay for experiences above everything else. Remembering past tourism experiences is also crucial for an understanding of the present, including the predicted behaviours of visitors to tourist destinations. We adopt a longitudinal...... approach to memory data collection from psychological science, which has the potential to contribute to our understanding of tourist behaviour. In this study, we examine the impact of remembered tourist experiences in a safari park. In particular, using matched survey data collected longitudinally and PLS...... path modelling, we examine the impact of positive affect tourist experiences on the development of revisit intentions. We find that longer-term remembered experiences have the strongest impact on revisit intentions, more so than predicted or immediate memory after an event. We also find that remembered...

  16. Review of microfluidic cell culture devices for the control of gaseous microenvironments in vitro

    Science.gov (United States)

    Wu, H.-M.; Lee, T.-A.; Ko, P.-L.; Chiang, H.-J.; Peng, C.-C.; Tung, Y.-C.

    2018-04-01

    Gaseous microenvironments play important roles in various biological activities in vivo. However, it is challenging to precisely control gaseous microenvironments in vitro for cell culture due to the high diffusivity nature of gases. In recent years, microfluidics has paved the way for the development of new types of cell culture devices capable of manipulating cellular microenvironments, and provides a powerful tool for in vitro cell studies. This paper reviews recent developments of microfluidic cell culture devices for the control of gaseous microenvironments, and discusses the advantages and limitations of current devices. We conclude with suggestions for the future development of microfluidic cell culture devices for the control of gaseous microenvironments.

  17. Engineering three-dimensional cell mechanical microenvironment with hydrogels.

    Science.gov (United States)

    Huang, Guoyou; Wang, Lin; Wang, Shuqi; Han, Yulong; Wu, Jinhui; Zhang, Qiancheng; Xu, Feng; Lu, Tian Jian

    2012-12-01

    Cell mechanical microenvironment (CMM) significantly affects cell behaviors such as spreading, migration, proliferation and differentiation. However, most studies on cell response to mechanical stimulation are based on two-dimensional (2D) planar substrates, which cannot mimic native three-dimensional (3D) CMM. Accumulating evidence has shown that there is a significant difference in cell behavior in 2D and 3D microenvironments. Among the materials used for engineering 3D CMM, hydrogels have gained increasing attention due to their tunable properties (e.g. chemical and mechanical properties). In this paper, we provide an overview of recent advances in engineering hydrogel-based 3D CMM. Effects of mechanical cues (e.g. hydrogel stiffness and externally induced stress/strain in hydrogels) on cell behaviors are described. A variety of approaches to load mechanical stimuli in 3D hydrogel-based constructs are also discussed.

  18. A study for radiation-related tumor microenvironment

    International Nuclear Information System (INIS)

    Son, Young Sook; Hong, Seok Il; Kim, Young Soon; Jin Yong Jae; Lee, Tae Hee; Chung, Eun Kyung; Yi, Jae Yeun; Park, Myung Jin; Kim, Yun Young; Kang, Sin Keun

    1999-04-01

    In this study, we attempted to elucidate the mechanism involved in radiation-induced modification and changes of biological factors and physicochemical factors of tumor microenvironment and develop techniques and agents for the modification of tumor microenvironment which is favorable for efficient radio-cancer therapy based on our basic study. We established in vitro tumor invasion and angiogenesis model, elucidated the importance of MMPs activation and the MMPs/TIMPs complex in the invasive transition of tumor. Furthermore we showed the signaling pathway for MMPs induction through EGF receptor and TGF beta 1 stimulated E-M transition. We also established primary culture of human endothelial cells and tubule forming condition which is utilized for the detection of novel angiogenic factors. We also identified hypoxia induced signaling pathway and showed that GBE improved blood perfusion which may increase the effectiveness of radio-cancer therapy

  19. Engineering mechanical microenvironment of macrophage and its biomedical applications.

    Science.gov (United States)

    Li, Jing; Li, Yuhui; Gao, Bin; Qin, Chuanguang; He, Yining; Xu, Feng; Yang, Hui; Lin, Min

    2018-03-01

    Macrophages are the most plastic cells in the hematopoietic system and can be widely found in almost all tissues. Recently studies have shown that mechanical cues (e.g., matrix stiffness and stress/strain) can significantly affect macrophage behaviors. Although existing reviews on the physical and mechanical cues that regulate the macrophage's phenotype are available, engineering mechanical microenvironment of macrophages in vitro as well as a comprehensive overview and prospects for their biomedical applications (e.g., tissue engineering and immunotherapy) has yet to be summarized. Thus, this review provides an overview on the existing methods for engineering mechanical microenvironment of macrophages in vitro and then a section on their biomedical applications and further perspectives are presented.

  20. Engineering three-dimensional cell mechanical microenvironment with hydrogels

    International Nuclear Information System (INIS)

    Huang Guoyou; Wang Lin; Han Yulong; Zhang Qiancheng; Xu Feng; Lu Tianjian; Wang Shuqi; Wu Jinhui

    2012-01-01

    Cell mechanical microenvironment (CMM) significantly affects cell behaviors such as spreading, migration, proliferation and differentiation. However, most studies on cell response to mechanical stimulation are based on two-dimensional (2D) planar substrates, which cannot mimic native three-dimensional (3D) CMM. Accumulating evidence has shown that there is a significant difference in cell behavior in 2D and 3D microenvironments. Among the materials used for engineering 3D CMM, hydrogels have gained increasing attention due to their tunable properties (e.g. chemical and mechanical properties). In this paper, we provide an overview of recent advances in engineering hydrogel-based 3D CMM. Effects of mechanical cues (e.g. hydrogel stiffness and externally induced stress/strain in hydrogels) on cell behaviors are described. A variety of approaches to load mechanical stimuli in 3D hydrogel-based constructs are also discussed. (topical review)

  1. A study for radiation-related tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Son, Young Sook; Hong, Seok Il; Kim, Young Soon; Jin Yong Jae; Lee, Tae Hee; Chung, Eun Kyung; Yi, Jae Yeun; Park, Myung Jin; Kim, Yun Young; Kang, Sin Keun

    1999-04-01

    In this study, we attempted to elucidate the mechanism involved in radiation-induced modification and changes of biological factors and physicochemical factors of tumor microenvironment and develop techniques and agents for the modification of tumor microenvironment which is favorable for efficient radio-cancer therapy based on our basic study. We established in vitro tumor invasion and angiogenesis model, elucidated the importance of MMPs activation and the MMPs/TIMPs complex in the invasive transition of tumor. Furthermore we showed the signaling pathway for MMPs induction through EGF receptor and TGF beta 1 stimulated E-M transition. We also established primary culture of human endothelial cells and tubule forming condition which is utilized for the detection of novel angiogenic factors. We also identified hypoxia induced signaling pathway and showed that GBE improved blood perfusion which may increase the effectiveness of radio-cancer therapy.

  2. Revisiting Mutual Fund Performance Evaluation

    OpenAIRE

    Angelidis, Timotheos; Giamouridis, Daniel; Tessaromatis, Nikolaos

    2012-01-01

    Mutual fund manager excess performance should be measured relative to their self-reported benchmark rather than the return of a passive portfolio with the same risk characteristics. Ignoring the self-reported benchmark introduces biases in the measurement of stock selection and timing components of excess performance. We revisit baseline empirical evidence in mutual fund performance evaluation utilizing stock selection and timing measures that address these biases. We introduce a new factor e...

  3. Reprograming the Metastatic Microenvironment to Combat Disease Recurrence

    Science.gov (United States)

    2017-10-01

    0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing...truly eliminate “residual disease” and prevent metastatic recurrence. We believe we have found a way to accomplish this by inhibiting colony- stimulating ...the bone microenvironment lead to pathological bone loss, which can stimulate tumor cell outgrowth. In addition to contributing to morbidity, this

  4. Remodeling the Vascular Microenvironment of Glioblastoma with α-Particles.

    Science.gov (United States)

    Behling, Katja; Maguire, William F; Di Gialleonardo, Valentina; Heeb, Lukas E M; Hassan, Iman F; Veach, Darren R; Keshari, Kayvan R; Gutin, Philip H; Scheinberg, David A; McDevitt, Michael R

    2016-11-01

    Tumors escape antiangiogenic therapy by activation of proangiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We previously investigated targeted α-particle therapy with 225 Ac-E4G10 as an antivascular approach and showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here, we investigated changes in tumor vascular morphology and functionality caused by 225 Ac-E4G10. We investigated remodeling of the tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4-kBq dose of 225 Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphologic changes in the tumor blood-brain barrier microenvironment. Multicolor flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted MR imaged functional changes in the tumor vascular network. The mechanism of drug action is a combination of remodeling of the glioblastoma vascular microenvironment, relief of edema, and depletion of regulatory T and endothelial progenitor cells. The primary remodeling event is the reduction of both endothelial and perivascular cell populations. Tumor-associated edema and necrosis were lessened, resulting in increased perfusion and reduced diffusion. Pharmacologic uptake of dasatinib into tumor was enhanced after α-particle therapy. Targeted antivascular α-particle radiation remodels the glioblastoma vascular microenvironment via a multimodal mechanism of action and provides insight into the vascular architecture of platelet-derived growth factor-driven glioblastoma. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  5. Chemical and physical microenvironments at the Viking landing sites

    Science.gov (United States)

    Clark, B. C.

    1979-01-01

    Physical and chemical considerations permit the division of the near-surface regolith on Mars into at least six zones of distinct microenvironments. The zones are euphotic, duricrust/peds, tempofrost, permafrost, endolithic, and interfacial/transitional. Microenvironments vary significantly in temperature extremes, mean temperature, salt content, relative pressure of water vapor, UV and visible light irradiance, and exposure to ionizing radiation events (100 Mrad) and oxidative molecular species. From what is known of the chemistry of the atmosphere and regolith fines (soil), limits upon the aqueous chemistry of soil pastes may be estimated. Heat of wetting could reach 45 cal/g dry soil; initial pH is indeterminate between 1 and 10; ionic strength and salinity are predicted to be extremely high; freezing point depression is inadequate to provide quantities of liquid water except in special cases. The prospects for biotic survival are grim by terrestrial standards, but the extremes of biological resiliency are inaccessible to evaluation. Second-generation in situ experiments which will better define Martian microenvironments are clearly possible. Antarctic dry valleys are approximations to Martian conditions, but deviate significantly by at least half-a-dozen criteria.

  6. Mechanotransduction and Growth Factor Signalling to Engineer Cellular Microenvironments.

    Science.gov (United States)

    Cipitria, Amaia; Salmeron-Sanchez, Manuel

    2017-08-01

    Engineering cellular microenvironments involves biochemical factors, the extracellular matrix (ECM) and the interaction with neighbouring cells. This progress report provides a critical overview of key studies that incorporate growth factor (GF) signalling and mechanotransduction into the design of advanced microenvironments. Materials systems have been developed for surface-bound presentation of GFs, either covalently tethered or sequestered through physico-chemical affinity to the matrix, as an alternative to soluble GFs. Furthermore, some materials contain both GF and integrin binding regions and thereby enable synergistic signalling between the two. Mechanotransduction refers to the ability of the cells to sense physical properties of the ECM and to transduce them into biochemical signals. Various aspects of the physics of the ECM, i.e. stiffness, geometry and ligand spacing, as well as time-dependent properties, such as matrix stiffening, degradability, viscoelasticity, surface mobility as well as spatial patterns and gradients of physical cues are discussed. To conclude, various examples illustrate the potential for cooperative signalling of growth factors and the physical properties of the microenvironment for potential applications in regenerative medicine, cancer research and drug testing. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Global niche of marine anaerobic metabolisms expanded by particle microenvironments

    Science.gov (United States)

    Bianchi, Daniele; Weber, Thomas S.; Kiko, Rainer; Deutsch, Curtis

    2018-04-01

    In ocean waters, anaerobic microbial respiration should be confined to the anoxic waters found in coastal regions and tropical oxygen minimum zones, where it is energetically favourable. However, recent molecular and geochemical evidence has pointed to a much broader distribution of denitrifying and sulfate-reducing microbes. Anaerobic metabolisms are thought to thrive in microenvironments that develop inside sinking organic aggregates, but the global distribution and geochemical significance of these microenvironments is poorly understood. Here, we develop a new size-resolved particle model to predict anaerobic respiration from aggregate properties and seawater chemistry. Constrained by observations of the size spectrum of sinking particles, the model predicts that denitrification and sulfate reduction can be sustained throughout vast, hypoxic expanses of the ocean, and could explain the trace metal enrichment observed in particles due to sulfide precipitation. Globally, the expansion of the anaerobic niche due to particle microenvironments doubles the rate of water column denitrification compared with estimates based on anoxic zones alone, and changes the sensitivity of the marine nitrogen cycle to deoxygenation in a warming climate.

  8. Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2017-12-01

    Full Text Available Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents.

  9. Intraportal islet transplantation: the impact of the liver microenvironment.

    Science.gov (United States)

    Delaune, Vaihere; Berney, Thierry; Lacotte, Stéphanie; Toso, Christian

    2017-03-01

    The portal vein remains the preferred site for pancreatic islet transplantation due to its easy access and low morbidity. However, despite great progress in isolation and transplantation protocols over the past few years, it is still associated with the early loss of some 50-70% of transplanted islets. The complex liver microenvironment itself presumably plays an important role in this loss. The present review focuses on the specifics of the liver microenvironment, notably the localized hepatic ischemia/reperfusion injury following transplantation, the low oxygenation of the portal vein, the instant blood-mediated inflammatory reaction, the endogenous liver immune system, and the gut-liver axis, and how they can each have an impact on the transplanted islets. It identifies the potential, or already applied, clinical interventions for improving intraportal islet survival, and pinpoints those promising areas still lacking preclinical research. Future interventions on clinical intraportal islet transplantation need to take into account the global context of the liver microenvironment, with multi-point interventions being most likely to improve early islet survival and engraftment. © 2017 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

  10. Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

    Science.gov (United States)

    Zhang, Bo; Hu, Yu; Pang, Zhiqing

    2017-01-01

    Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents. PMID:29311946

  11. Role of the Microenvironment in Ovarian Cancer Stem Cell Maintenance

    Directory of Open Access Journals (Sweden)

    Jennifer Pasquier

    2013-01-01

    Full Text Available Despite recent progresses in cancer therapy and increased knowledge in cancer biology, ovarian cancer remains a challenging condition. Among the latest concepts developed in cancer biology, cancer stem cells and the role of microenvironment in tumor progression seem to be related. Indeed, cancer stem cells have been described in several solid tumors including ovarian cancers. These particular cells have the ability to self-renew and reconstitute a heterogeneous tumor. They are characterized by specific surface markers and display resistance to therapeutic regimens. During development, specific molecular cues from the tumor microenvironment can play a role in maintaining and expanding stemness of cancer cells. The tumor stroma contains several compartments: cellular component, cytokine network, and extracellular matrix. These different compartments interact to form a permissive niche for the cancer stem cells. Understanding the molecular cues underlying this crosstalk will allow the design of new therapeutic regimens targeting the niche. In this paper, we will discuss the mechanisms implicated in the interaction between ovarian cancer stem cells and their microenvironment.

  12. Designing the stem cell microenvironment for guided connective tissue regeneration.

    Science.gov (United States)

    Bogdanowicz, Danielle R; Lu, Helen H

    2017-12-01

    Adult mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine because of their ability to self-renew and their capacity for multilineage differentiation and tissue regeneration. For connective tissues, such as ligaments or tendons, MSCs are vital to the modulation of the inflammatory response following acute injury while also interacting with resident fibroblasts to promote cell proliferation and matrix synthesis. To date, MSC injection for connective tissue repair has yielded mixed results in vivo, likely due to a lack of appropriate environmental cues to effectively control MSC response and promote tissue healing instead of scar formation. In healthy tissues, stem cells reside within a complex microenvironment comprising cellular, structural, and signaling cues that collectively maintain stemness and modulate tissue homeostasis. Changes to the microenvironment following injury regulate stem cell differentiation, trophic signaling, and tissue healing. Here, we focus on models of the stem cell microenvironment that are used to elucidate the mechanisms of stem cell regulation and inspire functional approaches to tissue regeneration. Recent studies in this frontier area are highlighted, focusing on how microenvironmental cues modulate MSC response following connective tissue injury and, more importantly, how this unique cell environment can be programmed for stem cell-guided tissue regeneration. © 2017 New York Academy of Sciences.

  13. Tenarife Island, Canary Island Archipelago, Atlantic Ocean

    Science.gov (United States)

    1991-01-01

    Tenarife Island is one of the most volcanically active of the Canary Island archipelago, Atlantic Ocean, just off the NW coast of Africa, (28.5N, 16.5W). The old central caldera, nearly filled in by successive volcanic activity culminating in two stratocones. From those two peaks, a line of smaller cinder cones extend to the point of the island. Extensive gullies dissect the west side of the island and some forests still remain on the east side.

  14. The effect of allometric scaling in coral thermal microenvironments.

    Directory of Open Access Journals (Sweden)

    Robert H Ong

    Full Text Available A long-standing interest in marine science is in the degree to which environmental conditions of flow and irradiance, combined with optical, thermal and morphological characteristics of individual coral colonies, affects their sensitivity of thermal microenvironments and susceptibility to stress-induced bleaching within and/or among colonies. The physiological processes in Scleractinian corals tend to scale allometrically as a result of physical and geometric constraints on body size and shape. There is a direct relationship between scaling to thermal stress, thus, the relationship between allometric scaling and rates of heating and cooling in coral microenvironments is a subject of great interest. The primary aim of this study was to develop an approximation that predicts coral thermal microenvironments as a function of colony morphology (shape and size, light or irradiance, and flow velocity or regime. To do so, we provided intuitive interpretation of their energy budgets for both massive and branching colonies, and then quantified the heat-size exponent (b* and allometric constant (m using logarithmic linear regression. The data demonstrated a positive relationship between thermal rates and changes in irradiance, A/V ratio, and flow, with an interaction where turbulent regime had less influence on overall stress which may serve to ameliorate the effects of temperature rise compared to the laminar regime. These findings indicated that smaller corals have disproportionately higher stress, however they can reach thermal equilibrium quicker. Moreover, excellent agreements between the predicted and simulated microscale temperature values with no significant bias were observed for both the massive and branching colonies, indicating that the numerical approximation should be within the accuracy with which they could be measured. This study may assist in estimating the coral microscale temperature under known conditions of water flow and irradiance

  15. Dysregulated pH in Tumor Microenvironment Checkmates Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jaleh Barar

    2013-12-01

    Full Text Available Introduction: The dysregulation of pH by cancerous cells of solid tumors is able to create a unique milieu that is in favor of progression, invasion and metastasis as well as chemo-/immuno-resistance traits of solid tumors. Bioelements involved in pH dysregulation provide new set of oncotargets, inhibition of which may result in better clinical outcome. Methods: To study the impacts of pH dysregulation, we investigated the tumor development and progression in relation with Warburg effect, glycolysis and formation of aberrant tumor microenvironment. Results: The upregulation of glucose transporter GLUT-1 and several enzymes involve in glycolysis exacerbates this phenomenon. The accumulation of lactic acids in cancer cells provokes upregulation of several transport machineries (MCT-1, NHE-1, CA IX and H+ pump V-ATPase resulting in reinforced efflux of proton into extracellular fluid. This deviant event makes pH to be settled at 7.4 and 6.6 respectively in cancer cells cytoplasm and extracellular fluid within the tumor microenvironment, which in return triggers secretion of lysosomal components (various enzymes in acidic milieu with pH 5 into cytoplasm. All these anomalous phenomena make tumor microenvironment (TME to be exposed to cocktail of various enzymes with acidic pH, upon which extracellular matrix (ECM can be remodeled and even deformed, resulting in emergence of a complex viscose TME with high interstitial fluid pressure. Conclusion: It seems that pH dysregulation is able to remodel various physiologic functions and make solid tumors to become much more invasive and metastatic. It also can cause undesired resistance to chemotherapy and immunotherapy. Hence, cancer therapy needs to be reinforced using specific inhibitors of bioelements involved in pH dysregulation of TME in solid tumors.

  16. Effect of Interleukin 1b on rat thymus microenvironment

    Directory of Open Access Journals (Sweden)

    M Artico

    2009-12-01

    Full Text Available The effect of interleukin 1b on the thymus of control and chemically sympathectomized adult and aged rats was studied with the aim of assessing the importance of adrenergic nerve fibres (ANF in the regulation of some immunological functions.The whole thymus was removed from normal, sympathectomized (with the neurotoxin 6-OH-dopamine and treated (interleukin 1b rats. Thymic slices were stained with eosin orange (for the recognition of microanatomical details of the thymic microenvironment and with Bodian’s method for staining of nerve fibres. Histofluorescence microscopy was employed for staining ANF and immunofluorescence was used for detecting NPY-like immunoreactivity. All images were submitted to quantitative morphometrical analysis and statistical analysis of data. Moreover, the amount of proteins and noradrenaline was measured on thymic homogenates. The results indicate that in normal conditions the formation of the thymic nerve plexi in the rat is complex: the majority of ANF are destroyed after chemical sympathectomy with 6-OH-dopamine and do not change after treatment with interleukin 1b; on the contrary, treatment with interleukin 1b induces substantial changes in the fresh weight of the thymus, the thymic microenvironment, thymic nerve fibers, ANF, NPY-like positive nerve fibres, and on the total amount of proteins and noradrenaline in rat thymic tissue homogenates.Immunostimulation with interleukin 1b induces substantial changes in the whole thymus, in its microenvironment and in ANF and NPY-like nerve fibres. After chemical sympathectomy, no significant immune response was evoked by interleukin 1b, since the majority of ANF was destroyed by chemical sympathectomy.

  17. Bone marker gene expression in calvarial bones: different bone microenvironments.

    Science.gov (United States)

    Al-Amer, Osama

    2017-12-01

    In calvarial mice, mesenchymal stem cells (MSCs) differentiate into osteoprogenitor cells and then differentiate into osteoblasts that differentiate into osteocytes, which become embedded within the bone matrix. In this case, the cells participating in bone formation include MSCs, osteoprogenitor cells, osteoblasts and osteocytes. The calvariae of C57BL/KaLwRijHsD mice consist of the following five bones: two frontal bones, two parietal bones and one interparietal bone. This study aimed to analyse some bone marker genes and bone related genes to determine whether these calvarial bones have different bone microenvironments. C57BL/KaLwRijHsD calvariae were carefully excised from five male mice that were 4-6 weeks of age. Frontal, parietal, and interparietal bones were dissected to determine the bone microenvironment in calvariae. Haematoxylin and eosin staining was used to determine the morphology of different calvarial bones under microscopy. TaqMan was used to analyse the relative expression of Runx2, OC, OSX, RANK, RANKL, OPG, N-cadherin, E-cadherin, FGF2 and FGFR1 genes in different parts of the calvariae. Histological analysis demonstrated different bone marrow (BM) areas between the different parts of the calvariae. The data show that parietal bones have the smallest BM area compared to frontal and interparietal bones. TaqMan data show a significant increase in the expression level of Runx2, OC, OSX, RANKL, OPG, FGF2 and FGFR1 genes in the parietal bones compared with the frontal and interparietal bones of calvariae. This study provides evidence that different calvarial bones, frontal, parietal and interparietal, contain different bone microenvironments.

  18. Local iron homeostasis in the breast ductal carcinoma microenvironment

    International Nuclear Information System (INIS)

    Marques, Oriana; Porto, Graça; Rêma, Alexandra; Faria, Fátima; Cruz Paula, Arnaud; Gomez-Lazaro, Maria; Silva, Paula; Martins da Silva, Berta; Lopes, Carlos

    2016-01-01

    While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. We confirm previous results by showing that breast cancer epithelial cells present an ‘iron-utilization phenotype’ with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an ‘iron-donor’ phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context

  19. Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets.

    Science.gov (United States)

    Nakagawa, Saki; Miki, Yasuhiro; Miyashita, Minoru; Hata, Shuko; Takahashi, Yayoi; Rai, Yoshiaki; Sagara, Yasuaki; Ohi, Yasuyo; Hirakawa, Hisashi; Tamaki, Kentaro; Ishida, Takanori; Watanabe, Mika; Suzuki, Takashi; Ohuchi, Noriaki; Sasano, Hironobu

    2016-01-01

    Invasive ductal and lobular carcinomas (IDC and ILC) are the two most common histological types of breast cancer, and have been considered to develop from terminal duct lobular unit but their molecular, pathological, and clinical features are markedly different between them. These differences could be due to different mechanisms of carcinogenesis and tumor microenvironment, especially cancer-associated fibroblasts (CAFs) but little has been explored in this aspect. Therefore, in this study, we evaluated the status of angiogenesis, maturation of intratumoral microvessels, and proliferation of CAFs using immunohistochemistry and PCR array analysis to explore the differences of tumor microenvironment between ILC and IDC. We studied grade- and age-matched, luminal-like ILC and IDC. We immunolocalized CD34 and αSMA for an evaluation of CAFs and CD31, Vasohibin-1, a specific marker of proliferative endothelial cells and nestin, a marker of pericytes for studying the status of proliferation and maturation of intratumoral microvessel. We also performed PCR array analysis to evaluate angiogenic factors in tumor stromal components. The number of CAFs, microvessel density, and vasohibin-1/CD31 positive ratio were all significantly higher in ILC than IDC but nestin immunoreactivity in intratumoral microvessel was significantly lower in ILC. These results did indicate that proliferation of CAFs and endothelial cells was more pronounced in ILC than IDC but newly formed microvessels were less mature than those in IDC. PCR array analysis also revealed that IGF-1 expression was higher in ILC than IDC. This is the first study to demonstrate the differences of tumor microenvironment including CAFs and proliferation and maturation of intratumoral vessels between ILC and IDC.

  20. Combined Effects of Pericytes in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Aline Lopes Ribeiro

    2015-01-01

    Full Text Available Pericytes are multipotent perivascular cells whose involvement in vasculature development is well established. Evidences in the literature also suggest that pericytes display immune properties and that these cells may serve as an in vivo reservoir of stem cells, contributing to the regeneration of diverse tissues. Pericytes are also capable of tumor homing and are important cellular components of the tumor microenvironment (TME. In this review, we highlight the contribution of pericytes to some classical hallmarks of cancer, namely, tumor angiogenesis, growth, metastasis, and evasion of immune destruction, and discuss how collectively these hallmarks could be tackled by therapies targeting pericytes, providing a rationale for cancer drugs aiming at the TME.

  1. Biomolecule delivery to engineer the cellular microenvironment for regenerative medicine.

    Science.gov (United States)

    Bishop, Corey J; Kim, Jayoung; Green, Jordan J

    2014-07-01

    To realize the potential of regenerative medicine, controlling the delivery of biomolecules in the cellular microenvironment is important as these factors control cell fate. Controlled delivery for tissue engineering and regenerative medicine often requires bioengineered materials and cells capable of spatiotemporal modulation of biomolecule release and presentation. This review discusses biomolecule delivery from the outside of the cell inwards through the delivery of soluble and insoluble biomolecules as well as from the inside of the cell outwards through gene transfer. Ex vivo and in vivo therapeutic strategies are discussed, as well as combination delivery of biomolecules, scaffolds, and cells. Various applications in regenerative medicine are highlighted including bone tissue engineering and wound healing.

  2. Cancer Stem Cells and Their Microenvironment: Biology and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Eunice Yuen-Ting Lau

    2017-01-01

    Full Text Available Tumor consists of heterogeneous cancer cells including cancer stem cells (CSCs that can terminally differentiate into tumor bulk. Normal stem cells in normal organs regulate self-renewal within a stem cell niche. Likewise, accumulating evidence has also suggested that CSCs are maintained extrinsically within the tumor microenvironment, which includes both cellular and physical factors. Here, we review the significance of stromal cells, immune cells, extracellular matrix, tumor stiffness, and hypoxia in regulation of CSC plasticity and therapeutic resistance. With a better understanding of how CSC interacts with its niche, we are able to identify potential therapeutic targets for the development of more effective treatments against cancer.

  3. Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yubing Xie

    2011-11-01

    Full Text Available Breast cancer is the most prevalent disease amongst women worldwide and metastasis is the main cause of death due to breast cancer. Metastatic breast cancer cells and embryonic stem (ES cells display similar characteristics. However, unlike metastatic breast cancer cells, ES cells are nonmalignant. Furthermore, embryonic microenvironments have the potential to convert metastatic breast cancer cells into a less invasive phenotype. The creation of in vitro embryonic microenvironments will enable better understanding of ES cell-breast cancer cell interactions, help elucidate tumorigenesis, and lead to the restriction of breast cancer metastasis. In this article, we will present the characteristics of breast cancer cells and ES cells as well as their microenvironments, importance of embryonic microenvironments in inhibiting tumorigenesis, convergence of tumorigenic and embryonic signaling pathways, and state of the art in bioengineering embryonic microenvironments for breast cancer research. Additionally, the potential application of bioengineered embryonic microenvironments for the prevention and treatment of invasive breast cancer will be discussed.

  4. Schroedinger's variational method of quantization revisited

    International Nuclear Information System (INIS)

    Yasue, K.

    1980-01-01

    Schroedinger's original quantization procedure is revisited in the light of Nelson's stochastic framework of quantum mechanics. It is clarified why Schroedinger's proposal of a variational problem led us to a true description of quantum mechanics. (orig.)

  5. Pulmonary emphysema and tumor microenvironment in primary lung cancer.

    Science.gov (United States)

    Murakami, Junichi; Ueda, Kazuhiro; Sano, Fumiho; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

    2016-02-01

    To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Metabolomics of the tumor microenvironment in pediatric acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Stefano Tiziani

    Full Text Available The tumor microenvironment is emerging as an important therapeutic target. Most studies, however, are focused on the protein components, and relatively little is known of how the microenvironmental metabolome might influence tumor survival. In this study, we examined the metabolic profiles of paired bone marrow (BM and peripheral blood (PB samples from 10 children with acute lymphoblastic leukemia (ALL. BM and PB samples from the same patient were collected at the time of diagnosis and after 29 days of induction therapy, at which point all patients were in remission. We employed two analytical platforms, high-resolution magnetic resonance spectroscopy and gas chromatography-mass spectrometry, to identify and quantify 102 metabolites in the BM and PB. Standard ALL therapy, which includes l-asparaginase, completely removed circulating asparagine, but not glutamine. Statistical analyses of metabolite correlations and network reconstructions showed that the untreated BM microenvironment was characterized by a significant network-level signature: a cluster of highly correlated lipids and metabolites involved in lipid metabolism (p<0.006. In contrast, the strongest correlations in the BM upon remission were observed among amino acid metabolites and derivatives (p<9.2 × 10(-10. This study provides evidence that metabolic characterization of the cancer niche could generate new hypotheses for the development of cancer therapies.

  7. Absorbed dose in fibrotic microenvironment models employing Monte Carlo simulation

    International Nuclear Information System (INIS)

    Zambrano Ramírez, O.D.; Rojas Calderón, E.L.; Azorín Vega, E.P.; Ferro Flores, G.; Martínez Caballero, E.

    2015-01-01

    The presence or absence of fibrosis and yet more, the multimeric and multivalent nature of the radiopharmaceutical have recently been reported to have an effect on the radiation absorbed dose in tumor microenvironment models. Fibroblast and myofibroblast cells produce the extracellular matrix by the secretion of proteins which provide structural and biochemical support to cells. The reactive and reparative mechanisms triggered during the inflammatory process causes the production and deposition of extracellular matrix proteins, the abnormal excessive growth of the connective tissue leads to fibrosis. In this work, microenvironment (either not fibrotic or fibrotic) models composed of seven spheres representing cancer cells of 10 μm in diameter each with a 5 μm diameter inner sphere (cell nucleus) were created in two distinct radiation transport codes (PENELOPE and MCNP). The purpose of creating these models was to determine the radiation absorbed dose in the nucleus of cancer cells, based on previously reported radiopharmaceutical retain (by HeLa cells) percentages of the 177 Lu-Tyr 3 -octreotate (monomeric) and 177 Lu-Tyr 3 -octreotate-AuNP (multimeric) radiopharmaceuticals. A comparison in the results between the PENELOPE and MCNP was done. We found a good agreement in the results of the codes. The percent difference between the increase percentages of the absorbed dose in the not fibrotic model with respect to the fibrotic model of the codes PENELOPE and MCNP was found to be under 1% for both radiopharmaceuticals. (authors)

  8. Hypoxia alters the physical properties of the tumor microenvironment

    Science.gov (United States)

    Gilkes, Daniele

    Of all the deaths attributed to cancer, 90% are due to metastasis, or the spread of cancer cells from a primary tumor to distant organs, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that low oxygen states within a tumor, termed hypoxia, can alter the chemical and physical parameters of the extracellular matrix (ECM), or scaffold of the tumor tissue. These changes generate a microenvironment that may be more conducive for promoting metastasis. During tumor evolution, changes in the composition and the overall content of the ECM reflect both its biophysical and biological properties and these strongly influence the cells properties, such as cellular proliferation and cell motility. The talk will cover how hypoxia arises within normal tissue and also in tumors. We will cover the role of hypoxia in collagen biogenesis which influences compositional changes to the tumor microenvironment and discuss how these changes lead to a stiffer tumor stroma. The challenges in determining the influence of chemical versus physical cues on cancer progression will also be considered.

  9. Targeting Gas6/TAM in cancer cells and tumor microenvironment.

    Science.gov (United States)

    Wu, Guiling; Ma, Zhiqiang; Cheng, Yicheng; Hu, Wei; Deng, Chao; Jiang, Shuai; Li, Tian; Chen, Fulin; Yang, Yang

    2018-01-31

    Growth arrest-specific 6, also known as Gas6, is a human gene encoding the Gas6 protein, which was originally found to be upregulated in growth-arrested fibroblasts. Gas6 is a member of the vitamin K-dependent family of proteins expressed in many human tissues and regulates several biological processes in cells, including proliferation, survival and migration, by binding to its receptors Tyro3, Axl and Mer (TAM). In recent years, the roles of Gas6/TAM signalling in cancer cells and the tumour microenvironment have been studied, and some progress has made in targeted therapy, providing new potential directions for future investigations of cancer treatment. In this review, we introduce the Gas6 and TAM receptors and describe their involvement in different cancers and discuss the roles of Gas6 in cancer cells, the tumour microenvironment and metastasis. Finally, we introduce recent studies on Gas6/TAM targeting in cancer therapy, which will assist in the experimental design of future analyses and increase the potential use of Gas6 as a therapeutic target for cancer.

  10. Tungsten Targets the Tumor Microenvironment to Enhance Breast Cancer Metastasis

    Science.gov (United States)

    Bolt, Alicia M.; Sabourin, Valérie; Molina, Manuel Flores; Police, Alice M.; Negro Silva, Luis Fernando; Plourde, Dany; Lemaire, Maryse; Ursini-Siegel, Josie; Mann, Koren K.

    2015-01-01

    The number of individuals exposed to high levels of tungsten is increasing, yet there is limited knowledge of the potential human health risks. Recently, a cohort of breast cancer patients was left with tungsten in their breasts following testing of a tungsten-based shield during intraoperative radiotherapy. While monitoring tungsten levels in the blood and urine of these patients, we utilized the 66Cl4 cell model, in vitro and in mice to study the effects of tungsten exposure on mammary tumor growth and metastasis. We still detect tungsten in the urine of patients’ years after surgery (mean urinary tungsten concentration at least 20 months post-surgery = 1.76 ng/ml), even in those who have opted for mastectomy, indicating that tungsten does not remain in the breast. In addition, standard chelation therapy was ineffective at mobilizing tungsten. In the mouse model, tungsten slightly delayed primary tumor growth, but significantly enhanced lung metastasis. In vitro, tungsten did not enhance 66Cl4 proliferation or invasion, suggesting that tungsten was not directly acting on 66Cl4 primary tumor cells to enhance invasion. In contrast, tungsten changed the tumor microenvironment, enhancing parameters known to be important for cell invasion and metastasis including activated fibroblasts, matrix metalloproteinases, and myeloid-derived suppressor cells. We show, for the first time, that tungsten enhances metastasis in an animal model of breast cancer by targeting the microenvironment. Importantly, all these tumor microenvironmental changes are associated with a poor prognosis in humans. PMID:25324207

  11. Multiple Myeloma Macrophages: Pivotal Players in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Simona Berardi

    2013-01-01

    Full Text Available Tumor microenvironment is essential for multiple myeloma (MM growth, progression, and drug resistance through provision of survival signals and secretion of growth and proangiogenic factors. This paper examines the importance of macrophages within MM bone marrow (BM microenvironment, referred to as MM-associated macrophages, as a potential niche component that supports tumor plasma cells. These macrophages are derived from peripheral blood monocytes recruited into the tumor. Upon activation by MM plasma cells and mesenchymal stromal cells, macrophages can release growth factors, proteolytic enzymes, cytokines, and inflammatory mediators that promote plasma cell growth and survival. Macrophages promote tumor progression through several mechanisms including angiogenesis, growth, and drug resistance. Indeed, these macrophages are essential for the induction of an angiogenic response through vasculogenic mimicry, and this ability proceeds in step with progression of the plasma cell tumors. Data suggest that macrophages play an important role in the biology and survival of patients with MM, and they may be a target for the MM antivascular management.

  12. Tourists' perceptions and intention to revisit Norway

    OpenAIRE

    Lazar, Ana Florina; Komolikova-Blindheim, Galyna

    2016-01-01

    Purpose - The overall purpose of this study is to explore tourists' perceptions and their intention to revisit Norway. The aim is to find out what are the factors that drive the overall satisfaction, the willingness to recommend and the revisit intention of international tourists that spend their holiday in Norway. Design-Method-Approach - the Theory of Planned Behavior (Ajzen 1991), is used as a framework to investigate tourists' intention and behavior towards Norway as destination. The o...

  13. Targets in the microenvironment of rectal cancer : A focus on angiogenic growth factors and chemokines

    NARCIS (Netherlands)

    Tamas, Karin Rita

    2015-01-01

    Cancer cells interact with each other, and with cells of the tumor microenvironment. This coincides with the production of numerous soluble factors which can stimulate cancer cell growth and migration. In addition the tumor microenvironment can facilitate cancer cells to escape the effect of

  14. Fabrication of highly modulable fibrous 3D extracellular microenvironments

    KAUST Repository

    Zhang, Xixiang; Han, Fangfei; Syed, Ahad; Bukhari, Ebtihaj M.; Siang, Basil Chew Joo; Yang, Shan; Zhou, Bingpu; Wen, Wei-jia; Jiang, Dechen

    2017-01-01

    Three-dimensional (3D) in vitro scaffolds that mimic the irregular fibrous structures of in vivo extracellular matrix (ECM) are critical for many important biological applications. However, structural properties modulation of fibrous 3D scaffolds remains a challenge. Here, we report the first highly modulable 3D fibrous scaffolds self-assembled by high-aspect-ratio (HAR) microfibers. The scaffolds structural properties can be easily tailored to incorporate various physical cues, including geometry, stiffness, heterogeneity and nanotopography. Moreover, the fibrous scaffolds are readily and accurately patterned on desired locations of the substrate. Cell culture exhibits that our scaffolds can elicit strong bidirectional cell-material interactions. Furthermore, a functional disparity between the two-dimensional substrate and our 3D scaffolds is identified by cell spreading and proliferation data. These results prove the potential of the proposed scaffold as a biomimetic extracellular microenvironment for cell study.

  15. Neuro-immune modulation of the thymus microenvironment (review).

    Science.gov (United States)

    Mignini, Fiorenzo; Sabbatini, Maurizio; Mattioli, Laura; Cosenza, Monica; Artico, Marco; Cavallotti, Carlo

    2014-06-01

    The thymus is the primary site for T-cell lympho-poiesis. Its function includes the maturation and selection of antigen specific T cells and selective release of these cells to the periphery. These highly complex processes require precise parenchymal organization and compartmentation where a plethora of signalling pathways occur, performing strict control on the maturation and selection processes of T lymphocytes. In this review, the main morphological characteristics of the thymus microenvironment, with particular emphasis on nerve fibers and neuropeptides were assessed, as both are responsible for neuro-immune‑modulation functions. Among several neurotransmitters that affect thymus function, we highlight the dopaminergic system as only recently has its importance on thymus function and lymphocyte physiology come to light.

  16. Fabrication of highly modulable fibrous 3D extracellular microenvironments

    KAUST Repository

    Zhang, Xixiang

    2017-06-13

    Three-dimensional (3D) in vitro scaffolds that mimic the irregular fibrous structures of in vivo extracellular matrix (ECM) are critical for many important biological applications. However, structural properties modulation of fibrous 3D scaffolds remains a challenge. Here, we report the first highly modulable 3D fibrous scaffolds self-assembled by high-aspect-ratio (HAR) microfibers. The scaffolds structural properties can be easily tailored to incorporate various physical cues, including geometry, stiffness, heterogeneity and nanotopography. Moreover, the fibrous scaffolds are readily and accurately patterned on desired locations of the substrate. Cell culture exhibits that our scaffolds can elicit strong bidirectional cell-material interactions. Furthermore, a functional disparity between the two-dimensional substrate and our 3D scaffolds is identified by cell spreading and proliferation data. These results prove the potential of the proposed scaffold as a biomimetic extracellular microenvironment for cell study.

  17. Novel "Elements" of Immune Suppression within the Tumor Microenvironment.

    Science.gov (United States)

    Gurusamy, Devikala; Clever, David; Eil, Robert; Restifo, Nicholas P

    2017-06-01

    Adaptive evolution has prompted immune cells to use a wide variety of inhibitory signals, many of which are usurped by tumor cells to evade immune surveillance. Although tumor immunologists often focus on genes and proteins as mediators of immune function, here we highlight two elements from the periodic table-oxygen and potassium-that suppress the immune system in previously unappreciated ways. While both are key to the maintenance of T-cell function and tissue homeostasis, they are exploited by tumors to suppress immuno-surveillance and promote metastatic spread. We discuss the temporal and spatial roles of these elements within the tumor microenvironment and explore possible therapeutic interventions for effective and promising anticancer therapies. Cancer Immunol Res; 5(6); 426-33. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland

    Science.gov (United States)

    2017-11-01

    Danvers, MA, USA), andro- gen receptor (1:500, Santa Cruz Biotechnologies, Santa Cruz, CA, USA) and guinea pig antibodies against Vimentin (1:1,000...Problems…………………………………………………….29 6. Products ………………………………………………………………..29-30 7. Participants/Collaborators……………………………………………30-31 8. Special Reporting...a prometastatic microenvironment. The production of the Ltbp1-TGF-beta complex by luminal cells has consequences for our understanding of the

  19. Microenvironment Dependent Photobiomodulation on Function-Specific Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    Timon Cheng-Yi Liu

    2014-01-01

    Full Text Available Cellular photobiomodulation on a cellular function has been shown to be homeostatic. Its function-specific pathway mechanism would be further discussed in this paper. The signal transduction pathways maintaining a normal function in its function-specific homeostasis (FSH, resisting the activation of many other irrelative signal transduction pathways, are so sparse that it can be supposed that there may be normal function-specific signal transduction pathways (NSPs. A low level laser irradiation or monochromatic light may promote the activation of partially activated NSP and/or its redundant NSP so that it may induce the second-order phase transition of a function from its dysfunctional one far from its FSH to its normal one in a function-specific microenvironment and may also induce the first-order functional phase transition of the normal function from low level to high level.

  20. Emerging Roles for Eosinophils in the Tumor Microenvironment.

    Science.gov (United States)

    Reichman, Hadar; Karo-Atar, Danielle; Munitz, Ariel

    2016-11-01

    Eosinophils are evolutionary conserved cells largely studied in the context of allergy. Although eosinophils were first described in tumors more than 120 years ago, their roles in cancer are often overlooked. This is puzzling given their potent immune modulatory, cytotoxic, and/or tissue repair capabilities, and recent studies demonstrating key roles for eosinophils in contexts far beyond their 'classical' field (e.g., metabolism, thermogenesis, and tissue regeneration). Recent data suggest that this frequently ignored cell is emerging as a potent immune effector and immune modulator in the tumor microenvironment. This review discusses the relevance of eosinophils to tumorigenesis and the potential to harness their function in cancer therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The multifaceted role of the microenvironment in liver metastasis

    DEFF Research Database (Denmark)

    Van den Eynden, Gert G; Majeed, Ali W; Illemann, Martin

    2013-01-01

    arriving in the liver via the bloodstream encounter the microenvironment of the hepatic sinusoid. The interactions of the tumor cells with hepatic sinusoidal and extrasinusoidal cells (endothelial, Kupffer, stellate, and inflammatory cells) determine their fate. The sinusoidal cells can have a dual role......The liver is host to many metastatic cancers, particularly colorectal cancer, for which the last 2 decades have seen major advances in diagnosis and treatment. The liver is a vital organ, and the extent of its involvement with metastatic disease is a major determinant of survival. Metastatic cells...... arrested and survived the initial onslaught, tumors can grow within the liver in 3 distinct patterns, reflecting differing host responses, mechanisms of vascularization, and proteolytic activity. This review aims to present current knowledge of the interactions between the host liver cells and the invading...

  2. Researching Pacific island livelihoods:

    DEFF Research Database (Denmark)

    Egelund Christensen, Andreas; Mertz, Ole

    2010-01-01

    on contemporary theories of nissology and conceptual analytical frameworks for island research. Through a review of selected case-study-based island literature on changing livelihoods coming out of the South Pacific, we wish to illustrate and discuss advantages of finding common grounds for small island studies....... The focus is on two dimensions of island livelihood, migration and natural resource management, both of which are significant contributors in making island livelihoods and shaping Pacific seascapes. We argue that there is still a substantial lack of studies targeting small island dynamics that are empirical...

  3. The Levy sections theorem revisited

    International Nuclear Information System (INIS)

    Figueiredo, Annibal; Gleria, Iram; Matsushita, Raul; Silva, Sergio Da

    2007-01-01

    This paper revisits the Levy sections theorem. We extend the scope of the theorem to time series and apply it to historical daily returns of selected dollar exchange rates. The elevated kurtosis usually observed in such series is then explained by their volatility patterns. And the duration of exchange rate pegs explains the extra elevated kurtosis in the exchange rates of emerging markets. In the end, our extension of the theorem provides an approach that is simpler than the more common explicit modelling of fat tails and dependence. Our main purpose is to build up a technique based on the sections that allows one to artificially remove the fat tails and dependence present in a data set. By analysing data through the lenses of the Levy sections theorem one can find common patterns in otherwise very different data sets

  4. The power reinforcement framework revisited

    DEFF Research Database (Denmark)

    Nielsen, Jeppe; Andersen, Kim Normann; Danziger, James N.

    2016-01-01

    Whereas digital technologies are often depicted as being capable of disrupting long-standing power structures and facilitating new governance mechanisms, the power reinforcement framework suggests that information and communications technologies tend to strengthen existing power arrangements within...... public organizations. This article revisits the 30-yearold power reinforcement framework by means of an empirical analysis on the use of mobile technology in a large-scale programme in Danish public sector home care. It explores whether and to what extent administrative management has controlled decision......-making and gained most benefits from mobile technology use, relative to the effects of the technology on the street-level workers who deliver services. Current mobile technology-in-use might be less likely to be power reinforcing because it is far more decentralized and individualized than the mainly expert...

