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Sample records for exploit host hyaluronan

  1. Host exploitation strategies of the social parasite Maculinea alcon

    DEFF Research Database (Denmark)

    Fürst, Matthias Alois

    as model systems. These enable the study of adaptations and counter-adaptations that might evolve in the arms-race between a parasite pursuing maximum gain and a host trying to avoid exploitation. One such system is the socially parasitic butterfly Maculinea alcon and its host the ant Myrmica rubra....... Throughout the first instars M. alcon lives on a specific food plant, however, in the last instar before pupation it develops into an obligate social parasite, posing a considerably cost to its host ant colony. I here focus on the different exploitation strategies of M. alcon throughout its lifecycle...... a fitness cost to infected host ant colonies, the host ants are expected to have developed defense mechanisms in response to the presence of the social parasite. I was able to demonstrate that the efficiency of ant colonies to defend themselves against intruders depends on a multitude of often correlated...

  2. Hyaluronan in human malignancies

    International Nuclear Information System (INIS)

    Sironen, R.K.; Tammi, M.; Tammi, R.; Auvinen, P.K.; Anttila, M.; Kosma, V-M.

    2011-01-01

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  3. Hyaluronan in human malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Sironen, R.K. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Tammi, M.; Tammi, R. [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Auvinen, P.K. [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Anttila, M. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Kosma, V-M., E-mail: Veli-Matti.Kosma@uef.fi [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  4. Pseudomonas predators: understanding and exploiting phage-host interactions.

    Science.gov (United States)

    De Smet, Jeroen; Hendrix, Hanne; Blasdel, Bob G; Danis-Wlodarczyk, Katarzyna; Lavigne, Rob

    2017-09-01

    Species in the genus Pseudomonas thrive in a diverse set of ecological niches and include crucial pathogens, such as the human pathogen Pseudomonas aeruginosa and the plant pathogen Pseudomonas syringae. The bacteriophages that infect Pseudomonas spp. mirror the widespread and diverse nature of their hosts. Therefore, Pseudomonas spp. and their phages are an ideal system to study the molecular mechanisms that govern virus-host interactions. Furthermore, phages are principal catalysts of host evolution and diversity, which directly affects the ecological roles of environmental and pathogenic Pseudomonas spp. Understanding these interactions not only provides novel insights into phage biology but also advances the development of phage therapy, phage-derived antimicrobial strategies and innovative biotechnological tools that may be derived from phage-bacteria interactions.

  5. Lipids in host-pathogen interactions: pathogens exploit the complexity of the host cell lipidome.

    Science.gov (United States)

    van der Meer-Janssen, Ynske P M; van Galen, Josse; Batenburg, Joseph J; Helms, J Bernd

    2010-01-01

    Lipids were long believed to have a structural role in biomembranes and a role in energy storage utilizing cellular lipid droplets and plasma lipoproteins. Research over the last decades has identified an additional role of lipids in cellular signaling, membrane microdomain organization and dynamics, and membrane trafficking. These properties make lipids an attractive target for pathogens to modulate host cell processes in order to allow their survival and replication. In this review we will summarize the often ingenious strategies of pathogens to modify the lipid homeostasis of host cells, allowing them to divert cellular processes. To this end pathogens take full advantage of the complexity of the lipidome. The examples are categorized in generalized and emerging principles describing the involvement of lipids in host-pathogen interactions. Several pathogens are described that simultaneously induce multiple changes in the host cell signaling and trafficking mechanisms. Elucidation of these pathogen-induced changes may have important implications for drug development. The emergence of high-throughput lipidomic techniques will allow the description of changes of the host cell lipidome at the level of individual molecular lipid species and the identification of lipid biomarkers.

  6. Constraints on host choice: why do parasitic birds rarely exploit some common potential hosts?

    Czech Academy of Sciences Publication Activity Database

    Grim, T.; Samaš, P.; Moskát, C.; Kleven, O.; Honza, Marcel; Moksnes, A.; Roskaft, E.; Stokke, B. G.

    2011-01-01

    Roč. 80, č. 3 (2011), s. 508-518 ISSN 0021-8790 R&D Projects: GA AV ČR IAA600930605 Institutional research plan: CEZ:AV0Z60930519 Keywords : antiparasite defence * co-evolution * host selection * interactive effects * parasite avoidance Subject RIV: EG - Zoology Impact factor: 4.937, year: 2011

  7. Production methods for hyaluronan

    NARCIS (Netherlands)

    Boeriu, C.G.; Springer, J.; Kooy, F.K.; Broek, van den L.A.M.; Eggink, G.

    2013-01-01

    Hyaluronan is a polysaccharide with multiple functions in the human body being involved in creating flexible and protective layers in tissues and in many signalling pathways during embryonic development, wound healing, inflammation, and cancer. Hyaluronan is an important component of active

  8. Hyaluronan in vaginal secretions: association with recurrent vulvovaginal candidiasis.

    Science.gov (United States)

    Lev-Sagie, Ahinoam; Nyirjesy, Paul; Tarangelo, Nicholas; Bongiovanni, Ann Marie; Bayer, Cynthia; Linhares, Iara M; Giraldo, Paulo C; Ledger, William J; Witkin, Steven S

    2009-08-01

    We evaluated whether vaginal concentrations of hyaluronan were altered in women with recurrent vulvovaginal candidiasis (RVVC). Lavage samples from 17 women with acute RVVC, 27 women who were receiving a maintenance antifungal regimen, and 24 control women were tested for hyaluronan and interleukin (IL)-6, IL-12, and IL-23 by enzyme-linked immunosorbent assay. Median vaginal hyaluronan concentrations were 33.8 ng/mL (range, 21.6-66.3 ng/mL) in women with acute RVVC, 15.0 ng/mL (range, 11.2-50.6 ng/mL) in women who were receiving maintenance therapy, and 4.2 ng/mL (range, 3.6-12.0 ng/mL) in control subjects (P vaginal hyaluronan concentration was 27.4 ng/mL (range, 15.4-37.7 ng/mL) when Candida was detected by microscopy and 9.5 ng/mL (range, 7.7-14.6 ng/mL) in microscopy-negative cases (P = .0354). Elevated hyaluronan levels were associated with itching plus burning (40.7 ng/mL) or itching plus discharge (42.1 ng/mL), as opposed to itching only (6.2 ng/mL; P = .0152). Hyaluronan and IL-6 levels were correlated (P = .0009). Hyaluronan release is a component of the host response to a candidal infection and may contribute to symptoms.

  9. Exploitation of the host cell ubiquitin machinery by microbial effector proteins.

    Science.gov (United States)

    Lin, Yi-Han; Machner, Matthias P

    2017-06-15

    Pathogenic bacteria are in a constant battle for survival with their host. In order to gain a competitive edge, they employ a variety of sophisticated strategies that allow them to modify conserved host cell processes in ways that favor bacterial survival and growth. Ubiquitylation, the covalent attachment of the small modifier ubiquitin to target proteins, is such a pathway. Ubiquitylation profoundly alters the fate of a myriad of cellular proteins by inducing changes in their stability or function, subcellular localization or interaction with other proteins. Given the importance of ubiquitylation in cell development, protein homeostasis and innate immunity, it is not surprising that this post-translational modification is exploited by a variety of effector proteins from microbial pathogens. Here, we highlight recent advances in our understanding of the many ways microbes take advantage of host ubiquitylation, along with some surprising deviations from the canonical theme. The lessons learned from the in-depth analyses of these host-pathogen interactions provide a fresh perspective on an ancient post-translational modification that we thought was well understood.This article is part of a Minifocus on Ubiquitin Regulation and Function. For further reading, please see related articles: 'Mechanisms of regulation and diversification of deubiquitylating enzyme function' by Pawel Leznicki and Yogesh Kulathu ( J. Cell Sci. 130 , 1997-2006). 'Cell scientist to watch - Mads Gyrd-Hansen' ( J. Cell Sci. 130 , 1981-1983). © 2017. Published by The Company of Biologists Ltd.

  10. Hyaluronan and Stone Disease

    Science.gov (United States)

    Asselman, Marino

    2008-09-01

    Kidney stones cannot be formed as long as crystals are passed in the urine. However, when crystals are retained it becomes possible for them to aggregate and form a stone. Crystals are expected to be formed not earlier than the distal tubules and collecting ducts. Studies both in vitro and in vivo demonstrate that calcium oxalate monohydrate crystals do not adhere to intact distal epithelium, but only when the epithelium is proliferating or regenerating, so that it possesses dedifferentiated cells expressing hyaluronan, osteopontin (OPN) and their mutual receptor CD44 at the apical cell membrane. The polysaccharide hyaluronan is an excellent crystal binding molecule because of its negative ionic charge. We hypothesized that the risk for crystal retention in the human kidney would be increased when tubular cells express hyaluronan at their apical cell membrane. Two different patient categories in which nephrocalcinosis frequently occurs were studied to test this hypothesis (preterm neonates and kidney transplant patients). Hyaluronan (and OPN) expression at the luminal membrane of tubular cells indeed was observed, which preceded subsequent retention of crystals in the distal tubules. Tubular nephrocalcinosis has been reported to be associated with decline of renal function and thus further studies to extend our knowledge of the mechanisms of retention and accumulation of crystals in the kidney are warranted. Ultimately, this may allow the design of new strategies for the prevention and treatment of both nephrocalcinosis and nephrolithiasis in patients.

  11. Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery.

    Directory of Open Access Journals (Sweden)

    Tsung-Hsien Chang

    2009-06-01

    Full Text Available Ebola Zaire virus is highly pathogenic for humans, with case fatality rates approaching 90% in large outbreaks in Africa. The virus replicates in macrophages and dendritic cells (DCs, suppressing production of type I interferons (IFNs while inducing the release of large quantities of proinflammatory cytokines. Although the viral VP35 protein has been shown to inhibit IFN responses, the mechanism by which it blocks IFN production has not been fully elucidated. We expressed VP35 from a mouse-adapted variant of Ebola Zaire virus in murine DCs by retroviral gene transfer, and tested for IFN transcription upon Newcastle Disease virus (NDV infection and toll-like receptor signaling. We found that VP35 inhibited IFN transcription in DCs following these stimuli by disabling the activity of IRF7, a transcription factor required for IFN transcription. By yeast two-hybrid screens and coimmunoprecipitation assays, we found that VP35 interacted with IRF7, Ubc9 and PIAS1. The latter two are the host SUMO E2 enzyme and E3 ligase, respectively. VP35, while not itself a SUMO ligase, increased PIAS1-mediated SUMOylation of IRF7, and repressed Ifn transcription. In contrast, VP35 did not interfere with the activation of NF-kappaB, which is required for induction of many proinflammatory cytokines. Our findings indicate that Ebola Zaire virus exploits the cellular SUMOylation machinery for its advantage and help to explain how the virus overcomes host innate defenses, causing rapidly overwhelming infection to produce a syndrome resembling fulminant septic shock.

  12. The expression of virulence during double infections by different parasites with conflicting host exploitation and transmission strategies.

    Science.gov (United States)

    Ben-Ami, F; Rigaud, T; Ebert, D

    2011-06-01

    In many natural populations, hosts are found to be infected by more than one parasite species. When these parasites have different host exploitation strategies and transmission modes, a conflict among them may arise. Such a conflict may reduce the success of both parasites, but could work to the benefit of the host. For example, the less-virulent parasite may protect the host against the more-virulent competitor. We examine this conflict using the waterflea Daphnia magna and two of its sympatric parasites: the blood-infecting bacterium Pasteuria ramosa that transmits horizontally and the intracellular microsporidium Octosporea bayeri that can concurrently transmit horizontally and vertically after infecting ovaries and fat tissues of the host. We quantified host and parasite fitness after exposing Daphnia to one or both parasites, both simultaneously and sequentially. Under conditions of strict horizontal transmission, Pasteuria competitively excluded Octosporea in both simultaneous and sequential double infections, regardless of the order of exposure. Host lifespan, host reproduction and parasite spore production in double infections resembled those of single infection by Pasteuria. When hosts became first vertically (transovarilly) infected with O. bayeri, Octosporea was able to withstand competition with P. ramosa to some degree, but both parasites produced less transmission stages than they did in single infections. At the same time, the host suffered from reduced fecundity and longevity. Our study demonstrates that even when competing parasite species utilize different host tissues to proliferate, double infections lead to the expression of higher virulence and ultimately may select for higher virulence. Furthermore, we found no evidence that the less-virulent and vertically transmitting O. bayeri protects its host against the highly virulent P. ramosa. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  13. Hyaluronan Biosynthesis in Prostate Cancer

    National Research Council Canada - National Science Library

    McCarthy, James B

    2006-01-01

    Despite advances in the diagnosis and treatment of prostate cancer in the last several years metastasis represents the major cause of frustration and failure in the successful treatment of prostate cancer patients. Hyaluronan (HA...

  14. Semiochemical exploitation of host-associated cues by seven Melittobia parasitoid species

    NARCIS (Netherlands)

    González, Jorge M.; Camino, Dakota; Simon, Sabrina; Cusumano, Antonino

    2018-01-01

    Chemical compounds (infochemicals or semiochemicals) play an important role both in intra-specific and inter-specific communication. For example, chemical cues appear to play a key role in the host selection process adopted by insect parasitoids. In recent years significant advances have been made

  15. Plasma Membrane-Located Purine Nucleotide Transport Proteins Are Key Components for Host Exploitation by Microsporidian Intracellular Parasites

    Science.gov (United States)

    Heinz, Eva; Hacker, Christian; Dean, Paul; Mifsud, John; Goldberg, Alina V.; Williams, Tom A.; Nakjang, Sirintra; Gregory, Alison; Hirt, Robert P.; Lucocq, John M.; Kunji, Edmund R. S.; Embley, T. Martin

    2014-01-01

    Microsporidia are obligate intracellular parasites of most animal groups including humans, but despite their significant economic and medical importance there are major gaps in our understanding of how they exploit infected host cells. We have investigated the evolution, cellular locations and substrate specificities of a family of nucleotide transport (NTT) proteins from Trachipleistophora hominis, a microsporidian isolated from an HIV/AIDS patient. Transport proteins are critical to microsporidian success because they compensate for the dramatic loss of metabolic pathways that is a hallmark of the group. Our data demonstrate that the use of plasma membrane-located nucleotide transport proteins (NTT) is a key strategy adopted by microsporidians to exploit host cells. Acquisition of an ancestral transporter gene at the base of the microsporidian radiation was followed by lineage-specific events of gene duplication, which in the case of T. hominis has generated four paralogous NTT transporters. All four T. hominis NTT proteins are located predominantly to the plasma membrane of replicating intracellular cells where they can mediate transport at the host-parasite interface. In contrast to published data for Encephalitozoon cuniculi, we found no evidence for the location for any of the T. hominis NTT transporters to its minimal mitochondria (mitosomes), consistent with lineage-specific differences in transporter and mitosome evolution. All of the T. hominis NTTs transported radiolabelled purine nucleotides (ATP, ADP, GTP and GDP) when expressed in Escherichia coli, but did not transport radiolabelled pyrimidine nucleotides. Genome analysis suggests that imported purine nucleotides could be used by T. hominis to make all of the critical purine-based building-blocks for DNA and RNA biosynthesis during parasite intracellular replication, as well as providing essential energy for parasite cellular metabolism and protein synthesis. PMID:25474405

  16. Plasma membrane-located purine nucleotide transport proteins are key components for host exploitation by microsporidian intracellular parasites.

    Directory of Open Access Journals (Sweden)

    Eva Heinz

    2014-12-01

    Full Text Available Microsporidia are obligate intracellular parasites of most animal groups including humans, but despite their significant economic and medical importance there are major gaps in our understanding of how they exploit infected host cells. We have investigated the evolution, cellular locations and substrate specificities of a family of nucleotide transport (NTT proteins from Trachipleistophora hominis, a microsporidian isolated from an HIV/AIDS patient. Transport proteins are critical to microsporidian success because they compensate for the dramatic loss of metabolic pathways that is a hallmark of the group. Our data demonstrate that the use of plasma membrane-located nucleotide transport proteins (NTT is a key strategy adopted by microsporidians to exploit host cells. Acquisition of an ancestral transporter gene at the base of the microsporidian radiation was followed by lineage-specific events of gene duplication, which in the case of T. hominis has generated four paralogous NTT transporters. All four T. hominis NTT proteins are located predominantly to the plasma membrane of replicating intracellular cells where they can mediate transport at the host-parasite interface. In contrast to published data for Encephalitozoon cuniculi, we found no evidence for the location for any of the T. hominis NTT transporters to its minimal mitochondria (mitosomes, consistent with lineage-specific differences in transporter and mitosome evolution. All of the T. hominis NTTs transported radiolabelled purine nucleotides (ATP, ADP, GTP and GDP when expressed in Escherichia coli, but did not transport radiolabelled pyrimidine nucleotides. Genome analysis suggests that imported purine nucleotides could be used by T. hominis to make all of the critical purine-based building-blocks for DNA and RNA biosynthesis during parasite intracellular replication, as well as providing essential energy for parasite cellular metabolism and protein synthesis.

  17. Immunologic roles of hyaluronan.

    Science.gov (United States)

    Mummert, Mark E

    2005-01-01

    Hyaluronan (HA), a large glycosaminoglycan composed of D-N-acetylglucosamine and D-glucuronic acid, is expressed in virtually all tissues and has long been considered to serve as a structural component or filling material in the tissue interstitium (Filler Theory). This idea was revised with the discovery of HA-binding proteins that introduced the concept that HA may also serve as an adhesive substrate for cellular trafficking (Adhesion Theory). Most recently, it has been shown that HA fragments can deliver maturational signals to dendritic cells (DCs) and high molecular weight HA polymers can deliver costimulatory signals to T-cells (Signaling Theory). Thus, HA may represent an important component of the immune system. Recently, we have evaluated the impact of HA on Langerhans cell (LC) maturation and migration using a novel peptide inhibitor of HA function, termed Pep-1 (GAHWQFNALTVR). As skin-specific members of the DC family, LCs are crucial for the initiation of cutaneous immune responses. Local injections of Pep-1 prevented hapten-induced LC migration from the epidermis, providing the first experimental evidence that HA facilitates their emigration. Moreover, Pep-1 also significantly inhibited the hapten-induced maturation of LCs in vivo as assessed by cell morphology, costimulatory molecule expression, and their ability to induce proliferation of allogeneic T-cells. HA therefore has dual functionality to facilitate LC migration and maturation, the two critical events for the initiation of adaptive immune responses. Finally, we have observed that DC-dependent, antigen-specific T-cell proliferation and cytokine secretion is blocked by Pep-1. These results have revealed a previously unrecognized role for HA in antigen presentation. Thus, far from an inert structural biopolymer, HA represents a multifunctional carbohydrate mediator of immune processes.

  18. The Arf GTPase-activating protein family is exploited by Salmonella enterica serovar Typhimurium to invade nonphagocytic host cells.

    Science.gov (United States)

    Davidson, Anthony C; Humphreys, Daniel; Brooks, Andrew B E; Hume, Peter J; Koronakis, Vassilis

    2015-02-10

    To establish intracellular infections, Salmonella bacteria trigger host cell membrane ruffling and invasion by subverting cellular Arf guanine nucleotide exchange factors (GEFs) that activate Arf1 and Arf6 GTPases by promoting GTP binding. A family of cellular Arf GTPase-activating proteins (GAPs) can downregulate Arf signaling by stimulating GTP hydrolysis, but whether they do this during infection is unknown. Here, we uncovered a remarkable role for distinct Arf GAP family members in Salmonella invasion. The Arf6 GAPs ACAP1 and ADAP1 and the Arf1 GAP ASAP1 localized at Salmonella-induced ruffles, which was not the case for the plasma membrane-localized Arf6 GAPs ARAP3 and GIT1 or the Golgi-associated Arf1 GAP1. Surprisingly, we found that loss of ACAP1, ADAP1, or ASAP1 impaired Salmonella invasion, revealing that GAPs cannot be considered mere terminators of cytoskeleton remodeling. Salmonella invasion was restored in Arf GAP-depleted cells by expressing fast-cycling Arf derivatives, demonstrating that Arf GTP/GDP cycles facilitate Salmonella invasion. Consistent with this view, both constitutively active and dominant-negative Arf derivatives that cannot undergo GTP/GDP cycles inhibited invasion. Furthermore, we demonstrated that Arf GEFs and GAPs colocalize at invading Salmonella and collaborate to drive Arf1-dependent pathogen invasion. This study revealed that Salmonella bacteria exploit a remarkable interplay between Arf GEFs and GAPs to direct cycles of Arf GTPase activation and inactivation. These cycles drive Salmonella cytoskeleton remodeling and enable intracellular infections. To initiate infections, the Salmonella bacterial pathogen remodels the mammalian actin cytoskeleton and invades host cells by subverting host Arf GEFs that activate Arf1 and Arf6 GTPases. Cellular Arf GAPs deactivate Arf GTPases and negatively regulate cell processes, but whether they target Arfs during infection is unknown. Here, we uncovered an important role for the Arf GAP

  19. Enzymatic production of hyaluronan oligo- and polysaccharides

    NARCIS (Netherlands)

    Kooy, F.K.

    2010-01-01

    Hyaluronan oligo- and polysaccharides are abundant in the human body. Depending on the chain length, hyaluronan is an important structural component or is involved in influencing cell responses during embryonic development, healing processes, inflammation and cancer. Due to these diverse roles of

  20. Hyaluronan: from biomimetic to industrial business strategy.

    Science.gov (United States)

    Murano, Erminio; Perin, Danilo; Khan, Riaz; Bergamin, Massimo

    2011-04-01

    Hyaluronan (hyaluronic acid) is a naturally occurring polysaccharide of a linear repeating disaccharide unit consisting of beta-(1-->4)-linked D-glucopyranuronic acid and beta-(1-->3)-linked 2-acetamido-2-deoxy-D-glucopyranose, which is present in extracellular matrices, the synovial fluid of joints, and scaffolding that comprises cartilage. In its mechanism of synthesis, its size, and its physico-chemical properties, hyaluronan is unique amongst other glycosaminoglycans. The network-forming, viscoelastic and its charge characteristics are important to many biochemical properties of living tissues. It is an important pericellular and cell surface constituent; its interaction with other macromolecules such as proteins, participates in regulating cell behavior during numerous morphogenic, restorative, and pathological processes in the body. The knowledge of HA in diseases such as various forms of cancers, arthritis and osteoporosis has led to new impetus in research and development in the preparation of biomaterials for surgical implants and drug conjugates for targeted delivery. A concise and focused review on hyaluronan is timely. This review will cover the following important aspects of hyaluronan: (i) biological functions and synthesis in nature; (ii) current industrial production and potential biosynthetic processes of hyaluronan; (iii) chemical modifications of hyaluronan leading to products of commercial significance; and (iv) and the global market position and manufacturers of hyaluronan.

  1. Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity

    International Nuclear Information System (INIS)

    Nishida, Yoshihiro; Knudson, Warren; Knudson, Cheryl B.; Ishiguro, Naoki

    2005-01-01

    Osteosarcoma is a common malignant bone tumor associated with childhood and adolescence. The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion

  2. Hydration dynamics of hyaluronan and dextran.

    Science.gov (United States)

    Hunger, Johannes; Bernecker, Anja; Bakker, Huib J; Bonn, Mischa; Richter, Ralf P

    2012-07-03

    Hyaluronan is a polysaccharide, which is ubiquitous in vertebrates and has been reported to be strongly hydrated in a biological environment. We study the hydration of hyaluronan in solution using the rotational dynamics of water as a probe. We measure these dynamics with polarization-resolved femtosecond-infrared and terahertz time-domain spectroscopies. Both experiments reveal that a subensemble of water molecules is slowed down in aqueous solutions of hyaluronan amounting to ∼15 water molecules per disaccharide unit. This quantity is consistent with what would be expected for the first hydration shell. Comparison of these results to the water dynamics in aqueous dextran solution, a structurally similar polysaccharide, yields remarkably similar results. This suggests that the observed interaction with water is a common feature for hydrophilic polysaccharides and is not specific to hyaluronan. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Transcriptome of an entomophthoralean fungus (Pandora formicae) shows molecular machinery adjusted for successful host exploitation and transmission

    DEFF Research Database (Denmark)

    Malagocka, Joanna; Grell, Morten Nedergaard; Lange, Lene

    2015-01-01

    Pandora formicae is an obligate entomopathogenic fungus from the phylum Entomophthoromycota, known to infect only ants from the genus Formica. In the final stages of infection, the fungus induces the so-called summit disease syndrome, manipulating the host to climb up vegetation prior to death......, but the fungus had not grown out through the cuticle and (2) when the fungus was growing out from host cadaver and producing spores. These phases mark the switch from within-host growth to reproduction on the host surface, after fungus outgrowth through host integument. In this first de novo transcriptome...... of an entomophthoralean fungus, we detected expression of many pathogenicity-related genes, including secreted hydrolytic enzymes and genes related to morphological reorganization and nutrition uptake. Differences in expression of genes in these two infection phases were compared and showed a switch in enzyme expression...

  4. Smuggling across the border: how arthropod-borne pathogens evade and exploit the host defense system of the skin.

    Science.gov (United States)

    Bernard, Quentin; Jaulhac, Benoit; Boulanger, Nathalie

    2014-05-01

    The skin is a critical barrier between hosts and pathogens in arthropod-borne diseases. It harbors many resident cells and specific immune cells to arrest or limit infections by secreting inflammatory molecules or by directly killing pathogens. However, some pathogens are able to use specific skin cells and arthropod saliva for their initial development, to hide from the host immune system, and to establish persistent infection in the vertebrate host. A better understanding of the initial mechanisms taking place in the skin should allow the development of new strategies to fight these vector-borne pathogens that are spread worldwide and are of major medical importance.

  5. Inactivation of the host lipin gene accelerates RNA virus replication through viral exploitation of the expanded endoplasmic reticulum membrane.

    Directory of Open Access Journals (Sweden)

    Chingkai Chuang

    2014-02-01

    Full Text Available RNA viruses take advantage of cellular resources, such as membranes and lipids, to assemble viral replicase complexes (VRCs that drive viral replication. The host lipins (phosphatidate phosphatases are particularly interesting because these proteins play key roles in cellular decisions about membrane biogenesis versus lipid storage. Therefore, we examined the relationship between host lipins and tombusviruses, based on yeast model host. We show that deletion of PAH1 (phosphatidic acid phosphohydrolase, which is the single yeast homolog of the lipin gene family of phosphatidate phosphatases, whose inactivation is responsible for proliferation and expansion of the endoplasmic reticulum (ER membrane, facilitates robust RNA virus replication in yeast. We document increased tombusvirus replicase activity in pah1Δ yeast due to the efficient assembly of VRCs. We show that the ER membranes generated in pah1Δ yeast is efficiently subverted by this RNA virus, thus emphasizing the connection between host lipins and RNA viruses. Thus, instead of utilizing the peroxisomal membranes as observed in wt yeast and plants, TBSV readily switches to the vastly expanded ER membranes in lipin-deficient cells to build VRCs and support increased level of viral replication. Over-expression of the Arabidopsis Pah2p in Nicotiana benthamiana decreased tombusvirus accumulation, validating that our findings are also relevant in a plant host. Over-expression of AtPah2p also inhibited the ER-based replication of another plant RNA virus, suggesting that the role of lipins in RNA virus replication might include several more eukaryotic viruses.

  6. Hyaluronan polymeric micelles for topical drug delivery

    Czech Academy of Sciences Publication Activity Database

    Šmejkalová, D.; Muthný, T.; Nešporová, K.; Hermannová, M.; Achbergerová, E.; Huerta-Angelesa, G.; Marek Svoboda, M.; Čepa, M.; Machalová, V.; Luptáková, Dominika; Velebný, V.

    2017-01-01

    Roč. 156, JAN 20 (2017), s. 86-96 ISSN 0144-8617 Institutional support: RVO:61388971 Keywords : Skin penetration * Polymeric micelle * Hyaluronan Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 4.811, year: 2016

  7. Pleural tissue hyaluronan produced by postmortem ventilation in rabbits.

    Science.gov (United States)

    Wang, P M; Lai-Fook, S J

    2000-01-01

    We developed a method that used Alcian blue bound to hyaluronan to measure pleural hyaluronan in rabbits postmortem. Rabbits were killed, then ventilated with 21% O2--5% CO2--74% N2 for 3 h. The pleural liquid was removed by suction and 5 ml Alcian blue stock solution (0.33 mg/ml, 3.3 pH) was injected into each chest cavity. After 10 min, the Alcian blue solution was removed and the unbound Alcian blue solution (supernatant) separated by centrifugation and filtration. The supernatant transmissibility (T) was measured spectrophotometrically at 613 nm. Supernatant Alcian blue concentration (Cab) was obtained from a calibration curve of T versus dilutions of stock solution Cab. Alcian blue bound to pleural tissue hyaluronan was obtained by subtracting supernatant Cab from stock solution Cab. Pleural tissue hyaluronan was obtained from a calibration curve of hyaluronan versus Alcian blue bound to hyaluronan. Compared with control rabbits, pleural tissue hyaluronan (0.21 +/- 0.04 mg/kg) increased twofold, whereas pleural liquid volume decreased by 30% after 3 h of ventilation. Pleural effusions present 3 h postmortem without ventilation did not change pleural tissue hyaluronan from control values. Thus ventilation-induced pleural liquid shear stress, not increased filtration, was the stimulus for the increased hyaluronan produced from pleural mesothelial cells.

  8. Formation and properties of hyaluronan/nano Ag and hyaluronan-lecithin/nano Ag films.

    Science.gov (United States)

    Khachatryan, Gohar; Khachatryan, Karen; Grzyb, Jacek; Fiedorowicz, Maciej

    2016-10-20

    A facile and environmentally friendly method of the preparation of silver nanoparticles embedded in hyaluronan (Hyal/Ag) and hyaluronan-lecithin (Hyal-L/Ag) matrix was developed. Thin, elastic foils were prepared from gels by an in situ synthesis of Ag in an aqueous solution of sodium hyaluronate (Hyal), using aq. d-(+)-xylose solution as a reducing agent. The gels were applied to a clean, smooth, defatted Teflon surface and left for drying in the air. The dry foils were stored in a closed container. UV-vis spectroscopy, transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectra confirmed formation of about 10nm ball-shaped Ag nanoparticles situated within the polysaccharide template. Thermal properties of the composites were characterized involving differential scanning calorimetry (DSC) and thermogravimetric (TGA) analyses, whereas molecular weights of polysaccharide chains of the matrix were estimated with the size exclusion chromatography coupled with multiangle laser light scattering and refractometric detectors (HPSEC-MALLS-RI). An increase in the molecular weight of the hyaluronate after generation of Ag nanoparticles was observed. The foils showed specific properties. The study confirmed that silver nanoparticles can be successfully prepared with environmentally friendly method, using hyaluronan as a stabilizing template. Hyaluronan and hyaluronan-lecithin matrices provide nanocrystals uniform in size and shape. The composites demonstrated a bacteriostatic activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Exploit Kit traffic analysis

    OpenAIRE

    Καπίρης, Σταμάτης; Kapiris, Stamatis

    2017-01-01

    Exploit kits have become one of the most widespread and destructive threat that Internet users face on a daily basis. Since the first actor, which has been categorized as exploit kit, namely MPack, appeared in 2006, we have seen a new era on exploit kit variants compromising popular websites, infecting hosts and delivering destructive malware, following an exponentially evolvement to date. With the growing threat landscape, large enterprises to domestic networks, have starte...

  10. Hyaluronan and calcium carbonate hybrid nanoparticles for colorectal cancer chemotherapy

    Science.gov (United States)

    Bai, Jinghui; Xu, Jian; Zhao, Jian; Zhang, Rui

    2017-09-01

    A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan-CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan-CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan-CC/Adr nanoparticles. On the other hand, we also found that hyaluronan-CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan-CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.

  11. Factors that influence serum hyaluronan levels in hemodialysis patients.

    Science.gov (United States)

    de Medina, M; Ashby, M; Diego, J; Pennell, J P; Hill, M; Schiff, E R; Perez, G O

    1999-01-01

    Serum hyaluronan levels are increased in dialysis patients. We evaluated several factors that influence serum hyaluronan levels in 184 patients on chronic hemodialysis (duration 2.3 +/- 2.3 [SD] years). The levels were higher than normal in the whole group and in a subgroup of 133 patients without chronic infection, liver disease, or rheumatoid arthritis (215 +/- 19 and 205 +/- 22 microg/L, respectively). There was a tendency for the levels to be higher in a subgroup of patients with hepatitis c virus (HCV) infection. There was no correlation between hyaluronan levels, alanine aminotransferase (ALT), and duration or dose of dialysis. A weak but highly significant negative correlation between serum albumin levels and serum hyaluronan and ferritin levels was seen. The data suggest that chronic inflammation may explain, at least in part, the increased hyaluronan levels found in chronic dialysis patients.

  12. Importance of hyaluronan biosynthesis and degradation in cell differentiation and tumor formation

    Directory of Open Access Journals (Sweden)

    Heldin P.

    2003-01-01

    Full Text Available Hyaluronan is an important connective tissue glycosaminoglycan. Elevated hyaluronan biosynthesis is a common feature during tissue remodeling under both physiological and pathological conditions. Through its interactions with hyaladherins, hyaluronan affects several cellular functions such as cell migration and differentiation. The activities of hyaluronan-synthesizing and -degrading enzymes have been shown to be regulated in response to growth factors. During tumor progression hyaluronan stimulates tumor cell growth and invasiveness. Thus, elucidation of the molecular mechanisms which regulate the activities of hyaluronan-synthesizing and -degrading enzymes during tumor progression is highly desired.

  13. Lubrication synergy: Mixture of hyaluronan and dipalmitoylphosphatidylcholine (DPPC) vesicles

    DEFF Research Database (Denmark)

    Raj, Akanksha; Wang, Min; Zander, Thomas

    2017-01-01

    consisting of non-homogeneous phospholipid bilayer with hyaluronan/DPPC aggregates on top. The presence of these aggregates generates a long-range repulsive surface force as two such surfaces are brought together. However, the aggregates are easily deformed, partly rearranged into multilayer structures......Phospholipids and hyaluronan have been implied to fulfil important roles in synovial joint lubrication. Since both components are present in synovial fluid, self-assembly structures formed by them should also be present. We demonstrate by small angle X-ray scattering that hyaluronan associates...... with the outer shell of dipalmitoylphophatidylcholine (DPPC) vesicles in bulk solution. Further, we follow adsorption to silica from mixed hyaluronan/DPPC vesicle solution by Quartz Crystal Microbalance with Dissipation measurements. Atomic Force Microscope imaging visualises the adsorbed layer structure...

  14. Hyaluronan-lecithin foils and their properties

    International Nuclear Information System (INIS)

    BiaIopiotrowicz, Tomasz; Janczuk, BronisIaw; Fiedorowicz, Maciej; Khachatryan, Gohar; Tomasik, Piotr; Bakos, Dusan

    2006-01-01

    Thin, elastic foils of good resistance to the air exposure, patented as wound healing aids, were prepared by evaporation of a blend of lecithin (L) and sodium hyaluronan (H) taken under varying proportions. The contact angle for water, glycerol, formamide, ethylene glycol and diiodomethane, was determined for these foils. The contact angle was correlated against the H:L foil composition. For all liquids but formamide the highest contact angle was noted for the H:L = 2:1 (g g -1 ) ratio. The contact angles provided estimation of the work of adhesion. At the same L:H ratio the work of adhesion was the lowest. It was suggested that lecithin cross-linked hyaluronan. Since the work of adhesion of the studied liquids was similar to that of diiodomethane, it could be concluded that almost all functional groups on the foil surface were completely blocked. Perhaps, at H:L = 2:1 (g g -1 ) a stoichiometric complex of hyaluronic acid with lecithin was formed, and polar functional groups from both reagents were involved. Foils seem to be electrostatic complexes of H with L. Foils with the H:L equal to 2:1 exhibited specific properties confirmed by the IR reflectance spectra of the foils. The thermogravimetry (TG/DTG) also revealed unique thermal behaviour confirming other specific properties of the foil of this composition. For the same ratio a thorough inspection of the scanning electron micrographs (SEM) revealed few irregularly distributed perforations of 1-2 μm in diameter seen as black points, which can be recognized as pores. Properties of the foils determined in the contact angle measurements are nicely backed by the results from thermogravimetric and scanning electron microscopic studies

  15. Altered expression of versican and hyaluronan in melanocytic tumors of dogs.

    Science.gov (United States)

    Docampo, María-José; Rabanal, Rosa M; Miquel-Serra, Laia; Hernández, Daniel; Domenzain, Clelia; Bassols, Anna

    2007-12-01

    To analyze the expression of versican and hyaluronan in melanocytomas and malignant melanomas of dogs, to correlate their expression with expression of the hyaluronan receptor CD44, and to identify enzymes responsible for the synthesis and degradation of hyaluronan in canine dermal fibroblasts and canine melanoma cell lines. 35 biopsy specimens from melanocytic tumors of dogs, canine primary dermal fibroblasts, and 3 canine melanoma cell lines. Versican, hyaluronan, and CD44 were detected in tumor samples by use of histochemical or immunohistochemical methods. Expression of hyaluronan-metabolizing enzymes was analyzed with a reverse transcriptase-PCR assay. Versican was found only in some hair follicles and around some blood vessels in normal canine skin, whereas hyaluronan was primarily found within the dermis. Hyaluronan was found in connective tissue of the oral mucosa. Versican and, to a lesser extent, hyaluronan were significantly overexpressed in malignant melanomas, compared with expression in melanocytomas. No significant difference was found between malignant tumors from oral or cutaneous origin. The expression of both molecules was correlated, but hyaluronan had a more extensive distribution than versican. Versican and hyaluronan were mainly associated with tumor stroma. Canine fibroblasts and melanoma cell lines expressed hyaluronan synthase 2 and 3 (but not 1) and hyaluronidase 1 and 2. Versican may be useful as a diagnostic marker for melanocytic tumors in dogs. Knowledge of the enzymes involved in hyaluronan metabolism could reveal new potential therapeutic targets.

  16. Recombinant Brugia malayi pepsin inhibitor (rBm33) exploits host signaling events to regulate inflammatory responses associated with lymphatic filarial infections.

    Science.gov (United States)

    Sreenivas, Kirthika; Kalyanaraman, Haripriya; Babu, Subash; Narayanan, Rangarajan Badri

    2017-11-01

    Prolonged existence of filarial parasites and their molecules within the host modulate the host immune system to instigate their survival and induce inflammatory responses that contribute to disease progression. Recombinant Brugia malayi pepsin inhibitor (rBm33) modulates the host immune responses by skewing towards Th1 responses characterized by secretion of inflammatory molecules such as TNF-α, IL-6, nitric oxide (NO). Here we also specified the molecular signaling events triggered by rBm33 in peripheral blood mononuclear cells (PBMCs) of filarial endemic normals (EN). rBm33 predominantly enhanced the levels of nitric oxide in cultured PBMCs but did not result in oxidative stress to the host cells. Further, rBm33 treatment of human PBMCs resulted in higher GSH/GSSG levels. MYD88 dependent activation was found to be associated with rBm33 specific inflammatory cytokine production. rBm33 triggered intracellular signaling events also involved JNK activation in host PBMCs. In addition, c-Fos and not NF-κB was identified as the transcription factor regulating the expression of inflammatory cytokines in rBm33 stimulated PBMCs. rBm33 marked its role in filarial pathology by altered levels of growth factors but did not have a significant impact on matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) activity of host PBMCs. Thus, the study outlines the signaling network of rBm33 induced inflammatory responses within the host immune cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Provisional matrix: A role for versican and hyaluronan.

    Science.gov (United States)

    Wight, Thomas N

    2017-07-01

    Hyaluronan and versican are extracellular matrix (ECM) components that are enriched in the provisional matrices that form during the early stages of development and disease. These two molecules interact to create pericellular "coats" and "open space" that facilitate cell sorting, proliferation, migration, and survival. Such complexes also impact the recruitment of leukocytes during development and in the early stages of disease. Once thought to be inert components of the ECM that help hold cells together, it is now quite clear that they play important roles in controlling cell phenotype, shaping tissue response to injury and maintaining tissue homeostasis. Conversion of hyaluronan-/versican-enriched provisional matrix to collagen-rich matrix is a "hallmark" of tissue fibrosis. Targeting the hyaluronan and versican content of provisional matrices in a variety of diseases including, cardiovascular disease and cancer, is becoming an attractive strategy for intervention. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Hyaluronidase and hyaluronan in insect venom allergy.