  5. The Levy sections theorem revisited

    Science.gov (United States)

    Figueiredo, Annibal; Gleria, Iram; Matsushita, Raul; Da Silva, Sergio

    2007-06-01

    This paper revisits the Levy sections theorem. We extend the scope of the theorem to time series and apply it to historical daily returns of selected dollar exchange rates. The elevated kurtosis usually observed in such series is then explained by their volatility patterns. And the duration of exchange rate pegs explains the extra elevated kurtosis in the exchange rates of emerging markets. In the end, our extension of the theorem provides an approach that is simpler than the more common explicit modelling of fat tails and dependence. Our main purpose is to build up a technique based on the sections that allows one to artificially remove the fat tails and dependence present in a data set. By analysing data through the lenses of the Levy sections theorem one can find common patterns in otherwise very different data sets.

  6. Diomede Islands, Bering Straight

    Science.gov (United States)

    2008-01-01

    The Diomede Islands consisting of the western island Big Diomede (also known as Imaqliq, Nunarbuk or Ratmanov Island), and the eastern island Little Diomede (also known as Krusenstern Island or Inaliq), are two rocky islands located in the middle of the Bering Strait between Russia and Alaska. The islands are separated by an international border and the International Date Line which is approximately 1.5 km from each island; you can look from Alaska into tomorrow in Russia. At the closest land approach between the United States, which controls Little Diomede, and Russia, which controls Big Diomede, they are 3 km apart. Little Diomede Island constitutes the Alaskan City of Diomede, while Big Diomede Island is Russia's easternmost point. The first European to reach the islands was the Russian explorer Semyon Dezhnev in 1648. The text of the 1867 treaty finalizing the sale of Alaska uses the islands to designate the border between the two nations. The image was acquired July 8, 2000, covers an area of 13.5 x 10.8 km, and is located at 65.8 degrees north latitude, 169 degrees west longitude. The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  7. Tales of island tails

    NARCIS (Netherlands)

    Groot, de Alma V.; Oost, Albert P.; Veeneklaas, Roos M.; Lammerts, Evert Jan; Duin, van Willem E.; Wesenbeeck, van Bregje K.

    2016-01-01

    The Frisian islands (Southern North Sea) have extensive island tails, i.e. the entire downdrift side of an island consisting of salt marshes, dunes, beaches and beach plains, and green beaches. Currently, large parts of these tails are ageing and losing dynamics, partly due to human influence.

  8. Rhode Island unemployment

    OpenAIRE

    Leonard Lardaro

    2010-01-01

    How can a state like Rhode Island have such a high unemployment rate? This question has been asked often over the past year, especially since at one point, Rhode Island found itself with the dubious distinction of having the highest unemployment rate in the United States. Following that extreme, Rhode Island seemed to settle into a niche where its rank was third nationally.

  9. NANIVID: A New Research Tool for Tissue Microenvironment Studies

    Science.gov (United States)

    Raja, Waseem K.

    Metastatic tumors are heterogeneous in nature and composed of subpopulations of cells having various metastatic potentials. The time progression of a tumor creates a unique microenvironment to improve the invasion capabilities and survivability of cancer cells in different microenvironments. In the early stages of intravasation, cancer cells establish communication with other cell types through a paracrine loop and covers long distances by sensing growth factor gradients through extracellular matrices. Cellular migration both in vitro and in vivo is a complex process and to understand their motility in depth, sophisticated techniques are required to document and record events in real time. This study presents the design and optimization of a new versatile chemotaxis device called the NANIVID (NANo IntraVital Imaging Device), developed using advanced Nano/Micro fabrication techniques. The current version of this device has been demonstrated to form a stable (epidermal growth factor) EGF gradient in vitro (2D and 3D) while a miniaturized size of NANIVID is used as an implantable device for intravital studies of chemotaxis and to collect cells in vivo. The device is fabricated using microfabrication techniques in which two substrates are bonded together using a thin polymer layer creating a bonded device with one point source (approximately 150 im x 50 im) outlet. The main structures of the device consist of two transparent substrates: one having etched chambers and channel while the second consists of a microelectrode system to measure real time cell arrival inside the device. The chamber of the device is loaded with a growth factor reservoir consisting of hydrogel to sustain a steady release of growth factor into the surrounding environment for long periods of time and establishing a concentration gradient from the device. The focus of this study was to design and optimize the new device for cell chemotaxis studies in breast cancer cells in cell culture. Our results

  10. Revisiting tourist behavior via destination brand worldness

    Directory of Open Access Journals (Sweden)

    Murat Kayak

    2016-11-01

    Full Text Available Taking tourists’ perspective rather than destination offerings as its core concept, this study introduces “perceived destination brand worldness” as a variable. Perceived destination brand worldness is defined as the positive perception that a tourist has of a country that is visited by tourists from all over the world. Then, the relationship between perceived destination brand worldness and intention to revisit is analyzed using partial least squares regression. This empirical study selects Taiwanese tourists as its sample, and the results show that perceived destination brand worldness is a direct predictor of intention to revisit. In light of these empirical findings and observations, practical and theoretical implications are discussed.

  11. GPS-based Microenvironment Tracker (MicroTrac) Model to ...

    Science.gov (United States)

    A critical aspect of air pollution exposure assessment is the estimation of the time spent by individuals in various microenvironments (ME). Accounting for the time spent in different ME with different pollutant concentrations can reduce exposure misclassifications, while failure to do so can add uncertainty and bias to risk estimates. In this study, a classification model, called MicroTrac, was developed to estimate time of day and duration spent in eight ME (indoors and outdoors at home, work, school; inside vehicles; other locations) from global positioning system (GPS) data and geocoded building boundaries. Based on a panel study, MicroTrac estimates were compared to 24 h diary data from 7 participants on workdays and 2 participants on nonworkdays, with corresponding GPS data and building boundaries of home, school, and work. MicroTrac correctly classified the ME for 99.5% of the daily time spent by the participants. The capability of MicroTrac could help to reduce the time-location uncertainty in air pollution exposure models and exposure metrics for individuals in health studies. The National Exposure Research Laboratory’s (NERL’s) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA’s mission to protect human health and the environment. HEASD’s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA’s strategic plan. More specifically, our division conducts research to characterize

  12. Influence of the neural microenvironment on prostate cancer.

    Science.gov (United States)

    Coarfa, Christian; Florentin, Diego; Putluri, NagiReddy; Ding, Yi; Au, Jason; He, Dandan; Ragheb, Ahmed; Frolov, Anna; Michailidis, George; Lee, MinJae; Kadmon, Dov; Miles, Brian; Smith, Christopher; Ittmann, Michael; Rowley, David; Sreekumar, Arun; Creighton, Chad J; Ayala, Gustavo

    2018-02-01

    Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non-neoplastic epithelial cells. Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc.

  13. Acidity generated by the tumor microenvironment drives local invasion.

    Science.gov (United States)

    Estrella, Veronica; Chen, Tingan; Lloyd, Mark; Wojtkowiak, Jonathan; Cornnell, Heather H; Ibrahim-Hashim, Arig; Bailey, Kate; Balagurunathan, Yoganand; Rothberg, Jennifer M; Sloane, Bonnie F; Johnson, Joseph; Gatenby, Robert A; Gillies, Robert J

    2013-03-01

    The pH of solid tumors is acidic due to increased fermentative metabolism and poor perfusion. It has been hypothesized that acid pH promotes local invasive growth and metastasis. The hypothesis that acid mediates invasion proposes that H(+) diffuses from the proximal tumor microenvironment into adjacent normal tissues where it causes tissue remodeling that permits local invasion. In the current work, tumor invasion and peritumoral pH were monitored over time using intravital microscopy. In every case, the peritumoral pH was acidic and heterogeneous and the regions of highest tumor invasion corresponded to areas of lowest pH. Tumor invasion did not occur into regions with normal or near-normal extracellular pH. Immunohistochemical analyses revealed that cells in the invasive edges expressed the glucose transporter-1 and the sodium-hydrogen exchanger-1, both of which were associated with peritumoral acidosis. In support of the functional importance of our findings, oral administration of sodium bicarbonate was sufficient to increase peritumoral pH and inhibit tumor growth and local invasion in a preclinical model, supporting the acid-mediated invasion hypothesis. Cancer Res; 73(5); 1524-35. ©2012 AACR. ©2012 AACR.

  14. Peritoneal inflammation – A microenvironment for Epithelial Ovarian Cancer (EOC

    Directory of Open Access Journals (Sweden)

    Liu Jinsong

    2004-06-01

    Full Text Available Abstract Epithelial ovarian cancer (EOC is a significant cause of cancer related morbidity and mortality in women. Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients. Advances in biotechnology, such as cDNA microarray, are a product of the Human Genome Project and are beginning to provide fresh opportunities to understand the biology of EOC. In particular, it is now possible to examine in depth, at the molecular level, the complex relationship between the tumor itself and its surrounding microenvironment. This review focuses on the anatomy, physiology, and current immunobiologic research of peritoneal structures, and addresses certain potentially useful animal models. Changes in both the inflammatory and non-inflammatory cell compartments, as well as alterations to the extracellular matrix, appear to be signal events that contribute to the remodeling effects of the peritoneal stroma and surface epithelial cells on tumor growth and spread. These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins. Interactions between these molecules and molecular structures within the extracellular matrix, such as collagens and the proteoglycans, may contribute to a peritoneal mesothelial surface and stromal environment that is conducive to tumor cell proliferation and invasion. These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.

  15. Natural Compounds Regulate Glycolysis in Hypoxic Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jian-Li Gao

    2015-01-01

    Full Text Available In the early twentieth century, Otto Heinrich Warburg described an elevated rate of glycolysis occurring in cancer cells, even in the presence of atmospheric oxygen (the Warburg effect. Recently it became a therapeutically interesting strategy and is considered as an emerging hallmark of cancer. Hypoxia inducible factor-1 (HIF-1 is one of the key transcription factors that play major roles in tumor glycolysis and could directly trigger Warburg effect. Thus, how to inhibit HIF-1-depended Warburg effect to assist the cancer therapy is becoming a hot issue in cancer research. In fact, HIF-1 upregulates the glucose transporters (GLUT and induces the expression of glycolytic enzymes, such as hexokinase, pyruvate kinase, and lactate dehydrogenase. So small molecules of natural origin used as GLUT, hexokinase, or pyruvate kinase isoform M2 inhibitors could represent a major challenge in the field of cancer treatment. These compounds aim to suppress tumor hypoxia induced glycolysis process to suppress the cell energy metabolism or enhance the susceptibility of tumor cells to radio- and chemotherapy. In this review, we highlight the role of natural compounds in regulating tumor glycolysis, with a main focus on the glycolysis under hypoxic tumor microenvironment.

  16. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism.

    Science.gov (United States)

    Zhao, Hongyun; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Bernard, Vincent; Moss, Tyler; Marini, Juan C; Tudawe, Thavisha; Seviour, Elena G; San Lucas, F Anthony; Alvarez, Hector; Gupta, Sonal; Maiti, Sourindra N; Cooper, Laurence; Peehl, Donna; Ram, Prahlad T; Maitra, Anirban; Nagrath, Deepak

    2016-02-27

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions.

  17. Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

    Science.gov (United States)

    Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

    2009-01-01

    Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

  18. Inflammatory breast cancer biology: the tumour microenvironment is key.

    Science.gov (United States)

    Lim, Bora; Woodward, Wendy A; Wang, Xiaoping; Reuben, James M; Ueno, Naoto T

    2018-04-27

    Inflammatory breast cancer (IBC) is a rare and aggressive disease that accounts for ~2-4% of all breast cancers. However, despite its low incidence rate, IBC is responsible for 7-10% of breast cancer-related mortality in Western countries. Thus, the discovery of robust biological targets and the development of more effective therapeutics in IBC are crucial. Despite major international efforts to understand IBC biology, genomic studies have not led to the discovery of distinct biological mechanisms in IBC that can be translated into novel therapeutic strategies. In this Review, we discuss these molecular profiling efforts and highlight other important aspects of IBC biology. We present the intrinsic characteristics of IBC, including stemness, metastatic potential and hormone receptor positivity; the extrinsic features of the IBC tumour microenvironment (TME), including various constituent cell types; and lastly, the communication between these intrinsic and extrinsic components. We summarize the latest perspectives on the key biological features of IBC, with particular emphasis on the TME as an important contributor to the aggressive nature of IBC. On the basis of the current understanding of IBC, we hope to develop the next generation of translational studies, which will lead to much-needed survival improvements in patients with this deadly disease.

  19. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

    Science.gov (United States)

    Zhao, Hongyun; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Bernard, Vincent; Moss, Tyler; Marini, Juan C; Tudawe, Thavisha; Seviour, Elena G; San Lucas, F Anthony; Alvarez, Hector; Gupta, Sonal; Maiti, Sourindra N; Cooper, Laurence; Peehl, Donna; Ram, Prahlad T; Maitra, Anirban; Nagrath, Deepak

    2016-01-01

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions. DOI: http://dx.doi.org/10.7554/eLife.10250.001 PMID:26920219

  20. [Development of a microenvironment test chamber for airborne microbe research].

    Science.gov (United States)

    Zhan, Ningbo; Chen, Feng; Du, Yaohua; Cheng, Zhi; Li, Chenyu; Wu, Jinlong; Wu, Taihu

    2017-10-01

    One of the most important environmental cleanliness indicators is airborne microbe. However, the particularity of clean operating environment and controlled experimental environment often leads to the limitation of the airborne microbe research. This paper designed and implemented a microenvironment test chamber for airborne microbe research in normal test conditions. Numerical simulation by Fluent showed that airborne microbes were evenly dispersed in the upper part of test chamber, and had a bottom-up concentration growth distribution. According to the simulation results, the verification experiment was carried out by selecting 5 sampling points in different space positions in the test chamber. Experimental results showed that average particle concentrations of all sampling points reached 10 7 counts/m 3 after 5 minutes' distributing of Staphylococcus aureus , and all sampling points showed the accordant mapping of concentration distribution. The concentration of airborne microbe in the upper chamber was slightly higher than that in the middle chamber, and that was also slightly higher than that in the bottom chamber. It is consistent with the results of numerical simulation, and it proves that the system can be well used for airborne microbe research.

  1. Leukemia and ionizing radiation revisited

    Energy Technology Data Exchange (ETDEWEB)

    Cuttler, J.M. [Cuttler & Associates Inc., Vaughan, Ontario (Canada); Welsh, J.S. [Loyola University-Chicago, Dept. or Radiation Oncology, Stritch School of Medicine, Maywood, Illinois (United States)

    2016-03-15

    A world-wide radiation health scare was created in the late 19508 to stop the testing of atomic bombs and block the development of nuclear energy. In spite of the large amount of evidence that contradicts the cancer predictions, this fear continues. It impairs the use of low radiation doses in medical diagnostic imaging and radiation therapy. This brief article revisits the second of two key studies, which revolutionized radiation protection, and identifies a serious error that was missed. This error in analyzing the leukemia incidence among the 195,000 survivors, in the combined exposed populations of Hiroshima and Nagasaki, invalidates use of the LNT model for assessing the risk of cancer from ionizing radiation. The threshold acute dose for radiation-induced leukemia, based on about 96,800 humans, is identified to be about 50 rem, or 0.5 Sv. It is reasonable to expect that the thresholds for other cancer types are higher than this level. No predictions or hints of excess cancer risk (or any other health risk) should be made for an acute exposure below this value until there is scientific evidence to support the LNT hypothesis. (author)

  2. Individualist Biocentrism vs. Holism Revisited

    Directory of Open Access Journals (Sweden)

    Katie McShane

    2014-06-01

    Full Text Available While holist views such as ecocentrism have considerable intuitive appeal, arguing for the moral considerability of ecological wholes such as ecosystems has turned out to be a very difficult task. In the environmental ethics literature, individualist biocentrists have persuasively argued that individual organisms—but not ecological wholes—are properly regarded as having a good of their own . In this paper, I revisit those arguments and contend that they are fatally flawed. The paper proceeds in five parts. First, I consider some problems brought about by climate change for environmental conservation strategies and argue that these problems give us good pragmatic reasons to want a better account of the welfare of ecological wholes. Second, I describe the theoretical assumptions from normative ethics that form the background of the arguments against holism. Third, I review the arguments given by individualist biocentrists in favour of individualism over holism. Fourth, I review recent work in the philosophy of biology on the units of selection problem, work in medicine on the human biome, and work in evolutionary biology on epigenetics and endogenous viral elements. I show how these developments undermine both the individualist arguments described above as well as the distinction between individuals and wholes as it has been understood by individualists. Finally, I consider five possible theoretical responses to these problems.

  3. Revisiting the safety of aspartame.

    Science.gov (United States)

    Choudhary, Arbind Kumar; Pretorius, Etheresia

    2017-09-01

    Aspartame is a synthetic dipeptide artificial sweetener, frequently used in foods, medications, and beverages, notably carbonated and powdered soft drinks. Since 1981, when aspartame was first approved by the US Food and Drug Administration, researchers have debated both its recommended safe dosage (40 mg/kg/d) and its general safety to organ systems. This review examines papers published between 2000 and 2016 on both the safe dosage and higher-than-recommended dosages and presents a concise synthesis of current trends. Data on the safe aspartame dosage are controversial, and the literature suggests there are potential side effects associated with aspartame consumption. Since aspartame consumption is on the rise, the safety of this sweetener should be revisited. Most of the literature available on the safety of aspartame is included in this review. Safety studies are based primarily on animal models, as data from human studies are limited. The existing animal studies and the limited human studies suggest that aspartame and its metabolites, whether consumed in quantities significantly higher than the recommended safe dosage or within recommended safe levels, may disrupt the oxidant/antioxidant balance, induce oxidative stress, and damage cell membrane integrity, potentially affecting a variety of cells and tissues and causing a deregulation of cellular function, ultimately leading to systemic inflammation. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Neutrino assisted GUT baryogenesis revisited

    Science.gov (United States)

    Huang, Wei-Chih; Päs, Heinrich; Zeißner, Sinan

    2018-03-01

    Many grand unified theory (GUT) models conserve the difference between the baryon and lepton number, B -L . These models can create baryon and lepton asymmetries from heavy Higgs or gauge boson decays with B +L ≠0 but with B -L =0 . Since the sphaleron processes violate B +L , such GUT-generated asymmetries will finally be washed out completely, making GUT baryogenesis scenarios incapable of reproducing the observed baryon asymmetry of the Universe. In this work, we revisit the idea to revive GUT baryogenesis, proposed by Fukugita and Yanagida, where right-handed neutrinos erase the lepton asymmetry before the sphaleron processes can significantly wash out the original B +L asymmetry, and in this way one can prevent a total washout of the initial baryon asymmetry. By solving the Boltzmann equations numerically for baryon and lepton asymmetries in a simplified 1 +1 flavor scenario, we can confirm the results of the original work. We further generalize the analysis to a more realistic scenario of three active and two right-handed neutrinos to highlight flavor effects of the right-handed neutrinos. Large regions in the parameter space of the Yukawa coupling and the right-handed neutrino mass featuring successful baryogenesis are identified.

  5. Paradise Islands? Island States and Environmental Performance

    Directory of Open Access Journals (Sweden)

    Sverker C. Jagers

    2016-03-01

    Full Text Available Island states have been shown to outperform continental states on a number of large-scale coordination-related outcomes, such as levels of democracy and institutional quality. The argument developed and tested in this article contends that the same kind of logic may apply to islands’ environmental performance, too. However, the empirical analysis shows mixed results. Among the 105 environmental outcomes that we analyzed, being an island only has a positive impact on 20 of them. For example, island states tend to outcompete continental states with respect to several indicators related to water quality but not in aspects related to biodiversity, protected areas, or environmental regulations. In addition, the causal factors previously suggested to make islands outperform continental states in terms of coordination have weak explanatory power in predicting islands’ environmental performance. We conclude the paper by discussing how these interesting findings can be further explored.

  6. Cutaneous mast cell maturation does not depend on an intact bone marrow microenvironment

    International Nuclear Information System (INIS)

    Charley, M.R.; Mikhael, A.; Sontheimer, R.D.; Gilliam, J.N.; Bennett, M.

    1984-01-01

    A study was made to determine whether the maturation of murine cutaneous mast cells from stem cells depends on an intact bone marrow microenvironment. Normal bone marrow cells (+/+) were infused into 2 groups of mast cell-deficient mice: WBB6F1-W/Wv mice and 89 Sr-pretreated W/Wv mice. 89 Sr is a long-lived bone-seeking radioisotope which provides continuous irradiation of the marrow and thereby ablates the marrow microenvironment. Skin biopsies revealed that the 89 Sr-pretreated mice and the controls had repopulated their skin with mast cells equally well. Natural killer cell function was significantly depressed in the 89 Sr-treated mice, confirming that the marrow microenvironment had been functionally altered. It appears that, although the precursors for cutaneous mast cells are marrow derived, they do not need an intact marrow microenvironment for maturation

  7. Revisiting Hansen Solubility Parameters by Including Thermodynamics

    NARCIS (Netherlands)

    Louwerse, Manuel J; Fernández-Maldonado, Ana María; Rousseau, Simon; Moreau-Masselon, Chloe; Roux, Bernard; Rothenberg, Gadi

    2017-01-01

    The Hansen solubility parameter approach is revisited by implementing the thermodynamics of dissolution and mixing. Hansen's pragmatic approach has earned its spurs in predicting solvents for polymer solutions, but for molecular solutes improvements are needed. By going into the details of entropy

  8. The Future of Engineering Education--Revisited

    Science.gov (United States)

    Wankat, Phillip C.; Bullard, Lisa G.

    2016-01-01

    This paper revisits the landmark CEE series, "The Future of Engineering Education," published in 2000 (available free in the CEE archives on the internet) to examine the predictions made in the original paper as well as the tools and approaches documented. Most of the advice offered in the original series remains current. Despite new…

  9. Revisiting the formal foundation of Probabilistic Databases

    NARCIS (Netherlands)

    Wanders, B.; van Keulen, Maurice

    2015-01-01

    One of the core problems in soft computing is dealing with uncertainty in data. In this paper, we revisit the formal foundation of a class of probabilistic databases with the purpose to (1) obtain data model independence, (2) separate metadata on uncertainty and probabilities from the raw data, (3)

  10. Revisiting Weak Simulation for Substochastic Markov Chains

    DEFF Research Database (Denmark)

    Jansen, David N.; Song, Lei; Zhang, Lijun

    2013-01-01

    of the logic PCTL\\x, and its completeness was conjectured. We revisit this result and show that soundness does not hold in general, but only for Markov chains without divergence. It is refuted for some systems with substochastic distributions. Moreover, we provide a counterexample to completeness...

  11. Coccolithophorids in polar waters: Wigwamma spp. revisited

    DEFF Research Database (Denmark)

    Thomsen, Helge Abildhauge; Østergaard, Jette B.; Heldal, Mikal

    2013-01-01

    A contingent of weakly calcified coccolithophorid genera and species were described from polar regions almost 40 years ago. In the interim period a few additional findings have been reported enlarging the realm of some of the species. The genus Wigwamma is revisited here with the purpose of provi...... appearance of the coccolith armour of the cell...

  12. The Faraday effect revisited: General theory

    DEFF Research Database (Denmark)

    Cornean, Horia Decebal; Nenciu, Gheorghe; Pedersen, Thomas Garm

    2006-01-01

    This paper is the first in a series revisiting the Faraday effect, or more generally, the theory of electronic quantum transport/optical response in bulk media in the presence of a constant magnetic field. The independent electron approximation is assumed. At zero temperature and zero frequency...

  13. The Faraday effect revisited: General theory

    DEFF Research Database (Denmark)

    Cornean, Horia Decebal; Nenciu, Gheorghe; Pedersen, Thomas Garm

    This paper is the first in a series revisiting the Faraday effect, or more generally, the theory of electronic quantum transport/optical response in bulk media in the presence of a constant magnetic field. The independent electron approximation is assumed. For free electrons, the transverse...

  14. Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2017-12-01

    AWARD NUMBER: W81XWH-13-1-0163 TITLE: Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-resistant Prostate Cancer ...Prostate Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Feng Yang, Ph.D. 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: fyang@bcm.edu...W81XWH-13-1-0163 " Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-resistant Prostate Cancer " Introduction AR signaling

  15. Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment

    Directory of Open Access Journals (Sweden)

    Bo Jiang

    2017-03-01

    Full Text Available Metabolic abnormalities is a hallmark of cancer. About 100 years ago, Nobel laureate Otto Heinrich Warburg first described high rate of glycolysis in cancer cells. Recently more and more novel opinions about cancer metabolism supplement to this hypothesis, consist of glucose uptake, lactic acid generation and secretion, acidification of the microenvironment and cancer immune evasion. Here we briefly review metabolic pathways generating lactate, and discuss the function of higher lactic acid in cancer microenvironments.

  16. Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target

    Science.gov (United States)

    2016-06-01

    AWARD NUMBER: W81XWH-14-1-0107 TITLE: Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target PRINCIPAL...AND SUBTITLE Tumor Microenvironment Gene Signature as a 5a. CONTRACT NUMBER W81XWH-14-1-0107 Prognostic Classifier and Therapeutic Target 5b...gene signature that correlates with poor survival in ovarian cancer patients. We are refining this gene signature to develop biomarkers for the

  17. Immune Microenvironment in Colorectal Cancer: A New Hallmark to Change Old Paradigms

    OpenAIRE

    de la Cruz-Merino, Luis; Henao Carrasco, Fernando; Vicente Baz, David; Nogales Fernández, Esteban; Reina Zoilo, Juan José; Codes Manuel de Villena, Manuel; Pulido, Enrique Grande

    2011-01-01

    Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cance...

  18. Breast cancer by proxy: can the microenvironment be both the cause and consequence?

    DEFF Research Database (Denmark)

    Rønnov-Jessen, Lone; Bissell, Mina J

    2009-01-01

    development because of the dramatic loss or aberration of basement membrane (BM) and myoepithelial cells and the gain of peritumoral myofibroblasts. We suggest that the microenvironment, defined here as all components of the mammary gland other than luminal and/or tumor epithelial cells, might be instrumental...... in maintaining organ integrity and in promoting, and at times even initiating, breast cancer development. As such, the tumor microenvironment and its constituents, alone or in combination, might serve as promising targets for therapy....

  19. Mola'a Revisited: Reef Panpipes

    DEFF Research Database (Denmark)

    2017-01-01

    The first main shoot for the Reef Islands Ethnographic Film Series in the Solomon Islands, in 1996, was seriously affected by the un- expected death of one of the main characters and partners in the project, Alfred Melotu, the paramount chief of the Aiwoo-speaking people on the island of Ngasinue...

  20. Radiation impairs perineural invasion by modulating the nerve microenvironment.

    Directory of Open Access Journals (Sweden)

    Richard L Bakst

    Full Text Available Perineural invasion (PNI by cancer cells is an ominous clinical event that is associated with increased local recurrence and poor prognosis. Although radiation therapy (RT may be delivered along the course of an invaded nerve, the mechanisms through which radiation may potentially control PNI remain undefined.An in vitro co-culture system of dorsal root ganglia (DRG and pancreatic cancer cells was used as a model of PNI. An in vivo murine sciatic nerve model was used to study how RT to nerve or cancer affects nerve invasion by cancer.Cancer cell invasion of the DRG was partially dependent on DRG secretion of glial-derived neurotrophic factor (GDNF. A single 4 Gy dose of radiation to the DRG alone, cultured with non-radiated cancer cells, significantly inhibited PNI and was associated with decreased GDNF secretion but intact DRG viability. Radiation of cancer cells alone, co-cultured with non-radiated nerves, inhibited PNI through predominantly compromised cancer cell viability. In a murine model of PNI, a single 8 Gy dose of radiation to the sciatic nerve prior to implantation of non-radiated cancer cells resulted in decreased GDNF expression, decreased PNI by imaging and histology, and preservation of sciatic nerve motor function.Radiation may impair PNI through not only direct effects on cancer cell viability, but also an independent interruption of paracrine mechanisms underlying PNI. RT modulation of the nerve microenvironment may decrease PNI, and hold significant therapeutic implications for RT dosing and field design for patients with cancers exhibiting PNI.

  1. Adipose, Bone, and Myeloma: Contributions from the Microenvironment.

    Science.gov (United States)

    McDonald, Michelle M; Fairfield, Heather; Falank, Carolyne; Reagan, Michaela R

    2017-05-01

    Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide (Podar et al. in Expert Opin Emerg Drugs 14:99-127, 2009). Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90 % of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes, and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies.

  2. WE-E-BRE-12: Tumor Microenvironment Dynamics Following Radiation

    International Nuclear Information System (INIS)

    Campos, D; Niles, D; Adamson, E; Torres, A; Kissick, M; Eliceiri, K; Kimple, R

    2014-01-01

    Purpose: This work aims to understand the radiation-induced interplay between tumor oxygenation and metabolic activity. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Using patient-derived xenografts of head and neck cancer we assessed tumor oxygenation via fiber-optic probe monitored hemoglobin saturation and Blood Oxygen Level Dependent (BOLD) MRI. Measurements were taken before and after a 10 Gy dose of radiation. Changes in metabolic activity were measured via Fluorescence Lifetime IMaging (FLIM) with the appropriate controls following a 10 Gy dose of radiation. FLIM can non-invasively monitor changes in fluorescence in response to the microenvironment including being able to detect free and bound states of the intrinsically fluorescent metabolite NADH (Nicotinamide Adenine Dinucleotide). With this information FLIM can accurately quantify the metabolic state of cells that have been radiated. To model the observed changes, a two-compartment, source-sink simulation relating hemoglobin saturation and metabolic activity was performed using MATLAB. Results: Hemoglobin saturation as measured by interstitial probe and BOLD-MRI decreased by 30% within 15 minutes following radiation. FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways. Simulation of radiation-induced alterations in tumor oxygenation demonstrated that these changes can be the result of changes in either vasculature or metabolic activity. Conclusion: Radiation induces significant changes in hemoglobin saturation and metabolic activity. These alterations occur on time scales approximately the duration of common radiation treatments. Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response

  3. Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances.

    Science.gov (United States)

    Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul; Vrana, Nihal Engin

    2014-01-01

    In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.

  4. Cell Microenvironment Engineering and Monitoring for Tissue Engineering and Regenerative Medicine: The Recent Advances

    Directory of Open Access Journals (Sweden)

    Julien Barthes

    2014-01-01

    Full Text Available In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells’ behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.

  5. Development and characterization of a microfluidic model of the tumour microenvironment.

    Science.gov (United States)

    Ayuso, Jose M; Virumbrales-Muñoz, María; Lacueva, Alodia; Lanuza, Pilar M; Checa-Chavarria, Elisa; Botella, Pablo; Fernández, Eduardo; Doblare, Manuel; Allison, Simon J; Phillips, Roger M; Pardo, Julián; Fernandez, Luis J; Ochoa, Ignacio

    2016-10-31

    The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live 'window' into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device's potential to enable more physiological in vitro drug screening.

  6. Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy.

    Science.gov (United States)

    Zhang, Bo; Shi, Wei; Jiang, Ting; Wang, Lanting; Mei, Heng; Lu, Heng; Hu, Yu; Pang, Zhiqing

    2016-09-20

    Effective delivery of nanomedicines to tumor tissues depends on both the tumor microenvironment and nanomedicine properties. Accordingly, tumor microenvironment modification or advanced design of nanomedicine was emerging to improve nanomedicine delivery to tumors. However, few studies have emphasized the necessity to optimize the tumor microenvironment and nanomedicine properties simultaneously to improve tumor treatment. In the present study, imatinib mesylate (IMA) was used to normalize the tumor microenvironment including platelet-derived growth factor receptor-β expression inhibition, tumor vessel normalization, and tumor perfusion improvement as demonstrated by immunofluorescence staining. In addition, the effect of tumor microenvironment normalization on tumor delivery of nanomedicines with different sizes was carefully investigated. It was shown that IMA treatment significantly reduced the accumulation of nanoparticles (NPs) around 110 nm but enhanced the accumulation of micelles around 23 nm by in vivo fluorescence imaging experiment. Furthermore, IMA treatment limited the distribution of NPs inside tumors but increased that of micelles with a more homogeneous pattern. Finally, the anti-tumor efficacy study displayed that IMA pretreatment could significantly increase the therapeutic effects of paclitaxel-loaded micelles. All-together, a new strategy to improve nanomedicine delivery to tumor was provided by optimizing both nanomedicine size and the tumor microenvironment simultaneously, and it will have great potential in clinics for tumor treatment.

  7. Porcine spermatogonial stem cells self-renew effectively in a three dimensional culture microenvironment.

    Science.gov (United States)

    Park, Ji Eun; Park, Min Hee; Kim, Min Seong; Park, Yeo Reum; Yun, Jung Im; Cheong, Hee Tae; Kim, Minseok; Choi, Jung Hoon; Lee, Eunsong; Lee, Seung Tae

    2017-12-01

    Generally, self-renewal of spermatogonial stem cells (SSCs) is maintained in vivo in a three-dimensional (3D) microenvironment consisting of the seminiferous tubule basement membrane, indicating the importance of the 3D microenvironment for in vitro culture of SSCs. Here, we report a 3D culture microenvironment that effectively maintains porcine SSC self-renewal during culture. Porcine SSCs were cultured in an agarose-based 3D hydrogel and in 2D culture plates either with or without feeder cells. Subsequently, the effects of 3D culture on the maintenance of undifferentiated SSCs were identified by analyzing cell colony formation and morphology, AP activity, and transcriptional and translational regulation of self-renewal-related genes and the effects on proliferation by analyzing cell viability and single cell-derived colony number. The 3D culture microenvironment constructed using a 0.2% (w/v) agarose-based 3D hydrogel showed the strongest maintenance of porcine SSC self-renewal and induced significant improvements in proliferation compared with 2D culture microenvironments. These results demonstrate that self-renewal of porcine SSCs can be maintained more effectively in a 3D than in a 2D culture microenvironment. Moreover, this will play a significant role in developing novel culture systems for SSCs derived from diverse species in the future, which will contribute to SSC-related research. © 2017 International Federation for Cell Biology.

  8. eWOM, Revisit Intention, Destination Trust and Gender

    OpenAIRE

    Abubakar, Abubakar Mohammed; Ilkan, Mustafa; Al-Tal, Raad Meshall; Eluwole, Kayode

    2017-01-01

    This article investigates the impact of eWOM on intention to revisit and destination trust, and the moderating role of gender in medical tourism industry. Result from structural equation modeling (n=240) suggests the following: (1) that eWOM influences intention to revisit and destination trust; (2) that destination trust influences intention to revisit; (3) that the impact of eWOM on intention to revisit is about 1.3 times higher in men; (4) that the impact of eWOM on destination trust is ab...

  9. Tanzania - Mafia Island Airport

    Data.gov (United States)

    Millennium Challenge Corporation — The evaluation design and subsequent data gathering activities will address the following key research questions: a) Has the Mafia Island Airport Upgrade Project...

  10. Roles of effective helical ripple rates in nonlinear stability of externally induced magnetic islands

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Seiya, E-mail: n-seiya@kobe-kosen.ac.jp [Kobe City College of Technology, Kobe, Hyogo 651-2194 (Japan)

    2015-02-15

    Magnetic islands are externally produced by resonant magnetic perturbations (RMPs) in toroidal plasmas. Spontaneous annihilation of RMP-induced magnetic islands called self-healing has been observed in helical systems. A possible mechanism of the self-healing is shielding of RMP penetration by helical ripple-induced neoclassical flows, which give rise to neoclassical viscous torques. In this study, effective helical ripple rates in multi-helicity helical systems are revisited, and a multi-helicity effect on the self-healing is investigated, based on a theoretical model of rotating magnetic islands. It is confirmed that effective helical ripple rates are sensitive to magnetic axis positions. It is newly found that self-healing thresholds also strongly depend on magnetic axis positions, which is due to dependence of neoclassical viscous torques on effective helical ripple rates.

  11. Assembly of hydrogel units for 3D microenvironment in a poly(dimethylsiloxane) channel

    Science.gov (United States)

    Cho, Chang Hyun; Kwon, Seyong; Park, Je-Kyun

    2017-12-01

    Construction of three-dimensional (3D) microenvironment become an important issue in recent biological studies due to their biological relevance compared to conventional two-dimensional (2D) microenvironment. Various fabrication techniques have been employed to construct a 3D microenvironment, however, it is difficult to fully satisfy the biological and mechanical properties required for the 3D cell culture system, such as heterogeneous tissue structures generated from the functional differences or diseases. We propose here an assembly method for facile construction of 3D microenvironment in a poly(dimethylsiloxane) (PDMS) channel using hydrogel units. The high-aspect-ratio of hydrogel units was achieved by fabricating these units using a 2D mold. With this approach, 3D heterogeneous hydrogel units were produced and assembled in a PDMS channel by structural hookup. In vivo-like 3D heterogeneous microenvironment in a precisely controllable fluidic system was also demonstrated using a controlled assembly of different types of hydrogel units, which was difficult to obtain from previous methods. By regulating the flow condition, the mechanical stability of the assembled hydrogel units was verified by the flow-induced deformation of hydrogel units. In addition, in vivo-like cell culture environment was demonstrated using an assembly of cell-coated hydrogel units in the fluidic channel. Based on these features, our method expects to provide a beneficial tool for the 3D cell culture module and biomimetic engineering.

  12. Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance

    Institute of Scientific and Technical Information of China (English)

    Tianjian Yu; Genhong Di

    2017-01-01

    Breast cancer has been shown to live in the tumor microenvironment,which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells.Diverse components of the breast cancer microenvironment,such as suppressive immune cells,re-programmed fibroblast cells,altered extracellular matrix (ECM) and certain soluble factors,synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis.Among these components,stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways,whereas the ECM features biochemical and biomechanical changes.However,triple-negative breast cancer (TNBC),the most aggressive subtype of this disease that lacks effective therapies available for other subtypes,is considered to feature a unique microenvironment distinct from that of other subtypes,especially compared to Luminal A subtype.Because these changes are now considered to significantly impact breast cancer development and progression,these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC.In this review,we focus on the composition of the TNBC microenvironment,concomitant distinct biological alteration,specific interplay between various cell types and TNBC cells,and the prognostic implications of these findings.

  13. Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment

    Science.gov (United States)

    Kim, Yong Sook; Jeong, Hye-yun; Kim, Ah Ra; Kim, Woong-Hee; Cho, Haaglim; Um, JungIn; Seo, Youngha; Kang, Wan Seok; Jin, Suk-Won; Kim, Min Chul; Kim, Yong-Chul; Jung, Da-Woon; Williams, Darren R.; Ahn, Youngkeun

    2016-01-01

    The cardiac microenvironment includes cardiomyocytes, fibroblasts and macrophages, which regulate remodeling after myocardial infarction (MI). Targeting this microenvironment is a novel therapeutic approach for MI. We found that the natural compound derivative, BIO ((2′Z,3′E)-6-Bromoindirubin-3′-oxime) modulated the cardiac microenvironment to exert a therapeutic effect on MI. Using a series of co-culture studies, BIO induced proliferation in cardiomyocytes and inhibited proliferation in cardiac fibroblasts. BIO produced multiple anti-fibrotic effects in cardiac fibroblasts. In macrophages, BIO inhibited the expression of pro-inflammatory factors. Significantly, BIO modulated the molecular crosstalk between cardiac fibroblasts and differentiating macrophages to induce polarization to the anti-inflammatory M2 phenotype. In the optically transparent zebrafish-based heart failure model, BIO induced cardiomyocyte proliferation and completely recovered survival rate. BIO is a known glycogen synthase kinase-3β inhibitor, but these effects could not be recapitulated using the classical inhibitor, lithium chloride; indicating novel therapeutic effects of BIO. We identified the mechanism of BIO as differential modulation of p27 protein expression and potent induction of anti-inflammatory interleukin-10. In a rat MI model, BIO reduced fibrosis and improved cardiac performance. Histological analysis revealed modulation of the cardiac microenvironment by BIO, with increased presence of anti-inflammatory M2 macrophages. Our results demonstrate that BIO produces unique effects in the cardiac microenvironment to promote recovery post-MI. PMID:27510556

  14. KEY FEATURES OF THE INTRAGRAFT MICROENVIRONMENT THAT DETERMINE LONG-TERM SURVIVAL FOLLOWING TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Sarah eBruneau

    2012-04-01

    Full Text Available In this review, we discuss how changes in the intragraft microenvironment serve to promote or sustain the development of chronic allograft rejection. We propose two key elements within the microenvironment that contribute to the rejection process. The first is endothelial cell proliferation and angiogenesis that serve to create abnormal microvascular blood flow patterns as well as local tissue hypoxia, and precedes endothelial-to-mesenchymal transition (EndMT. The second is the overexpression of local cytokines and growth factors that serve to sustain inflammation and, in turn, function to promote a leukocyte-induced angiogenesis reaction. Central to both events is overexpression of vascular endothelial growth factor (VEGF, which is both pro-inflammatory and pro-angiogenic, and thus drives progression of the chronic rejection microenvironment. In our discussion, we focus on how inflammation results in angiogenesis and how leukocyte-induced angiogenesis is pathological. We also discuss how VEGF is a master control factor that fosters the development of the chronic rejection microenvironment. Overall, this review provides insight into the intragraft microenvironment as an important paradigm for future direction in the field.

  15. Key Features of the Intragraft Microenvironment that Determine Long-Term Survival Following Transplantation

    Science.gov (United States)

    Bruneau, Sarah; Woda, Craig Bryan; Daly, Kevin Patrick; Boneschansker, Leonard; Jain, Namrata Gargee; Kochupurakkal, Nora; Contreras, Alan Gabriel; Seto, Tatsuichiro; Briscoe, David Michael

    2012-01-01

    In this review, we discuss how changes in the intragraft microenvironment serve to promote or sustain the development of chronic allograft rejection. We propose two key elements within the microenvironment that contribute to the rejection process. The first is endothelial cell proliferation and angiogenesis that serve to create abnormal microvascular blood flow patterns as well as local tissue hypoxia, and precedes endothelial-to-mesenchymal transition. The second is the overexpression of local cytokines and growth factors that serve to sustain inflammation and, in turn, function to promote a leukocyte-induced angiogenesis reaction. Central to both events is overexpression of vascular endothelial growth factor (VEGF), which is both pro-inflammatory and pro-angiogenic, and thus drives progression of the chronic rejection microenvironment. In our discussion, we focus on how inflammation results in angiogenesis and how leukocyte-induced angiogenesis is pathological. We also discuss how VEGF is a master control factor that fosters the development of the chronic rejection microenvironment. Overall, this review provides insight into the intragraft microenvironment as an important paradigm for future direction in the field. PMID:22566935

  16. Revisiting Cementoblastoma with a Rare Case Presentation

    Directory of Open Access Journals (Sweden)

    Vijayanirmala Subramani

    2017-01-01

    Full Text Available Cementoblastoma is a rare benign odontogenic neoplasm which is characterized by the proliferation of cellular cementum. Diagnosis of cementoblastoma is challenging because of its protracted clinical, radiographic features, and bland histological appearance; most often cementoblastoma is often confused with other cementum and bone originated lesions. The aim of this article is to overview/revisit, approach the diagnosis of cementoblastoma, and also present a unique radiographic appearance of a cementoblastoma lesion associated with an impacted tooth.

  17. Epigenetic silencing of CYP24 in the tumor microenvironment

    Science.gov (United States)

    Johnson, Candace S.; Chung, Ivy; Trump, Donald L.

    2010-01-01

    Calcitriol (1,25 dihydroxycholecalciferol) has significant antitumor activity in vitro and in vivo in a number of tumor model systems. We developed a system for isolation of fresh endothelial cells from tumors and Matrigel environments which demonstrate that CYP24, the catabolic enzyme involved in vitamin D signaling, is epigenetically silenced selectively in tumor-derived endothelial cells (TDEC). TDEC maintain phenotypic characteristics which are distinct from endothelial cells isolated from normal tissues and from Matrigel plugs (MDEC). In TDEC, calcitriol induces G0/G1 arrest, modulates p27 and p21, and induces apoptotic cell death and decreases P-Erk and P-Akt. In contrast, endothelial cells isolated from normal tissues and MDEC are unresponsive to calcitriol-mediated anti-proliferative effects despite intact signaling through the vitamin D receptor (VDR). In TDEC, which is sensitive to calcitriol, the CYP24 promoter is hypermethylated in two CpG island regions located at the 5′end; this hypermethylation may contribute to gene silencing of CYP24. The extent of methylation in these two regions is significantly less in MDEC. Lastly, treatment of TDEC with a DNA methyltransferase inhibitor restores calcitriol-mediated induction of CYP24 and resistance to calcitriol. These data suggest that epigenetic silencing of CYP24 modulates cellular responses to calcitriol. PMID:20304059

  18. Vancouver Island gas supply

    International Nuclear Information System (INIS)

    Des Brisay, C.

    2005-01-01

    Terasen Gas is pursuing alternatives for the supply of additional natural gas capacity to Vancouver Island. Its subsidiary, Terasen Gas (Vancouver Island) Inc. (TGVI), is responding to the need for delivery of increased gas supply and, is supporting plans for new gas-fired power generation on Vancouver Island. TGVI's proposal for new natural gas capacity involves a combination of compression and pipeline loops as well as the addition of a storage facility for liquefied natural gas (LNG) at Mt. Hayes to help manage price volatility. This presentation outlined the objectives and components of the resource planning process, including demand forecast scenarios and the preferred infrastructure options. tabs., figs

  19. [Design of an anesthesia and micro-environment information management system in mobile operating room].

    Science.gov (United States)

    Wang, Xianwen; Liu, Zhiguo; Zhang, Wenchang; Wu, Qingfu; Tan, Shulin

    2013-08-01

    We have designed a mobile operating room information management system. The system is composed of a client and a server. A client, consisting of a PC, medical equipments, PLC and sensors, provides the acquisition and processing of anesthesia and micro-environment data. A server is a powerful computer that stores the data of the system. The client gathers the medical device data by using the C/S mode, and analyzes the obtained HL7 messages through the class library call. The client collects the micro-environment information with PLC, and finishes the data reading with the OPC technology. Experiment results showed that the designed system could manage the patient anesthesia and micro-environment information well, and improve the efficiency of the doctors' works and the digital level of the mobile operating room.

  20. Breast cancer by proxy: Can the microenvironment be both the cause and consequence?

    Energy Technology Data Exchange (ETDEWEB)

    Ronnov-Jessen, Lone; Bissell, Mina J

    2008-11-16

    Breast cancer is one of the most clear-cut examples of a solid tumor in which systemic cues play a decisive part in its development. The breast tissue is constantly subjected to changes in hormone levels and modifications in the microenvironment. This scenario is even more striking during tumor development because of the dramatic loss or aberration of basement membrane (BM) and myoepithelial cells and the gain of peritumoral myofibroblasts. We suggest that the microenvironment, defined here as all components of the mammary gland other than luminal and/or tumor epithelial cells, might be instrumental in maintaining organ integrity and in promoting, and at times even initiating, breast cancer development. As such, the tumor microenvironment and its constituents, alone or in combination, might serve as promising targets for therapy.

  1. Island formation without attractive interaction

    NARCIS (Netherlands)

    Jansen, A.P.J.

    2008-01-01

    We show that adsorbates on surfaces can form islands even if there are no attractive interactions. Instead, strong repulsion between adsorbates at short distances can lead to islands, because such islands increase the entropy of the adsorbates that are not part of the islands. We suggest that this

  2. Comparison of radiofrequency electromagnetic field exposure levels in different everyday microenvironments in an international context.

    Science.gov (United States)

    Sagar, Sanjay; Adem, Seid M; Struchen, Benjamin; Loughran, Sarah P; Brunjes, Michael E; Arangua, Lisa; Dalvie, Mohamed Aqiel; Croft, Rodney J; Jerrett, Michael; Moskowitz, Joel M; Kuo, Tony; Röösli, Martin

    2018-05-01

    The aim of this study was to quantify RF-EMF exposure applying a tested protocol of RF-EMF exposure measurements using portable devices with a high sampling rate in different microenvironments of Switzerland, Ethiopia, Nepal, South Africa, Australia and the United States of America. We used portable measurement devices for assessing RF-EMF exposure in 94 outdoor microenvironments and 18 public transport vehicles. The measurements were taken either by walking with a backpack with the devices at the height of the head and a distance of 20-30 cm from the body, or driving a car with the devices mounted on its roof, which was 170-180 cm above the ground. The measurements were taken for about 30 min while walking and about 15-20 min while driving in each microenvironment, with a sampling rate of once every 4 s (ExpoM-RF) and 5 s (EME Spy 201). Mean total RF-EMF exposure in various outdoor microenvironments varied between 0.23 V/m (non-central residential area in Switzerland) and 1.85 V/m (university area in Australia), and across modes of public transport between 0.32 V/m (bus in rural area in Switzerland) and 0.86 V/m (Auto rickshaw in urban area in Nepal). For most outdoor areas the major exposure contribution was from mobile phone base stations. Otherwise broadcasting was dominant. Uplink from mobile phone handsets was generally very small, except in Swiss trains and some Swiss buses. This study demonstrates high RF-EMF variability between the 94 selected microenvironments from all over the world. Exposure levels tended to increase with increasing urbanity. In most microenvironments downlink from mobile phone base stations is the most relevant contributor. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. [Study on sweat gland regeneration induced by microenvironment of three-dimensional bioprinting].

    Science.gov (United States)

    Yao, B; Xie, J F; Huang, S; Fu, X B

    2017-01-20

    Sweat glands are abundant in the body surface and essential for thermoregulation. Sweat glands fail to conduct self-repair in patients with large area of burn and trauma, and the body temperature of patients increases in hot climate, which may cause shock or even death. Now, co-culture system, reprogramming, and tissue engineering have made progresses in inducing sweat gland regeneration, but the inductive efficiency and duration need to be improved. Cellular microenvironment can regulate cell biological behavior, including cell migration and cell differentiation. This article reviews the studies of establishment of microenvironment in vitro by three-dimensional bioprinting technology to induce sweat gland regeneration.

  4. Coalescence of magnetic islands

    International Nuclear Information System (INIS)

    Pellat, R.

    1982-01-01

    The paper gives the analytical theory of the coalescence instability and of a new, one island, instability. These instabilities are expected to be relevant for the disruptions observed in Tokamak experiments and astrophysical plasmas

  5. Heat Island Compendium

    Science.gov (United States)

    Heat islands can be mitigated through measures like planting trees and vegetation, installing green roofs and cool roofs, and using cool pavements. The compendium describes all of these strategies and shows how communities around the country are being used

  6. Islands and Islandness in Rock Music Lyrics

    Directory of Open Access Journals (Sweden)

    Daniele Mezzana

    2012-05-01

    Full Text Available This paper presents a first exploration, qualitative in character, based on a review of 412 songs produced in the period 1960-2009, about islands in rock music as both social products and social tools potentially contributing to shaping ideas, emotions, will, and desires. An initial taxonomy of 24 themes clustered under five meta-themes of space, lifestyle, emotions, symbolism, and social-political relations is provided, together with some proposals for further research.

  7. Personal exposure monitoring of PM2.5 in indoor and outdoor microenvironments

    DEFF Research Database (Denmark)

    Steinle, Susanne; Reis, Stefan; Sabel, Clive E

    2015-01-01

    to define six microenvironments (MEs) to assess everyday exposure of individuals to short-term PM2.5 concentrations. The Dylos was combined with a GPS receiver to track movement and exposure of individuals across the MEs. Seventeen volunteers collected 35 profiles. Profiles may have a different overall...

  8. Remodeling the blood–brain barrier microenvironment by natural products for brain tumor therapy

    Institute of Scientific and Technical Information of China (English)

    Xiao Zhao; Rujing Chen; Mei Liu; Jianfang Feng; Jun Chen; Kaili Hu

    2017-01-01

    Brain tumor incidence shows an upward trend in recent years; brain tumors account for 5% of adult tumors, while in children, this figure has increased to 70%. Moreover, 20%–30% of malignant tumors will eventually metastasize into the brain. Both benign and malignant tumors can cause an increase in intracranial pressure and brain tissue compression, leading to central nervous system(CNS) damage which endangers the patients’ lives. Despite the many approaches to treating brain tumors and the progress that has been made, only modest gains in survival time of brain tumor patients have been achieved. At present, chemotherapy is the treatment of choice for many cancers, but the special structure of the blood–brain barrier(BBB) limits most chemotherapeutic agents from passing through the BBB and penetrating into tumors in the brain. The BBB microenvironment contains numerous cell types, including endothelial cells, astrocytes, peripheral cells and microglia, and extracellular matrix(ECM). Many chemical components of natural products are reported to regulate the BBB microenvironment near brain tumors and assist in their treatment. This review focuses on the composition and function of the BBB microenvironment under both physiological and pathological conditions, and the current research progress in regulating the BBB microenvironment by natural products to promote the treatment of brain tumors.

  9. Immunotherapeutic Potential of Oncolytic H-1 Parvovirus: Hints of Glioblastoma Microenvironment Conversion towards Immunogenicity.

    Science.gov (United States)

    Angelova, Assia L; Barf, Milena; Geletneky, Karsten; Unterberg, Andreas; Rommelaere, Jean

    2017-12-15

    Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV), show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01), H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients. The virus was able to cross the blood-brain (tumor) barrier after intravenous infusion. Importantly, H-1PV treatment of glioblastoma patients was associated with immunogenic changes in the tumor microenvironment. Tumor infiltration with activated cytotoxic T cells, induction of cathepsin B and inducible nitric oxide (NO) synthase (iNOS) expression in tumor-associated microglia/macrophages (TAM), and accumulation of activated TAM in cluster of differentiation (CD) 40 ligand (CD40L)-positive glioblastoma regions was detected. These are the first-in-human observations of H-1PV capacity to switch the immunosuppressed tumor microenvironment towards immunogenicity. Based on this pilot study, we present a tentative model of H-1PV-mediated modulation of glioblastoma microenvironment and propose a combinatorial therapeutic approach taking advantage of H-1PV-induced microglia/macrophage activation for further (pre)clinical testing.

  10. 3D bioprinting: improving in vitro models of metastasis with heterogeneous tumor microenvironments

    Directory of Open Access Journals (Sweden)

    Jacob L. Albritton

    2017-01-01

    Full Text Available Even with many advances in treatment over the past decades, cancer still remains a leading cause of death worldwide. Despite the recognized relationship between metastasis and increased mortality rate, surprisingly little is known about the exact mechanism of metastatic progression. Currently available in vitro models cannot replicate the three-dimensionality and heterogeneity of the tumor microenvironment sufficiently to recapitulate many of the known characteristics of tumors in vivo. Our understanding of metastatic progression would thus be boosted by the development of in vitro models that could more completely capture the salient features of cancer biology. Bioengineering groups have been working for over two decades to create in vitro microenvironments for application in regenerative medicine and tissue engineering. Over this time, advances in 3D printing technology and biomaterials research have jointly led to the creation of 3D bioprinting, which has improved our ability to develop in vitro models with complexity approaching that of the in vivo tumor microenvironment. In this Review, we give an overview of 3D bioprinting methods developed for tissue engineering, which can be directly applied to constructing in vitro models of heterogeneous tumor microenvironments. We discuss considerations and limitations associated with 3D printing and highlight how these advances could be harnessed to better model metastasis and potentially guide the development of anti-cancer strategies.

  11. 3D bioprinting: improving in vitro models of metastasis with heterogeneous tumor microenvironments.

    Science.gov (United States)

    Albritton, Jacob L; Miller, Jordan S

    2017-01-01

    Even with many advances in treatment over the past decades, cancer still remains a leading cause of death worldwide. Despite the recognized relationship between metastasis and increased mortality rate, surprisingly little is known about the exact mechanism of metastatic progression. Currently available in vitro models cannot replicate the three-dimensionality and heterogeneity of the tumor microenvironment sufficiently to recapitulate many of the known characteristics of tumors in vivo Our understanding of metastatic progression would thus be boosted by the development of in vitro models that could more completely capture the salient features of cancer biology. Bioengineering groups have been working for over two decades to create in vitro microenvironments for application in regenerative medicine and tissue engineering. Over this time, advances in 3D printing technology and biomaterials research have jointly led to the creation of 3D bioprinting, which has improved our ability to develop in vitro models with complexity approaching that of the in vivo tumor microenvironment. In this Review, we give an overview of 3D bioprinting methods developed for tissue engineering, which can be directly applied to constructing in vitro models of heterogeneous tumor microenvironments. We discuss considerations and limitations associated with 3D printing and highlight how these advances could be harnessed to better model metastasis and potentially guide the development of anti-cancer strategies. © 2017. Published by The Company of Biologists Ltd.

  12. Effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice

    International Nuclear Information System (INIS)

    Huston, D.P.; Smathers, P.A.; Reeves, J.P.; Steinberg, A.D.

    1983-01-01

    The effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice were studied. Neonatally thymectomized male and female F1 mice reconstituted with a parental or F1-irradiated thymic lobe were compared to nonreconstituted and sham-thymectomized controls. While maleness retarded the spontaneous production of ss- and ds-DNA antibodies, thymic grafts did not suppress antibodies to ss-DNA in either sex, but did suppress the production of antibodies to ds-DNA in female mice. A unique property of NZB thymic grafts was the inability to suppress anti-RBC antibodies in male mice. Thus, (i) the gender of the F1 recipient was the most important determinant of production of antibodies to ss-DNA, (ii) either maleness or the thymic microenvironment could retard production of anti-ds-DNA antibodies, and (iii) both gender and the thymic microenvironment were important in the regulation of anti-RBC antibody production. Since the administration of thymosin did not suppress autoantibody production, the effects of the thymic grafts was not solely via thymic hormone production. These studies suggest that sex hormones and/or the thymic microenvironment can exert a suppressive effect on autoantibody production and that autoantibodies differ in their susceptibility to such suppression

  13. Acidic tumor microenvironment and pH-sensing G protein-coupled receptors.

    Science.gov (United States)

    Justus, Calvin R; Dong, Lixue; Yang, Li V

    2013-12-05

    The tumor microenvironment is acidic due to glycolytic cancer cell metabolism, hypoxia, and deficient blood perfusion. It is proposed that acidosis in the tumor microenvironment is an important stress factor and selection force for cancer cell somatic evolution. Acidic pH has pleiotropic effects on the proliferation, migration, invasion, metastasis, and therapeutic response of cancer cells and the function of immune cells, vascular cells, and other stromal cells. However, the molecular mechanisms by which cancer cells and stromal cells sense and respond to acidic pH in the tumor microenvironment are poorly understood. In this article the role of a family of pH-sensing G protein-coupled receptors (GPCRs) in tumor biology is reviewed. Recent studies show that the pH-sensing GPCRs, including GPR4, GPR65 (TDAG8), GPR68 (OGR1), and GPR132 (G2A), regulate cancer cell metastasis and proliferation, immune cell function, inflammation, and blood vessel formation. Activation of the proton-sensing GPCRs by acidosis transduces multiple downstream G protein signaling pathways. Since GPCRs are major drug targets, small molecule modulators of the pH-sensing GPCRs are being actively developed and evaluated. Research on the pH-sensing GPCRs will continue to provide important insights into the molecular interaction between tumor and its acidic microenvironment and may identify new targets for cancer therapy and chemoprevention.

  14. Carbonic anhydrase IX (CA IX) mediates tumor cell interactions with microenvironment

    Czech Academy of Sciences Publication Activity Database

    Závadová, Zuzana; Závada, Jan

    2005-01-01

    Roč. 13, č. 5 (2005), s. 977-982 ISSN 1021-335X R&D Projects: GA ČR(CZ) GA203/02/0405 Institutional research plan: CEZ:AV0Z50520514 Keywords : carbonic anhydrase IX * cell adhesion * microenvironment Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.572, year: 2005

  15. Tumour microenvironment and radiation response in sarcomas originating from tumourigenic human mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Safwat, Akmal Ahmed; Burns, Jorge S.

    2012-01-01

    : Immune deficient female mice were implanted on the backs with cells from one of the clones. The subsequent tumours were subjected to either radiation treatment or had the tumour microenvironment assayed, when they reached 400mm3. Radiation was given as a single fraction of 0 to 15 Gy and the degree...

  16. Metastasis in context : modeling the tumor microenvironment with cancer-on-a-chip approaches

    NARCIS (Netherlands)

    Sleeboom, Jelle J.F.; Amirabadi, Hossein Eslami; Nair, Poornima; Sahlgren, Cecilia M.; Den Toonder, Jaap M.J.

    2018-01-01

    Most cancer deaths are not caused by the primary tumor, but by secondary tumors formed through metastasis, a complex and poorly understood process. Cues from the tumor microenvironment, such as the biochemical composition, cellular population, extracellular matrix, and tissue (fluid) mechanics, have

  17. Bed Microenvironment in Hospital Patient Rooms with Natural or Mechanical Ventilation

    DEFF Research Database (Denmark)

    Melikov, Arsen Krikor; Li, Yuguo; Georgiev, Emanuil

    2012-01-01

    We studied how to provide patients in bed with thermally comfortable microenvironment in both naturally and mechanically ventilated hospital rooms for both winter and summer seasons. A climate chamber was used to resemble a hospital room and thermal manikin to simulate a patient lying in a bed...

  18. Molecular imaging of the tumor microenvironment for precision medicine and theranostics.

    Science.gov (United States)

    Penet, Marie-France; Krishnamachary, Balaji; Chen, Zhihang; Jin, Jiefu; Bhujwalla, Zaver M

    2014-01-01

    Morbidity and mortality from cancer and their associated conditions and treatments continue to extract a heavy social and economic global burden despite the transformative advances in science and technology in the twenty-first century. In fact, cancer incidence and mortality are expected to reach pandemic proportions by 2025, and costs of managing cancer will escalate to trillions of dollars. The inability to establish effective cancer treatments arises from the complexity of conditions that exist within tumors, the plasticity and adaptability of cancer cells coupled with their ability to escape immune surveillance, and the co-opted stromal cells and microenvironment that assist cancer cells in survival. Stromal cells, although destroyed together with cancer cells, have an ever-replenishing source that can assist in resurrecting tumors from any residual cancer cells that may survive treatment. The tumor microenvironment landscape is a continually changing landscape, with spatial and temporal heterogeneities that impact and influence cancer treatment outcome. Importantly, the changing landscape of the tumor microenvironment can be exploited for precision medicine and theranostics. Molecular and functional imaging can play important roles in shaping and selecting treatments to match this landscape. Our purpose in this review is to examine the roles of molecular and functional imaging, within the context of the tumor microenvironment, and the feasibility of their applications for precision medicine and theranostics in humans. © 2014 Elsevier Inc. All rights reserved.

  19. Human body micro-environment: The benefits of controlling airflow interaction

    DEFF Research Database (Denmark)

    Melikov, Arsen Krikor

    2015-01-01

    This paper focuses on the micro-environment around a human body, and especially on its interaction with the surrounding environment. Research on the free convection flow generated by a human body (including the convective boundary layer around the body and the thermal plume above the body), its...

  20. Advanced Change Theory Revisited: An Article Critique

    Directory of Open Access Journals (Sweden)

    R. Scott Pochron

    2008-12-01

    Full Text Available The complexity of life in 21st century society requires new models for leading and managing change. With that in mind, this paper revisits the model for Advanced Change Theory (ACT as presented by Quinn, Spreitzer, and Brown in their article, “Changing Others Through Changing Ourselves: The Transformation of Human Systems” (2000. The authors present ACT as a potential model for facilitating change in complex organizations. This paper presents a critique of the article and summarizes opportunities for further exploring the model in the light of current trends in developmental and integral theory.

  1. Resolution of Reflection Seismic Data Revisited

    DEFF Research Database (Denmark)

    Hansen, Thomas Mejer; Mosegaard, Klaus; Zunino, Andrea

    The Rayleigh Principle states that the minimum separation between two reflectors that allows them to be visually separated is the separation where the wavelet maxima from the two superimposed reflections combine into one maximum. This happens around Δtres = λb/8, where λb is the predominant...... lower vertical resolution of reflection seismic data. In the following we will revisit think layer model and demonstrate that there is in practice no limit to the vertical resolution using the parameterization of Widess (1973), and that the vertical resolution is limited by the noise in the data...

  2. Revisiting fifth forces in the Galileon model

    Energy Technology Data Exchange (ETDEWEB)

    Burrage, Clare [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Gruppe Theorie; Seery, David [Sussex Univ., Brighton (United Kingdom). Dept. of Physics and Astronomy

    2010-05-15

    A Galileon field is one which obeys a spacetime generalization of the non- relativistic Galilean invariance. Such a field may possess non-canonical kinetic terms, but ghost-free theories with a well-defined Cauchy problem exist, constructed using a finite number of relevant operators. The interactions of this scalar with matter are hidden by the Vainshtein effect, causing the Galileon to become weakly coupled near heavy sources. We revisit estimates of the fifth force mediated by a Galileon field, and show that the parameters of the model are less constrained by experiment than previously supposed. (orig.)

  3. Large J expansion in ABJM theory revisited.

    Science.gov (United States)

    Dimov, H; Mladenov, S; Rashkov, R C

    Recently there has been progress in the computation of the anomalous dimensions of gauge theory operators at strong coupling by making use of the AdS/CFT correspondence. On the string theory side they are given by dispersion relations in the semiclassical regime. We revisit the problem of a large-charge expansion of the dispersion relations for simple semiclassical strings in an [Formula: see text] background. We present the calculation of the corresponding anomalous dimensions of the gauge theory operators to an arbitrary order using three different methods. Although the results of the three methods look different, power series expansions show their consistency.

  4. Sloan Digital Sky Survey Photometric Calibration Revisited

    International Nuclear Information System (INIS)

    Marriner, John

    2012-01-01

    The Sloan Digital Sky Survey calibration is revisited to obtain the most accurate photometric calibration. A small but significant error is found in the flat-fielding of the Photometric telescope used for calibration. Two SDSS star catalogs are compared and the average difference in magnitude as a function of right ascension and declination exhibits small systematic errors in relative calibration. The photometric transformation from the SDSS Photometric Telescope to the 2.5 m telescope is recomputed and compared to synthetic magnitudes computed from measured filter bandpasses.

  5. Revisiting the Political Economy of Communication

    Directory of Open Access Journals (Sweden)

    Nicholas Garnham

    2014-02-01

    The task of the paper and the seminar was to revisit some of Nicholas Garnham’s ideas, writings and contributions to the study of the Political Economy of Communication and to reflect on the concepts, history, current status and perspectives of this field and the broader study of political economy today. The topics covered include Raymond Williams’ cultural materialism, Pierre Bourdieu’s sociology of culture, the debate between Political Economy and Cultural Studies, information society theory, Karl Marx’s theory and the critique of capitalism.

  6. Sloan Digital Sky Survey Photometric Calibration Revisited

    Energy Technology Data Exchange (ETDEWEB)

    Marriner, John; /Fermilab

    2012-06-29

    The Sloan Digital Sky Survey calibration is revisited to obtain the most accurate photometric calibration. A small but significant error is found in the flat-fielding of the Photometric telescope used for calibration. Two SDSS star catalogs are compared and the average difference in magnitude as a function of right ascension and declination exhibits small systematic errors in relative calibration. The photometric transformation from the SDSS Photometric Telescope to the 2.5 m telescope is recomputed and compared to synthetic magnitudes computed from measured filter bandpasses.

  7. Differential immune microenvironments and response to immune checkpoint blockade amongst molecular subtypes of murine medulloblastoma

    Science.gov (United States)

    Pham, Christina D.; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M.; Yearley, Jennifer H.; Sayour, Elias J.; Pei, Yanxin; Moore, Colin; McLendon, Roger E.; Huang, Jianping; Sampson, John H.; Wechsler-Reya, Robert; Mitchell, Duane A.

    2016-01-01

    PURPOSE Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma (MB), the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and Group 3 MB for preclinical evaluation in immunocompetent C57BL/6 mice. METHODS AND RESULTS Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid derived suppressor cells and tumor-associated macrophages in murine SHH model tumors compared with Group 3 tumors. However, murine Group 3 tumors had higher percentages of CD8+ PD-1+ T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial Group 3 tumors compared to SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1+ peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3+ T cells within the tumor microenvironment. CONCLUSIONS This is the first immunologic characterization of preclinical models of molecular subtypes of MB and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. PMID:26405194

  8. Probing the electrostatics of active site microenvironments along the catalytic cycle for Escherichia coli dihydrofolate reductase.

    Science.gov (United States)

    Liu, C Tony; Layfield, Joshua P; Stewart, Robert J; French, Jarrod B; Hanoian, Philip; Asbury, John B; Hammes-Schiffer, Sharon; Benkovic, Stephen J

    2014-07-23

    Electrostatic interactions play an important role in enzyme catalysis by guiding ligand binding and facilitating chemical reactions. These electrostatic interactions are modulated by conformational changes occurring over the catalytic cycle. Herein, the changes in active site electrostatic microenvironments are examined for all enzyme complexes along the catalytic cycle of Escherichia coli dihydrofolate reductase (ecDHFR) by incorporation of thiocyanate probes at two site-specific locations in the active site. The electrostatics and degree of hydration of the microenvironments surrounding the probes are investigated with spectroscopic techniques and mixed quantum mechanical/molecular mechanical (QM/MM) calculations. Changes in the electrostatic microenvironments along the catalytic environment lead to different nitrile (CN) vibrational stretching frequencies and (13)C NMR chemical shifts. These environmental changes arise from protein conformational rearrangements during catalysis. The QM/MM calculations reproduce the experimentally measured vibrational frequency shifts of the thiocyanate probes across the catalyzed hydride transfer step, which spans the closed and occluded conformations of the enzyme. Analysis of the molecular dynamics trajectories provides insight into the conformational changes occurring between these two states and the resulting changes in classical electrostatics and specific hydrogen-bonding interactions. The electric fields along the CN axes of the probes are decomposed into contributions from specific residues, ligands, and solvent molecules that make up the microenvironments around the probes. Moreover, calculation of the electric field along the hydride donor-acceptor axis, along with decomposition of this field into specific contributions, indicates that the cofactor and substrate, as well as the enzyme, impose a substantial electric field that facilitates hydride transfer. Overall, experimental and theoretical data provide evidence for

  9. Differential Immune Microenvironments and Response to Immune Checkpoint Blockade among Molecular Subtypes of Murine Medulloblastoma.

    Science.gov (United States)

    Pham, Christina D; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M; Yearley, Jennifer H; Sayour, Elias J; Pei, Yanxin; Moore, Colin; McLendon, Roger E; Huang, Jianping; Sampson, John H; Wechsler-Reya, Robert; Mitchell, Duane A

    2016-02-01

    Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma, the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and group 3 medulloblastoma for preclinical evaluation in immunocompetent C57BL/6 mice. Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid-derived suppressor cells, and tumor-associated macrophages in murine SHH model tumors compared with group 3 tumors. However, murine group 3 tumors had higher percentages of CD8(+) PD-1(+) T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial group 3 tumors compared with SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1(+) peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3(+) T cells within the tumor microenvironment. This is the first immunologic characterization of preclinical models of molecular subtypes of medulloblastoma and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. ©2015 American Association for Cancer Research.

  10. Heron Island, Australia

    Science.gov (United States)

    2002-01-01

    Heron Island is located at the sourthern end of Australia's 2,050 km-long Great Barrier Reef. Surrounded by coral reef and home to over 1000 species of fish, scuba divers and scientists alike are drawn to the island's resort and research station. The true-color image above was taken by Space Imaging's Ikonos satellite with a resolution of 4 meters per pixel-high enough to see individual boats tied up at the small marina. The narrow channel leading from the marina to the ocean was blasted and dredged decades ago, before the island became a national park. Since then the Australian government has implemented conservation measures, such as limiting the number of tourists and removing or recycling, instead of incinerating, all trash. One of the applications of remote sensing data from Ikonos is environmental monitoring, including studies of coral reef health. For more information about the island, read Heron Island. Image by Robert Simmon, based on data copyright Space Imaging

  11. Small Island Visitor Attractions

    Directory of Open Access Journals (Sweden)

    Haven Allahar

    2015-03-01

    Full Text Available This article proposes a process framework for developing and managing visitor attractions (VA in small island developing states with Trinidad and Tobago, a two-island state in the Caribbean, as the case study. An extensive literature review was conducted, supported by field observations, individual depth interviews, and small and large focus group meetings. The process framework identified four sets of processes: national policy formulation and legislation; inventory, classification, evaluation, and ranking of VA; general operations management involving project management activities; and site specific activities of development, operations, and maintenance. The value of the framework lies in the fact that no similar framework applicable to small islands was covered in the literature and validation was obtained from a panel of experts and a cross section of tourism stakeholders in Tobago.

  12. Benefits, barriers, and intentions/desires of nurses related to distance learning in rural island communities.

    Science.gov (United States)

    Kataoka-Yahiro, Merle R; Richardson, Karol; Mobley, Joseph

    2011-03-01

    This study assessed distance learning needs among nurses on the Neighbor Islands in Hawaii. An exploratory study was conducted using a descriptive qualitative design. Of the 37 nurses who completed the study, 7 were nurse administrators and 30 were staff nurses. There were 18 focus groups of nurses recruited from six public hospitals on the Neighbor Islands. Three major themes related to distance learning emerged in this study: benefits, barriers, and intentions/desires. Each major theme had several linkages to categories and subcategories. Overall findings were as follows: (1) cost was mentioned more often in three major thematic areas (benefit, barriers, and intentions/desires); (2) the need to revisit and address current curriculum approaches and practices in distance learning programs was identified; and (3) strong recommendations were made for programs and organizational support for distance learning in hospital settings. These findings have implications for nursing research, education, and practice. Copyright 2011, SLACK Incorporated.

  13. Island of Luzon, Philippines

    Science.gov (United States)

    1990-01-01

    In this north to south view of the Island of Luzon, Philippines (13.0N, 120.0E), the prominent Cordillera Central mountain range where gold, copper and silver are mined. The several large rivers that drain this region normally carry a heavy silt load to the sea but the absence of sediment plumes in this view is evidence of hot dry weather and lack of recent rains. Manila, the capital city is just visible at the south end of the island.

  14. Chatham Islands Climate Change

    International Nuclear Information System (INIS)

    Mullan, B.; Salinger, J.; Thompson, C.; Ramsay, D.; Wild, M.

    2005-06-01

    This brief report provides guidance on climate change specific to the Chatham Islands, to complement the information recently produced for local government by the Ministry for the Environment in 'Climate Change Effects and Impacts Assessment: A guidance manual for Local Government in New Zealand' and 'Coastal Hazards and Climate Change: A guidance manual for Local Government in New Zealand'. These previous reports contain a lot of generic information on climate change, and how to assess associated risks, that is relevant to the Chatham Islands Council.

  15. Island in the Air

    DEFF Research Database (Denmark)

    Simonsen, Dorthe Gert

    2017-01-01

    In this article, I explore the formation of airspace in Britain from 1910 to 1913. The technology of flight challenged the “flat discourse” of nationalized geography, drawing up instead a volumetric space in the sky as airplanes flew from the Continent to England. The drive to control aerial...... extension of the Island Kingdom, extrapolating its coastal borders into the sky. However, even as Parliament passed the Aerial Navigation Act in 1913, this legal construction of an island in the air could not endure the agency of airplanes. The formation of airspace, I argue, is a history particularly well...

  16. Archaeoastronomy of Easter Island

    Science.gov (United States)

    Edwards, Edmundo

    Astronomer priests or "skywatchers" on Easter Island lived in stone towers that were used as observatories and built stone markers in the periphery that indicated the heliacal rising of certain stars that served to indicate the arrival of marine birds, turtles, the offshore fishing season, and times for planting and harvest. Petroglyphs related to such sites depict outriggers, fishhooks, pelagic fish, and turtles and supposedly represented a star map. In this chapter, we analyze a set of such skywatchers dwellings, and stone markers located upon the North coast of Easter Island that have astronomic orientations, its related petroglyphs, and the relations between these directions with their yearly activities and their ritual calendar.

  17. Long Island Solar Farm

    Energy Technology Data Exchange (ETDEWEB)

    Anders, R.

    2013-05-01

    The Long Island Solar Farm (LISF) is a remarkable success story, whereby very different interest groups found a way to capitalize on unusual circumstances to develop a mutually beneficial source of renewable energy. The uniqueness of the circumstances that were necessary to develop the Long Island Solar Farm make it very difficult to replicate. The project is, however, an unparalleled resource for solar energy research, which will greatly inform large-scale PV solar development in the East. Lastly, the LISF is a superb model for the process by which the project developed and the innovation and leadership shown by the different players.

  18. Direct laser writing by two-photon polymerization as a tool for developing microenvironments for evaluation of bacterial growth

    International Nuclear Information System (INIS)

    Otuka, A.J.G.; Corrêa, D.S.; Fontana, C.R.; Mendonça, C.R.

    2014-01-01

    Monitoring bacteria growth and motion in environments is fundamental to understand, for instance, how they proliferate and contaminate organism. Therefore, techniques to fabricate microenvironments for in situ and in vivo studies are interesting for that purpose. In this work we used two-photon polymerization to fabricate microenvironments and, as a proof of principle, we demonstrated the development of the bacteria ATCC 25922 Escherichia coli (E. coli) into the microstructure surroundings. Two varieties of polymeric microenvironments are presented: (i) a microenvironment doped at specific site with ciprofloxacin, an antibiotic typically used in the treatment of diseases caused by E. coli and (ii) micro-fences, which serve as traps for bacteria. These microenvironments, fabricated by two-photon polymerization, may be a potential platform for drug delivery system, by promoting or inhibiting the growth of bacteria in specific biological or synthetic sites. - Highlights: • Microenvironments were fabricated by two-photon polymerization. • We demonstrated the development of Escherichia coli into the microstructure surroundings. • Microenvironment doped with the antibiotic ciprofloxacin was fabricated. • Micro-fences, which serve as traps for bacteria, were also produced

  19. Direct laser writing by two-photon polymerization as a tool for developing microenvironments for evaluation of bacterial growth

    Energy Technology Data Exchange (ETDEWEB)

    Otuka, A.J.G. [Instituto de Física de São Carlos, Universidade de São Paulo, CP.369, 13560-970 São Carlos, SP (Brazil); Corrêa, D.S. [Laboratório Nacional de Nanotecnologia para o Agronegócio (LNNA), Embrapa Instrumentação, Rua XV de Novembro, 1452, CP.741, 13560-970 São Carlos, SP (Brazil); Fontana, C.R. [Department of Clinical Analysis, School of Pharmaceutical Sciences, University of São Paulo State (UNESP), 1621 Expedicionarios do Brasil Street, Araraquara, Sao Paulo 14801-960 (Brazil); Mendonça, C.R., E-mail: crmendon@ifsc.usp.br [Instituto de Física de São Carlos, Universidade de São Paulo, CP.369, 13560-970 São Carlos, SP (Brazil)

    2014-02-01

    Monitoring bacteria growth and motion in environments is fundamental to understand, for instance, how they proliferate and contaminate organism. Therefore, techniques to fabricate microenvironments for in situ and in vivo studies are interesting for that purpose. In this work we used two-photon polymerization to fabricate microenvironments and, as a proof of principle, we demonstrated the development of the bacteria ATCC 25922 Escherichia coli (E. coli) into the microstructure surroundings. Two varieties of polymeric microenvironments are presented: (i) a microenvironment doped at specific site with ciprofloxacin, an antibiotic typically used in the treatment of diseases caused by E. coli and (ii) micro-fences, which serve as traps for bacteria. These microenvironments, fabricated by two-photon polymerization, may be a potential platform for drug delivery system, by promoting or inhibiting the growth of bacteria in specific biological or synthetic sites. - Highlights: • Microenvironments were fabricated by two-photon polymerization. • We demonstrated the development of Escherichia coli into the microstructure surroundings. • Microenvironment doped with the antibiotic ciprofloxacin was fabricated. • Micro-fences, which serve as traps for bacteria, were also produced.

  20. Islanded operation of distribution networks

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This report summarises the results of a study assessing the benefits and risks to distribution network of generator islanding and examining the technical, commercial and regulatory changes required to facilitate the operation of islanding. The background to the study is traced, and details are given of a literature review, the technical criteria for operating sections of the network in islanding mode, and the impact of islanding on trading. Case studies and a detailed implementation plan, data acquisition, and commercial incentives are discussed.

  1. Islanded operation of distribution networks

    International Nuclear Information System (INIS)

    2005-01-01

    This report summarises the results of a study assessing the benefits and risks to distribution network of generator islanding and examining the technical, commercial and regulatory changes required to facilitate the operation of islanding. The background to the study is traced, and details are given of a literature review, the technical criteria for operating sections of the network in islanding mode, and the impact of islanding on trading. Case studies and a detailed implementation plan, data acquisition, and commercial incentives are discussed

  2. Pediatrics in the Marshall Islands

    International Nuclear Information System (INIS)

    Dungy, C.I.; Morgan, B.C.; Adams, W.H.

    1984-01-01

    The delivery of health care to children living on isolated island communities presents unique challenges to health professionals. An evolved method of providing longitudinal services to infants and children residing on islands of the Marshall Island chain - a central Pacific portion of the Micronesian archipelago - is presented. The difficulties associated with provision of comprehensive health care in a vast ocean area are discussed

  3. The Island Smart Energy System and Market

    DEFF Research Database (Denmark)

    Ma, Zheng; Billanes, Joy Dalmacio; Jørgensen, Bo Nørregaard

    2017-01-01

    developing island smart energy systems with the integration of renewable energy resources can increase the energy supply and address the global island energy issues. The island smart energy system operates either in a single-island or in multi-islands. However the island characteristics and influ...

  4. Solomon Islands Botany

    NARCIS (Netherlands)

    Steenis, van C.G.G.J.

    1969-01-01

    A discussion of the Results of the Royal Society Expedition to the British Solomon Islands Protectorate, 1965. Organized by E.J.H. Corner. Phil. Trans. R. Soc. B 255 (1969) 185-631, 196 fig. University Printing House, Shaftesbury Road, Cambridge. Obtainable through booksellers or direct to the Royal

  5. Pacific Island Pharmacovigilance

    DEFF Research Database (Denmark)

    McEwen, John; Vestergaard, Lasse S.; Sanburg, Amanda L C

    2016-01-01

    Many Pacific Island countries (PICs) are recipients of funding support from the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). However, most of these countries cannot be expected to meet Global Fund and World Health Organization (WHO) minimum requirements for a functioning...

  6. Magnetic-island formation

    International Nuclear Information System (INIS)

    Boozer, A.H.

    1983-08-01

    The response of a finite conductivity plasma to resonant magnetic perturbations is studied. The equations, which are derived for the time development of magnetic islands, help one interpret the singular currents which occur under the assumption of perfect plasma conductivity. The relation to the Rutherford regime of resistive instabilities is given

  7. Bone island and leprosy

    Energy Technology Data Exchange (ETDEWEB)

    Carpintero, P.; Garcia-Frasquet, A. [Department of Orthopaedic Surgery, Cordoba University, Medical School, Reina Sofia University Hospital, Cordoba (Spain); Tarradas, E. [Department of Imaging, Cordoba University, Medical School, Cordoba (Spain); Logrono, C. [Department of Dermatology, Reina Sofia University Hospital, Cordoba (Spain); Carrascal, A. [Department of Radiology, Infanta Elena Hospital, Huelva (Spain); Carreto, A. [Department of Radiology, Reina Sofia University Hospital, Cordoba (Spain)

    1998-06-01

    Objective. To determine the incidence of bone islands in leprosy patients. Design. X-rays of feet and hands of patients with Hansen`s disease (leprosy) were reviewed retrospectively. A second group of related age- and sex-matched patients who did not have Hansen`s disease was used for control purposes. Controls had undergone hand or foot X-rays during diagnosis of other pathologies. The patients with Hansen`s disease were compared with the control group, and were also analyzed as subgroups with different types of leprosy. The results were subjected to statistical analysis. Patients. Ninety patients with Hansen`s disease were randomly selected for this study. Patients who had had ulcers on hands or feet were excluded from the study. Results and conclusions. Bone islands were demonstrated in 20 patients with Hansen`s disease; no bone islands were observed in the controls. This was statistically significant (P<0.01). Bone islands were only seen in patients with lepromatous leprosy and borderline types but were not demonstrated in patients with tuberculoid leprosy. There was also a statistically significant relationship for a disease duration of 15 years or more. The cause of this raised incidence of enostosis in leprosy patients is not clear, but there may be a genetic predisposition in patients with leprosy, or it may be a side effect of leprosy, especially the lepromatous form. (orig.) With 4 figs., 2 tabs., 9 refs.

  8. Bone island and leprosy

    International Nuclear Information System (INIS)

    Carpintero, P.; Garcia-Frasquet, A.; Tarradas, E.; Logrono, C.; Carrascal, A.; Carreto, A.

    1998-01-01

    Objective. To determine the incidence of bone islands in leprosy patients. Design. X-rays of feet and hands of patients with Hansen's disease (leprosy) were reviewed retrospectively. A second group of related age- and sex-matched patients who did not have Hansen's disease was used for control purposes. Controls had undergone hand or foot X-rays during diagnosis of other pathologies. The patients with Hansen's disease were compared with the control group, and were also analyzed as subgroups with different types of leprosy. The results were subjected to statistical analysis. Patients. Ninety patients with Hansen's disease were randomly selected for this study. Patients who had had ulcers on hands or feet were excluded from the study. Results and conclusions. Bone islands were demonstrated in 20 patients with Hansen's disease; no bone islands were observed in the controls. This was statistically significant (P<0.01). Bone islands were only seen in patients with lepromatous leprosy and borderline types but were not demonstrated in patients with tuberculoid leprosy. There was also a statistically significant relationship for a disease duration of 15 years or more. The cause of this raised incidence of enostosis in leprosy patients is not clear, but there may be a genetic predisposition in patients with leprosy, or it may be a side effect of leprosy, especially the lepromatous form. (orig.)

  9. Multidecadal shoreline changes of atoll islands in the Marshall Islands

    Science.gov (United States)

    Ford, M.

    2012-12-01

    Atoll islands are considered highly vulnerable to the impacts of continued sea level rise. One of the most commonly predicted outcomes of continued sea level rise is widespread and chronic shoreline erosion. Despite the widespread implications of predicted erosion, the decadal scale changes of atoll island shorelines are poorly resolved. The Marshall Islands is one of only four countries where the majority of inhabited land is comprised of reef and atoll islands. Consisting of 29 atolls and 5 mid-ocean reef islands, the Marshall Islands are considered highly vulnerable to the impacts of sea level rise. A detailed analysis of shoreline change on over 300 islands on 10 atolls was undertaken using historic aerial photos (1945-1978) and modern high resolution satellite imagery (2004-2012). Results highlight the complex and dynamic nature of atoll islands, with significant shifts in shoreline position observed over the period of analysis. Results suggest shoreline accretion is the dominant mode of change on the islands studied, often associated with a net increase in vegetated island area. However, considerable inter- and intra-atoll variability exists with regards to shoreline stability. Findings are discussed with respect to island morphodynamics and potential hazard mitigation and planning responses within atoll settings.

  10. The amphibians and reptiles of Mindanao Island, southern Philippines, II: the herpetofauna of northeast Mindanao and adjacent islands

    Directory of Open Access Journals (Sweden)

    Marites B. Sanguila

    2016-10-01

    Full Text Available We summarize all available amphibian and reptile species distribution data from the northeast Mindanao faunal region, including small islands associated with this subcenter of endemic vertebrate biodiversity. Together with all publicly available historical information from biodiversity repositories, we present new data from several major herpetological surveys, including recently conducted inventories on four major mountains of northeast Mindanao, and adjacent islands of Camiguin Sur, Dinagat, and Siargao. We present species accounts for all taxa, comment on unresolved taxonomic problems, and provide revisions to outdated IUCN conservation status assessments in cases where our new data significantly alter earlier classification status summaries. Together, our comprehensive analysis of this fauna suggests that the greater Mindanao faunal region possesses distinct subcenters of amphibian and reptile species diversity, and that until this area is revisited and its fauna and actually studied, with on-the-ground field work including targeted surveys of species distributions coupled to the study their natural history, our understanding of the diversity and conservation status of southern Philippine herpetological fauna will remain incomplete. Nevertheless, the northeast Mindanao geographical area (Caraga Region appears to have the highest herpetological species diversity (at least 126 species of any comparably-sized Philippine faunal subregion.

  11. PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis.

    Science.gov (United States)

    Zigler, Maya; Kamiya, Takafumi; Brantley, Emily C; Villares, Gabriel J; Bar-Eli, Menashe

    2011-11-01

    Progression of melanoma is dependent on cross-talk between tumor cells and the adjacent microenvironment. The thrombin receptor, protease-activated receptor-1 (PAR-1), plays a key role in exerting this function during melanoma progression. PAR-1 and its activating factors, which are expressed on tumor cells and the surrounding stroma, induce not only coagulation but also cell signaling, which promotes the metastatic phenotype. Several adhesion molecules, cytokines, growth factors, and proteases have recently been identified as downstream targets of PAR-1 and have been shown to modulate interactions between tumor cells and the microenvironment in the process of melanoma growth and metastasis. Inhibiting such interactions by targeting PAR-1 could potentially be a useful therapeutic modality for melanoma patients. ©2011 AACR.

  12. The role of the tissue microenvironment in the regulation of cancer cell motility and invasion

    Directory of Open Access Journals (Sweden)

    Brábek Jan

    2010-09-01

    Full Text Available Abstract During malignant neoplastic progression the cells undergo genetic and epigenetic cancer-specific alterations that finally lead to a loss of tissue homeostasis and restructuring of the microenvironment. The invasion of cancer cells through connective tissue is a crucial prerequisite for metastasis formation. Although cell invasion is foremost a mechanical process, cancer research has focused largely on gene regulation and signaling that underlie uncontrolled cell growth. More recently, the genes and signals involved in the invasion and transendothelial migration of cancer cells, such as the role of adhesion molecules and matrix degrading enzymes, have become the focus of research. In this review we discuss how the structural and biomechanical properties of extracellular matrix and surrounding cells such as endothelial cells influence cancer cell motility and invasion. We conclude that the microenvironment is a critical determinant of the migration strategy and the efficiency of cancer cell invasion.

  13. Trabectedin and Plitidepsin: Drugs from the Sea that Strike the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Carlos M. Galmarini

    2014-01-01

    Full Text Available The prevailing paradigm states that cancer cells acquire multiple genetic mutations in oncogenes or tumor suppressor genes whose respective activation/up-regulation or loss of function serve to impart aberrant properties, such as hyperproliferation or inhibition of cell death. However, a tumor is now considered as an organ-like structure, a complex system composed of multiple cell types (e.g., tumor cells, inflammatory cells, endothelial cells, fibroblasts, etc. all embedded in an inflammatory stroma. All these components influence each other in a complex and dynamic cross-talk, leading to tumor cell survival and progression. As the microenvironment has such a crucial role in tumor pathophysiology, it represents an attractive target for cancer therapy. In this review, we describe the mechanism of action of trabectedin and plitidepsin as an example of how these specific drugs of marine origin elicit their antitumor activity not only by targeting tumor cells but also the tumor microenvironment.

  14. The Immunomodulatory Effects of Mesenchymal Stem Cell Polarization within the Tumor Microenvironment Niche

    Directory of Open Access Journals (Sweden)

    Cosette M. Rivera-Cruz

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs represent a promising tool for cell therapy, particularly for their antitumor effects. This cell population can be isolated from multiple tissue sources and also display an innate ability to home to areas of inflammation, such as tumors. Upon entry into the tumor microenvironment niche, MSCs promote or inhibit tumor progression by various mechanisms, largely through the release of soluble factors. These factors can be immunomodulatory by activating or inhibiting both the adaptive and innate immune responses. The mechanisms by which MSCs modulate the immune response are not well understood. Because of this, the relationship between MSCs and immune cells within the tumor microenvironment niche continues to be an active area of research in order to help explain the apparent contradictory findings currently available in the literature. The ongoing research aims to enhance the potential of MSCs in future therapeutic applications.

  15. Tumor Microenvironment and Immune Effects of Antineoplastic Therapy in Lymphoproliferative Syndromes

    Science.gov (United States)

    Álvaro, Tomás; de la Cruz-Merino, Luis; Henao-Carrasco, Fernando; Villar Rodríguez, José Luis; Vicente Baz, David; Codes Manuel de Villena, Manuel; Provencio, Mariano

    2010-01-01

    Lymphomas represent a wide group of heterogenic diseases with different biological and clinical behavior. The underlying microenvironment-specific composition seems to play an essential role in this scenario, harboring the ability to develop successful immune responses or, on the contrary, leading to immune evasion and even promotion of tumor growth. Depending on surrounding lymphoid infiltrates, lymphomas may have different prognosis. Moreover, recent evidences have emerged that confer a significant impact of main lymphoma's treatment over microenvironment, with clinical consequences. In this review, we summarize these concepts from a pathological and clinical perspective. Also, the state of the art of lymphoma's anti-idiotype vaccine development is revised, highlighting the situations where this strategy has proven to be successful and eventual clues to obtain better results in the future. PMID:20814546

  16. Immune microenvironment in colorectal cancer: a new hallmark to change old paradigms.

    Science.gov (United States)

    de la Cruz-Merino, Luis; Henao Carrasco, Fernando; Vicente Baz, David; Nogales Fernández, Esteban; Reina Zoilo, Juan José; Codes Manuel de Villena, Manuel; Pulido, Enrique Grande

    2011-01-01

    Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cancer, paying special attention to infiltration by T-infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its eventual clinical translation in terms of long-term prognosis. Finally, we suggest some possible investigational approaches based on combinatorial strategies to trigger and boost immune reaction against tumor cells.