    Science.gov (United States)

    King, Te Piao; Wittkowski, Knut M

    2011-01-01

    Insect venoms contain an allergen hyaluronidase that catalyzes the hydrolysis of hyaluronan (HA), a polymer of disaccharide GlcUA-GlcNAc in skin. HAs depending on their size have variable function in inflammation and immunity. This paper reports on whether hyaluronidase, HA polymers and oligomers can promote antibody response in mice. HA oligomers (8- to 50-mer; 3-20 kDa) were obtained by bee venom hyaluronidase digestion of HA polymers (750- to 5,000-mer; 300-2,000 kDa). Antibody responses in mice were compared following 3 biweekly subcutaneous injection of ovalbumin (OVA) with or without test adjuvant. OVA-specific IgG1 levels were approximately 2 times higher in BALB/c and C3H/HeJ mice receiving OVA and HA oligomer or polymer than those treated with OVA alone, and no increase in total IgE level was observed. In C57Bl/6 mice, observed increases in IgG1 and IgE were 3.5- and 1.7-fold, respectively, for the oligomer and 16- and 5-fold (p Insect venoms also have cytolytic peptides and phospholipases with inflammatory roles. These activities found in mice may contribute to venom allergenicity in susceptible people. Copyright © 2011 S. Karger AG, Basel.

  19. 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3

    International Nuclear Information System (INIS)

    Kultti, Anne; Pasonen-Seppaenen, Sanna; Jauhiainen, Marjo; Rilla, Kirsi J.; Kaernae, Riikka; Pyoeriae, Emma; Tammi, Raija H.; Tammi, Markku I.

    2009-01-01

    Hyaluronan accumulation on cancer cells and their surrounding stroma predicts an unfavourable disease outcome, suggesting that hyaluronan enhances tumor growth and spreading. 4-Methylumbelliferone (4-MU) inhibits hyaluronan synthesis and retards cancer spreading in experimental animals through mechanisms not fully understood. These mechanisms were studied in A2058 melanoma cells, MCF-7 and MDA-MB-361 breast, SKOV-3 ovarian and UT-SCC118 squamous carcinoma cells by analysing hyaluronan synthesis, UDP-glucuronic acid (UDP-GlcUA) content, and hyaluronan synthase (HAS) mRNA levels. The maximal inhibition in hyaluronan synthesis ranged 22-80% in the cell lines tested. Active glucuronidation of 4-MU produced large quantities of 4-MU-glucuronide, depleting the cellular UDP-GlcUA pool. The maximal reduction varied between 38 and 95%. 4-MU also downregulated HAS mRNA levels: HAS3 was 84-60% lower in MDA-MB-361, A2058 and SKOV-3 cells. HAS2 was the major isoenzyme in MCF-7 cells and lowered by 81%, similar to 88% in A2058 cells. These data indicate that both HAS substrate and HAS2 and/or HAS3 mRNA are targeted by 4-MU. Despite different target point sensitivities, the reduction of hyaluronan caused by 4-MU was associated with a significant inhibition of cell migration, proliferation and invasion, supporting the importance of hyaluronan synthesis in cancer, and the therapeutic potential of hyaluronan synthesis inhibition.

  20. 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3

    Energy Technology Data Exchange (ETDEWEB)

    Kultti, Anne, E-mail: anne.kultti@uku.fi [Institute of Biomedicine, Anatomy, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio (Finland); Pasonen-Seppaenen, Sanna [Institute of Biomedicine, Anatomy, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio (Finland); Jauhiainen, Marjo [Department of Pharmaceutical Chemistry, University of Kuopio, FIN-70211 Kuopio (Finland); Rilla, Kirsi J.; Kaernae, Riikka; Pyoeriae, Emma; Tammi, Raija H.; Tammi, Markku I. [Institute of Biomedicine, Anatomy, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio (Finland)

    2009-07-01

    Hyaluronan accumulation on cancer cells and their surrounding stroma predicts an unfavourable disease outcome, suggesting that hyaluronan enhances tumor growth and spreading. 4-Methylumbelliferone (4-MU) inhibits hyaluronan synthesis and retards cancer spreading in experimental animals through mechanisms not fully understood. These mechanisms were studied in A2058 melanoma cells, MCF-7 and MDA-MB-361 breast, SKOV-3 ovarian and UT-SCC118 squamous carcinoma cells by analysing hyaluronan synthesis, UDP-glucuronic acid (UDP-GlcUA) content, and hyaluronan synthase (HAS) mRNA levels. The maximal inhibition in hyaluronan synthesis ranged 22-80% in the cell lines tested. Active glucuronidation of 4-MU produced large quantities of 4-MU-glucuronide, depleting the cellular UDP-GlcUA pool. The maximal reduction varied between 38 and 95%. 4-MU also downregulated HAS mRNA levels: HAS3 was 84-60% lower in MDA-MB-361, A2058 and SKOV-3 cells. HAS2 was the major isoenzyme in MCF-7 cells and lowered by 81%, similar to 88% in A2058 cells. These data indicate that both HAS substrate and HAS2 and/or HAS3 mRNA are targeted by 4-MU. Despite different target point sensitivities, the reduction of hyaluronan caused by 4-MU was associated with a significant inhibition of cell migration, proliferation and invasion, supporting the importance of hyaluronan synthesis in cancer, and the therapeutic potential of hyaluronan synthesis inhibition.

  1. Molecular basis of Trypanosoma cruzi and Leishmania interaction with their host(s): exploitation of immune and defense mechanisms by the parasite leading to persistence and chronicity, features reminiscent of immune system evasion strategies in cancer diseases.

    Science.gov (United States)

    Ouaissi, Ali; Ouaissi, Mehdi

    2005-01-01

    A number of features occurring during host-parasite interactions in Chagas disease caused by the protozoan parasite, Trypanosoma cruzi, and Leishmaniasis, caused by a group of kinetoplastid protozoan parasites are reminiscent of those observed in cancer diseases. In fact,although the cancer is not a single disease, and that T.cruzi and Leishmania are sophisticated eukaryotic parasites presenting a high level of genotypic variability the growth of the parasites in their host and that of cancer cells share at least one common feature, that is their mutual capacity for rapid cell division. Surprisingly, the parasitic diseases and cancers share some immune evasion strategies. Consideration of these immunological alterations must be added to the evaluation of the pathogenic processes. The molecular and functional characterization of virulence factors and the study of their effect on the arms of the immune system have greatly improved understanding of the regulation of immune effectors functions. The purpose of this review is to analyze some of the current data related to the regulatory components or processes originating from the parasite that control or interfere with host cell physiology. Attempts are also made to delineate some similarities between the immune evasion strategies that parasites and tumors employ. The elucidation of the mode of action of parasite virulence factors toward the host cell allow not only provide us with a more comprehensive view of the host-parasite relationships but may also represent a step forward in efforts aimed to identify new target molecules for therapeutic intervention.

  2. Removal rate of ( sup 3 H)hyaluronan injected subcutaneously in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Reed, R.K.; Laurent, U.B.; Fraser, J.R.; Laurent, T.C. (Univ. of Bergen (Norway))

    1990-08-01

    Hyaluronan is an important constituent of the extracellular matrix in skin, and recent studies suggest that there is a pool of easily removable (free) hyaluronan drained by lymph. The removal rate of free hyaluronan in skin was measured from the elimination of ({sup 3}H)hyaluronan, injected subcutaneously in 13 rabbits. The removal of radioactivity was determined from appearance of {sup 3}H in plasma. During the first 24 h after injection, 10-87% of the tracer entered blood, less in injectates with high concentrations of hyaluronan. The removal was monoexponential with a half-life of 0.5-1 day when concentration of hyaluronan was 5 mg/ml or less. When hyaluronan concentration was 10 mg/ml or higher, the removal was slow for about 24 h and then became similar to that in experiments with low hyaluronan concentration. Free hyaluronan at physiological concentrations is thus turned over with the same rate as serum albumin, supporting the concept that hyaluronan is removed essentially by lymph flow to be degraded in lymph nodes and liver.

  3. Removal rate of [3H]hyaluronan injected subcutaneously in rabbits

    International Nuclear Information System (INIS)

    Reed, R.K.; Laurent, U.B.; Fraser, J.R.; Laurent, T.C.

    1990-01-01

    Hyaluronan is an important constituent of the extracellular matrix in skin, and recent studies suggest that there is a pool of easily removable (free) hyaluronan drained by lymph. The removal rate of free hyaluronan in skin was measured from the elimination of [ 3 H]hyaluronan, injected subcutaneously in 13 rabbits. The removal of radioactivity was determined from appearance of 3 H in plasma. During the first 24 h after injection, 10-87% of the tracer entered blood, less in injectates with high concentrations of hyaluronan. The removal was monoexponential with a half-life of 0.5-1 day when concentration of hyaluronan was 5 mg/ml or less. When hyaluronan concentration was 10 mg/ml or higher, the removal was slow for about 24 h and then became similar to that in experiments with low hyaluronan concentration. Free hyaluronan at physiological concentrations is thus turned over with the same rate as serum albumin, supporting the concept that hyaluronan is removed essentially by lymph flow to be degraded in lymph nodes and liver

  4. Nanostructure of hyaluronan acyl-derivatives in the solid state

    Czech Academy of Sciences Publication Activity Database

    Chmelař, J.; Bělský, P.; Mrázek, J.; Švadlák, D.; Hermannová, M.; Šlouf, Miroslav; Krakovský, I.; Šmejkalová, D.; Velebný, V.

    2018-01-01

    Roč. 195, 1 September (2018), s. 468-475 ISSN 0144-8617 R&D Projects: GA TA ČR(CZ) TE01020118 Institutional support: RVO:61389013 Keywords : hyaluronan * hydrophobization * nanostructure Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 4.811, year: 2016

  5. Atomistic fingerprint of hyaluronan-CD44 binding

    DEFF Research Database (Denmark)

    Vuorio, Joni; Vattulainen, Ilpo; Martinez-Seara, Hector

    2017-01-01

    that hyaluronan can bind CD44 with three topographically different binding modes that in unison define an interaction fingerprint, thus providing a plausible explanation for the disagreement between the earlier studies. Our results confirm that the known crystallographic mode is the strongest of the three binding...

  6. Hyaluronan minimizes effects of UV irradiation on human keratinocytes

    Czech Academy of Sciences Publication Activity Database

    Hašová, M.; Crhák, Tomáš; Šafaříková, Barbora; Dvořáková, J.; Muthný, T.; Velebný, V.; Kubala, Lukáš

    2011-01-01

    Roč. 303, č. 4 (2011), s. 277-284 ISSN 0340-3696 R&D Projects: GA ČR(CZ) GA305/08/1704 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : hyaluronan * keratinocyte * ultraviolet light Subject RIV: BO - Biophysics Impact factor: 2.279, year: 2011

  7. The effect of different molecular weight hyaluronan on macrophage physiology

    Czech Academy of Sciences Publication Activity Database

    Krejčová, Daniela; Pekarová, Michaela; Šafránková, B.; Kubala, Lukáš

    2009-01-01

    Roč. 30, č. 1 (2009), s. 106-111 ISSN 0172-780X R&D Projects: GA ČR(CZ) GA305/08/1704 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : inflammation * phagocytes * hyaluronan Subject RIV: BO - Biophysics Impact factor: 1.047, year: 2009

  8. Redefining Exploitation

    DEFF Research Database (Denmark)

    Agarwala, Rina

    2016-01-01

    This article examines how self-employed workers are organizing in the garments and waste collection industries in India. Although the question of who is profiting from self-employed workers’ labor is complex, the cases outlined in this paper highlight telling instances of how some self......-employed workers are organizing as workers. They are fighting labor exploitation by redefining the concept to include additional exploitation axes (from the state and middle class) and forms (including sexual). In doing so, they are redefining potential solutions, including identities and material benefits, to fit...... their unique needs. By expanding the category of “workers” beyond those defined by a narrow focus on a standard employer-employee relationship, these movements are also fighting exclusion from earlier labor protections by increasing the number of entitled beneficiaries. These struggles provide an important...

  9. Study of interactions between hyaluronan and cationic surfactants by means of calorimetry, turbidimetry, potentiometry and conductometry.

    Science.gov (United States)

    Krouská, J; Pekař, M; Klučáková, M; Šarac, B; Bešter-Rogač, M

    2017-02-10

    The thermodynamics of the micelle formation of the cationic surfactants tetradecyltrimethylammonium bromide (TTAB) and cetyltrimethylammonium bromide (CTAB) with and without the addition of hyaluronan of two molecular weights was studied in aqueous solution by titration calorimetry. Macroscopic phase separation, which was detected by calorimetry and also by conductometry, occurs when charges on the surfactant and hyaluronan are balanced. In contrast, turbidimetry and potentiometry showed hyaluronan-surfactant interactions at very low surfactant concentrations. The observed differences between systems prepared with CTAB and TTAB indicate that besides the electrostatic interactions, which probably predominate, hydrophobic effects also play a significant role in hyaluronan interactions with cationic surfactants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Herbivory eliminates fitness costs of mutualism exploiters.

    Science.gov (United States)

    Simonsen, Anna K; Stinchcombe, John R

    2014-04-01

    A common empirical observation in mutualistic interactions is the persistence of variation in partner quality and, in particular, the persistence of exploitative phenotypes. For mutualisms between hosts and symbionts, most mutualism theory assumes that exploiters always impose fitness costs on their host. We exposed legume hosts to mutualistic (nitrogen-fixing) and exploitative (non-nitrogen-fixing) symbiotic rhizobia in field conditions, and manipulated the presence or absence of insect herbivory to determine if the costly fitness effects of exploitative rhizobia are context-dependent. Exploitative rhizobia predictably reduced host fitness when herbivores were excluded. However, insects caused greater damage on hosts associating with mutualistic rhizobia, as a consequence of feeding preferences related to leaf nitrogen content, resulting in the elimination of fitness costs imposed on hosts by exploitative rhizobia. Our experiment shows that herbivory is potentially an important factor in influencing the evolutionary dynamic between legumes and rhizobia. Partner choice and host sanctioning are theoretically predicted to stabilize mutualisms by reducing the frequency of exploitative symbionts. We argue that herbivore pressure may actually weaken selection on choice and sanction mechanisms, thus providing one explanation of why host-based discrimination mechanisms may not be completely effective in eliminating nonbeneficial partners. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  12. Modulation of hyaluronan synthase activity in cellular membrane fractions

    OpenAIRE

    Vigetti, Davide; Genasetti, A; Karousou, Evgenia; Viola, Manuela; Clerici, M; Bartolini, B; Moretto, Paola; DE LUCA, Giancarlo; Hascall, Vc; Passi, Alberto

    2009-01-01

    Hyaluronan (HA), the only non-sulfated glycosaminoglycan, is involved in morphogenesis, wound healing, inflammation, angiogenesis, and cancer. In mammals, HA is synthesized by three homologous HA synthases, HAS1, HAS2, and HAS3, that polymerize the HA chain using UDP-glucuronic acid and UDP-N-acetylglucosamine as precursors. Since the amount of HA is critical in several pathophysiological conditions, we developed a non-radioactive assay for measuring the activity of HA synthases (HASs) in euk...

  13. Quantification and characterization of enzymatically produced hyaluronan with fluorophore-assisted carbohydrate electrophoresis

    NARCIS (Netherlands)

    Kooy, F.K.; Muyuan Ma,; Beeftink, H.H.; Eggink, G.; Tramper, J.; Boeriu, C.G.

    2009-01-01

    Hyaluronan (HA) is a polysaccharide with high-potential medical applications, depending on the chain length and the chain length distribution. Special interest goes to homogeneous HA oligosaccharides, which can be enzymatically produced using Pasteurella multocida hyaluronan synthase (PmHAS). We

  14. Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Laura Julia Starost

    2016-10-01

    Full Text Available Pertussis toxin (PTx, the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood–brain barrier (BBB in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218’s effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB.

  15. Expression of Hyaluronan Synthases (HAS1–3) and Hyaluronidases (HYAL1–2) in Serous Ovarian Carcinomas: Inverse Correlation between HYAL1 and Hyaluronan Content

    International Nuclear Information System (INIS)

    Nykopp, Timo K; Anttila, Maarit; Rilla, Kirsi; Sironen, Reijo; Tammi, Markku I; Tammi, Raija H; Hämäläinen, Kirsi; Heikkinen, Anna-Mari; Komulainen, Marja; Kosma, Veli-Matti

    2009-01-01

    Hyaluronan, a tumor promoting extracellular matrix polysaccharide, is elevated in malignant epithelial ovarian tumors, and associates with an unfavorable prognosis. To explore possible contributors to the accumulation of hyaluronan, we examined the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), correlated with hyaluronidase enzyme activity hyaluronan content and HAS1–3 immunoreactivity. Normal ovaries (n = 5) and 34 serous epithelial ovarian tumors, divided into 4 groups: malignant grades 1+2 (n = 10); malignant grade 3 (n = 10); borderline (n = 4) and benign epithelial tumors (n = 10), were analyzed for mRNA by real-time RT-PCR and compared to hyaluronidase activity, hyaluronan staining, and HAS1–3 immunoreactivity in tissue sections of the same specimens. The levels of HAS2 and HAS3 mRNA (HAS1 was low or absent), were not consistently increased in the carcinomas, and were not significantly correlated with HAS protein or hyaluronan accumulation in individual samples. Instead, the median of HYAL1 mRNA level was 69% lower in grade 3 serous ovarian cancers compared to normal ovaries (P = 0.01). The expression of HYAL1, but not HYAL2, significantly correlated with the enzymatic activity of tissue hyaluronidases (r = 0.5; P = 0.006). An inverse correlation was noted between HYAL1 mRNA and the intensity of hyaluronan staining of the corresponding tissue sections (r = -0.4; P = 0.025). The results indicate that in serous epithelial ovarian malignancies HAS expression is not consistently elevated but HYAL1 expression is significantly reduced and correlates with the accumulation of hyaluronan. (233 words)

  16. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion

    International Nuclear Information System (INIS)

    Takabe, Piia; Bart, Geneviève; Ropponen, Antti; Rilla, Kirsi; Tammi, Markku; Tammi, Raija; Pasonen-Seppänen, Sanna

    2015-01-01

    Malignant skin melanoma is one of the most deadly human cancers. Extracellular matrix (ECM) influences the growth of malignant tumors by modulating tumor cells adhesion and migration. Hyaluronan is an essential component of the ECM, and its amount is altered in many tumors, suggesting an important role for hyaluronan in tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and decreased melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation was receptor independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling was responsible for these suppressive effects on the malignant phenotype of MV3 melanoma cells. - Highlights: • Inducible HAS3-MV3 melanoma cell line was generated using Lentiviral transduction. • HAS3 overexpression inhibits MV3 cell migration via hyaluronan–receptor interaction. • HAS3 overexpression decreases MV3 melanoma cell proliferation and adhesion. • ERK1/2 phosphorylation is downregulated by 50% in HAS3 overexpressing cells. • The results suggest that hyaluronan has anti-cancer like effects in melanoma

  17. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Takabe, Piia, E-mail: piia.takabe@uef.fi [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland); Bart, Geneviève [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland); Ropponen, Antti [University of Eastern Finland, Institute of Clinical Medicine, 70211 Kuopio (Finland); Rilla, Kirsi; Tammi, Markku; Tammi, Raija; Pasonen-Seppänen, Sanna [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland)

    2015-09-10

    Malignant skin melanoma is one of the most deadly human cancers. Extracellular matrix (ECM) influences the growth of malignant tumors by modulating tumor cells adhesion and migration. Hyaluronan is an essential component of the ECM, and its amount is altered in many tumors, suggesting an important role for hyaluronan in tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and decreased melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation was receptor independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling was responsible for these suppressive effects on the malignant phenotype of MV3 melanoma cells. - Highlights: • Inducible HAS3-MV3 melanoma cell line was generated using Lentiviral transduction. • HAS3 overexpression inhibits MV3 cell migration via hyaluronan–receptor interaction. • HAS3 overexpression decreases MV3 melanoma cell proliferation and adhesion. • ERK1/2 phosphorylation is downregulated by 50% in HAS3 overexpressing cells. • The results suggest that hyaluronan has anti-cancer like effects in melanoma.

  18. Effect of Carboxymethylation on the Rheological Properties of Hyaluronan.

    Science.gov (United States)

    Wendling, Rian J; Christensen, Amanda M; Quast, Arthur D; Atzet, Sarah K; Mann, Brenda K

    2016-01-01

    Chemical modifications made to hyaluronan to enable covalent crosslinking to form a hydrogel or to attach other molecules may alter the physical properties as well, which have physiological importance. Here we created carboxymethyl hyaluronan (CMHA) with varied degree of modification and investigated the effect on the viscosity of CMHA solutions. Viscosity decreased initially as modification increased, with a minimum viscosity for about 30-40% modification. This was followed by an increase in viscosity around 45-50% modification. The pH of the solution had a variable effect on viscosity, depending on the degree of carboxymethyl modification and buffer. The presence of phosphates in the buffer led to decreased viscosity. We also compared large-scale production lots of CMHA to lab-scale and found that large-scale required extended reaction times to achieve the same degree of modification. Finally, thiolated CMHA was disulfide crosslinked to create hydrogels with increased viscosity and shear-thinning aspects compared to CMHA solutions.

  19. The Anomalies of Hyaluronan Structures in Presence of Surface Active Phospholipids—Molecular Mass Dependence

    Directory of Open Access Journals (Sweden)

    Piotr Bełdowski

    2018-03-01

    Full Text Available Interactions between hyaluronan (A- and phospholipids play a key role in many systems in the human body. One example is the articular cartilage system, where the synergistic effect of such interactions supports nanoscale lubrication. A molecular dynamics simulation has been performed to understand the process of formation of hydrogen bonds inside the hyaluronan network, both in the presence and absence of phospholipids. Additionally, the effect of the molecular mass of (A- was analyzed. The main finding of this work is a robust demonstration of the optimal parameters (H-bond energy, molecular mass influencing the facilitated lubrication mechanism of the articular cartilage system. Simulation results show that the presence of phospholipids has the greatest influence on hyaluronan at low molecular mass. We also show the specific sites of H-bonding between chains. Simulation results can help to understand how hyaluronan and phospholipids interact at several levels of articular cartilage system functioning.

  20. Influence of serum albumin on intracellular delivery of drug-loaded hyaluronan polymeric micelles

    Czech Academy of Sciences Publication Activity Database

    Nešporová, K.; Sogorková, J.; Smejkalova, D.; Kulhánek, J.; Huerta-Angeles, G.; Kubala, Lukáš; Velebný, V.

    2016-01-01

    Roč. 511, č. 1 (2016), s. 638-647 ISSN 0378-5173 Institutional support: RVO:68081707 Keywords : Polymeric micelle * Hyaluronan * Fatty acid Subject RIV: BO - Biophysics Impact factor: 3.649, year: 2016

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

    Science.gov (United States)

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

    1993-01-01

    Hyaluronan (HA) and the hyaluronan-binding glycoprotein hyaluronectin (HN) were measured in 23 gliomas and 8 meningiomas and their location was revisited in 35 tumours. A clear-cut difference was found in the HN/HA ratio values of glioblastomas (below 0.5) and that of astrocytomas (above 0.5 P edification of the extracellular matrix. In meningiomas only the stroma would be responsible for HA and HN production.

  2. A Hyaluronan-Based Scaffold for the in Vitro Construction of Dental Pulp-Like Tissue

    Directory of Open Access Journals (Sweden)

    Letizia Ferroni

    2015-03-01

    Full Text Available Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based on the use of a tridimensional (3D hyaluronan scaffold and human dental pulp stem cells (DPSCs to produce a functional dental pulp-like tissue in vitro. An enriched population of DPSCs was seeded onto hyaluronan-based non-woven meshes in the presence of differentiation factors to induce the commitment of stem cells to neuronal, glial, endothelial and osteogenic phenotypes. In vitro experiments, among which were gene expression profiling and immunofluorescence (IF staining, proved the commitment of DPSCs to the main components of dental pulp tissue. In particular, the hyaluronan-DPSCs construct showed a dental pulp-like morphology consisting of several specialized cells growing inside the hyaluronan fibers. Furthermore, these constructs were implanted into rat calvarial critical-size defects. Histological analyses and gene expression profiling performed on hyaluronan-DPSCs grafts showed the regeneration of osteodentin-like tissue. Altogether, these data suggest the regenerative potential of the hyaluronan-DPSC engineered tissue.

  3. The effects of hyaluronan and its fragments on lipid models exposed to UV irradiation.

    Science.gov (United States)

    Trommer, Hagen; Wartewig, Siegfried; Böttcher, Rolf; Pöppl, Andreas; Hoentsch, Joachim; Ozegowski, Jörg H; Neubert, Reinhard H H

    2003-03-26

    The effects of hyaluronan and its degradation products on irradiation-induced lipid peroxidation were investigated. Liposomal skin lipid models with increasing complexity were used. Hyaluronan and its fragments were able to reduce the amount of lipid peroxidation secondary products quantified by the thiobarbituric acid (TBA) assay. The qualitative changes were studied by mass spectrometry. To elucidate the nature of free radical involvement electron paramagnetic resonance (EPR) studies were carried out. The influence of hyaluronan and its fragments on the concentration of hydroxyl radicals generated by the Fenton system was examined using the spin trapping technique. Moreover, the mucopolysaccharide's ability to react with stable radicals was checked. The quantification assay of 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) showed no concentration changes of the stable radical caused by hyaluronan. Hyaluronan was found to exhibit prooxidative effects in the Fenton assay in a concentration dependent manner. A transition metal chelation was proposed as a mechanism of this behavior. Considering human skin and its constant exposure to UV light and oxygen and an increased pool of iron in irradiated skin the administration of hyaluronan or its fragments in cosmetic formulations or sunscreens could be helpful for the protection of the human skin. Copyright 2003 Elsevier Science B.V.

  4. A hyaluronan-based scaffold for the in vitro construction of dental pulp-like tissue.

    Science.gov (United States)

    Ferroni, Letizia; Gardin, Chiara; Sivolella, Stefano; Brunello, Giulia; Berengo, Mario; Piattelli, Adriano; Bressan, Eriberto; Zavan, Barbara

    2015-03-02

    Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based on the use of a tridimensional (3D) hyaluronan scaffold and human dental pulp stem cells (DPSCs) to produce a functional dental pulp-like tissue in vitro. An enriched population of DPSCs was seeded onto hyaluronan-based non-woven meshes in the presence of differentiation factors to induce the commitment of stem cells to neuronal, glial, endothelial and osteogenic phenotypes. In vitro experiments, among which were gene expression profiling and immunofluorescence (IF) staining, proved the commitment of DPSCs to the main components of dental pulp tissue. In particular, the hyaluronan-DPSCs construct showed a dental pulp-like morphology consisting of several specialized cells growing inside the hyaluronan fibers. Furthermore, these constructs were implanted into rat calvarial critical-size defects. Histological analyses and gene expression profiling performed on hyaluronan-DPSCs grafts showed the regeneration of osteodentin-like tissue. Altogether, these data suggest the regenerative potential of the hyaluronan-DPSC engineered tissue.

  5. Controlling adsorption of albumin with hyaluronan on silica surfaces and sulfonated latex particles.

    Science.gov (United States)

    Berts, Ida; Fragneto, Giovanna; Porcar, Lionel; Hellsing, Maja S; Rennie, Adrian R

    2017-10-15

    Polysaccharides are known to modify binding of proteins at interfaces and this paper describes studies of these interactions and how they are modified by pH. Specifically, the adsorption of human serum albumin on to polystyrene latex and to silica is described, focusing on how this is affected by hyaluronan. Experiments were designed to test how such binding might be modified under relevant physiological conditions. Changes in adsorption of albumin alone and the co-adsorption of albumin and hyaluronan are driven by electrostatic interactions. Multilayer binding is found to be regulated by the pH of the solution and the molecular mass and concentration of hyaluronan. Highest adsorption was observed at pH below 4.8 and for low molecular mass hyaluronan (≤150kDa) at concentrations above 2mgml -1 . On silica with grafted hyaluronan, albumin absorption is reversed by changes in solvent pH due to their strong electrostatic attraction. Albumin physisorbed on silica surfaces is also rinsed away with dilute hyaluronan solution at pH 4.8. The results demonstrate that the protein adsorption can be controlled both by changes of pH and by interaction with other biological macromolecules. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Peter Succar

    2016-01-01

    Full Text Available Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC therapy are gaining acceptance for knee-osteoarthritis (OA treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL. At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA.

  7. Hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in the accumulation of hyaluronan in endometrioid endometrial carcinoma

    International Nuclear Information System (INIS)

    Nykopp, Timo K; Rilla, Kirsi; Tammi, Markku I; Tammi, Raija H; Sironen, Reijo; Hämäläinen, Kirsi; Kosma, Veli-Matti; Heinonen, Seppo; Anttila, Maarit

    2010-01-01

    Hyaluronan accumulation correlates with the degree of malignancy in many solid tumor types, including malignant endometrial carcinomas. To elucidate the mechanism of hyaluronan accumulation, we examined the expression levels of the hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), and correlated them with hyaluronan content and HAS1-3 immunoreactivity. A total of 35 endometrial tissue biopsies from 35 patients, including proliferative and secretory endometrium (n = 10), post-menopausal proliferative endometrium (n = 5), complex atypical hyperplasia (n = 4), grade 1 (n = 8) and grade 2 + 3 (n = 8) endometrioid adenocarcinomas were divided for gene expression by real-time RT-PCR, and paraffin embedded blocks for hyaluronan and HAS1-3 cytochemistry. The mRNA levels of HAS1-3 were not consistently changed, while the immunoreactivity of all HAS proteins was increased in the cancer epithelium. Interestingly, HAS3 mRNA, but not HAS3 immunoreactivity, was increased in post-menopausal endometrium compared to normal endometrium (p = 0.003). The median of HYAL1 mRNA was 10-fold and 15-fold lower in both grade 1 and grade 2+3 endometrioid endometrial cancers, as compared to normal endometrium (p = 0.004-0.006), and post-menopausal endometrium (p = 0.002), respectively. HYAL2 mRNA was also reduced in cancer (p = 0.02) and correlated with HYAL1 (r = 0.8, p = 0.0001). There was an inverse correlation between HYAL1 mRNA and the epithelial hyaluronan staining intensity (r = -0.6; P = 0.001). The results indicated that HYAL1 and HYAL2 were coexpressed and significantly downregulated in endometrioid endometrial cancer and correlated with the accumulation of hyaluronan. While immunoreactivity for HASs increased in the cancer cells, tumor mRNA levels for HASs were not changed, suggesting that reduced turnover of HAS protein may also have contributed to the accumulation of hyaluronan

  8. Hyaluronan- and heparin-reduced silver nanoparticles with antimicrobial properties

    Science.gov (United States)

    Kemp, Melissa M; Kumar, Ashavani; Clement, Dylan; Ajayan, Pulickel; Mousa, Shaker

    2009-01-01

    Aims Silver nanoparticles exhibit unique antibacterial properties that make these ideal candidates for biological and medical applications. We utilized a clean method involving a single synthetic step to prepare silver nanoparticles that exhibit antimicrobial activity. Materials & methods These nanoparticles were prepared by reducing silver nitrate with diaminopyridinylated heparin (DAPHP) and hyaluronan (HA) polysaccharides and tested for their efficacy in inhibiting microbial growth. Results & discussion The resulting silver nanoparticles exhibit potent antimicrobial activity against Staphylococcus aureus and modest activity against Escherichia coli. Silver–HA showed greater antimicrobial activity than silver–DAPHP, while silver–glucose nanoparticles exhibited very weak antimicrobial activity. Neither HA nor DAPHP showed activity against S. aureus or E. coli. Conclusion These results suggest that DAPHP and HA silver nanoparticles have potential in antimicrobial therapeutic applications. PMID:19505245

  9. Hyaluronan synthase mediates dye translocation across liposomal membranes

    Directory of Open Access Journals (Sweden)

    Medina Andria P

    2012-01-01

    Full Text Available Abstract Background Hyaluronan (HA is made at the plasma membrane and secreted into the extracellular medium or matrix by phospolipid-dependent hyaluronan synthase (HAS, which is active as a monomer. Since the mechanism by which HA is translocated across membranes is still unresolved, we assessed the presence of an intraprotein pore within HAS by adding purified Streptococcus equisimilis HAS (SeHAS to liposomes preloaded with the fluorophore Cascade Blue (CB. Results CB translocation (efflux was not observed with mock-purified material from empty vector control E. coli membranes, but was induced by SeHAS, purified from membranes, in a time- and dose-dependent manner. CB efflux was eliminated or greatly reduced when purified SeHAS was first treated under conditions that inhibit enzyme activity: heating, oxidization or cysteine modification with N-ethylmaleimide. Reduced CB efflux also occurred with SeHAS K48E or K48F mutants, in which alteration of K48 within membrane domain 2 causes decreased activity and HA product size. The above results used liposomes containing bovine cardiolipin (BCL. An earlier study testing many synthetic lipids found that the best activating lipid for SeHAS is tetraoleoyl cardiolipin (TO-CL and that, in contrast, tetramyristoyl cardiolipin (TM-CL is an inactivating lipid (Weigel et al, J. Biol. Chem. 281, 36542, 2006. Consistent with the effects of these CL species on SeHAS activity, CB efflux was more than 2-fold greater in liposomes made with TO-CL compared to TM-CL. Conclusions The results indicate the presence of an intraprotein pore in HAS and support a model in which HA is translocated to the exterior by HAS itself.

  10. Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium*

    Science.gov (United States)

    Hill, David R.; Rho, Hyunjin K.; Kessler, Sean P.; Amin, Ripal; Homer, Craig R.; McDonald, Christine; Cowman, Mary K.; de la Motte, Carol A.

    2013-01-01

    Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179

  11. Effect of depletion of interstitial hyaluronan on hydraulic conductance in rabbit knee synovium

    Science.gov (United States)

    Coleman, P J; Scott, D; Abiona, A; Ashhurst, D E; Mason, R M; Levick, J R

    1998-01-01

    The hydraulic resistance of the synovial lining to fluid outflow from a joint cavity () is important for the retention of intra-articular lubricant. The resistance has been attributed in part to extracellular glycosaminoglycans, including hyaluronan and chondroitin sulphates. Increased permeability in joints infused with testicular hyaluronidase, which digests both chondroitin sulphates and hyaluronan, supports this view. In this study the importance of interstitial hyaluronan per se was assessed using leech and Streptomyces hyaluronidases, which degrade only hyaluronan. Ringer solution was infused into the knee joint cavity of anaesthetized rabbits for 30 min, with or without hyaluronidase, after which intra-articular pressure (Pj) was raised and the relation between pressure and outflow determined. Treatment with Streptomyces, leech or testicular hyaluronidases increased the fluid escape rates by similar factors, namely 4- to 6-fold. After Streptomyces hyaluronidase treatment the slope d/dPj, which at low pressures represents synovial hydraulic conductance, increased from a control of 0.90 ± 0.20 μl min−1 cmH2O−1 (mean ± s.e.m., n = 6) to 4.52 ± 0.70 μl min−1 cmH2O−1. The slope d/dPj increased to a similar level after testicular hyaluronidase, namely to 4.14 ± 1.06 μl min−1 cmH2O−1 (control, 0.54 ± 0.24 μl min−1 cmH2O−1). Streptomyces and leech hyaluronidases were as effective as testicular hyaluronidase (no statistically significant differences) despite differences in substrate specificity. It was shown using histochemical and immunohistochemical techniques that hyaluronan was removed from the synovium by leech, Streptomyces and testicular hyaluronidases. The binding of antibodies 2-B-6 and 3-B-3 showed that the core proteins of the chondroitin sulphate proteoglycans remained intact after treatment with hyaluronidases, and the binding of 5-D-4 showed that keratan sulphate was unaffected. An azocasein digestion assay confirmed that the

  12. Modulation of Hyaluronan Synthesis by the Interaction between Mesenchymal Stem Cells and Osteoarthritic Chondrocytes

    Directory of Open Access Journals (Sweden)

    Eliane Antonioli

    2015-01-01

    Full Text Available Bone marrow mesenchymal stem cells (BM-MSCs are considered a good source for cellular therapy in cartilage repair. But, their potential to repair the extracellular matrix, in an osteoarthritic environment, is still controversial. In osteoarthritis (OA, anti-inflammatory action and extracellular matrix production are important steps for cartilage healing. This study examined the interaction of BM-MSC and OA-chondrocyte on the production of hyaluronan and inflammatory cytokines in a Transwell system. We compared cocultured BM-MSCs and OA-chondrocytes with the individually cultured controls (monocultures. There was a decrease in BM-MSCs cell count in coculture with OA-chondrocytes when compared to BM-MSCs alone. In monoculture, BM-MSCs produced higher amounts of hyaluronan than OA-chondrocytes and coculture of BM-MSCs with OA-chondrocytes increased hyaluronan production per cell. Hyaluronan synthase-1 mRNA expression was upregulated in BM-MSCs after coculture with OA-chondrocytes, whereas hyaluronidase-1 was downregulated. After coculture, lower IL-6 levels were detected in BM-MSCs compared with OA-chondrocytes. These results indicate that, in response to coculture with OA-chondrocytes, BM-MSCs change their behavior by increasing production of hyaluronan and decreasing inflammatory cytokines. Our results indicate that BM-MSCs per se could be a potential tool for OA regenerative therapy, exerting short-term effects on the local microenvironment even when cell:cell contact is not occurring.

  13. The Ethics of Exploitation

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    Paul McLaughlin

    2008-11-01

    Full Text Available Philosophical inquiry into exploitation has two major deficiencies to date: it assumes that exploitation is wrong by definition; and it pays too much attention to the Marxian account of exploitation. Two senses of exploitation should be distinguished: the ‘moral’ or pejorative sense and the ‘non-moral’ or ‘non-prejudicial’ sense. By demonstrating the conceptual inadequacy of exploitation as defined in the first sense, and by defining exploitation adequately in the latter sense, we seek to demonstrate the moral complexity of exploitation. We contend, moreover, that moral evaluation of exploitation is only possible once we abandon a strictly Marxian framework and attempt, in the long run, to develop an integral ethic along Godwinian lines.

  14. Hyaluronan synthesis in cultured tobacco cells (BY-2) expressing a chlorovirus enzyme: cytological studies.

    Science.gov (United States)

    Rakkhumkaew, Numfon; Shibatani, Shigeo; Kawasaki, Takeru; Fujie, Makoto; Yamada, Takashi

    2013-04-01

    Extraction of hyaluronan from animals or microbial fermentation has risks including contamination with pathogens and microbial toxins. In this work, tobacco cultured-cells (BY-2) were successfully transformed with a chloroviral hyaluronan synthase (cvHAS) gene to produce hyaluronan. Cytological studies revealed accumulation of HA on the cells, and also in subcellular fractions (protoplasts, miniplasts, vacuoplasts, and vacuoles). Transgenic BY-2 cells harboring a vSPO-cvHAS construct containing the vacuolar targeting signal of sporamin connected to the N-terminus of cvHAS accumulated significant amounts of HA in vacuoles. These results suggested that cvHAS successfully functions on the vacuolar membrane and synthesizes/transports HA into vacuoles. Efficient synthesis of HA using this system provides a new method for practical production of HA. Copyright © 2012 Wiley Periodicals, Inc.

  15. Hyaluronan Immobilized Polyurethane as a Blood Contacting Material

    Directory of Open Access Journals (Sweden)

    Feirong Gong

    2010-01-01

    Full Text Available Hyaluronan (hyaluronic acid, HA was immobilized onto the surface of amino-functionalized polyurethane films with the goal of obtaining a novel kind of biomaterial which had the potential in blood-contacting applications. The amino-functionalized polyurethane was prepared by synthesized acidic polyurethane whose pendant carboxyl groups were treated with an excess amount of 1,3-diaminopropane in the presence of N,N-carbonyldiimidazole (CDI. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR, Raman spectroscopy (RS, scanning electron microscopy (SEM, and water contact angle measurement were used to confirm the surface changes at each step of treatment, both in morphologies and chemical compositions. APTT and PT results showed that HA immobilization could prolong the blood coagulation time, thus HA-immobilized polyurethane (PU-HA exhibited improved blood compatibility. Cytotoxicity analysis showed that the PU-HA films synthesized in this study were cytocompatible and could support human vein endothelial cells (HUVECs adhesion and proliferation.

  16. Modulation of hyaluronan synthase activity in cellular membrane fractions.

    Science.gov (United States)

    Vigetti, Davide; Genasetti, Anna; Karousou, Evgenia; Viola, Manuela; Clerici, Moira; Bartolini, Barbara; Moretto, Paola; De Luca, Giancarlo; Hascall, Vincent C; Passi, Alberto

    2009-10-30

    Hyaluronan (HA), the only non-sulfated glycosaminoglycan, is involved in morphogenesis, wound healing, inflammation, angiogenesis, and cancer. In mammals, HA is synthesized by three homologous HA synthases, HAS1, HAS2, and HAS3, that polymerize the HA chain using UDP-glucuronic acid and UDP-N-acetylglucosamine as precursors. Since the amount of HA is critical in several pathophysiological conditions, we developed a non-radioactive assay for measuring the activity of HA synthases (HASs) in eukaryotic cells and addressed the question of HAS activity during intracellular protein trafficking. We prepared three cellular fractions: plasma membrane, cytosol (containing membrane proteins mainly from the endoplasmic reticulum and Golgi), and nuclei. After incubation with UDP-sugar precursors, newly synthesized HA was quantified by polyacrylamide gel electrophoresis of fluorophore-labeled saccharides and high performance liquid chromatography. This new method measured HAS activity not only in the plasma membrane fraction but also in the cytosolic membranes. This new technique was used to evaluate the effects of 4-methylumbeliferone, phorbol 12-myristate 13-acetate, interleukin 1beta, platelet-derived growth factor BB, and tunicamycin on HAS activities. We found that HAS activity can be modulated by post-translational modification, such as phosphorylation and N-glycosylation. Interestingly, we detected a significant increase in HAS activity in the cytosolic membrane fraction after tunicamycin treatment. Since this compound is known to induce HA cable structures, this result links HAS activity alteration with the capability of the cell to promote HA cable formation.

  17. Cervical hyaluronan biology in pregnancy, parturition and preterm birth.

    Science.gov (United States)

    Mahendroo, Mala

    2018-03-03

    Cervical hyaluronan (HA) synthesis is robustly induced in late pregnancy in numerous species including women and mice. Recent evidence highlights the diverse and dynamic functions of HA in cervical biology that stem from its expression in the cervical stroma, epithelia and immune cells, changes in HA molecular weight and cell specific expression of HA binding partners. Mice deficient in HA in the lower reproductive tract confirm a structural role of HA to increase spacing and disorganization of fibrillar collagen, though this function is not critical for pregnancy and parturition. In addition, cervical HA depletion via targeted deletion of HA synthase genes, disrupts cell signaling required for the differentiation of epithelia and their mucosal and junctional barrier, resulting in increased susceptibility to ascending infection-mediated preterm birth. Finally the generation of HA disaccharides by bacterial hyaluronidases as made by Group B streptococcus can ligate toll like receptors TLR2/4 thus preventing appropriate inflammatory responses as needed to fight ascending infection and preterm birth. This review summarizes our current understanding of HA's novel and unique roles in cervical remodeling in the process of birth. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  18. Chromosomal localization of the human and mouse hyaluronan synthase genes

    Energy Technology Data Exchange (ETDEWEB)

    Spicer, A.P.; McDonald, J.A. [Mayo Clinic Scottsdale, AZ (United States); Seldin, M.F. [Univ. of California Davis, CA (United States)] [and others

    1997-05-01

    We have recently identified a new vertebrate gene family encoding putative hyaluronan (HA) synthases. Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse. All three genes encode predicted plasma membrane proteins with multiple transmembrane domains and approximately 25% amino acid sequence identity to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any one HAS gene in transfected mammalian cells leads to high levels of HA biosynthesis. We now report the chromosomal localization of the three HAS genes in human and in mouse. The genes localized to three different positions within both the human and the mouse genomes. HAS1 was localized to the human chromosome 19q13.3-q13.4 boundary and Has1 to mouse Chr 17. HAS2 was localized to human chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces the recently reported relationship between a small region of human chromosome 19q and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical region delineated for the Langer-Giedion syndrome and can thus be excluded as a candidate gene for this genetic syndrome. 33 refs., 2 figs.

  19. IL-10 Induction from Implants Delivering Pancreatic Islets and Hyaluronan

    Directory of Open Access Journals (Sweden)

    Paul L. Bollyky

    2013-01-01

    Full Text Available Local induction of pro-tolerogenic cytokines, such as IL-10, is an appealing strategy to help facilitate transplantation of islets and other tissues. Here, we describe a pair of implantable devices that capitalize on our recent finding that hyaluronan (HA promotes IL-10 production by activated T cells. The first device is an injectable hydrogel made of crosslinked HA and heparan sulfate loaded with anti-CD3/anti-CD28 antibodies and IL-2. T cells embedded within this hydrogel prior to polymerization go on to produce IL-10 in vivo. The second device is a bioengineered implant consisting of a polyvinyl alcohol sponge scaffold, supportive collagen hydrogel, and alginate spheres mediating sustained release of HA in fluid form. Pancreatic islets that expressed ovalbumin (OVA antigen were implanted within this device for 14 days into immunodeficient mice that received OVA-specific DO.11.10 T cells and a subsequent immunization with OVA peptide. Splenocytes harvested from these mice produced IL-10 upon re-challenge with OVA or anti-CD3 antibodies. Both of these devices represent model systems that will be used, in future studies, to further evaluate IL-10 induction by HA, with the objective of improving the survival and function of transplanted islets in the setting of autoimmune (type 1 diabetes.

  20. Regulation of Hyaluronan Synthesis in Vascular Diseases and Diabetes

    Directory of Open Access Journals (Sweden)

    Paola Moretto

    2015-01-01

    Full Text Available Cell microenvironment has a critical role determining cell fate and modulating cell responses to injuries. Hyaluronan (HA is a ubiquitous extracellular matrix glycosaminoglycan that can be considered a signaling molecule. In fact, interacting with several cell surface receptors can deeply shape cell behavior. In vascular biology, HA triggers smooth muscle cells (SMCs dedifferentiation which contributes to vessel wall thickening. Furthermore, HA is able to modulate inflammation by altering the adhesive properties of endothelial cells. In hyperglycemic conditions, HA accumulates in vessels and can contribute to the diabetic complications at micro- and macrovasculature. Due to the pivotal role in favoring atherogenesis and neointima formation after injuries, HA could be a new target for cardiovascular pathologies. This review will focus on the recent findings regarding the regulation of HA synthesis in human vascular SMCs. In particular, the effects of the intracellular HA substrates availability, adenosine monophosphate-activated protein kinase (AMPK, and protein O-GlcNAcylation on the main HA synthetic enzyme (i.e., HAS2 will be discussed.

  1. Hyaluronan Protects Bovine Articular Chondrocytes against Cell Death Induced by Bupivacaine under Supraphysiologic Temperatures

    Science.gov (United States)

    Liu, Sen; Zhang, Qing-Song; Hester, William; O’Brien, Michael J.; Savoie, Felix H.; You, Zongbing

    2013-01-01

    Background Bupivacaine and supraphysiologic temperature can independently reduce cell viability of articular chondrocytes. In combination these two deleterious factors could further impair cell viability. Hypothesis Hyaluronan may protect chondrocytes from death induced by bupivacaine at supraphysiologic temperatures. Study Design Controlled laboratory study. Methods Bovine articular chondrocytes were treated with hyaluronan at physiologic (37°C) and supraphysiologic temperatures (45°C and 50°C) for one hour, and then exposed to bupivacaine for one hour at room temperature. Cell viability was assessed at three time points: immediately after treatment, six hours later, and twenty-four hours later using flow cytometry and fluorescence microscopy. The effects of hyaluronan on the levels of sulfated glycosaminoglycan in the chondrocytes were determined using Alcian blue staining. Results (1) Bupivacaine alone did not induce noticeable chondrocyte death at 37°C; (2) bupivacaine and temperature synergistically increased chondrocyte death, that is, when the chondrocytes were conditioned to 45°C and 50°C, 0.25% and 0.5% bupivacaine increased the cell death rate by 131% to 383% in comparison to the phosphate-buffered saline control group; and, (3) addition of hyaluronan reduced chondrocyte death rates to approximately 14% and 25% at 45°C and 50°C, respectively. Hyaluronan’s protective effects were still observed at six and twenty-four hours after bupivacaine treatment at 45°C. However, at 50°C, hyaluronan delayed but did not prevent the cell death caused by bupivacaine. One-hour treatment with hyaluronan significantly increased sulfated glycosaminoglycan levels in the chondrocytes. Conclusions Bupivacaine and supraphysiologic temperature synergistically increase chondrocyte death and hyaluronan may protect articular chondrocytes from death caused by bupivacaine. Clinical Relevance This study provides a rationale to perform pre-clinical and clinical studies to

  2. Localization of hyaluronan with a hyaluronan-specific hyaluronic acid binding protein in the placenta in pre-eclampsia.

    Science.gov (United States)

    Matejevic, D; Neudeck, H; Graf, R; Müller, T; Dietl, J

    2001-01-01

    Hyaluronan (HA), a high molecular weight polysaccharide, is a major component of connective tissue and is thus present in the extracellular matrix of most tissues. Increased serum concentrations have been reported in association with pre-eclampsia and liver malfunction, amongst other disorders. We have performed histochemical investigations with a HA-specific hyaluronic acid binding protein in placentas from uncomplicated pregnancies and from patients with pre-eclampsia. Staining for HA was found in the stroma and blood vessel walls of stem villi in all the placentas investigated. The syncytiotrophoblast and cytotrophoblast cells usually remained unstained. In addition, reactivity for HA was found within and on the surface of intervillous and perivillous fibrinoid deposits. Since fibrinoid deposits are increased in pre-eclampsia, our findings suggest that the increased HA serum concentrations in cases of pre-eclampsia could result from the stroma of the infarcted villi and from the fibrinoid deposits. HA may reach the maternal blood through fibrinoid gaps. Copyright 2001 S. Karger AG, Basel

  3. Exploitability Assessment with TEASER

    Science.gov (United States)

    2017-05-01

    for architectural neutral taint analysis on top of LLVM and QEMU. POC Proof of Concept : Demonstration of an exploit on a program . vii RCE Remote Code...bug with a Proof of Concept (POC), or input to a program demonstrating the ability to use a bug to exploit the application, to demonstrate the...often leads to either computationally difficult constraint solving problems or taint explosion. Given the computational difficulty of exploit

  4. Anthropology of sexual exploitation

    Directory of Open Access Journals (Sweden)

    Lalić Velibor

    2009-01-01

    Full Text Available In this paper, the authors observe sexual exploitation from an anthropological perspective. They analyze the rational, ethical, emotional and mythological dimensions of human sexuality. Consequently, after setting the phenomenon in a social and historical context, sexual exploitation is closely observed in the contemporary age. Based on thoughts of relevant thinkers, they make the conclusion that the elimination of sexual exploitation is not an utterly legal issue, but political and economical issues as well. Namely, legal norms are not sufficient to overcome sexual exploitation, but, political and economical relationships in contemporary societies, which will be based on sincere equal opportunities must be established.

  5. Hyaluronan degrading silica nanoparticles for skin cancer therapy

    Science.gov (United States)

    Scodeller, P.; Catalano, P. N.; Salguero, N.; Duran, H.; Wolosiuk, A.; Soler-Illia, G. J. A. A.

    2013-09-01

    We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human melanoma bearing mice and compared with the non-immobilized enzyme, on the basis of equal enzymatic activity. Alcian Blue staining of A375 tumors indicated large overexpression of hyaluronan. At the end of the experiment, tumor volume reduction with SiNP-immobilized Hyal was significantly enhanced compared to non-immobilized Hyal. Field emission scanning electron microscopy (FE-SEM) images together with energy dispersive X-ray spectroscopy (EDS) spectra confirmed the presence of SiNP on the tumor. We mean a proof of concept: this extracellular matrix (ECM) degrading enzyme, immobilized on SiNP, is a more effective local adjuvant of cancer drugs than the non-immobilized enzyme. This could prove useful in future therapies using other or a combination of ECM degrading enzymes.We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human

  6. Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery.

    Science.gov (United States)

    Woodman, Jessica L; Suh, Min Sung; Zhang, Jianxing; Kondaveeti, Yuvabharath; Burgess, Diane J; White, Bruce A; Prestwich, Glenn D; Kuhn, Liisa T

    2015-01-01

    Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units. These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44(+)/CD24(-/low) human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP. nCaP(CMHA)CDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a -43 mV zeta potential. nCaP(CMHA)CDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaP(CMHA)CDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaP(CMHA-AF488) was taken up by CD44(+)/CD24(-) BT-474EMT breast cancer cells within 18 hours. nCaP(CMHA)CDDP was as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaP(CMHA)CDDP. This was likely due to a lack of distribution of nCaP(CMHA)CDDP throughout the dense tumor tissue that limited drug diffusion.

  7. Hyaluronan in aged collagen matrix increases prostate epithelial cell proliferation

    Science.gov (United States)

    Damodarasamy, Mamatha; Vernon, Robert B.; Chan, Christina K.; Plymate, Stephen R.; Wight, Thomas N.

    2015-01-01

    The extracellular matrix (ECM) of the prostate, which is comprised primarily of collagen, becomes increasingly disorganized with age, a property that may influence the development of hyperplasia and cancer. Collageous ECM extracted from the tails of aged mice exhibits many characteristics of collagen in aged tissues, including the prostate. When polymerized into a 3-dimensional (3D) gel, these collagen extracts can serve as models for the study of specific cell-ECM interactions. In the present study, we examined the behaviors of human prostatic epithelial cell lines representing normal prostate epithelial cells (PEC), benign prostatic hyperplasia (BPH-1), and adenocarcinoma (LNCaP) cultured in contact with 3D gels made from collagen extracts of young and aged mice. We found that proliferation of PEC, BPH-1, and LNCaP cells were all increased by culture on aged collagen gels relative to young collagen gels. In examining age-associated differences in the composition of the collagen extracts, we found that aged and young collagen had a similar amount of several collagen-associated ECM components, but aged collagen had a much greater content of the glycosaminoglycan hyaluronan (HA) than young collagen. The addition of HA (of similar size and concentration to that found in aged collagen extracts) to cells placed in young collagen elicited significantly increased proliferation in BPH-1 cells, but not in PEC or LNCaP cells, relative to controls not exposed to HA. Of note, histochemical analyses of human prostatic tissues showed significantly higher expression of HA in BPH and prostate cancer stroma relative to stroma of normal prostate. Collectively, these results suggest that changes in ECM involving increased levels of HA contribute to the growth of prostatic epithelium with aging. PMID:25124870

  8. Biodistribution imaging of a paclitaxel-hyaluronan bioconjugate

    Energy Technology Data Exchange (ETDEWEB)

    Banzato, Alessandra; Rondina, Maria [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Melendez-Alafort, Laura; Zangoni, Elena; Nadali, Anna [Department of Pharmaceutical Sciences, University of Padua, Padova (Italy); Renier, Davide [Fidia Farmaceutici, Abano Terme (Italy); Moschini, Giuliano [Department of Physics, University of Padua, Padova (Italy); Mazzi, Ulderico [Department of Pharmaceutical Sciences, University of Padua, Padova (Italy); Zanovello, Paola [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Istituto Oncologico Veneto, IOV-IRCCS, Padova (Italy); Rosato, Antonio [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Istituto Oncologico Veneto, IOV-IRCCS, Padova (Italy)], E-mail: antonio.rosato@unipd.it

    2009-07-15

    Introduction: Gamma-ray detectors represent sensitive and noninvasive instruments to evaluate in vivo the metabolic trapping of radiopharmaceuticals. This study aimed to assess the imaging biodistribution of a [{sup 99m}Tc]-radiolabelled new prototype bioconjugate composed of paclitaxel linked to hyaluronan (ONCOFID-P). Methods: A small gamma camera providing high-resolution images was employed. Imaging of biodistribution following intravenous, intraperitoneal, intravesical and oral administration was carried out for a 2-h period in anesthetized mice receiving [{sup 99m}Tc]ONCOFID-P. At the end of the observation time, radioactivity in organs was directly measured. As a control, groups of mice were treated with free [{sup 3}H]paclitaxel given according to the same administration routes, and organ biodistribution of the drug was assessed after 2 h. Results: Intravenous inoculation of [{sup 99m}Tc]ONCOFID-P was followed by a rapid and strong liver uptake. In fact, almost 80% of the imaging signal was detected in this organ 10 min after injection and such value remained constant thereafter, thus indicating that the bioconjugate given through the intravenous route could be well suited to targeting primary or metastatic liver neoplasias. Imaging of the bladder, abdomen and gastrointestinal tract after local administration disclosed that the radiolabelled compound remained confined to the cavities, suggesting a potential regional application for transitional bladder cell carcinomas, ovarian cancers and gastric tumors, respectively. Free [{sup 3}H]paclitaxel biodistribution profoundly differed from that of [{sup 99m}Tc]ONCOFID-P. Conclusions: Conjugation of drugs with polymers results in new chemical entities characterized by a modified biodistribution pattern. Therefore, preclinical studies based on imaging analysis of such new compounds can suggest novel therapeutic applications.

  9. Exploitation and disadvantage

    NARCIS (Netherlands)

    Ferguson, B.

    2016-01-01

    According to some accounts of exploitation, most notably Ruth Sample's (2003) degradation-based account and Robert Goodin's (1987) vulnerability-based account, exploitation occurs when an advantaged party fails to constrain their advantage in light of another's disadvantage, regardless of the cause

  10. EXPLOITATION OF GRANITE BOULDER

    Directory of Open Access Journals (Sweden)

    Ivan Cotman

    1994-12-01

    Full Text Available The processes of forming, petrography, features, properties and exploitation of granite boulders are described. The directional drilling and black powder blasting is the succesful method in exploitation of granite boulders (boulder technology (the paper is published in Croatian.

  11. Force Spectroscopy of Hyaluronan by AFM; From H-bonded Networks Towards Single Chain Behavior

    NARCIS (Netherlands)

    Giannotti, M.I.; Rinaudo, Marguerite; Vancso, Gyula J.

    2007-01-01

    The conformational behavior of hyaluronan (HA) polysaccharide chains in aqueous NaCl solution was characterized directly at the single-molecule level. This comunication reports on one of the first single-chain atomic force microscopy (AFM) experiments performed at variable temperatures,

  12. Effects of ventilation on hyaluronan and protein concentration in pleural liquid of anesthetized and conscious rabbits.

    Science.gov (United States)

    Wang, P M; Lai-Fook, S J

    1998-01-01

    The hypothesis of this study is that pleural lubrication is enhanced by hyaluronan acting as a boundary lubricant in pleural liquid and by pleural filtration as reflected in changes in protein concentration with ventilation. Anesthetized rabbits were injected intravenously with Evans blue dye and ventilated with 100% O2 at either of two levels of ventilation for 6 h. Postmortem values of hyaluronan, total protein, and Evans blue-dyed albumin (EBA) concentrations in pleural liquid were greater at the higher ventilation, consistent with increases in boundary lubrication, pleural membrane permeability, and pleural filtration. To determine whether these effects were caused by hyperoxia or anesthesia, conscious rabbits were ventilated with either 3% CO2 or room air in a box for 6, 12, or 24 h. Similar to the anesthetized rabbits, pleural liquid hyaluronan concentration after 24 h was higher in the conscious rabbits with the hypercapnic-induced greater ventilation. By contrast, the time course of total protein and EBA in pleural liquid was similar in both groups of conscious rabbits, indicating no effect of ventilation on pleural permeability. The increase in pleural liquid hyaluronan concentration might be the result of mesothelial cell stimulation by a ventilation-induced increase in pleural liquid shear stress.

  13. Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

    Directory of Open Access Journals (Sweden)

    Marina Bantzi

    2015-04-01

    Full Text Available In the present work, the synthesis of a hexasaccharide partial sequence of hyaluronan equipped with a terminal azido moiety is reported. This hexasaccharide can be used for the attachment on surfaces by means of click chemistry and after suitable deprotection for biophysical studies.

  14. Hyaluronan hydrogels with a low degree of modification as scaffolds for cartilage engineering.

    Science.gov (United States)

    La Gatta, Annalisa; Ricci, Giulia; Stellavato, Antonietta; Cammarota, Marcella; Filosa, Rosanna; Papa, Agata; D'Agostino, Antonella; Portaccio, Marianna; Delfino, Ines; De Rosa, Mario; Schiraldi, Chiara

    2017-10-01

    In the field of cartilage engineering, continuing efforts have focused on fabricating scaffolds that favor maintenance of the chondrocytic phenotype and matrix formation, in addition to providing a permeable, hydrated, microporous structure and mechanical support. The potential of hyaluronan-based hydrogels has been well established, but the ideal matrix remains to be developed. This study describes the development of hyaluronan sponges-based scaffolds obtained by lysine methyl-ester crosslinking. The reaction conditions are optimized with minimal chemical modifications to obtain materials that closely resemble elements in physiological cellular environments. Three hydrogels with different amounts of crosslinkers were produced that show morphological, water-uptake, mechanical, and stability properties comparable or superior to those of currently available hyaluronan-scaffolds, but with significantly fewer hyaluronan modifications. Primary human chondrocytes cultured with the most promising hydrogel were viable and maintained lineage identity for 3 weeks. They also secreted cartilage-specific matrix proteins. These scaffolds represent promising candidates for cartilage engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Effect of hyaluronan on osteogenic differentiation of porcine bone marrow stromal cells in vitro

    DEFF Research Database (Denmark)

    Zou, Lijin; Zou, Xuenong; Chen, Li

    2007-01-01

    Hyaluronan (HA) plays a predominant role in tissue morphogenesis, cell migration, proliferation, and cell differentiation. The aims of the present study were to investigate whether (i) prolonged presence of high concentration (4.0 mg/mL) 800 KDa HA and (ii) pretreatment with HA can modify osteoge...

  16. Increased Levels of Type I and III Collagen and Hyaluronan in Scleroderma Skin

    DEFF Research Database (Denmark)

    Søndergaard, Klaus; Heickendorff, Lene; L, Risteli

    1997-01-01

    The aminoterminal propeptide of type III procollagen (PIIINP) and the carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were measured in plasma and suction blister fluid from 13 systemic sclerosis patients and 11 healthy volunteers. Suction blisters and skin biopsies were...

  17. Chondroitin sulfate addition to CD44H negatively regulates hyaluronan binding

    International Nuclear Information System (INIS)

    Ruffell, Brian; Johnson, Pauline

    2005-01-01

    CD44 is a widely expressed cell adhesion molecule that binds hyaluronan, an extracellular matrix glycosaminoglycan, in a tightly regulated manner. This regulated interaction has been implicated in inflammation and tumor metastasis. CD44 exists in the standard form, CD44H, or as higher molecular mass isoforms due to alternative splicing. Here, we identify serine 180 in human CD44H as the site of chondroitin sulfate addition and show that lack of chondroitin sulfate addition at this site enhances hyaluronan binding by CD44. A CD44H-immunoglobulin fusion protein expressed in HEK293 cells, and CD44H expressed in murine L fibroblast cells were modified by chondroitin sulfate, as determined by reduced sulfate incorporation after chondroitinase ABC treatment. Mutation of serine 180 or glycine 181 in CD44H reduced chondroitin sulfate addition and increased hyaluronan binding, indicating that serine 180 is the site for chondroitin sulfate addition in CD44H and that this negatively regulates hyaluronan binding

  18. Poverty-Exploitation-Alienation.

    Science.gov (United States)

    Bronfenbrenner, Martin

    1980-01-01

    Illustrates how knowledge derived from the discipline of economics can be used to help shed light on social problems such as poverty, exploitation, and alienation, and can help decision makers form policy to minimize these and similar problems. (DB)

  19. Nebulized hyaluronan ameliorates lung inflammation in cystic fibrosis mice.

    Science.gov (United States)

    Gavina, Manuela; Luciani, Alessandro; Villella, Valeria R; Esposito, Speranza; Ferrari, Eleonora; Bressani, Ilaria; Casale, Alida; Bruscia, Emanuela M; Maiuri, Luigi; Raia, Valeria

    2013-08-01

    Chronic lung inflammation with increased susceptibility to bacterial infections cause much of the morbidity and mortality in patients with cystic fibrosis (CF), the most common severe, autosomal recessively inherited disease in the Caucasian population. Exogenous inhaled hyaluronan (HA) can exert a protective effect against injury and beneficial effects of HA have been shown in experimental models of chronic respiratory diseases. Our objective was to examine whether exogenous administration of nebulized HA might interfere with lung inflammation in CF. F508del homozygous mice (Cftr(F508del) ) and transgenic mice overexpressing the ENaC channel β-subunit (Scnn1b-Tg) were treated with nebulized HA (0.5 mg/mouse/day for 7 days). Tumor necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), myeloperoxidase (MPO) levels, and macrophage infiltration were assessed on lung tissues. IB3-1 and CFBE41o-epithelial cell lines were cultured with HA (24 hr, 100 µg/ml) and Reactive Oxygen Species (ROS), Tissue Transglutaminase (TG2) SUMOylation and Peroxisome Proliferator Activated Receptor gamma (PPARγ) and phospho-p42/p44 levels were measured by dichlorodihydrofluorescein assay, or fluorescence resonance energy transfer (FRET) microscopy or immunoblots. Nebulized HA reduced TNFα expression (P < 0.005); TNFα, MIP-2, and MPO protein levels (P < 0.05); MPO activity (P < 0.05); and CD68+ cells counts (P < 0.005) in lung tissues of Cftr(F508del) and Scnn1b-Tg mice, compared with saline-treated mice. HA reduced ROS, TG2 SUMOylation, TG2 activity, phospho-p42-44, and increased PPARγ protein in both IB3-1 and CFBE41o cells (P < 0.05). Nebulized HA is effective in controlling inflammation in vivo in mice CF airways and in vitro in human airway epithelial cells. We provide the proof of concept for the use of inhaled HA as a potential anti-inflammatory drug in CF therapy. Copyright © 2012 Wiley Periodicals, Inc.

  20. Exploiting VM/XA

    International Nuclear Information System (INIS)

    Boeheim, C.

    1990-03-01

    The Stanford Linear Accelerator Center has recently completed a conversion to IBM's VM/XA SP Release 2 operating system. The primary physics application had been constrained by the previous 16 megabyte memory limit. Work is underway to enable this application to exploit the new features of VM/XA. This paper presents a brief tutorial on how to convert an application to exploit VM/XA and discusses some of the SLAC experiences in doing so. 13 figs

  1. Hybrid Complexes of High and Low Molecular Weight Hyaluronans Highly Enhance HASCs Differentiation: Implication for Facial Bioremodelling

    Directory of Open Access Journals (Sweden)

    Antonietta Stellavato

    2017-11-01

    Full Text Available Background/Aims: Adipose-derived Stem Cells (ASCs are used in Regenerative Medicine, including fat grafting, recovery from local tissue ischemia and scar remodeling. The aim of this study was to evaluate hyaluronan based gel effects on ASCs differentiation and proliferation. Methods: Comparative analyses using high (H and low (L molecular weight hyaluronans (HA, hyaluronan hybrid cooperative complexes (HCCs, and high and medium cross-linked hyaluronan based dermal fillers were performed. Human ASCs were characterized by flow cytometry using CD90, CD34, CD105, CD29, CD31, CD45 and CD14 markers. Then, cells were treated for 7, 14 and 21 days with hyaluronans. Adipogenic differentiation was evaluated using Oil red-O staining and expression of leptin, PPAR-γ, LPL and adiponectin using qRT-PCR. Adiponectin was analyzed by immunofluorescence, PPAR-γ and adiponectin were analyzed using western blotting. ELISA assays for adiponectin and leptin were performed. Results: HCCs highly affected ASCs differentiation by up-regulating adipogenic genes and related proteins, that were also secreted in the culture medium. H-HA and L-HA induced a lower level of ASCs differentiation. Conclusion: HCCs-based formulations clearly enhance adipogenic differentiation and proliferation, when compared with linear HA and cross-linked hyaluronans. Injection of HCCs in subdermal fat compartment may recruit and differentiate stem cells in adipocytes, and considerably improving fat tissue renewal.

  2. Advances and advantages of nanomedicine in the pharmacological targeting of hyaluronan-CD44 interactions and signaling in cancer.

    Science.gov (United States)

    Skandalis, Spyros S; Gialeli, Chrisostomi; Theocharis, Achilleas D; Karamanos, Nikos K

    2014-01-01

    Extensive experimental evidence in cell and animal tumor models show that hyaluronan-CD44 interactions are crucial in both malignancy and resistance to cancer therapy. Because of the intimate relationship between the hyaluronan-CD44 system and tumor cell survival and growth, it is an increasingly investigated area for applications to anticancer chemotherapeutics. Interference with the hyaluronan-CD44 interaction by targeting drugs to CD44, targeting drugs to the hyaluronan matrix, or interfering with hyaluronan matrix/tumor cell-associated CD44 interactions is a viable strategy for cancer treatment. Many of these methods can decrease tumor burden in animal models but have yet to show significant clinical utility. Recent advances in nanomedicine have offered new valuable tools for cancer detection, prevention, and treatment. The enhanced permeability and retention effect has served as key rationale for using nanoparticles to treat solid tumors. However, the targeted and uniform delivery of these particles to all regions of tumors in sufficient quantities requires optimization. An ideal nanocarrier should be equipped with selective ligands that are highly or exclusively expressed on target cells and thus endow the carriers with specific targeting capabilities. In this review, we describe how the hyaluronan-CD44 system may provide such an alternative in tumors expressing specific CD44 variants. © 2014 Elsevier Inc. All rights reserved.

  3. Hyaluronan, CD44, and Emmprin Regulate Lactate Efflux and Membrane Localization of Monocarboxylate Transporters in Human Breast Carcinoma Cells

    Science.gov (United States)

    Slomiany, Mark G.; Grass, G. Daniel; Robertson, Angela D.; Yang, Xiao Y.; Maria, Bernard L.; Beeson, Craig; Toole, Bryan P.

    2013-01-01

    Interactions of hyaluronan with CD44 in tumor cells play important cooperative roles in various aspects of malignancy and drug resistance. Emmprin (CD147; basigin)is a cell surface glycoprotein of the immunoglobulin superfamily that is highly up-regulated in malignant cancer cells and stimulates hyaluronan production, as well as several downstream signaling pathways. Emmprin also interacts with various monocarboxylate transporters (MCT). Malignant cancer cells use the glycolytic pathway and require MCTs to efflux lactate that results from glycolysis. Glycolysis and lactate secretion contribute to malignant cell behaviors and drug resistance in tumor cells. In the present study, we find that perturbation of endogenous hyaluronan, using small hyaluronan oligosaccharides, rapidly inhibits lactate efflux from breast carcinoma cells; down-regulation of emmprin, using emmprin small interfering RNA, also results in decreased efflux. In addition, we find that CD44 coimmunoprecipitates with MCT1, MCT4, and emmprin and colocalizes with these proteins at the plasma membrane. Moreover, after treatment of the cells with hyaluronan oligosaccharides, CD44, MCT1, and MCT4 become localized intracellularly whereas emmprin remains at the cell membrane. Together, these data indicate that constitutive interactions among hyaluronan, CD44, and emmprin contribute to regulation of MCT localization and function in the plasma membrane of breast carcinoma cells. PMID:19176383

  4. Post-secretory fate of host defence components in mucus.

    Science.gov (United States)

    Salathe, Matthias; Forteza, Rosanna; Conner, Gregory E

    2002-01-01

    Airway mucus is a complex mixture of secretory products that provide a multifaceted defence against infection. Among many antimicrobial substances, mucus contains a peroxidase identical to milk lactoperoxidase (LPO) that is produced by goblet cells and submucosal glands. Airway secretions contain the substrates for LPO, namely thiocyanate and hydrogen peroxide, at concentrations sufficient for production of the biocidal compound hypothiocyanite, a fact confirmed by us in vitro. In vivo, inhibition of airway LPO in sheep significantly inhibits bacterial clearance, suggesting that the LPO system is a major contributor to host defences. Since secretory products including LPO are believed to be steadily removed by mucociliary clearance, their amount and availability on the surface is thought to be controlled solely by secretion. In contrast to this paradigm, new data suggest that LPO and other substances are retained at the ciliary border of the airway epithelium by binding to surface-associated hyaluronan, thereby providing an apical, fully active enzyme pool. Thus, hyaluronan, secreted from submucosal gland cells, plays a previously unrecognized pivotal role in mucosal host defence by retaining LPO and possibly other substances important for first line host defence at the apical surface 'ready for use' and protected from ciliary clearance.

  5. Adiponectin promotes hyaluronan synthesis along with increases in hyaluronan synthase 2 transcripts through an AMP-activated protein kinase/peroxisome proliferator-activated receptor-α-dependent pathway in human dermal fibroblasts

    International Nuclear Information System (INIS)

    Yamane, Takumi; Kobayashi-Hattori, Kazuo; Oishi, Yuichi

    2011-01-01

    Highlights: ► Adiponectin promotes hyaluronan synthesis along with an increase in HAS2 transcripts. ► Adiponectin also increases the phosphorylation of AMPK. ► A pharmacological activator of AMPK increases mRNA levels of PPARα and HAS2. ► Adiponectin-induced HAS2 mRNA expression is blocked by a PPARα antagonist. ► Adiponectin promotes hyaluronan synthesis via an AMPK/PPARα-dependent pathway. -- Abstract: Although adipocytokines affect the functions of skin, little information is available on the effect of adiponectin on the skin. In this study, we investigated the effect of adiponectin on hyaluronan synthesis and its regulatory mechanisms in human dermal fibroblasts. Adiponectin promoted hyaluronan synthesis along with an increase in the mRNA levels of hyaluronan synthase 2 (HAS2), which plays a primary role in hyaluronan synthesis. Adiponectin also increased the phosphorylation of AMP-activated protein kinase (AMPK). A pharmacological activator of AMPK, 5-aminoimidazole-4-carboxamide-1β-ribofuranoside (AICAR), increased mRNA levels of peroxisome proliferator-activated receptor-α (PPARα), which enhances the expression of HAS2 mRNA. In addition, AICAR increased the mRNA levels of HAS2. Adiponectin-induced HAS2 mRNA expression was blocked by GW6471, a PPARα antagonist, in a concentration-dependent manner. These results show that adiponectin promotes hyaluronan synthesis along with increases in HAS2 transcripts through an AMPK/PPARα-dependent pathway in human dermal fibroblasts. Thus, our study suggests that adiponectin may be beneficial for retaining moisture in the skin, anti-inflammatory activity, and the treatment of a variety of cutaneous diseases.

  6. Dissemination and Exploitation Strategy

    DEFF Research Database (Denmark)

    Badger, Merete; Monaco, Lucio; Fransson, Torsten

    of Technology in Sweden, Politecnico di Torino in Italy, and Eindhoven University of Technology in the Netherlands. The project is partially funded by the European Commission under the 7th Framework Programme (project no. RI-283746). This report describes the final dissemination and exploitation strategy...... for project Virtual Campus Hub. A preliminary dissemination and exploitation plan was setup early in the project as described in the deliverable D6.1 Dissemination strategy paper - preliminary version. The plan has been revised on a monthly basis during the project’s lifecycle in connection with the virtual...

  7. The Biological Role of Hyaluronan-Rich Oocyte-Cumulus Extracellular Matrix in Female Reproduction

    Czech Academy of Sciences Publication Activity Database

    Nagyová, Eva

    2018-01-01

    Roč. 19, č. 1 (2018), č. článku 283. E-ISSN 1422-0067 R&D Projects: GA MŠk EF15_003/0000460 Institutional support: RVO:67985904 Keywords : extracellular matrix * hyaluronan * inter-alpha-trypsin inhibitor Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 3.226, year: 2016

  8. Charged Triazole Cross-Linkers for Hyaluronan-Based Hybrid Hydrogels

    Directory of Open Access Journals (Sweden)

    Maike Martini

    2016-09-01

    Full Text Available Polyelectrolyte hydrogels play an important role in tissue engineering and can be produced from natural polymers, such as the glycosaminoglycan hyaluronan. In order to control charge density and mechanical properties of hyaluronan-based hydrogels, we developed cross-linkers with a neutral or positively charged triazole core with different lengths of spacer arms and two terminal maleimide groups. These cross-linkers react with thiolated hyaluronan in a fast, stoichiometric thio-Michael addition. Introducing a positive charge on the core of the cross-linker enabled us to compare hydrogels with the same interconnectivity, but a different charge density. Positively charged cross-linkers form stiffer hydrogels relatively independent of the size of the cross-linker, whereas neutral cross-linkers only form stable hydrogels at small spacer lengths. These novel cross-linkers provide a platform to tune the hydrogel network charge and thus the mechanical properties of the network. In addition, they might offer a wide range of applications especially in bioprinting for precise design of hydrogels.

  9. The ESA Geohazard Exploitation Platform

    Science.gov (United States)

    Bally, Philippe; Laur, Henri; Mathieu, Pierre-Philippe; Pinto, Salvatore

    2015-04-01

    expanded to address broader objectives of the geohazards community. In particular it is a contribution to the CEOS WG Disasters and its Seismic Hazards Pilot and terrain deformation applications of its Volcano Pilot. The geohazards platform is sourced with elements - data, tools, and processing- relevant to the geohazards theme and related exploitation scenarios. For example, platform provides access to large SAR data collections and services to support SAR Interferometry (InSAR), in particular the Persistent Scatterer Interferometry (PSI) and Small Baseline Subset (SBAS) techniques, to provide precise terrain deformation. The GEP includes data coming from the ENVISAT ASAR and ERS archives, already hosted in the ESA clusters and in ESA's Virtual Archive and further extended to cover the requirements of the CEOS Pilot on Seismic Hazards. The GEP is gradually accessing Sentinel-1A data alongside with EO data from other space agencies with an interest in the geohazard exploitation platform. Further to this, the platform is intended to be available in the framework of the European Plate Observing System (EPOS) initiative, in order to help its users exploit EO data to support solid Earth monitoring and geophysical and geological analysis.

  10. Hacking the art of exploitation

    CERN Document Server

    Erickson, Jon

    2003-01-01

    A comprehensive introduction to the techniques of exploitation and creative problem-solving methods commonly referred to as "hacking," Hacking: The Art of Exploitation is for both technical and non-technical people who are interested in computer security. It shows how hackers exploit programs and write exploits, instead of just how to run other people's exploits. Unlike many so-called hacking books, this book explains the technical aspects of hacking, including stack based overflows, heap based overflows, string exploits, return-into-libc, shellcode, and cryptographic attacks on 802.11b.

  11. Butyrate-Loaded Chitosan/Hyaluronan Nanoparticles: A Suitable Tool for Sustained Inhibition of ROS Release by Activated Neutrophils

    DEFF Research Database (Denmark)

    Sacco, Pasquale; Decleva, Eva; Tentor, Fabio

    2017-01-01

    that butyrate inhibits neutrophil ROS release in a dose and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition...... of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B-NPs appear...

  12. Nanostructured Basaltfiberconcrete Exploitational Characteristics

    Science.gov (United States)

    Saraykina, K. A.; Shamanov, V. A.

    2017-11-01

    The article demonstrates that the mass use of basalt fiber concrete (BFC) is constrained by insufficient study of their durability and serviceability in a variety of environments. This research is aimed at the study of the basalt fiber corrosion processes in the cement stone of BFC, the control of the new products structure formation in order to protect the reinforcing fiber from alkaline destruction and thereby improve the exploitational characteristics of the composite. The research result revealed that the modification of basaltfiber concrete by the dispersion of MWNTs contributes to the directional formation of new products in the cement matrix. The HAM additive in basaltfiberconcrete provides for the binding of portlandite to low-basic calcium hydroaluminosilicates, thus reducing the aggressive effect of the cement environment on the reinforcing fibers properties. The complex modification of BFC with nanostructured additives provides for an increase in its durability and exploitational properties (strength, frost resistance and water resistance) due to basalt fiber protection from alkali corrosion on account of the compacting of the contact zone “basalt fiber - cement stone” and designing of the new products structure and morphology of cement matrix over the fiber surface.