  17. Nocardia brasiliensis induces an immunosuppressive microenvironment that favors chronic infection in BALB/c mice.

    Science.gov (United States)

    Rosas-Taraco, Adrian G; Perez-Liñan, Amira R; Bocanegra-Ibarias, Paola; Perez-Rivera, Luz I; Salinas-Carmona, Mario C

    2012-07-01

    Nocardia brasiliensis is an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+ Foxp3+ regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whether N. brasiliensis modulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship between N. brasiliensis immunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P 1 log) was also observed (P brasiliensis modulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.

  18. Individual and population intake fractions of diesel particulate matter (DPM) in bus stop microenvironments

    International Nuclear Information System (INIS)

    Xu, Jia; Jin, Taosheng; Miao, Yaning; Han, Bin; Gao, Jiajia; Bai, Zhipeng; Xu, Xiaohong

    2015-01-01

    Diesel particulate matter (DPM) is associated with adverse human health effects. This study aims to investigate the relationship between DPM exposure and emissions by estimating the individual intake fraction (iF_i) and population intake fraction (iF_p) of DPM. Daily average concentrations of particulate matter at two bus stops during rush hours were measured, and then they were apportioned to DPM due to heavy-duty diesel bus emissions using Chemical Mass Balance Model. The DPM emissions of diesel buses for different driving conditions (idling, creeping and traveling) were estimated on the basis of field observations and published emission factors. The median iF_i of DPM was 0.67 and 1.39 per million for commuters standing at the bus stop and pedestrians/cyclists passing through the bus stop during rush hours, respectively. The median iF_p of DPM was 94 per million. Estimations of iF_i and iF_p of DPM are potentially significant for exposure assessment and risk management. - Highlights: • Methods to estimate the individual and population intake fraction in bus stop microenvironments were established. • Source apportionment was performed to estimate the DPM due to diesel bus emissions in bus stop microenvironments. • The DPM emission in bus stop microenvironments rather than in the entire urban area was considered. • The movement of people and their exposure duration were introduced in the estimation of population intake fraction. - This work established a method to estimate the individual and population intake fraction in transportation microenvironments on the basis of PM source apportionment.

  19. Registered report: Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: David Blum, Samuel LaBarge, The Reproducibility Project: Cancer Biology†* ### Abstract The [Reproducibility Project: Cancer Biology](https://osf.io/e81xl/wiki/home/) seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered Report describes the proposed replication plan of key experiments from “Tumour micro-environment elicits innate res...

  20. CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment.

    Science.gov (United States)

    Han, Yan; Wu, Chunlei; Wang, Jing; Liu, Na

    2017-05-01

    The major cause of death in osteosarcoma is the invasion and metastasis. Better understanding of the molecular mechanism of osteosarcoma invasion is essential in developing effective tumor-suppressive therapies. Interaction between chemokine receptors plays a crucial role in regulating osteosarcoma invasion. Here, we investigated the relationship between CXCR7 and CXCR4 in osteosarcoma invasion induced by bone marrow microenvironment. Human bone marrow mesenchymal stem cells were co-cultured with osteosarcoma cells to mimic actual bone marrow microenvironment. Osteosarcoma cell invasion and CXCL12/CXCR4 activation were observed within this co-culture model. Interestingly, in this co-culture model, osteosarcoma cell invasion was not inhibited by suppressing CXCR4 expression with neutralizing antibody or specific inhibitor AMD3100. Downstream signaling extracellular signal-regulated kinase and signal transducer and activator of transcription 3 were not significantly affected by CXCR4 inhibition. However, suppressing CXCR4 led to CXCR7 upregulation. Constitutive expression of CXCR7 could maintain osteosarcoma cell invasion when CXCR4 was suppressed. Simultaneously, inhibiting CXCR4 and CXCR7 compromised osteosarcoma invasion in co-culture system and suppressed extracellular signal-regulated kinase and signal transducer and activator of transcription 3 signals. Moreover, bone marrow microenvironment, not CXCL12 alone, is required for CXCR7 activation after CXCR4 suppression. Taken together, suppressing CXCR4 is not enough to impede osteosarcoma invasion in bone marrow microenvironment since CXCR7 is activated to sustain invasion. Therefore, inhibiting both CXCR4 and CXCR7 could be a promising strategy in controlling osteosarcoma invasion.

  1. Alexa Fluor-labeled Fluorescent Cellulose Nanocrystals for Bioimaging Solid Cellulose in Spatially Structured Microenvironments

    Energy Technology Data Exchange (ETDEWEB)

    Grate, Jay W.; Mo, Kai-For; Shin, Yongsoon; Vasdekis, Andreas; Warner, Marvin G.; Kelly, Ryan T.; Orr, Galya; Hu, Dehong; Dehoff, Karl J.; Brockman, Fred J.; Wilkins, Michael J.

    2015-03-18

    Cellulose nanocrystal materials have been labeled with modern Alexa Fluor dyes in a process that first links the dye to a cyanuric chloride molecule. Subsequent reaction with cellulose nanocrystals provides dyed solid microcrystalline cellulose material that can be used for bioimaging and suitable for deposition in films and spatially structured microenvironments. It is demonstrated with single molecular fluorescence microscopy that these films are subject to hydrolysis by cellulose enzymes.

  2. Targeting Autophagy in the Tumor Microenvironment: New Challenges and Opportunities for Regulating Tumor Immunity

    Directory of Open Access Journals (Sweden)

    Bassam Janji

    2018-04-01

    Full Text Available Cancer cells evolve in the tumor microenvironment, which is now well established as an integral part of the tumor and a determinant player in cancer cell adaptation and resistance to anti-cancer therapies. Despite the remarkable and fairly rapid progress over the past two decades regarding our understanding of the role of the tumor microenvironment in cancer development, its precise contribution to cancer resistance is still fragmented. This is mainly related to the complexity of the “tumor ecosystem” and the diversity of the stromal cell types that constitute the tumor microenvironment. Emerging data indicate that several factors, such as hypoxic stress, activate a plethora of resistance mechanisms, including autophagy, in tumor cells. Hypoxia-induced autophagy in the tumor microenvironment also activates several tumor escape mechanisms, which effectively counteract anti-tumor immune responses mediated by natural killer and cytotoxic T lymphocytes. Therefore, strategies aiming at targeting autophagy in cancer cells in combination with other therapeutic strategies have inspired significant interest to overcome immunological tolerance and promote tumor regression. However, a number of obstacles still hamper the application of autophagy inhibitors in clinics. First, the lack of selectivity of the current pharmacological inhibitors of autophagy makes difficult to draw a clear statement about its effective contribution in cancer. Second, autophagy has been also described as an important mechanism in tumor cells involved in presentation of antigens to T cells. Third, there is a circumstantial evidence that autophagy activation in some innate immune cells may support the maturation of these cells, and it is required for their anti-tumor activity. In this review, we will address these aspects and discuss our current knowledge on the benefits and the drawbacks of targeting autophagy in the context of anti-tumor immunity. We believe that it is

  3. Gamma irradiation of the fetus damages the developing hemopoietic microenvironment rather than the hemopoietic progenitor cells

    International Nuclear Information System (INIS)

    Yang, F.T.; Lord, B.I.; Hendry, J.H.

    1995-01-01

    Hemopoiesis is the product of two components: the hemopoietic tissue and the regulatory stromal microenvironment in which it resides. Plutonium-239, incorporated during fetal development in mice, is known to cause deficient hemopoiesis. A predetermined equivalent γ-ray dose has now been used in combination with cross-transplantation experiments to separate these two components and define where the damage arises. It was confirmed that 1.8 Gy γ irradiation at midterm gestation caused a 40% reduction in the hemopoietic stem (spleen colony-forming) cell population of their offspring which persisted to at least 24 weeks of age. Spleen colony formation after sublethal doses of γ rays reflected this reduced complement of endogenous stem cells. The regulatory hemopoietic microenvironment, measured as fibroblastoid colony-forming cells, was similarly depleted. Normal growth of the CFU-S population after transplantation into standard recipients showed that the quality of the stem cell population in the offspring of irradiated mothers was not affected. By contrast, when used as recipients of a bone marrow transplant from either normal or irradiated offspring, the offspring of irradiated mothers were unable to support normal growth: there was a twofold difference in the number of CFU-S per femur for at least 100 days after transplantation. There were 70% fewer CFU-F in the femur 1 month after bone marrow transplantation when the offspring of irradiated mothers were used as transplant recipients compared to when normal offspring were used. This not only confirmed their reduced capacity to host normal stem cells but also indicated that CFU-F in the transplant were unable to compensate for the poor microenvironment in the irradiated offspring hosts. It is concluded that irradiation at midterm gestation damages the developing regulatory microenvironment but not the hemopoietic stem cell population that it hosts. 12 refs., 1 fig., 4 tabs

  4. Activity pattern and personal exposure to nitrogen dioxide in indoor and outdoor microenvironments.

    Science.gov (United States)

    Kornartit, C; Sokhi, R S; Burton, M A; Ravindra, Khaiwal

    2010-01-01

    People are exposed to air pollution from a range of indoor and outdoor sources. Concentrations of nitrogen dioxide (NO(2)), which is hazardous to health, can be significant in both types of environments. This paper reports on the measurement and analysis of indoor and outdoor NO(2) concentrations and their comparison with measured personal exposure in various microenvironments during winter and summer seasons. Furthermore, the relationship between NO(2) personal exposure in various microenvironments and including activities patterns were also studied. Personal, indoor microenvironments and outdoor measurements of NO(2) levels were conducted using Palmes tubes for 60 subjects. The results showed significant differences in indoor and outdoor NO(2) concentrations in winter but not for summer. In winter, indoor NO(2) concentrations were found to be strongly correlated with personal exposure levels. NO(2) concentration in houses using a gas cooker was higher in all rooms than those with an electric cooker during the winter campaign, whereas there was no significant difference noticed in summer. The average NO(2) levels in kitchens with a gas cooker were twice as high as those with an electric cooker, with no significant difference in the summer period. A time-weighted average personal exposure was calculated and compared with measured personal exposures in various indoor microenvironments (e.g. front doors, bedroom, living room and kitchen); including non-smokers, passive smokers and smoker. The estimated results were closely correlated, but showed some underestimation of the measured personal exposures to NO(2) concentrations. Interestingly, for our particular study higher NO(2) personal exposure levels were found during summer (14.0+/-1.5) than winter (9.5+/-2.4).

  5. T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments.

    Science.gov (United States)

    Hawkins, Edwin D; Duarte, Delfim; Akinduro, Olufolake; Khorshed, Reema A; Passaro, Diana; Nowicka, Malgorzata; Straszkowski, Lenny; Scott, Mark K; Rothery, Steve; Ruivo, Nicola; Foster, Katie; Waibel, Michaela; Johnstone, Ricky W; Harrison, Simon J; Westerman, David A; Quach, Hang; Gribben, John; Robinson, Mark D; Purton, Louise E; Bonnet, Dominique; Lo Celso, Cristina

    2016-10-27

    It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment

  6. Subjective Evaluation of the Microenvironment Generated by a Hospital Bed with Localized Ventilation System

    DEFF Research Database (Denmark)

    Kehayova, Nushka; Bolashikov, Zhecho Dimitrov; Melikov, Arsen Krikor

    2016-01-01

    A novel method for local hospital bed ventilation, called HBIVCU (Hospital Bed with Integrated Ventilation and Cleansing Unit), was studied in a human subject experiment. The goal of this study was to identify human response to the microenvironment generated by a hospital bed with installed HBIVC...... and the LTS acceptability votes between the two conditions could be found only for some body parts and time intervals. No draught was reported....

  7. Brief Communication: Tissue-engineered Microenvironment Systems for Modeling Human Vasculature

    Science.gov (United States)

    Tourovskaia, Anna; Fauver, Mark; Kramer, Gregory; Simonson, Sara; Neumann, Thomas

    2015-01-01

    The high attrition rate of drug candidates late in the development process has led to an increasing demand for test assays that predict clinical outcome better than conventional 2D cell culture systems and animal models. Government agencies, the military, and the pharmaceutical industry have started initiatives for the development of novel in-vitro systems that recapitulate functional units of human tissues and organs. There is growing evidence that 3D cell arrangement, co-culture of different cell types, and physico-chemical cues lead to improved predictive power. A key element of all tissue microenvironments is the vasculature. Beyond transporting blood the microvasculature assumes important organ-specific functions. It is also involved in pathologic conditions, such as inflammation, tumor growth, metastasis, and degenerative diseases. To provide a tool for modeling this important feature of human tissue microenvironments, we developed a microfluidic chip for creating tissue-engineered microenvironment systems (TEMS) composed of tubular cell structures. Our chip design encompasses a small chamber that is filled with an extracellular matrix (ECM) surrounding one or more tubular channels. Endothelial cells seeded into the channels adhere to the ECM walls and grow into perfusable tubular tissue structures that are fluidically connected to upstream and downstream fluid channels in the chip. Using these chips we created models of angiogenesis, the blood-brain-barrier (BBB), and tumor-cell extravasation. Our angiogenesis model recapitulates true angiogenesis, in which sprouting occurs from a “parent” vessel in response to a gradient of growth factors. Our BBB model is composed of a microvessel generated from brain-specific endothelial cells (ECs) within an ECM populated with astrocytes and pericytes. Our tumor-cell extravasation model can be utilized to visualize and measure tumor-cell migration through vessel walls into the surrounding matrix. The described

  8. Persistent injury-associated anemia: the role of the bone marrow microenvironment.

    Science.gov (United States)

    Millar, Jessica K; Kannan, Kolenkode B; Loftus, Tyler J; Alamo, Ines G; Plazas, Jessica; Efron, Philip A; Mohr, Alicia M

    2017-06-15

    The regulation of erythropoiesis involves hematopoietic progenitor cells, bone marrow stroma, and the microenvironment. Following severe injury, a hypercatecholamine state develops that is associated with increased mobilization of hematopoietic progenitor cells to peripheral blood and decreased growth of bone marrow erythroid progenitor cells that manifests clinically as a persistent injury-associated anemia. Changes within the bone marrow microenvironment influence the development of erythroid progenitor cells. Therefore, we sought to determine the effects of lung contusion, hemorrhagic shock, and chronic stress on the hematopoietic cytokine response. Bone marrow was obtained from male Sprague-Dawley rats (n = 6/group) killed 7 d after lung contusion followed by hemorrhagic shock (LCHS) or LCHS followed by daily chronic restraint stress (LCHS/CS). End point polymerase chain reaction was performed for interleukin-1β, interleukin-10, stem cell factor, transforming growth factor-β, high-mobility group box-1 (HMGB-1), and B-cell lymphoma-extra large. Seven days following LCHS and LCHS/CS, bone marrow expression of prohematopoietic cytokines (interleukin-1β, interleukin-10, stem cell factor, and transforming growth factor-β) was significantly decreased, and bone marrow expression of HMGB-1 was significantly increased. B-cell lymphoma-extra large bone marrow expression was not affected by LCHS or LCHS/CS (naïve: 44 ± 12, LCHS: 44 ± 12, LCHS/CS: 37 ± 1, all P > 0.05). The bone marrow microenvironment was significantly altered following severe trauma in a rodent model. Prohematopoietic cytokines were downregulated, and the proinflammatory cytokine HMGB-1 had increased bone marrow expression. Modulation of the bone marrow microenvironment may represent a therapeutic strategy following severe trauma to alleviate persistent injury-associated anemia. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Donna M. Sosnoski

    2012-01-01

    Full Text Available It is commonly accepted that cancer cells interact with host cells to create a microenvironment favoring malignant colonization. The complex bone microenvironment produces an ever changing array of cytokines and growth factors. In this study, we examined levels of MCP-1, IL-6, KC, MIP-2, VEGF, MIG, and eotaxin in femurs of athymic nude mice inoculated via intracardiac injection with MDA-MB-231GFP human metastatic breast cancer cells, MDA-MB-231BRMS1GFP, a metastasis suppressed variant, or PBS. Animals were euthanized (day 3, 11, 19, 27 after injection to examine femoral cytokine levels at various stages of cancer cell colonization. The epiphysis contained significantly more cytokines than the diaphysis except for MIG which was similar throughout the bone. Variation among femurs was evident within all groups. By day 27, MCP-1, MIG, VEGF and eotaxin levels were significantly greater in femurs of cancer cell-inoculated mice. These pro-osteoclastic and angiogenic cytokines may manipulate the bone microenvironment to enhance cancer cell colonization.

  10. Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

    International Nuclear Information System (INIS)

    Sosnoski, D.M.; Krishnan, V.; Mastro, A.M.; Kraemer, W.J.; Dunn-Lewis, C.

    2012-01-01

    It is commonly accepted that cancer cells interact with host cells to create a microenvironment favoring malignant colonization. The complex bone microenvironment produces an ever changing array of cytokines and growth factors. In this study, we examined levels of MCP-1, IL-6, KC, MIP-2, VEGF, MIG, and eotaxin in femurs of athymic nude mice inoculated via intracardiac injection with MDA-MB-231GFP human metastatic breast cancer cells, MDA-MB-231 BRMS1GFP, a metastasis suppressed variant, or PBS. Animals were euthanized (day 3, 11, 19, 27 after injection) to examine femoral cytokine levels at various stages of cancer cell colonization. The epiphysis contained significantly more cytokines than the diaphysis except for MIG which was similar throughout the bone. Variation among femurs was evident within all groups. By day 27, MCP-1, MIG, VEGF and eotaxin levels were significantly greater in femurs of cancer cell-inoculated mice. These pro-osteoclastic and angiogenic cytokines may manipulate the bone microenvironment to enhance cancer cell colonization

  11. Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment.

    Science.gov (United States)

    Ito, Koichi; Stannard, Kimberley; Gabutero, Elwyn; Clark, Amanda M; Neo, Shi-Yong; Onturk, Selda; Blanchard, Helen; Ralph, Stephen J

    2012-12-01

    The microenvironment of a tumor is a highly complex milieu, primarily characterized by immunosuppression, abnormal angiogenesis, and hypoxic regions. These features promote tumor progression and metastasis, resulting in poor prognosis and greater resistance to existing cancer therapies. Galectin-1 is a β-galactoside binding protein that is abundantly secreted by almost all types of malignant tumor cells. The expression of galectin-1 is regulated by hypoxia-inducible factor-1 (HIF-1) and it plays vital pro-tumorigenic roles within the tumor microenvironment. In particular, galectin-1 suppresses T cell-mediated cytotoxic immune responses and promotes tumor angiogenesis. However, since galectin-1 displays many different activities by binding to a number of diverse N- or O-glycan modified target proteins, it has been difficult to fully understand how galectin-1 supports tumor growth and metastasis. This review explores the importance of galectin-1 and glycan expression patterns in the tumor microenvironment and the potential effects of inhibiting galectin-1 as a therapeutic target for cancer treatment.

  12. Impacts of exhalation flow on the microenvironment around the human body under different room temperatures

    Science.gov (United States)

    Jafari, Mohammad Javad; Gharari, Noradin; Azari, Mansour Rezazade; Ashrafi, Khosro

    2018-04-01

    Exhalation flow and room temperature can have a considerable effect on the microenvironment in the vicinity of human body. In this study, impacts of exhalation flow and room temperature on the microenvironment around a human body were investigated using a numerical simulation. For this purpose, a computational fluid dynamic program was applied to study thermal plume around a sitting human body at different room temperatures of a calm indoor room by considering the exhalation flow. The simulation was supported by some experimental measurements. Six different room temperatures (18 to 28 °C) with two nose exhalation modes (exhalation and non-exhalation) were investigated. Overhead and breathing zone velocities and temperatures were simulated in different scenarios. This study finds out that the exhalation through the nose has a significant impact on both quantitative and qualitative features of the human microenvironment in different room temperatures. At a given temperature, the exhalation through the nose can change the location and size of maximum velocity at the top of the head. In the breathing zone, the effect of exhalation through the nose on velocity and temperature distribution was pronounced for the point close to mouth. Also, the exhalation through the nose strongly influences the thermal boundary layer on the breathing zone while it only minimally influences the convective boundary layer on the breathing zone. Overall results demonstrate that it is important to take the exhalation flow into consideration in all areas, especially at a quiescent flow condition with low temperature.

  13. Evaluation of daily time spent in transportation and traffic-influenced microenvironments by urban Canadians.

    Science.gov (United States)

    Matz, Carlyn J; Stieb, David M; Egyed, Marika; Brion, Orly; Johnson, Markey

    2018-01-01

    Exposure to traffic and traffic-related air pollution is associated with a wide array of health effects. Time spent in a vehicle, in active transportation, along roadsides, and in close proximity to traffic can substantially contribute to daily exposure to air pollutants. For this study, we evaluated daily time spent in transportation and traffic-influenced microenvironments by urban Canadians using the Canadian Human Activity Pattern Survey (CHAPS) 2 results. Approximately 4-7% of daily time was spent in on- or near-road locations, mainly associated with being in a vehicle and smaller contributions from active transportation. Indoor microenvironments can be impacted by traffic emissions, especially when located near major roadways. Over 60% of the target population reported living within one block of a roadway with moderate to heavy traffic, which was variable with income level and city, and confirmed based on elevated NO 2 exposure estimated using land use regression. Furthermore, over 55% of the target population ≤ 18 years reported attending a school or daycare in close proximity to moderate to heavy traffic, and little variation was observed based on income or city. The results underline the importance of traffic emissions as a major source of exposure in Canadian urban centers, given the time spent in traffic-influenced microenvironments.

  14. The senescent microenvironment promotes the emergence of heterogeneous cancer stem-like cells.

    Science.gov (United States)

    Castro-Vega, Luis Jaime; Jouravleva, Karina; Ortiz-Montero, Paola; Liu, Win-Yan; Galeano, Jorge Luis; Romero, Martha; Popova, Tatiana; Bacchetti, Silvia; Vernot, Jean Paul; Londoño-Vallejo, Arturo

    2015-10-01

    There is a well-established association between aging and the onset of metastasis. Although the mechanisms through which age impinges upon the malignant phenotype remain uncharacterized, the role of a senescent microenvironment has been emphasized. We reported previously that human epithelial cells that undergo telomere-driven chromosome instability (T-CIN) display global microRNA (miR) deregulation and develop migration and invasion capacities. Here, we show that post-crisis cells are not able to form tumors unless a senescent microenvironment is provided. The characterization of cell lines established from such tumors revealed that these cells have acquired cell autonomous tumorigenicity, giving rise to heterogeneous tumors. Further experiments demonstrate that explanted cells, while displaying differences in cell differentiation markers, are all endowed of enhanced stem cell properties including self-renewal and multilineage differentiation capacity. Treatments of T-CIN+ cells with senescence-conditioned media induce sphere formation exclusively in cells with senescence-associated tumorigenicity, a capacity that depends on miR-145 repression. These results indicate that the senescent microenvironment, while promoting further transdifferentiations in cells with genome instability, is able to propel the progression of premalignant cells towards a malignant, cell stem-like state. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Visceral Congestion in Heart Failure: Right Ventricular Dysfunction, Splanchnic Hemodynamics, and the Intestinal Microenvironment.

    Science.gov (United States)

    Polsinelli, Vincenzo B; Sinha, Arjun; Shah, Sanjiv J

    2017-12-01

    Visceral venous congestion of the gut may play a key role in the pathogenesis of right-sided heart failure (HF) and cardiorenal syndromes. Here, we review the role of right ventricular (RV) dysfunction, visceral congestion, splanchnic hemodynamics, and the intestinal microenvironment in the setting of right-sided HF. We review recent literature on this topic, outline possible mechanisms of disease pathogenesis, and discuss potential therapeutics. There are several mechanisms linking RV-gut interactions via visceral venous congestion which could result in (1) hypoxia and acidosis in enterocytes, which may lead to enhanced sodium-hydrogen exchanger 3 (NHE3) expression with increased sodium and fluid retention; (2) decreased luminal pH in the intestines, which could lead to alteration of the gut microbiome which could increase gut permeability and inflammation; (3) alteration of renal hemodynamics with triggering of the cardiorenal syndrome; and (4) altered phosphate metabolism resulting in increased pulmonary artery stiffening, thereby increasing RV afterload. A wide variety of therapeutic interventions that act on the RV, pulmonary vasculature, intestinal microenvironment, and the kidney could alter these pathways and should be tested in patients with right-sided HF. The RV-gut axis is an important aspect of HF pathogenesis that deserves more attention. Modulation of the pathways interconnecting the right heart, visceral congestion, and the intestinal microenvironment could be a novel avenue of intervention for right-sided HF.

  16. The inflammatory milieu within the pancreatic cancer microenvironment correlates with clinicopathologic parameters, chemoresistance and survival

    International Nuclear Information System (INIS)

    Delitto, Daniel; Black, Brian S.; Sorenson, Heather L.; Knowlton, Andrea E.; Thomas, Ryan M.; Sarosi, George A.; Moldawer, Lyle L.; Behrns, Kevin E.; Liu, Chen; George, Thomas J.; Trevino, Jose G.; Wallet, Shannon M.; Hughes, Steven J.

    2015-01-01

    The tumor microenvironment impacts pancreatic cancer (PC) development, progression and metastasis. How intratumoral inflammatory mediators modulate this biology remains poorly understood. We hypothesized that the inflammatory milieu within the PC microenvironment would correlate with clinicopathologic findings and survival. Pancreatic specimens from normal pancreas (n = 6), chronic pancreatitis (n = 9) and pancreatic adenocarcinoma (n = 36) were homogenized immediately upon resection. Homogenates were subjected to multiplex analysis of 41 inflammatory mediators. Twenty-three mediators were significantly elevated in adenocarcinoma specimens compared to nonmalignant controls. Increased intratumoral IL-8 concentrations associated with larger tumors (P = .045) and poor differentiation (P = .038); the administration of neoadjuvant chemotherapy associated with reduced IL-8 concentrations (P = .003). Neoadjuvant therapy was also associated with elevated concentrations of Flt-3 L (P = .005). Elevated levels of pro-inflammatory cytokines IL-1β (P = .017) and TNFα (P = .033) were associated with a poor histopathologic response to neoadjuvant therapy. Elevated concentrations of G-CSF (P = .016) and PDGF-AA (P = .012) correlated with reduced overall survival. Conversely, elevated concentrations of FGF-2 (P = .038), TNFα (P = .031) and MIP-1α (P = .036) were associated with prolonged survival. The pancreatic cancer microenvironment harbors a unique inflammatory milieu with potential diagnostic and prognostic value

  17. Adipocytes and Macrophages Interplay in the Orchestration of Tumor Microenvironment: New Implications in Cancer Progression

    Directory of Open Access Journals (Sweden)

    Luís Henrique Corrêa

    2017-09-01

    Full Text Available Inflammation has been known as one of the main keys to the establishment and progression of cancers. Chronic low-grade inflammation is also a strategic condition that underlies the causes and development of metabolic syndrome and obesity. Moreover, obesity has been largely related to poor prognosis of tumors by modulating tumor microenvironment with secretion of several inflammatory mediators by tumor-associated adipocytes (TAAs, which can modulate and recruit tumor-associated macrophages. Thus, the understanding of cellular and molecular mechanisms that underlay and link inflammation, obesity, and cancer is crucial to identify potential targets that interfere with this important route. Knowledge about the exact role of each component of the tumor microenvironment is not yet fully understood, but the new insights in literature highlight the essential role of adipocytes and macrophages interplay as key factor to determine the fate of cancer progression. In this review article, we focus on the functions of adipocytes and macrophages orchestrating cellular and molecular mechanisms that lead to inflammatory modulation in tumor microenvironment, which will be crucial to cancer establishment. We also emphasized the mechanisms by which the tumor promotes itself by recruiting and polarizing macrophages, discussing the role of adipocytes in this process. In addition, we discuss here the newest possible anticancer therapeutic treatments aiming to retard the development of the tumor based on what is known about cancer, adipocyte, and macrophage polarization.

  18. Evaluation of cage micro-environment of mice housed on various types of bedding materials.

    Science.gov (United States)

    Smith, Ellen; Stockwell, Jason D; Schweitzer, Isabelle; Langley, Stephen H; Smith, Abigail L

    2004-07-01

    A variety of environmental factors can affect the outcomes of studies using laboratory rodents. One such factor is bedding. Several new bedding materials and processing methods have been introduced to the market in recent years, but there are few reports of their performance. In the studies reported here, we have assessed the cage micro-environment (in-cage ammonia levels, temperature, and humidity) of mice housed on various kinds of bedding and their combinations. We also compared results for bedding supplied as Nestpaks versus loose bedding. We studied C57BL/6J mice (commonly used) and NOD/LtJ mice (heavy soilers) that were maintained, except in one study, in static duplex cages. In general, we observed little effect of bedding type on in-cage temperature or humidity; however, there was considerable variation in ammonia concentrations. The lowest ammonia concentrations occurred in cages housing mice on hardwood bedding or a mixture of corncob and alpha cellulose. In one experiment comparing the micro-environments of NOD/LtJ male mice housed on woodpulp fiber bedding in static versus ventilated caging, we showed a statistically significant decrease in ammonia concentrations in ventilated cages. Therefore, our data show that bedding type affects the micro-environment in static cages and that effects may differ for ventilated cages, which are being used in vivaria with increasing frequency. Copyright 2004 American Association for Laboratory Animal Science

  19. Oxygen microenvironment affects the uptake of nanoparticles in head and neck tumor cells

    Science.gov (United States)

    Chen, Eunice Y.; Hodge, Sasson; Tai, Katherine; Hou, Huagang; Khan, Nadeem; Hoopes, P. Jack; Samkoe, Kimberley S.

    2013-02-01

    Survival of head and neck cancer patients has not improved in several decades despite advances in diagnostic and therapeutic techniques. Tumor hypoxia in head and neck cancers is a critical factor that leads to poor prognosis, resistance to radiation and chemotherapies, and increased metastatic potential. Magnetic nanoparticle hyperthermia (mNPHT) is a promising therapy for hypoxic tumors because nanoparticles (NP) can be directly injected into, or targeted to, hypoxic tumor cells and exposed to alternating magnetic fields (AMF) to induce hyperthermia. Magnetic NPHT can improve therapeutic effectiveness by two modes of action: 1) direct killing of hypoxic tumor cells; and 2) increase in tumor oxygenation, which has the potential to make the tumor more susceptible to adjuvant therapies such as radiation and chemotherapy. Prior studies in breast cancer cells demonstrated that a hypoxic microenvironment diminished NP uptake in vitro; however, mNPHT with intratumoral NP injection in hypoxic tumors increased tumor oxygenation and delayed tumor growth. In this study, head and neck squamous cell carcinoma (HNSCC) cell lines were incubated in normoxic, hypoxic, and hyperoxic conditions with iron oxide NP for 4-72 hours. After incubation, the cells were analyzed for iron uptake by mass spectrometry, Prussian blue staining, and electron microscopy. In contrast to breast cancer cells, uptake of NPs was increased in hypoxic microenvironments as compared to normoxic conditions in HNSCC cells. In future studies, we will confirm the effect of the oxygen microenvironment on NP uptake and efficacy of mNPHT both in vitro and in vivo.

  20. Microenvironment is involved in cellular response to hydrostatic pressures during chondrogenesis of mesenchymal stem cells.

    Science.gov (United States)

    Ye, Rui; Hao, Jin; Song, Jinlin; Zhao, Zhihe; Fang, Shanbao; Wang, Yating; Li, Juan

    2014-06-01

    Chondrocytes integrate numerous microenvironmental cues to mount physiologically relevant differentiation responses, and the regulation of mechanical signaling in chondrogenic differentiation is now coming into intensive focus. To facilitate tissue-engineered chondrogenesis by mechanical strategy, a thorough understanding about the interactional roles of chemical factors under mechanical stimuli in regulating chondrogenesis is in great need. Therefore, this study attempts to investigate the interaction of rat MSCs with their microenvironment by imposing dynamic and static hydrostatic pressure through modulating gaseous tension above the culture medium. Under dynamic pressure, chemical parameters (pH, pO2, and pCO2) were kept in homeostasis. In contrast, pH was remarkably reduced due to increased pCO2 under static pressure. MSCs under the dynamically pressured microenvironment exhibited a strong accumulation of GAG within and outside the alginate beads, while cells under the statically pressured environment lost newly synthesized GAG into the medium with a speed higher than its production. In addition, the synergic influence on expression of chondrogenic genes was more persistent under dynamic pressure than that under static pressure. This temporal contrast was similar to that of activation of endogenous TGF-β1. Taken altogether, it indicates that a loading strategy which can keep a homeostatic chemical microenvironment is preferred, since it might sustain the stimulatory effects of mechanical stimuli on chondrogenesis via activation of endogenous TGF-β1. © 2013 Wiley Periodicals, Inc.

  1. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

    International Nuclear Information System (INIS)

    Chanmee, Theerawut; Ontong, Pawared; Konno, Kenjiro; Itano, Naoki

    2014-01-01

    During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy

  2. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Chanmee, Theerawut [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Ontong, Pawared [Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Konno, Kenjiro [Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Itano, Naoki, E-mail: itanon@cc.kyoto-su.ac.jp [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan)

    2014-08-13

    During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

  3. The effects of electric fields on charged molecules and particles in individual microenvironments

    Science.gov (United States)

    Jamieson, K. S.; ApSimon, H. M.; Jamieson, S. S.; Bell, J. N. B.; Yost, M. G.

    Measurements of small air ion concentrations, electrostatic potential and AC electric field strengths were taken in an office setting to investigate the link between electric fields and charged molecule and particle concentrations in individual microenvironments. The results obtained indicate that the electromagnetic environments individuals can be exposed to whilst indoors can often bear little resemblance to those experienced outdoors in nature, and that many individuals may spend large periods of their time in "Faraday cage"-like conditions exposed to inappropriate levels and types of electric fields that can reduce localised concentrations of biologically essential and microbiocidal small air ions. Such conditions may escalate their risk of infection from airborne contaminants, including microbes, whilst increasing localised surface contamination. The degree of "electro-pollution" that individuals are exposed to was shown to be influenced by the type of microenvironment they occupy, with it being possible for very different types of microenvironment to exist within the same room. It is suggested that adopting suitable electromagnetic hygiene/productivity guidelines that seek to replicate the beneficial effects created by natural environments may greatly mitigate such problems.

  4. Household air pollution (HAP), microenvironment and child health: Strategies for mitigating HAP exposure in urban Rwanda

    Science.gov (United States)

    Das, Ipsita; Pedit, Joseph; Handa, Sudhanshu; Jagger, Pamela

    2018-04-01

    Exposure to household air pollution (HAP) from cooking and heating with solid fuels is a major risk factor for morbidity and mortality in sub-Saharan Africa. Children under five are particularly at risk for acute lower respiratory infection. We use baseline data from a randomized controlled trial evaluating a household energy intervention in Gisenyi, Rwanda to investigate the role of the microenvironment as a determinant of children’s HAP-related health symptoms. Our sample includes 529 households, with 694 children under five. We examine the association between likelihood of HAP-related health symptom prevalence and characteristics of the microenvironment including: dwelling and cooking area structure; distance to nearest road; and tree cover. We find that children residing in groups of enclosed dwellings, in households that cook indoors, and in households proximate to tree cover, are significantly more likely to experience symptoms of respiratory infection, illness with cough and difficulty breathing. On the other hand, children in households with cemented floors and ventilation holes in the cooking area, are significantly less likely to experience the same symptoms. Our findings suggest that in addition to promoting increased access to clean cooking technologies, there are important infrastructure and microenvironment-related interventions that mitigate HAP exposure.

  5. Construction of extracellular microenvironment to improve surface endothelialization of NiTi alloy substrate

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Peng, E-mail: liupeng79@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433 (China); Zhao, Yongchun; Yan, Ying; Hu, Yan; Yang, Weihu [Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Cai, Kaiyong, E-mail: kaiyong_cai@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

    2015-10-01

    To mimic extracellular microenvironment of endothelial cell, a bioactive multilayered structure of gelatin/chitosan pair, embedding with vascular endothelial growth factor (VEGF), was constructed onto NiTi alloy substrate surface via a layer-by-layer assembly technique. The successful fabrication of the multilayered structure was demonstrated by scanning electron microscopy, atomic force microscopy, contact angle measurement, attenuated total reflection-fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, respectively. The growth behaviors of endothelial cells on various NiTi alloy substrates were investigated in vitro. Cytoskeleton observation, MTT assay, and wound healing assay proved that the VEGF-embedded multilayer structure positively stimulated adhesion, proliferation and motogenic responses of endothelial cells. More importantly, the present system promoted the nitric oxide production of endothelial cells. The approach affords an alternative to construct extracellular microenvironment for improving surface endothelialization of a cardiovascular implant. - Highlights: • Biofunctional multilayer films mimicking extracellular microenvironment were successfully fabricated. • Multilayered structure stimulated the biological responses of endothelial cells. • The approach affords an efficient approach for surface endothelialization of stent implant.

  6. Age-related inflammatory bone marrow microenvironment induces ineffective erythropoiesis mimicking del(5q) MDS.

    Science.gov (United States)

    Mei, Y; Zhao, B; Basiorka, A A; Yang, J; Cao, L; Zhang, J; List, A; Ji, P

    2018-04-01

    Anemia is characteristic of myelodysplastic syndromes (MDS). The mechanisms of anemia in MDS are unclear. Using a mouse genetic approach, here we show that dual deficiency of mDia1 and miR-146a, encoded on chromosome 5q and commonly deleted in MDS (del(5q) MDS), causes an age-related anemia and ineffective erythropoiesis mimicking human MDS. We demonstrate that the ageing bone marrow microenvironment is important for the development of ineffective erythropoiesis in these mice. Damage-associated molecular pattern molecules (DAMPs), whose levels increase in ageing bone marrow, induced TNFα and IL-6 upregulation in myeloid-derived suppressor cells (MDSCs) in mDia1/miR-146a double knockout mice. Mechanistically, we reveal that pathologic levels of TNFα and IL-6 inhibit erythroid colony formation and differentially affect terminal erythropoiesis through reactive oxygen species-induced caspase-3 activation and apoptosis. Treatment of the mDia1/miR-146a double knockout mice with all-trans retinoic acid, which promoted the differentiation of MDSCs and ameliorated the inflammatory bone marrow microenvironment, significantly rescued anemia and ineffective erythropoiesis. Our study underscores the dual roles of the ageing microenvironment and genetic abnormalities in the pathogenesis of ineffective erythropoiesis in del(5q) MDS.

  7. The Bioelectric Code: Reprogramming Cancer and Aging From the Interface of Mechanical and Chemical Microenvironments

    Directory of Open Access Journals (Sweden)

    Brian B. Silver

    2018-03-01

    Full Text Available Cancer is a complex, heterogeneous group of diseases that can develop through many routes. Broad treatments such as chemotherapy destroy healthy cells in addition to cancerous ones, but more refined strategies that target specific pathways are usually only effective for a limited number of cancer types. This is largely due to the multitude of physiological variables that differ between cells and their surroundings. It is therefore important to understand how nature coordinates these variables into concerted regulation of growth at the tissue scale. The cellular microenvironment might then be manipulated to drive cells toward a desired outcome at the tissue level. One unexpected parameter, cellular membrane voltage (Vm, has been documented to exert control over cellular behavior both in culture and in vivo. Manipulating this fundamental cellular property influences a remarkable array of organism-wide patterning events, producing striking outcomes in both tumorigenesis as well as regeneration. These studies suggest that Vm is not only a key intrinsic cellular property, but also an integral part of the microenvironment that acts in both space and time to guide cellular behavior. As a result, there is considerable interest in manipulating Vm both to treat cancer as well as to regenerate organs damaged or deteriorated during aging. However, such manipulations have produced conflicting outcomes experimentally, which poses a substantial barrier to understanding the fundamentals of bioelectrical reprogramming. Here, we summarize these inconsistencies and discuss how the mechanical microenvironment may impact bioelectric regulation.

  8. Catalog of gene expression in adult neural stem cells and their in vivo microenvironment

    International Nuclear Information System (INIS)

    Williams, Cecilia; Wirta, Valtteri; Meletis, Konstantinos; Wikstroem, Lilian; Carlsson, Leif; Frisen, Jonas; Lundeberg, Joakim

    2006-01-01

    Stem cells generally reside in a stem cell microenvironment, where cues for self-renewal and differentiation are present. However, the genetic program underlying stem cell proliferation and multipotency is poorly understood. Transcriptome analysis of stem cells and their in vivo microenvironment is one way of uncovering the unique stemness properties and provides a framework for the elucidation of stem cell function. Here, we characterize the gene expression profile of the in vivo neural stem cell microenvironment in the lateral ventricle wall of adult mouse brain and of in vitro proliferating neural stem cells. We have also analyzed an Lhx2-expressing hematopoietic-stem-cell-like cell line in order to define the transcriptome of a well-characterized and pure cell population with stem cell characteristics. We report the generation, assembly and annotation of 50,792 high-quality 5'-end expressed sequence tag sequences. We further describe a shared expression of 1065 transcripts by all three stem cell libraries and a large overlap with previously published gene expression signatures for neural stem/progenitor cells and other multipotent stem cells. The sequences and cDNA clones obtained within this framework provide a comprehensive resource for the analysis of genes in adult stem cells that can accelerate future stem cell research

  9. Lactic acid in tumor microenvironments causes dysfunction of NKT cells by interfering with mTOR signaling.

    Science.gov (United States)

    Xie, Di; Zhu, Shasha; Bai, Li

    2016-12-01

    Cellular metabolism has been shown to regulate differentiation and function of immune cells. Tumor associated immune cells undergo phenotypic and functional alterations due to the change of cellular metabolism in tumor microenvironments. NKT cells are good candidates for immunotherapies against tumors and have been used in several clinical trials. However, the influences of tumor microenvironments on NKT cell functions remain unclear. In our studies, lactic acid in tumor microenvironments inhibited IFNγ and IL4 productions from NKT cells, and more profound influence on IFNγ was observed. By adjusting the pH of culture medium we further showed that, dysfunction of NKT cells could simply be induced by low extracellular pH. Moreover, low extracellular pH inhibited NKT cell functions by inhibiting mammalian target of rapamycin (mTOR) signaling and nuclear translocation of promyelocytic leukemia zinc-finger (PLZF). Together, our results suggest that tumor acidic microenvironments could interfere with NKT cell functions through metabolic controls.

  10. Post-Inflationary Gravitino Production Revisited

    CERN Document Server

    Ellis, John; Nanopoulos, Dimitri V.; Olive, Keith A.; Peloso, Marco

    2016-01-01

    We revisit gravitino production following inflation. As a first step, we review the standard calculation of gravitino production in the thermal plasma formed at the end of post-inflationary reheating when the inflaton has completely decayed. Next we consider gravitino production prior to the completion of reheating, assuming that the inflaton decay products thermalize instantaneously while they are still dilute. We then argue that instantaneous thermalization is in general a good approximation, and also show that the contribution of non-thermal gravitino production via the collisions of inflaton decay products prior to thermalization is relatively small. Our final estimate of the gravitino-to-entropy ratio is approximated well by a standard calculation of gravitino production in the post-inflationary thermal plasma assuming total instantaneous decay and thermalization at a time $t \\simeq 1.2/\\Gamma_\\phi$. Finally, in light of our calculations, we consider potential implications of upper limits on the gravitin...

  11. Revisiting R-invariant direct gauge mediation

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Cheng-Wei [Center for Mathematics and Theoretical Physics andDepartment of Physics, National Central University,Taoyuan, Taiwan 32001, R.O.C. (China); Institute of Physics, Academia Sinica,Taipei, Taiwan 11529, R.O.C. (China); Physics Division, National Center for Theoretical Sciences,Hsinchu, Taiwan 30013, R.O.C. (China); Kavli IPMU (WPI), UTIAS, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); Harigaya, Keisuke [Department of Physics, University of California,Berkeley, California 94720 (United States); Theoretical Physics Group, Lawrence Berkeley National Laboratory,Berkeley, California 94720 (United States); ICRR, University of Tokyo,Kashiwa, Chiba 277-8582 (Japan); Ibe, Masahiro [Kavli IPMU (WPI), UTIAS, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); ICRR, University of Tokyo,Kashiwa, Chiba 277-8582 (Japan); Yanagida, Tsutomu T. [Kavli IPMU (WPI), UTIAS, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan)

    2016-03-21

    We revisit a special model of gauge mediated supersymmetry breaking, the “R-invariant direct gauge mediation.” We pay particular attention to whether the model is consistent with the minimal model of the μ-term, i.e., a simple mass term of the Higgs doublets in the superpotential. Although the incompatibility is highlighted in view of the current experimental constraints on the superparticle masses and the observed Higgs boson mass, the minimal μ-term can be consistent with the R-invariant gauge mediation model via a careful choice of model parameters. We derive an upper limit on the gluino mass from the observed Higgs boson mass. We also discuss whether the model can explain the 3σ excess of the Z+jets+E{sub T}{sup miss} events reported by the ATLAS collaboration.

  12. The Faraday effect revisited General theory

    CERN Document Server

    Cornean, H D; Pedersen, T G

    2005-01-01

    This paper is the first in a series revisiting the Faraday effect, or more generally, the theory of electronic quantum transport/optical response in bulk media in the presence of a constant magnetic field. The independent electron approximation is assumed. For free electrons, the transverse conductivity can be explicitly computed and coincides with the classical result. In the general case, using magnetic perturbation theory, the conductivity tensor is expanded in powers of the strength of the magnetic field $B$. Then the linear term in $B$ of this expansion is written down in terms of the zero magnetic field Green function and the zero field current operator. In the periodic case, the linear term in $B$ of the conductivity tensor is expressed in terms of zero magnetic field Bloch functions and energies. No derivatives with respect to the quasimomentum appear and thereby all ambiguities are removed, in contrast to earlier work.

  13. Revisiting instanton corrections to the Konishi multiplet

    Energy Technology Data Exchange (ETDEWEB)

    Alday, Luis F. [Mathematical Institute, University of Oxford,Andrew Wiles Building, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG (United Kingdom); Korchemsky, Gregory P. [Institut de Physique Théorique, Université Paris Saclay, CNRS, CEA,F-91191 Gif-sur-Yvette (France)

    2016-12-01

    We revisit the calculation of instanton effects in correlation functions in N=4 SYM involving the Konishi operator and operators of twist two. Previous studies revealed that the scaling dimensions and the OPE coefficients of these operators do not receive instanton corrections in the semiclassical approximation. We go beyond this approximation and demonstrate that, while operators belonging to the same N=4 supermultiplet ought to have the same conformal data, the evaluation of quantum instanton corrections for one operator can be mapped into a semiclassical computation for another operator in the same supermultiplet. This observation allows us to compute explicitly the leading instanton correction to the scaling dimension of operators in the Konishi supermultiplet as well as to their structure constants in the OPE of two half-BPS scalar operators. We then use these results, together with crossing symmetry, to determine instanton corrections to scaling dimensions of twist-four operators with large spin.

  14. Revisiting kaon physics in general Z scenario

    Directory of Open Access Journals (Sweden)

    Motoi Endo

    2017-08-01

    Full Text Available New physics contributions to the Z penguin are revisited in the light of the recently-reported discrepancy of the direct CP violation in K→ππ. Interference effects between the standard model and new physics contributions to ΔS=2 observables are taken into account. Although the effects are overlooked in the literature, they make experimental bounds significantly severer. It is shown that the new physics contributions must be tuned to enhance B(KL→π0νν¯, if the discrepancy of the direct CP violation is explained with satisfying the experimental constraints. The branching ratio can be as large as 6×10−10 when the contributions are tuned at the 10% level.

  15. Sparse random matrices: The eigenvalue spectrum revisited

    International Nuclear Information System (INIS)

    Semerjian, Guilhem; Cugliandolo, Leticia F.

    2003-08-01

    We revisit the derivation of the density of states of sparse random matrices. We derive a recursion relation that allows one to compute the spectrum of the matrix of incidence for finite trees that determines completely the low concentration limit. Using the iterative scheme introduced by Biroli and Monasson [J. Phys. A 32, L255 (1999)] we find an approximate expression for the density of states expected to hold exactly in the opposite limit of large but finite concentration. The combination of the two methods yields a very simple geometric interpretation of the tails of the spectrum. We test the analytic results with numerical simulations and we suggest an indirect numerical method to explore the tails of the spectrum. (author)

  16. Neutrino dark energy. Revisiting the stability issue

    Energy Technology Data Exchange (ETDEWEB)

    Eggers Bjaelde, O.; Hannestad, S. [Aarhus Univ. (Denmark). Dept. of Physics and Astronomy; Brookfield, A.W. [Sheffield Univ. (United Kingdom). Dept. of Applied Mathematics and Dept. of Physics, Astro-Particle Theory and Cosmology Group; Van de Bruck, C. [Sheffield Univ. (United Kingdom). Dept. of Applied Mathematics, Astro-Particle Theory and Cosmology Group; Mota, D.F. [Heidelberg Univ. (Germany). Inst. fuer Theoretische Physik]|[Institute of Theoretical Astrophysics, Oslo (Norway); Schrempp, L. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Tocchini-Valentini, D. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Physics and Astronomy

    2007-05-15

    A coupling between a light scalar field and neutrinos has been widely discussed as a mechanism for linking (time varying) neutrino masses and the present energy density and equation of state of dark energy. However, it has been pointed out that the viability of this scenario in the non-relativistic neutrino regime is threatened by the strong growth of hydrodynamic perturbations associated with a negative adiabatic sound speed squared. In this paper we revisit the stability issue in the framework of linear perturbation theory in a model independent way. The criterion for the stability of a model is translated into a constraint on the scalar-neutrino coupling, which depends on the ratio of the energy densities in neutrinos and cold dark matter. We illustrate our results by providing meaningful examples both for stable and unstable models. (orig.)

  17. Re-visiting the electrophysiology of language.

    Science.gov (United States)

    Obleser, Jonas

    2015-09-01

    This editorial accompanies a special issue of Brain and Language re-visiting old themes and new leads in the electrophysiology of language. The event-related potential (ERP) as a series of characteristic deflections ("components") over time and their distribution on the scalp has been exploited by speech and language researchers over decades to find support for diverse psycholinguistic models. Fortunately, methodological and statistical advances have allowed human neuroscience to move beyond some of the limitations imposed when looking at the ERP only. Most importantly, we currently witness a refined and refreshed look at "event-related" (in the literal sense) brain activity that relates itself more closely to the actual neurobiology of speech and language processes. It is this imminent change in handling and interpreting electrophysiological data of speech and language experiments that this special issue intends to capture. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Inorganic Arsenic?Related Changes in the Stromal Tumor Microenvironment in a Prostate Cancer Cell?Conditioned Media Model

    OpenAIRE

    Shearer, Joseph J.; Wold, Eric A.; Umbaugh, Charles S.; Lichti, Cheryl F.; Nilsson, Carol L.; Figueiredo, Marxa L.

    2015-01-01

    Background: The tumor microenvironment plays an important role in the progression of cancer by mediating stromal?epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic arsenic (iAs), has also been implicated in the progression of prostate cancer. Objective: The role of iAs exposure in stromal signaling in the tumor microenvironment has been largely unexplored. Our objective was to elucidate...

  19. Video-rate resonant scanning multiphoton microscopy: An emerging technique for intravital imaging of the tumor microenvironment

    OpenAIRE

    Kirkpatrick, Nathaniel D.; Chung, Euiheon; Cook, Daniel C.; Han, Xiaoxing; Gruionu, Gabriel; Liao, Shan; Munn, Lance L.; Padera, Timothy P.; Fukumura, Dai; Jain, Rakesh K.

    2012-01-01

    The abnormal tumor microenvironment fuels tumor progression, metastasis, immune suppression, and treatment resistance. Over last several decades, developments in and applications of intravital microscopy have provided unprecedented insights into the dynamics of the tumor microenvironment. In particular, intravital multiphoton microscopy has revealed the abnormal structure and function of tumor-associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug delivery, invasion...

  20. Island solution; Inselloesung

    Energy Technology Data Exchange (ETDEWEB)

    Bah, Isaac

    2013-06-15

    On the Azores island Graciosa the Berlin-based company Younicos has installed a new electricity system with advanced storage technology, which will make the islanders independent from fossil fuels. With an energy mix of wind power, photovoltaics and biomass the dependence on fossil fuels should be terminated. In the center of the flagship project specifically developed hybrid batteries are used (combination of sodium-sulfur- and lithium-ion batteries) with 2.7 MW of power and a storage capacity of ten megawatts hours. [German] Auf der Azoren-Insel Graciosa installiert das Berliner Unternehmen Younicos ein neues Stromsystem mit modernster Speichertechnologie, das die Bewohner unabhaengig von fossilen Energietraegern machen soll. Mit einem Energiemix aus Windkraft, Photovoltaik und Biomasse soll die Abhaengigkeit von fossilen Brennstoffen beendet werden. Im Zentrum des Vorzeigeprojekts stehen speziell fuer den Inseleinsatz entwickelte Hybridbatterien (Kombination aus Natrium-Schwefel- und Lithium-Ionen-Akkus) mit 2,7 Megawatt Leistung und eine Speicherkapazitaet von zehn Megawattestunden.

  1. Urban heat island 1

    DEFF Research Database (Denmark)

    Bühler, Oliver; Jensen, Marina Bergen; Petersen, Karen Sejr

    2010-01-01

    Urban Heat Island beskriver det forhold, at temperaturen i byområder er højere end temperaturen i tilgrænsede landområder. Årsagen hertil ligger i den urbane arealanvendelse, hvor en mindre andel af arealerne er dækket af vegetation, og en større andel består af forseglede arealer.......Urban Heat Island beskriver det forhold, at temperaturen i byområder er højere end temperaturen i tilgrænsede landområder. Årsagen hertil ligger i den urbane arealanvendelse, hvor en mindre andel af arealerne er dækket af vegetation, og en større andel består af forseglede arealer....

  2. Charge Islands Through Tunneling

    Science.gov (United States)

    Robinson, Daryl C.

    2002-01-01

    It has been recently reported that the electrical charge in a semiconductive carbon nanotube is not evenly distributed, but rather it is divided into charge "islands." This paper links the aforementioned phenomenon to tunneling and provides further insight into the higher rate of tunneling processes, which makes tunneling devices attractive. This paper also provides a basis for calculating the charge profile over the length of the tube so that nanoscale devices' conductive properties may be fully exploited.

  3. Islands in the Ocean

    Directory of Open Access Journals (Sweden)

    Elena Bagina

    2017-12-01

    Full Text Available Today’s China is an outpost of modern western architecture. All famous architects and firms build here. Having lost their historical context, the objects of traditional Chinese architecture become islands in the ocean of new development. Their destiny is controversial. Architectural masterpieces are perceived in a superficial manner not only by tourists, but also by local people. The link of times that used to be cherished in Chinese culture is being broken today.

  4. Oncoprotein metastasis and its suppression revisited

    Directory of Open Access Journals (Sweden)

    Radulescu Razvan T

    2010-04-01

    Full Text Available Abstract The past two decades have witnessed an increasing appreciation of the role of the tumor microenvironment, of genetic and epigenetic alterations in normal cells adjacent to tumors and of the migration of normal cells with aberrant intrinsic properties in cancer pathophysiology. Aside from these insights, a novel concept termed "oncoprotein metastasis" (OPM has recently been advanced and proposed to reflect protein-based neoplastic phenomena that might occur even before any modifications relating to the morphology, location or (epigenetic outfit of cells during the malignant process. Here, evidence is presented that supports the OPM perception and thus should contribute not only to further rethink the definition of a normal cell, but also the treatment of cancer disease in the years to come.

  5. MARICULTURE ON CROATIAN ISLANDS

    Directory of Open Access Journals (Sweden)

    Gordana Šarušić

    2000-09-01

    Full Text Available The first attempts of intensive mariculture in Croatia commenced at the very beginning of 1980’s. The mid-eighties brought an expansion of mariculture production, which has been continuously increasing. A few different marine organisms are intensively cultured - both fish and shellfish. Among them commercially most important and highly valued species are sea bass Dicentrarchus labrax and sea bream Sparus aurata. Mussel Mytilus galloprovincialis and oyster Ostrea edulis are the most important shellfish. Fish species such as dentex Dentex dentex, red sea bream Pagrus major and sheepshead bream Puntazzo puntazzo are reared too, but in a rather small quantities. Only recently the rearing, on-growing- of bluefin tuna Thunnus thynnus started in Croatia. The juveniles (70% are reared in a Croatian hatcheries, and 30% has to be imported mainly from Italy and France, due to a higher demand for this kind of culture among the small growers. Croatian part of Adriatic sea possesses a number of geomorfologicaly suitable sites and meteorological conditions which determined the choice - type - of intensive culture. All fish species are reared in a floating cages. The choice of cages i. e. semi off-shore or floating frames, size, rearing volume and design depend on the investors personal preference. The annual turnouf of a market size bass was about 600t and 300t bream in 1996., by 10 island farms which is 70% of total production in Croatia. Including other cultured fish species last year production was up to 1000t, and it™s being estimated to be about 1300t in the following year. The shellfish production on the islands is usually individual attempt of farmers, producing minor quantities mostly in polyculture. This production has bigger potential but it’s limited owing to the EU quality control regulations which do not allow the export, and by domestic market which has drastically decreased due to the collapse of tourism during the recent war. Almost 80

  6. Evidence for the Fundamental Difference Hypothesis or Not?: Island Constraints Revisited

    Science.gov (United States)

    Belikova, Alyona; White, Lydia

    2009-01-01

    This article examines how changes in linguistic theory affect the debate between the fundamental difference hypothesis and the access-to-Universal Grammar (UG) approach to SLA. With a focus on subjacency (Chomsky, 1973), a principle of UG that places constraints on "wh"-movement and that has frequently been taken as a test case for verifying…

  7. Holocene reef building on eastern St. Croix, US Virgin Islands: Lang Bank revisited

    Science.gov (United States)

    Hubbard, D. K.; Gill, I. P.; Burke, R. B.

    2013-09-01

    New core and seismic data suggest that widespread reef building started on Lang Bank by 8,900 CalBP and was dominated by Acropora palmata for the next three millennia. Accretion rates averaged 5.81 m ky-1, a rate that was sufficient for reefs to keep pace with rising sea level on the bank throughout their history. Seismic data show a deep platform interior that was flooded well in advance of reef building along the elevated rim. As a result, those reefs were buffered from sediment stress by their higher positions and active water flow to the west. A. palmata disappeared from the shallow margin by 6,350 yr ago, and reef building on Lang Bank largely ceased by 5,035 CalBP. The reasons for these dramatic events are unclear. Water depth over the reefs was generally shallower than when they started to build, and sea level was slowing dramatically. The new data described here show that reefs flourished on Lang Bank throughout the hiatus suggested by earlier studies (10-7 kyrs BP), and the ultimate demise of shelf-edge reefs is clearly not associated with either poor water quality or sudden sea-level rise. In addition, accretion rates from eastern St. Croix and throughout the Caribbean were well below the high values (≥10 m ky-1) that have been widely assumed. These data collectively argue against models that require extreme environmental or oceanographic phenomena to drown reefs on Lang Bank where reef building was too fast to be outpaced by Holocene sea-level rise. This also bears on more generalized Caribbean models that depend on the presumed reef history on eastern St. Croix.

  8. Revisiting Caveiro Lake sediment record: the Holocene NAO and AMO impact on Pico Island (Azores archipelago)

    Science.gov (United States)

    Hernandez, A.; Giralt, S.; Raposeiro, P. M.; Gonçalves, V. M.; Pueyo, J. J.; Trigo, R. M.; Bao, R.; Sáez, A.

    2017-12-01

    Northern Hemisphere climate is partly conditioned by a number of atmospheric and oceanic patterns which occur in the North Atlantic sector. The favourable location of the Azores Archipelago (37°-40° N, 25°-31° W) results in a privileged place to generate high-resolution Holocene climatic proxy data that can contribute to deep our understanding on the evolution of these atmospheric and oceanic patterns. In the frame of three research projects, namely PALEONAO (CGL2010-15767), RAPIDNAO (CGL2013-40608-R) and PALEOMODES (CGL2016-75281-C2), high-resolution proxy-based reconstructions from Azores Archipelago have recently shown a combined impact of atmospheric and oceanic patterns at multiannual and decadal time-scales (Rubio-Inglés et al. 2016; Hernández et al. 2017). However, the long-term evolution coupling/uncoupling of these patterns is not well-determined yet. Here, we present a new high-resolution climate reconstruction based on the Caveiro Lake sedimentary sequence in order to fill this gap. Previously, Björck et al. (2006) studied a section of this sequence (the uppermost 4.6 m covering last 6 Ka cal BP) concluding that changes in the thermohaline circulation and the SST were the main drivers in the long-term precipitation variability, whereas the NAO impact was the main atmospheric driver of short-term precipitation changes. However, they only distinguished the NAO impact for the last 600 years owing to the low resolution of the study for the lower portion of the core. The new studied sequence (8.40 m long, 8.2 Ka cal BP) has been analysed at decadal-to centennial time-scale resolution for X-ray diffraction (XRD), X-ray fluorescence (XRF) core scanning and elemental and isotope geochemistry on bulk organic matter. The statistical multivariate analysis of the data highlights the main drivers triggering the sedimentary infill of the lake would be the NAO and AMO by controlling the lacustrine productivity via nutrients input. This new high-resolution climate reconstruction from Caveiro Lake disentangles the combined influences of the NAO and AMO through the Holocene at decadal-to-centennial time scales. References Björck et al. (2006) - Quat Sci Rev 25, 9-32. Rubio-Inglés et al. (2016) - AGU fall meeting, PP51A­-2287. Hernández et al. (2017) - Glob Planet Change 154, 61-74.

  9. Self-sustained magnetic islands

    Energy Technology Data Exchange (ETDEWEB)

    Chatenet, J H; Luciani, J F [Ecole Polytechnique, 91 - Palaiseau (France); Garbet, X [Association Euratom-CEA, Centre d` Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France). Dept. de Recherches sur la Fusion Controlee

    1996-06-01

    Numerical simulations of a single magnetic island evolution are presented in the regime where the island width is smaller than an ion Larmor radius. It is shown that the island rotation is controlled by particle diffusion due to collisions or a background of microturbulence. As expected from the theory of a stationary island, there exist cases where linearly stable magnetic perturbation are nonlinearly self-sustained. This situation corresponds to large poloidal beta and temperature gradient. The drive is due to diamagnetic frequency effects. However, this situation is not generic, and islands can also decay. It is found that a magnetic island is self-sustained for a negative off-diagonal diffusion coefficient. This case occurs in a tokamak if the inward particle pinch is due to the temperature gradient. (author). 30 refs.

  10. Self-sustained magnetic islands

    International Nuclear Information System (INIS)

    Chatenet, J.H.; Luciani, J.F.; Garbet, X.

    1996-06-01

    Numerical simulations of a single magnetic island evolution are presented in the regime where the island width is smaller than an ion Larmor radius. It is shown that the island rotation is controlled by particle diffusion due to collisions or a background of microturbulence. As expected from the theory of a stationary island, there exist cases where linearly stable magnetic perturbation are nonlinearly self-sustained. This situation corresponds to large poloidal beta and temperature gradient. The drive is due to diamagnetic frequency effects. However, this situation is not generic, and islands can also decay. It is found that a magnetic island is self-sustained for a negative off-diagonal diffusion coefficient. This case occurs in a tokamak if the inward particle pinch is due to the temperature gradient. (author)

  11. Dilmun revisited: excavations at Saar, Bahrain

    Directory of Open Access Journals (Sweden)

    Harriet Crawford

    1997-11-01

    Full Text Available About 2000 BC the island of Bahrain was at the centre of a prosperous trading community - the Early Dilmun civilization - that stretched from Mesopotamia to the Indus Valley. Excavations at the site of Saar have, since 1989, recovered much new information about the layout of the settlement and its local economy and social system.

  12. Demographic Ageing on Croatian Islands

    Directory of Open Access Journals (Sweden)

    Ivo Nejašmić

    2013-08-01

    Full Text Available This paper analyses the changes in the population structure of the Croatian islands by age, warns of the degree of ageing, provides spatial differentiation of this process and presents perspective of ageing at the level of settlement. Typing of population ageing is based on scores and has seven types. The total island population in 2011 belongs to the type 5 – very old population. Almost a half of the settlements (out of 303 have been affected by the highest levels of ageing (types 6 and 7. It was found that a quarter of island settlements will become “dead villages” in a foreseeable future; most of them are on small islands but also in the interior of larger islands. These are villages decaying in every respect, in which the way of life, as we know it, veins and goes out. The present ageing villagers are their last residents in most cases. Eve¬rything suggests that demographic recovery of the islands is not possible with the forces in situ. It is important to strike a balance between the needs and opportunities in order to successfully organize life on the islands, both small and large ones, and the fact is that there is a continuing disparity, which is especially profound in small islands. A sensitive and selective approach is needed to overcome the unfavourable demographic trends. Therefore it is necessary to respect the particularities of indi¬vidual islands and island groups in devising development strategy. Solutions to the problems must come of the local and wider community in synergy with relevant professional and scientific institutions. However, if the solutions are not found or measures do not give results, if the islands are left to desorganisation and senilisation, a part of the islands will become a wasteland. With regard to the value of this area whose wealth are people in the first place, this would be an intolerable civilization decline.

  13. Renewable energy islands in Europe

    Energy Technology Data Exchange (ETDEWEB)

    Oestergaard, Iben [ed.

    1998-12-31

    This publication includes a compiled presentation of various aspects concerning the possible transformation of some European islands into renewable energy communities and these projects were presented by a selection of pioneer islands at the first European Seminar on Renewable Energy Islands, held on the Danish island of Samsoee, 29-30 June 1998. This issue has increased in importance with the presentation of the ambitious EU-White Paper: `Energy for the future: Renewable Sources of Energy` which was adopted in 1998. One of the key elements of the strategy for an accelerated implementation of renewable energy is to transform 100 localities within Europe into communities which are to be 100% self-sufficient with renewable energy before 2010. In line with this strategy, the Danish Government appointed the island of Samsoe towards the end of 1997 to be the first `official` Danish, renewable energy island. This is to serve as a demonstration project for other local communities, both in Denmark as well as in the rest Europe. Gothland, Madeira, Canary Islands, Cape Verde, Arki, Crete, Minorca and Orkney Islands were represented. Environmental advantages of wind, solar and wave power for distant island communities were indicated. Serious savings would be achieved by limitation of fossil fuel import and utilization of local resources. (EG)

  14. Critical assessment of day time traffic noise level at curbside open-air microenvironment of Kolkata City, India.

    Science.gov (United States)

    Kundu Chowdhury, Anirban; Debsarkar, Anupam; Chakrabarty, Shibnath

    2015-01-01

    The objective of the research work is to assess day time traffic noise level at curbside open-air microenvironment of Kolkata city, India under heterogeneous environmental conditions. Prevailing traffic noise level in terms of A-weighted equivalent noise level (Leq) at the microenvironment was in excess of 12.6 ± 2.1 dB(A) from the day time standard of 65 dB(A) for commercial area recommended by the Central Pollution Control Board (CPCB) of India. Noise Climate and Traffic Noise Index of the microenvironment were accounted for 13 ± 1.8 dB(A) and 88.8 ± 6.1 dB(A) respectively. A correlation analysis explored that prevailing traffic noise level of the microenvironment had weak negative (-0.21; p air temperature and relative humidity. A Varimax rotated principal component analysis explored that motorized traffic volume had moderate positive loading with background noise component (L90, L95, L99) and prevailing traffic noise level had very strong positive loading with peak noise component (L1, L5, L10). Background and peak noise component cumulatively explained 80.98 % of variance in the data set. Traffic noise level at curbside open-air microenvironment of Kolkata City was higher than the standard recommended by CPCB of India. It was highly annoying also. Air temperature and relative humidity had little influence and the peak noise component had the most significant influence on the prevailing traffic noise level at curbside open-air microenvironment. Therefore, traffic noise level at the microenvironment of the city can be reduced with careful honking and driving.

  15. Cancer stem cells and the tumor microenvironment: interplay in tumor heterogeneity.

    Science.gov (United States)

    Albini, Adriana; Bruno, Antonino; Gallo, Cristina; Pajardi, Giorgio; Noonan, Douglas M; Dallaglio, Katiuscia

    2015-01-01

    Tumor cells able to recapitulate tumor heterogeneity have been tracked, isolated and characterized in different tumor types, and are commonly named Cancer Stem Cells or Cancer Initiating Cells (CSC/CIC). CSC/CIC are disseminated in the tumor mass and are resistant to anti-cancer therapies and adverse conditions. They are able to divide into another stem cell and a "proliferating" cancer cell. They appear to be responsible for disease recurrence and metastatic dissemination even after apparent eradication of the primary tumor. The modulation of CSC/CIC activities by the tumor microenvironment (TUMIC) is still poorly known. CSC/CIC may mutually interact with the TUMIC in a special and unique manner depending on the TUMIC cells or proteins encountered. The TUMIC consists of extracellular matrix components as well as cellular players among which endothelial, stromal and immune cells, providing and responding to signals to/from the CSC/CIC. This interplay can contribute to the mechanisms through which CSC/CIC may reside in a dormant state in a tissue for years, later giving rise to tumor recurrence or metastasis in patients. Different TUMIC components, including the connective tissue, can differentially activate CIC/CSC in different areas of a tumor and contribute to the generation of cancer heterogeneity. Here, we review possible networking activities between the different components of the tumor microenvironment and CSC/CIC, with a focus on its role in tumor heterogeneity and progression. We also summarize novel therapeutic options that could target both CSC/CIC and the microenvironment to elude resistance mechanisms activated by CSC/CIC, responsible for disease recurrence and metastases.

  16. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    International Nuclear Information System (INIS)

    Hamm, Christopher A; Wang, Deli; Malchenko, Sergey; Fatima Bonaldo, Maria de; Casavant, Thomas L; Hendrix, Mary JC; Soares, Marcelo B; Stevens, Jeff W; Xie, Hehuang; Vanin, Elio F; Morcuende, Jose A; Abdulkawy, Hakeem; Seftor, Elisabeth A; Sredni, Simone T; Bischof, Jared M

    2010-01-01

    Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis

  17. Navy and black bean supplementation primes the colonic mucosal microenvironment to improve gut health.

    Science.gov (United States)

    Monk, Jennifer M; Lepp, Dion; Wu, Wenqing; Pauls, K Peter; Robinson, Lindsay E; Power, Krista A

    2017-11-01

    Common beans (Phaseolus vulgaris L.) are enriched in non-digestible fermentable carbohydrates and phenolic compounds that can modulate the colonic microenvironment (microbiota and host epithelial barrier) to improve gut health. In a comprehensive assessment of the impact of two commonly consumed bean varieties (differing in levels and types of phenolic compounds) within the colonic microenvironment, C57Bl/6 mice were fed diets supplemented with 20% cooked navy bean (NB) or black bean (BB) flours or an isocaloric basal diet control (BD) for 3 weeks. NB and BB similarly altered the fecal microbiota community structure (16S rRNA sequencing) notably by increasing the abundance of carbohydrate fermenting bacteria such as Prevotella, S24-7 and Ruminococcus flavefaciens, which coincided with enhanced short chain fatty acid (SCFA) production (microbial-derived carbohydrate fermentation products) and colonic expression of the SCFA receptors GPR-41/-43/-109a. Both NB and BB enhanced multiple aspects of mucus and epithelial barrier integrity vs. BD including: (i) goblet cell number, crypt mucus content and mucin mRNA expression, (ii) anti-microbial defenses (Reg3γ), (iii) crypt length and epithelial cell proliferation, (iv) apical junctional complex components (occludin, JAM-A, ZO-1 and E-cadherin) mRNA expression and (v) reduced serum endotoxin concentrations. Interestingly, biomarkers of colon barrier integrity (crypt height, mucus content, cell proliferation and goblet cell number) were enhanced in BB vs. NB-fed mice, suggesting added benefits attributable to unique BB components (e.g., phenolics). Overall, NB and BB improved baseline colonic microenvironment function by altering the microbial community structure and activity and promoting colon barrier integrity and function; effects which may prove beneficial in attenuating gut-associated diseases. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  18. In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.

    Science.gov (United States)

    Ozcelikkale, Altug; Moon, Hye-Ran; Linnes, Michael; Han, Bumsoo

    2017-09-01

    Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high-throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  19. Enhanced Suppressive Activity of Regulatory T Cells in the Microenvironment of Malignant Pleural Effusions

    Directory of Open Access Journals (Sweden)

    Joanna Budna

    2018-01-01

    Full Text Available Cancer metastatic spread to serous cavity causes malignant pleural effusions (MPEs, indicating dismal prognosis. Tumor microenvironment can implement suppressive activity on host immune responses. Thus, we investigated the prevalence of Tregs and the relationship between them and TGF-β and IL-10 concentrations and measured expression of FOXP3, CTLA-4, CD28, and GITR genes, as well as protein expression of selected genes in benign effusions and MPEs. The percentage of Tregs was determined by means of multicolor flow cytometry system. TGF-β and IL-10 concentrations were measured using human TGF-β1 and IL-10 ELISA kit. Relative mRNA expression of studied genes was analyzed by real-time PCR. The frequency of Tregs was significantly higher in MPEs compared to benign effusions; however, the level of TGF-β and IL-10 in analyzed groups was comparable, and no correlation between concentrations of TGF-β and IL-10 and percentage of Tregs was observed. Relative mRNA expression of all the genes was higher in CD4+CD25+ compared to CD4+CD25− cells. In CD4+CD25+ cells from MPEs, relative mRNA expression of FOXP3, CTLA-4, and CD28 genes was significantly higher than in benign effusions; however, the level of CD4+CD25+CTLA-4+ cells in analyzed groups showed no significant differences. We found numerous genes correlations in an entire CD4+CD25+ cell subset and CD4+CD25+ cells from MPEs. Enhanced suppressive activity of Tregs is observed in the microenvironment of MPEs. Understanding of relations between cellular and cytokine immunosuppressive factors in tumor microenvironment may determine success of anticancer response.

  20. Phenotypic characterization of prostate cancer LNCaP cells cultured within a bioengineered microenvironment.

    Directory of Open Access Journals (Sweden)

    Shirly Sieh

    Full Text Available Biophysical and biochemical properties of the microenvironment regulate cellular responses such as growth, differentiation, morphogenesis and migration in normal and cancer cells. Since two-dimensional (2D cultures lack the essential characteristics of the native cellular microenvironment, three-dimensional (3D cultures have been developed to better mimic the natural extracellular matrix. To date, 3D culture systems have relied mostly on collagen and Matrigel™ hydrogels, allowing only limited control over matrix stiffness, proteolytic degradability, and ligand density. In contrast, bioengineered hydrogels allow us to independently tune and systematically investigate the influence of these parameters on cell growth and differentiation. In this study, polyethylene glycol (PEG hydrogels, functionalized with the Arginine-glycine-aspartic acid (RGD motifs, common cell-binding motifs in extracellular matrix proteins, and matrix metalloproteinase (MMP cleavage sites, were characterized regarding their stiffness, diffusive properties, and ability to support growth of androgen-dependent LNCaP prostate cancer cells. We found that the mechanical properties modulated the growth kinetics of LNCaP cells in the PEG hydrogel. At culture periods of 28 days, LNCaP cells underwent morphogenic changes, forming tumor-like structures in 3D culture, with hypoxic and apoptotic cores. We further compared protein and gene expression levels between 3D and 2D cultures upon stimulation with the synthetic androgen R1881. Interestingly, the kinetics of R1881 stimulated androgen receptor (AR nuclear translocation differed between 2D and 3D cultures when observed by immunofluorescent staining. Furthermore, microarray studies revealed that changes in expression levels of androgen responsive genes upon R1881 treatment differed greatly between 2D and 3D cultures. Taken together, culturing LNCaP cells in the tunable PEG hydrogels reveals differences in the cellular responses to

  1. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    Directory of Open Access Journals (Sweden)

    Hamm Christopher A

    2010-09-01

    Full Text Available Abstract Background Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. Methods To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. Results The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. Conclusion This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that

  2. Inflammatory models drastically alter tumor growth and the immune microenvironment in hepatocellular carcinoma.

    Science.gov (United States)

    Markowitz, Geoffrey J; Michelotti, Gregory A; Diehl, Anna Mae; Wang, Xiao-Fan

    2015-04-01

    Initiation and progression of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue. This diseased liver tissue background is a drastically different microenvironment from the healthy liver, especially with regard to immune cell prevalence and presence of mediators of immune function. To better understand the consequences of liver disease on tumor growth and the interplay with its microenvironment, we utilized two standard methods of fibrosis induction and orthotopic implantation of tumors into the inflamed and fibrotic liver to mimic the liver condition in human HCC patients. Compared to non-diseased controls, tumor growth was significantly enhanced under fibrotic conditions. The immune cells that infiltrated the tumors were also drastically different, with decreased numbers of natural killer cells but greatly increased numbers of immune-suppressive CD11b + Gr1 hi myeloid cells in both models of fibrosis. In addition, there were model-specific differences: Increased numbers of CD11b + myeloid cells and CD4 + CD25 + T cells were found in tumors in the bile duct ligation model but not in the carbon tetrachloride model. Induction of fibrosis altered the cytokine production of implanted tumor cells, which could have farreaching consequences on the immune infiltrate and its functionality. Taken together, this work demonstrates that the combination of fibrosis induction with orthotopic tumor implantation results in a markedly different tumor microenvironment and tumor growth kinetics, emphasizing the necessity for more accurate modeling of HCC progression in mice, which takes into account the drastic changes in the tissue caused by chronic liver disease.

  3. Of plasticity and specificity: dialectics of the microenvironment and macroenvironment and the organ phenotype.

    Science.gov (United States)

    Bhat, Ramray; Bissell, Mina J

    2014-01-01

    The study of biological form and how it arises is the domain of the developmental biologists; but once the form is achieved, the organ poses a fascinating conundrum for all the life scientists: how are form and function maintained in adult organs throughout most of the life of the organism? That they do appears to contradict the inherently plastic nature of organogenesis during development. How do cells with the same genetic information arrive at, and maintain such different architectures and functions, and how do they keep remembering that they are different from each other? It is now clear that narratives based solely on genes and an irreversible regulatory dynamics cannot answer these questions satisfactorily, and the concept of microenvironmental signaling needs to be added to the equation. During development, cells rearrange and differentiate in response to diffusive morphogens, juxtacrine signals, and the extracellular matrix (ECM). These components, which constitute the modular microenvironment, are sensitive to cues from other tissues and organs of the developing embryo as well as from the external macroenvironment. On the other hand, once the organ is formed, these modular constituents integrate and constrain the organ architecture, which ensures structural and functional homeostasis and therefore, organ specificity. We argue here that a corollary of the above is that once the organ architecture is compromised in adults by mutations or by changes in the microenvironment such as aging or inflammation, that organ becomes subjected to the developmental and embryonic circuits in search of a new identity. But since the microenvironment is no longer embryonic, the confusion leads to cancer: hence as we have argued, tumors become new evolutionary organs perhaps in search of an elusive homeostasis. © 2013 Wiley Periodicals, Inc.

  4. Cellular Microenvironment Dictates Androgen Production by Murine Fetal Leydig Cells in Primary Culture1

    Science.gov (United States)

    Carney, Colleen M.; Muszynski, Jessica L.; Strotman, Lindsay N.; Lewis, Samantha R.; O'Connell, Rachel L.; Beebe, David J.; Theberge, Ashleigh B.; Jorgensen, Joan S.

    2014-01-01

    ABSTRACT Despite the fact that fetal Leydig cells are recognized as the primary source of androgens in male embryos, the mechanisms by which steroidogenesis occurs within the developing testis remain unclear. A genetic approach was used to visualize and isolate fetal Leydig cells from remaining cells within developing mouse testes. Cyp11a1-Cre mice were bred to mT/mG dual reporter mice to target membrane-tagged enhanced green fluorescent protein (GFP) within steroidogenic cells, whereas other cells expressed membrane-tagged tandem-dimer tomato red. Fetal Leydig cell identity was validated using double-labeled immunohistochemistry against GFP and the steroidogenic enzyme 3beta-HSD, and cells were successfully isolated as indicated by qPCR results from sorted cell populations. Because fetal Leydig cells must collaborate with neighboring cells to synthesize testosterone, we hypothesized that the fetal Leydig cell microenvironment defined their capacity for androgen production. Microfluidic culture devices were used to measure androstenedione and testosterone production of fetal Leydig cells that were cultured in cell-cell contact within a mixed population, were isolated but remained in medium contact via compartmentalized co-culture with other testicular cells, or were isolated and cultured alone. Results showed that fetal Leydig cells maintained their identity and steroidogenic activity for 3–5 days in primary culture. Microenvironment dictated proficiency of testosterone production. As expected, fetal Leydig cells produced androstenedione but not testosterone when cultured in isolation. More testosterone accumulated in medium from mixed cultures than from compartmentalized co-cultures initially; however, co-cultures maintained testosterone synthesis for a longer time. These data suggest that a combination of cell-cell contact and soluble factors constitute the ideal microenvironment for fetal Leydig cell activity in primary culture. PMID:25143354

  5. Organizations as Designed Islands

    Directory of Open Access Journals (Sweden)

    Pasquale Gagliardi

    2009-05-01

    Full Text Available The literature and practice of organizational design are mostly based on simplistic conceptions which ignore recent theoretical developments in organizational studies. Conceiving of organizations as ‘designed islands’, it is argued, can contribute to a more solid theoretical foundation to organization theory, viewed as normative science. Relying on the work of Peter Sloterdijk, who describes the forms of life in space in terms of spheres, the heuristic power of the island metaphor is explored. What can be learnt from the art of isolating in order to construct lived organizational environments is then discussed, and the paradoxical relationship between connection and isolation is highlighted.

  6. Three Mile Island

    International Nuclear Information System (INIS)

    Wood, M.S.; Shultz, S.M.

    1988-01-01

    This bibliography is divided into the following categories: Accident Overviews, Sequence and Causes; International Commentary and Reaction; Emergency Preparedness and Disaster Planning; Health Effects; Radioactive Releases and the Environment; Accident Investigations/Commissions; Nuclear Industry: Safety, Occupational, and Financial Issues; Media and Communications; Cleanup; Sociopolitical Response and Commentary; Restart; Legal Ramifications; Federal Documents: President's Commission on the Accident at Three Mile Island; Federal Documents: Nuclear Regulatory Commission; Federal Documents: United States Department of Energy; Federal Documents: Miscellaneous Reports; Pennsylvania State Documents; Federal and State Hearings; and Popular Literature

  7. Weather In Some Islands

    Institute of Scientific and Technical Information of China (English)

    王良华

    2007-01-01

    There are four seasons in a year. When spring comes, the weather is mild(温和的). Summer comes after spring. Summer is the hottest season of the year. Autumn follows summer. It is the best season of the year. Winter is the coldest season of the year. Some islands(岛) have their own particular(特别的) seasons because their weather is very much affected(影响) by the oceans(海洋) around them. In Britain, winter is not very cold and summer is not very hot.

  8. Islands and non-islands in native and heritage Korean

    Directory of Open Access Journals (Sweden)

    Boyoung eKim

    2016-02-01

    Full Text Available To a large extent, island phenomena are cross-linguistically invariable, but English and Korean present some striking differences in this domain. English has wh-movement and Korean does not, and while both languages show sensitivity to wh-islands, only English has island effects for adjunct clauses. Given this complex set of differences, one might expect Korean/English bilinguals, and especially heritage Korean speakers (i.e. early bilinguals whose L2 became their dominant language during childhood to be different from native speakers, since heritage speakers have had more limited exposure to Korean, may have had incomplete acquisition and/or attrition, and may show significant transfer effects from the L2. Here we examine islands in heritage speakers of Korean in the U.S. Through a series of four formal acceptability experiments comparing these heritage speakers with native speakers residing in Korea, we show that the two groups are remarkably similar. Both show clear evidence for wh-islands and an equally clear lack of adjunct island effects. Given the very different linguistic environment that the heritage speakers have had since early childhood, this result lends support to the idea that island phenomena are largely immune to environmental influences and stem from deeper properties of the processor and/or grammar. Similarly, it casts some doubt on recent proposals that islands are learned from the input.

  9. Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells.

    Science.gov (United States)

    Sadtler, Kaitlyn; Estrellas, Kenneth; Allen, Brian W; Wolf, Matthew T; Fan, Hongni; Tam, Ada J; Patel, Chirag H; Luber, Brandon S; Wang, Hao; Wagner, Kathryn R; Powell, Jonathan D; Housseau, Franck; Pardoll, Drew M; Elisseeff, Jennifer H

    2016-04-15

    Immune-mediated tissue regeneration driven by a biomaterial scaffold is emerging as an innovative regenerative strategy to repair damaged tissues. We investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration. The scaffolds induced a pro-regenerative response, characterized by an mTOR/Rictor-dependent T helper 2 pathway that guides interleukin-4-dependent macrophage polarization, which is critical for functional muscle recovery. Manipulating the adaptive immune system using biomaterials engineering may support the development of therapies that promote both systemic and local pro-regenerative immune responses, ultimately stimulating tissue repair. Copyright © 2016, American Association for the Advancement of Science.

  10. DNA released by leukemic cells contributes to the disruption of the bone marrow microenvironment

    Czech Academy of Sciences Publication Activity Database

    Dvořáková, Marta; Karafiát, Vít; Pajer, Petr; Kluzáková, E.; Jarkovská, Karla; Peková, S.; Krutílková, L.; Dvořák, Michal

    2013-01-01

    Roč. 32, č. 44 (2013), s. 5201-5209 ISSN 0950-9232 R&D Projects: GA AV ČR KAN200520801; GA MŠk(CZ) LC06061; GA ČR GA204/06/1728; GA ČR GA301/09/1727 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 ; RVO:67985904 Keywords : acute leukemia * tumor microenvironment * extracellular nucleosomes * extracellular DNA * DNA damage response * cell death Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.559, year: 2013

  11. Alkaline biodegradable implants for osteoporotic bone defects--importance of microenvironment pH.

    Science.gov (United States)

    Liu, W; Wang, T; Yang, C; Darvell, B W; Wu, J; Lin, K; Chang, J; Pan, H; Lu, W W

    2016-01-01

    Change of microenvironment pH by biodegradable implants may ameliorate unbalanced osteoporotic bone remodeling. The present work demonstrated that a weak alkaline condition stimulated osteoblasts differentiation while suppressed osteoclast generation. In vivo, implants with an alkaline microenvironment pH (monitored by a pH microelectrode) exhibited a promising healing effect for the repair of osteoporotic bone defects. Under osteoporotic conditions, the response of the bone microenvironment to an endosseous implant is significantly impaired, and this substantially increases the risk of fracture, non-union and aseptic implant loosening. Acid-base equilibrium is an important factor influencing bone cell behaviour. The present purpose was to study the effect of a series of alkaline biodegradable implant materials on regeneration of osteoporotic bone defect, monitoring the microenvironment pH (μe-pH) over time. The proliferation and differentiation potential of osteoporotic rat bone marrow stromal cells and RAW 264.7 cells were examined under various pH conditions. Ovariectomized rat bone defects were filled with specific biodegradable materials, and μe-pH was measured by pH microelectrode. New osteoid and tartrate-resistant acid phosphatase-positive osteoclast-like cells were examined by Goldner's trichrome and TRAP staining, respectively. The intermediate layer between implants and new bone were studied using energy-dispersive X-ray spectroscopy (EDX) linear scanning. In vitro, weak alkaline conditions stimulated osteoporotic rat bone marrow stromal cells (oBMSC) differentiation, while inhibiting the formation of osteoclasts. In vivo, μe-pH differs from that of the homogeneous peripheral blood and exhibits variations over time particular to each material. Higher initial μe-pH was associated with more new bone formation, late response of TRAP-positive osteoclast-like cells and the development of an intermediate 'apatitic' layer in vivo. EDX suggested that

  12. Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong-Hyuk, E-mail: jhkim@umn.edu [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Frantz, Aric M.; Anderson, Katie L.; Graef, Ashley J.; Scott, Milcah C. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Robinson, Sally [Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Sharkey, Leslie C. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); O' Brien, Timothy D. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Dickerson, Erin B. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Modiano, Jaime F., E-mail: modiano@umn.edu [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States)

    2014-04-15

    Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into “IL-8 high” and “IL-8 low” groups. Genome-wide gene expression profiling showed that samples in the “IL-8 high” tumor group were enriched for genes associated with a “reactive microenvironment,” including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA. - Highlights: • IL-8 is expressed in canine hemangiosarcoma tumor samples and cell lines. • IL-8 transduces a relevant biological signal in canine hemangiosarcoma cells. • IL-8 gene signature is associated

  13. Biochemical characterization of nuclear receptors for vitamin D3 and glucocorticoids in prostate stroma cell microenvironment

    International Nuclear Information System (INIS)

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

    2011-01-01

    Highlights: → Fibroblasts from benign and carcinoma-associated stroma were biochemically characterized for VDR and GR function as transcription factors in prostate stroma cell microenvironment. → Decreased SRC-1/CBP coactivators recruitment to VDR and GR may result in hormone resistance to 1,25D 3 in stromal cell microenvironment prostate cancer. → 1a,25-Dyhidroxyvitamin D 3 (1,25D 3 ) and glucocorticoids, either alone or in combination, may not be an alternative for 'some' advanced prostate cancers that fails androgen therapies. -- Abstract: The disruption of stromal cell signals in prostate tissue microenvironment influences the development of prostate cancer to androgen independence. 1α,25-Dihydroxyvitamin D 3 (1,25D 3 ) and glucocorticoids, either alone or in combination, have been investigated as alternatives for the treatment of advanced prostate cancers that fails androgen therapies. The effects of glucocorticoids are mediated by the intracellular glucocorticoid receptor (GR). Similarly, the effect of 1,25D 3 is mediated by the 1,25D 3 nuclear receptor (VDR). In this study, fibroblasts from benign- (BAS) and carcinoma-associated stroma (CAS) were isolated from human prostates to characterize VDR and GR function as transcription factors in prostate stroma. The VDR-mediated transcriptional activity assessed using the CYP24-luciferase reporter was limited to 3-fold induction by 1,25D 3 in 9 out of 13 CAS (70%), as compared to >10-fold induction in the BAS clinical sample pair. Expression of His-tagged VDR (Ad-his-VDR) failed to recover the low transcriptional activity of the luciferase reporter in 7 out of 9 CAS. Interestingly, expression of Ad-his-VDR successfully recovered receptor-mediated induction in 2 out of the 9 CAS analyzed, suggesting that changes in the receptor protein itself was responsible for decreased response and resistance to 1,25D 3 action. Conversely, VDR-mediated transcriptional activity was more efficient in 4 out of 13 CAS (30

  14. Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes.

    Science.gov (United States)

    Allison, Katrina E; Coomber, Brenda L; Bridle, Byram W

    2017-10-01

    Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and up-regulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system. Immune checkpoint blockade provides an example of how metabolism can be differentially impacted to impair cancer cells but support T cells. Implications for research with metabolic inhibitors are discussed. © 2017 John Wiley & Sons Ltd.

  15. A study on the effects of relativistic heavy charged particles on the cellular microenvironment

    Science.gov (United States)

    Costes, Sylvain Vincent

    This study was done under the National Aeronautics Space Administration (NASA) effort to assess the effect of cosmic radiation on astronauts during a 3 year mission to Mars. Carcinogenesis is known to be induced more efficiently by cosmic radiation. Our attention was turned towards one of the most efficient cosmic particles in inducing cancer, relativistic Fe, and focused in assessing its effect on the cellular microenvironment (ECM). Previous observations on mammary glands were showing irregularities in the immunoreactivity of the ECM protein laminin one hour after whole body irradiation with 1GeV/amu Fe ions for a dose of 0.8 Gy. This effect was not observed after 5 Gy γ-rays exposure. The rapidity of such a change suggested that the effect might be due to a physical event specific to relativistic charged particles (HZE), rather than a biological event. Our study showed that this effect is actually a complex and rapid response of the microenvironment to highly ionizing radiation. It involves a fast disruption of the basement membrane of the ECM induced by the highly localized ionization and reactive oxygen formation around the track of the Fe ion. This disruption triggers further chemical and biological responses involved in the remodeling of the laminin network in the basement membrane. A metalloproteinase is suspected to be the intermediate protease affecting laminin. The HZE effect on the microenvironment was seen in both mouse mammary glands and skin, but the laminin isoforms sensitive to Fe ions were different for each organ, with a clear disruption of laminin-1 network in skin and of laminin-5 in mammary glands. In addition, the laminin receptor integrins seem to be involved in this mechanism, but its contribution is unclear at this point. Finally, such studies suggest a shift from the concept of relative biological effectiveness (RBE) used in classical radiation biology since the effect is only seen with HZE at viable whole body doses. In addition, this

  16. Fungal intelligence; Or on the behaviour of microorganisms in confined micro-environments

    International Nuclear Information System (INIS)

    Held, M; Nicolau, D V; Edwards, C

    2009-01-01

    Filamentous fungi are very successful in colonising various microconfined environments, but their behaviour is usually tested on flat surfaces. This contribution presents the design, the fabrication and the use of microstructures, made of a biocompatible polymer (poly(dimethylsiloxane), PDMS) for studying the dynamic micro-scale behaviour of the filamentous fungus Neurospora crassa. The proposed methodology is simple to implement and uses low cost fabrication methods. The observations of the fungus growing through a variety of fabricated micro-environments revealed distinct structure-dependent and structure-induced responses. Generalising the proposed methodology we propose a tool for high-throughput studies of numerous fungal species.

  17. Cell pairing ratio controlled micro-environment with valve-less electrolytic isolation

    KAUST Repository

    Chen, Yu-Chih

    2012-01-01

    We present a ratio controlled cell-to-cell interaction chip using valve-less isolation. We incorporated electrolysis in a microfluidic channel. In each microfluidic chamber, we loaded two types of different cells at various pairing ratios. More than 80% of the microchambers were successfully loaded with a specific target pairing ratio. For the proof of concept, we have demonstrated the cell-to-cell interaction between prostate cancer cells and muscle stem cells can be controlled by cell pairing ratios through growth factor secretion. The experimental data shows that sealing of microenvironment by air generated from electrolysis does not affect cell viability and cell interaction assay results. © 2012 IEEE.