  13. Hyaluronan protection of corneal endothelial cells against extracellular histones after phacoemulsification.

    Science.gov (United States)

    Kawano, Hiroki; Sakamoto, Taiji; Ito, Takashi; Miyata, Kazunori; Hashiguchi, Teruto; Maruyama, Ikuro

    2014-11-01

    To determine the effect of histones on corneal endothelial cells generated during cataract surgery. Kagoshima University Hospital, Kagoshima, Japan. Experimental study. Standard phacoemulsification was performed on enucleated pig eyes. Histones in the anterior segment of the eye were determined by immunohistochemistry. Cultured human corneal endothelial cells were exposed to histones for 18 hours, and cell viability was determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitro-phenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt assay. The concentration of interleukin-6 (IL-6) in the culture medium of human corneal endothelial cells was measured using enzyme-linked immunosorbent assay. The effects of signal inhibitors U0126, SB203580, and SP600125 were evaluated. The protective effect of hyaluronan against histones was evaluated in human corneal endothelial cells with and without hyaluronan. Cellular debris containing histones was observed in the anterior chamber of pig eyes after phacoemulsification. Exposure of human corneal endothelial cells to 50 μg/mL of histones or more led to cytotoxic effects. The IL-6 concentration was significantly increased dose dependently after exposure of human corneal endothelial cells to histones (Phistone-induced IL-6 production was significantly decreased by extracellular signal-regulated kinases 1/2 and p-38 mitogen-activated protein kinase inhibitors (Phistones caused formation of histone aggregates, decreased the cytotoxic effects of the histones, and blocked the increase in IL-6 (PHistones were released extracellularly during phacoemulsification and exposure of human corneal endothelial cells to histones increased the IL-6 secretion. The intraoperative use of hyaluronan may decrease the cytotoxic effects of histones released during cataract surgery. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  14. Cleavage of Hyaluronan and CD44 Adhesion Molecule Regulate Astrocyte Morphology via Rac1 Signalling.

    Directory of Open Access Journals (Sweden)

    Anna Konopka

    Full Text Available Communication of cells with their extracellular environment is crucial to fulfill their function in physiological and pathophysiological conditions. The literature data provide evidence that such a communication is also important in case of astrocytes. Mechanisms that contribute to the interaction between astrocytes and extracellular matrix (ECM proteins are still poorly understood. Hyaluronan is the main component of ECM in the brain, where its major receptor protein CD44 is expressed by a subset of astrocytes. Considering the fact that functions of astrocytes are tightly coupled with changes in their morphology (e.g.: glutamate clearance in the synaptic cleft, migration, astrogliosis, we investigated the influence of hyaluronan cleavage by hyaluronidase, knockdown of CD44 by specific shRNA and CD44 overexpression on astrocyte morphology. Our results show that hyaluronidase treatment, as well as knockdown of CD44, in astrocytes result in a "stellate"-like morphology, whereas overexpression of CD44 causes an increase in cell body size and changes the shape of astrocytes into flattened cells. Moreover, as a dynamic reorganization of the actin cytoskeleton is supposed to be responsible for morphological changes of cells, and this reorganization is controlled by small GTPases of the Rho family, we hypothesized that GTPase Rac1 acts as a downstream effector for hyaluronan and CD44 in astrocytes. We used FRET-based biosensor and a dominant negative mutant of Rac1 to investigate the involvement of Rac1 activity in hyaluronidase- and CD44-dependent morphological changes of astrocytes. Both, hyaluronidase treatment and knockdown of CD44, enhances Rac1 activity while overexpression of CD44 reduces the activity state in astrocytes. Furthermore, morphological changes were blocked by specific inhibition of Rac1 activity. These findings indicate for the first time that regulation of Rac1 activity is responsible for hyaluronidase and CD44-driven morphological

  15. Cleavage of Hyaluronan and CD44 Adhesion Molecule Regulate Astrocyte Morphology via Rac1 Signalling.

    Science.gov (United States)

    Konopka, Anna; Zeug, Andre; Skupien, Anna; Kaza, Beata; Mueller, Franziska; Chwedorowicz, Agnieszka; Ponimaskin, Evgeni; Wilczynski, Grzegorz M; Dzwonek, Joanna

    2016-01-01

    Communication of cells with their extracellular environment is crucial to fulfill their function in physiological and pathophysiological conditions. The literature data provide evidence that such a communication is also important in case of astrocytes. Mechanisms that contribute to the interaction between astrocytes and extracellular matrix (ECM) proteins are still poorly understood. Hyaluronan is the main component of ECM in the brain, where its major receptor protein CD44 is expressed by a subset of astrocytes. Considering the fact that functions of astrocytes are tightly coupled with changes in their morphology (e.g.: glutamate clearance in the synaptic cleft, migration, astrogliosis), we investigated the influence of hyaluronan cleavage by hyaluronidase, knockdown of CD44 by specific shRNA and CD44 overexpression on astrocyte morphology. Our results show that hyaluronidase treatment, as well as knockdown of CD44, in astrocytes result in a "stellate"-like morphology, whereas overexpression of CD44 causes an increase in cell body size and changes the shape of astrocytes into flattened cells. Moreover, as a dynamic reorganization of the actin cytoskeleton is supposed to be responsible for morphological changes of cells, and this reorganization is controlled by small GTPases of the Rho family, we hypothesized that GTPase Rac1 acts as a downstream effector for hyaluronan and CD44 in astrocytes. We used FRET-based biosensor and a dominant negative mutant of Rac1 to investigate the involvement of Rac1 activity in hyaluronidase- and CD44-dependent morphological changes of astrocytes. Both, hyaluronidase treatment and knockdown of CD44, enhances Rac1 activity while overexpression of CD44 reduces the activity state in astrocytes. Furthermore, morphological changes were blocked by specific inhibition of Rac1 activity. These findings indicate for the first time that regulation of Rac1 activity is responsible for hyaluronidase and CD44-driven morphological changes of

  16. Synthesis and Characterization of Rhodamine B-ethylenediamine-hyaluronan Acid as Potential Biological Functional Materials

    Science.gov (United States)

    Li, Y. L.; Wang, W. X.; Wang, Y.; Zhang, W. B.; Gong, H. M.; Liu, M. X.

    2018-05-01

    The purpose of this study is to synthesize and characterize fluorescent polymers, rhodamine B-ethylenediamine-hyaluronan acid (RhB-EA-HA). RhB-EA-HA was successfully synthesized by ester ammonolysis reaction and amidation reaction. Moreover, the structural properties of RhB-EA-HA were characterized by 1H-NMR spectra, UV-vis spectrometry and Fourier transform infrared spectroscopy (FT-IR). RhB-EA-HA can be grafted on the surface of silica nanomaterials, which may be potential biological functional materials for drug delivery system.

  17. Hyaluronan in the neonatal period. An experimental and clinical study in asphyxia and infection

    OpenAIRE

    Østerholt, Helene C. Dale

    2014-01-01

    List of papers. Paper II is removed from the thesis due to publisher restrictions. I. Østerholt HCD, Dannevig I, Wyckoff MH, Liao J, Akgul Y, Ramgopal M, Milja, DS, Cheong N, Longoria C, Mahendroo M, Nakstad B, Saugstad OD and Savani RC Antioxidant protects against increases in low molecular weight hyaluronan and inflammation in asphyxiated newborn pigs resuscitated with 100% oxygen. PLoS One 2012;7(6):e38839 doi:10.1371/journal.pone.0038839 © 2012 Østerholt et al. This is an open-access ...

  18. Exploitation by Economic Necessity

    Directory of Open Access Journals (Sweden)

    Kristian F. Braekkan

    2015-10-01

    Full Text Available This study develops and tests a model that proposes economic necessity moderates the relationship between psychological contract violations (PCVs and organizational commitment and trust in the employing organization among non-unionized manufacturing workers (N = 226. Moderated regression analyses revealed that there was a significant interaction between PCV and economic necessity in predicting both outcomes. Specifically, the findings indicated that individuals experiencing high PCV and high economic necessity did not decrease their organizational commitment like their counterparts who endorsed lower economic necessity. They did, however, experience significantly decreased trust in their employer. The findings suggest that individuals who are forced to sell their labor power and obtain what they need through the market are more likely to continue to be exploited by their employer, as they have no other options than to continue the relationship. The importance of the findings is discussed, and recommendations for future research are provided.

  19. Exploitative Learning by Exporting

    DEFF Research Database (Denmark)

    Golovko, Elena; Lopes Bento, Cindy; Sofka, Wolfgang

    Decisions on entering foreign markets are among the most challenging but also potentially rewarding strategy choices managers can make. In this study, we examine the effect of export entry on the firm investment decisions in two activities associated with learning about new technologies...... and learning about new markets ? R&D investments and marketing investments, in search of novel insights into the content and process underlying learning by exporting. We draw from organizational learning theory for predicting changes in both R&D and marketing investment patterns that accompany firm entry......, it is predominantly the marketing-related investment decisions associated with starting to export that lead to increases in firm productivity. We conclude that learning-by-exporting might be more properly characterized as ?learning about and exploiting new markets? rather than ?learning about new technologies...

  20. Learning Metasploit exploitation and development

    CERN Document Server

    Balapure, Aditya

    2013-01-01

    A practical, hands-on tutorial with step-by-step instructions. The book will follow a smooth and easy-to-follow tutorial approach, covering the essentials and then showing the readers how to write more sophisticated exploits.This book targets exploit developers, vulnerability analysts and researchers, network administrators, and ethical hackers looking to gain advanced knowledge in exploitation development and identifying vulnerabilities. The primary goal is to take readers wishing to get into more advanced exploitation discovery and reaching the next level.Prior experience exploiting basic st

  1. Can Plasma Hyaluronan and Hyaluronidase Be Used As Markers of the Endothelial Glycocalyx State in Patients with Kidney Disease?

    NARCIS (Netherlands)

    Vlahu, Carmen A.; Krediet, Raymond T.

    2015-01-01

    Hyaluronan (HA) is widely spread in the body and is an important component of the extracellular matrix, including the endothelial glycocalyx (EG). Essential for its vasculoprotective function, HA is involved in vascular permeability and many other processes. In patients with kidney disease, plasma

  2. A hyaluronan-based nerve guide : in vitro cytotoxicity, subcutaneous tissue reactions, and degradation in the rat

    NARCIS (Netherlands)

    Jansen, K; van Wachem, PB; Nicolai, JPA; de Leij, LFMH; van Luyn, MJA; van der Werf, J.F.A.

    We investigated possible cytotoxic effects, biocompatibility, and degradation of a hyaluronan-based conduit for peripheral nerve repair. We subjected the conduits to an in vitro fibroblast cytotoxicity test and concluded that the conduits were not cytotoxic. Subsequently, we implanted the conduits

  3. Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer.

    Science.gov (United States)

    Pályi-Krekk, Zsuzsanna; Barok, Márk; Isola, Jorma; Tammi, Markku; Szöllosi, János; Nagy, Peter

    2007-11-01

    Although trastuzumab, a recombinant humanised anti-ErbB2 antibody, is widely used in the treatment of breast cancer, neither its mechanism of action, nor the factors leading to resistance are fully understood. We have previously shown that antibody-dependent cellular cytotoxicity is pivotal in the in vivo effect of trastuzumab against JIMT-1, a cell line showing in vitro resistance to the antibody, and suggested that masking of the trastuzumab-binding epitope by MUC-4, a cell surface mucin, took place. Here, we further explored the role of masking of ErbB2 in connection with CD44 expression and synthesis of its ligand, hyaluronan. We show that high expression of CD44 observed in JIMT-1 cells correlates with ErbB2 downregulation in vivo, while siRNA-mediated inhibition of CD44 expression leads to decreased rate of trastuzumab internalisation and low cell proliferation in vitro. An inhibitor of hyaluronan synthesis, 4-methylumbelliferon (4-MU) significantly reduced the hyaluronan level of JIMT-1 cells both in vivo and in vitro leading to enhanced binding of trastuzumab to ErbB2 and increased ErbB2 down-regulation. Furthermore, the inhibitory effect of trastuzumab on the growth of JIMT-1 xenografts was significantly increased by 4-MU treatment. Our results point to the importance of the CD44-hyaluronan pathway in the escape of tumour cells from receptor-oriented therapy.

  4. EFFECTS OF HYALURONAN ON THREE-DIMENSIONAL MICROARCHITECTURE OF SUBCHONDRAL BONE TISSUES IN GUINEA PIG PRIMARY OSTEOARTHROSIS

    DEFF Research Database (Denmark)

    Ding, Ming

    Introduction: It is not known whether hyaluronan (HA) has any effect on the underlying subchondral bone tissues. This study was to investigate the effects of high molecular weight HA (1.5x106 Daltons) intra-articular injection on subchondral bone tissues. Methods: Fifty-six male guinea pigs (6...

  5. Survival of cord blood haematopoietic stem cells in a hyaluronan hydrogel for ex vivo biomimicry.

    Science.gov (United States)

    Demange, Elise; Kassim, Yusra; Petit, Cyrille; Buquet, Catherine; Dulong, Virginie; Cerf, Didier Le; Buchonnet, Gérard; Vannier, Jean-Pierre

    2013-11-01

    Haematopoietic stem cells (HSCs) and haematopoietic progenitor cells (HPCs) grow in a specified niche in close association with the microenvironment, the so-called 'haematopoietic niche'. Scaffolds have been introduced to overcome the liquid culture limitations, mimicking the presence of the extracellular matrix (ECM). In the present study the hyaluronic acid scaffold, already developed in the laboratory, has been used for the first time to maintain long-term cultures of CD34⁺ haematopoietic cells obtained from human cord blood. One parameter investigated was the impact on ex vivo survival of CD34⁺ cord blood cells (CBCs) on the hyaluronic acid surface, immobilized with peptides containing the RGD motif. This peptide was conjugated by coating the hyaluronan hydrogel and cultured in serum-free liquid phase complemented with stem cell factor (SCF), a commonly indispensable cytokine for haematopoiesis. Our work demonstrated that these hyaluronan hydrogels were superior to traditional liquid cultures by maintaining and expanding the HPCs without the need for additional cytokines, and a colonization of 280-fold increment in the hydrogel compared with liquid culture after 28 days of ex vivo expansion. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Hyaluronan functionalizing QDs as turn-on fluorescent probe for targeted recognition CD44 receptor

    Science.gov (United States)

    Zhou, Shang; Huo, Danqun; Hou, Changjun; Yang, Mei; Fa, Huanbao

    2017-09-01

    The recognition of tumor markers in living cancer cells has attracted increasing interest. In the present study, the turn-on fluorescence probe was designed based on the fluorescence of thiolated chitosan-coated CdTe QDs (CdTe/TCS QDs) quenched by hyaluronan, which could provide the low background signal for sensitive cellular imaging. This system is expected to offer specific recognition of CD44 receptor over other substances owing to the specific affinity of hyaluronan and CD44 receptor ( 8-9 kcal/mol). The probe is stable in aqueous and has little toxicity to living cells; thus, it can be utilized for targeted cancer cell imaging. The living lung cancer cell imaging experiments further demonstrate its value in recognizing cell-surface CD44 receptor with turn-on mode. In addition, the probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. And, the western blot test further confirmed that the expression level of the CD44 receptor in lung cancer cells is different. Therefore, this probe may be potentially applied in recognizing lung cancer cells with higher contrast and sensitivity and provide new tools for cancer prognosis and therapy. [Figure not available: see fulltext.

  7. Quantification and characterization of enzymatically produced hyaluronan with fluorophore-assisted carbohydrate electrophoresis.

    Science.gov (United States)

    Kooy, Floor K; Ma, Muyuan; Beeftink, Hendrik H; Eggink, Gerrit; Tramper, Johannes; Boeriu, Carmen G

    2009-01-15

    Hyaluronan (HA) is a polysaccharide with high-potential medical applications, depending on the chain length and the chain length distribution. Special interest goes to homogeneous HA oligosaccharides, which can be enzymatically produced using Pasteurella multocida hyaluronan synthase (PmHAS). We have developed a sensitive, simple, and fast method, based on fluorophore-assisted carbohydrate electrophoresis (FACE), for characterization and quantification of polymerization products. A chromatographic pure fluorescent template was synthesized from HA tetrasaccharide (HA4) and 2-aminobenzoic acid. HA4-fluor and HA4 were used as template for PmHAS-mediated polymerization of nucleotide sugars. All products, fluorescent and nonfluorescent, were analyzed with gel electrophoresis and quantified using lane densitometry. Comparison of HA4- and HA4-fluor-derived polymers showed that the fluorophore did not negatively influence the PmHAS-mediated polymerization. Only even-numbered oligosaccharide products were observed using HA4-fluor or HA4 as template. The fluorophore intensity was linearly related to its concentration, and the limit of detection was determined to be 7.4pmol per product band. With this assay, we can now differentiate oligosaccharides of size range DP2 (degree of polymerization 2) to approximately DP400, monitor the progress of polymerization reactions, and measure subtle differences in polymerization rate. Quantifying polymerization products enables us to study the influence of experimental conditions on HA synthesis.

  8. Self-reinforcement and protein sustained delivery of hyaluronan hydrogel by tailoring a dually cross-linked network

    International Nuclear Information System (INIS)

    Luo, Chunhong; Xu, Guoguang; Wang, Xinghui; Tu, Mei; Zeng, Rong; Rong, Jianhua; Zhao, Jianhao

    2015-01-01

    A series of self-reinforcing hyaluronan hydrogels were developed to improve mechanical properties and protein sustained delivery thanks to a dually cross-linked network. Hyaluronan gel particles (HGPs, 1–5 μm in diameter) with different cross-linking densities, i.e. HGPs-1.5, HGPs-3 and HGPs-15, were prepared in an inverse emulsion system and used as the reinforcing phase after glycidyl methacrylation, while glycidyl methacrylated hyaluronan with a substitution degree of 45.2% was synthesized as the matrix phase. These two phases were cross-linked under ultraviolet irradiation to form self-reinforcing hyaluronan hydrogels (srHAs) that showed typical cross-linked structure of HGPs connecting the matrix phase by cross-section observation. In comparison to hyaluronan bulk gels and their blends with HGPs, srHAs distinctly enhanced the mechanical properties and BSA long-term sustained delivery, especially srHA-1.5 showed the highest compressive modulus of 220 ± 15 kPa and the slowest BSA delivery (67% release at 14 d). The 3T3 fibroblast cell culture showed that all the srHAs had no cytotoxicity. - Highlights: • New self-reinforcing HA hydrogels with a dually cross-linked network were developed. • Self-reinforcing HA hydrogels greatly enhanced the mechanical properties. • Self-reinforcing HA hydrogels prolonged the sustained delivery of BSA. • The self-reinforcing mechanism and BSA diffusion mechanism were discussed. • Self-reinforcing HA hydrogels had no cytotoxicity to 3T3 fibroblast cells

  9. The effect of different doses of hyaluronan on sperm morphology, motility, vitality and fertilization capability in mouse

    Directory of Open Access Journals (Sweden)

    S. Sayadi

    2006-07-01

    Full Text Available Background: Hyaluronan has an important role on the permeability and motility of sperm and the interaction of gametes and these can play a considerable role on the fertility rate. Therefore, in this study, we assessed the effect of different doses of hyaluronan on the morphology, motility, vitality and fertility rate of mice. Methods: We used 40 mice (6-8 week in this study which twenty of them were male and the rest were female. The sperm of each male mouse were divided into four groups. The group 1 (control: They were maintained in RPMI media without any hyaluronan supplementation for 2 hour. Hyaluronan with the doses of 750, 1000 and 1250 µg/ml were added into RPMI media in groups 2, 3 and 4, respectively. After 2 hour. incubation, the numbers of sperms were assessed, using haemocytometer. Also, their morphology with papanicolaeu staining and their vitality with Eosin B dye were assessed. As well as sperms motility measured under inverted microscope by observation and fertility rate evaluated after routine IVF by counting two-cell stage embryos. Results: Our results demonstrated that, the dose of 750 µ g/ml has the greatest effect on the motility, vitality and fertility rate of sperms. The effect of dose of 1000 µ g/ml also was positive on them. On the other hand, none of these doses had any effect on sperm morphology. Conclusion: Hyaluronan may have an influence on motility, vitality and fertility rate of sperms and the dose of 750µ g/ml had a significant effect on these factors.

  10. Effect of molecular weight and concentration of hyaluronan on cell proliferation and osteogenic differentiation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Ningbo, E-mail: curl-zhao@163.com; Wang, Xin, E-mail: 394041230@qq.com; Qin, Lei, E-mail: qinlei30@126.com; Guo, Zhengze, E-mail: zhzeguo@163.com; Li, Dehua, E-mail: lidehuafmmu@163.com

    2015-09-25

    Hyaluronan (HA), the simplest glycosaminoglycan and a major component of the extracellular matrix, exists in various tissues. It is involved in some critical biological procedures, including cellular signaling, cell adhesion and proliferation, and cell differentiation. The effect of molecular weight (MW) and concentration of HA on cell proliferation and differentiation was controversial. In this study, we investigated the effect of MW and concentration of HA on the proliferation and osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro. Results showed that high MW HA decreased the cell adhesion rate in a concentration-dependant manner. The cell adhesion rate was decreased by increasing MW of HA. Cell proliferation was significantly enhanced by low MW HA (P < 0.05). The factorial analysis indicated that MW and concentration had an interactive effect on the cell adhesion rate and cell proliferation (P < 0.05). High MW HA increased the mRNA expressions of ALP, RUNX-2 and OCN. The higher the MW was, the higher the mRNA expressions were. The factorial analysis indicated that MW and concentration had an interactive effect on ALP mRNA expression (P < 0.05). HA of higher MW and higher concentration promoted bone formation. These findings provide some useful information in understanding the mechanism underlying the effect of MW and concentration of HA on cell proliferation and differentiation. - Highlights: • Effect of hyaluronan on cell proliferation and differentiation is evaluated in vitro. • Hyaluronan of low molecular weight increases cell proliferation. • Hyaluronan of high molecular weight promotes cell osteogenic differentiation. • Molecular weight and concentration of hyaluronan show interactive effect.

  11. Self-reinforcement and protein sustained delivery of hyaluronan hydrogel by tailoring a dually cross-linked network

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Chunhong; Xu, Guoguang; Wang, Xinghui [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Tu, Mei; Zeng, Rong; Rong, Jianhua [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China); Zhao, Jianhao, E-mail: jhzhao@jnu.edu.cn [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China)

    2015-01-01

    A series of self-reinforcing hyaluronan hydrogels were developed to improve mechanical properties and protein sustained delivery thanks to a dually cross-linked network. Hyaluronan gel particles (HGPs, 1–5 μm in diameter) with different cross-linking densities, i.e. HGPs-1.5, HGPs-3 and HGPs-15, were prepared in an inverse emulsion system and used as the reinforcing phase after glycidyl methacrylation, while glycidyl methacrylated hyaluronan with a substitution degree of 45.2% was synthesized as the matrix phase. These two phases were cross-linked under ultraviolet irradiation to form self-reinforcing hyaluronan hydrogels (srHAs) that showed typical cross-linked structure of HGPs connecting the matrix phase by cross-section observation. In comparison to hyaluronan bulk gels and their blends with HGPs, srHAs distinctly enhanced the mechanical properties and BSA long-term sustained delivery, especially srHA-1.5 showed the highest compressive modulus of 220 ± 15 kPa and the slowest BSA delivery (67% release at 14 d). The 3T3 fibroblast cell culture showed that all the srHAs had no cytotoxicity. - Highlights: • New self-reinforcing HA hydrogels with a dually cross-linked network were developed. • Self-reinforcing HA hydrogels greatly enhanced the mechanical properties. • Self-reinforcing HA hydrogels prolonged the sustained delivery of BSA. • The self-reinforcing mechanism and BSA diffusion mechanism were discussed. • Self-reinforcing HA hydrogels had no cytotoxicity to 3T3 fibroblast cells.

  12. Hyaluronan signaling during ozone-induced lung injury requires TLR4, MyD88, and TIRAP.

    Directory of Open Access Journals (Sweden)

    Zhuowei Li

    Full Text Available Ozone exposure is associated with exacerbation of reactive airways disease. We have previously reported that the damage-associated molecular pattern, hyaluronan, is required for the complete biological response to ambient ozone and that hyaluronan fragments signal through toll-like receptor 4 (TLR4. In this study, we further investigated the role of TLR4 adaptors in ozone-induced airway hyperresponsiveness (AHR and the direct response to hyaluronan fragments (HA. Using a murine model of AHR, C57BL/6J, TLR4-/-, MyD88-/-, and TIRAP-/- mice were characterized for AHR after exposure to either ozone (1 ppm × 3 h or HA fragments. Animals were characterized for AHR with methacholine challenge, cellular inflammation, lung injury, and production of pro-inflammatory cytokines. Ozone-exposed C57BL/6J mice developed cellular inflammation, lung injury, pro-inflammatory cytokines, and AHR, while mice deficient in TLR4, MyD88 or TIRAP demonstrated both reduced AHR and reduced levels of pro-inflammatory cytokines including TNFα, IL-1β, MCP-1, IL-6 and KC. The level of hyaluronan was increased after inhalation of ozone in each strain of mice. Direct challenge of mice to hyaluronan resulted in AHR in C57BL/6J mice, but not in TLR4-/-, MyD88-/-, or TIRAP-/- mice. HA-induced cytokine production in wild-type mice was significantly reduced in TLR4-/-, MyD88-/-, or TIRAP-/- mice. In conclusion, our findings support that ozone-induced airway hyperresponsiveness is dependent on the HA-TLR4-MyD88-TIRAP signaling pathway.

  13. Profits and Exploitation: A Reappraisal

    OpenAIRE

    Yoshihara, Naoki; Veneziani, Roberto

    2011-01-01

    This paper provides a mathematical analysis of the Marxian theory of the exploitation of labour in general equilibrium models. The two main definitions of Marxian exploitation in the literature, proposed by Morishima (1974) and Roemer (1982), respectively, are analysed in the context of general convex economies. It is shown that, contrary to the received view, in general these definitions do not preserve the so-called Fundamental Marxian Theorem (FMT), which states that the exploitation of la...

  14. Desiring TESOL and International Education: Market Abuse and Exploitation

    Science.gov (United States)

    Chowdhury, Raqib; Ha, Phan Le

    2014-01-01

    This book addresses how Western universities have constructed themselves as global providers of education, and are driven to be globally competitive. It examines how the term "international" has been exploited by the market in the form of government educational policies and agencies, host institutions, academia and the mass media. The…

  15. Synergy in spreading processes: from exploitative to explorative foraging strategies.

    Science.gov (United States)

    Pérez-Reche, Francisco J; Ludlam, Jonathan J; Taraskin, Sergei N; Gilligan, Christopher A

    2011-05-27

    An epidemiological model which incorporates synergistic effects that allow the infectivity and/or susceptibility of hosts to be dependent on the number of infected neighbors is proposed. Constructive synergy induces an exploitative behavior which results in a rapid invasion that infects a large number of hosts. Interfering synergy leads to a slower and sparser explorative foraging strategy that traverses larger distances by infecting fewer hosts. The model can be mapped to a dynamical bond percolation with spatial correlations that affect the mechanism of spread but do not influence the critical behavior of epidemics. © 2011 American Physical Society

  16. Consensual exploitation : the moral wrong in exploitation and legal restrictions on consensual exploitative transactions

    OpenAIRE

    van der Neut, Wendy

    2014-01-01

    This thesis is about so-­‐called consensual exploitative transactions: transactions to which all parties agree voluntarily, and which are beneficial for all parties, but which are still widely considered exploitative, and for that reason legally restricted in many countries. The thesis asks two main questions: 1. What is wrong with consensual exploitation? 2.What implications does the answer to this question have for the legal restriction of consensual transactions ...

  17. Modeling of hyaluronan clearance with application to estimation of lymph flow

    International Nuclear Information System (INIS)

    Rössler, Andreas; Goswami, Nandu; Fink, Martin; Batzel, Jerry J

    2011-01-01

    One of the important factors in blood pressure regulation is the maintenance of the level of blood volume, which depends on several factors including the rate of lymph flow. Lymph flow can be measured directly using cannulation of lymphatic vessels, which is not clinically feasible, or indirectly by the tracer appearance rate, which is the rate at which macromolecules appear into the blood from the peritoneal cavity. However, indirect lymph flow measurements do not always provide consistent results. Through its contribution to osmotic pressure and resistance to flow, the macromolecule hyaluronan takes part in the regulation of tissue hydration and the maintenance of water and protein homeostasis. It arrives in blood plasma through lymph flow. Lymphatic hyaluronic acid (HA, hyaluronan) concentration is several times higher than that in plasma, suggesting that the lymphatic route may account for the majority of HA found in plasma. Furthermore, circulating levels of HA reflect the dynamic state between delivery to—and removal from—the bloodstream. To develop an accurate estimation of the fluid volume distribution and dynamics, the rate of lymph flow needs to be taken into account and hyaluronan could be used as a marker in estimating this flow. To examine the HA distribution and system fluid dynamics, a six-compartment model, which could reflect both the steady-state relationships and qualitative characteristics of the dynamics, was developed. This was then applied to estimate fluid shifts from the interstitial space via the lymphatic system to the plasma during different physiological stresses (orthostatic stress and the stress of ultrafiltration during dialysis). Sensitivity analysis shows that during ultrafiltration, lymph flow is a key parameter influencing the total HA level, thus suggesting that the model may find applications in addressing the problem of estimating lymph flow. Since the fluid balance between interstitium and plasma is maintained by lymph

  18. Thermo-and pH-sensitive hydrogel membranes composed of poly(N-isopropylacrylamide)-hyaluronan for biomedical applications: Influence of hyaluronan incorporation on the membrane properties.

    Science.gov (United States)

    Kamoun, Elbadawy A; Fahmy, Alaa; Taha, Tarek H; El-Fakharany, Esmail M; Makram, Mohamed; Soliman, Hesham M A; Shehata, Hassan

    2018-01-01

    Interpenetrating hydrogel membranes consisting of pH-sensitive hyaluronan (HA) and thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAM) were synthesized using redox polymerization, followed by N,N-methylenebisacrylamide (BIS) and epichlorohydrin (EPI) were added as chemical crosslinkers. The interaction between membrane compositions has been characterized by FTIR spectroscopy and discussed intensively. The result indicates that HA incorporation in membranes increase the gel fraction, swelling uptake, and the flexibility/elasticity of crosslinked membranes, however it reduced oppositely the mechanical elongation of membranes. PNIPAAm-HA hydrogels responded to both temperature and pH changes and the stimuli-responsiveness was reversible. However, in vitro bioevaluation results revealed that the released ampicillin during the burst release time was sharply influenced and increased with increasing HA contents in membranes; afterwards it became sustainable. Whereas, high HA contents in hydrogels unexpectedly impacted negatively on the cells viability, owing to the viscosity of cell culture media changed. A big resistance was observed against microbial growth of Staphylococcus aureus, Salmonella typhi, and Candida albicans in case of pure PNIPAAm hydrogel membranes without HA or ampicillin. However, HA incorporation or the loaded ampicillin in membranes showed unexpected easily microbial growth. The fast release performance with dual pH-thermo-sensitive hydrogels were suggested as promising materials for quick drug carrier in the biomedical field. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Hyaluronan and Hyaluronan-Binding Proteins Accumulate in Both Human Type 1 Diabetic Islets and Lymphoid Tissues and Associate With Inflammatory Cells in Insulitis

    Science.gov (United States)

    Bogdani, Marika; Johnson, Pamela Y.; Potter-Perigo, Susan; Nagy, Nadine; Day, Anthony J.; Bollyky, Paul L.

    2014-01-01

    Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that is present in pancreatic islets, but little is known about its involvement in the development of human type 1 diabetes (T1D). We have evaluated whether pancreatic islets and lymphoid tissues of T1D and nondiabetic organ donors differ in the amount and distribution of HA and HA-binding proteins (hyaladherins), such as inter-α-inhibitor (IαI), versican, and tumor necrosis factor–stimulated gene-6 (TSG-6). HA was dramatically increased both within the islet and outside the islet endocrine cells, juxtaposed to islet microvessels in T1D. In addition, HA was prominent surrounding immune cells in areas of insulitis. IαI and versican were present in HA-rich areas of islets, and both molecules accumulated in diabetic islets and regions exhibiting insulitis. TSG-6 was observed within the islet endocrine cells and in inflammatory infiltrates. These patterns were only observed in tissues from younger donors with disease duration of <10 years. Furthermore, HA and IαI amassed in follicular germinal centers and in T-cell areas in lymph nodes and spleens in T1D patients compared with control subjects. Our observations highlight potential roles for HA and hyaladherins in the pathogenesis of diabetes. PMID:24677718

  20. Brood parasitic cowbird nestlings use host young to procure resources.

    Science.gov (United States)

    Kilner, Rebecca M; Madden, Joah R; Hauber, Mark E

    2004-08-06

    Young brood parasites that tolerate the company of host offspring challenge the existing evolutionary view of family life. In theory, all parasitic nestlings should be ruthlessly self-interested and should kill host offspring soon after hatching. Yet many species allow host young to live, even though they are rivals for host resources. Here we show that the tolerance of host nestlings by the parasitic brown-headed cowbird Molothrus ater is adaptive. Host young procure the cowbird a higher provisioning rate, so it grows more rapidly. The cowbird's unexpected altruism toward host offspring simply promotes its selfish interests in exploiting host parents.

  1. Exploitation Strategies in Social Parasites of Fungus Growing Ants

    DEFF Research Database (Denmark)

    Clement, Janni Dolby

    One of the most remarkable and complex parasitic interactions is social parasitism, where a parasite exploits a complete society, rather than an individual organism. By integrating into a society the parasite gains protection against predators and diseases, and can redirect resources from the host...... to increase its own fitness. The host will use a sophisticated recognition system in order to accept nestmates and expel intruders from their societies. However this defence barrier can be overcome by parasites. Among the most specialized social parasites are the inquilines that exploit social insect colonies...... to this are Acromyrmex insinuator and Acromyrmex ameliae, parasites of fungus-growing ants. By still producing a worker caste both species offers a rare opportunity to study adaptive features in parasite worker behaviour. Furthermore can closely related inquiline-host combinations give us an insight in the trade...

  2. Nanofilms of hyaluronan/chitosan assembled layer-by-layer: An antibacterial surface for Xylella fastidiosa.

    Science.gov (United States)

    Hernández-Montelongo, Jacobo; Nascimento, Vicente F; Murillo, Duber; Taketa, Thiago B; Sahoo, Prasana; de Souza, Alessandra A; Beppu, Marisa M; Cotta, Monica A

    2016-01-20

    In this work, nanofilms of hyaluronan/chitosan (HA/CHI) assembled layer by layer were synthesized; their application as a potential antimicrobial material was demonstrated for the phytopathogen Xylella fastidiosa, a gram-negative bacterium, here used as a model. For the synthesis, the influence of pH and ionic strength of these natural polymer stem-solutions on final characteristics of the HA/CHI nanofilms was studied in detail. The antibacterial effect was evaluated using widefield fluorescence microscopy. These results were correlated with the chemical properties of the nanofilms, studied by FTIR and Raman spectroscopy, as well as with their morphology and surface properties characterized using SEM and AFM. The present findings can be extended to design and optimize HA/CHI nanofilms with enhanced antimicrobial behavior for other type of phytopathogenic gram-negative bacteria species, such as Xanthomonas citri, Xanthomas campestri and Ralstonia solanacearum. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Hypochlorite-mediated fragmentation of hyaluronan, chondroitin sulfates, and related N-acetyl glycosamines

    DEFF Research Database (Denmark)

    Rees, Martin D; Hawkins, Clare Louise; Davies, Michael Jonathan

    2003-01-01

    Myeloperoxidase released from activated phagocytes reacts with H(2)O(2) in the presence of chloride ions to give hypochlorous acid. This oxidant has been implicated in the fragmentation of glycosaminoglycans, such as hyaluronan and chondroitin sulfates. In this study it is shown that reaction...... processes. In the case of glycosaminoglycan-derived amidyl radicals, evidence has been obtained in studies with model glycosides that these radicals undergo rapid intramolecular abstraction reactions to give carbon-centered radicals at C-2 on the N-acetyl glycosamine rings (via a 1,2-hydrogen atom shift......) and at C-4 on the neighboring uronic acid residues (via 1,5-hydrogen atom shifts). The C-4 carbon-centered radicals, and analogous species derived from model glycosides, undergo pH-independent beta-scission reactions that result in glycosidic bond cleavage. With N-acetyl glucosamine C-1 alkyl glycosides...

  4. Local injection of high-molecular hyaluronan promotes wound healing in old rats by increasing angiogenesis.

    Science.gov (United States)

    Huang, Luying; Wang, Yi; Liu, Hua; Huang, Jianhua

    2018-02-02

    Impaired angiogenesis contributes to delayed wound healing in aging. Hyaluronan (HA) has a close relationship with angiogenesis and wound healing. However, HA content decreases with age. In this study, we used high molecular weight HA (HMW-HA) (1650 kDa), and investigated its effects on wound healing in old rats by local injection. We found that HMW-HA significantly increases proliferation, migration and tube formation in endothelial cells, and protects endothelial cells against apoptosis. Local injection of HMW-HA promotes wound healing by increasing angiogenesis in old rats. HMW-HA increases the phosphorylation of Src, ERK and AKT, leading to increased angiogenesis, suggesting that local injection of HMW-HA promotes wound healing in elderly patients.

  5. Effects of inhaled high-molecular weight hyaluronan in inflammatory airway disease.

    Science.gov (United States)

    Lamas, Adelaida; Marshburn, Jamie; Stober, Vandy P; Donaldson, Scott H; Garantziotis, Stavros

    2016-10-03

    Cystic fibrosis (CF) is a chronic inflammatory disease that is affecting thousands of patients worldwide. Adjuvant anti-inflammatory treatment is an important component of cystic fibrosis treatment, and has shown promise in preserving lung function and prolonging life expectancy. Inhaled high molecular weight hyaluronan (HMW-HA) is reported to improve tolerability of hypertonic saline and thus increase compliance, and has been approved in some European countries for use as an adjunct to hypertonic saline treatment in cystic fibrosis. However, there are theoretical concerns that HMW-HA breakdown products may be pro-inflammatory. In this clinical pilot study we show that sputum cytokines in CF patients receiving HMW-HA are not increased, and therefore HMW-HA does not appear to adversely affect inflammatory status in CF airways.

  6. Study on gamma radiation-induced synthesis of gold nanoparticles stabilized by hyaluronan

    International Nuclear Information System (INIS)

    Dang Van Phu; Bui Duy Du

    2013-01-01

    Gold nanoparticles (AuNPs) with diameter from 4 to 10 nm were synthesized by γ-irradiation in hyaluronan (HA) solution without usage of any OH radical scavenger. The size distribution of AuNPs were determined by TEM images. The λ max (517-525 nm) of colloidal AuNPs solutions as prepared was measured by UV-Vis spectroscopy. The influence factor on the size of AuNPs particularly the concentration of Au 3+ , HA and dose rate were investigated. The colloidal solution of AuNPs/HA as synthesized was stable more than 6 months stored under ambient condition. AuNPs with the size less than 10 nm narrow size distribution stabilized by HA which is biocompatible polysaccharide can potentially be applied in biomedicine and cosmetic. (author)

  7. Study on gamma radiation-induced synthesis of gold nanoparticles stabilized by hyaluronan

    International Nuclear Information System (INIS)

    Dang Van Phu; Nguyen Ngoc Duy; Nguyen Tue Anh; Nguyen Quoc Hien

    2011-01-01

    Gold nanoparticles (AuNPs) with diameter from 4 to 10 nm were synthesized in hyaluronan (HA) solution without usage of any reductant and *OH radical scavenger by gamma irradiation reduction. The size and size distribution of AuNPs were determined by TEM images. The λ max (517 - 525 nm) of colloidal AuNPs solutions as prepared were measured by UV-Vis spectroscopy. The influence factors on the size of AuNPs particularly the concentration of Au 3+ , HA and dose rate were investigated. The stability of AuNPs/HA as synthesized was more than 6 months in storage under atmospheric condition. AuNPs with the size less than 10 nm and narrow size distribution stabilized by HA which is biocompatible natural polysaccharide so that AuNPs/HA can potentially be applied in biomedicine and cosmetic. (author)

  8. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-01-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 ± 3mm (mean ± SD) and 10 ± 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 ± 13cGy with Hylaform vs. 106 ± 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  9. Chemotherapy-induced hyaluronan production: a novel chemoresistance mechanism in ovarian cancer

    International Nuclear Information System (INIS)

    Ricciardelli, Carmela; Ween, Miranda P; Lokman, Noor A; Tan, Izza A; Pyragius, Carmen E; Oehler, Martin K

    2013-01-01

    Hyaluronan (HA) an important component of the extracellular matrix, has been linked to tumor progression and drug resistance in several malignancies. However, limited data is available for ovarian cancer. This study investigated the role of hyaluronan (HA) and a potential link between the HA-CD44 pathway and membrane ATP binding cassette (ABC) transporter proteins in ovarian cancer chemoresistance. We investigated the ability of HA to block the cytotoxic effects of the chemotherapy drug carboplatin, and to regulate the expression of ABC transporters in ovarian cancer cells. We also examined HA serum levels in ovarian cancer patients prior to and following chemotherapy and assessed its prognostic relevance. HA increased the survival of carboplatin treated ovarian cancer cells expressing the HA receptor, CD44 (OVCAR-5 and OV-90). Carboplatin significantly increased expression of HAS2, HAS3 and ABCC2 and HA secretion in ovarian cancer cell conditioned media. Serum HA levels were significantly increased in patients following platinum based chemotherapy and at both 1st and 2nd recurrence when compared with HA levels prior to treatment. High serum HA levels (>50 μg/ml) prior to chemotherapy treatment were associated with significantly reduced progression-free (P = 0.014) and overall survival (P = 0.036). HA production in ovarian cancer cells was increased in cancer tissues collected following chemotherapy treatment and at recurrence. Furthermore HA treatment significantly increased the expression of ABC drug transporters (ABCB3, ABCC1, ABCC2, and ABCC3), but only in ovarian cancer cells expressing CD44. The effects of HA and carboplatin on ABC transporter expression in ovarian cancer cells could be abrogated by HA oligomer treatment. Importantly, HA oligomers increased the sensitivity of chemoresistant SKOV3 cells to carboplatin. Our findings indicate that carboplatin chemotherapy induces HA production which can contribute to chemoresistance by regulating ABC

  10. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat.

    Science.gov (United States)

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-07-18

    The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30 years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer. Here we identify a mechanism responsible for the naked mole rat's cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.

  11. High molecular weight hyaluronan mediates the cancer resistance of the naked mole-rat

    Science.gov (United States)

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-01-01

    The naked mole-rat displays exceptional longevity, with a maximum lifespan exceeding 30 years1–3. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole-rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years4,5. In addition to their longevity, naked mole-rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer2,6. Here we identify a mechanism responsible for the naked mole-rat’s cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high molecular weight hyaluronan (HA), which is over five times larger than human or mouse HA. This high molecular weight HA accumulates abundantly in naked mole rat tissues due to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signaling, as the naked mole rat cells have a higher affinity to HA than the mouse or human cells. Perturbation of the signaling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high molecular weight HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, Hyal2, naked mole-rat cells become susceptible to malignant transformation and readily form tumors in mice. We speculate that naked mole-rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species. PMID:23783513

  12. Glucose regulated proteins 78 and 75 bind to the receptor for hyaluronan mediated motility in interphase microtubules

    International Nuclear Information System (INIS)

    Kuwabara, Hiroko; Yoneda, Masahiko; Hayasaki, Hana; Nakamura, Toshiya; Mori, Hiroshi

    2006-01-01

    The receptor for hyaluronan mediated motility (RHAMM), which is a hyaluronan-binding protein, is a centrosomal and microtubal protein. Here, we have identified two RHAMM-binding proteins, glucose regulated protein (GRP) 78 and GRP75, using co-immunoprecipitation analysis. These two proteins directly bound to glutathione-S-transferase-RHAMM fusion proteins. By double immunostaining, GRP78 and GRP75 colocalized with RHAMM in interphase microtubules, but were separated in mitotic spindles. Prevention of microtubule polymerization by TN-16 and vincristine sulfate induced RHAMM overexpression without a significant change in GRP78/75. Taken together, GRP78/75 and RHAMM complexes may stabilize microtubules in the interphase, associated with a downregulation of RHAMM. These results reveal a new biochemical activity of RHAMM

  13. Malware Sandbox Analysis for Secure Observation of Vulnerability Exploitation

    Science.gov (United States)

    Yoshioka, Katsunari; Inoue, Daisuke; Eto, Masashi; Hoshizawa, Yuji; Nogawa, Hiroki; Nakao, Koji

    Exploiting vulnerabilities of remote systems is one of the fundamental behaviors of malware that determines their potential hazards. Understanding what kind of propagation tactics each malware uses is essential in incident response because such information directly links with countermeasures such as writing a signature for IDS. Although recently malware sandbox analysis has been studied intensively, little work is done on securely observing the vulnerability exploitation by malware. In this paper, we propose a novel sandbox analysis method for securely observing malware's vulnerability exploitation in a totally isolated environment. In our sandbox, we prepare two victim hosts. We first execute the sample malware on one of these hosts and then let it attack the other host which is running multiple vulnerable services. As a simple realization of the proposed method, we have implemented a sandbox using Nepenthes, a low-interaction honeypot, as the second victim. Because Nepenthes can emulate a variety of vulnerable services, we can efficiently observe the propagation of sample malware. In the experiments, among 382 samples whose scan capabilities are confirmed, 381 samples successfully started exploiting vulnerabilities of the second victim. This indicates the certain level of feasibility of the proposed method.

  14. Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period

    OpenAIRE

    Oe, Mariko; Sakai, Seigo; Yoshida, Hideto; Okado, Nao; Kaneda, Haruna; Masuda, Yasunobu; Urushibata, Osamu

    2017-01-01

    Mariko Oe,1 Seigo Sakai,1 Hideto Yoshida,1 Nao Okado,1 Haruna Kaneda,1 Yasunobu Masuda,1 Osamu Urushibata2 1R&D Division, Kewpie Corporation, Sengawa-cho, Chofu-shi, 2Department of Dermatology, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Background: Hyaluronan (HA) has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA. Methods: The mean molecular weight (MW...

  15. Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Seong Uk Son

    2017-12-01

    Full Text Available We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA-based nanohydrogels for effective transdermal delivery. First, hyaluronan-conjugated dodecylamine (HA–Do HA-based polymers to load the lipophilic agents were synthesized with hyaluronan (HA and dodecylamine (Do by varying the substitution ratio of Do to HA. The synthetic yield of HA–Do was more than 80% (HA–Do (A: 82.7 ± 4.7%, HA–Do (B: 87.1 ± 3.9% and HA–Do (C: 81.4 ± 4.5%. Subsequently, nanohydrogels were fabricated using the nanoemulsion method. Indocyanine green (ICG simultaneously self-assembled with HA–Do, and the size depended on the substitution ratio of Do in HA–Do (nanohydrogel (A: 118.0 ± 2.2 nm, nanohydrogel (B: 121.9 ± 11.4 nm, and nanohydrogel (C: 142.2 ± 3.8 nm. The nanohydrogels were delivered into cells, and had excellent biocompatibility. Especially, nanohydrogel (A could deliver and permeate ICG into the deep skin layer, the dermis. This suggests that nanohydrogels can be potent transdermal delivery systems.

  16. Cytocompatible in situ forming chitosan/hyaluronan hydrogels via a metal-free click chemistry for soft tissue engineering.

    Science.gov (United States)

    Fan, Ming; Ma, Ye; Mao, Jiahui; Zhang, Ziwei; Tan, Huaping

    2015-07-01

    Injectable hydrogels are important cell scaffolding materials for tissue engineering and regenerative medicine. Here, we report a new class of biocompatible and biodegradable polysaccharide hydrogels derived from chitosan and hyaluronan via a metal-free click chemistry, without the addition of copper catalyst. For the metal-free click reaction, chitosan and hyaluronan were modified with oxanorbornadiene (OB) and 11-azido-3,6,9-trioxaundecan-1-amine (AA), respectively. The gelation is attributed to the triazole ring formation between OB and azido groups of polysaccharide derivatives. The molecular structures were verified by FT-IR spectroscopy and elemental analysis, giving substitution degrees of 58% and 47% for chitosan-OB and hyaluronan-AA, respectively. The in vitro gelation, morphologies, equilibrium swelling, compressive modulus and degradation of the composite hydrogels were examined. The potential of the metal-free hydrogel as a cell scaffold was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) within the gel matrix in vitro. Cell culture showed that this metal-free hydrogel could support survival and proliferation of ASCs. A preliminary in vivo study demonstrated the usefulness of the hydrogel as an injectable scaffold for adipose tissue engineering. These characteristics provide a potential opportunity to use the metal-free click chemistry in preparation of biocompatible hydrogels for soft tissue engineering applications. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  17. Plasticity in host utilization by two host-associated populations of Aphis gossypii Glover.

    Science.gov (United States)

    Barman, A K; Gadhave, K R; Dutta, B; Srinivasan, R

    2018-06-01

    Biological and morphological plasticity in polyphagous insect herbivores allow them to exploit diverse host plant species. Geographical differences in resource availability can lead to preferential host exploitation and result in inconsistent host specialization. Biological and molecular data provide insights into specialization and plasticity of such herbivore populations. In agricultural landscapes, Aphis gossypii encounters several crop and non-crop hosts, which exist in temporal and spatial proximity. We investigated the host-specialization of two A. gossypii host-associated populations (HAPs), which were field collected from cotton and squash (cotton-associated population and melon-associated population), and later maintained separately in the greenhouse. The two aphid populations were exposed to seven plant species (cotton, okra, watermelon, squash, cucumber, pigweed, and morning glory), and evaluated for their host utilization plasticity by estimating aphid's fitness parameters (nymphal period, adult period, fecundity, and intrinsic rate of increase). Four phenotypical characters (body length, head capsule width, hind tibia length and cornicle length) were also measured from the resulting 14 different HAP × host plant combinations. Phylogenetic analysis of mitochondrial COI sequences showed no genetic variation between the two HAPs. Fitness parameters indicated a significant variation between the two aphid populations, and the variation was influenced by host plants. The performance of melon-aphids was poor (up to 89% reduction in fecundity) on malvaceous hosts, cotton and okra. However, cotton-aphids performed better on cucurbitaceous hosts, squash and watermelon (up to 66% increased fecundity) compared with the natal host, cotton. Both HAPs were able to reproduce on two weed hosts. Cotton-aphids were smaller than melon-aphids irrespective of their host plants. Results from this study suggest that the two HAPs in the study area do not have strict host

  18. Gait patterns after intraarticular treatment of patients with osteoarthritis of the Knee - Hyaluronan versus triamcinolone: a prospective, randomized, doubleblind, monocentric study

    Directory of Open Access Journals (Sweden)

    Skwara A

    2009-04-01

    Full Text Available Abstract Objective Evaluation of gait performance and muscle activity patterns as well as clinical efficacy and safety after single intraarticular injection with hyaluronan compared with triamcinolone in patients with knee osteoarthritis. Materials and Methods This trial evaluated the influence of a single injection of hyaluronan or triamcinolone on gait pattern and muscle activity. For clinical evaluation a visual analogue scale for pain, Lequesne index, and Knee Society Score were used. Quality of life was assessed with the SF-36. Results The complete analysis was performed in 50 of 60 patients. 26 patients were treated with triamcinolone and 24 with hyaluronan. Hyaluronan treatment led to significant improvement of range of motion at hip and knee. Significant improvement could be either demonstrated for the pain scale, Lequesne and Knee Society score in both groups. Quality of life showed greater improvement in the triamcinolone group. Conclusion Single application of high-viscosity hyaluronan shows superior range of motion and pain reduction as well as improvement in clinical results. Even if there was a lack of significant differences compared to triamcinolone, this therapy classified as safe and effective in the short follow up.

  19. Green synthesis, characterization, and anticancer activity of hyaluronan/zinc oxide nanocomposites

    Directory of Open Access Journals (Sweden)

    Namvar F

    2016-07-01

    Full Text Available Farideh Namvar,1,2 Susan Azizi,3 Heshu Sulaiman Rahman,4–6 Rosfarizan Mohamad,1,3 Abdullah Rasedee,4 Mozhgan Soltani,2 Raha Abdul Rahim71Institute of Tropical Forestry and Forest Products (INTROP, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia; 2Research Center for Animal Development Applied Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran; 3Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, 4Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia; 5Department of Clinic and Internal Medicine, College of Veterinary Medicine, University of Sulaimani, 6Department of Laboratory Medical Sciences, Komar University of Science and Technology, Sulaimani City, Kurdistan Region, Northern Iraq; 7Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia Abstract: The study describes an in situ green biosynthesis of zinc oxide nanocomposite using the seaweed Sargassum muticum water extract and hyaluronan biopolymer. The morphology and optical properties of the hyaluronan/zinc oxide (HA/ZnO nanocomposite were determined by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, and ultraviolet–vis analysis. Electron microscopy and X-ray diffraction analysis showed that the zinc oxide nanoparticles were polydispersed with a mean size of 10.2±1.5 nm. The nanoparticles were mostly hexagonal in crystalline form. The HA/ZnO nanocomposite showed the absorption properties in the ultraviolet zone that is ascribed to the band gap of zinc oxide nanocomposite. In the cytotoxicity study, cancer cells, pancreatic adenocarcinoma (PANC-1, ovarian adenocarcinoma (CaOV-3, colonic adenocarcinoma (COLO205, and acute promyelocytic leukemia (HL-60 cells

  20. Ultra-low friction between boundary layers of hyaluronan-phosphatidylcholine complexes.

    Science.gov (United States)

    Zhu, Linyi; Seror, Jasmine; Day, Anthony J; Kampf, Nir; Klein, Jacob

    2017-09-01

    The boundary layers coating articular cartilage in synovial joints constitute unique biomaterials, providing lubricity at levels unmatched by any human-made materials. The underlying molecular mechanism of this lubricity, essential to joint function, is not well understood. Here we study the interactions between surfaces bearing attached hyaluronan (hyaluronic acid, or HA) to which different phosphatidylcholine (PC) lipids had been added, in the form of small unilamellar vesicles (SUVs or liposomes), using a surface force balance, to shed light on possible cartilage boundary lubrication by such complexes. Surface-attached HA was complexed with different PC lipids (hydrogenated soy PC (HSPC), 1,2-dimyristoyl-sn-glycero-3-PC (DMPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-PC (POPC)), followed by rinsing. Atomic force microscopy (AFM) and cryo-scanning electron microscopy (Cryo-SEM) were used to image the HA-PC surface complexes following addition of the SUVs. HA-HSPC complexes provide very efficient lubrication, with friction coefficients as low as μ∼0.001 at physiological pressures P≈150atm, while HA-DMPC and HA-POPC complexes are efficient only at low P (up to 10-20atm). The friction reduction in all cases is attributed to hydration lubrication by highly-hydrated phosphocholine groups exposed by the PC-HA complexes. The greater robustness at high P of the HSPC (C 16(15%) ,C 18(85%) ) complexes relative to the DMPC ((C 14 ) 2 ) or POPC (C 16 , C 18:1 ) complexes is attributed to the stronger van der Waals attraction between the HSPC acyl tails, relative to the shorter or un-saturated tails of the other two lipids. Our results shed light on possible lubrication mechanisms at the articular cartilage surface in joints. Can designed biomaterials emulate the unique lubrication ability of articular cartilage, and thus provide potential alleviation to friction-related joint diseases? This is the motivation behind the present study. The principles of cartilage lubrication

  1. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year

    DEFF Research Database (Denmark)

    Jørgensen, Anette; Stengaard-Pedersen, Kristian; Simonsen, Ole

    2010-01-01

    OBJECTIVE: To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis. METHODS: A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee...... osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n=167) or saline (n=170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary...... the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity (LFI > or = 10), five intra-articular injections of hyaluronan did not improve pain, function, paracetamol consumption or other efficacy parameters 3, 6, 9 and 12 months after the treatment....

  2. MDA-MB-231 breast cancer cell viability, motility and matrix adhesion are regulated by a complex interplay of heparan sulfate, chondroitin-/dermatan sulfate and hyaluronan biosynthesis.

    Science.gov (United States)

    Viola, Manuela; Brüggemann, Kathrin; Karousou, Evgenia; Caon, Ilaria; Caravà, Elena; Vigetti, Davide; Greve, Burkhard; Stock, Christian; De Luca, Giancarlo; Passi, Alberto; Götte, Martin

    2017-06-01

    Proteoglycans and glycosaminoglycans modulate numerous cellular processes relevant to tumour progression, including cell proliferation, cell-matrix interactions, cell motility and invasive growth. Among the glycosaminoglycans with a well-documented role in tumour progression are heparan sulphate, chondroitin/dermatan sulphate and hyaluronic acid/hyaluronan. While the mode of biosynthesis differs for sulphated glycosaminoglycans, which are synthesised in the ER and Golgi compartments, and hyaluronan, which is synthesized at the plasma membrane, these polysaccharides partially compete for common substrates. In this study, we employed a siRNA knockdown approach for heparan sulphate (EXT1) and heparan/chondroitin/dermatan sulphate-biosynthetic enzymes (β4GalT7) in the aggressive human breast cancer cell line MDA-MB-231 to study the impact on cell behaviour and hyaluronan biosynthesis. Knockdown of β4GalT7 expression resulted in a decrease in cell viability, motility and adhesion to fibronectin, while these parameters were unchanged in EXT1-silenced cells. Importantly, these changes were associated with a decreased expression of syndecan-1, decreased signalling response to HGF and an increase in the synthesis of hyaluronan, due to an upregulation of the hyaluronan synthases HAS2 and HAS3. Interestingly, EXT1-depleted cells showed a downregulation of the UDP-sugar transporter SLC35D1, whereas SLC35D2 was downregulated in β4GalT7-depleted cells, indicating an intricate regulatory network that connects all glycosaminoglycans synthesis. The results of our in vitro study suggest that a modulation of breast cancer cell behaviour via interference with heparan sulphate biosynthesis may result in a compensatory upregulation of hyaluronan biosynthesis. These findings have important implications for the development of glycosaminoglycan-targeted therapeutic approaches for malignant diseases.

  3. Elasticity, biodegradability and cell adhesive properties of chitosan/hyaluronan multilayer films

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Aurore; Richert, Ludovic; Francius, Gregory; Voegel, Jean-Claude; Picart, Catherine [Present address: Universite de Montpellier II, CNRS-UMR 5539, cc107, Place Eugene Bataillon, 34 095 Montpellier Cedex 5 (France)

    2007-03-01

    In the bioengineering field, a recent and promising approach to modifying biomaterial surfaces is the layer-by-layer (LbL) technique used to build thin polyelectrolyte multilayer films. In this work, we focused on polyelectrolyte multilayer films made of two polysaccharides, chitosan (CHI) and hyaluronan (HA), and on the control of their physico-chemical and cell adhesive properties by chemical cross-linking. CHI/HA films were cross-linked using a water soluble carbodiimide and observed by confocal laser scanning microscopy (CLSM) with a fluorescently labeled CHI. Film thicknesses were similar for native and cross-linked films. The film nanometer roughness was measured by atomic force microscopy and was found to be higher for cross-linked films. Cross-linking the films also leads to a drastic change in film stiffness. The elastic modulus of the films (Young's modulus) as measured by AFM nano-indentation was about tenfold increased for cross-linked films as compared to native ones. From a biological point of view, cross-liked films are more resistant to enzymatic degradation by hyaluronidase. Furthermore, the increase in film stiffness has a favorable effect on the adhesion and spreading of chondrosarcoma cells. Thus, the CHI/HA cross-linked films could be used for various applications due to their adhesive properties and to their mechanical properties (including stability in enzymatic media)

  4. Chitosan-hyaluronan/nano chondroitin sulfate ternary composite sponges for medical use.

    Science.gov (United States)

    Anisha, B S; Sankar, Deepthi; Mohandas, Annapoorna; Chennazhi, K P; Nair, Shantikumar V; Jayakumar, R

    2013-02-15

    In this work chitosan-hyaluronan composite sponge incorporated with chondroitin sulfate nanoparticle (nCS) was developed. The fabrication of hydrogel was based on simple ionic cross-linking using EDC, followed by lyophilization to obtain the composite sponge. nCS suspension was characterized using DLS and SEM and showed a size range of 100-150 nm. The composite sponges were characterized using SEM, FT-IR and TG-DTA. Porosity, swelling, biodegradation, blood clotting and platelet activation of the prepared sponges were also evaluated. Nanocomposites showed a porosity of 67% and showed enhanced swelling and blood clotting ability. Cytocompatibility and cell adhesion studies of the sponges were done using human dermal fibroblast (HDF) cells and the nanocomposite sponges showed more than 90% viability. Nanocomposite sponges also showed enhanced proliferation of HDF cells within two days of study. These results indicated that this nanocomposite sponges would be a potential candidate for wound dressing. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Composite Alginate-Hyaluronan Sponges for the Delivery of Tranexamic Acid in Postextractive Alveolar Wounds.

    Science.gov (United States)

    Catanzano, Ovidio; D'Esposito, Vittoria; Formisano, Pietro; Boateng, Joshua S; Quaglia, Fabiana

    2018-02-01

    The management of wounds in patients on anticoagulant therapy who require oral surgical procedures is problematic and often results in a nonsatisfactory healing process. Here, we report a method to prepare an advanced dressing able to avoid uncontrolled bleeding by occluding the postextractive alveolar wounds, and simultaneously, capable of a fast release of tranexamic acid (TA). Composite alginate/hyaluronan (ALG/HA) sponge dressings loaded with TA were prepared by a straightforward internal gelation method followed by a freeze-drying step. Both blank and drug-loaded sponges were soft, flexible, and elegant in appearance and nonbrittle in nature. Scanning electron microscopy analysis confirmed the porous nature of these dressings. The integration of HA influenced the microstructure, reducing the porosity, modifying the water uptake kinetic, and increasing the resistance to compression. TA release from ALG/HA sponges showed a controlled release up to 3 h, and it was faster in the presence of HA. Finally, an in vitro clotting test performed on human whole blood confirmed that the TA-loaded sponges significantly reduce the blood clotting index by 30% compared with ALG/HA 20 sponges. These results suggest that, if placed in a socket cavity, these dressings could give a relevant help to the blood hemostasis after dental extractions, especially in patients with coagulation disorders. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  6. Selective in vitro anticancer effect of superparamagnetic iron oxide nanoparticles loaded in hyaluronan polymeric micelles.

    Science.gov (United States)

    Smejkalová, Daniela; Nešporová, Kristina; Huerta-Angeles, Gloria; Syrovátka, Jakub; Jirák, Daniel; Gálisová, Andrea; Velebný, Vladimír

    2014-11-10

    Due to its native origin, excellent biocompatibility and biodegradability, hyaluronan (HA) represents an attractive polymer for superparamagnetic iron oxide nanoparticles (SPION) coating. Herein, we report HA polymeric micelles encapsulating oleic acid coated SPIONs, having a hydrodynamic size of about 100 nm and SPION loading capacity of 1-2 wt %. The HA-SPION polymeric micelles were found to be selectively cytotoxic toward a number of human cancer cell lines, mainly those of colon adenocarcinoma (HT-29). The selective inhibition of cell growth was even observed when the SPION loaded HA polymeric micelles were incubated with a mixture of control and cancer cells. The selective in vitro inhibition could not be connected with an enhanced CD44 uptake or radical oxygen species formation and was rather connected with a different way of SPION intracellular release. While aggregated iron particles were visualized in control cells, nonaggregated solubilized iron oxide particles were detected in cancer cells. In vivo SPION accumulation in intramuscular tumor following an intravenous micelle administration was confirmed by magnetic resonance (MR) imaging and histological analysis. Having a suitable hydrodynamic size, high magnetic relaxivity, and being cancer specific and able to accumulate in vivo in tumors, SPION-loaded HA micelles represent a promising platform for theranostic applications.

  7. Serum inter-alpha-trypsin inhibitor and matrix hyaluronan promote angiogenesis in fibrotic lung injury.

    Science.gov (United States)

    Garantziotis, Stavros; Zudaire, Enrique; Trempus, Carol S; Hollingsworth, John W; Jiang, Dianhua; Lancaster, Lisa H; Richardson, Elizabeth; Zhuo, Lisheng; Cuttitta, Frank; Brown, Kevin K; Noble, Paul W; Kimata, Koji; Schwartz, David A

    2008-11-01

    The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-alpha-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan (HA) and may contribute to the angiogenic response to tissue injury. To determine whether IaI promotes HA-mediated angiogenesis in tissue injury. An examination was undertaken of angiogenesis in IaI-sufficient and -deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. IaI and HA in patients with IPF were examined. IaI significantly enhances the angiogenic response to short-fragment HA in vivo and in vitro. lal deficiency Ieads to decreased angiogenesis in the matrigel model, and decreases lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it colocalizes with HA. The colocalization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and HA are significantly elevated in patients with IPF compared with control subjects. High serum IaI and HA levels are associated with decreased lung diffusing capacity, but not FVC. Our findings indicate that serum IaI interacts with HA, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis. Clinical trial registered with www.clinicaltrials.gov (NCT00016627).

  8. Serum Inter–α-Trypsin Inhibitor and Matrix Hyaluronan Promote Angiogenesis in Fibrotic Lung Injury

    Science.gov (United States)

    Garantziotis, Stavros; Zudaire, Enrique; Trempus, Carol S.; Hollingsworth, John W.; Jiang, Dianhua; Lancaster, Lisa H.; Richardson, Elizabeth; Zhuo, Lisheng; Cuttitta, Frank; Brown, Kevin K.; Noble, Paul W.; Kimata, Koji; Schwartz, David A.

    2008-01-01

    Rationale: The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-α-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan (HA) and may contribute to the angiogenic response to tissue injury. Objectives: To determine whether IaI promotes HA-mediated angiogenesis in tissue injury. Methods: An examination was undertaken of angiogenesis in IaI-sufficient and -deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. IaI and HA in patients with IPF were examined. Measurements and Main Results: IaI significantly enhances the angiogenic response to short-fragment HA in vivo and in vitro. lal deficiency Ieads to decreased angiogenesis in the matrigel model, and decreases lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it colocalizes with HA. The colocalization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and HA are significantly elevated in patients with IPF compared with control subjects. High serum IaI and HA levels are associated with decreased lung diffusing capacity, but not FVC. Conclusions: Our findings indicate that serum IaI interacts with HA, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis. Clinical trial registered with www.clinicaltrials.gov (NCT00016627). PMID:18703791

  9. Formulation and Evaluation of Organogels Containing Hyaluronan Microparticles for Topical Delivery of Caffeine.

    Science.gov (United States)

    Simsolo, Erol Eli; Eroğlu, İpek; Tanrıverdi, Sakine Tuncay; Özer, Özgen

    2018-04-01

    Cellulite is a dermal disorder including the extracellular matrix, the lymphatic and microcirculatory systems and the adipose tissue. Caffeine is used as the active moiety depending its preventive effect on localization of fat in the cellular structure. Hyaluronic acid (hyaluronan-HA) is a natural constituent of skin that generates formation and poliferation of new cells having a remarkable moisturizing ability. The aim of this study is to formulate HA microparticles loaded with caffeine via spray-drying method. Resulting microparticle formulations (33.97 ± 0.3 μm, span < 2, 88.56 ± 0.42% encapsulation efficiency) were distributed in lecithin organogels to maintain the proper viscosity for topical application. Following the characterization and cell culture studies, in vitro drug release and ex vivo permeation studies were performed. The accumulated amount of caffeine was twice higher than the aqueous solution for the microparticle-loaded organogels at 24 h (8262,673 μg/cm 2 versus 4676,691 μg/cm 2 ). It was related to the sustained behaviour of caffeine release from the microparticles. As a result, lecithin organogel containing HA-encapsulated microparticles could be considered as suitable candidate formulations for efficient topical drug delivery system of caffeine. In addition to that, synergistic effect of this combination appears as a promising approach for long-acting treatment of cellulite.

  10. Oleyl-hyaluronan micelles loaded with upconverting nanoparticles for bio-imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pospisilova, Martina, E-mail: martina.pospisilova@contipro.com; Mrazek, Jiri; Matuska, Vit; Kettou, Sofiane; Dusikova, Monika; Svozil, Vit; Nesporova, Kristina; Huerta-Angeles, Gloria; Vagnerova, Hana; Velebny, Vladimir [Contipro Biotech (Czech Republic)

    2015-09-15

    Hyaluronan (HA) represents an interesting polymer for nanoparticle coating due to its biocompatibility and enhanced cell interaction via CD44 receptor. Here, we describe incorporation of oleate-capped β–NaYF{sub 4}:Yb{sup 3+}, Er{sup 3+} nanoparticles (UCNP-OA) into amphiphilic HA by microemulsion method. Resulting structures have a spherical, micelle-like appearance with a hydrodynamic diameter of 180 nm. UCNP-OA-loaded HA micelles show a good stability in PBS buffer and cell culture media. The intensity of green emission of UCNP-OA-loaded HA micelles in water is about five times higher than that of ligand-free UCNP, indicating that amphiphilic HA effectively protects UCNP luminescence from quenching by water molecules. We found that UCNP-OA-loaded HA micelles in concentrations up to 50 μg mL{sup −1} increase cell viability of normal human dermal fibroblasts (NHDF), while viability of human breast adenocarcinoma cells MDA–MB–231 is reduced at these concentrations. The utility of UCNP-OA-loaded HA micelles as a bio-imaging probe was demonstrated in vitro by successful labelling of NHDF and MDA–MB–231 cells overexpressing the CD44 receptor.

  11. Hyaluronan/Tween 80-assisted synthesis of silver nanoparticles for biological application

    Science.gov (United States)

    Li, Hui-Jun; Zhang, An-Qi; Sui, Li; Qian, Dong-Jin; Chen, Meng

    2015-02-01

    Water-soluble and well-stabilized silver nanoparticles (NPs) of small size have been synthesized using hyaluronan (HA) and Tween 80 as reducing and stabilizing agents. The effect of reaction conditions on the formation process of silver NPs was studied, and an aggregative growth mechanism of the silver NPs dominated in HA/Tween 80 system at pH 12 has been proposed. The obtained Ag NPs were characterized by UV-Vis spectroscopy, transmission electron microscopy, X-ray powder diffraction, and X-ray photoelectron spectroscopy. Moreover, the stability of the HA-Tween 80-silver NPs in normal saline was also studied, and a flexible blend membrane containing chitosan, gelatin, and the HA-Tween 80-silver NPs was prepared for further biological applications. Due to the high specific surface area and improved stability of silver NPs, the chitosan-gelatin-silver membrane has shown high antibacterial activity for strains of Escherichia coli. The cell viability tests indicate that the polymer membrane is non-cytotoxic to HepG2 cells, which might be attributed to its good biocompatibility.

  12. Hyaluronan/Tween 80-assisted synthesis of silver nanoparticles for biological application

    International Nuclear Information System (INIS)

    Li, Hui-Jun; Zhang, An-Qi; Sui, Li; Qian, Dong-Jin; Chen, Meng

    2015-01-01

    Water-soluble and well-stabilized silver nanoparticles (NPs) of small size have been synthesized using hyaluronan (HA) and Tween 80 as reducing and stabilizing agents. The effect of reaction conditions on the formation process of silver NPs was studied, and an aggregative growth mechanism of the silver NPs dominated in HA/Tween 80 system at pH 12 has been proposed. The obtained Ag NPs were characterized by UV–Vis spectroscopy, transmission electron microscopy, X-ray powder diffraction, and X-ray photoelectron spectroscopy. Moreover, the stability of the HA–Tween 80-silver NPs in normal saline was also studied, and a flexible blend membrane containing chitosan, gelatin, and the HA–Tween 80-silver NPs was prepared for further biological applications. Due to the high specific surface area and improved stability of silver NPs, the chitosan–gelatin-silver membrane has shown high antibacterial activity for strains of Escherichia coli. The cell viability tests indicate that the polymer membrane is non-cytotoxic to HepG2 cells, which might be attributed to its good biocompatibility

  13. Anticancer Effects of Sinulariolide-Conjugated Hyaluronan Nanoparticles on Lung Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Kuan Yin Hsiao

    2016-03-01

    Full Text Available Lung cancer is one of the most clinically challenging malignant diseases worldwide. Sinulariolide (SNL, extracted from the farmed coral species Sinularia flexibilis, has been used for suppressing malignant cells. For developing anticancer therapeutic agents, we aimed to find an alternative for non-small cell lung cancer treatment by using SNL as the target drug. We investigated the SNL bioactivity on A549 lung cancer cells by conjugating SNL with hyaluronan nanoparticles to form HA/SNL aggregates by using a high-voltage electrostatic field system. SNL was toxic on A549 cells with an IC50 of 75 µg/mL. The anticancer effects of HA/SNL aggregates were assessed through cell viability assay, apoptosis assays, cell cycle analyses, and western blotting. The size of HA/SNL aggregates was approximately 33–77 nm in diameter with a thin continuous layer after aggregating numerous HA nanoparticles. Flow cytometric analysis revealed that the HA/SNL aggregate-induced apoptosis was more effective at a lower SNL dose of 25 µg/mL than pure SNL. Western blotting indicated that caspases-3, -8, and -9 and Bcl-xL and Bax played crucial roles in the apoptotic signal transduction pathway. In summary, HA/SNL aggregates exerted stronger anticancer effects on A549 cells than did pure SNL via mitochondria-related pathways.

  14. Hyaluronan - a functional and structural sweet spot in the tissue microenvironment

    Directory of Open Access Journals (Sweden)

    James eMonslow

    2015-05-01

    Full Text Available Transition from homeostatic to reactive matrix remodeling is a fundamental adaptive tissue response to injury, inflammatory disease, fibrosis and cancer. Alterations in architecture, physical properties and matrix composition result in changes in biomechanical and biochemical cellular signaling. The dynamics of pericellular and extracellular matrices, including matrix protein, proteoglycan and glycosaminoglycan modification are continually emerging as essential regulatory mechanisms underlying cellular and tissue function. Nevertheless, the impact of matrix organization on inflammation and immunity in particular, and the consequent effects on tissue healing and disease outcome are arguably under-studied aspects of adaptive stress responses. Herein, we review how the predominant glycosaminoglycan hyaluronan (HA contributes to the structure and function of the tissue microenvironment. Specifically, we examine the evidence of HA degradation and the generation of biologically-active smaller HA fragments in pathological settings in vivo. We discuss how HA fragments versus nascent HA via alternate receptor-mediated signaling influence inflammatory cell recruitment and differentiation, resident cell activation, as well as tumor growth, survival and metastasis. Finally, we discuss how HA fragmentation impacts restoration of normal tissue function and pathological outcomes in disease.

  15. Novel enzymatically cross-linked hyaluronan hydrogels support the formation of 3D neuronal networks.

    Science.gov (United States)

    Broguiere, Nicolas; Isenmann, Luca; Zenobi-Wong, Marcy

    2016-08-01

    Hyaluronan (HA) is an essential component of the central nervous system's extracellular matrix and its high molecular weight (MW) form has anti-inflammatory and anti-fibrotic properties relevant for regenerative medicine. Here, we introduce a new hydrogel based on high MW HA which is cross-linked using the transglutaminase (TG) activity of the activated blood coagulation factor XIII (FXIIIa). These HA-TG gels have significant advantages for neural tissue engineering compared to previous HA gels. Due to their chemical inertness in the absence of FXIIIa, the material can be stored long-term, is stable in solution, and shows no cytotoxicity. The gelation is completely cell-friendly due to the specificity of the enzyme and the gelation rate can be tuned from seconds to hours at physiological pH and independently of stiffness. The gels are injectable, and attach covalently to fibrinogen and fibrin, two common bioactive components in in vitro tissue engineering, as well as proteins present in vivo, allowing the gels to covalently bind to brain or spinal cord defects. These optimal chemical and bioactive properties of HA-TG gels enabled the formation of 3D neuronal cultures of unprecedented performance, showing fast neurite outgrowth, axonal and dendritic speciation, strong synaptic connectivity in 3D networks, and rapidly-occurring and long-lasting coordinated electrical activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Fabrication of Hyaluronan-Poly(vinylphosphonic acid-Chitosan Hydrogel for Wound Healing Application

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    Dang Hoang Phuc

    2016-01-01

    Full Text Available A new hydrogel made of hyaluronan, poly(vinylphosphonic acid, and chitosan (HA/PVPA/CS hydrogel was fabricated and characterized to be used for skin wound healing application. Firstly, the component ratio of hydrogel was studied to optimize the reaction effectiveness. Next, its microstructure was observed by light microscope. The chemical interaction in hydrogel was evaluated by nuclear magnetic resonance spectroscopy and Fourier transform-infrared spectroscopy. Then, a study on its degradation rate was performed. After that, antibacterial activity of the hydrogel was examined by agar diffusion method. Finally, in vivo study was performed to evaluate hydrogel’s biocompatibility. The results showed that the optimized hydrogel had a three-dimensional highly porous structure with the pore size ranging from about 25 µm to less than 125 µm. Besides, with a degradation time of two weeks, it could give enough time for the formation of extracellular matrix framework during remodeling stages. Furthermore, the antibacterial test showed that hydrogel has antimicrobial activity against E. coli. Finally, in vivo study indicated that the hydrogel was not rejected by the immune system and could enhance wound healing process. Overall, HA/PVPA/CS hydrogel was successfully fabricated and results implied its potential for wound healing applications.

  17. Layilin, a cell surface hyaluronan receptor, interacts with merlin and radixin

    International Nuclear Information System (INIS)

    Bono, Petri; Cordero, Etchell; Johnson, Kristen; Borowsky, Mark; Ramesh, Vijaya; Jacks, Tyler; Hynes, Richard O.

    2005-01-01

    Layilin is a widely expressed integral membrane hyaluronan receptor, originally identified as a binding partner of talin located in membrane ruffles. We have identified merlin, the neurofibromatosis type 2 tumor suppressor protein and radixin, as other interactors with the carboxy-terminal domain of layilin. We show that the carboxy-terminal domain of layilin is capable of binding to the amino-terminal domain of radixin. An interdomain interaction between the amino- and the carboxy-terminal domains of radixin inhibits its ability to bind to layilin. In the presence of acidic phospholipids, the interdomain interaction of radixin is inhibited and layilin can bind to full-length radixin. In contrast, layilin binds both full-length and amino-terminal merlin-GST fusion proteins without a requirement for phospholipids. Furthermore, layilin antibody can immunoprecipitate merlin, confirming association in vivo between these two proteins, which also display similar subcellular localizations in ruffling membranes. No interaction was observed between layilin and ezrin or layilin and moesin. These findings expand the known binding partners of layilin to include other members of the talin/band 4.1/ERM (ezrin, radixin, and moesin) family of cytoskeletal-membrane linker molecules. This in turn suggests that layilin may mediate signals from extracellular matrix to the cell cytoskeleton via interaction with different intracellular binding partners and thereby be involved in the modulation of cortical structures in the cell

  18. Chemical similarity between historical and novel host plants promotes range and host expansion of the mountain pine beetle in a naïve host ecosystem.