  18. Upregulation of Syndecan-1 in the bone marrow microenvironment in multiple myeloma is associated with angiogenesis

    DEFF Research Database (Denmark)

    Andersen, Niels F; Kristensen, Ida B; Preiss, Birgitte S

    2014-01-01

    : In this study, we examined the association between bone marrow angiogenesis estimated as micro-vessel density (MVD) and gene expression of SDC1, HGF, VEGF and IL6 in whole bone marrow biopsies from healthy volunteers (n = 10), patients with monoclonal gammopathy of undetermined significance (MGUS) (n = 35...... plasma cell percentage and SDC1 gene expression was detected in patients with MM (P angiogenesis and gene...... expression of HGF, VEGF and IL6 was seen. CONCLUSION: Our study indicates that SDC1 expressed by the bone marrow microenvironment is involved in angiogenesis in MM....

  19. Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

    International Nuclear Information System (INIS)

    Kim, Jong-Hyuk; Frantz, Aric M.; Anderson, Katie L.; Graef, Ashley J.; Scott, Milcah C.; Robinson, Sally; Sharkey, Leslie C.; O'Brien, Timothy D.; Dickerson, Erin B.; Modiano, Jaime F.

    2014-01-01

    Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into “IL-8 high” and “IL-8 low” groups. Genome-wide gene expression profiling showed that samples in the “IL-8 high” tumor group were enriched for genes associated with a “reactive microenvironment,” including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA. - Highlights: • IL-8 is expressed in canine hemangiosarcoma tumor samples and cell lines. • IL-8 transduces a relevant biological signal in canine hemangiosarcoma cells. • IL-8 gene signature is associated

  20. Human mammary progenitor cell fate decisions are productsof interactions with combinatorial microenvironments

    DEFF Research Database (Denmark)

    LaBarge, Mark A.; Nelson, Celeste M.; Villadsen, René

    2009-01-01

    factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify...... combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells.Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well...

  1. New and paradoxical roles of matrix metalloproteinases in the tumor microenvironment

    DEFF Research Database (Denmark)

    Noël, Agnès; Gutiérrez-Fernández, Ana; Sounni, Nor Eddine

    2012-01-01

    Processes such as cell proliferation, angiogenesis, apoptosis, or invasion are strongly influenced by the surrounding microenvironment of the tumor. Therefore, the ability to change these surroundings represents an important property through which tumor cells are able to acquire specific functions....... Despite the pro-tumorigenic function of certain metalloproteinases, recent studies have shown that other members of these families, such as MMP8 or MMP11, have a protective role against tumor growth and metastasis in animal models. These studies have been further expanded by large-scale genomic analysis...

  2. Enjebi Island dose assessment

    International Nuclear Information System (INIS)

    Robison, W.L.; Conrado, C.L.; Phillips, W.A.

    1987-07-01

    We have updeated the radiological dose assessment for Enjebi Island at Enewetak Atoll using data derived from analysis of food crops grown on Enjebi. This is a much more precise assessment of potential doses to people resettling Enjebi Island than the 1980 assessment in which there were no data available from food crops on Enjebi. Details of the methods and data used to evaluate each exposure pathway are presented. The terrestrial food chain is the most significant potential exposure pathway and 137 Cs is the radionuclide responsible for most of the estimated dose over the next 50 y. The doses are calculated assuming a resettlement date of 1990. The average wholebody maximum annual estimated dose equivalent derived using our diet model is 166 mremy;the effective dose equivalent is 169 mremy. The estimated 30-, 50-, and 70-y integral whole-body dose equivalents are 3.5 rem, 5.1 rem, and 6.2 rem, respectively. Bone-marrow dose equivalents are only slightly higher than the whole-body estimates in each case. The bone-surface cells (endosteal cells) receive the highest dose, but they are a less sensitive cell population and are less sensitive to fatal cancer induction than whole body and bone marrow. The effective dose equivalents for 30, 50, and 70 y are 3.6 rem, 5.3 rem, and 6.6 rem, respectively. 79 refs., 17 figs., 24 tabs

  3. An Island Called Cuba

    Directory of Open Access Journals (Sweden)

    Jean Stubbs

    2011-06-01

    Full Text Available Review of: An Island Called Home: Returning to Jewish Cuba. Ruth Behar, photographs by Humberto Mayol. New Brunswick NJ: Rutgers University Press, 2007. xiii + 297 pp. (Cloth US$ 29.95 Fidel Castro: My Life: A Spoken Autobiography. Fidel Castro & Ignacio Ramonet. New York: Scribner/Simon & Schuster, 2008. vii + 724 pp. (Paper US$ 22.00, e-book US$ 14.99 Cuba: What Everyone Needs to Know. Julia E. Sweig. New York: Oxford University Press, 2009. xiv + 279 pp. (Paper US$ 16.95 [First paragraph] These three ostensibly very different books tell a compelling story of each author’s approach, as much as the subject matter itself. Fidel Castro: My Life: A Spoken Autobiography is based on a series of long interviews granted by the then-president of Cuba, Fidel Castro, to Spanish-Franco journalist Ignacio Ramonet. Cuba: What Everyone Needs to Know, by U.S. political analyst Julia Sweig, is one of a set country series, and, like Ramonet’s, presented in question/answer format. An Island Called Home: Returning to Jewish Cuba, with a narrative by Cuban-American anthropologist Ruth Behar and photographs by Cuban photographer Humberto Mayol, is a retrospective/introspective account of the Jewish presence in Cuba. While from Ramonet and Sweig we learn much about the revolutionary project, Behar and Mayol convey the lived experience of the small Jewish community against that backdrop.

  4. Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?

    Directory of Open Access Journals (Sweden)

    Jessica Hoarau-Véchot

    2018-01-01

    Full Text Available An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment.

  5. Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?

    Science.gov (United States)

    Hoarau-Véchot, Jessica; Rafii, Arash; Touboul, Cyril; Pasquier, Jennifer

    2018-01-18

    An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME) comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites) and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D) models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D) cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment.

  6. Monitoring developments in island waters

    International Nuclear Information System (INIS)

    Crellin, L.V.

    1995-01-01

    The environmental effects of islands in the Irish Sea of the offshore oil and gas industry are discussed in this paper, in particular on sand and gravel resources. This information is considered by the Department of Trade and Industry when granting prospecting, exploration and production licenses. Consultation between industry and islanders forms part of the license granting process. (UK)

  7. Islands for nuclear power stations

    International Nuclear Information System (INIS)

    Usher, E.F.F.W.; Fraser, A.P.

    1981-01-01

    The safety principles, design criteria and types of artificial island for an offshore nuclear power station are discussed with particular reference to siting adjacent to an industrial island. The paper concludes that the engineering problems are soluble and that offshore nuclear power stations will eventually be built but that much fundamental work is still required. (author)

  8. Pair Production Constraints on Superluminal Neutrinos Revisited

    International Nuclear Information System (INIS)

    Brodsky, Stanley

    2012-01-01

    We revisit the pair creation constraint on superluminal neutrinos considered by Cohen and Glashow in order to clarify which types of superluminal models are constrained. We show that a model in which the superluminal neutrino is effectively light-like can evade the Cohen-Glashow constraint. In summary, any model for which the CG pair production process operates is excluded because such timelike neutrinos would not be detected by OPERA or other experiments. However, a superluminal neutrino which is effectively lightlike with fixed p 2 can evade the Cohen-Glashow constraint because of energy-momentum conservation. The coincidence involved in explaining the SN1987A constraint certainly makes such a picture improbable - but it is still intrinsically possible. The lightlike model is appealing in that it does not violate Lorentz symmetry in particle interactions, although one would expect Hughes-Drever tests to turn up a violation eventually. Other evasions of the CG constraints are also possible; perhaps, e.g., the neutrino takes a 'short cut' through extra dimensions or suffers anomalous acceleration in matter. Irrespective of the OPERA result, Lorentz-violating interactions remain possible, and ongoing experimental investigation of such possibilities should continue.

  9. Carbon emission from global hydroelectric reservoirs revisited.

    Science.gov (United States)

    Li, Siyue; Zhang, Quanfa

    2014-12-01

    Substantial greenhouse gas (GHG) emissions from hydropower reservoirs have been of great concerns recently, yet the significant carbon emitters of drawdown area and reservoir downstream (including spillways and turbines as well as river reaches below dams) have not been included in global carbon budget. Here, we revisit GHG emission from hydropower reservoirs by considering reservoir surface area, drawdown zone and reservoir downstream. Our estimates demonstrate around 301.3 Tg carbon dioxide (CO2)/year and 18.7 Tg methane (CH4)/year from global hydroelectric reservoirs, which are much higher than recent observations. The sum of drawdown and downstream emission, which is generally overlooked, represents 42 % CO2 and 67 % CH4 of the total emissions from hydropower reservoirs. Accordingly, the global average emissions from hydropower are estimated to be 92 g CO2/kWh and 5.7 g CH4/kWh. Nonetheless, global hydroelectricity could currently reduce approximate 2,351 Tg CO2eq/year with respect to fuel fossil plant alternative. The new findings show a substantial revision of carbon emission from the global hydropower reservoirs.

  10. Meta-analysis in clinical trials revisited.

    Science.gov (United States)

    DerSimonian, Rebecca; Laird, Nan

    2015-11-01

    In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effects model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the "DerSimonian and Laird method" is now often referred to as the 'standard approach' or a 'popular' method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. Published by Elsevier Inc.

  11. Critical boundary sine-Gordon revisited

    International Nuclear Information System (INIS)

    Hasselfield, M.; Lee, Taejin; Semenoff, G.W.; Stamp, P.C.E.

    2006-01-01

    We revisit the exact solution of the two space-time dimensional quantum field theory of a free massless boson with a periodic boundary interaction and self-dual period. We analyze the model by using a mapping to free fermions with a boundary mass term originally suggested in Ref. [J. Polchinski, L. Thorlacius, Phys. Rev. D 50 (1994) 622]. We find that the entire SL (2, C) family of boundary states of a single boson are boundary sine-Gordon states and we derive a simple explicit expression for the boundary state in fermion variables and as a function of sine-Gordon coupling constants. We use this expression to compute the partition function. We observe that the solution of the model has a strong-weak coupling generalization of T-duality. We then examine a class of recently discovered conformal boundary states for compact bosons with radii which are rational numbers times the self-dual radius. These have simple expression in fermion variables. We postulate sine-Gordon-like field theories with discrete gauge symmetries for which they are the appropriate boundary states

  12. The drive revisited: Mastery and satisfaction.

    Science.gov (United States)

    Denis, Paul

    2016-06-01

    Starting from the theory of the libido and the notions of the experience of satisfaction and the drive for mastery introduced by Freud, the author revisits the notion of the drive by proposing the following model: the drive takes shape in the combination of two currents of libidinal cathexis, one which takes the paths of the 'apparatus for obtaining mastery' (the sense-organs, motricity, etc.) and strives to appropriate the object, and the other which cathects the erotogenic zones and the experience of satisfaction that is experienced through stimulation in contact with the object. The result of this combination of cathexes constitutes a 'representation', the subsequent evocation of which makes it possible to tolerate for a certain period of time the absence of a satisfying object. On the basis of this conception, the author distinguishes the representations proper, vehicles of satisfaction, from imagos and traumatic images which give rise to excitation that does not link up with the paths taken by the drives. This model makes it possible to conciliate the points of view of the advocates of 'object-seeking' and of those who give precedence to the search for pleasure, and, further, to renew our understanding of object-relations, which can then be approached from the angle of their relations to infantile sexuality. Destructiveness is considered in terms of "mastery madness" and not in terms of the late Freudian hypothesis of the death drive. Copyright © 2015 Institute of Psychoanalysis.

  13. Revisiting the argument from fetal potential

    Directory of Open Access Journals (Sweden)

    Manninen Bertha

    2007-05-01

    Full Text Available Abstract One of the most famous, and most derided, arguments against the morality of abortion is the argument from potential, which maintains that the fetus' potential to become a person and enjoy the valuable life common to persons, entails that its destruction is prima facie morally impermissible. In this paper, I will revisit and offer a defense of the argument from potential. First, I will criticize the classical arguments proffered against the importance of fetal potential, specifically the arguments put forth by philosophers Peter Singer and David Boonin, by carefully unpacking the claims made in these arguments and illustrating why they are flawed. Secondly, I will maintain that fetal potential is morally relevant when it comes to the morality of abortion, but that it must be accorded a proper place in the argument. This proper place, however, cannot be found until we first answer a very important and complex question: we must first address the issue of personal identity, and when the fetus becomes the type of being who is relevantly identical to a future person. I will illustrate why the question of fetal potential can only be meaningfully addressed after we have first answered the question of personal identity and how it relates to the human fetus.

  14. THE CONCEPT OF REFERENCE CONDITION, REVISITED ...

    Science.gov (United States)

    Ecological assessments of aquatic ecosystems depend on the ability to compare current conditions against some expectation of how they could be in the absence of significant human disturbance. The concept of a ‘‘reference condition’’ is often used to describe the standard or benchmark against which current condition is compared. If assessments are to be conducted consistently, then a common understanding of the definitions and complications of reference condition is necessary. A 2006 paper (Stoddard et al., 2006, Ecological Applications 16:1267-1276) made an early attempt at codifying the reference condition concept; in this presentation we will revisit the points raised in that paper (and others) and examine how our thinking has changed in a little over 10 years.Among the issues to be discussed: (1) the “moving target” created when reference site data are used to set thresholds in large scale assessments; (2) natural vs. human disturbance and their effects on reference site distributions; (3) circularity and the use of biological data to assist in reference site identification; (4) using site-scale (in-stream or in-lake) measurements vs. landscape-level human activity to identify reference conditions. Ecological assessments of aquatic ecosystems depend on the ability to compare current conditions against some expectation of how they could be in the absence of significant human disturbance. The concept of a ‘‘reference condition’’ is often use

  15. The Super-GUT CMSSM Revisited

    CERN Document Server

    Ellis, John

    2016-01-01

    We revisit minimal supersymmetric SU(5) grand unification (GUT) models in which the soft supersymmetry-breaking parameters of the minimal supersymmetric Standard Model (MSSM) are universal at some input scale, $M_{in}$, above the supersymmetric gauge coupling unification scale, $M_{GUT}$. As in the constrained MSSM (CMSSM), we assume that the scalar masses and gaugino masses have common values, $m_0$ and $m_{1/2}$ respectively, at $M_{in}$, as do the trilinear soft supersymmetry-breaking parameters $A_0$. Going beyond previous studies of such a super-GUT CMSSM scenario, we explore the constraints imposed by the lower limit on the proton lifetime and the LHC measurement of the Higgs mass, $m_h$. We find regions of $m_0$, $m_{1/2}$, $A_0$ and the parameters of the SU(5) superpotential that are compatible with these and other phenomenological constraints such as the density of cold dark matter, which we assume to be provided by the lightest neutralino. Typically, these allowed regions appear for $m_0$ and $m_{1/...

  16. Searle's"Dualism Revisited"

    Energy Technology Data Exchange (ETDEWEB)

    P., Henry

    2008-11-20

    A recent article in which John Searle claims to refute dualism is examined from a scientific perspective. John Searle begins his recent article 'Dualism Revisited' by stating his belief that the philosophical problem of consciousness has a scientific solution. He then claims to refute dualism. It is therefore appropriate to examine his arguments against dualism from a scientific perspective. Scientific physical theories contain two kinds of descriptions: (1) Descriptions of our empirical findings, expressed in an every-day language that allows us communicate to each other our sensory experiences pertaining to what we have done and what we have learned; and (2) Descriptions of a theoretical model, expressed in a mathematical language that allows us to communicate to each other certain ideas that exist in our mathematical imaginations, and that are believed to represent, within our streams of consciousness, certain aspects of reality that we deem to exist independently of their being perceived by any human observer. These two parts of our scientific description correspond to the two aspects of our general contemporary dualistic understanding of the total reality in which we are imbedded, namely the empirical-mental aspect and the theoretical-physical aspect. The duality question is whether this general dualistic understanding of ourselves should be regarded as false in some important philosophical or scientific sense.

  17. Early-Transition Output Decline Revisited

    Directory of Open Access Journals (Sweden)

    Crt Kostevc

    2016-05-01

    Full Text Available In this paper we revisit the issue of aggregate output decline that took place in the early transition period. We propose an alternative explanation of output decline that is applicable to Central- and Eastern-European countries. In the first part of the paper we develop a simple dynamic general equilibrium model that builds on work by Gomulka and Lane (2001. In particular, we consider price liberalization, interpreted as elimination of distortionary taxation, as a trigger of the output decline. We show that price liberalization in interaction with heterogeneous adjustment costs and non-employment benefits lead to aggregate output decline and surge in wage inequality. While these patterns are consistent with actual dynamics in CEE countries, this model cannot generate output decline in all sectors. Instead sectors that were initially taxed even exhibit output growth. Thus, in the second part we consider an alternative general equilibrium model with only one production sector and two types of labor and distortion in a form of wage compression during the socialist era. The trigger for labor mobility and consequently output decline is wage liberalization. Assuming heterogeneity of workers in terms of adjustment costs and non-employment benefits can explain output decline in all industries.

  18. Post-inflationary gravitino production revisited

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, John [Theoretical Particle Physics and Cosmology Group, Department of Physics, King' s College London, London WC2R 2LS (United Kingdom); Garcia, Marcos A.G.; Olive, Keith A. [William I. Fine Theoretical Physics Institute, School of Physics and Astronomy, University of Minnesota, 116 Church Street SE, Minneapolis, MN 55455 (United States); Nanopoulos, Dimitri V. [George P. and Cynthia W. Mitchell Institute for Fundamental Physics and Astronomy, Texas A and M University, College Station, TX 77843 (United States); Peloso, Marco, E-mail: john.ellis@cern.ch, E-mail: garciagarcia@physics.umn.edu, E-mail: dimitri@physics.tamu.edu, E-mail: olive@physics.umn.edu, E-mail: peloso@physics.umn.edu [School of Physics and Astronomy and Minnesota Institute for Astrophysics, University of Minnesota, 116 Church Street SE, Minneapolis, MN 55455 (United States)

    2016-03-01

    We revisit gravitino production following inflation. As a first step, we review the standard calculation of gravitino production in the thermal plasma formed at the end of post-inflationary reheating when the inflaton has completely decayed. Next we consider gravitino production prior to the completion of reheating, assuming that the inflaton decay products thermalize instantaneously while they are still dilute. We then argue that instantaneous thermalization is in general a good approximation, and also show that the contribution of non-thermal gravitino production via the collisions of inflaton decay products prior to thermalization is relatively small. Our final estimate of the gravitino-to-entropy ratio is approximated well by a standard calculation of gravitino production in the post-inflationary thermal plasma assuming total instantaneous decay and thermalization at a time t ≅ 1.2/Γ{sub φ}. Finally, in light of our calculations, we consider potential implications of upper limits on the gravitino abundance for models of inflation, with particular attention to scenarios for inflaton decays in supersymmetric Starobinsky-like models.

  19. Pipe failure probability - the Thomas paper revisited

    International Nuclear Information System (INIS)

    Lydell, B.O.Y.

    2000-01-01

    Almost twenty years ago, in Volume 2 of Reliability Engineering (the predecessor of Reliability Engineering and System Safety), a paper by H. M. Thomas of Rolls Royce and Associates Ltd. presented a generalized approach to the estimation of piping and vessel failure probability. The 'Thomas-approach' used insights from actual failure statistics to calculate the probability of leakage and conditional probability of rupture given leakage. It was intended for practitioners without access to data on the service experience with piping and piping system components. This article revisits the Thomas paper by drawing on insights from development of a new database on piping failures in commercial nuclear power plants worldwide (SKI-PIPE). Partially sponsored by the Swedish Nuclear Power Inspectorate (SKI), the R and D leading up to this note was performed during 1994-1999. Motivated by data requirements of reliability analysis and probabilistic safety assessment (PSA), the new database supports statistical analysis of piping failure data. Against the background of this database development program, the article reviews the applicability of the 'Thomas approach' in applied risk and reliability analysis. It addresses the question whether a new and expanded database on the service experience with piping systems would alter the original piping reliability correlation as suggested by H. M. Thomas

  20. Revisit to diffraction anomalous fine structure

    International Nuclear Information System (INIS)

    Kawaguchi, T.; Fukuda, K.; Tokuda, K.; Shimada, K.; Ichitsubo, T.; Oishi, M.; Mizuki, J.; Matsubara, E.

    2014-01-01

    The diffraction anomalous fine structure method has been revisited by applying this measurement technique to polycrystalline samples and using an analytical method with the logarithmic dispersion relation. The diffraction anomalous fine structure (DAFS) method that is a spectroscopic analysis combined with resonant X-ray diffraction enables the determination of the valence state and local structure of a selected element at a specific crystalline site and/or phase. This method has been improved by using a polycrystalline sample, channel-cut monochromator optics with an undulator synchrotron radiation source, an area detector and direct determination of resonant terms with a logarithmic dispersion relation. This study makes the DAFS method more convenient and saves a large amount of measurement time in comparison with the conventional DAFS method with a single crystal. The improved DAFS method has been applied to some model samples, Ni foil and Fe 3 O 4 powder, to demonstrate the validity of the measurement and the analysis of the present DAFS method

  1. Revisiting the Survival Mnemonic Effect in Children

    Directory of Open Access Journals (Sweden)

    Josefa N. S. Pand Eirada

    2014-04-01

    Full Text Available The survival processing paradigm is designed to explore the adaptive nature of memory functioning. The mnemonic advantage of processing information in fitness-relevant contexts, as has been demonstrated using this paradigm, is now well established, particularly in young adults; this phenomenon is often referred to as the “survival processing effect.” In the current experiment, we revisited the investigation of this effect in children and tested it in a new cultural group, using a procedure that differs from the existing studies with children. A group of 40 Portuguese children rated the relevance of unrelated words to a survival and a new moving scenario. This encoding task was followed by a surprise free-recall task. Akin to what is typically found, survival processing produced better memory performance than the control condition (moving. These data put on firmer ground the idea that a mnemonic tuning to fitness-relevant encodings is present early in development. The theoretical importance of this result to the adaptive memory literature is discussed, as well as potential practical implications of this kind of approach to the study of memory in children.

  2. Islanded operation of distributed networks

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This report summarises the findings of a study to investigate the regulatory, commercial and technical risks and benefits associated with the operation of distributed generation to power an islanded section of distributed network. A review of published literature was carried out, and UK generators were identified who could operate as part of an island network under the existing technical, regulatory, and safety framework. Agreement on case studies for consideration with distributed network operators (DNOs) is discussed as well as the quantification of the risks, benefits and costs of islanding, and the production of a case implementation plan for each case study. Technical issues associated with operating sections of network in islanded mode are described, and impacts of islanding on trading and settlement, and technical and commercial modelling are explored.

  3. A roadmap for island biology

    DEFF Research Database (Denmark)

    Patino, Jairo; Whittaker, Robert J.; Borges, Paulo A.V.

    2017-01-01

    Aims: The 50th anniversary of the publication of the seminal book, The Theory of Island Biogeography, by Robert H. MacArthur and Edward O. Wilson, is a timely moment to review and identify key research foci that could advance island biology. Here, we take a collaborative horizon-scanning approach...... to identify 50 fundamental questions for the continued development of the field. Location: Worldwide. Methods: We adapted a well-established methodology of horizon scanning to identify priority research questions in island biology, and initiated it during the Island Biology 2016 conference held in the Azores......); global change (5); conservation and management policies (5); and invasive alien species (4). Main conclusions: Collectively, this cross-disciplinary set of topics covering the 50 fundamental questions has the potential to stimulate and guide future research in island biology. By covering fields ranging...

  4. Islanded operation of distributed networks

    International Nuclear Information System (INIS)

    2005-01-01

    This report summarises the findings of a study to investigate the regulatory, commercial and technical risks and benefits associated with the operation of distributed generation to power an islanded section of distributed network. A review of published literature was carried out, and UK generators were identified who could operate as part of an island network under the existing technical, regulatory, and safety framework. Agreement on case studies for consideration with distributed network operators (DNOs) is discussed as well as the quantification of the risks, benefits and costs of islanding, and the production of a case implementation plan for each case study. Technical issues associated with operating sections of network in islanded mode are described, and impacts of islanding on trading and settlement, and technical and commercial modelling are explored

  5. Extracellular Vesicles As Modulators of Tumor Microenvironment and Disease Progression in Glioma

    Directory of Open Access Journals (Sweden)

    Abir Mondal

    2017-07-01

    Full Text Available Diffuse gliomas are lethal tumors of the central nervous system (CNS characterized by infiltrative growth, aggressive nature, and therapeutic resistance. The recent 2016 WHO classification for CNS tumors categorizes diffuse glioma into two major types that include IDH wild-type glioblastoma, which is the predominant type and IDH-mutant glioblastoma, which is less common and displays better prognosis. Recent studies suggest presence of a distinct cell population with stem cell features termed as glioma stem cells (GSCs to be causal in driving tumor growth in glioblastoma. The presence of a stem and progenitor population possibly makes glioblastoma highly heterogeneous. Significantly, tumor growth is driven by interaction of cells residing within the tumor with the surrounding milieu termed as the tumor microenvironment. It comprises of various cell types such as endothelial cells, secreted factors, and the surrounding extracellular matrix, which altogether help perpetuate the proliferation of GSCs. One of the important mediators critical to the cross talk is extracellular vesicles (EVs. These nano-sized vesicles play important roles in intercellular communication by transporting bioactive molecules into the surrounding milieu, thereby altering cellular functions and/or reprogramming recipient cells. With the growing information on the contribution of EVs in modulation of the tumor microenvironment, it is important to determine their role in both supporting as well as promoting tumor growth in glioma. In this review, we provide a comprehensive overview of the role of EVs in tumor progression and glioma pathogenesis.

  6. Probing Microenvironment in Ionic Liquids by Time-Resolved EPR of Photoexcited Triplets.

    Science.gov (United States)

    Ivanov, M Yu; Veber, S L; Prikhod'ko, S A; Adonin, N Yu; Bagryanskaya, E G; Fedin, M V

    2015-10-22

    Unusual physicochemical properties of ionic liquids (ILs) open vistas for a variety of new applications. Herewith, we investigate the influence of microviscosity and nanostructuring of ILs on spin dynamics of the dissolved photoexcited molecules. We use two most common ILs [Bmim]PF6 and [Bmim]BF4 (with its close analogue [C10mim]BF4) as solvents and photoexcited Zn tetraphenylporphyrin (ZnTPP) as a probe. Time-resolved electron paramagnetic resonance (TR EPR) is employed to investigate spectra and kinetics of spin-polarized triplet ZnTPP in the temperature range 100-270 K. TR EPR data clearly indicate the presence of two microenvironments of ZnTPP in frozen ILs at 100-200 K, being manifested in different spectral shapes and different spin relaxation rates. For one of these microenvironments TR EPR data is quite similar to those obtained in common frozen organic solvents (toluene, glycerol, N-methyl-2-pyrrolidone). However, the second one favors the remarkably slow relaxation of spin polarization, being much longer than in the case of common solvents. Additional experiments using continuous wave EPR and stable nitroxide as a probe confirmed the formation of heterogeneities upon freezing of ILs and complemented TR EPR results. Thus, TR EPR of photoexcited triplets can be effectively used for probing heterogeneities and nanostructuring in frozen ILs. In addition, the increase of polarization lifetime in frozen ILs is an interesting finding that might allow investigation of short-lived intermediates inaccessible otherwise.

  7. Silica-induced Chronic Inflammation Promotes Lung Carcinogenesis in the Context of an Immunosuppressive Microenvironment

    Directory of Open Access Journals (Sweden)

    Javier Freire

    2013-08-01

    Full Text Available The association between inflammation and lung tumor development has been clearly demonstrated. However, little is known concerning the molecular events preceding the development of lung cancer. In this study, we characterize a chemically induced lung cancer mouse model in which lung cancer developed in the presence of silicotic chronic inflammation. Silica-induced lung inflammation increased the incidence and multiplicity of lung cancer in mice treated with N-nitrosodimethylamine, a carcinogen found in tobacco smoke. Histologic and molecular analysis revealed that concomitant chronic inflammation contributed to lung tumorigenesis through induction of preneoplastic changes in lung epithelial cells. In addition, silica-mediated inflammation generated an immunosuppressive microenvironment in which we observed increased expression of programmed cell death protein 1 (PD-1, transforming growth factor-β1, monocyte chemotactic protein 1 (MCP-1, lymphocyte-activation gene 3 (LAG3, and forkhead box P3 (FOXP3, as well as the presence of regulatory T cells. Finally, the K-RAS mutational profile of the tumors changed from Q61R to G12D mutations in the inflammatory milieu. In summary, we describe some of the early molecular changes associated to lung carcinogenesis in a chronic inflammatory microenvironment and provide novel information concerning the mechanisms underlying the formation and the fate of preneoplastic lesions in the silicotic lung.

  8. Nutrient sensing via mTOR in T cells maintains a tolerogenic microenvironment

    Directory of Open Access Journals (Sweden)

    Duncan eHowie

    2014-08-01

    Full Text Available We have proposed that tolerance can be maintained by the induction, by Treg cells, of a tolerogenic microenvironment within tolerated tissues that inhibits effector cell activity but which supports the generation of further Treg cells by infectious tolerance. Two important components of this tolerogenic microenvironment depend on metabolism and nutrient sensing. The first is due to the up-regulation of multiple enzymes that consume essential amino acids (EAAs, which are sensed in naive T cells primarily via inhibition of the mTOR pathway, which in turn encourages their further differentiation into foxp3+ Treg cells. The second mechanism is the metabolism of extracellular ATP to adenosine by the ectoenzymes CD39 and CD73. These two enzymes are constitutively co-expressed on Treg cells, but can also be induced on a wide variety of cell types by TGFbeta and the adenosine generated can be shown to be a potent inhibitor of T cell proliferation. This review will focus on mechanisms of nutrient sensing in T cells, how these are integrated with TCR and cytokine signals via the mnTOR pathway, and what impact this has on intracellular metabolism and subsequently the control of differentiation into different effector or regulatory T cell subsets.

  9. Real-time monitoring of thermodynamic microenvironment in a pan coater.

    Science.gov (United States)

    Pandey, Preetanshu; Bindra, Dilbir S

    2013-02-01

    The current study demonstrates the use of tablet-size data logging devices (PyroButtons) to quantify the microenvironment experienced by tablets during pan coating process. PyroButtons were fixed at the inlet and exhaust plenums, and were also placed to freely move with the tablets. The effects of process parameters (spray rate and inlet-air humidity) on the thermodynamic conditions inside the pan coater were studied. It was shown that the same exhaust temperature (a parameter most commonly monitored and controlled during film coating) can be attained with very different tablet-bed conditions. The tablet-bed conditions were found to be more sensitive to the changes in spray rate as compared with the inlet-air humidity. Both spray rate and inlet-air humidity were shown to have an effect on the number of tablet defects (loss of logo definition), and a good correlation between number of tablet defects and tablet-bed humidity was observed. The ability to quantify the thermodynamic microenvironment experienced by the tablets during coating and be able to correlate that to macroscopic tablet defects can be an invaluable tool that can help to establish a process design space during product development. Copyright © 2012 Wiley Periodicals, Inc.

  10. An abnormal bone marrow microenvironment contributes to hematopoietic dysfunction in Fanconi anemia.

    Science.gov (United States)

    Zhou, Yuan; He, Yongzheng; Xing, Wen; Zhang, Peng; Shi, Hui; Chen, Shi; Shi, Jun; Bai, Jie; Rhodes, Steven D; Zhang, Fengqui; Yuan, Jin; Yang, Xianlin; Zhu, Xiaofan; Li, Yan; Hanenberg, Helmut; Xu, Mingjiang; Robertson, Kent A; Yuan, Weiping; Nalepa, Grzegorz; Cheng, Tao; Clapp, D Wade; Yang, Feng-Chun

    2017-06-01

    Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells. Mesenchymal stem/progenitor cells from the double knockout mice showed impaired hematopoietic supportive activity. Mesenchymal stem/progenitor cells of patients with Fanconi anemia exhibited similar cellular deficits, including increased senescence, reduced proliferation, impaired osteoblast differentiation and defective hematopoietic stem/progenitor cell supportive activity. Collectively, these studies provide unique insights into the physiological significance of mesenchymal stem/progenitor cells in supporting the marrow microenvironment, which is potentially of broad relevance in hematopoietic stem cell transplantation. Copyright© Ferrata Storti Foundation.

  11. Out on a limb: Thermal microenvironments in the tropical forest canopy and their relevance to ants.

    Science.gov (United States)

    Stark, Alyssa Y; Adams, Benjamin J; Fredley, Jennifer L; Yanoviak, Stephen P

    2017-10-01

    Small, cursorial ectotherms like ants often are immersed in the superheated air layers that develop millimeters above exposed, insolated surfaces (i.e., the thermal boundary layer). We quantified the thermal microenvironments around tree branches in the tropical rainforest canopy, and explored the effects of substrate color on the internal body temperature and species composition of arboreal ants. Branch temperatures during the day (09:00-16:00) were hottest (often > 50°C) and most variable on the upper surface, while the lowest and least variable temperatures occurred on the underside. Temperatures on black substrates declined with increasing distance above the surface in both the field and the laboratory. By contrast, a micro-scale temperature inversion occurred above white substrates. Wind events (ca. 2ms -1 ) eliminated these patterns. Internal temperatures of bodies of Cephalotes atratus workers experimentally heated in the laboratory were 6°C warmer on white vs. black substrates, and 6°C cooler than ambient in windy conditions. The composition of ant species foraging at baits differed between black-painted and unpainted tree branches, with a tendency for smaller ants to avoid the significantly hotter black surfaces. Collectively, these outcomes show that ants traversing canopy branches experience very heterogeneous thermal microenvironments that are partly influenced in predictable ways by branch surface coloration and breezy conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Targeting Angiogenesis and Tumor Microenvironment in Metastatic Colorectal Cancer: Role of Aflibercept

    Directory of Open Access Journals (Sweden)

    Guido Giordano

    2014-01-01

    Full Text Available In the last decades, we have progressively observed an improvement in therapeutic options for metastatic colorectal cancer (mCRC treatment with a progressive prolongation of survival. mCRC prognosis still remains poor with low percentage of 5-year survival. Targeted agents have improved results obtained with standard chemotherapy. Angiogenesis plays a crucial role in colorectal cancer growth, proliferation, and metastasization and it has been investigated as a potential target for mCRC treatment. Accordingly, novel antiangiogenic targeted agents bevacizumab, regorafenib, and aflibercept have been approved for mCRC treatment as the result of several phase III randomized trials. The development of a tumor permissive microenvironment via the aberrant expression by tumor cells of paracrine factors alters the tumor-stroma interactions inducing an expansion of proangiogenic signals. Recently, the VELOUR study showed that addition of aflibercept to FOLFIRI regimen as a second-line therapy for mCRC improved significantly OS, PFS, and RR. This molecule represents a valid second-line therapeutic option and its peculiar ability to interfere with placental growth factor (PlGF/vascular endothelial growth factor receptor 1 (VEGFR1 axis makes it effective in targeting angiogenesis, inflammatory cells and in overcoming resistances to anti-angiogenic first-line treatment. Here, we discuss about Aflibercept peculiar ability to interfere with tumor microenvironment and angiogenic pathway.

  13. Contribution to Tumor Angiogenesis From Innate Immune Cells Within the Tumor Microenvironment: Implications for Immunotherapy

    Directory of Open Access Journals (Sweden)

    Adriana Albini

    2018-04-01

    Full Text Available The critical role of angiogenesis in promoting tumor growth and metastasis is strongly established. However, tumors show considerable variation in angiogenic characteristics and in their sensitivity to antiangiogenic therapy. Tumor angiogenesis involves not only cancer cells but also various tumor-associated leukocytes (TALs and stromal cells. TALs produce chemokines, cytokines, proteases, structural proteins, and microvescicles. Vascular endothelial growth factor (VEGF and inflammatory chemokines are not only major proangiogenic factors but are also immune modulators, which increase angiogenesis and lead to immune suppression. In our review, we discuss the regulation of angiogenesis by innate immune cells in the tumor microenvironment, specific features, and roles of major players: macrophages, neutrophils, myeloid-derived suppressor and dendritic cells, mast cells, γδT cells, innate lymphoid cells, and natural killer cells. Anti-VEGF or anti-inflammatory drugs could balance an immunosuppressive microenvironment to an immune permissive one. Anti-VEGF as well as anti-inflammatory drugs could therefore represent partners for combinations with immune checkpoint inhibitors, enhancing the effects of immune therapy.

  14. Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

    Energy Technology Data Exchange (ETDEWEB)

    Goffart, Nicolas [Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000 (Belgium); Kroonen, Jérôme [Human Genetics, CHU and University of Liège, Liège 4000 (Belgium); The T& P Bohnenn Laboratory for Neuro-Oncology, Department of Neurology and Neurosurgery, UMC Utrecht, Utrecht 3556 (Netherlands); Rogister, Bernard, E-mail: Bernard.Register@ulg.ac.be [Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000 (Belgium); Department of Neurology, CHU and University of Liège, Liège 4000 (Belgium); GIGA-Development, Stem Cells and Regenerative Medicine, University of Liège, Liège 4000 (Belgium)

    2013-08-14

    Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

  15. Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

    International Nuclear Information System (INIS)

    Goffart, Nicolas; Kroonen, Jérôme; Rogister, Bernard

    2013-01-01

    Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology

  16. Acidic Microenvironments in Waste Rock Characterized by Neutral Drainage: Bacteria–Mineral Interactions at Sulfide Surfaces

    Directory of Open Access Journals (Sweden)

    John W. Dockrey

    2014-03-01

    Full Text Available Microbial populations and microbe-mineral interactions were examined in waste rock characterized by neutral rock drainage (NRD. Samples of three primary sulfide-bearing waste rock types (i.e., marble-hornfels, intrusive, exoskarn were collected from field-scale experiments at the Antamina Cu–Zn–Mo mine, Peru. Microbial communities within all samples were dominated by neutrophilic thiosulfate oxidizing bacteria. However, acidophilic iron and sulfur oxidizers were present within intrusive waste rock characterized by bulk circumneutral pH drainage. The extensive development of microbially colonized porous Fe(III (oxyhydroxide and Fe(III (oxyhydroxysulfate precipitates was observed at sulfide-mineral surfaces during examination by field emission-scanning electron microscopy-energy dispersive X-ray spectroscopy (FE-SEM-EDS. Linear combination fitting of bulk extended X-ray absorption fine structure (EXAFS spectra for these precipitates indicated they were composed of schwertmannite [Fe8O8(OH6–4.5(SO41–1.75], lepidocrocite [γ-FeO(OH] and K-jarosite [KFe3(OH6(SO42]. The presence of schwertmannite and K-jarosite is indicative of the development of localized acidic microenvironments at sulfide-mineral surfaces. Extensive bacterial colonization of this porous layer and pitting of underlying sulfide-mineral surfaces suggests that acidic microenvironments can play an important role in sulfide-mineral oxidation under bulk circumneutral pH conditions. These findings have important implications for water quality management in NRD settings.

  17. Design and development of microbioreactors for long-term cell culture in controlled oxygen microenvironments.

    Science.gov (United States)

    Abaci, Hasan E; Devendra, Raghavendra; Smith, Quinton; Gerecht, Sharon; Drazer, German

    2012-02-01

    The ability to control the oxygen level to which cells are exposed in tissue culture experiments is crucial for many applications. Here, we design, develop and test a microbioreactor (MBR) for long-term cell culture studies with the capability to accurately control and continuously monitor the dissolved oxygen (DO) level in the cell microenvironment. In addition, the DO level can be controlled independently from other cues, such as the viscous shear-stress acting on the cells. We first analyze the transport of oxygen in the proposed device and determine the materials and dimensions that are compatible with uniform oxygen tension and low shear-stress at the cell level. The device is also designed to culture a statistically significant number of cells. We use fully transparent materials and the overall design of the device is compatible with live-cell imaging. The proposed system includes real-time read-out of actual DO levels, is simple to fabricate at low cost, and can be easily expanded to control the concentration of other microenvironmental solutes. We performed control experiments in the absence of cells to demonstrate that the MBR can be used to accurately modulate DO levels ranging from atmospheric level to 1%, both under no flow and perfusion conditions. We also demonstrate cancer cell attachment and viability within the MBR. The proposed MBR offers the unprecedented capability to perform on-line measurement and analysis of DO levels in the microenvironment of adherent cultures and to correlate them with various cellular responses.

  18. Dissecting the hematopoietic microenvironment. V: Limitations of repair following damage to the hematopoietic support stroma

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, N.S.

    1982-01-01

    Damage and repair of the hematopoietic microenvironment of the spleen was studied using X-irradiation, anoxic necrosis induced by splenic ligation, or a combination of the two, as the destructive agents. Spleen colony number, size and type, /sup 59/Fe uptake, and microscopic study of splenic structure were used as means of assessment. The most severe or least repaired damage was induced by high dose irradiation (4000 r), by 1000 r followed immediately by splenic ligation, and by two successive splenic ligations separated by a 30 day recovery period. It was seen that reduction of CFUlt. slashsub slt. slash lodgment, as measured by f factor, played a very major role in the lesser number of spleen colonies formed after either kind of damage. Following the several treatments, the numbers of spleen colonies formed, their size and their typing as erythrocytic or granulocytic varied independently of each other, suggesting that these functions of the microenvironment, and the cell types responsible for them, are independent of each other. The exhaustion of regenerative capacity displayed by repeatedly ligated spleens suggested a maximal limit for stromal cell replications commensurate with Hayflick's hypothesis.

  19. Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance

    Directory of Open Access Journals (Sweden)

    Alessia Fidoamore

    2016-01-01

    Full Text Available Among all solid tumors, the high-grade glioma appears to be the most vascularized one. In fact, “microvascular hyperplasia” is a hallmark of GBM. An altered vascular network determines irregular blood flow, so that tumor cells spread rapidly beyond the diffusion distance of oxygen in the tissue, with the consequent formation of hypoxic or anoxic areas, where the bulk of glioblastoma stem cells (GSCs reside. The response to this event is the induction of angiogenesis, a process mediated by hypoxia inducible factors. However, this new capillary network is not efficient in maintaining a proper oxygen supply to the tumor mass, thereby causing an oxygen gradient within the neoplastic zone. This microenvironment helps GSCs to remain in a “quiescent” state preserving their potential to proliferate and differentiate, thus protecting them by the effects of chemo- and radiotherapy. Recent evidences suggest that responses of glioblastoma to standard therapies are determined by the microenvironment of the niche, where the GSCs reside, allowing a variety of mechanisms that contribute to the chemo- and radioresistance, by preserving GSCs. It is, therefore, crucial to investigate the components/factors of the niche in order to formulate new adjuvant therapies rendering more efficiently the gold standard therapies for this neoplasm.

  20. Engineering Enriched Microenvironments with Gradients of Platelet Lysate in Hydrogel Fibers.

    Science.gov (United States)

    Santo, Vítor E; Babo, Pedro; Amador, Miguel; Correia, Cláudia; Cunha, Bárbara; Coutinho, Daniela F; Neves, Nuno M; Mano, João F; Reis, Rui L; Gomes, Manuela E

    2016-06-13

    Gradients of physical and chemical cues are characteristic of specific tissue microenvironments and contribute toward morphogenesis and tissue regeneration upon injury. Recent advances on microfluidics and hydrogel manipulation raised the possibility of generating biomimetic biomaterials enriched with bioactive factors and encapsulating cells following designs specifically tailored for a target application. The novelty of this work relies on the combination of methacrylated gellan gum (MeGG) with platelet lysate (PL), aiming to generate novel advanced 3D PL-enriched photo-cross-linkable hydrogels and overcoming the lack of adhesion sites provided by the native MeGG hydrogels. This combination takes advantage of the availability, enriched growth factor composition, and potential autologous application of PL while simultaneously preserving the ability provided by MeGG to tailor mechanical properties, protein release kinetics, and shape of the construct according to the desired goal. Incorporation of PL in the hydrogels significantly improved cellular adhesion and viability in the constructs. The use of microfluidic tools allowed the design of a fiber-like hydrogel incorporating a gradient of PL along the length of the fiber. These spatial protein gradients led to the viability and cell number gradients caused by maintenance of human umbilical vein endothelial cells (HUVECs) survival in the fibers toward the PL-enriched sections in comparison with the nonloaded MeGG sections of the fibers. Altogether, we propose a proof of concept strategy to design a PL gradient biomaterial with potential in tissue engineering approaches and analysis of cell-microenvironment interactions.

  1. Neuroblastoma arginase activity creates an immunosuppressive microenvironment that impairs autologous and engineered immunity

    Science.gov (United States)

    Mussai, Francis; Egan, Sharon; Hunter, Stuart; Webber, Hannah; Fisher, Jonathan; Wheat, Rachel; McConville, Carmel; Sbirkov, Yordan; Wheeler, Kate; Bendle, Gavin; Petrie, Kevin; Anderson, John; Chesler, Louis; De Santo, Carmela

    2015-01-01

    Neuroblastoma is the most common extra cranial solid tumour of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumour cells suppress T cell proliferation, through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34+ progenitor proliferation. Finally we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1 specific TCR and GD2-specific CAR engineered T cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for neuroblastoma patients. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumour and blood that leads to impaired immune surveillance and sub-optimal efficacy of immunotherapeutic approaches. PMID:26054597

  2. Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Alessandro Poggi

    2016-11-01

    Full Text Available The tumor microenvironment is a good target for therapy in solid tumors and hematological malignancies. Indeed, solid tumor cells’ growth and expansion can influence neighboring cells’ behavior, leading to a modulation of mesenchymal stromal cell (MSC activities and remodeling of extracellular matrix components. This leads to an altered microenvironment, where reparative mechanisms, in the presence of sub-acute inflammation, are not able to reconstitute healthy tissue. Carcinoma cells can undergo epithelial mesenchymal transition (EMT, a key step to generate metastasis; these mesenchymal-like cells display the functional behavior of MSC. Furthermore, MSC can support the survival and growth of leukemic cells within bone marrow participating in the leukemic cell niche. Notably, MSC can inhibit the anti-tumor immune response through either carcinoma-associated fibroblasts or bone marrow stromal cells. Experimental data have indicated their relevance in regulating cytolytic effector lymphocytes of the innate and adaptive arms of the immune system. Herein, we will discuss some of the evidence in hematological malignancies and solid tumors. In particular, we will focus our attention on the means by which it is conceivable to inhibit MSC-mediated immune suppression and trigger anti-tumor innate immunity.