    Science.gov (United States)

    Erbilgin, Nadir; Ma, Cary; Whitehouse, Caroline; Shan, Bin; Najar, Ahmed; Evenden, Maya

    2014-02-01

    Host plant secondary chemistry can have cascading impacts on host and range expansion of herbivorous insect populations. We investigated the role of host secondary compounds on pheromone production by the mountain pine beetle (Dendroctonus ponderosae) (MPB) and beetle attraction in response to a historical (lodgepole pine, Pinus contorta var. latifolia) and a novel (jack pine, Pinus banksiana) hosts, as pheromones regulate the host colonization process. Beetles emit the same pheromones from both hosts, but more trans-verbenol, the primary aggregation pheromone, was emitted by female beetles on the novel host. The phloem of the novel host contains more α-pinene, a secondary compound that is the precursor for trans-verbenol production in beetle, than the historical host. Beetle-induced emission of 3-carene, another secondary compound found in both hosts, was also higher from the novel host. Field tests showed that the addition of 3-carene to the pheromone mixture mimicking the aggregation pheromones produced from the two host species increased beetle capture. We conclude that chemical similarity between historical and novel hosts has facilitated host expansion of MPB in jack pine forests through the exploitation of common host secondary compounds for pheromone production and aggregation on the hosts. Furthermore, broods emerging from the novel host were larger in terms of body size. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  19. Teotihuacan, tepeapulco, and obsidian exploitation.

    Science.gov (United States)

    Charlton, T H

    1978-06-16

    Current cultural ecological models of the development of civilization in central Mexico emphasize the role of subsistence production techniques and organization. The recent use of established and productive archeological surface survey techniques along natural corridors of communication between favorable niches for cultural development within the Central Mexican symbiotic region resulted in the location of sites that indicate an early development of a decentralized resource exploitation, manufacturing, and exchange network. The association of the development of this system with Teotihuacán indicates the importance such nonsubsistence production and exchange had in the evolution of this first central Mexican civilization. The later expansion of Teotihuacán into more distant areas of Mesoamerica was based on this resource exploitation model. Later civilizations centered at Tula and Tenochtitlán also used such a model in their expansion.

  20. Network exploitation using WAMI tracks

    Science.gov (United States)

    Rimey, Ray; Record, Jim; Keefe, Dan; Kennedy, Levi; Cramer, Chris

    2011-06-01

    Creating and exploiting network models from wide area motion imagery (WAMI) is an important task for intelligence analysis. Tracks of entities observed moving in the WAMI sensor data are extracted, then large numbers of tracks are studied over long time intervals to determine specific locations that are visited (e.g., buildings in an urban environment), what locations are related to other locations, and the function of each location. This paper describes several parts of the network detection/exploitation problem, and summarizes a solution technique for each: (a) Detecting nodes; (b) Detecting links between known nodes; (c) Node attributes to characterize a node; (d) Link attributes to characterize each link; (e) Link structure inferred from node attributes and vice versa; and (f) Decomposing a detected network into smaller networks. Experimental results are presented for each solution technique, and those are used to discuss issues for each problem part and its solution technique.

  1. Standing genetic variation in host preference for mutualist microbial symbionts.

    Science.gov (United States)

    Simonsen, Anna K; Stinchcombe, John R

    2014-12-22

    Many models of mutualisms show that mutualisms are unstable if hosts lack mechanisms enabling preferential associations with mutualistic symbiotic partners over exploitative partners. Despite the theoretical importance of mutualism-stabilizing mechanisms, we have little empirical evidence to infer their evolutionary dynamics in response to exploitation by non-beneficial partners. Using a model mutualism-the interaction between legumes and nitrogen-fixing soil symbionts-we tested for quantitative genetic variation in plant responses to mutualistic and exploitative symbiotic rhizobia in controlled greenhouse conditions. We found significant broad-sense heritability in a legume host's preferential association with mutualistic over exploitative symbionts and selection to reduce frequency of associations with exploitative partners. We failed to detect evidence that selection will favour the loss of mutualism-stabilizing mechanisms in the absence of exploitation, as we found no evidence for a fitness cost to the host trait or indirect selection on genetically correlated traits. Our results show that genetic variation in the ability to preferentially reduce associations with an exploitative partner exists within mutualisms and is under selection, indicating that micro-evolutionary responses in mutualism-stabilizing traits in the face of rapidly evolving mutualistic and exploitative symbiotic bacteria can occur in natural host populations. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  2. Viscoelastic Properties of Hyaluronan in Physiological Conditions [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Mary K. Cowman

    2015-08-01

    Full Text Available Hyaluronan (HA is a high molecular weight glycosaminoglycan of the extracellular matrix (ECM, which is particularly abundant in soft connective tissues. Solutions of HA can be highly viscous with non-Newtonian flow properties. These properties affect the movement of HA-containing fluid layers within and underlying the deep fascia. Changes in the concentration, molecular weight, or even covalent modification of HA in inflammatory conditions, as well as changes in binding interactions with other macromolecules, can have dramatic effects on the sliding movement of fascia. The high molecular weight and the semi-flexible chain of HA are key factors leading to the high viscosity of dilute solutions, and real HA solutions show additional nonideality and greatly increased viscosity due to mutual macromolecular crowding. The shear rate dependence of the viscosity, and the viscoelasticity of HA solutions, depend on the relaxation time of the molecule, which in turn depends on the HA concentration and molecular weight. Temperature can also have an effect on these properties. High viscosity can additionally affect the lubricating function of HA solutions. Immobility can increase the concentration of HA, increase the viscosity, and reduce lubrication and gliding of the layers of connective tissue and muscle. Over time, these changes can alter both muscle structure and function. Inflammation can further increase the viscosity of HA-containing fluids if the HA is modified via covalent attachment of heavy chains derived from Inter-α-Inhibitor. Hyaluronidase hydrolyzes HA, thus reducing its molecular weight, lowering the viscosity of the extracellular matrix fluid and making outflow easier. It can also disrupt any aggregates or gel-like structures that result from HA being modified. Hyaluronidase is used medically primarily as a dispersion agent, but may also be useful in conditions where altered viscosity of the fascia is desired, such as in the treatment of

  3. Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair.

    Directory of Open Access Journals (Sweden)

    Cornelia Tolg

    Full Text Available The extracellular matrix polysaccharide hyaluronan (HA plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous.

  4. Peritoneal Adhesion and Angiogenesis in Ovarian Carcinoma Are Inversely Regulated by Hyaluronan: The Role of Gonadotropins

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    Yael Chagit Tzuman

    2010-01-01

    Full Text Available Ovarian carcinoma is the leading cause of death among gynecologic cancers. Although transformation of the outer ovarian epithelium was linked with ovulation, the disease is significantly more prevalent and severe in postmenopausal women. We postulated that menopause could augment ovarian cancer progression through the effects of gonadotropins on multifocal seeding to the mesothelial layer lining the peritoneum. This seeding is mediated by integrins as well as by CD44 interaction with hyaluronan (HA. Here, we report the effect of gonadotropins on HA synthesis and degradation and on peritoneal adhesion. A significant concentration- and time-dependent induction in expression levels of HA synthases (HASs and hyaluronidases (Hyals was observed in vitro on stimulation of human epithelial ovarian carcinoma cells by gonadotropins. Hormonal regulation of HA-mediated adhesion was manifested in vivo as well, by fluorescence microscopy of stained MLS multicellular tumor spheroids. The number of spheroids adhered to the mesothelium of ovariectomized CD-1 nude mice 9.5 hours after intraperitoneal insertion was significantly higher than in nonovariectomized mice. Inhibition of HA synthesis by 6-diazo-5-oxo-1-norleucine (DON both in spheroids and ovariectomized mice significantly reduced the number of adhered spheroids. Thus, the change in the hormonal environment during menopause assists in HA-dependent adherence of ovarian cancer spheroids onto the peritoneum. However, HA is antiangiogenic and it can significantly suppress tumor progression. Accordingly, angiogenesis of the adhered spheroids was significantly elevated in DON-treated tumors. These results can explain the selective pressure that can lead to simultaneously increased tumor expression of both HASs and Hyals.

  5. Mucoadhesive Polymer Hyaluronan as Biodegradable Cationic/Zwitterionic-Drug Delivery Vehicle

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    Francisco Torrens

    2015-01-01

    Full Text Available Mucoadhesive polymers in pharmaceutical formulations release drugs in mucosal areas. They interact and fix to mucus via molecular interpenetration, etc., which increase drug bioavailability. Polymers physicochemical properties affect formulation mucoadhesion, rheological behaviour and drug absorption. Hyaluronan (HA is selected as a mucoadhesive and biodegradable polymer. Geometric, topological and fractal analyses are carried out with program TOPO. Reference calculations are performed with algorithm GEPOL. Procedure TOPO underestimates molecular volume by 0.7%. Error results 5% in surface area and derived topological indices. Solvent-accessible surface is undercalculated by 3%: from hexamer HA to HA·3Ca and hydrate, the hydrophobic term rises by 42% and decays by 26%, and hydrophilic part drops by 14% and rises by 58% in agreement with the number of H-bonds. Accessibility rises by 9% and decays by 8%. Fractal dimension is underevaluated by 1% and for HA it results 1.566; on going to HA·3Ca and hydrate it rises by 2% and 1%. External-atoms dimension increases by 11%: for HA it results 1.725. When going to HA·3Ca and hydrate, it augments by 4% and 0.3%. On going from HA to HA·3Ca and hydrate, nonburied minus molecular dimension enlarges by 20% and decays by 9%. The hydrate globularity is lower than for water, Ca2+ and averages of O-atoms in HA. Ca2+ rugosity is smaller than for hydrate, averages of O-atoms in HA and water. Ca2+ and water accessibilities are greater than for hydrate. As cations exchange in HA·3Ca requires Ca2+ alteration, rises of drug zwitterionic character and acidic pH increase absorption.

  6. Changes in condylar coefficient of friction after osteochondral graft transplantation and modulation with hyaluronan.

    Science.gov (United States)

    Lane, John; Healey, Robert; Amiel, David

    2009-12-01

    To better understand the changes in the cartilage coefficient of friction (COF) after an osteochondral repair, an assessment of dynamic loads has been developed using a goat knee model. The application of hyaluronan (HA) was also assessed for its lubricative properties and the resulting COF of the knee after osteochondral repair. A total of 18 caprine knees were dissected and mounted into an Instron load frame (Instron, Norwood, MA) for testing. The COF was measured in 10 knees relative to the normal, unaltered joint and then calibrated to account for friction of the system. These experimental knees were tested in 5 modes: normal; empty 4.5-mm defect; and osteochondral repairs that were elevated, flush, or depressed relative to the cartilage surface. Saline solution lavage kept the knees moist during testing. The effect of HA was evaluated after mechanical testing. Eight knees were used to study the effect of lavage on the joints because of the significant increase in the COF that it produced. Whereas all modes increased the COF from normal levels, the most significant changes occurred when there was proud placement. Increases of 4 times the normal friction levels were measured. Increases in the COF were also associated with saline solution lavage (0.006 to 0.046). There was a significant reduction in friction after HA injection, which reduced the COF to near-normal levels. There is a significant increase in the COF associated with saline solution lavage and an osteochondral plug being left proud, which can be temporarily reduced with a lubricative material such as HA. Dramatic increases in the COF can potentially damage chondrocytes when the patient begins articulating the joint after surgery. Such injuries may affect the ability of the cartilage to heal fully. Reducing the elevated COF with lubricating materials, such as HA, is recommended based on the results of this study.

  7. Breaching the Castle Walls: Hyaluronan-Depletion as a Therapeutic Approach to Cancer Therapy

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    H Michael eShepard

    2015-08-01

    Full Text Available Hyaluronan (HA has many functions in the extracellular milieu of normal and diseased tissues. Disease-associated HA accumulation has been shown to predict a worsened prognosis in cancer patients, with tumors having a high extracellular HA content (HA-high being more aggressive than their HA-low counterparts. HA-high tumor aggressiveness is derived from the specialized biomechanical and molecular properties of the HA-based assembly of HA binding proteins and the growth-promoting factors that accumulate in it. Biophysical characteristics of an HA-high tumor microenvironment include high tumor interstitial pressure, compression of tumor vasculature, and resulting tumor hypoxia. Within the tumor cell membrane, HA receptors, primarily CD44 and RHAMM, anchor the HA-high extracellular network. HA-CD44 association on the tumor cell surface enhances receptor tyrosine kinase activity to drive tumor progression and treatment resistance. Together, malignant cells in this HA-high matrix may evolve dependency on it for growth. This yields the hypothesis that depleting HA in HA-high tumors may be associated with a therapeutic benefit. A pegylated form of recombinant human hyaluronidase PH20 (PEGPH20 has been deployed as a potential cancer therapeutic in HA-high tumors. PEGPH20 can collapse this matrix by degrading the HA-assembled tumor extracellular framework, leading to tumor growth inhibition, preferentially in HA-high tumors. Enzymatic depletion of HA by PEGPH20 results in re-expansion of the tumor vasculature, reduction in tumor hypoxia, and increased penetration of therapeutic molecules into the tumor. Finally, HA depletion results in reduced signaling via CD44/RHAMM. Taken together, HA-depletion strategies accomplish their antitumor effects by multiple mechanisms that include targeting both biophysical and molecular signaling pathways. Ongoing clinical trials are examining the potential of PEGPH20 in combination with partner therapeutics in several

  8. Regulation of proximal tubular epithelial cell CD44-mediated binding and internalisation of hyaluronan.

    Science.gov (United States)

    Jones, Stuart George; Ito, Takafumi; Phillips, Aled Owain

    2003-09-01

    Increased expression of the connective tissue polysaccharide hyaluronan (HA) in the renal corticointerstitium is associated with progressive renal fibrosis. Numerous studies have demonstrated involvement proximal tubular epithelial cells in the fibrotic process and in the current study we have characterised their expression of the HA receptor, CD44, and examined changes in CD44 expression and function in response to either IL-1beta or glucose. Characterisation of CD44 splice variant expression was carried out in primary cultures of human proximal tubular cells (PTC) and HK2 cells. Binding and internalisation HA was examined by addition of exogenous of fluorescein-HA (fl-HA), and expression of CD44 examined by immunoblot analysis and flow cytometry. Alteration in "functional" CD44 was determined by immunoprecipitation of CD44 following stimulation in the presence of fl-HA. PTC, both primary culture and the PTC cell line, HK2, express at least 5 CD44 splice variants, the expression of which are not altered by addition of either IL-1beta or 25mM D-glucose. Addition of either stimulus increased cell surface binding and internalisation of fl-HA and increased expression of functionally active CD44. Increased binding and internalisation of fl-HA, was blocked by anti-CD44 antibody, and by the inhibition of O-glycosylation. The data demonstrate that stimuli inducing PTC HA synthesis also regulate PTC-HA interactions. Furthermore increased HA binding and internalisation is the result of post-translational modification of CD44 by O-glycosylation, rather than by alteration in expression of CD44 at the cell surface, or by alternate use of CD44 splice variants.

  9. Dietary flavonoid fisetin increases abundance of high-molecular-mass hyaluronan conferring resistance to prostate oncogenesis.

    Science.gov (United States)

    Lall, Rahul K; Syed, Deeba N; Khan, Mohammad Imran; Adhami, Vaqar M; Gong, Yuansheng; Lucey, John A; Mukhtar, Hasan

    2016-09-01

    We and others have shown previously that fisetin, a plant flavonoid, has therapeutic potential against many cancer types. Here, we examined the probable mechanism of its action in prostate cancer (PCa) using a global metabolomics approach. HPLC-ESI-MS analysis of tumor xenografts from fisetin-treated animals identified several metabolic targets with hyaluronan (HA) as the most affected. Efficacy of fisetin on HA was then evaluated in vitro and also in vivo in the transgenic TRAMP mouse model of PCa. Size exclusion chromatography-multiangle laser light scattering (SEC-MALS) was performed to analyze the molar mass (Mw) distribution of HA. Fisetin treatment downregulated intracellular and secreted HA levels both in vitro and in vivo Fisetin inhibited HA synthesis and degradation enzymes, which led to cessation of HA synthesis and also repressed the degradation of the available high-molecular-mass (HMM)-HA. SEC-MALS analysis of intact HA fragment size revealed that cells and animals have more abundance of HMM-HA and less of low-molecular-mass (LMM)-HA upon fisetin treatment. Elevated HA levels have been shown to be associated with disease progression in certain cancer types. Biological responses triggered by HA mainly depend on the HA polymer length where HMM-HA represses mitogenic signaling and has anti-inflammatory properties whereas LMM-HA promotes proliferation and inflammation. Similarly, Mw analysis of secreted HA fragment size revealed less HMM-HA is secreted that allowed more HMM-HA to be retained within the cells and tissues. Our findings establish that fisetin is an effective, non-toxic, potent HA synthesis inhibitor, which increases abundance of antiangiogenic HMM-HA and could be used for the management of PCa. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Microneedle fractional radiofrequency increases epidermal hyaluronan and reverses age-related epidermal dysfunction.

    Science.gov (United States)

    Lee, Hee Jung; Seo, Seong Rak; Yoon, Moon Soo; Song, Ji-Ye; Lee, Eun Young; Lee, Sang Eun

    2016-02-01

    Skin aging results in physiological alterations in keratinocyte activities and epidermal function, as well as dermal changes. Yet, the cellular and molecular mechanisms that cause epidermal dysfunction during skin aging are not well understood. Recently, the role of epidermal hyaluronan (HA) as an active regulator of dynamic cellular processes is getting attention and alterations in HA metabolism are thought to be important in age-related epidermal dysfunction. Microneedle fractional radiofrequency (RF) has shown effects for improving cutaneous aging. However, little is known about the effects of fractional RF on the epidermal HA and epidermal function. We investigated the effect of microneedle fractional RF on the expression of epidermal HA in young and aged mice epidermis. We performed fractional RF on the dorsal skin of 30 8-week-old (young) hairless mice and 15 47-week-old (aged) C57BL/6J mice. Skin samples were collected on day 1, 3, and 7. HA content was measured by ELISA. Gene expressions of CD 44, HABP4, and HAS3 were measured using real time RT-PCR. Immunohistochemistry for detection of HA, CD44, PCNA, and filaggrin were performed. HA content and the mRNA levels of HABP4, CD44, and HAS3 were upregulated in the epidermis of both young and aged mice after microneedle fractional RF treatment. The expression was increased from day 1 after treatment and increased expression persisted on day 7. Fractional RF treatment significantly increased PCNA and filaggrin expression only in the aged mice skin. Microneedle fractional RF increased epidermal HA and CD44 expression in both young and aged mice and reversed age-related epidermal dysfunction especially in aged mice, suggesting a new mechanism involved in the skin rejuvenation effect of microneedle fractional RF. © 2015 Wiley Periodicals, Inc.

  11. Hyaluronan-modified superparamagnetic iron oxide nanoparticles for bimodal breast cancer imaging and photothermal therapy

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    Yang R

    2016-12-01

    Full Text Available Rui-Meng Yang,1,* Chao-Ping Fu,2,* Jin-Zhi Fang,1 Xiang-Dong Xu,1 Xin-Hua Wei,1 Wen-Jie Tang,1 Xin-Qing Jiang,1 Li-Ming Zhang2 1Department of Radiology, Guangzhou First People’s Hospital, Guangzhou Medical University, 2School of Materials Science and Engineering, School of Chemistry, Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Abstract: Theranostic nanoparticles with both imaging and therapeutic abilities are highly promising in successful diagnosis and treatment of the most devastating cancers. In this study, the dual-modal imaging and photothermal effect of hyaluronan (HA-modified superparamagnetic iron oxide nanoparticles (HA-SPIONs, which was developed in a previous study, were investigated for CD44 HA receptor-overexpressing breast cancer in both in vitro and in vivo experiments. Heat is found to be rapidly generated by near-infrared laser range irradiation of HA-SPIONs. When incubated with CD44 HA receptor-overexpressing MDA-MB-231 cells in vitro, HA-SPIONs exhibited significant specific cellular uptake and specific accumulation confirmed by Prussian blue staining. The in vitro and in vivo results of magnetic resonance imaging and photothermal ablation demonstrated that HA-SPIONs exhibited significant negative contrast enhancement on T2-weighted magnetic resonance imaging and photothermal effect targeted CD44 HA receptor-overexpressing breast cancer. All these results indicated that HA-SPIONs have great potential for effective diagnosis and treatment of cancer. Keywords: iron oxide nanoparticles, surface functionalization, bioactive glycosaminoglycan, magnetic resonance imaging, cellular uptake, breast carcinoma

  12. The influence of hyaluronan on the structure of a DPPC-bilayer under high pressures.

    Science.gov (United States)

    Zander, Thomas; Wieland, D C Florian; Raj, Akanksha; Wang, Min; Nowak, Benedikt; Krywka, Christina; Dėdinaitė, Andra; Claesson, Per Martin; Garamus, Vasil M; Schreyer, Andreas; Willumeit-Römer, Regine

    2016-06-01

    The superior lubrication properties of synovial joints have inspired many studies aiming at uncovering the molecular mechanisms which give rise to low friction and wear. However, the mechanisms are not fully understood yet, and, in particular, it has not been elucidated how the biolubricants present at the interface of cartilage respond to high pressures, which arise during high loads of joints. In this study we utilize a simple model system composed of two biomolecules that have been implied as being important for joint lubrication. It consists of a solid supported dipalmitoylphosphatidylcholin (DPPC) bilayer, which was formed via vesicles fusion on a flat Si wafer, and the anionic polysaccharide hyaluronan (HA). We first characterized the structure of the HA layer that adsorbed to the DPPC bilayers at ambient pressure and different temperatures using X-ray reflectivity (XRR) measurements. Next, XRR was utilized to evaluate the response of the system to high hydrostatic pressures, up to 2kbar (200MPa), at three different temperatures. By means of fluorescence microscopy images the distribution of DPPC and HA on the surface was visualized. Our data suggest that HA adsorbs to the headgroup region that is oriented towards the water side of the supported bilayer. Phase transitions of the bilayer in response to temperature and pressure changes were also observed in presence and absence of HA. Our results reveal a higher stability against high hydrostatic pressures for DPPC/HA composite layers compared to that of the DPPC bilayer in absence of HA. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. A Novel Eliminase from a Marine Bacterium That Degrades Hyaluronan and Chondroitin Sulfate*

    Science.gov (United States)

    Han, Wenjun; Wang, Wenshuang; Zhao, Mei; Sugahara, Kazuyuki; Li, Fuchuan

    2014-01-01

    Lyases cleave glycosaminoglycans (GAGs) in an eliminative mechanism and are important tools for the structural analysis and oligosaccharide preparation of GAGs. Various GAG lyases have been identified from terrestrial but not marine organisms even though marine animals are rich in GAGs with unique structures and functions. Herein we isolated a novel GAG lyase for the first time from the marine bacterium Vibrio sp. FC509 and then recombinantly expressed and characterized it. It showed strong lyase activity toward hyaluronan (HA) and chondroitin sulfate (CS) and was designated as HA and CS lyase (HCLase). It exhibited the highest activities to both substrates at pH 8.0 and 0.5 m NaCl at 30 °C. Its activity toward HA was less sensitive to pH than its CS lyase activity. As with most other marine enzymes, HCLase is a halophilic enzyme and very stable at temperatures from 0 to 40 °C for up to 24 h, but its activity is independent of divalent metal ions. The specific activity of HCLase against HA and CS reached a markedly high level of hundreds of thousands units/mg of protein under optimum conditions. The HCLase-resistant tetrasaccharide Δ4,5HexUAα1-3GalNAc(6-O-sulfate)β1-4GlcUA(2-O-sulfate)β1-3GalNAc(6-O-sulfate) was isolated from CS-D, the structure of which indicated that HCLase could not cleave the galactosaminidic linkage bound to 2-O-sulfated d-glucuronic acid (GlcUA) in CS chains. Site-directed mutagenesis indicated that HCLase may work via a catalytic mechanism in which Tyr-His acts as the Brønsted base and acid. Thus, the identification of HCLase provides a useful tool for HA- and CS-related research and applications. PMID:25122756

  14. Inhibition of hyaluronan synthesis reduces versican and fibronectin levels in trabecular meshwork cells.

    Directory of Open Access Journals (Sweden)

    Kate E Keller

    Full Text Available Hyaluronan (HA is a major component of the extracellular matrix (ECM and is synthesized by three HA synthases (HAS. Similarities between the HAS2 knockout mouse and the hdf mutant mouse, which has a mutation in the versican gene, suggest that HA and versican expression may be linked. In this study, the relationship between HA synthesis and levels of versican, fibronectin and several other ECM components in trabecular meshwork cells from the anterior segment of the eye was investigated. HA synthesis was inhibited using 4-methylumbelliferone (4MU, or reduced by RNAi silencing of each individual HAS gene. Quantitative RT-PCR and immunoblotting demonstrated a reduction in mRNA and protein levels of versican and fibronectin. Hyaluronidase treatment also reduced versican and fibronectin levels. These effects could not be reversed by addition of excess glucose or glucosamine or exogenous HA to the culture medium. CD44, tenascin C and fibrillin-1 mRNA levels were reduced by 4MU treatment, but SPARC and CSPG6 mRNA levels were unaffected. Immunostaining of trabecular meshwork tissue after exposure to 4MU showed an altered localization pattern of HA-binding protein, versican and fibronectin. Reduction of versican by RNAi silencing did not affect HA concentration as assessed by ELISA. Together, these data imply that HA concentration affects synthesis of certain ECM components. Since precise regulation of the trabecular meshwork ECM composition and organization is required to maintain the aqueous humor outflow resistance and intraocular pressure homeostasis in the eye, coordinated coupling of HA levels and several of its ECM binding partners should facilitate this process.

  15. Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Nehrer, S. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)]. E-mail: stefan.nehrer@meduniwien.ac.at; Domayer, S. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Dorotka, R. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Schatz, K. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bindreiter, U. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Kotz, R. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2006-01-15

    Repair of articular cartilage represents a significant clinical problem and although various new techniques - including the use of autologous chondrocytes - have been developed within the last century the clinical efficacy of these procedures is still discussed controversially. Although autologous chondrocyte transplantation (ACT) has been widely used with success, it has several inherent limitations, including its invasive nature and problems related to the use of the periosteal flap. To overcome these problems autologous chondrocytes transplantation combined with the use of biodegradable scaffolds has received wide attention. Among these, a hyaluronan-based scaffold has been found useful for inducing hyaline cartilage regeneration. In the present study, we have investigated the mid-term efficacy and safety of Hyalograft[reg] C grafts in a group of 36 patients undergoing surgery for chronic cartilage lesions of the knee. Clinical Outcome was assessed prospectively before and at 12, 24, and 36 months after surgery. No major adverse events have been reported during the 3-year follow-up. Significant improvements of the evaluated scores were observed (P < 0.02) at 1 year and a continued increase of clinical performance was evident at 2 and 3 years follow-up. Patients under 30 years of age with single lesions showed statistically significant improvements at all follow-up visits compared to those over 30 with multiple defects (P < 0.01). Hyalograft[reg] C compares favorably with classic ACT and is particularly indicated in younger patients with single lesions. The graft can be implanted through a miniarthrotomy and needs no additional fixation with sutures except optional fibrin gluing at the defect borders. These results suggest that Hyalograft[reg] C is a valid alternative to ACT.

  16. Arrival time distributions of product ions reveal isomeric ratio of deprotonated molecules in ion mobility-mass spectrometry of hyaluronan-derived oligosaccharides

    Czech Academy of Sciences Publication Activity Database

    Hermanová, M.; Iordache, A.-M.; Slováková, K.; Havlíček, Vladimír; Pelantová, Helena; Lemr, Karel

    2015-01-01

    Roč. 50, č. 6 (2015), s. 854-863 ISSN 1076-5174 R&D Projects: GA ČR(CZ) GAP206/12/1150 Institutional support: RVO:61388971 Keywords : tyramine-based hyaluronan derivatives * isomer discrimination * ion mobility Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.541, year: 2015

  17. Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma.

    Science.gov (United States)

    Mundt, Filip; Nilsonne, Gustav; Arslan, Sertaç; Csürös, Karola; Hillerdal, Gunnar; Yildirim, Huseyin; Metintas, Muzaffer; Dobra, Katalin; Hjerpe, Anders

    2013-01-01

    Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39), N-ERC/mesothelin (4.81, 3.19-7.93), CERC/mesothelin (3.58, 2.43-5.59) and syndecan-1 (1.34, 1.03-1.77). A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00) in the model generation dataset and 0.83 (0.74-0.91) in the validation dataset, respectively. A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.

  18. Effects of low molecular weight hyaluronan combined with carprofen on canine osteoarthritis articular chondrocytes and cartilage explants in vitro.

    Science.gov (United States)

    Euppayo, Thippaporn; Siengdee, Puntita; Buddhachat, Kittisak; Pradit, Waranee; Viriyakhasem, Nawarat; Chomdej, Siriwadee; Ongchai, Siriwan; Harada, Yasuji; Nganvongpanit, Korakot

    2015-09-01

    Intra-articular injection with non-steroidal anti-inflammatory drugs (NSAIDs) is used to treat inflammatory joint disease, but the side effects of NSAIDs include chondrotoxicity. Hyaluronan has shown positive effects on chondrocytes by reducing apoptosis and increasing proteoglycan synthesis. The purposes of this study were to evaluate the effects of low molecular weight hyaluronan (low MW HA), carprofen 25 mg/ml, carprofen 12.5 mg/ml, and a combination of HA and carprofen on canine osteoarthritis (OA) articular chondrocytes and a cartilage explant model in terms of cell viability, extracellular matrix remaining, and gene expression after exposure. In chondrocyte culture, MTT assay was used to evaluate the chondrotoxicity of IC50 and IC80 of carprofen with HA. In cartilage explant culture, two kinds of extracellular matrix (uronic acid and collagen) remaining in cartilage were used to evaluate cartilage damage for 14 d after treatment. Expression of COL2A1, AGG, and MMP3 was used to evaluate the synthesis and degradation of the matrix for 7 d after treatment. In chondrocyte culture, low MW HA could preserve OA chondrocyte viability but could not reduce the chondrotoxicity level of carprofen (P carprofen caused less destruction of uronic acid and collagen structure when compared with the control (P carprofen resulted in higher COL2A1 and AGG expression levels than carprofen alone.

  19. The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity.

    Science.gov (United States)

    Oohashi, Toshitaka; Edamatsu, Midori; Bekku, Yoko; Carulli, Daniela

    2015-12-01

    The hyaluronan and proteoglycanbinding link protein (Hapln) is a key molecule in the formation and control of hyaluronan-based condensed perineuronal matrix in the adult brain. This review summarizes the recent advances in understanding the role of Haplns in the formation and control of two distinct types of perineuronal matrices, one for "classical" PNN and the other for the specialized extracellular matrix (ECM) at the node of Ranvier in the central nervous system (CNS). We introduce the structural components of each ECM organization including the basic concept of supramolecular structure named "HLT model". We furthermore summarize the developmental and physiological role of perineuronal ECMs from the studies of Haplns and related molecules. Finally, we also discuss the potential mechanism modulating PNNs in the adult CNS. This layer of organized matrices may exert a direct effect via core protein or sugar moiety from the structure or by acting as a binding site for biologically active molecules, which are important for neuronal plasticity and saltatory conduction. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Local delivery of hyaluronan as an adjunct to scaling and root planing in the treatment of chronic periodontitis.

    Science.gov (United States)

    Johannsen, Annsofi; Tellefsen, Monica; Wikesjö, Ulf; Johannsen, Gunnar

    2009-09-01

    The aim of the present study was to evaluate the adjunctive effect of the local application of a hyaluronan gel to scaling and root planing in the treatment of chronic periodontitis. Twelve patients with chronic periodontitis were recruited to participate in a study with a split-mouth design and provided informed consent. Plaque formation and bleeding on probing were evaluated pretreatment (baseline) and at 1, 4, and 12 weeks post-treatment. Probing depths and attachment levels were evaluated at baseline and at 12 weeks. The patients received full-mouth scaling and root planing. A hyaluronan gel was administered subgingivally in the test sites at baseline and after 1 week. Significant differences between test and control were evaluated using the paired t test, repeated-measures analysis of variance (Wilks lambda), and a non-parametric Wilcoxon signed-rank test. A significant reduction in bleeding on probing scores and probing depths was observed in both groups at 12 weeks (P scaling and root planing may have a beneficial effect on periodontal health in patients with chronic periodontitis.

  1. A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation

    International Nuclear Information System (INIS)

    Nilsson, K.; Bjermer, L.; Hellstroem, S.H.; Henriksson, R.; Haellgren, R.

    1990-01-01

    Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue

  2. Prospects of geothermal resource exploitation

    International Nuclear Information System (INIS)

    Bourrelier, P.H.; Cornet, F.; Fouillac, C.

    1994-01-01

    The use of geothermal energy to generate electricity has only occurred during the past 50 years by drilling wells in aquifers close to magmas and producing either dry steam or hot water. The world's production of electricity from geothermal energy is over 6000 MWe and is still growing. The direct use of geothermal energy for major urban communities has been developed recently by exploitation of aquifers in sedimentary basins under large towns. Scaling up the extraction of heat implies the exploitation of larger and better located fields requiring an appropriate method of extraction; the objective of present attempts in USA, Japan and Europe is to create heat exchangers by the circulation of water between several deep wells. Two field categories are considered: the extension of classical geothermal fields beyond the aquifer areas, and areas favoured by both a high geothermal gradient, fractures inducing a natural permeability at large scale, and good commercial prospects (such as in the Rhenan Graben). Hot dry rocks concept has gained a large interest. 1 fig., 5 tabs., 11 refs

  3. A new measure of interpersonal exploitativeness

    Directory of Open Access Journals (Sweden)

    Amy B. Brunell

    2013-05-01

    Full Text Available Measures of exploitativeness evidence problems with validity and reliability. The present set of studies assessed a new measure (the Interpersonal Exploitativeness Scale that defines exploitativeness in terms of reciprocity. In Studies 1 and 2, 33 items were administered to participants. Exploratory and Confirmatory Factor Analysis demonstrated that a single factor consisting of six items adequately assess interpersonal exploitativeness. Study 3 results revealed that the Interpersonal Exploitativeness Scale was positively associated with normal narcissism, pathological narcissism, psychological entitlement, and negative reciprocity and negatively correlated with positive reciprocity. In Study 4, participants competed in a commons dilemma. Those who scored higher on the Interpersonal Exploitativeness Scale were more likely to harvest a greater share of resources over time, even while controlling for other relevant variables, such as entitlement. Together, these studies show the Interpersonal Exploitativeness Scale to be a valid and reliable measure of interpersonal exploitativeness. The authors discuss the implications of these studies.

  4. Exploitation in International Paid Surrogacy Arrangements

    OpenAIRE

    Wilkinson, Stephen

    2015-01-01

    Abstract Many critics have suggested that international paid surrogacy is exploitative. Taking such concerns as its starting point, this article asks: (1) how defensible is the claim that international paid surrogacy is exploitative and what could be done to make it less exploitative? (2) In the light of the answer to (1), how strong is the case for prohibiting it? Exploitation could in principle be dealt with by improving surrogates' pay and conditions. However, doing so may exacerbate probl...

  5. The exploitation argument against commercial surrogacy.

    Science.gov (United States)

    Wilkinson, Stephen

    2003-04-01

    This paper discusses the exploitation argument against commercial surrogacy: the claim that commercial surrogacy is morally objectionable because it is exploitative. The following questions are addressed. First, what exactly does the exploitation argument amount to? Second, is commercial surrogacy in fact exploitative? Third, if it were exploitative, would this provide a sufficient reason to prohibit (or otherwise legislatively discourage) it? The focus throughout is on the exploitation of paid surrogates, although it is noted that other parties (e.g. 'commissioning parents') may also be the victims of exploitation. It is argued that there are good reasons for believing that commercial surrogacy is often exploitative. However, even if we accept this, the exploitation argument for prohibiting (or otherwise legislatively discouraging) commercial surrogacy remains quite weak. One reason for this is that prohibition may well 'backfire' and lead to potential surrogates having to do other things that are more exploitative and/or more harmful than paid surrogacy. It is concluded therefore that those who oppose exploitation should (rather than attempting to stop particular practices like commercial surrogacy) concentrate on: (a) improving the conditions under which paid surrogates 'work'; and (b) changing the background conditions (in particular, the unequal distribution of power and wealth) which generate exploitative relationships.

  6. The Exploitation of Evolving Resources

    CERN Document Server

    McGlade, Jacqueline; Law, Richard

    1993-01-01

    The impact of man on the biosphere is profound. Quite apart from our capacity to destroy natural ecosystems and to drive species to extinction, we mould the evolution of the survivors by the selection pressures we apply to them. This has implications for the continued health of our natural biological resources and for the way in which we seek to optimise yield from those resources. Of these biological resources, fish stocks are particularly important to mankind as a source of protein. On a global basis, fish stocks provide the major source of protein for human consumption from natural ecosystems, amounting to some seventy million tonnes in 1970. Although fisheries management has been extensively developed over the last century, it has not hitherto considered the evolutionary consequences of fishing activity. While this omission may not have been serious in the past, the ever increasing intensity of exploitation and the deteriorating health of fish stocks has generated an urgent need for a better understanding...

  7. Swedish mines. Underground exploitation methods

    International Nuclear Information System (INIS)

    Paucard, A.

    1960-01-01

    Between 1949 and 1957, 10 engineers of the Mining research and exploitation department of the CEA visited 17 Swedish mines during 5 field trips. This paper presents a compilation of the information gathered during these field trips concerning the different underground mining techniques used in Swedish iron mines: mining with backfilling (Central Sweden and Boliden mines); mining without backfilling (mines of the polar circle area). The following techniques are described successively: pillar drawing and backfilled slices (Ammeberg, Falun, Garpenberg, Boliden group), sub-level pillar drawing (Grangesberg, Bloettberget, Haeksberg), empty room and sub-level pillar drawing (Bodas, Haksberg, Stripa, Bastkarn), storage chamber pillar drawing (Bodas, Haeksberg, Bastkarn), and pillar drawing by block caving (ldkerberget). Reprint of a paper published in Revue de l'Industrie Minerale, vol. 41, no. 12, 1959 [fr

  8. Exploiting social evolution in biofilms

    DEFF Research Database (Denmark)

    Boyle, Kerry E; Heilmann, Silja; van Ditmarsch, Dave

    2013-01-01

    Bacteria are highly social organisms that communicate via signaling molecules, move collectively over surfaces and make biofilm communities. Nonetheless, our main line of defense against pathogenic bacteria consists of antibiotics-drugs that target individual-level traits of bacterial cells...... and thus, regrettably, select for resistance against their own action. A possible solution lies in targeting the mechanisms by which bacteria interact with each other within biofilms. The emerging field of microbial social evolution combines molecular microbiology with evolutionary theory to dissect...... the molecular mechanisms and the evolutionary pressures underpinning bacterial sociality. This exciting new research can ultimately lead to new therapies against biofilm infections that exploit evolutionary cheating or the trade-off between biofilm formation and dispersal....

  9. Energy for lunar resource exploitation

    Science.gov (United States)

    Glaser, Peter E.

    1992-02-01

    Humanity stands at the threshold of exploiting the known lunar resources that have opened up with the access to space. America's role in the future exploitation of space, and specifically of lunar resources, may well determine the level of achievement in technology development and global economic competition. Space activities during the coming decades will significantly influence the events on Earth. The 'shifting of history's tectonic plates' is a process that will be hastened by the increasingly insistent demands for higher living standards of the exponentially growing global population. Key to the achievement of a peaceful world in the 21st century, will be the development of a mix of energy resources at a societally acceptable and affordable cost within a realistic planning horizon. This must be the theme for the globally applicable energy sources that are compatible with the Earth's ecology. It is in this context that lunar resources development should be a primary goal for science missions to the Moon, and for establishing an expanding human presence. The economic viability and commercial business potential of mining, extracting, manufacturing, and transporting lunar resource based materials to Earth, Earth orbits, and to undertake macroengineering projects on the Moon remains to be demonstrated. These extensive activities will be supportive of the realization of the potential of space energy sources for use on Earth. These may include generating electricity for use on Earth based on beaming power from Earth orbits and from the Moon to the Earth, and for the production of helium 3 as a fuel for advanced fusion reactors.

  10. Proba-V Mission Exploitation Platform

    Science.gov (United States)

    Goor, E.

    2017-12-01

    VITO and partners developed the Proba-V Mission Exploitation Platform (MEP) as an end-to-end solution to drastically improve the exploitation of the Proba-V (an EC Copernicus contributing mission) EO-data archive, the past mission SPOT-VEGETATION and derived vegetation parameters by researchers, service providers (e.g. the EC Copernicus Global Land Service) and end-users. The analysis of time series of data (PB range) is addressed, as well as the large scale on-demand processing of near real-time data on a powerful and scalable processing environment. New features are still developed, but the platform is yet fully operational since November 2016 and offers A time series viewer (browser web client and API), showing the evolution of Proba-V bands and derived vegetation parameters for any country, region, pixel or polygon defined by the user. Full-resolution viewing services for the complete data archive. On-demand processing chains on a powerfull Hadoop/Spark backend. Virtual Machines can be requested by users with access to the complete data archive mentioned above and pre-configured tools to work with this data, e.g. various toolboxes and support for R and Python. This allows users to immediately work with the data without having to install tools or download data, but as well to design, debug and test applications on the platform. Jupyter Notebooks is available with some examples python and R projects worked out to show the potential of the data. Today the platform is already used by several international third party projects to perform R&D activities on the data, and to develop/host data analysis toolboxes. From the Proba-V MEP, access to other data sources such as Sentinel-2 and landsat data is also addressed. Selected components of the MEP are also deployed on public cloud infrastructures in various R&D projects. Users can make use of powerful Web based tools and can self-manage virtual machines to perform their work on the infrastructure at VITO with access to

  11. Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Han NK

    2016-04-01

    Full Text Available Na-Kyung Han,1,* Dae Hwan Shin,1,* Jung Seok Kim,1 Kwon Yeon Weon,2 Chang-Young Jang,1 Jin-Seok Kim1 1Research Center for Cell Fate Control (RCCFC and College of Pharmacy, Sookmyung Women’s University, Seoul, 2College of Pharmacy, Catholic University of Daegu, Gyeongbuk, Korea *These authors contributed equally to this work Abstract: Investigation of potential therapeutics for targeting breast cancer stem cells (BCSCs is important because these cells are regarded as culprit of breast cancer relapse. Accomplishing this kind of strategy requires a specific drug-delivery system using the distinct features of liposomes. Studies on targeted liposomal delivery systems have indicated the conjugation of hyaluronan (HA, a primary ligand for CD44 surface markers, as an appropriate method for targeting BCSCs. For this study, enriched BCSCs were obtained by culturing MCF-7 breast cancer cells in nonadherent conditions. The enriched BCSCs were challenged with HA-conjugated liposomes encapsulating gemcitabine (2, 2-difluoro-2-deoxycytidine, GEM. In vitro study showed that the HA-conjugated liposomes significantly enhanced the cytotoxicity, anti-migration, and anti-colony formation abilities of GEM through targeting of CD44 expressed on BCSCs. In pharmacokinetic study, area under the drug concentration vs time curve (AUC of the immunoliposomal GEM was 3.5 times higher than that of free GEM, indicating that the HA-conjugated liposomes enhanced the stability of GEM in the bloodstream and therefore prolonged its half-life time. The antitumor effect of the immunoliposomal GEM was 3.3 times higher than that of free GEM in a xenograft mouse model, probably reflecting the unique targeting of the CD44 receptor by HA and the increased cytotoxicity and stability through the liposomal formulation. Furthermore, marginal change in body weight demonstrated that the use of liposomes considerably reduced the systemic toxicity of GEM on normal healthy cells. Taken together

  12. Hyaluronan microgel as a potential carrier for protein sustained delivery by tailoring the crosslink network

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Chunhong [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Zhao, Jianhao, E-mail: jhzhao@jnu.edu.cn [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China); Tu, Mei; Zeng, Rong; Rong, Jianhua [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China)

    2014-03-01

    Hyaluronan (HA) microgels with different crosslink network, i.e. HGPs-1, HGPs-1.5, HGPs-3, HGPs-6 and HGPs-15, were synthesized using divinyl sulfone (DVS) as the crosslinker in an inverse microemulsion system for controlling the sustained delivery of bovine serum albumin (BSA). With increasing the crosslinker content, the average particle size slightly increased from 1.9 ± 0.3 μm to 3.6 ± 0.5 μm by dynamic laser scattering analysis. However, the crosslinker content had no significant effect on the morphology of HA microgels by scanning and transmission electron microscopes. Fourier transform infrared spectroscopy and elemental analysis proved more sulfur participated in the crosslink reaction when raising the crosslinker amount. The water swelling test confirmed the increasing crosslink density with the crosslinker content by calculating the average molecular weight between two crosslink points to be 8.25 ± 2.51 × 10{sup 5}, 1.26 ± 0.43 × 10{sup 5}, 0.96 ± 0.09 × 10{sup 5}, 0.64 ± 0.03 × 10{sup 5}, and 0.11 ± 0.01 × 10{sup 5} respectively. The degradation of HA microgels by hyaluronidase slowed down by enhancing the crosslink density, only about 5% of HGPs-15 was degraded as opposed to over 90% for HGPs-1. BSA loading had no obvious influence on the surface morphology of HA microgels but seemed to induce their aggregation. The increase of crosslink density decreased the BSA loading capacity but facilitated its long-term sustained delivery. When the molar ratio of DVS to repeating unit of HA reached 3 or higher, similar delivery profiles were obtained. Among all these HA microgels, HGPs-3 was the optimal carrier for BSA sustained delivery in this system because it possessed both high BSA loading capacity and long-term delivery profile simultaneously. - Highlights: • HA microgels with different crosslink densities were prepared. • The crosslinker content had little effect on the morphology and size of HA microgels. • The crosslink density

  13. A novel eliminase from a marine bacterium that degrades hyaluronan and chondroitin sulfate.

    Science.gov (United States)

    Han, Wenjun; Wang, Wenshuang; Zhao, Mei; Sugahara, Kazuyuki; Li, Fuchuan

    2014-10-03

    Lyases cleave glycosaminoglycans (GAGs) in an eliminative mechanism and are important tools for the structural analysis and oligosaccharide preparation of GAGs. Various GAG lyases have been identified from terrestrial but not marine organisms even though marine animals are rich in GAGs with unique structures and functions. Herein we isolated a novel GAG lyase for the first time from the marine bacterium Vibrio sp. FC509 and then recombinantly expressed and characterized it. It showed strong lyase activity toward hyaluronan (HA) and chondroitin sulfate (CS) and was designated as HA and CS lyase (HCLase). It exhibited the highest activities to both substrates at pH 8.0 and 0.5 m NaCl at 30 °C. Its activity toward HA was less sensitive to pH than its CS lyase activity. As with most other marine enzymes, HCLase is a halophilic enzyme and very stable at temperatures from 0 to 40 °C for up to 24 h, but its activity is independent of divalent metal ions. The specific activity of HCLase against HA and CS reached a markedly high level of hundreds of thousands units/mg of protein under optimum conditions. The HCLase-resistant tetrasaccharide Δ(4,5)HexUAα1-3GalNAc(6-O-sulfate)β1-4GlcUA(2-O-sulfate)β1-3GalNAc(6-O-sulfate) was isolated from CS-D, the structure of which indicated that HCLase could not cleave the galactosaminidic linkage bound to 2-O-sulfated d-glucuronic acid (GlcUA) in CS chains. Site-directed mutagenesis indicated that HCLase may work via a catalytic mechanism in which Tyr-His acts as the Brønsted base and acid. Thus, the identification of HCLase provides a useful tool for HA- and CS-related research and applications. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Exploiting Symmetry on Parallel Architectures.

    Science.gov (United States)

    Stiller, Lewis Benjamin

    1995-01-01

    This thesis describes techniques for the design of parallel programs that solve well-structured problems with inherent symmetry. Part I demonstrates the reduction of such problems to generalized matrix multiplication by a group-equivariant matrix. Fast techniques for this multiplication are described, including factorization, orbit decomposition, and Fourier transforms over finite groups. Our algorithms entail interaction between two symmetry groups: one arising at the software level from the problem's symmetry and the other arising at the hardware level from the processors' communication network. Part II illustrates the applicability of our symmetry -exploitation techniques by presenting a series of case studies of the design and implementation of parallel programs. First, a parallel program that solves chess endgames by factorization of an associated dihedral group-equivariant matrix is described. This code runs faster than previous serial programs, and discovered it a number of results. Second, parallel algorithms for Fourier transforms for finite groups are developed, and preliminary parallel implementations for group transforms of dihedral and of symmetric groups are described. Applications in learning, vision, pattern recognition, and statistics are proposed. Third, parallel implementations solving several computational science problems are described, including the direct n-body problem, convolutions arising from molecular biology, and some communication primitives such as broadcast and reduce. Some of our implementations ran orders of magnitude faster than previous techniques, and were used in the investigation of various physical phenomena.

  15. Two questions about surrogacy and exploitation.

    Science.gov (United States)

    Wertheimer, Alan

    1992-01-01

    In this article I will consider two related questions about surrogacy and exploitation: (1) Is surrogacy exploitative? (2) If surrogacy is exploitative, what is the moral force of this exploitation? Briefly stated, I shall argue that whether surrogacy is exploitative depends on whether exploitation must be harmful to the exploited party or whether (as I think) there can be mutually advantageous exploitation. It also depends on some facts about surrogacy about which we have little reliable evidence and on our philosophical view on what counts as a harm to the surrogate. Our answer to the second question will turn in part on the account of exploitation we invoke in answering the first question and in part on the way in which we resolve some other questions about the justification of state interference. I shall suggest, however, that if surrogacy is a form of voluntary and mutually advantageous exploitation, then there is a strong presumption that surrogacy contracts should be permitted and even enforceable, although that presumption may be overridden on other grounds.

  16. A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

    Directory of Open Access Journals (Sweden)

    Brian G. Ballios

    2015-06-01

    Full Text Available The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs. The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

  17. Revealing the mechanisms of protein disorder and N-glycosylation in CD44-hyaluronan binding using molecular simulation

    Directory of Open Access Journals (Sweden)

    Olgun eGuvench

    2015-06-01

    Full Text Available The extracellular N-terminal hyaluronan binding domain (HABD of CD44 is a small globular domain that confers hyaluronan (HA binding functionality to this large transmembrane glycoprotein. When recombinantly expressed by itself, HABD exists as a globular water-soluble protein that retains the capacity to bind HA. This has enabled atomic-resolution structural biology experiments that have revealed the structure of HABD and its binding mode with oligomeric HA. Such experiments have also pointed to an order-to-disorder transition in HABD that is associated with HA binding. However, it had remained unclear how this structural transition was involved in binding since it occurs in a region of HABD distant from the HA-binding site. Furthermore, HABD is known to be N-glycosylated, and such glycosylation can diminish HA binding when the associated N-glycans are capped with sialic acid residues. The intrinsic flexibility of disordered proteins and of N-glycans makes it difficult to apply experimental structural biology approaches to probe the molecular mechanisms of how the order-to-disorder transition and N-glycosylation can modulate HA binding by HABD. We review recent results from molecular dynamics simulations that provide atomic-resolution mechanistic understanding of such modulation to help bridge gaps between existing experimental binding and structural biology data. Findings from these simulations include: Tyr42 may function as a molecular switch that converts the HA binding site from a low affinity to a high affinity state; in the partially-disordered form of HABD, basic amino acids in the C-terminal region can gain sufficient mobility to form direct contacts with bound HA to further stabilize binding; and terminal sialic acids on covalently-attached N-glycans can form charge-paired hydrogen bonding interactions with basic amino acids that could otherwise bind to HA, thereby blocking HA binding to glycosylated CD44 HABD.

  18. Altered expression of hyaluronan, HAS1-2, and HYAL1-2 in oral lichen planus.

    Science.gov (United States)

    Siponen, Maria; Kullaa, Arja; Nieminen, Pentti; Salo, Tuula; Pasonen-Seppänen, Sanna

    2015-07-01

    Oral lichen planus (OLP) is an immune-mediated mucosal disease of unclear etiology and of unresolved pathogenesis. Hyaluronan (HA) is an extracellular matrix glycosaminoglycan involved in inflammation and tumor progression. However, its presence in OLP has not been reported. We therefore aimed to study the immunohistochemical expression of HA, its receptor CD44, hyaluronan synthases (HAS1-3), and hyaluronidases (HYAL1-2) in OLP. The presence of HA, CD44, HAS1-3, and HYAL1-2 was studied by immunohistochemical methods in 55 OLP and 23 control oral mucosal specimens (CTR). The localization, intensity, and differences of the epithelial expression between OLP and CTRs were analyzed. HA and CD44 were found on cell membranes in the epithelial basal and intermediate layers in CTR and OLP specimens. The HA staining intensity was stronger in the basal layer of the epithelium in OLP than in CTRs (P < 0.001). HAS1 (P = 0.001) and HAS2 (P < 0.001) showed stronger staining in the basal and weaker staining in the superficial (P < 0.001) epithelial layers in OLP than in CTRs. The immunostaining of HAS3 was low in both OLP and CTRs. Positive HYAL1 and HYAL2 staining were mainly found in the basal and intermediate epithelial layers, and their intensities were significantly increased in OLP, except HYAL 2 in the intermediate epithelial layer. HA, HAS1-2, and HYAL1-2 have altered expression in OLP compared to CTRs and may therefore have a role in OLP pathogenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Glycoconjugates in host-helminth interactions

    Directory of Open Access Journals (Sweden)

    Nina Salinger Prasanphanich

    2013-08-01

    Full Text Available Helminths are multicellular parasitic worms that comprise a major class of human pathogens and cause an immense amount of suffering worldwide. Helminths possess an abundance of complex and unique glycoconjugates that interact with both the innate and adaptive arms of immunity in definitive and intermediate hosts. These glycoconjugates represent a major untapped reservoir of immunomodulatory compounds, which have the potential to treat autoimmune and inflammatory disorders, and antigenic glycans, which could be exploited as vaccines and diagnostics. This review will survey current knowledge of the interactions between helminth glycans and host immunity and highlight the gaps in our understanding which are relevant to advancing therapeutics, vaccine development and diagnostics.

  20. Radiation environmental impact assessment of copper exploitation

    International Nuclear Information System (INIS)

    Fan Guang; Wen Zhijian

    2010-01-01

    The radiation environmental impact of mineral exploitation on the surrounding environment has become a public concern. This paper presents the radiation environmental impact assessment of copper exploitation. Based on the project description and detailed investigations of surrounding environment, systematic radiation environmental impacts have been identified. The environmental impacts are assessed during both construction and operation phase. The environmental protection measures have also been proposed. The related conclusion and measures can play an active role in copper exploitation and environmental protection. (authors)

  1. Exploitation and exploration dynamics in recessionary times

    OpenAIRE

    Walrave, B.

    2012-01-01

    Firm performance largely depends on the ability to adapt to, and exploit, changes in the business environment. That is, firms should maintain ecological fitness by reconfiguring their resource base to cope with emerging threats and explore new opportunities, while at the same time exploiting existing resources. As such, firms possessing the ability to simultaneously perform exploitative and explorative initiatives are more resilient. In this respect, the performance implications of balancing ...

  2. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year

    DEFF Research Database (Denmark)

    Jørgensen, Anette; Stengaard-Pedersen, Kristian; Simonsen, Lars Ole

    2010-01-01

    Objective To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis. Methods A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee...... osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n= 167) or saline (n= 170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary...... efficacy parameter. LFI, pain on walking 50 m based on visual analogue scale (VAS pain 50 m), paracetamol consumption, patients' global assessment, Nottingham health profile, joint effusion and number of responders were secondary efficacy parameters. The efficacy parameters were analysed by intention...

  3. Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma.

    Directory of Open Access Journals (Sweden)

    Filip Mundt

    Full Text Available PURPOSE: Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. PATIENTS AND METHODS: Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. RESULTS: Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39, N-ERC/mesothelin (4.81, 3.19-7.93, CERC/mesothelin (3.58, 2.43-5.59 and syndecan-1 (1.34, 1.03-1.77. A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00 in the model generation dataset and 0.83 (0.74-0.91 in the validation dataset, respectively. CONCLUSIONS: A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.

  4. The economics of exploiting gas hydrates

    International Nuclear Information System (INIS)

    Döpke, Lena-Katharina; Requate, Till

    2014-01-01

    We investigate the optimal exploitation of methane hydrates, a recent discovery of methane resources under the sea floor, mainly located along the continental margins. Combustion of methane (releasing CO2) and leakage through blow-outs (releasing CH4) contribute to the accumulation of greenhouse gases. A second externality arises since removing solid gas hydrates from the sea bottom destabilizes continental margins and thus increases the risk of marine earthquakes. We show that in such a model three regimes can occur: i) resource exploitation will be stopped in finite time, and some of the resource will stay in situ, ii) the resource will be used up completely in finite time, and iii) the resource will be exhausted in infinite time. We also show how to internalize the externalities by policy instruments. - Highlights: • We set up a model of optimal has hydrate exploitation • We incorporate to types of damages: contribution to global warming and geo-hazards • We characterize optimal exploitation paths and study decentralization with an exploitation tax. • Three regimes can occur: • i) exploitation in finite time and some of the stock remaining in situ, • ii) exploitation in finite time and the resource will be exhausted, • iii) exploitation and exhaustion in infinite time

  5. Exploitation and exploration dynamics in recessionary times

    NARCIS (Netherlands)

    Walrave, B.

    2012-01-01

    Firm performance largely depends on the ability to adapt to, and exploit, changes in the business environment. That is, firms should maintain ecological fitness by reconfiguring their resource base to cope with emerging threats and explore new opportunities, while at the same time exploiting

  6. Packaging of Sin Goods - Commitment or Exploitation?

    DEFF Research Database (Denmark)

    Nafziger, Julia

    to such self-control problems, and possibly exploit them, by offering different package sizes. In a competitive market, either one or three (small, medium and large) packages are offered. In contrast to common intuition, the large, and not the small package is a commitment device. The latter serves to exploit...

  7. SEXUAL EXPLOITATION AND ABUSE BY UN PEACEKEEPERS ...

    African Journals Online (AJOL)

    Allaiac

    sexual exploitation of children by peacekeepers is particularly insidious. ... sexual exploitation and abuse should involve an understanding of the social .... The charges of sexual misconduct, and the consequent media exposure, have ..... awareness programmes such as video tapes, lectures and training manuals, designed.

  8. Exploration, Exploitation, and Organizational Coordination Mechanisms

    Directory of Open Access Journals (Sweden)

    Silvio Popadiuk

    2016-03-01

    Full Text Available This paper presents an empirical relationship among exploration, exploitation, and organizational coordination mechanisms, classified as the centralization of decision-making, formalization, and connectedness. In order to analyze the findings of this survey, we used two techniques: Principal Component Analysis (PCA and Partial Least Squares Path Modeling (PLS-PM. Our analysis was supported by 249 answers from managers of companies located in Brazil (convenience sampling. Contrary to expectations, centralization and exploitation were negatively associated. Our data supports the research hypothesis that formalization is positively associated with exploitation. Although the relationship between formalization and exploration were significant, the result is contrary to the research hypothesis that we made. The relationships among connectedness and exploitation, and connectedness and exploration were both positive and significant. This relationship means that the more connectedness increases, the higher the likelihood of exploitation and exploration.

  9. Proba-V Mission Exploitation Platform

    Science.gov (United States)

    Goor, Erwin; Dries, Jeroen

    2017-04-01

    VITO and partners developed the Proba-V Mission Exploitation Platform (MEP) as an end-to-end solution to drastically improve the exploitation of the Proba-V (a Copernicus contributing mission) EO-data archive (http://proba-v.vgt.vito.be/), the past mission SPOT-VEGETATION and derived vegetation parameters by researchers, service providers and end-users. The analysis of time series of data (+1PB) is addressed, as well as the large scale on-demand processing of near real-time data on a powerful and scalable processing environment. Furthermore data from the Copernicus Global Land Service is in scope of the platform. From November 2015 an operational Proba-V MEP environment, as an ESA operation service, is gradually deployed at the VITO data center with direct access to the complete data archive. Since autumn 2016 the platform is operational and yet several applications are released to the users, e.g. - A time series viewer, showing the evolution of Proba-V bands and derived vegetation parameters from the Copernicus Global Land Service for any area of interest. - Full-resolution viewing services for the complete data archive. - On-demand processing chains on a powerfull Hadoop/Spark backend e.g. for the calculation of N-daily composites. - Virtual Machines can be provided with access to the data archive and tools to work with this data, e.g. various toolboxes (GDAL, QGIS, GrassGIS, SNAP toolbox, …) and support for R and Python. This allows users to immediately work with the data without having to install tools or download data, but as well to design, debug and test applications on the platform. - A prototype of jupyter Notebooks is available with some examples worked out to show the potential of the data. Today the platform is used by several third party projects to perform R&D activities on the data, and to develop/host data analysis toolboxes. In parallel the platform is further improved and extended. From the MEP PROBA-V, access to Sentinel-2 and landsat data will

  10. Environmental Factors and Zoonotic Pathogen Ecology in Urban Exploiter Species.

    Science.gov (United States)

    Rothenburger, Jamie L; Himsworth, Chelsea H; Nemeth, Nicole M; Pearl, David L; Jardine, Claire M

    2017-09-01

    Knowledge of pathogen ecology, including the impacts of environmental factors on pathogen and host dynamics, is essential for determining the risk that zoonotic pathogens pose to people. This review synthesizes the scientific literature on environmental factors that influence the ecology and epidemiology of zoonotic microparasites (bacteria, viruses and protozoa) in globally invasive urban exploiter wildlife species (i.e., rock doves [Columba livia domestica], European starlings [Sturnus vulgaris], house sparrows [Passer domesticus], Norway rats [Rattus norvegicus], black rats [R. rattus] and house mice [Mus musculus]). Pathogen ecology, including prevalence and pathogen characteristics, is influenced by geographical location, habitat, season and weather. The prevalence of zoonotic pathogens in mice and rats varies markedly over short geographical distances, but tends to be highest in ports, disadvantaged (e.g., low income) and residential areas. Future research should use epidemiological approaches, including random sampling and robust statistical analyses, to evaluate a range of biotic and abiotic environmental factors at spatial scales suitable for host home range sizes. Moving beyond descriptive studies to uncover the causal factors contributing to uneven pathogen distribution among wildlife hosts in urban environments may lead to targeted surveillance and intervention strategies. Application of this knowledge to urban maintenance and planning may reduce the potential impacts of urban wildlife-associated zoonotic diseases on people.

  11. Sevoflurane mitigates shedding of hyaluronan from the coronary endothelium, also during ischemia/reperfusion: an ex vivo animal study

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-04-01

    Full Text Available Congcong Chen,1,3 Daniel Chappell,2,3 Thorsten Annecke,2,3 Peter Conzen,2 Matthias Jacob,2,3 Ulrich Welsch,4 Bernhard Zwissler,2 Bernhard F Becker3 1Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; 2Clinic of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany; 3Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany; 4Institute of Anatomy, Ludwig-Maximilians-University, Munich, Germany Abstract: Glycosaminoglycan hyaluronan (HA, a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA. The effect of pre-ischemic treatment with sevoflurane (15 minutes at 2% vol/vol gas on shedding of HA was evaluated in 28 isolated, beating guinea pig hearts, subjected to warm ischemia (20 minutes at 37°C followed by reperfusion (40 minutes, half with and half without preconditioning by sevoflurane. HA concentration was measured in the coronary effluent. Over the last 20 minutes of reperfusion hydroxyethyl starch (1 g% was continuously infused and the epicardial transudate collected over the last 5 minutes for measuring the colloid extravasation. Additional hearts were fixed by perfusion after the end of reperfusion for immunohistology and electron microscopy. Sevoflurane did not significantly affect post-ischemic oxidative stress, but strongly inhibited shedding of HA during the whole period, surprisingly even prior to ischemia. Immunohistology demonstrated that heparan sulfates and SDC1 of the glycocalyx were also preserved by sevoflurane. Electron microscopy revealed shedding of glycocalyx caused by ischemia and a mostly intact glycocalyx in hearts exposed to sevoflurane. Coronary vascular permeability of the

  12. LIF inhibits osteoblast differentiation at least in part by regulation of HAS2 and its product hyaluronan.

    Science.gov (United States)

    Falconi, Dominic; Aubin, Jane E

    2007-08-01

    LIF arrests osteogenesis in fetal rat calvaria cells in a differentiation stage-specific manner. Differential display identified HAS2 as a LIF-induced gene and its product, HA, modulated osteoblast differentiation similarly to LIF. Our data suggest that LIF arrests osteoblast differentiation by altering HA content of the extracellular matrix. Leukemia inhibitory factor (LIF) elicits both anabolic and catabolic effects on bone. We previously showed in the fetal rat calvaria (RC) cell system that LIF inhibits osteoblast differentiation at the late osteoprogenitor/early osteoblast stage. To uncover potential molecular mediators of this inhibitory activity, we used a positive-negative genome-wide differential display screen to identify LIF-induced changes in the developing osteoblast transcriptome. Although LIF signaling is active throughout the RC cell proliferation-differentiation sequence, only a relatively small number of genes, in several different functional clusters, are modulated by LIF specifically during the LIF-sensitive inhibitory time window. Based on their known and predicted functions, most of the LIF-regulated genes identified are plausible candidates to be involved in the LIF-induced arrest of osteoprogenitor differentiation. To test this hypothesis, we further analyzed the function of one of the genes identified, hyaluronan synthase 2 (HAS2), in the LIF-induced inhibition. Synthesis of hyaluronan (HA), the product of HAS enzymatic activity, was stimulated by LIF and mimicked the HAS2 expression profile, with highest expression in early/proliferative and late/maturing cultures and lowest levels in intermediate/late osteoprogenitor-early osteoblast cultures. Exogenously added high molecular weight HA, the product of HAS2, dose-dependently inhibited osteoblast differentiation, with pulse-treatment effective in the same differentiation stage-specific inhibitory window as seen with LIF. In addition, however, pulse treatment with HA in early cultures

  13. Peat exploitation - Environment. Effects and measures

    International Nuclear Information System (INIS)

    Stenbeck, G.

    1996-01-01

    This report gives a detailed description of the influence of peat exploitation on the land-, water- and atmospheric environments. Proposals for mitigatory measures to minimize damage to the environment are also given

  14. SEXUAL EXPLOITATION AND ABUSE BY UN PEACEKEEPERS ...

    African Journals Online (AJOL)

    Allaiac

    from sexual exploitation and sexual abuse (ST/SGB/2003/13) (UN, Secretary .... In addition, in most situations, UN personnel have enjoyed immunity from local .... 9 Official UN statistics show a higher incidence of allegations reported against.

  15. Exploitation of linkage learning in evolutionary algorithms

    CERN Document Server

    Chen, Ying-ping

    2010-01-01

    The exploitation of linkage learning is enhancing the performance of evolutionary algorithms. This monograph examines recent progress in linkage learning, with a series of focused technical chapters that cover developments and trends in the field.

  16. Exploitative and Deceptive Resource Acquisition Strategies

    Directory of Open Access Journals (Sweden)

    Joshua J. Reynolds

    2015-07-01

    Full Text Available Life history strategy (LHS and life history contingencies (LHCs should theoretically influence the use of exploitative and deceptive resource acquisition strategies. However, little research has been done in this area. The purpose of the present work was to create measures of exploitative strategies and test the predictions of life history theory. Pilot studies developed and validated a behavioral measure of cheating called the Dot Game. The role of individual LHS and LHCs (manipulated via validated story primes on cheating was investigated in Study 1. Studies 2a through 2c were conducted to develop and validate a self-report measure called the Exploitative and Deceptive Resource Acquisition Strategy Scale (EDRASS. Finally, Study 3 investigated life history and EDRASS. Results indicated that while LHS influences exploitative strategies, life history contingences had little effect. Implications of these findings are discussed.

  17. Organ sales: exploitative at any price?

    Science.gov (United States)

    Lawlor, Rob

    2014-05-01

    In many cases, claims that a transaction is exploitative will focus on the details of the transaction, such as the price paid or conditions. For example, in a claim that a worker is exploited, the grounds for the claim are usually that the pay is not sufficient or the working conditions too dangerous. In some cases, however, the claim that a transaction is exploitative is not seen to rely on these finer details. Many, for example, claim that organ sales would be exploitative, in a way that doesn't seem to depend on the details. This article considers, but ultimately rejects, a number of arguments which could be used to defend this sort of claim. © 2012 John Wiley & Sons Ltd.

  18. A Theory of Exploitative Child Labor

    OpenAIRE

    Carol Ann Rogers; Kenneth A. Swinnerton

    2003-01-01

    Child labor laws should aim to protect children who work, instead of trying to remove children from work. In this paper, we identify an instance when the risk of exploitation lowers the expected bene…t of child labor to the child,and therefore suppresses child labor force participation. Targeted legal intervention that lowers or removes the risk of exploitation raises child participation in the labor market, child welfare, and overall societal welfare. Targeting on child labor more broadly ma...

  19. Managing the Innovators for Exploration and Exploitation

    Directory of Open Access Journals (Sweden)

    C. Annique UN

    2007-09-01

    Full Text Available I analyze how to manage employees to achieve a balance between exploration and exploitation in large established firms. Previous studies suggest that, although firms need to undertake both exploration and exploitation simultaneously, this is difficult either because of the scarcity of resources or because of the incompatibility of these two processes. Proposed solutions have been ambidexterity, punctuated equilibrium or specialization. I suggest another method: managing employees. Specifically, I argue that using the so-called “innovative” system of human resource management practices, consisting of team-based incentive system, team-based job design, and job rotation, enables the firm to undertake exploration and exploitation simultaneously because it provides the psychological safety for people to explore new knowledge to make novel products and develops employees to have the perspective-taking capability that enables the integration of knowledge cross-functionally for efficiency. Using the so-called “traditional” system of human resource management practices, consisting of individual-based incentive system, individual-based job design, and no job rotation, has limited impact on either exploration or exploitation because it does not create the psychological safety for people to explore new knowledge and does not develop the perspective-taking capability needed for exploitation. Moreover, mixing practices from both systems is better than only using the traditional system in achieving exploration or exploitation, but less effective than only using the innovative system as the mix of practices can create inconsistent expectations on employees.

  20. Hacking the Cell: Network Intrusion and Exploitation by Adenovirus E1A.

    Science.gov (United States)

    King, Cason R; Zhang, Ali; Tessier, Tanner M; Gameiro, Steven F; Mymryk, Joe S

    2018-05-01

    As obligate intracellular parasites, viruses are dependent on their infected hosts for survival. Consequently, viruses are under enormous selective pressure to utilize available cellular components and processes to their own advantage. As most, if not all, cellular activities are regulated at some level via protein interactions, host protein interaction networks are particularly vulnerable to viral exploitation. Indeed, viral proteins frequently target highly connected "hub" proteins to "hack" the cellular network, defining the molecular basis for viral control over the host. This widespread and successful strategy of network intrusion and exploitation has evolved convergently among numerous genetically distinct viruses as a result of the endless evolutionary arms race between pathogens and hosts. Here we examine the means by which a particularly well-connected viral hub protein, human adenovirus E1A, compromises and exploits the vulnerabilities of eukaryotic protein interaction networks. Importantly, these interactions identify critical regulatory hubs in the human proteome and help define the molecular basis of their function. Copyright © 2018 King et al.

  1. Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Rangel, M.P.; Sá, V.K. de; Martins, V. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, J.R.M. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Disciplina de Endocrinologia e Metabolismo, Laboratório de Endocrinologia Molecular e Translacional-LEMT, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Parra, E.R. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mendes, A. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Andrade, P.C. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Reis, R.M. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Longatto-Filho, A. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Laboratório de Investigação Médica (LIM 14), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Oliveira, C.Z. [Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Takagaki, T. [Divisão de Pneumologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carraro, D.M. [Centro Internacional de Pesquisa/CIPE, AC Camargo Cancer Center, São Paulo, SP (Brazil); Nader, H.B. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-05-08

    Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

  2. Radiation-induced increase in hyaluronan and fibronectin in bronchoalveolar lavage fluid from breast cancer patients is suppressed by smoking

    International Nuclear Information System (INIS)

    Bjermer, L.; Nilsson, K.; Haellgren, R.; Franzen, L.; Henriksson, R.; Sandstroem, T.; Saernstrand, B.

    1992-01-01

    Bronchoalveolar lavage (BAL) fluid was analysed from 21 patients with breast cancer, stage T 1 N 0 M 0 , who had undergone tumour resection and postoperative local irradiation (accumulated dose 56 Gy). The lavage was performed two months after radiotherapy, in the anterior part of the lingula (left side) or of the right middle lobe (right side), depending on which side had been exposed to radiation. The patients had significantly increased concentrations of fibronectin (FN) (p<0.001), hyaluronan (HA) (p<0.01) and albumin (p<0.05) in BAL fluid compared with the healthy controls (n=19). However, when the patients were separated, according to smoking history, it was obvious that the inflammatory reaction occurred entirely in the nonsmoking patient group (n=10), whilst no difference could be found between the smoking patients (n=11) and the controls. In the nonsmoking patient group, there was a sevenfold increase in BAL concentrations of FN and a threefold increase in HA. Moreover, four patients had detectable levels of procollagen III peptide in BAL, all were nonsmokers. The smoking habits of the controls had no influence on the BAL measurements. These findings indicate that smoking interferes with the radiation-induced early inflammatory connective tissue reaction of the lung. Finally, the results justify further investigation of interaction of smoking with cancer treatment, both from the view of therapy effectiveness and reduction of adverse effects. (au)

  3. Chitin-Hyaluronan Nanoparticles: A Multifunctional Carrier to Deliver Anti-Aging Active Ingredients through the Skin

    Directory of Open Access Journals (Sweden)

    Pierfrancesco Morganti

    2014-07-01

    Full Text Available The paper describes the process to produce Chitin Nanofibril-Hyaluronan nanoparticles (CN-HA, showing their ability to easily load active ingredients, facilitate penetration through the skin layers, and increase their effectiveness and safety as an anti-aging agent. Size and characterization of CN-HA nanoparticles were determined by Scanning Electron Microscopy (SEM and Zetasizer, while encapsulation efficiency and loading capacity of the entrapped ingredients were controlled by chromatographic and spectrophotometric methods. Safeness was evidenced on fibroblasts and keratinocytes culture viability by the MTT (Methylthiazol assay; anti-aging activity was evaluated in vitro measuring antioxidant capacity, anti-collagenase activity, and metalloproteinase and pro-inflammatory release; efficacy was shown in vivo by a double-blind vehicle-controlled study for 60 days on 60 women affected by photo-aging. In addition, the CN-HA nanoparticles have shown interesting possibility to be used as active ingredients, for designing and making advanced medication by the electrospinning technology, as well as to produce transparent films for food packaging, by the casting method, and can be used also in their dry form as tissues or films without adding preservatives. These unusual CN-HA nanoparticles obtained from the use of raw materials of waste origin may offer an unprecedented occasion for making innovative products, ameliorating the quality of life, reducing pollution and safeguarding the environment’s integrity.

  4. Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

    International Nuclear Information System (INIS)

    Chen, P.-Y.; Huang, Lynn L.H.; Hsieh, H.-J.

    2007-01-01

    For long-term culture, murine adipose-derived stromal cells (mADSCs) at latter passages demonstrated a marked decline in proliferative activity, exhibited senescent morphology and reduced differentiation potentials, particularly osteogenesis. To extend the lifespan of mADSCs, two culture conditions containing hyaluronan (HA) was compared in our study, one as a culture medium supplement (SHA), and the other where HA was pre-coated on culture surface (CHA). mADSCs cultivated with SHA exhibited a prolonged lifespan, reduced cellular senescence, and enhanced osteogenic potential compared to regular culture condition (control). Upon CHA treatment, mADSCs tended to form cell aggregates with gradual growth profiles, while their differentiation activities remained similar to SHA groups. After transferring mADSCs from CHA to control surface, they were shown to have an extended lifespan and an increase of osteogenic potential. Our results suggested that HA can be useful for preserving the proliferation and differentiation potentials of long-term cultured mADSCs

  5. Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

    International Nuclear Information System (INIS)

    Rangel, M.P.; Sá, V.K. de; Martins, V.; Martins, J.R.M.; Parra, E.R.; Mendes, A.; Andrade, P.C.; Reis, R.M.; Longatto-Filho, A.; Oliveira, C.Z.; Takagaki, T.; Carraro, D.M.; Nader, H.B.; Capelozzi, V.L.

    2015-01-01

    Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology

  6. Pursuing Intracellular Pathogens with Hyaluronan. From a 'Pro-Infection' Polymer to a Biomaterial for 'Trojan Horse' Systems.

    Science.gov (United States)

    Montanari, Elita; Di Meo, Chiara; Oates, Angela; Coviello, Tommasina; Matricardi, Pietro

    2018-04-18

    Hyaluronan (HA) is among the most important bioactive polymers in mammals, playing a key role in a number of biological functions. In the last decades, it has been increasingly studied as a biomaterial for drug delivery systems, thanks to its physico-chemical features and ability to target and enter certain cells. The most important receptor of HA is ‘Cluster of Differentiation 44’ (CD44), a cell surface glycoprotein over-expressed by a number of cancers and heavily involved in HA endocytosis. Moreover, CD44 is highly expressed by keratinocytes, activated macrophages and fibroblasts, all of which can act as ‘reservoirs’ for intracellular pathogens. Interestingly, both CD44 and HA appear to play a key role for the invasion and persistence of such microorganisms within the cells. As such, HA is increasingly recognised as a potential target for nano-carriers development, to pursuit and target intracellular pathogens, acting as a ‘Trojan Horse’. This review describes the biological relationship between HA, CD44 and the entry and survival of a number of pathogens within the cells and the subsequent development of HA-based nano-carriers for enhancing the intracellular activity of antimicrobials.

  7. A Modified ELISA Accurately Measures Secretion of High Molecular Weight Hyaluronan (HA) by Graves' Disease Orbital Cells

    Science.gov (United States)

    Krieger, Christine C.

    2014-01-01

    Excess production of hyaluronan (hyaluronic acid [HA]) in the retro-orbital space is a major component of Graves' ophthalmopathy, and regulation of HA production by orbital cells is a major research area. In most previous studies, HA was measured by ELISAs that used HA-binding proteins for detection and rooster comb HA as standards. We show that the binding efficiency of HA-binding protein in the ELISA is a function of HA polymer size. Using gel electrophoresis, we show that HA secreted from orbital cells is primarily comprised of polymers more than 500 000. We modified a commercially available ELISA by using 1 million molecular weight HA as standard to accurately measure HA of this size. We demonstrated that IL-1β-stimulated HA secretion is at least 2-fold greater than previously reported, and activation of the TSH receptor by an activating antibody M22 from a patient with Graves' disease led to more than 3-fold increase in HA production in both fibroblasts/preadipocytes and adipocytes. These effects were not consistently detected with the commercial ELISA using rooster comb HA as standard and suggest that fibroblasts/preadipocytes may play a more prominent role in HA remodeling in Graves' ophthalmopathy than previously appreciated. PMID:24302624

  8. Hyaluronan suppresses prostate tumor cell proliferation through diminished expression of N-cadherin and aberrant growth factor receptor signaling

    International Nuclear Information System (INIS)

    Bharadwaj, Alamelu G.; Goodrich, Nathaniel P.; McAtee, Caitlin O.; Haferbier, Katie; Oakley, Gregory G.; Wahl, James K.; Simpson, Melanie A.

    2011-01-01

    Hyaluronan (HA) production has been functionally implicated in prostate tumorigenesis and metastasis. We previously used prostate tumor cells overexpressing the HA synthesizing enzyme HAS3 or the clinically relevant hyaluronidase Hyal1 to show that excess HA production suppresses tumor growth, while HA turnover accelerates spontaneous metastasis from the prostate. Here, we examined pathways responsible for effects of HAS3 and Hyal1 on tumor cell phenotype. Detailed characterization of cell cycle progression revealed that expression of Hyal1 accelerated cell cycle re-entry following synchronization, whereas HAS3 alone delayed entry. Hyal1 expressing cells exhibited a significant reduction in their ability to sustain ERK phosphorylation upon stimulation by growth factors, and in their expression of the cyclin-dependent kinase inhibitor p21. In contrast, HAS3 expressing cells showed prolonged ERK phosphorylation and increased expression of both p21 and p27, in asynchronous and synchronized cultures. Changes in cell cycle regulatory proteins were accompanied by HA-induced suppression of N-cadherin, while E-cadherin expression and β-catenin expression and distribution remained unchanged. Our results are consistent with a model in which excess HA synthesis suppresses cell proliferation by promoting homotypic E-cadherin mediated cell-cell adhesion, consequently signaling to elevate cell cycle inhibitor expression and suppress G1- to S-phase transition.