  3. Urban air pollution in school-related microenvironments in Bogota, Colombia

    Directory of Open Access Journals (Sweden)

    Juan Felipe Franco

    2013-05-01

    Full Text Available Particle-related pollution (PM10, PM2.5 and soot was measured in both indoor and outdoor microenvironments at four public elementary schools in Bogota, Colombia. Three of these schools were located alongside major urban roads in which different types of public transit systems are used (bus rapid transit system and conventional transit buses. The fourth school was located on a non-congested road (background school. Pollutant levels at schools situated on major-roads were higher than those found at the low-congestion-road school. Outdoor black carbon daily mean concentrations at the schools located near major roads were up to six times higher than those recorded at the background school. Mean particulate matter concentrations at schools near major roads were above international standards, suggesting that school-age children in Bogota are exposed to pollution levels that are considered to be harmful by environmental and public health authorities. Elevated indoor and outdoor pollutant concentrations documented in this study suggested that traffic has a direct impact on air quality regarding the schools’ characterised microenvironments.

  4. Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease

    Science.gov (United States)

    Cruz, Nelly M.; Song, Xuewen; Czerniecki, Stefan M.; Gulieva, Ramila E.; Churchill, Angela J.; Kim, Yong Kyun; Winston, Kosuke; Tran, Linh M.; Diaz, Marco A.; Fu, Hongxia; Finn, Laura S.; Pei, York; Himmelfarb, Jonathan; Freedman, Benjamin S.

    2017-11-01

    Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular epithelia form fluid-filled cysts. A major barrier to understanding PKD is the absence of human cellular models that accurately and efficiently recapitulate cystogenesis. Previously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidney organoids. Here we show that systematic substitution of physical components can dramatically increase or decrease cyst formation, unveiling a critical role for microenvironment in PKD. Removal of adherent cues increases cystogenesis 10-fold, producing cysts phenotypically resembling PKD that expand massively to 1-centimetre diameters. Removal of stroma enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression and collagen compaction. Cyclic adenosine monophosphate (cAMP), when added, induces cysts in both PKD organoids and controls. These biomaterials establish a highly efficient model of PKD cystogenesis that directly implicates the microenvironment at the earliest stages of the disease.

  5. Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

    Directory of Open Access Journals (Sweden)

    Nicolas Goffart

    2013-08-01

    Full Text Available Glioblastoma multiforme (GBM, WHO grade IV is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

  6. Human Pluripotent Stem Cell Mechanobiology: Manipulating the Biophysical Microenvironment for Regenerative Medicine and Tissue Engineering Applications.

    Science.gov (United States)

    Ireland, Ronald G; Simmons, Craig A

    2015-11-01

    A stem cell in its microenvironment is subjected to a myriad of soluble chemical cues and mechanical forces that act in concert to orchestrate cell fate. Intuitively, many of these soluble and biophysical factors have been the focus of intense study to successfully influence and direct cell differentiation in vitro. Human pluripotent stem cells (hPSCs) have been of considerable interest in these studies due to their great promise for regenerative medicine. Culturing and directing differentiation of hPSCs, however, is currently extremely labor-intensive and lacks the efficiency required to generate large populations of clinical-grade cells. Improved efficiency may come from efforts to understand how the cell biophysical signals can complement biochemical signals to regulate cell pluripotency and direct differentiation. In this concise review, we explore hPSC mechanobiology and how the hPSC biophysical microenvironment can be manipulated to maintain and differentiate hPSCs into functional cell types for regenerative medicine and tissue engineering applications. © 2015 AlphaMed Press.

  7. Microtissues in Cardiovascular Medicine: Regenerative Potential Based on a 3D Microenvironment

    Directory of Open Access Journals (Sweden)

    Julia Günter

    2016-01-01

    Full Text Available More people die annually from cardiovascular diseases than from any other cause. In particular, patients who suffer from myocardial infarction may be affected by ongoing adverse remodeling processes of the heart that may ultimately lead to heart failure. The introduction of stem and progenitor cell-based applications has raised substantial hope for reversing these processes and inducing cardiac regeneration. However, current stem cell therapies using single-cell suspensions have failed to demonstrate long-lasting efficacy due to the overall low retention rate after cell delivery to the myocardium. To overcome this obstacle, the concept of 3D cell culture techniques has been proposed to enhance therapeutic efficacy and cell engraftment based on the simulation of an in vivo-like microenvironment. Of great interest is the use of so-called microtissues or spheroids, which have evolved from their traditional role as in vitro models to their novel role as therapeutic agents. This review will provide an overview of the therapeutic potential of microtissues by addressing primarily cardiovascular regeneration. It will accentuate their advantages compared to other regenerative approaches and summarize the methods for generating clinically applicable microtissues. In addition, this review will illustrate the unique properties of the microenvironment within microtissues that makes them a promising next-generation therapeutic approach.

  8. Choline-Deficient-Diet-Induced Fatty Liver Is a Metastasis-Resistant Microenvironment.

    Science.gov (United States)

    Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kosuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

    2017-07-01

    Fatty liver disease is increasing in the developed and developing world. Liver metastasis from malignant lymphoma in the fatty liver is poorly understood. In a previous report, we developed color-coded imaging of the tumor microenvironment (TME) of the murine EL4-RFP malignant lymphoma during metastasis, including the lung. In the present report, we investigated the potential and microenvironment of the fatty liver induced by a choline-deficient diet as a metastatic site in this mouse lymphoma model. C57BL/6-GFP transgenic mice were fed with a choline-deficient diet in order to establish a fatty liver model. EL4-RFP cells were injected in the spleen of normal mice and fatty-liver mice. Metastases in mice with fatty liver or normal liver were imaged with the Olympus SZX7 microscope and the Olympus FV1000 confocal microscope. Metastases of EL4-RFP were observed in the liver, ascites and bone marrow. Primary tumors were imaged in the spleen at the injection site. The fewest metastases were observed in the fatty liver. In addition, the fewest cancer-associated fibroblasts (CAFs) were observed in the fatty liver. The relative metastatic resistance of the fatty liver may be due to the reduced number of CAFs in the fatty livers. The mechanism of the effect of the choline-deficient diet is discussed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Island in an island – The suggestions for transportation improvement plan for Haidian Island, Haikou, Hainan

    Directory of Open Access Journals (Sweden)

    Sia Rosalind Juo Ling

    2017-01-01

    Full Text Available Haidian Island, which situated at the Northern part of Haikou City of Hainan Province, is an island within a city. Haidian Island is unique in term of it's development which centered around an university, the Hainan University, besides some others important landmarks, such as Haikou city hospital, Baishamen municipal park, Golf Driving Range etc. All commercials, residential, recreational activities etc are planned to serve Hainan University in particular. The study, taking ‘Haidian Island Area Development Control Plan’ as case study, would like to look into the importance of transportation and traffic planning. The study used observation, site investigation and traffic study methods to gather data needed. Firstly the study analyzed the current state of transportation system for Haidian Island in accordance to the Island Development Control plan and Haikou master plan and identified the problems. Then, the study made some recommendations for these problems. The study highlighted the important of non-motorized, cycling and walking as the main transportation system for an education-based island and as supportive to domestic tourism activities found. The transportation planning suggested by the study took ‘green and low-carbon’ approaches considered the role of University as the core activity in the island.

  10. Effect of the Premalignant and Tumor Microenvironment on Immune Cell Cytokine Production in Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Sara D. [Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425 (United States); De Costa, Anna-Maria A. [Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC 29425 (United States); Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425 (United States); Young, M. Rita I., E-mail: rita.young@va.gov [Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC 29425 (United States); Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425 (United States); Medical Research Service (151), Ralph H. Johnson Veterans Affairs Medical Center, 109 Bee Street, Charleston, SC 29401 (United States)

    2014-04-02

    Head and neck squamous cell carcinoma (HNSCC) is marked by immunosuppression, a state in which the established tumor escapes immune attack. However, the impact of the premalignant and tumor microenvironments on immune reactivity has yet to be elucidated. The purpose of this study was to determine how soluble mediators from cells established from carcinogen-induced oral premalignant lesions and HNSCC modulate immune cell cytokine production. It was found that premalignant cells secrete significantly increased levels of G-CSF, RANTES, MCP-1, and PGE{sub 2} compared to HNSCC cells. Splenocytes incubated with premalignant supernatant secreted significantly increased levels of Th1-, Th2-, and Th17-associated cytokines compared to splenocytes incubated with HNSCC supernatant. These studies demonstrate that whereas the premalignant microenvironment elicits proinflammatory cytokine production, the tumor microenvironment is significantly less immune stimulatory and may contribute to immunosuppression in established HNSCC.

  11. Energy Self-Sufficient Island

    International Nuclear Information System (INIS)

    Bratic, S.; Krajacic, G.; Duic, N.; Cotar, A.; Jardas, D.

    2011-01-01

    In order to analyze energy self-sufficient island, example of a smaller island, connected to the power system of a bigger island with an undersea cable, was taken. Mounting substation 10/0,4 is situated on the island and for the moment it provides enough electricity using the medium voltage line. It is assumed that the island is situated on the north part of the Adriatic Sea. The most important problem that occurs on the island is the population drop that occurs for a significant number of years, therefore, life standard needs to be improved, and economic development needs to be encouraged immediately. Local authorities to stimulate sustainable development on the island through different projects, to breath in a new life to the island, open new jobs and attract new people to come live there. Because of the planned development and increase of the population, energy projects, planned as a support to sustainable development, and later achievement of the energy self-sufficiency, is described in this paper. Therefore, Rewisland methodology appliance is described taking into the account three possible scenarios of energy development. Each scenario is calculated until year 2030. Also, what is taken into the account is 100% usage of renewable sources of energy in 2030. Scenario PTV, PP, EE - This scenario includes installation of solar photovoltaic modules and solar thermal collectors on the buildings roofs, as well as well as implementation of energy efficiency on the island (replacement of the street light bulbs with LED lightning, replacement of the old windows and doors on the houses, as well as the installation of the thermal insulation). Scenario PV island - This scenario, similarly to the previous one, includes installation of solar photovoltaic modules and solar thermal collectors an the residential buildings, as well as the 2 MW photovoltaic power plant and ''Green Hotel'', a building that satisfies all of its energy needs completely from renewable energy sources

  12. Pockets of Participation: Revisiting Child-Centred Participation Research

    Science.gov (United States)

    Franks, Myfanwy

    2011-01-01

    This article revisits the theme of the clash of interests and power relations at work in participatory research which is prescribed from above. It offers a possible route toward solving conflict between adult-led research carried out by young researchers, funding requirements and organisational constraints. The article explores issues of…

  13. Rereading Albert B. Lord's The Singer of Tales . Revisiting the ...

    African Journals Online (AJOL)

    Access to a fresh set of video-recordings of Sesotho praise-poetry made in the year 2000 enabled the author to revisit his adaptation of Albert Lord's definition of the formula as a dynamic compositional device that the oral poet utilizes during delivery. The basic adaptation made in 1983 pertains to heroic praises (dithoko tsa ...

  14. Literary Origins of the Term "School Psychologist" Revisited

    Science.gov (United States)

    Fagan, Thomas K.

    2005-01-01

    Previous research on the literary origins of the term "school psychologist" is revisited, and conclusions are revised in light of new evidence. It appears that the origin of the term in the American literature occurred as early as 1898 in an article by Hugo Munsterberg, predating the usage by Wilhelm Stern in 1911. The early references to the…

  15. The Neutrosophic Logic View to Schrodinger's Cat Paradox, Revisited

    Directory of Open Access Journals (Sweden)

    Florentin Smarandache

    2008-07-01

    Full Text Available The present article discusses Neutrosophic logic view to Schrodinger's cat paradox. We argue that this paradox involves some degree of indeterminacy (unknown which Neutrosophic logic can take into consideration, whereas other methods including Fuzzy logic cannot. To make this proposition clear, we revisit our previous paper by offering an illustration using modified coin tossing problem, known as Parrondo's game.

  16. Revisiting Constructivist Teaching Methods in Ontario Colleges Preparing for Accreditation

    Science.gov (United States)

    Schultz, Rachel A.

    2015-01-01

    At the time of writing, the first community colleges in Ontario were preparing for transition to an accreditation model from an audit system. This paper revisits constructivist literature, arguing that a more pragmatic definition of constructivism effectively blends positivist and interactionist philosophies to achieve both student centred…

  17. High precision mass measurements in Ψ and Υ families revisited

    International Nuclear Information System (INIS)

    Artamonov, A.S.; Baru, S.E.; Blinov, A.E.

    2000-01-01

    High precision mass measurements in Ψ and Υ families performed in 1980-1984 at the VEPP-4 collider with OLYA and MD-1 detectors are revisited. The corrections for the new value of the electron mass are presented. The effect of the updated radiative corrections has been calculated for the J/Ψ(1S) and Ψ(2S) mass measurements [ru

  18. Surface tension in soap films: revisiting a classic demonstration

    International Nuclear Information System (INIS)

    Behroozi, F

    2010-01-01

    We revisit a classic demonstration for surface tension in soap films and introduce a more striking variation of it. The demonstration shows how the film, pulling uniformly and normally on a loose string, transforms it into a circular arc under tension. The relationship between the surface tension and the string tension is analysed and presented in a useful graphical form. (letters and comments)

  19. Additively homomorphic encryption with a double decryption mechanism, revisited

    NARCIS (Netherlands)

    Peter, Andreas; Kronberg, M.; Trei, W.; Katzenbeisser, S.

    We revisit the notion of additively homomorphic encryption with a double decryption mechanism (DD-PKE), which allows for additions in the encrypted domain while having a master decryption procedure that can decrypt all properly formed ciphertexts by using a special master secret. This type of

  20. Revisiting Jack Goody to Rethink Determinisms in Literacy Studies

    Science.gov (United States)

    Collin, Ross

    2013-01-01

    This article revisits Goody's arguments about literacy's influence on social arrangements, culture, cognition, economics, and other domains of existence. Whereas some of his arguments tend toward technological determinism (i.e., literacy causes change in the world), other of his arguments construe literacy as a force that shapes and is shaped by…

  1. Surface tension in soap films: revisiting a classic demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Behroozi, F [Department of Physics, University of Northern Iowa, Cedar Falls, IA 50614 (United States)], E-mail: behroozi@uni.edu

    2010-01-15

    We revisit a classic demonstration for surface tension in soap films and introduce a more striking variation of it. The demonstration shows how the film, pulling uniformly and normally on a loose string, transforms it into a circular arc under tension. The relationship between the surface tension and the string tension is analysed and presented in a useful graphical form. (letters and comments)

  2. A control center design revisited: learning from users’ appropriation

    DEFF Research Database (Denmark)

    Souza da Conceição, Carolina; Cordeiro, Cláudia

    2014-01-01

    This paper aims to present the lessons learned during a control center design project by revisiting another control center from the same company designed two and a half years before by the same project team. In light of the experience with the first project and its analysis, the designers and res...

  3. A Feminist Revisit to the First-Year Curriculum.

    Science.gov (United States)

    Bernstein, Anita

    1996-01-01

    A seminar at Chicago-Kent College of Law (Illinois) that reviews six first-year law school courses by focusing on feminist issues in course content and structure is described. The seminar functions as both a review and a shift in perspective. Courses revisited include civil procedure, contracts, criminal law, justice and the legal system,…

  4. Revisiting deforestation in Africa (1990–2010): One more lost ...

    African Journals Online (AJOL)

    This spotlight revisits the dynamics and prognosis outlined in the late 1980's published in Déforestation en Afrique. This book on deforestation in Africa utilized available statistical data from the 1980's and was a pioneering self - styled attempt to provide a holistic viewpoint of the ongoing trends pertaining to deforestation in ...

  5. Moral Judgment Development across Cultures: Revisiting Kohlberg's Universality Claims

    Science.gov (United States)

    Gibbs, John C.; Basinger, Karen S.; Grime, Rebecca L.; Snarey, John R.

    2007-01-01

    This article revisits Kohlberg's cognitive developmental claims that stages of moral judgment, facilitative processes of social perspective-taking, and moral values are commonly identifiable across cultures. Snarey [Snarey, J. (1985). "The cross-cultural universality of social-moral development: A critical review of Kohlbergian research."…

  6. Revisiting the quantum harmonic oscillator via unilateral Fourier transforms

    International Nuclear Information System (INIS)

    Nogueira, Pedro H F; Castro, Antonio S de

    2016-01-01

    The literature on the exponential Fourier approach to the one-dimensional quantum harmonic oscillator problem is revised and criticized. It is shown that the solution of this problem has been built on faulty premises. The problem is revisited via the Fourier sine and cosine transform method and the stationary states are properly determined by requiring definite parity and square-integrable eigenfunctions. (paper)

  7. Transport benchmarks for one-dimensional binary Markovian mixtures revisited

    International Nuclear Information System (INIS)

    Malvagi, F.

    2013-01-01

    The classic benchmarks for transport through a binary Markovian mixture are revisited to look at the probability distribution function of the chosen 'results': reflection, transmission and scalar flux. We argue that the knowledge of the ensemble averaged results is not sufficient for reliable predictions: a measure of the dispersion must also be obtained. An algorithm to estimate this dispersion is tested. (author)

  8. Thorbecke Revisited : The Role of Doctrinaire Liberalism in Dutch Politics

    NARCIS (Netherlands)

    Drentje, Jan

    2011-01-01

    Thorbecke Revisited: The Role of Doctrinaire Liberalism in Dutch Politics In the political history of the nineteenth century Thorbecke played a crucial role. As the architect of the 1848 liberal constitutional reform he led three cabinets. In many ways he dominated the political discourse during the

  9. Faraday effect revisited: sum rules and convergence issues

    DEFF Research Database (Denmark)

    Cornean, Horia; Nenciu, Gheorghe

    2010-01-01

    This is the third paper of a series revisiting the Faraday effect. The question of the absolute convergence of the sums over the band indices entering the Verdet constant is considered. In general, sum rules and traces per unit volume play an important role in solid-state physics, and they give...

  10. A Multi-Level Model of Moral Functioning Revisited

    Science.gov (United States)

    Reed, Don Collins

    2009-01-01

    The model of moral functioning scaffolded in the 2008 "JME" Special Issue is here revisited in response to three papers criticising that volume. As guest editor of that Special Issue I have formulated the main body of this response, concerning the dynamic systems approach to moral development, the problem of moral relativism and the role of…

  11. Three Mile Island accident

    International Nuclear Information System (INIS)

    Barre, B.; Olivier, E.; Roux, J.P.; Pelle, P.

    2010-01-01

    Deluded by equivocal instrumentation signals, operators at TMI-2 (Three Mile Island - unit 2) misunderstood what was going on in the reactor and for 2 hours were taking inadequate decisions that turned a reactor incident into a major nuclear event that led to the melting of about one third of the core. The TMI accident had worldwide impacts in the domain of nuclear safety. The main consequences in France were: 1) the introduction of the major accident approach and the reinforcement of crisis management; 2) the improvement of the reactor design, particularly that of the pressurizer valves; 3) the implementation of safety probabilistic studies; 4) a better taking into account of the feedback experience in reactor operations; and 5) a better taking into account of the humane factor in reactor safety. (A.C.)

  12. Three Mile Island update

    International Nuclear Information System (INIS)

    Snyder, B.J.

    1984-01-01

    Almost six years after the accident at Three Mile Island-2, cleanup operations are proceeding and the financial condition of the owners has improved. The author reviews some of the cleanup activities and notes the milestones ahead before reaching the September, 1988 target date for completion. A decision to decommission or refurbish will follow the completion of fuel removal activities in 1987. The cleanup has produced considerable data and useful information. In particular, the experience of large-scale decontamination and radioactive waste processing, along with information on fission product transport, is relevant for maintenance and safe operation of other plants. Both macro- and microscopic examination of the core could help in developing safer reactors in the future. 3 figures, 1 table

  13. PWR: nuclear islands

    International Nuclear Information System (INIS)

    1989-01-01

    Framatome and its partners have produced this glossary of technical terms that can be used in writing English language documents relating to power plants (nuclear islands, individual components, nuclear services, etc.) with the hope of improving the quality of the documents intended for their clients, suppliers and partners and for others. This glossary will be particularly useful to the translators and authors of technical proposals, design documents, manufacturing documents, construction and operating documents concerning Pressurized Water Reactors written in English or French. It can also be useful as a reference document for students, researchers, journalists, etc., having to write on this subject. We would like to thank all those individuals working at the Ministere de la Recherche et de la Technologie, Electricite de France, Jeumont Schneider and Framatome who have contributed to this glossary. We would also appreciate any comments or sugestions intended to improve subsequent editions of this glossary [fr

  14. Mauritius - a Sustainable Island

    DEFF Research Database (Denmark)

    Larsen, Anders

    2010-01-01

    production is determined to be the way forward. A step in this direction is to devolve upon citizens the ability and motivation to produce electricity via small-scale distributed generation (SSDG), i.e. wind, photovoltaic and hydro installations below 50 kW. Given that SSDG is more expensive per installed......The Government of Mauritius has a long-term vision of transforming Mauritius into a sustainable Island. One important element towards the achievement of this vision is to increase the country's renewable energy usage and thereby reducing dependence on fossil fuels. Democratisation of energy...... capacity than the existing much larger power plants, subsidies are needed so as to provide incentives to small independent power producers (SIPP), households and firms to invest in SSDG.The paper presents the context, the theoretical considerations and the proposed incentive schemes to enable electricity...

  15. SRTM Anaglyph: Fiji Islands

    Science.gov (United States)

    2000-01-01

    The Sovereign Democratic Republic of the Fiji Islands, commonly known as Fiji, is an independent nation consisting of some 332 islands surrounding the Koro Sea in the South Pacific Ocean. This topographic image shows Viti Levu, the largest island in the group. With an area of 10,429 square kilometers (about 4000 square miles), it comprises more than half the area of the Fiji Islands. Suva, the capital city, lies on the southeast shore. The Nakauvadra, the rugged mountain range running from north to south, has several peaks rising above 900 meters (about 3000 feet). Mount Tomanivi, in the upper center, is the highest peak at 1324 meters (4341 feet). The distinct circular feature on the north shore is the Tavua Caldera, the remnant of a large shield volcano that was active about 4 million years ago. Gold has been mined on the margin of the caldera since the 1930s. The Nadrau plateau is the low relief highland in the center of the mountain range. The coastal plains in the west, northwest and southeast account for only 15 percent of Viti Levu's area but are the main centers of agriculture and settlement.This shaded relief anaglyph image was generated using preliminary topographic data from the Shuttle Radar Topography Mission. A computer-generated artificial light source illuminates the elevation data from the top (north) to produce a pattern of light and shadows. Slopes facing the light appear bright, while those facing away are shaded. The stereoscopic effect was created by first draping the shaded relief image back over the topographic data and then generating two differing perspectives, one for each eye. When viewed through special glasses, the result is a vertically exaggerated view of the Earth's surface in its full three dimensions. Anaglyph glasses cover the left eye with a red filter and cover the right eye with a blue filter.This image was acquired by SRTM aboard the Space Shuttle Endeavour, launched on February 11, 2000. SRTM used the same radar instrument

  16. Who should do the dishes now? Revisiting gender and housework in contemporary urban South Wales

    OpenAIRE

    Mannay, Dawn

    2016-01-01

    This chapter revisits Jane Pilcher’s (1994) seminal work ‘Who should do the dishes? Three generations of Welsh women talking about men and housework’, which was originally published in Our Sister’s Land: the changing identities of women in Wales. As discussed in the introductory chapter, I began revisiting classic Welsh studies as part of my doctoral study Mothers and daughters on the margins: gender, generation and education (Mannay, 2012); this lead to the later publication of a revisiting ...

  17. A Structural Equation Model of Risk Perception of Rockfall for Revisit Intention

    OpenAIRE

    Ya-Fen Lee; Yun-Yao Chi

    2014-01-01

    The study aims to explore the relationship between risk perception of rockfall and revisit intention using a Structural Equation Modeling (SEM) analysis. A total of 573 valid questionnaires are collected from travelers to Taroko National Park, Taiwan. The findings show the majority of travelers have the medium perception of rockfall risk, and are willing to revisit the Taroko National Park. The revisit intention to Taroko National Park is influenced by hazardous preferences, willingness-to-pa...

  18. Potential Demand of Relatively New and Emerging Marine Ecotourism in Kei Islands

    Science.gov (United States)

    Dewa Ayu Raka Susanti, Ida I.; Teniwut, Wellem A.; Kahfi, Syahibul; M. K Teniwut, Roberto; Picaulima, Simon; Hungan, Marselus; Rahantoknam, Meyske; Hasyim, Cawalinya; Rahakbauw, Siska D.; Renjaan, M. R.; Ngabalin, Anna M.; Ngangun, Tati A.; Pentury, Frischila; Betaubun, Kamilius D.; Ngamel, A. K.; Ohoiwutun, Elisabeth C.

    2017-10-01

    One of the main resources for the economic development of coastal are marine ecotourism. Although for developing country such as Indonesia and especially for an area that located far from a big city like Kei Islands in Maluku, development of marine ecotourism might face a greater challenge than any other places. Considering the potential for multiplier effect on economic of a coastal community, the purpose of this research was to analyze and measure the economic value of new, raw and emerging marine ecotourism spot and determine the demand based on domestic tourist perspective. We pick five new and emerging marine ecotourism spots in this area as case study and used purposive sampling technique to target potential domestic tourist who have visited those five marine ecotourism spots and measure their preference and measure their demand potential by used willingness to revisit (WTR) and logistic regression for analyze the data, this research conducted in Kei Islands, Indonesia. This result can provide broad and comprehensive perspective on developing marine ecotourism in a mildly isolated coastal area like Kei Islands and place similar.

  19. Influence of microenvironment pH, humidity, and temperature on the stability of polymorphic and amorphous forms of clopidogrel bisulfate

    DEFF Research Database (Denmark)

    Raijada, Dhara K; Singh, Saranjit; Bansal, Arvind K

    2010-01-01

    The effect of microenvironment pH, humidity, and temperature was evaluated on the stability of polymorphic and amorphous forms of clopidogrel bisulfate, when present alone or in combinations. Oxalic acid and sodium carbonate were used as solid stressors to create acidic and alkaline p...... more degradation than the individual forms above critical relative humidity (85% RH). Similar higher degradation was observed between 75% RH and 85% RH in case of acid-stressed samples. In alkaline microenvironment, all the samples showed identical decomposition attributed to conversion of bisulfate...

  20. Island biogeography of marine organisms

    Science.gov (United States)

    Pinheiro, Hudson T.; Bernardi, Giacomo; Simon, Thiony; Joyeux, Jean-Christophe; Macieira, Raphael M.; Gasparini, João Luiz; Rocha, Claudia; Rocha, Luiz A.

    2017-09-01

    Studies on the distribution and evolution of organisms on oceanic islands have advanced towards a dynamic perspective, where terrestrial endemicity results from island geographical aspects and geological history intertwined with sea-level fluctuations. Diversification on these islands may follow neutral models, decreasing over time as niches are filled, or disequilibrium states and progression rules, where richness and endemism rise with the age of the archipelago owing to the splitting of ancestral lineages (cladogenesis). However, marine organisms have received comparatively little scientific attention. Therefore, island and seamount evolutionary processes in the aquatic environment remain unclear. Here we analyse the evolutionary history of reef fishes that are endemic to a volcanic ridge of seamounts and islands to understand their relations to island evolution and sea-level fluctuations. We also test how this evolutionary history fits island biogeography theory. We found that most endemic species have evolved recently (Pleistocene epoch), during a period of recurrent sea-level changes and intermittent connectivity caused by repeated aerial exposure of seamounts, a finding that is consistent with an ephemeral ecological speciation process. Similar to findings for terrestrial biodiversity, our data suggest that the marine speciation rate on islands is negatively correlated with immigration rate. However, because marine species disperse better than terrestrial species, most niches are filled by immigration: speciation increases with the random accumulation of species with low dispersal ability, with few opportunities for in situ cladogenesis and adaptive radiation. Moreover, we confirm that sea-level fluctuations and seamount location play a critical role in marine evolution, mainly by intermittently providing stepping stones for island colonization.

  1. Bamboo Diversity in Sumba Island

    Directory of Open Access Journals (Sweden)

    KARSONO

    2005-04-01

    Full Text Available Bamboo is one of the economic plant which grow widely in the villages and have been used by the local people in the villages. Indonesia has about 10% of the world bamboo, 50% among them was endemic to Indonesia. According Widjaja (2001 Lesser Sunda Island which consists of Lombok, Sumbawa, Flores, Timor, Sumba and other small island eastern of Flores has 14 bamboo species, however, the information from the Sumba Island was lacking because of lacking data from this area except one species which was proposed by S. Soenarko in 1977 where the type specimens was collected by Iboet 443 in 1925. To fullfill data from the Sumba Island, an exploration to this area has been conducted on July 2003. The observation was done in West Sumba and East Sumba District, especially in two natioal parks at both districts. According to this inventory study in the Sumba Island, there were 10 bamboo species in Sumba Island, 1 species among them (Dinochloa sp. was a new species which has not been collected before, whereas the other species (Dinochloa kostermansiana has a new addition record from this area. The bamboo species in Sumba Island were Bambusa blumeana, Bambusa vulgaris, Dendocalamus asper, Dinochloa kostermansiana, Dinochloa sp., Gigantochloa atter, Nastus reholtumianus, Phyllostachys aurea, Schisotachyum brachycladum and Schizostachyum lima. From 10 recorded species, the genera Dinochloa and Nastus grow wild in the forest, whereas another species grow widly or cultivated in the garden. Furthermore, the genus Dinochloa was the only genus grow climbing. The endemic species found in Sumba Island was Nastus reholttumianus, whereas Dinochloa kostermansiana was also found in Flores Island.

  2. Highway 61 Revisited: Bob Dilan i francuski poststrukturalizam / Highway 61 Revisited: Bob Dilan and French Poststructuralism

    Directory of Open Access Journals (Sweden)

    Nikola Dedić

    2013-06-01

    Full Text Available The main aim of this text is to show parallels between rock music and poststructuralist philosophy. As a case study one of the most celebrated rock albums of all times – Bob Dylan’s Highway 61 Revisited from 1965 is taken. It is one of the crucial albums in the history of popular culture which influenced further development of rock music within American counter culture of the 60s. Dylan’s turn from the politics of American New Left and folk movement, his relation towards the notions of the author and intertextuality, and his connection with experimental usage of language in the manner of avant-garde and neoavant-garde poetry, are juxtaposed with the main philosophical standpoints of Jean-François Lyotard, Jean Baudrillard, Roland Barthes and Julia Kristeva which historically and chronologically coincide with the appearance of Dylan’s album.

  3. Reliving Island Life: Staging Stories of the Blasket Islands

    Directory of Open Access Journals (Sweden)

    Daithí Kearney

    2017-10-01

    Full Text Available The Blasket Islands are located off the south-west coast of Ireland. No longer inhabited, the Great Blasket Island and its distinctive culture have been documented by a variety of writers and are celebrated today in an interpretative centre on the mainland and in performances by Siamsa Tíre, The National Folk Theatre of Ireland. “Siamsa” developed from local initiatives in North Kerry during the early 1960s and is located today in Tralee, Co. Kerry. It aims to present Irish folklore and folk culture through the medium of theatre involving music, song, dance and mime but invariably no dialogue. In this paper, I focus on the production Oiléan, based loosely on the stories of the Blasket Islanders, which was initially devised as part of the fiftieth anniversary commemoration of the departure of the last inhabitants of the islands in 2003.

  4. The coordinate coherent states approach revisited

    International Nuclear Information System (INIS)

    Miao, Yan-Gang; Zhang, Shao-Jun

    2013-01-01

    We revisit the coordinate coherent states approach through two different quantization procedures in the quantum field theory on the noncommutative Minkowski plane. The first procedure, which is based on the normal commutation relation between an annihilation and creation operators, deduces that a point mass can be described by a Gaussian function instead of the usual Dirac delta function. However, we argue this specific quantization by adopting the canonical one (based on the canonical commutation relation between a field and its conjugate momentum) and show that a point mass should still be described by the Dirac delta function, which implies that the concept of point particles is still valid when we deal with the noncommutativity by following the coordinate coherent states approach. In order to investigate the dependence on quantization procedures, we apply the two quantization procedures to the Unruh effect and Hawking radiation and find that they give rise to significantly different results. Under the first quantization procedure, the Unruh temperature and Unruh spectrum are not deformed by noncommutativity, but the Hawking temperature is deformed by noncommutativity while the radiation specturm is untack. However, under the second quantization procedure, the Unruh temperature and Hawking temperature are untack but the both spectra are modified by an effective greybody (deformed) factor. - Highlights: ► Suggest a canonical quantization in the coordinate coherent states approach. ► Prove the validity of the concept of point particles. ► Apply the canonical quantization to the Unruh effect and Hawking radiation. ► Find no deformations in the Unruh temperature and Hawking temperature. ► Provide the modified spectra of the Unruh effect and Hawking radiation.

  5. Backwardation in energy futures markets: Metalgesellschaft revisited

    International Nuclear Information System (INIS)

    Charupat, N.; Deaves, R.

    2003-01-01

    Energy supply contracts negotiated by the US Subsidiary of Metalgesellschaft Refining and Marketing (MGRM), which were the subject of much subsequent debate, are re-examined. The contracts were hedged by the US Subsidiary barrel-for-barrel using short-dated energy derivatives. When the hedge program experienced difficulties, the derivatives positions were promptly liquidated by the parent company. Revisiting the MGRM contracts also provides the opportunity to explore the latest evidence on backwardation in energy markets. Accordingly, the paper discusses first the theoretical reasons for backwardation, followed by an empirical examination using the MGRM data available at the time of the hedge program in 1992 and a second set of data that became available in 2000. By using a more up-to-date data set covering a longer time period and by controlling the time series properties of the data, the authors expect to provide more reliable empirical evidence on the behaviour of energy futures prices. Results based on the 1992 data suggest that the strategy employed by MGRM could be expected to be profitable while the risks are relatively low. However, analysis based on the 2000 data shows lower, although still significant profits, but higher risks. The final conclusion was that the likelihood of problems similar to those faced by MGRM in 1992 are twice as high with the updated 2000 data, suggesting that the risk-return pattern of the stack-and-roll hedging strategy using short-dated energy future contracts to hedge long-tem contracts is less appealing now than when MGRM implemented its hedging program in 1992. 24 refs., 3 tabs., 6 figs

  6. Clifford Algebra Implying Three Fermion Generations Revisited

    International Nuclear Information System (INIS)

    Krolikowski, W.

    2002-01-01

    The author's idea of algebraic compositeness of fundamental particles, allowing to understand the existence in Nature of three fermion generations, is revisited. It is based on two postulates. Primo, for all fundamental particles of matter the Dirac square-root procedure √p 2 → Γ (N) ·p works, leading to a sequence N=1, 2, 3, ... of Dirac-type equations, where four Dirac-type matrices Γ (N) μ are embedded into a Clifford algebra via a Jacobi definition introducing four ''centre-of-mass'' and (N - 1) x four ''relative'' Dirac-type matrices. These define one ''centre-of-mass'' and N - 1 ''relative'' Dirac bispinor indices. Secundo, the ''centre-of-mass'' Dirac bispinor index is coupled to the Standard Model gauge fields, while N - 1 ''relative'' Dirac bispinor indices are all free indistinguishable physical objects obeying Fermi statistics along with the Pauli principle which requires the full antisymmetry with respect to ''relative'' Dirac indices. This allows only for three Dirac-type equations with N = 1, 3, 5 in the case of N odd, and two with N = 2, 4 in the case of N even. The first of these results implies unavoidably the existence of three and only three generations of fundamental fermions, namely leptons and quarks, as labelled by the Standard Model signature. At the end, a comment is added on the possible shape of Dirac 3 x 3 mass matrices for four sorts of spin-1/2 fundamental fermions appearing in three generations. For charged leptons a prediction is m τ = 1776.80 MeV, when the input of experimental m e and m μ is used. (author)

  7. Solar system anomalies: Revisiting Hubble's law

    Science.gov (United States)

    Plamondon, R.

    2017-12-01

    This paper investigates the impact of a new metric recently published [R. Plamondon and C. Ouellet-Plamondon, in On Recent Developments in Theoretical and Experimental General Relativity, Astrophysics, and Relativistic Field Theories, edited by K. Rosquist, R. T. Jantzen, and R. Ruffini (World Scientific, Singapore, 2015), p. 1301] for studying the space-time geometry of a static symmetric massive object. This metric depends on a complementary error function (erfc) potential that characterizes the emergent gravitation field predicted by the model. This results in two types of deviations as compared to computations made on the basis of a Newtonian potential: a constant and a radial outcome. One key feature of the metric is that it postulates the existence of an intrinsic physical constant σ , the massive object-specific proper length that scales measurements in its surroundings. Although σ must be evaluated experimentally, we use a heuristic to estimate its value and point out some latent relationships between the Hubble constant, the secular increase in the astronomical unit, and the Pioneers delay. Indeed, highlighting the systematic errors that emerge when the effect of σ is neglected, one can link the Hubble constant H 0 to σ Sun and the secular increase V AU to σ Earth . The accuracy of the resulting numerical predictions, H 0 = 74 . 42 ( 0 . 02 ) ( km / s ) / Mpc and V AU ≅ 7.8 cm yr-1 , calls for more investigations of this new metric by specific experts. Moreover, we investigate the expected impacts of the new metric on the flyby anomalies, and we revisit the Pioneers delay. It is shown that both phenomena could be partly taken into account within the context of this unifying paradigm, with quite accurate numerical predictions. A correction for the osculating asymptotic velocity at the perigee of the order of 10 mm/s and an inward radial acceleration of 8 . 34 × 10 - 10 m / s 2 affecting the Pioneer ! space crafts could be explained by this new model.

  8. Double neutron stars: merger rates revisited

    Science.gov (United States)

    Chruslinska, Martyna; Belczynski, Krzysztof; Klencki, Jakub; Benacquista, Matthew

    2018-03-01

    We revisit double neutron star (DNS) formation in the classical binary evolution scenario in light of the recent Laser Interferometer Gravitational-wave Observatory (LIGO)/Virgo DNS detection (GW170817). The observationally estimated Galactic DNS merger rate of R_MW = 21^{+28}_{-14} Myr-1, based on three Galactic DNS systems, fully supports our standard input physics model with RMW = 24 Myr-1. This estimate for the Galaxy translates in a non-trivial way (due to cosmological evolution of progenitor stars in chemically evolving Universe) into a local (z ≈ 0) DNS merger rate density of Rlocal = 48 Gpc-3 yr-1, which is not consistent with the current LIGO/Virgo DNS merger rate estimate (1540^{+3200}_{-1220} Gpc-3 yr-1). Within our study of the parameter space, we find solutions that allow for DNS merger rates as high as R_local ≈ 600^{+600}_{-300} Gpc-3 yr-1 which are thus consistent with the LIGO/Virgo estimate. However, our corresponding BH-BH merger rates for the models with high DNS merger rates exceed the current LIGO/Virgo estimate of local BH-BH merger rate (12-213 Gpc-3 yr-1). Apart from being particularly sensitive to the common envelope treatment, DNS merger rates are rather robust against variations of several of the key factors probed in our study (e.g. mass transfer, angular momentum loss, and natal kicks). This might suggest that either common envelope development/survival works differently for DNS (˜10-20 M⊙ stars) than for BH-BH (˜40-100 M⊙ stars) progenitors, or high black hole (BH) natal kicks are needed to meet observational constraints for both types of binaries. Our conclusion is based on a limited number of (21) evolutionary models and is valid within this particular DNS and BH-BH isolated binary formation scenario.

  9. Clifford Algebra Implying Three Fermion Generations Revisited

    Science.gov (United States)

    Krolikowski, Wojciech

    2002-09-01

    The author's idea of algebraic compositeness of fundamental particles, allowing to understand the existence in Nature of three fermion generations, is revisited. It is based on two postulates. Primo, for all fundamental particles of matter the Dirac square-root procedure √ {p2} → {Γ }(N)p works, leading to a sequence N = 1,2,3, ... of Dirac-type equations, where four Dirac-type matrices {Γ }(N)μ are embedded into a Clifford algebra via a Jacobi definition introducing four ``centre-of-mass'' and (N-1)× four ``relative'' Dirac-type matrices. These define one ``centre-of-mass'' and (N-1) ``relative'' Dirac bispinor indices. Secundo, the ``centre-of-mass'' Dirac bispinor index is coupled to the Standard Model gauge fields, while (N-1) ``relative'' Dirac bispinor indices are all free indistinguishable physical objects obeying Fermi statistics along with the Pauli principle which requires the full antisymmetry with respect to ``relative'' Dirac indices. This allows only for three Dirac-type equations with N = 1,3,5 in the case of N odd, and two with N = 2,4 in the case of N even. The first of these results implies unavoidably the existence of three and only three generations of fundamental fermions, namely leptons and quarks, as labelled by the Standard Model signature. At the end, a comment is added on the possible shape of Dirac 3x3 mass matrices for four sorts of spin-1/2 fundamental fermions appearing in three generations. For charged leptons a prediction is mτ = 1776.80 MeV, when the input of experimental me and mμ is used.

  10. Tetronic Star Block Copolymer Micelles: Photophysical Characterisation of Microenvironments and Applicability for Tuning Electron Transfer Reactions.

    Science.gov (United States)

    Samanta, Papu; Rane, Sonal; Bahadur, Pratap; Dutta Choudhury, Sharmistha; Pal, Haridas

    2018-05-10

    Detailed photophysical investigations have been carried out using a probe dye, Coumarin-153 (C153), to understand the microenvironments of micelles formed by the newly introduced Tetronic star block copolymers, T1304 and T1307, having the same polypropylene oxide (PPO) block size but different polyethylene oxide (PEO) block sizes. Ground state absorption, steady-state fluorescence and time-resolved fluorescence measurements have been used to estimate the micropolarity, microviscosity and solvation dynamics within the two micelles. To the best of our knowledge this is the first report on these important physicochemical parameters for this new class of the star block copolymer micelles. Our results indicate that T1307 micelle offers a relatively more polar and less viscous microenvironment in the corona region, compared to T1304. The effect of the two micellar systems has subsequently been investigated on the bimolecular photoinduced electron transfer (ET) reactions between coumarin dyes (electron acceptors) and aromatic amines (electron donors). On correlating the energetics and kinetics of the ET reactions, clear Marcus Inversion (MI) behavior is observed in both the micellar media. Interestingly, the ET rates for all the donor-acceptor pairs are much higher in T1307 than in T1304, and the onset of MI also appears at a relatively higher exergenocity (-Δ G 0 ) in the former micelle (~0.45 eV for T1307) than the latter (~0.37 eV for T1304). Effect of added NaCl salt studied selectively in T1307 micelle, shows that the ET rate decreases significantly along with a shift in the onset of MI toward lower exergenocity region, so that in the presence of 2 M NaCl the system becomes quite comparable to T1304. Based on the observed results, it is realized that the micropolarity and hence the dynamics of ET process can be tuned very effectively either by changing the constitution of the star block copolymer or by using a suitable additive as a modifier of the micellar

  11. Effect of Irradiation on Tumor Microenvironment and Bone Marrow Cell Migration in a Preclinical Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Kane, Jonathan L. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Krueger, Sarah A.; Hanna, Alaa [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Raffel, Thomas R. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Wilson, George D. [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Madlambayan, Gerard J. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Marples, Brian, E-mail: Brian.Marples@beaumont.edu [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States)

    2016-09-01

    Purpose: To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts. Methods and Materials: Subcutaneous LLC tumors were established in C57BL/6 mice. Standard RT or PRT was given at 2 Gy/d for a total dose of 20 Gy using a 5 days on, 2 days off schedule to mimic clinical delivery. Radiation-induced tumor microenvironment changes were examined after treatment using flow cytometry and antibody-specific histopathology. Normal tissue effects were measured using noninvasive {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography after naïve animals were given whole-lung irradiation to 40 Gy in 4 weeks using the same 2-Gy/d regimens. Results: Over the 2 weeks of therapy, PRT was more effective than SRT at reducing tumor growth rate (0.31 ± 0.02 mm{sup 3}/d and 0.55 ± 0.04 mm{sup 3}/d, respectively; P<.007). Histopathology showed a significant comparative reduction in the levels of Ki-67 (14.5% ± 3%), hypoxia (10% ± 3.5%), vascular endothelial growth factor (2.3% ± 1%), and stromal-derived factor-1α (2.5% ± 1.4%), as well as a concomitant decrease in CD45{sup +} bone marrow–derived cell (BMDC) migration (7.8% ± 2.2%) after PRT. The addition of AMD3100 also decreased CD45{sup +} BMDC migration in treated tumors (0.6% ± 0.1%). Higher vessel density was observed in treated tumors. No differences were observed in normal lung tissue after PRT or SRT. Conclusions: Pulsed RT–treated tumors exhibited slower growth and reduced hypoxia. Pulsed RT eliminated initiation of supportive mechanisms utilized by tumors in low oxygen microenvironments, including angiogenesis and recruitment of BMDCs.

  12. Heterogeneity of passenger exposure to air pollutants in public transport microenvironments

    Science.gov (United States)

    Yang, Fenhuan; Kaul, Daya; Wong, Ka Chun; Westerdahl, Dane; Sun, Li; Ho, Kin-fai; Tian, Linwei; Brimblecombe, Peter; Ning, Zhi

    2015-05-01

    Epidemiologic studies have linked human exposure to pollutants with adverse health effects. Passenger exposure in public transport systems contributes an important fraction of daily burden of air pollutants. While there is extensive literature reporting the concentrations of pollutants in public transport systems in different cities, there are few studies systematically addressing the heterogeneity of passenger exposure in different transit microenvironments, in cabins of different transit vehicles and in areas with different characteristics. The present study investigated PM2.5 (particulate matter with aerodynamic diameters smaller than 2.5 μm), black carbon (BC), ultrafine particles (UFP) and carbon monoxide (CO) pollutant concentrations in various public road transport systems in highly urbanized city of Hong Kong. Using a trolley case housing numerous portable air monitors, we conducted a total of 119 trips during the campaign. Transit microenvironments, classified as 1). busy and secondary roadside bus stops; 2). open and enclosed termini; 3). above- and under-ground Motor Rail Transport (MTR) platforms, were investigated and compared to identify the factors that may affect passenger exposures. The pollutants inside bus and MTR cabins were also investigated together with a comparison of time integrated exposure between the transit modes. Busy roadside and enclosed termini demonstrated the highest average particle concentrations while the lowest was found on the MTR platforms. Traffic-related pollutants BC, UFP and CO showed larger variations than PM2.5 across different microenvironments and areas confirming their heterogeneity in urban environments. In-cabin pollutant concentrations showed distinct patterns with BC and UFP high in diesel bus cabins and CO high in LPG bus cabins, suggesting possible self-pollution issues and/or penetration of on-road pollutants inside cabins during bus transit. The total passenger exposure along selected routes, showed bus

  13. Equilibrium theory of island biogeography: A review

    Science.gov (United States)

    Angela D. Yu; Simon A. Lei

    2001-01-01

    The topography, climatic pattern, location, and origin of islands generate unique patterns of species distribution. The equilibrium theory of island biogeography creates a general framework in which the study of taxon distribution and broad island trends may be conducted. Critical components of the equilibrium theory include the species-area relationship, island-...

  14. Oak restoration trials: Santa Catalina Island

    Science.gov (United States)

    Lisa Stratton

    2002-01-01

    Two restoration trials involving four oak species have been implemented as part of a larger restoration program for Catalina Island. In 1997 the Catalina Island Conservancy began an active program of restoration after 50 years of ranching and farming activities on the island. The restoration program includes removing feral goats and pigs island-wide and converting 80...

  15. Pathways and Distribution of Marine Debris Around a Remote Caribbean Island, Little Cayman

    Science.gov (United States)

    Camp, L.; Marsh, L.; O'Keefe, A.; Duran, J.; Wilcox, S. M.; James, R.; Cowan, E.

    2011-12-01

    Marine Debris is a major environmental concern that affects all levels of marine life. On remote beaches in the Caribbean, where human populations are minimal, marine debris is largely deposited by ocean currents. The ocean is estimated to be littered with over 6 million metric tons of trash per year with 90% coming from land sources, but little is known about the exact sources and pathways for the debris. In 2006, on Little Cayman Island, coastal debris was collected at two coastal areas where removal of debris had not occurred in at least 9 years and along 2000 meters squared. One site was located on the north side, while the other site was located on the south side of the island. Both sites were located in reef-protected coastal zones. These two sites were revisited in 2007, 2010, and 2011 to determine the volume, weight, and type of debris arriving annually and to assess the importance of different coastal processes in deposition. In 2011, eight turtle nesting beaches were added to the study and a total of 11,186 liters of debris was collected from 1600 meters of coastline. The island lies in a northeast southwest orientation. The south-side of the island is influenced largely by prevailing trade winds, currents and tropical storms, traveling across the Caribbean from the east. Currents, eddies, and Norwesters would presumably deposit debris on the north side of the island. Approximately five times the amount of debris is deposited on the south side of the island than on the north side of the island. From the total debris collected, 72.45% was plastic, 8.23% shoes, 6.37% ropes & nets , 5.13% glass, 4.37% styrofoam, and 3.44% contained other debris. The marine debris originated in 8 different countries, and it is estimated that there is collectively 223,721 liters (11,635 kg) covering the shores of the entire island. Remarkably, debris found on Little Cayman in 2011 was traced to the 2010 Haitian earthquake relief effort.

  16. THE INFLUENCE OF DESTINATION IMAGE AND TOURIST SATISFACTION TOWARD REVISIT INTENTION OF SETU BABAKAN BETAWI CULTURAL VILLAGE

    OpenAIRE

    Wibowo, Setyo Ferry; Sazali, Adnan; Kresnamurti R. P., Agung

    2016-01-01

    The purpose of this research are: 1) To find out the description of destination image, tourist satisfaction, and revisit intention of Betawi cultural village Setu Babakan, 2) test empirically the influence of destination image toward revisit intention of Betawi cultural village Setu Babakan, 3) test empirically the influence of tourist satisfaction toward revisit intention of Betawi cultural village Setu Babakan, 4) test empirically the influence of destination image toward revisit intention ...

  17. ASTER Images the Island of Hawaii

    Science.gov (United States)

    2000-01-01

    These images of the Island of Hawaii were acquired on March 19, 2000 by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER will image Earth for the next 6 years to map and monitor the changing surface of our planet. Data are shown from the short wavelength and thermal infrared spectral regions, illustrating how different and complementary information is contained in different parts of the spectrum.Left image: This false-color image covers an area 60 kilometers (37 miles) wide and 120 kilometers (75 miles) long in three bands of the short wavelength infrared region. While, much of the island was covered in clouds, the dominant central Mauna Loa volcano, rising to an altitude of 4115 meters (13,500 feet), is cloud-free. Lava flows can be seen radiating from the central crater in green and black tones. As they reach lower elevations, the flows become covered with vegetation, and their image color changes to yellow and orange. Mauna Kea volcano to the north of Mauna Loa has a thin cloud-cover, producing a bluish tone on the image. The ocean in the lower right appears brown due to the color processing.Right image: This image is a false-color composite of three thermal infrared bands. The brightness of the colors is proportional to the temperature, and the hues display differences in rock composition. Clouds are black, because they are the coldest objects in the scene. The ocean and thick vegetation appear dark green because they are colder than bare rock surfaces, and have no thermal spectral features. Lava flows are shades of magenta, green, pink and yellow, reflecting chemical changes due to weathering and relative age differences.Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) is one of five Earth-observing instruments launched

  18. Sensor Access to the Cellular Microenvironment Using the Sensing Cell Culture Flask.

    Science.gov (United States)

    Kieninger, Jochen; Tamari, Yaara; Enderle, Barbara; Jobst, Gerhard; Sandvik, Joe A; Pettersen, Erik O; Urban, Gerald A

    2018-04-26

    The Sensing Cell Culture Flask (SCCF) is a cell culture monitoring system accessing the cellular microenvironment in 2D cell culture using electrochemical microsensors. The system is based on microfabricated sensor chips embedded in standard cell culture flasks. Ideally, the sensor chips could be equipped with any electrochemical sensor. Its transparency allows optical inspection of the cells during measurement. The surface of the sensor chip is in-plane with the flask surface allowing undisturbed cell growth on the sensor chip. A custom developed rack system allows easy usage of multiple flasks in parallel within an incubator. The presented data demonstrates the application of the SCCF with brain tumor (T98G) and breast cancer (T-47D) cells. Amperometric oxygen sensors were used to monitor cellular respiration with different incubation conditions. Cellular acidification was accessed with potentiometric pH sensors using electrodeposited iridium oxide films. The system itself provides the foundation for electrochemical monitoring systems in 3D cell culture.

  19. Macromolecularly crowded in vitro microenvironments accelerate the production of extracellular matrix-rich supramolecular assemblies.

    Science.gov (United States)

    Kumar, Pramod; Satyam, Abhigyan; Fan, Xingliang; Collin, Estelle; Rochev, Yury; Rodriguez, Brian J; Gorelov, Alexander; Dillon, Simon; Joshi, Lokesh; Raghunath, Michael; Pandit, Abhay; Zeugolis, Dimitrios I

    2015-03-04

    Therapeutic strategies based on the principles of tissue engineering by self-assembly put forward the notion that functional regeneration can be achieved by utilising the inherent capacity of cells to create highly sophisticated supramolecular assemblies. However, in dilute ex vivo microenvironments, prolonged culture time is required to develop an extracellular matrix-rich implantable device. Herein, we assessed the influence of macromolecular crowding, a biophysical phenomenon that regulates intra- and extra-cellular activities in multicellular organisms, in human corneal fibroblast culture. In the presence of macromolecules, abundant extracellular matrix deposition was evidenced as fast as 48 h in culture, even at low serum concentration. Temperature responsive copolymers allowed the detachment of dense and cohesive supramolecularly assembled living substitutes within 6 days in culture. Morphological, histological, gene and protein analysis assays demonstrated maintenance of tissue-specific function. Macromolecular crowding opens new avenues for a more rational design in engineering of clinically relevant tissue modules in vitro.

  20. Proteomic analysis of Taenia hydatigena cyst fluid reveals unique internal microenvironment.

    Science.gov (United States)

    Zheng, Yadong

    2017-12-01

    Taenia hydatigena is a parasitic flatworm that is widely distributed around the world. Using MS/MS, the proteome of T. hydatigena cyst fluid (CF) was profiled and a total of 520 proteins were identified, 430 of which were of sheep origin. T. hydatigena shared 37 parasite-origin and 109 host-origin CF proteins with Echinococcus granulosus. Compared with E. granulosus, T. hydatigena had much more CF proteins associated with amino acid synthesis and complement cascades. In addition, glutamate metabolism and anti-oxidative reactions were identified as relatively more important events. These results suggest that T. hydatigena metacestodes have internal microenvironment with special immune and oxidative conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Oncogenic driver genes and the inflammatory microenvironment dictate liver tumor phenotype

    DEFF Research Database (Denmark)

    Matter, Matthias S; Marquardt, Jens U; Andersen, Jesper B

    2016-01-01

    The majority of hepatocellular carcinoma (HCC) develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or non-alcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated...... with transcriptome profiles from human HCCs further demonstrated that AKT-CAT tumors generated in the context of chronic liver inflammation showed enrichment of poor prognosis gene sets or decrease of good prognosis gene sets. In contrast, DDC had a more subtle effect on AKT-NRAS(G12V) tumors and primarily enhanced...... by distinct oncogenes is largely unresolved. To address this issue, we generated murine liver tumors by constitutively active AKT-1 (AKT) and β-catenin (CAT) followed by induction of chronic liver inflammation by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride (CCl4 ). Also...

  2. Expression of osteoblast and osteoclast regulatory genes in the bone marrow microenvironment in multiple myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida B; Christensen, Jacob Haaber; Lyng, Maria Bibi

    2014-01-01

    Multiple myeloma (MM) lytic bone disease (LBD) is caused by osteoclast activation and osteoblast inhibition. RANK/RANKL/OPG play central roles in osteoclast activation and Wnt inhibitor DKK1 in osteoblast inhibition. The role of other Wnt inhibitors is less clear. We evaluated gene expression...... of osteoclast regulators (RANK, RANKL, OPG, TRAIL, MIP1A), Wnt inhibitors (DKK1, SFRP2, SFRP3, sclerostin, WIF1) and osteoblast transcription factors (RUNX2, osterix) by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in the bone marrow (BM) microenvironment using snap-frozen BM biopsies...... radiographs and the bone resorption marker CTX-1. Protein levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Among Wnt inhibitors, only SFRP3 and DKK1 were significantly overexpressed in advanced LBD, correlating with protein levels. SFRP3 correlated with CTX-1. Our...

  3. Long noncoding RNA lnc-sox5 modulates CRC tumorigenesis by unbalancing tumor microenvironment.

    Science.gov (United States)

    Wu, Kaiming; Zhao, Zhenxian; Liu, Kuanzhi; Zhang, Jian; Li, Guanghua; Wang, Liang

    2017-07-03

    Long non-coding RNAs (LncRNAs) have been recently regarded as systemic regulators in multiple biologic processes including tumorigenesis. In this study, we observed the expression of lncRNA lnc-sox5 was significantly increased in colorectal cancer (CRC). Despite the CRC cell growth, cell cycle and cell apoptosis was not affected by lnc-sox5 knock-down, lnc-sox5 knock-down suppressed CRC cell migration and invasion. In addition, xenograft animal model suggested that lnc-sox5 knock-down significantly suppressed the CRC tumorigenesis. Our results also showed that the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was significantly reduced by lnc-sox5 knock-down and therefore modulated the infiltration and cytotoxicity of CD3 + CD8 + T cells. Taken together, these results suggested that lnc-sox5 unbalances tumor microenvironment to regulate colorectal cancer progression.

  4. Complement components of nerve regeneration conditioned fluid influence the microenvironment of nerve regeneration

    Directory of Open Access Journals (Sweden)

    Guang-shuai Li

    2016-01-01

    Full Text Available Nerve regeneration conditioned fluid is secreted by nerve stumps inside a nerve regeneration chamber. A better understanding of the proteinogram of nerve regeneration conditioned fluid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration. In this study, we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve. Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis confirmed that there were more than 10 complement components (complement factor I, C1q-A, C1q-B, C2, C3, C4, C5, C7, C8ß and complement factor D in the nerve regeneration conditioned fluid and each varied at different time points. These findings suggest that all these complement components have a functional role in nerve regeneration.

  5. Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment

    DEFF Research Database (Denmark)

    Celis, Julio E; Gromov, Pavel; Cabezón, Teresa

    2004-01-01

    of biomarkers, the tumor interstitial fluid (TIF) that perfuses the breast tumor microenvironment. We collected TIFs from small pieces of freshly dissected invasive breast carcinomas and analyzed them by two-dimensional polyacrylamide gel electrophoresis in combination with matrix-assisted laser desorption....../ionization time-of-flight mass spectrometry, Western immunoblotting, as well as by cytokine-specific antibody arrays. This approach provided for the first time a snapshot of the protein components of the TIF, which we show consists of more than one thousand proteins--either secreted, shed by membrane vesicles...... synthesis, energy metabolism, oxidative stress, the actin cytoskeleton assembly, protein folding, and transport. As expected, the TIF contained several classical serum proteins. Considering that the protein composition of the TIF reflects the physiological and pathological state of the tissue, it should...

  6. Crosstalk between Innate Lymphoid Cells and Other Immune Cells in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Fabian Flores-Borja

    2016-01-01

    Full Text Available Our knowledge and understanding of the tumor microenvironment (TME have been recently expanded with the recognition of the important role of innate lymphoid cells (ILC. Three different groups of ILC have been described based on their ability to produce cytokines that mediate the interactions between innate and adaptive immune cells in a variety of immune responses in infection, allergy, and autoimmunity. However, recent evidence from experimental models and clinical studies has demonstrated that ILC contribute to the mechanisms that generate suppressive or tolerant environments that allow tumor regression or progression. Defining the complex network of interactions and crosstalk of ILC with other immune cells and understanding the specific contributions of each type of ILC leading to tumor development will allow the manipulation of their function and will be important to develop new interventions and therapeutic strategies.

  7. Crosstalk between Innate Lymphoid Cells and Other Immune Cells in the Tumor Microenvironment

    Science.gov (United States)

    Irshad, Sheeba; Gordon, Peter; Wong, Felix; Sheriff, Ibrahim; Tutt, Andrew; Ng, Tony

    2016-01-01

    Our knowledge and understanding of the tumor microenvironment (TME) have been recently expanded with the recognition of the important role of innate lymphoid cells (ILC). Three different groups of ILC have been described based on their ability to produce cytokines that mediate the interactions between innate and adaptive immune cells in a variety of immune responses in infection, allergy, and autoimmunity. However, recent evidence from experimental models and clinical studies has demonstrated that ILC contribute to the mechanisms that generate suppressive or tolerant environments that allow tumor regression or progression. Defining the complex network of interactions and crosstalk of ILC with other immune cells and understanding the specific contributions of each type of ILC leading to tumor development will allow the manipulation of their function and will be important to develop new interventions and therapeutic strategies. PMID:27882334

  8. Corrosive microenvironments at lead solder surfaces arising from galvanic corrosion with copper pipe.

    Science.gov (United States)

    Nguyen, Caroline K; Stone, Kendall R; Dudi, Abhijeet; Edwards, Marc A

    2010-09-15

    As stagnant water contacts copper pipe and lead solder (simulated soldered joints), a corrosion cell is formed between the metals in solder (Pb, Sn) and the copper. If the resulting galvanic current exceeds about 2 μA/cm(2), a highly corrosive microenvironment can form at the solder surface, with pH chloride concentrations at least 11 times higher than bulk water levels. Waters with relatively high chloride tend to sustain high galvanic currents, preventing passivation of the solder surface, and contributing to lead contamination of potable water supplies. The total mass of lead corroded was consistent with predictions based on the galvanic current, and lead leaching to water was correlated with galvanic current. If the concentration of sulfate in the water increased relative to chloride, galvanic currents and associated lead contamination could be greatly reduced, and solder surfaces were readily passivated.

  9. Characterization of microenvironment polarity and solvent accessibility of polysilsesquioxane xerogels by the fluorescent probe technique

    Energy Technology Data Exchange (ETDEWEB)

    Shea, K.J.; Zhu, H.D. [Univ., of California, Irvine, CA (United States). Dept. of Chemistry; Loy, D.A. [Sandia National Labs., Albuquerque, NM (United States)

    1995-05-01

    Poly (1, 4 bis(triethoxysilyl)benzene) (PTESB), a representative of a new type of organic-inorganic hybrid polysilsesquioxane material, was characterized by fluorescence spectroscopy for both microenvironmental polarity and solvent accessibility. A dansyl fluorescent molecule was incorporated into the bulk as well as onto the surface of both PTESB and silica materials. Information about the microenvironment polarity and accessibility of PTESB to various organic solvents was determined and compared to that of silica gel. This study found that both the bulk and surface of PTESB are less polar than that of the silica material. The silica material is accessible to polar solvents and water, while YMB is accessible to polar solvents but not to water. The hydrophobicity of PTESB differentiates these new materials from silica gel.

  10. SPHINGOSINE-1 PHOSPHATE: A NEW MODULATOR OF IMMUNE PLASTICITY IN THE TUMOR MICROENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Yamila I Rodriguez

    2016-10-01

    Full Text Available In the last 15 years, increasing evidences demonstrate a strong link between sphingosine-1-phosphate (S1P in both normal physiology and progression of different diseases, including cancer and inflammation. Indeed, numerous studies show that tissue levels of this sphingolipid metabolite are augmented in many cancers, affecting survival, proliferation, angiogenesis and metastatic spread. Recent insights into the possible role of S1P as a therapeutic target has attracted enormous attention and opened new opportunities in this evolving field. In this review we will focus on the role of S1P in cancer with particular emphasis in new developments that highlight the many functions of this sphingolipid in the tumor microenvironment. We will discuss how S1P modulates phenotypic plasticity of macrophages and mast cells, tumor-induced immune evasion, differentiation and survival of immune cells in the tumor milieu, interaction between cancer and stromal cells and hypoxic response.

  11. Novel Luminescent Multilayer Films Containing π-Conjugated Anionic Polymer with Electronic Microenvironment

    Directory of Open Access Journals (Sweden)

    Tianlei Wang

    2016-09-01

    Full Text Available Layered double hydroxides (LDHs, luminescent π-conjugated anionic polymer and montmorillonite (MMT were orderly assembled into luminescent multilayer films via layer-by-layer self-assembly method. The electronic microenvironment (EME, the structure of which is like a traditional capacitor, can be constructed by exfoliated LDHs or MMT nanosheets. In addition, the rigid inorganic laminated configuration can offer stable surroundings between the interlayers. As a result, we conclude that EME can extend the luminescent lifespans of multilayer films substantially, due to affecting relaxation times of π-conjugated anionic polymer. Consequently, because of the remarkable impact on better photoemission behaviors of luminescent π-conjugated anionic polymer, EME assembled by LDHs or MMT nanosheets have had high hopes attached to them. They are expected to have the potential for designing, constructing, and investigating novel light-emitting thin films.

  12. Promotion of haematopoietic activity in embryonic stem cells by the aorta-gonad-mesonephros microenvironment

    International Nuclear Information System (INIS)

    Krassowska, Anna; Gordon-Keylock, Sabrina; Samuel, Kay; Gilchrist, Derek; Dzierzak, Elaine; Oostendorp, Robert; Forrester, Lesley M.; Ansell, John D.

    2006-01-01

    We investigated whether the in vitro differentiation of ES cells into haematopoietic progenitors could be enhanced by exposure to the aorta-gonadal-mesonephros (AGM) microenvironment that is involved in the generation of haematopoietic stem cells (HSC) during embryonic development. We established a co-culture system that combines the requirements for primary organ culture and differentiating ES cells and showed that exposure of differentiating ES cells to the primary AGM region results in a significant increase in the number of ES-derived haematopoietic progenitors. Co-culture of ES cells on the AM20-1B4 stromal cell line derived from the AGM region also increases haematopoietic activity. We conclude that factors promoting the haematopoietic activity of differentiating ES cells present in primary AGM explants are partially retained in the AM20.1B4 stromal cell line and that these factors are likely to be different to those required for adult HSC maintenance

  13. Impaired regeneration: A role for the muscle microenvironment in cancer cachexia.

    Science.gov (United States)

    Talbert, Erin E; Guttridge, Denis C

    2016-06-01

    While changes in muscle protein synthesis and degradation have long been known to contribute to muscle wasting, a body of literature has arisen which suggests that regulation of the satellite cell and its ensuing regenerative program are impaired in atrophied muscle. Lessons learned from cancer cachexia suggest that this regulation is simply not a consequence, but a contributing factor to the wasting process. In addition to satellite cells, evidence from mouse models of cancer cachexia also suggests that non-satellite progenitor cells from the muscle microenvironment are also involved. This chapter in the series reviews the evidence of dysfunctional muscle repair in multiple wasting conditions. Potential mechanisms for this dysfunctional regeneration are discussed, particularly in the context of cancer cachexia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The Three Mile Island Disaster.

    Science.gov (United States)

    Crosby, Emeral

    1980-01-01

    For the past decade, education has been experiencing meltdown, explosions, radiation leaks, heat pollution, and management crises, just like the Three Mile Island disaster. This article offers suggestions on how to deal with these problems. (Author/LD)

  15. Ship impact against protection islands

    DEFF Research Database (Denmark)

    Pedersen, Preben Terndrup

    1997-01-01

    The five most exposed piers and the anchor blocks on the East Bridge shall be protected by aritificial islands. Extensive analytical and experimental investitations were carried out to verify the efficiency of how these protection works....

  16. Three Mile Island Accident Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Three Mile Island Accident Data consists of mostly upper air and wind observations immediately following the nuclear meltdown occurring on March 28, 1979, near...

  17. Archaeology of Bet Dwarka Island

    Digital Repository Service at National Institute of Oceanography (India)

    Sundaresh; Gaur, A.S.

    Explorations along the shore and in the intertidal zone at Bet Dwarka island, Gujarat, India were carried out by the Marine Archaeology Centre of National Institute of Oceanography (NIO), Goa, India between 1981-1994. Artefacts of both...

  18. Tourism impacts of Three Mile Island and other adverse events: implications for Lincoln County and other rural counties bisected by radioactive wastes intended for Yucca Mountain

    International Nuclear Information System (INIS)

    Himmelberger, J.J.; Baughman, M.; Ogneva-Himmelberger, Y.A.

    1995-01-01

    Whether the proposed Yucca Mountain nuclear waste repository system will adversely impact tourism in southern Nevada is an open question of particular importance to visitor-oriented rural counties bisected by planned waste transportation corridors (highway or rail). As part of one such county's repository impact assessment program, tourism implications of Three Mile Island (TMI) and other major hazard events have been revisited to inform ongoing county-wide socioeconomic assessments and contingency planning efforts. This paper summarizes key research implications of such research as applied to Lincoln County, Nevada. Implications for other rural counties are discussed in light of the research findings

  19. Tourism impacts of Three Mile Island and other adverse events: Implications for Lincoln County and other rural counties bisected by radioactive wastes intended for Yucca Mountain

    Energy Technology Data Exchange (ETDEWEB)

    Himmelberger, J.J.; Ogneva-Himmelberger, Y.A. [Clark Univ., Worcester, MA (United States); Baughman, M. [Interech Services Corporation, Carson City, NV (United States)

    1995-11-01

    Whether the proposed Yucca Mountain nuclear waste repository system will adversely impact tourism in southern Nevada is an open question of particular importance to visitor-oriented rural counties bisected by planned waste transportation corridors (highway or rail). As part of one such county`s repository impact assessment program, tourism implications of Three Mile Island (TMI) and other major hazard events have been revisited to inform ongoing county-wide socioeconomic assessments and contingency planning efforts. This paper summarizes key research implications of such research as applied to Lincoln County, Nevada. Implications for other rural counties are discussed in light of the research findings. 29 refs., 3 figs., 1 tab.

  20. Myeloid cells in circulation and tumor microenvironment of breast cancer patients.

    Science.gov (United States)

    Toor, Salman M; Syed Khaja, Azharuddin Sajid; El Salhat, Haytham; Faour, Issam; Kanbar, Jihad; Quadri, Asif A; Albashir, Mohamed; Elkord, Eyad

    2017-06-01

    Pathological conditions including cancers lead to accumulation of a morphological mixture of highly immunosuppressive cells termed as myeloid-derived suppressor cells (MDSC). The lack of conclusive markers to identify human MDSC, due to their heterogeneous nature and close phenotypical and functional proximity with other cell subsets, made it challenging to identify these cells. Nevertheless, expansion of MDSC has been reported in periphery and tumor microenvironment of various cancers. The majority of studies on breast cancers were performed on murine models and hence limited literature is available on the relation of MDSC accumulation with clinical settings in breast cancer patients. The aim of this study was to investigate levels and phenotypes of myeloid cells in peripheral blood (n = 23) and tumor microenvironment of primary breast cancer patients (n = 7), compared with blood from healthy donors (n = 21) and paired non-tumor normal breast tissues from the same patients (n = 7). Using multicolor flow cytometric assays, we found that breast cancer patients had significantly higher levels of tumor-infiltrating myeloid cells, which comprised of granulocytes (P = 0.022) and immature cells that lack the expression of markers for fully differentiated monocytes or granulocytes (P = 0.016). Importantly, this expansion was not reflected in the peripheral blood. The immunosuppressive potential of these cells was confirmed by expression of Arginase 1 (ARG1), which is pivotal for T-cell suppression. These findings are important for developing therapeutic modalities to target mechanisms employed by immunosuppressive cells that generate an immune-permissive environment for the progression of cancer.

  1. Hyaluronan, Cancer-Associated Fibroblasts and the Tumor Microenvironment in Malignant Progression

    Directory of Open Access Journals (Sweden)

    James B. McCarthy

    2018-05-01

    Full Text Available This review summarizes the roles of CAFs in forming a “cancerized” fibrotic stroma favorable to tumor initiation and dissemination, in particular highlighting the functions of the extracellular matrix component hyaluronan (HA in these processes. The structural complexity of the tumor and its host microenvironment is now well appreciated to be an important contributing factor to malignant progression and resistance-to-therapy. There are multiple components of this complexity, which include an extensive remodeling of the extracellular matrix (ECM and associated biomechanical changes in tumor stroma. Tumor stroma is often fibrotic and rich in fibrillar type I collagen and hyaluronan (HA. Cancer-associated fibroblasts (CAFs are a major source of this fibrotic ECM. CAFs organize collagen fibrils and these biomechanical alterations provide highways for invading carcinoma cells either under the guidance of CAFs or following their epithelial to mesenchymal transition (EMT. The increased HA metabolism of a tumor microenvironment instructs carcinoma initiation and dissemination by performing multiple functions. The key effects of HA reviewed here are its role in activating CAFs in pre-malignant and malignant stroma, and facilitating invasion by promoting motility of both CAFs and tumor cells, thus facilitating their invasion. Circulating CAFs (cCAFs also form heterotypic clusters with circulating tumor cells (CTC, which are considered to be pre-cursors of metastatic colonies. cCAFs are likely required for extravasation of tumors cells and to form a metastatic niche suitable for new tumor colony growth. Therapeutic interventions designed to target both HA and CAFs in order to limit tumor spread and increase response to current therapies are discussed.

  2. Improving immunological tumor microenvironment using electro-hyperthermia followed by dendritic cell immunotherapy.

    Science.gov (United States)

    Tsang, Yuk-Wah; Huang, Cheng-Chung; Yang, Kai-Lin; Chi, Mau-Shin; Chiang, Hsin-Chien; Wang, Yu-Shan; Andocs, Gabor; Szasz, Andras; Li, Wen-Tyng; Chi, Kwan-Hwa

    2015-10-15

    The treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs. The CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied. mEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity. This study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy.

  3. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    LENUS (Irish Health Repository)

    Michielsen, Adriana J

    2011-01-01

    Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  4. Influence of cell microenvironment on the intrinsic radiosensitivity of mammalian cells

    International Nuclear Information System (INIS)

    Reddy, N.M.S.; Nori, Dattatreyudu

    1995-01-01

    Survival of cells cultured in the regular growth medium has been compared with that of cells cultured in media with reduced nutrient concentration. Nutrient concentration in the cell microenvironment cultured in regular physiological growth medium, composed of MEM with 15% serum, has been taken to be 100%. Relative to this, the nutrient concentration in the dilute media has been varied from 20 to 80%. The cell survival increased with the decrease in the nutrient concentration in the microenvironment, and reached a plateau in media with 40% or less of nutrient concentration. The magnitude of increase in the radioresistance of log phase cells in medium with 40% nutrient concentration was by a factor of 2.4. Growth kinetics in regular growth medium and in diluted media with nutrient concentration of 40% were nearly the same. The survival of cells cultured in reduced nutrient concentration was the same under growth and non growth post-irradiation repair conditions. Reduction in the concentration of serum, the source of hormones and growth factors, from 15% to 5% also increased the radioresistance of cell by a factor of 1.64. Conclusions: (1) cells in micro environments with reduced nutrient concentration are more refractory to radiation induced cell killing by a factor of as much as 2.4, (2) post-irradiation cell cycle progression does not appear to reduce the repair of x-ray induced damage, and (3) failure of radiotherapy in the local control of some large solid tumors may be related to the presence of pockets of cells in micro environments with inadequate and/or reduce supply of nutrients. 11 refs., 3 figs., 1 tab

  5. MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment.

    Science.gov (United States)

    Mukherjee, P; Ginardi, A R; Madsen, C S; Tinder, T L; Jacobs, F; Parker, J; Agrawal, B; Longenecker, B M; Gendler, S J

    2001-01-01

    Pancreatic cancer is a highly aggressive, treatment refractory disease and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas over-express altered forms of a tumor-associated antigen, MUC1 (an epithelial mucin glycoprotein), which is a target for immunotherapy. Using a clinically relevant mouse model of pancreas cancer that demonstrates peripheral and central tolerance to human MUC1 and develops spontaneous tumors of the pancreas, we have previously reported the presence of functionally active, low affinity, MUC1-specific precursor cytotoxic T cells (pCTLs). Hypothesis for this study is that MUC1-based immunization may enhance the low level MUC1-specific immunity that may lead to an effective anti-tumor response. Data demonstrate that MUC1 peptide-based immunization elicits mature MUC1-specific CTLs in the peripheral lymphoid organs. The mature CTLs secrete IFN-gamma and are cytolytic against MUC1-expressing tumor cells in vitro. However, active CTLs that infiltrate the pancreas tumor microenvironment become cytolytically anergic and are tolerized to MUC1 antigen, allowing the tumor to grow. We demonstrate that the CTL tolerance could be reversed at least in vitro with the use of anti-CD40 co-stimulation. The pancreas tumor cells secrete immunosuppressive cytokines, including IL-10 and TGF-beta that are partly responsible for the down-regulation of CTL activity. In addition, they down-regulate their MHC class I molecules to avoid immune recognition. CD4+ CD25+ T regulatory cells, which secrete IL-10, were also found in the tumor environment. Together these data indicate the use of several immune evasion mechanisms by tumor cells to evade CTL killing. Thus altering the tumor microenvironment to make it more conducive to CTL killing may be key in developing a successful anti-cancer immunotherapy.

  6. Pathologic bladder microenvironment attenuates smooth muscle differentiation of skin derived precursor cells: implications for tissue regeneration.

    Directory of Open Access Journals (Sweden)

    Cornelia Tolg

    Full Text Available Smooth muscle cell containing organs (bladder, heart, blood vessels are damaged by a variety of pathological conditions necessitating surgery or organ replacement. Currently, regeneration of contractile tissues is hampered by lack of functional smooth muscle cells. Multipotent skin derived progenitor cells (SKPs can easily be isolated from adult skin and can be differentiated in vitro into contractile smooth muscle cells by exposure to FBS. Here we demonstrate an inhibitory effect of a pathologic contractile organ microenvironment on smooth muscle cell differentiation of SKPs. In vivo, urinary bladder strain induces microenvironmental changes leading to de-differentiation of fully differentiated bladder smooth muscle cells. Co-culture of SKPs with organoids isolated from ex vivo stretched bladders or exposure of SKPs to diffusible factors released by stretched bladders (e.g. bFGF suppresses expression of smooth muscle markers (alpha SMactin, calponin, myocardin, myosin heavy chain as demonstrated by qPCR and immunofluorescent staining. Rapamycin, an inhibitor of mTOR signalling, previously observed to prevent bladder strain induced de-differentiation of fully differentiated smooth muscle cells in vitro, inhibits FBS-induced smooth muscle cell differentiation of undifferentiated SKPs. These results suggest that intended precursor cell differentiation may be paradoxically suppressed by the disease context for which regeneration may be required. Organ-specific microenvironment contexts, particularly prevailing disease, may play a significant role in modulating or attenuating an intended stem cell phenotypic fate, possibly explaining the variable and inefficient differentiation of stem cell constructs in in vivo settings. These observations must be considered in drafting any regeneration strategies.

  7. Mobile Monitoring of Diesel Particulate Matter Exposure within Five Urban Microenvironments, Portland, OR

    Science.gov (United States)

    Orlando, P. J.; Bennett, B. A.; George, L. A.

    2016-12-01

    Diesel particulate matter (DPM) is a hazardous air pollutant linked to mortality and morbidity outcomes including cancer, cardiovascular disease, and adverse respiratory effects. The EPA's Air Toxics Assessment indicated that more than 50% of Oregonians are exposed to 10 times the ambient benchmark concentration (ABC) of 0.1 μgm-3 for DPM. These model estimates have not been verified with measurements, potentially limiting policy action. We developed a mobile monitoring platform to ground-truth model predictions and characterize DPM spatial variation. Using black carbon (BC) as a marker, concentrations within five urban microenvironments (a construction site, an arterial, a bus mall, a city park, and an indoor workspace) were sampled within Portland, OR. The mobile monitoring platform consisted of a bicycle and trailer equipped with an aethalometer measuring BC mass, a Data Ram 4 measuring total PM2.5 mass, and a Q-Starz GPS recording location; each instrument was monitoring in 1 second intervals. Concentrations of BC were used as an indicator of DPM. The construction site had the highest DPM concentration (7 μg m-3). The indoor workspace and the park had the lowest DPM (0.3 μg m-3). Near the construction site, DPM constituted approximately 50% of the total PM2.5. However, at the park, DPM was attributed to only 6% of the total PM2.5, while the indoor space constituted 15%. Concentrations of BC near construction sites were observed to exceed 67 times the state ABC of 0.1 μg m-3 (Figure). These results signify the need to better characterize the urban exposure to DPM, as even the cleanest microenvironments may be 3 times above the ABC. Our mobile monitoring platform will help further elucidate how local-scale sources contribute to the broader distribution of DPM within Portland, while providing a tool for both residents and DEQ to effectively mitigate the health impacts from DPM exposure.

  8. Chitosan-alginate 3D scaffolds as a mimic of the glioma tumor microenvironment.

    Science.gov (United States)

    Kievit, Forrest M; Florczyk, Stephen J; Leung, Matthew C; Veiseh, Omid; Park, James O; Disis, Mary L; Zhang, Miqin

    2010-08-01

    Despite recent advances in the understanding of its cell biology, glioma remains highly lethal. Development of effective therapies requires a cost-effective in vitro tumor model that more accurately resembles the in vivo tumor microenvironment as standard two-dimensional (2D) tissue culture conditions do so poorly. Here we report on the use of a three-dimensional (3D) chitosan-alginate (CA) scaffold to serve as an extracellular matrix that promotes the conversion of cultured cancer cells to a more malignant in vivo-like phenotype. Human U-87 MG and U-118 MG glioma cells and rat C6 glioma cells were chosen for the study. In vitro tumor cell proliferation and secretion of factors that promote tumor malignancy, including VEGF, MMP-2, fibronectin, and laminin, were assessed. The scaffolds pre-cultured with U-87 MG and C6 cells were then implanted into nude mice to evaluate tumor growth and blood vessel recruitment compared to the standard 2D cell culture and 3D Matrigel matrix xenograft controls. Our results indicate that while the behavior of C6 cells showed minimal differences due to their highly malignant and invasive nature, U-87 MG and U-118 MG cells exhibited notably higher malignancy when cultured in CA scaffolds. CA scaffolds provide a 3D microenvironment for glioma cells that is more representative of the in vivo tumor, thus can serve as a more effective platform for development and study of anticancer therapeutics. This unique CA scaffold platform may offer a valuable alternative strategy to the time-consuming and costly animal studies for a wide variety of experimental designs. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Tissue-specific composite cell aggregates drive periodontium tissue regeneration by reconstructing a regenerative microenvironment.

    Science.gov (United States)

    Zhu, Bin; Liu, Wenjia; Zhang, Hao; Zhao, Xicong; Duan, Yan; Li, Dehua; Jin, Yan

    2017-06-01

    Periodontitis is the most common cause of periodontium destruction. Regeneration of damaged tissue is the expected treatment goal. However, the regeneration of a functional periodontal ligament (PDL) insertion remains a difficulty, due to complicated factors. Recently, periodontal ligament stem cells (PDLSCs) and bone marrow-derived mesenchymal stem cells (BMMSCs) have been shown to participate in PDL regeneration, both pathologically and physiologically. Besides, interactions affect the biofunctions of different derived cells during the regenerative process. Therefore, the purpose of this study was to discuss the different derived composite cell aggregate (CA) systems of PDLSCs and BMMSCs (iliac-derived or jaw-derived) for periodontium regeneration under regenerative microenvironment reconstruction. Our results showed although all three mono-MSC CAs were compacted and the cells arranged regularly in them, jaw-derived BMMSC (JBMMSC) CAs secreted more extracellular matrix than the others. Furthermore, PDLSC/JBMMSC compound CAs highly expressed ALP, Col-I, fibronectin, integrin-β1 and periostin, suggesting that their biofunction is more appropriate for periodontal structure regeneration. Inspiringly, PDLSC/JBMMSC compound CAs regenerated more functional PDL-like tissue insertions in both nude mice ectopic and minipig orthotopic transplantation. The results indicated that the different derived CAs of PDLSCs/JBMMSCs provided an appropriate regenerative microenvironment facilitating a more stable and regular regeneration of functional periodontium tissue. This method may provide a possible strategy to solve periodontium defects in periodontitis and powerful experimental evidence for clinical applications in the future. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Magnetic island formation in tokamaks

    International Nuclear Information System (INIS)

    Yoshikawa, S.

    1989-04-01

    The size of a magnetic island created by a perturbing helical field in a tokamak is estimated. A helical equilibrium of a current- carrying plasma is found in a helical coordinate and the helically flowing current in the cylinder that borders the plasma is calculated. From that solution, it is concluded that the helical perturbation of /approximately/10/sup /minus/4/ of the total plasma current is sufficient to cause an island width of approximately 5% of the plasma radius. 6 refs

  11. Island biodiversity conservation needs palaeoecology

    DEFF Research Database (Denmark)

    Nogué, Sandra; de Nascimento, Lea; Froyd, Cynthia A.

    2017-01-01

    to human activities. Consequently, even the most degraded islands are a focus for restoration, eradication, and monitoring programmes to protect the remaining endemic and/or relict populations. Here, we build a framework that incorporates an assessment of the degree of change from multiple baseline...... and the introduction of non-native species. We provide exemplification of how such approaches can provide valuable information for biodiversity conservation managers of island ecosystems....

  12. Effect of Microenvironment on Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Hepatocytes In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Gai Xue

    2016-01-01

    Full Text Available Human umbilical cord-derived mesenchymal stem cells (hUCMSCs are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCs in vitro and in vivo and to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironment in vivo using liver homogenate supernatant (LHS in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cells in vivo in the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (P<0.05. In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes both in vitro and in vivo.

  13. Effect of Microenvironment on Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Hepatocytes In Vitro and In Vivo

    Science.gov (United States)

    Xue, Gai; Han, Xiaolei; Ma, Xin; Wu, Honghai; Qin, Yabin; Liu, Jianfang; Hu, Yuqin; Hong, Yang; Hou, Yanning

    2016-01-01

    Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCs in vitro and in vivo and to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironment in vivo using liver homogenate supernatant (LHS) in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cells in vivo in the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (P < 0.05). In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes both in vitro and in vivo. PMID:27088093

  14. Impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. Introduction of a multiinstitutional research project

    International Nuclear Information System (INIS)

    Zips, D.; Petersen, C.; Adam, M.; Molls, M.; Philbrook, C.; Flentje, M.; Haase, A.; Schmitt, P.; Mueller-Klieser, W.; Thews, O.; Walenta, S.; Baumann, M.

    2004-01-01

    Background: recent developments in imaging technology and tumor biology have led to new techniques to detect hypoxia and related alterations of the metabolic microenvironment in tumors. However, whether these new methods can predict radiobiological hypoxia and outcome after fractionated radiotherapy still awaits experimental evaluation. Material and methods: the present article will introduce a multiinstitutional research project addressing the impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. The four laboratories involved are situated at the universities of Dresden, Mainz, Munich and Wuerzburg, Germany. Results: the joint scientific project started to collect data obtained on a set of ten different human tumor xenografts growing in nude mice by applying various imaging techniques to detect tumor hypoxia and related parameters of the metabolic microenvironment. These techniques include magnetic resonance imaging and spectroscopy, metabolic mapping with quantitative bioluminescence and single-photon imaging, histological multiparameter analysis of biochemical hypoxia, perfusion and vasculature, and immunohistochemistry of factors related to angiogenesis, invasion and metastasis. To evaluate the different methods, baseline functional radiobiological data including radiobiological hypoxic fraction and outcome after fractionated irradiation will be determined. Conclusion: besides increasing our understanding of tumor biology, the project will focus on new, clinically applicable strategies for microenvironment profiling and will help to identify those patients that might benefit from targeted interventions to improve tumor oxygenation. (orig.)

  15. Three Mile Island

    International Nuclear Information System (INIS)

    2015-01-01

    This document addresses the Three Mile Island accident which resulted in a core partial fusion. It recalls that other reactors of this plant are still being operated. The operation of this PWR is briefly described, and the main events and phases of the accident are briefly presented (failure of the secondary circuit supply pump, failure of a pressurizer component and wrong information about it, mistaken reaction in the control room, core partial fusion due to insufficient cooling means). It shows that the accident occurred because of a combination of technical failures and human mistakes. This situation has put operator education and organisation into question again. The main actors and their mistakes, weaknesses and responsibilities are indicated: Metropolitan Edison (the operator), the NRC (the US nuclear safety authority). Some key figures are recalled, as well as the context of construction of the plant. Impacts and consequences are reviewed: implementation of new standards, population concern. The document outlines that radioactive exposures due to the accident were minor

  16. Arctic Islands LNG

    Energy Technology Data Exchange (ETDEWEB)

    Hindle, W.

    1977-01-01

    Trans-Canada Pipe Lines Ltd. made a feasibility study of transporting LNG from the High Arctic Islands to a St. Lawrence River Terminal by means of a specially designed and built 125,000 cu m or 165,000 cu m icebreaking LNG tanker. Studies were made of the climatology and of ice conditions, using available statistical data as well as direct surveys in 1974, 1975, and 1976. For on-schedule and unimpeded (unescorted) passage of the LNG carriers at all times of the year, special navigation and communications systems can be made available. Available icebreaking experience, charting for the proposed tanker routes, and tide tables for the Canadian Arctic were surveyed. Preliminary design of a proposed Arctic LNG icebreaker tanker, including containment system, reliquefaction of boiloff, speed, power, number of trips for 345 day/yr operation, and liquefaction and regasification facilities are discussed. The use of a minimum of three Arctic Class 10 ships would enable delivery of volumes of natural gas averaging 11.3 million cu m/day over a period of a year to Canadian markets. The concept appears to be technically feasible with existing basic technology.

  17. The timeline of the lunar bombardment: Revisited

    Science.gov (United States)

    Morbidelli, A.; Nesvorny, D.; Laurenz, V.; Marchi, S.; Rubie, D. C.; Elkins-Tanton, L.; Wieczorek, M.; Jacobson, S.

    2018-05-01

    The timeline of the lunar bombardment in the first Gy of Solar System history remains unclear. Basin-forming impacts (e.g. Imbrium, Orientale), occurred 3.9-3.7 Gy ago, i.e. 600-800 My after the formation of the Moon itself. Many other basins formed before Imbrium, but their exact ages are not precisely known. There is an intense debate between two possible interpretations of the data: in the cataclysm scenario there was a surge in the impact rate approximately at the time of Imbrium formation, while in the accretion tail scenario the lunar bombardment declined since the era of planet formation and the latest basins formed in its tail-end. Here, we revisit the work of Morbidelli et al. (2012) that examined which scenario could be compatible with both the lunar crater record in the 3-4 Gy period and the abundance of highly siderophile elements (HSE) in the lunar mantle. We use updated numerical simulations of the fluxes of asteroids, comets and planetesimals leftover from the planet-formation process. Under the traditional assumption that the HSEs track the total amount of material accreted by the Moon since its formation, we conclude that only the cataclysm scenario can explain the data. The cataclysm should have started ∼ 3.95 Gy ago. However we also consider the possibility that HSEs are sequestered from the mantle of a planet during magma ocean crystallization, due to iron sulfide exsolution (O'Neil, 1991; Rubie et al., 2016). We show that this is likely true also for the Moon, if mantle overturn is taken into account. Based on the hypothesis that the lunar magma ocean crystallized about 100-150 My after Moon formation (Elkins-Tanton et al., 2011), and therefore that HSEs accumulated in the lunar mantle only after this timespan, we show that the bombardment in the 3-4 Gy period can be explained in the accretion tail scenario. This hypothesis would also explain why the Moon appears so depleted in HSEs relative to the Earth. We also extend our analysis of the

  18. Revisit ocean thermal energy conversion system

    International Nuclear Information System (INIS)

    Huang, J.C.; Krock, H.J.; Oney, S.K.

    2003-01-01

    by-products, especially drinking water, aquaculture and mariculture, can easily translate into billions of dollars in business opportunities. The current status of the OTEC system definitely deserves to be carefully revisited. This paper will examine recent major advancements in technology, evaluate costs and effectiveness, and assess the overall market environment of the OTEC system and describe its great renewable energy potential and overall benefits to the nations of the world

  19. Foundation Investigation for Ground Based Radar Project-Kwajalein Island, Marshall Islands

    Science.gov (United States)

    1990-04-01

    iL_ COPY MISCELLANEOUS PAPER GL-90-5 i iFOUNDATION INVESTIGATION FOR GROUND BASED RADAR PROJECT--KWAJALEIN ISLAND, MARSHALL ISLANDS by Donald E...C!assification) Foundatioa Investigation for Ground Based Radar Project -- Kwajalein Island, Marshall Islands 12. PERSONAL AUTHOR(S) Yule, Donald E...investigation for the Ground Based Radar Project -- Kwajalein Island, Marshall Islands , are presented.- eophysical tests comprised of surface refrac- tion

  20. Bryophytes from Simeonof Island in the Shumagin Islands, southwestern Alaska

    Science.gov (United States)

    Schofield, W.B.; Talbot, S. S.; Talbot, S.L.

    2004-01-01

    Simeonof Island is located south of the Alaska Peninsula in the hyperoceanic sector of the middle boreal subzone. We examined the bryoflora of Simeonof Island to determine species composition in an area where no previous collections had been reported. This field study was conducted in sites selected to represent the spectrum of environmental variation within Simeonof Island. Data were analyzed using published reports to compare bryophyte distribution patterns at three levels, the Northern Hemisphere, North America, and Alaska. A total of 271 bryophytes were identified: 202 mosses and 69 liverworts. The annotated list of species for Simeonof Island expands the known range for many species and fills distribution gaps within Hulte??n's Western Pacific Coast district. Maps and notes on the distribution of 14 significant distribution records are presented. Compared with bryophyte distribution in the Northern Hemisphere, the bryoflora of Simeonof Island primarily includes taxa of boreal (55%), temperate (20%), arctic (10%), and cosmopolitan (8%) distribution; 6% of the moss flora are western North America endemics. A description of the bryophytes present in the vegetation and habitat types is provided as is a quantitative analysis of the most frequently occurring bryophytes in crowberry heath.