  9. Effect of Hyaluronan on Developmental Competence and Quality of Oocytes and Obtained Blastocysts from In Vitro Maturation of Bovine Oocytes

    Directory of Open Access Journals (Sweden)

    Jolanta Opiela

    2014-01-01

    Full Text Available The objective of the present study was to evaluate the effect of hyaluronan (HA during IVM on meiotic maturation, embryonic development, and the quality of oocytes, granulosa cells (GC, and obtained blastocysts. COCs were matured in vitro in control medium and medium with additional 0.035% or 0.07% of exogenous HA. The meiotic maturity did not differ between the analysed groups. The best rate and the highest quality of obtained blastocysts were observed when 0.07% HA was used. A highly significant difference (P<0.001 was noted in the mean number of apoptotic nuclei per blastocyst and in the DCI between the 0.07% HA and the control blastocysts (P<0.01. Our results suggest that addition of 0.035% HA and 0.07% HA to oocyte maturation media does not affect oocyte nuclear maturation and DNA fragmentation. However, the addition of 0.07% HA during IVM decreases the level of blastocysts DNA fragmentation. Finally, our results suggest that it may be risky to increase the HA concentration during IVM above 0.07% as we found significantly higher Bax mRNA expression levels in GC cultured with 0.07% HA. The final concentration of HA being supplemented to oocyte maturation media is critical for the success of the IVP procedure.

  10. Exploiting GPUs in Virtual Machine for BioCloud

    Science.gov (United States)

    Jo, Heeseung; Jeong, Jinkyu; Lee, Myoungho; Choi, Dong Hoon

    2013-01-01

    Recently, biological applications start to be reimplemented into the applications which exploit many cores of GPUs for better computation performance. Therefore, by providing virtualized GPUs to VMs in cloud computing environment, many biological applications will willingly move into cloud environment to enhance their computation performance and utilize infinite cloud computing resource while reducing expenses for computations. In this paper, we propose a BioCloud system architecture that enables VMs to use GPUs in cloud environment. Because much of the previous research has focused on the sharing mechanism of GPUs among VMs, they cannot achieve enough performance for biological applications of which computation throughput is more crucial rather than sharing. The proposed system exploits the pass-through mode of PCI express (PCI-E) channel. By making each VM be able to access underlying GPUs directly, applications can show almost the same performance as when those are in native environment. In addition, our scheme multiplexes GPUs by using hot plug-in/out device features of PCI-E channel. By adding or removing GPUs in each VM in on-demand manner, VMs in the same physical host can time-share their GPUs. We implemented the proposed system using the Xen VMM and NVIDIA GPUs and showed that our prototype is highly effective for biological GPU applications in cloud environment. PMID:23710465

  11. Exploiting GPUs in Virtual Machine for BioCloud

    Directory of Open Access Journals (Sweden)

    Heeseung Jo

    2013-01-01

    Full Text Available Recently, biological applications start to be reimplemented into the applications which exploit many cores of GPUs for better computation performance. Therefore, by providing virtualized GPUs to VMs in cloud computing environment, many biological applications will willingly move into cloud environment to enhance their computation performance and utilize infinite cloud computing resource while reducing expenses for computations. In this paper, we propose a BioCloud system architecture that enables VMs to use GPUs in cloud environment. Because much of the previous research has focused on the sharing mechanism of GPUs among VMs, they cannot achieve enough performance for biological applications of which computation throughput is more crucial rather than sharing. The proposed system exploits the pass-through mode of PCI express (PCI-E channel. By making each VM be able to access underlying GPUs directly, applications can show almost the same performance as when those are in native environment. In addition, our scheme multiplexes GPUs by using hot plug-in/out device features of PCI-E channel. By adding or removing GPUs in each VM in on-demand manner, VMs in the same physical host can time-share their GPUs. We implemented the proposed system using the Xen VMM and NVIDIA GPUs and showed that our prototype is highly effective for biological GPU applications in cloud environment.

  12. Exploiting GPUs in virtual machine for BioCloud.

    Science.gov (United States)

    Jo, Heeseung; Jeong, Jinkyu; Lee, Myoungho; Choi, Dong Hoon

    2013-01-01

    Recently, biological applications start to be reimplemented into the applications which exploit many cores of GPUs for better computation performance. Therefore, by providing virtualized GPUs to VMs in cloud computing environment, many biological applications will willingly move into cloud environment to enhance their computation performance and utilize infinite cloud computing resource while reducing expenses for computations. In this paper, we propose a BioCloud system architecture that enables VMs to use GPUs in cloud environment. Because much of the previous research has focused on the sharing mechanism of GPUs among VMs, they cannot achieve enough performance for biological applications of which computation throughput is more crucial rather than sharing. The proposed system exploits the pass-through mode of PCI express (PCI-E) channel. By making each VM be able to access underlying GPUs directly, applications can show almost the same performance as when those are in native environment. In addition, our scheme multiplexes GPUs by using hot plug-in/out device features of PCI-E channel. By adding or removing GPUs in each VM in on-demand manner, VMs in the same physical host can time-share their GPUs. We implemented the proposed system using the Xen VMM and NVIDIA GPUs and showed that our prototype is highly effective for biological GPU applications in cloud environment.

  13. Exploitation of Labour and Exploitation of Commodities: a “New Interpretation”

    OpenAIRE

    Veneziani, Roberto; Yoshihara, Naoki

    2011-01-01

    In the standard Okishio-Morishima approach, the existence of profits is proved to be equivalent to the exploitation of labour. Yet, it can also be proved that the existence of profits is equivalent to the ‘exploitation’ of any good. Labour and commodity exploitation are just different numerical representations of the productiveness of the economy. This paper presents an alternative approach to exploitation theory which is related to the New Interpretation (Duménil 1980; Foley 1982). In this a...

  14. Exploitation in International Paid Surrogacy Arrangements

    Science.gov (United States)

    Wilkinson, Stephen

    2015-01-01

    Abstract Many critics have suggested that international paid surrogacy is exploitative. Taking such concerns as its starting point, this article asks: (1) how defensible is the claim that international paid surrogacy is exploitative and what could be done to make it less exploitative? (2) In the light of the answer to (1), how strong is the case for prohibiting it? Exploitation could in principle be dealt with by improving surrogates' pay and conditions. However, doing so may exacerbate problems with consent. Foremost amongst these is the argument that surrogates from economically disadvantaged countries cannot validly consent because their background circumstances are coercive. Several versions of this argument are examined and I conclude that at least one has some merit. The article's overall conclusion is that while ethically there is something to be concerned about, paid surrogacy is in no worse a position than many other exploitative commercial transactions which take place against a backdrop of global inequality and constrained options, such as poorly‐paid and dangerous construction work. Hence, there is little reason to single surrogacy out for special condemnation. On a policy level, the case for prohibiting international commercial surrogacy is weak, despite legitimate concerns about consent and background poverty. PMID:27471338

  15. Exploitation in International Paid Surrogacy Arrangements.

    Science.gov (United States)

    Wilkinson, Stephen

    2016-05-01

    Many critics have suggested that international paid surrogacy is exploitative. Taking such concerns as its starting point, this article asks: (1) how defensible is the claim that international paid surrogacy is exploitative and what could be done to make it less exploitative? (2) In the light of the answer to (1), how strong is the case for prohibiting it? Exploitation could in principle be dealt with by improving surrogates' pay and conditions. However, doing so may exacerbate problems with consent. Foremost amongst these is the argument that surrogates from economically disadvantaged countries cannot validly consent because their background circumstances are coercive. Several versions of this argument are examined and I conclude that at least one has some merit. The article's overall conclusion is that while ethically there is something to be concerned about, paid surrogacy is in no worse a position than many other exploitative commercial transactions which take place against a backdrop of global inequality and constrained options, such as poorly-paid and dangerous construction work. Hence, there is little reason to single surrogacy out for special condemnation. On a policy level, the case for prohibiting international commercial surrogacy is weak, despite legitimate concerns about consent and background poverty.

  16. Fluorescent molecularly imprinted polymers as plastic antibodies for selective labeling and imaging of hyaluronan and sialic acid on fixed and living cells.

    Science.gov (United States)

    Panagiotopoulou, Maria; Kunath, Stephanie; Medina-Rangel, Paulina Ximena; Haupt, Karsten; Tse Sum Bui, Bernadette

    2017-02-15

    Altered glycosylation levels or distribution of sialic acids (SA) or hyaluronan in animal cells are indicators of pathological conditions like infection or malignancy. We applied fluorescently-labeled molecularly imprinted polymer (MIP) particles for bioimaging of fixed and living human keratinocytes, to localize hyaluronan and sialylation sites. MIPs were prepared with the templates D-glucuronic acid (GlcA), a substructure of hyaluronan, and N-acetylneuraminic acid (NANA), the most common member of SA. Both MIPs were found to be highly selective towards their target monosaccharides, as no cross-reactivity was observed with other sugars like N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-glucose and D-galactose, present on the cell surface. The dye rhodamine and two InP/ZnS quantum dots (QDs) emitting in the green and in the red regions were used as fluorescent probes. Rhodamine-MIPGlcA and rhodamine-MIPNANA were synthesized as monodispersed 400nm sized particles and were found to bind selectively their targets located in the extracellular region, as imaged by epifluorescence and confocal microscopy. In contrast, when MIP-GlcA and MIP-NANA particles with a smaller size (125nm) were used, the MIPs being synthesized as thin shells around green and red emitting QDs respectively, it was possible to stain the intracellular and pericellular regions as well. In addition, simultaneous dual-color imaging with the two different colored QDs-MIPs was demonstrated. Importantly, the MIPs were not cytotoxic and did not affect cell viability; neither was the cells morphology affected as demonstrated by live cell imaging. These synthetic receptors could offer a new and promising imaging tool to monitor disease progression. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Hyaluronan (HA) interacting proteins RHAMM and hyaluronidase impact prostate cancer cell behavior and invadopodia formation in 3D HA-based hydrogels.

    Science.gov (United States)

    Gurski, Lisa A; Xu, Xian; Labrada, Lyana N; Nguyen, Ngoc T; Xiao, Longxi; van Golen, Kenneth L; Jia, Xinqiao; Farach-Carson, Mary C

    2012-01-01

    To study the individual functions of hyaluronan interacting proteins in prostate cancer (PCa) motility through connective tissues, we developed a novel three-dimensional (3D) hyaluronic acid (HA) hydrogel assay that provides a flexible, quantifiable, and physiologically relevant alternative to current methods. Invasion in this system reflects the prevalence of HA in connective tissues and its role in the promotion of cancer cell motility and tissue invasion, making the system ideal to study invasion through bone marrow or other HA-rich connective tissues. The bio-compatible cross-linking process we used allows for direct encapsulation of cancer cells within the gel where they adopt a distinct, cluster-like morphology. Metastatic PCa cells in these hydrogels develop fingerlike structures, "invadopodia", consistent with their invasive properties. The number of invadopodia, as well as cluster size, shape, and convergence, can provide a quantifiable measure of invasive potential. Among candidate hyaluronan interacting proteins that could be responsible for the behavior we observed, we found that culture in the HA hydrogel triggers invasive PCa cells to differentially express and localize receptor for hyaluronan mediated motility (RHAMM)/CD168 which, in the absence of CD44, appears to contribute to PCa motility and invasion by interacting with the HA hydrogel components. PCa cell invasion through the HA hydrogel also was found to depend on the activity of hyaluronidases. Studies shown here reveal that while hyaluronidase activity is necessary for invadopodia and inter-connecting cluster formation, activity alone is not sufficient for acquisition of invasiveness to occur. We therefore suggest that development of invasive behavior in 3D HA-based systems requires development of additional cellular features, such as activation of motility associated pathways that regulate formation of invadopodia. Thus, we report development of a 3D system amenable to dissection of

  18. Oil exploitation and the environmental Kuznets curve

    International Nuclear Information System (INIS)

    Esmaeili, Abdoulkarim; Abdollahzadeh, Negar

    2009-01-01

    This study refers to a panel estimation of an environmental Kuznets curve (EKC) for oil to determine the factors most affecting oil exploitation in 38 oil-producing countries during 1990-2000. Control variables such as oil reserves, oil price, population, political rights, and the Gini index were used to determine its contribution to the main EKC model. The empirical results fully support the existence of an EKC for oil exploitation. Furthermore, the result indicates that the proved oil reserves has a significant and positive role in oil production, but oil price and population do not significantly affect crude oil production. Also, increased freedoms and a better income distribution will reduce the rate of oil exploitation. Thus, policies aiming at enhancing democratic society and better income distribution would be more compatible with sustainability. (author)

  19. Oil exploitation and the environmental Kuznets curve

    Energy Technology Data Exchange (ETDEWEB)

    Esmaeili, Abdoulkarim; Abdollahzadeh, Negar [Department of Agricultural Economics, College of Agriculture, Shiraz University, Shiraz, Fars (Iran)

    2009-01-15

    This study refers to a panel estimation of an environmental Kuznets curve (EKC) for oil to determine the factors most affecting oil exploitation in 38 oil-producing countries during 1990-2000. Control variables such as oil reserves, oil price, population, political rights, and the Gini index were used to determine its contribution to the main EKC model. The empirical results fully support the existence of an EKC for oil exploitation. Furthermore, the result indicates that the proved oil reserves has a significant and positive role in oil production, but oil price and population do not significantly affect crude oil production. Also, increased freedoms and a better income distribution will reduce the rate of oil exploitation. Thus, policies aiming at enhancing democratic society and better income distribution would be more compatible with sustainability. (author)

  20. Rethinking exploitation: a process-centered account.

    Science.gov (United States)

    Jansen, Lynn A; Wall, Steven

    2013-12-01

    Exploitation has become an important topic in recent discussions of biomedical and research ethics. This is due in no small measure to the influence of Alan Wertheimer's path-breaking work on the subject. This paper presents some objections to Wertheimer's account of the concept. The objections attempt to show that his account places too much emphasis on outcome-based considerations and too little on process-based considerations. Building on these objections, the paper develops an alternative process-centered account of the concept. This alternative account of exploitation takes as its point of departure the broadly Kantian notion that it is wrong to use another as an instrument for the advancement of one's own ends. It sharpens this slippery notion and adds a number of refinements to it. The paper concludes by arguing that process-centered accounts of exploitation better illuminate the ethical challenges posed by research on human subjects than outcome-centered accounts.

  1. Shale gas exploitation: Status, problems and prospect

    Directory of Open Access Journals (Sweden)

    Shiqian Wang

    2018-02-01

    Full Text Available Over the past five years, great progress has been made in shale gas exploitation, which has become the most driving force for global gas output growth. Hydrocarbon extraction from shale helps drive the USA on the road to energy independence. Besides, shale oil & gas production has been kept in a sustained growth by continuous improvement in drilling efficiency and well productivity in the case of tumbling oil prices and rig counts. Shale gas reserves and production have been in a rapid growth in China owing to the Lower Paleozoic Wufeng and Longmaxi shale gas exploitation in the Sichuan Basin, which has become an important sector for the future increment of gas reserves and output in China. However, substantial progress has been made neither in non-marine shale gas exploitation as previously expected nor in the broad complicated tectonic areas in South China for which a considerable investment was made. Analysis of the basic situation and issues in domestic shale gas development shows that shale gas exploitation prospects are constrained by many problems in terms of resources endowment, horizontal well fracturing technology, etc. especially in non-marine shale deposits and complicated tectonic areas in South China where hot shales are widely distributed but geological structures are found severely deformed and over matured. Discussion on the prospects shows that the sustained and steady growth in shale gas reserves and production capacity in the coming years lies in the discovery and supersession of new shale plays in addition to Wufeng and Longmaxi shale plays, and that a technological breakthrough in ultra-high-pressure and ultra-deep (over 3500 m buried in the Sichuan Basin marine shale gas exploitation is the key and hope. Keywords: Shale gas, Exploitation, Marine facies, Hot shale, Resource endowment, Sichuan Basin, South China, Complicated tectonic area, Gas play

  2. Host manipulation by cancer cells: Expectations, facts, and therapeutic implications.

    Science.gov (United States)

    Tissot, Tazzio; Arnal, Audrey; Jacqueline, Camille; Poulin, Robert; Lefèvre, Thierry; Mery, Frédéric; Renaud, François; Roche, Benjamin; Massol, François; Salzet, Michel; Ewald, Paul; Tasiemski, Aurélie; Ujvari, Beata; Thomas, Frédéric

    2016-03-01

    Similar to parasites, cancer cells depend on their hosts for sustenance, proliferation and reproduction, exploiting the hosts for energy and resources, and thereby impairing their health and fitness. Because of this lifestyle similarity, it is predicted that cancer cells could, like numerous parasitic organisms, evolve the capacity to manipulate the phenotype of their hosts to increase their own fitness. We claim that the extent of this phenomenon and its therapeutic implications are, however, underappreciated. Here, we review and discuss what can be regarded as cases of host manipulation in the context of cancer development and progression. We elaborate on how acknowledging the applicability of these principles can offer novel therapeutic and preventive strategies. The manipulation of host phenotype by cancer cells is one more reason to adopt a Darwinian approach in cancer research. © 2016 WILEY Periodicals, Inc.

  3. Effects of an invasive plant on the performance of two parasitoids with different host exploitation strategies

    NARCIS (Netherlands)

    Fortuna, T.; Vet, L.E.M.; Harvey, J.A.

    2012-01-01

    In their new range, exotic plants create the possibility for novel interactions to occur with native consumers. Whereas there is evidence that these novel interactions can be negative for native insects, alien plants that are closely related to native species may in fact act as important food

  4. Creating Centralized Reporting for Microsoft Host Protection Technologies:The Enhanced Mitigation Experience Toolkit (EMET)

    Science.gov (United States)

    2016-08-11

    patching are helpful, though they offer little or no protection for attacks using specialized malware or unpatched “zero-day” exploits. 2.1 Benefits...that all host-based and net- work firewalls allow communications between Windows endpoints and hosts acting in the collec- tion service role. Define a

  5. On the dynamics of exploited fish populations

    National Research Council Canada - National Science Library

    Beverton, R. J. H; Holt, Sidney J

    1993-01-01

    ...-brooding cichlids, and viviparity in many sharks and toothcarps. Moreover, fish are of considerable importance to the survival of the human species in the form of nutritious, delicious and diverse food. Rational exploitation and management of our global stocks of fishes must rely upon a detailed and precise insight of their biology. The...

  6. Child Exploitation: Some Pieces of the Puzzle.

    Science.gov (United States)

    Rohlader, Dorothy

    The report addresses the status in North Carolina and in the nation of child exploitation. Legislative and judicial backgrounds of child pornography and child prostitution are reviewed, and difficulties in obtaining statistical data are noted. Law enforcement issues in pornography are cited, and suggestions for further legislation regarding child…

  7. Exploiting a natural auxotrophy for genetic selection.

    Science.gov (United States)

    Ramage, Elizabeth; Gallagher, Larry; Manoil, Colin

    2012-08-01

    We exploited the natural histidine auxotrophy of Francisella species to develop hisD (encodes histidinol dehydrogenase) as a positive selection marker. A shuttle plasmid (pBR103) carrying Escherichia coli hisD and designed for cloning of PCR fragments replicated in both attenuated and highly virulent Francisella strains. During this work, we formulated a simplified defined growth medium for Francisella novicida.

  8. Growth, Mortality and Exploitation Rates of Sarotherodon ...

    African Journals Online (AJOL)

    Evans

    ABSTRACT. Sarotherodon melanotheron population of Dominli Lagoon in the Western Region of Ghana was studied for its growth and mortality parameters as well as exploitation rate. The study generally aimed at providing basic information necessary for the assessment and management of the fish stock in the lagoon.

  9. Economic factors of vulnerability trade and exploitation

    NARCIS (Netherlands)

    Allodi, L.

    2017-01-01

    Cybercrime markets support the development and diffusion of new attack technologies, vulnerability exploits, and malware. Whereas the revenue streams of cyber attackers have been studied multiple times in the literature, no quantitative account currently exists on the economics of attack acquisition

  10. Exploiting indigenous knowledge in the environmental conservation ...

    African Journals Online (AJOL)

    ... of agriculture and reared livestock (especially goats). Over several years, they developed sustainable and effective exploitation mechanisms of the existing biodiversity resources to satisfy their individual needs and those of their societies in general. Journal of Language, Technology and Entrepreneurship in Africa Vol.

  11. Exploiting citation contexts for physics retrieval

    DEFF Research Database (Denmark)

    Dabrowska, Anna; Larsen, Birger

    2015-01-01

    The text surrounding citations within scientific papers may contain terms that usefully describe cited documents and can benefit retrieval. We present a preliminary study that investigates appending ci- tation contexts from citing documents to cited documents in the iSearch test collection. We ex...... in a large collection of physics papers, paving the way for future research that exploits citation contexts for retrieval....

  12. Use of Host-like Peptide Motifs in Viral Proteins Is a Prevalent Strategy in Host-Virus Interactions

    Directory of Open Access Journals (Sweden)

    Tzachi Hagai

    2014-06-01

    Full Text Available Viruses interact extensively with host proteins, but the mechanisms controlling these interactions are not well understood. We present a comprehensive analysis of eukaryotic linear motifs (ELMs in 2,208 viral genomes and reveal that viruses exploit molecular mimicry of host-like ELMs to possibly assist in host-virus interactions. Using a statistical genomics approach, we identify a large number of potentially functional ELMs and observe that the occurrence of ELMs is often evolutionarily conserved but not uniform across virus families. Some viral proteins contain multiple types of ELMs, in striking similarity to complex regulatory modules in host proteins, suggesting that ELMs may act combinatorially to assist viral replication. Furthermore, a simple evolutionary model suggests that the inherent structural simplicity of ELMs often enables them to tolerate mutations and evolve quickly. Our findings suggest that ELMs may allow fast rewiring of host-virus interactions, which likely assists rapid viral evolution and adaptation to diverse environments.

  13. Dissemination and Exploitation: Project Goals beyond Science

    Science.gov (United States)

    Hamann, Kristin; Reitz, Anja

    2017-04-01

    Dissemination and Exploitation are essential parts of public funded projects. In Horizon 2020 a plan for the exploitation and dissemination of results (PEDR) is a requirement. The plan should contain a clear vision on the objectives of the project in relation to actions for dissemination and potential exploitation of the project results. The actions follow the basic idea to spread the knowledge and results gathered within the project and face the challenge of how to bring the results into potentially relevant policy circle and how they impact the market. The plan follows the purpose to assess the impact of the project and to address various target groups who are interested in the project results. Simply put, dissemination concentrates on the transfer of knowledge and exploitation on the commercialization of the project. Beyond the question of the measurability of project`s impact, strategies within science marketing can serve purposes beyond internal and external communication. Accordingly, project managers are facing the challenge to implement a dissemination and exploitation strategy that ideally supports the identification of all partners with the project and matches the current discourse of the project`s content within the society, politics and economy. A consolidated plan might unite all projects partners under a central idea and supports the identification with the project beyond the individual research questions. Which applications, strategies and methods can be used to bring forward a PEDR that accompanies a project successfully and allows a comprehensive assessment of the project afterwards? Which hurdles might project managers experience in the dissemination process and which tasks should be fulfilled by the project manager?

  14. Trolling may intensify exploitation in crappie fisheries

    Science.gov (United States)

    Meals, K. O.; Dunn, A. W.; Miranda, Leandro E.

    2012-01-01

    In some parts of the USA, anglers targeting crappies Pomoxis spp. are transitioning from mostly stationary angling with a single pole around submerged structures to using multiple poles while drifting with the wind or under power. This shift in fishing methods could result in a change in catch efficiency, possibly increasing exploitation rates to levels that would be of concern to managers. We studied the catch statistics of anglers fishing while trolling with multiple poles (trollers) and those fishing with single poles (polers) in Mississippi reservoirs. Specifically, we tested whether (1) various catch statistics differed between trollers and polers, (2) catch rates of trollers were related to the number of poles fished, and (3) trollers could raise exploitation rates to potentially unsustainable levels. Results showed that participation in the crappie fisheries was about equally split between polers and trollers. In spring, 90% of crappie anglers were polers; in summer, 85% of crappie anglers were trollers. The size of harvested crappies was similar for the two angler groups, but the catch per hour was almost three times higher for trollers than for polers. Catch rates by trollers were directly correlated to the number of poles fished, although the relationship flattened as the number of poles increased. The average harvest rate for one troller fishing with three poles was similar to the harvest rate obtained by one poler. Simulations predicted that at the existing mix of about 50% polers and 50% trollers and with no restrictions on the number of poles used by trollers, exploitation of crappies is about 1.3 times higher than that in a polers-only fishery; under a scenario in which 100% of crappie anglers were trollers, exploitation was forecasted to increase to about 1.7 times the polers-only rate. The efficiency of trolling for crappies should be of concern to fishery managers because crappie fisheries are mostly consumptive and may increase exploitation

  15. Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed

    Science.gov (United States)

    Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

    2017-01-01

    Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed. PMID:27845895

  16. Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period

    Directory of Open Access Journals (Sweden)

    Oe M

    2017-07-01

    Full Text Available Mariko Oe,1 Seigo Sakai,1 Hideto Yoshida,1 Nao Okado,1 Haruna Kaneda,1 Yasunobu Masuda,1 Osamu Urushibata2 1R&D Division, Kewpie Corporation, Sengawa-cho, Chofu-shi, 2Department of Dermatology, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Background: Hyaluronan (HA has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA. Methods: The mean molecular weight (MW of HA is 2 k and 300 k. Sixty Japanese male and female subjects aged 22–59 years who presented with crow’s feet wrinkles were randomly assigned to the HA 2 k or HA 300 k at 120 mg/day or the placebo group. The subjects were administered HA at a rate of 120 mg/day or a placebo for 12 weeks. The skin wrinkles were evaluated by image analysis of skin wrinkle replicas, and their skin condition was evaluated using a questionnaire survey. Results: During the study period, the HA groups showed better level of the whole sulcus ­volume ratio, wrinkle area ratio, and wrinkle volume ratio than the placebo group. After 8 weeks of ingestion, the HA 300 k group showed significantly diminished wrinkles compared with the placebo group. Skin luster and suppleness significantly improved after 12 weeks in all groups compared with the baseline. Conclusion: The results suggest that oral HA (both HA 2 k and HA 300 k inhibits skin wrinkles and improves skin condition. Keywords: hyaluronic acid, dietary supplement, skin, wrinkle volume, molecular weight

  17. Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

    Science.gov (United States)

    Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

    2017-03-21

    Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

  18. Host plant use drives genetic differentiation in syntopic populations of Maculinea alcon

    DEFF Research Database (Denmark)

    Tartally, András; Kelager, Andreas; Fürst, Matthias Alois

    2016-01-01

    The rare socially parasitic butterfly Maculinea alcon occurs in two forms, which are characteristic of hygric or xeric habitats and which exploit different host plants and host ants. The status of these two forms has been the subject of considerable controversy. Populations of the two forms...... on different host plants, each with a distinct flowering phenology, providing a temporal rather than spatial barrier to gene flow....

  19. Intelligence, mapping, and geospatial exploitation system (IMAGES)

    Science.gov (United States)

    Moellman, Dennis E.; Cain, Joel M.

    1998-08-01

    This paper provides further detail to one facet of the battlespace visualization concept described in last year's paper Battlespace Situation Awareness for Force XXI. It focuses on the National Imagery and Mapping Agency (NIMA) goal to 'provide customers seamless access to tailorable imagery, imagery intelligence, and geospatial information.' This paper describes Intelligence, Mapping, and Geospatial Exploitation System (IMAGES), an exploitation element capable of CONUS baseplant operations or field deployment to provide NIMA geospatial information collaboratively into a reconnaissance, surveillance, and target acquisition (RSTA) environment through the United States Imagery and Geospatial Information System (USIGS). In a baseplant CONUS setting IMAGES could be used to produce foundation data to support mission planning. In the field it could be directly associated with a tactical sensor receiver or ground station (e.g. UAV or UGV) to provide near real-time and mission specific RSTA to support mission execution. This paper provides IMAGES functional level design; describes the technologies, their interactions and interdependencies; and presents a notional operational scenario to illustrate the system flexibility. Using as a system backbone an intelligent software agent technology, called Open Agent ArchitectureTM (OAATM), IMAGES combines multimodal data entry, natural language understanding, and perceptual and evidential reasoning for system management. Configured to be DII COE compliant, it would utilize, to the extent possible, COTS applications software for data management, processing, fusion, exploitation, and reporting. It would also be modular, scaleable, and reconfigurable. This paper describes how the OAATM achieves data synchronization and enables the necessary level of information to be rapidly available to various command echelons for making informed decisions. The reasoning component will provide for the best information to be developed in the timeline

  20. Sustainable exploitation and management of aquatic resources

    DEFF Research Database (Denmark)

    Neuenfeldt, Stefan; Köster, Fritz

    2014-01-01

    DTU Aqua conducts research, provides advice,educates at university level and contributes toinnovation in sustainable exploitation andmanagement of aquatic resources. The vision of DTUAqua is to enable ecologically and economicallysustainable exploitation of aquatic resourcesapplying an integrated...... management. Marineecosystems aims at understanding the mechanisms that govern the interaction between individuals,species and populations in an ecosystem enabling us to determine the stability and flexibility of theecosystem.Marine living resources looks at the sustainable utilization of fish and shellfish...... stocks.Ecosystem effects expands from the ecosystem approach to fisheries management to an integratedapproach where other human activities are taken into consideration. Fisheries management developsmethods, models and tools for predicting and evaluating the effects of management measures andregulations...

  1. Exploiting HRM in support of lean manufacturing

    DEFF Research Database (Denmark)

    Jørgensen, Frances; Matthiesen, Rikke

    The purpose of this paper is to investigate the ways in HRM practices are-and could potentially be-exploited to support lean manufacturing in practice. First, a review of the pertinent literature regarding HRM, SHRM, and lean manufacturing is presented to provide an understanding of the mechanisms...... by which HRM practices could, theoretically, be used to support a lean implementation. Data presented in the paper are derived from 1) a longitudinal case study on lean implementation and 2) from managers currently involved with lean manufacturing in a second company. The relevant literature and the data...... depicting the potential role in supporting HRM/lean integrated practices. The analysis of the model with respect to the theoretical background emphasizes a number of areas in which HRM could be more fully exploited in order to more successfully support lean implementation, for example, by stressing HRM...

  2. Exploiting Non-Markovianity for Quantum Control.

    Science.gov (United States)

    Reich, Daniel M; Katz, Nadav; Koch, Christiane P

    2015-07-22

    Quantum technology, exploiting entanglement and the wave nature of matter, relies on the ability to accurately control quantum systems. Quantum control is often compromised by the interaction of the system with its environment since this causes loss of amplitude and phase. However, when the dynamics of the open quantum system is non-Markovian, amplitude and phase flow not only from the system into the environment but also back. Interaction with the environment is then not necessarily detrimental. We show that the back-flow of amplitude and phase can be exploited to carry out quantum control tasks that could not be realized if the system was isolated. The control is facilitated by a few strongly coupled, sufficiently isolated environmental modes. Our paradigmatic example considers a weakly anharmonic ladder with resonant amplitude control only, restricting realizable operations to SO(N). The coupling to the environment, when harnessed with optimization techniques, allows for full SU(N) controllability.

  3. Exploiting Quantum Resonance to Solve Combinatorial Problems

    Science.gov (United States)

    Zak, Michail; Fijany, Amir

    2006-01-01

    Quantum resonance would be exploited in a proposed quantum-computing approach to the solution of combinatorial optimization problems. In quantum computing in general, one takes advantage of the fact that an algorithm cannot be decoupled from the physical effects available to implement it. Prior approaches to quantum computing have involved exploitation of only a subset of known quantum physical effects, notably including parallelism and entanglement, but not including resonance. In the proposed approach, one would utilize the combinatorial properties of tensor-product decomposability of unitary evolution of many-particle quantum systems for physically simulating solutions to NP-complete problems (a class of problems that are intractable with respect to classical methods of computation). In this approach, reinforcement and selection of a desired solution would be executed by means of quantum resonance. Classes of NP-complete problems that are important in practice and could be solved by the proposed approach include planning, scheduling, search, and optimal design.

  4. Exploiting Inhibitory Siglecs to Combat Food Allergies

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0302 TITLE: Exploiting Inhibitory Siglecs to Combat Food Allergies PRINCIPAL INVESTIGATOR: Michael Kulis, Ph.D...CONTRACTING ORGANIZATION: University of North Carolina at Chapel Hill Chapel Hill, NC 27599 REPORT DATES: October 2017 TYPE OF REPORT: Annual PREPARED FOR...Department of Defense, Washington Headquarters Services , Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite

  5. Dandruff: The most commercially exploited skin disease

    Directory of Open Access Journals (Sweden)

    Ranganathan S

    2010-01-01

    Full Text Available The article discuss in detail about the prevalence, pathophysiology, clinical manifestations of dandruff including the etio-pathology. The article also discusses in detail about various treatment methods available for dandruff. The status of dandruff being amphibious - a disease/disorder, and relatively less medical intervention is sought after for the treatment, dandruff is the most commercially exploited skin and scalp disorder/disease by personal care industries.

  6. Exploiting partial knowledge for efficient model analysis

    OpenAIRE

    Macedo, Nuno; Cunha, Alcino; Pessoa, Eduardo José Dias

    2017-01-01

    The advancement of constraint solvers and model checkers has enabled the effective analysis of high-level formal specification languages. However, these typically handle a specification in an opaque manner, amalgamating all its constraints in a single monolithic verification task, which often proves to be a performance bottleneck. This paper addresses this issue by proposing a solving strategy that exploits user-provided partial knowledge, namely by assigning symbolic bounds to the problem’s ...

  7. Amplifiers Exploiting Thermal Noise Canceling: A Review

    OpenAIRE

    Klumperink, Eric A.M.; Bruccoleri, Federico; Stroet, Peter; Nauta, Bram

    2004-01-01

    Wide-band LNAs suffer from a fundamental trade-off between noise figure NF and source impedance matching, which limits NF to values typically above 3dB. Recently, a feed-forward noise canceling technique has been proposed to break this trade-off. This paper reviews the principle of the technique and its key properties. Although the technique has been applied to wideband CMOS LNAs, it can just as well be implemented exploiting transconductance elements realized with oth...

  8. Exploiting thesauri knowledge in medical guideline formalization

    OpenAIRE

    Serban, R.C.; ten Teije, A.C.M.

    2009-01-01

    Objectives: As in software product lifecycle, the effort spent in maintaining medical knowl edge in guidelines can be reduced, if modularization, formalization and tracking of domain knowledge are employed across the guideline development phases. Methods: We propose to exploit and combine knowledge templates with medical background knowledge from existing thesauri in order to produce reusable building blocks used in guideline development. These tem- plates enable easier guideline formalizatio...

  9. Exploitation as the Unequal Exchange of Labour : An Axiomatic Approach

    OpenAIRE

    Yoshihara, Naoki; Veneziani, Roberto

    2009-01-01

    In subsistence economies with general convex technology and rational optimising agents, a new, axiomatic approach is developed, which allows an explicit analysis of the core positive and normative intuitions behind the concept of exploitation. Three main new axioms, called Labour Exploitation in Subsistence Economies , Relational Exploitation , and Feasibility of Non-Exploitation , are presented and it is proved that they uniquely characterise a definition of exploitation conceptually related...

  10. Security option file - Exploitation (DOS-Expl)

    International Nuclear Information System (INIS)

    2016-01-01

    This document aims at presenting functions performed by Cigeo during its exploitation phase, its main technical and security options which are envisaged with respect to different types of internal or external risks, and a first assessment of its impact on mankind and on the environment during its exploitation in normal operation as well as in incidental or accidental situations. A first volume addresses security principles, approach and management in relationship with the legal and regulatory framework. The second volume presents input data related to waste parcels and used for the installation sizing and operation, the main site characteristics, the main technical options regarding structures and equipment, and the main options regarding exploitation (parcel management, organisational and human aspects, and effluent management). The third volume describes how parcel are processed from their arrival to their setting in storage compartment, an inventory of internal and external risks, and a first assessment of consequences of scenarios on mankind and on the environment. The fourth volume presents options and operations which are envisaged regarding Cigeo closure, and inventory of associated risks

  11. Microbiological exploitation of the chemokine system

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Rosenkilde, Mette Marie

    2003-01-01

    Several viruses encode chemokine elements in their genome. This review focuses on the roles of such elements in the ongoing battle between the virus and the host. The biological and pharmacological characterizations of several of these chemokine elements have highlighted their importance in the m...

  12. Unique physiology of host-parasite interactions in microsporidia infections.

    Science.gov (United States)

    Williams, Bryony A P

    2009-11-01

    Microsporidia are intracellular parasites of all major animal lineages and have a described diversity of over 1200 species and an actual diversity that is estimated to be much higher. They are important pathogens of mammals, and are now one of the most common infections among immunocompromised humans. Although related to fungi, microsporidia are atypical in genomic biology, cell structure and infection mechanism. Host cell infection involves the rapid expulsion of a polar tube from a dormant spore to pierce the host cell membrane and allow the direct transfer of the spore contents into the host cell cytoplasm. This intimate relationship between parasite and host is unique. It allows the microsporidia to be highly exploitative of the host cell environment and cause such diverse effects as the induction of hypertrophied cells to harbour prolific spore development, host sex ratio distortion and host cell organelle and microtubule reorganization. Genome sequencing has revealed that microsporidia have achieved this high level of parasite sophistication with radically reduced proteomes and with many typical eukaryotic pathways pared-down to what appear to be minimal functional units. These traits make microsporidia intriguing model systems for understanding the extremes of reductive parasite evolution and host cell manipulation.

  13. Seasonal changes in english walnut (Juglans regia L.) (Juglandaceae), fruit properties and host use patterns by Rhagoletis zoqui (Diptera: Tephritidae)

    Science.gov (United States)

    Rhagoletis zoqui Bush is a Neosubtropical, univoltine, frugivorous tephritid fly that exploits both native Juglans spp. and the introduced, Palearctic English walnut, Juglans regia. The seasonal development of commercial J. regia fruit and the pattern of host exploitation by R. zoqui were tracked ov...

  14. Chitosan-hyaluronan based 3D co-culture platform for studying the crosstalk of lung cancer cells and mesenchymal stem cells.

    Science.gov (United States)

    Han, Hao-Wei; Hsu, Shan-Hui

    2016-09-15

    The controversial roles of mesenchymal stem cells (MSCs) in lung cancer development are not yet resolved because of the lack of an extracellular environment that mimics the tumor microenvironment. Three-dimensional (3D) culture system is an emerging research tool for biomedical applications such as drug screening. In this study, MSCs and human non-small cell lung carcinoma cells (A549) were co-cultured on a thin biomaterial-based substratum (hyaluronan-grafted chitosan, CS-HA; ∼2μm), and they were self-organized into the 3D tumor co-spheroids with core-shell structure. The gene expression levels of tumorigenicity markers in cancer cells associated with cancer stemness, epithelial-mesenchymal transition (EMT) property, and cell mobility were up-regulated for more than twofold in the MSC-tumor co-spheroids, through the promoted expression of certain tumor enhancers and the direct cell-cell interaction. To verify the different extents of tumorigenicity, A549 cells or those co-cultured with MSCs were transplanted into zebrafish embryos for evaluation in vivo. The tumorigenicity obtained from the zebrafish xenotransplantation model was consistent with that observed in vitro. These evidences suggest that the CS-HA substrate-based 3D co-culture platform for cancer cells and MSCs may be a convenient tool for studying the cell-cell interaction in a tumor-like microenvironment and potentially for cancer drug testing. Mesenchymal stem cells (MSCs) have been found in several types of tumor tissues. However, the controversial roles of MSCs in cancer development are still unsolved. Chitosan and hyaluronan are commonly used materials in the biomedical field. In the current study, we co-cultured lung cancer cells and MSCs on the planar hyaluronan-grafted chitosan (CS-HA) hybrid substrates, and discovered that lung cancer cells and MSCs were rapidly self-assembled into 3D tumor spheroids with core-shell structure on the substrates after only two days in culture. Therefore, CS

  15. Cloud Based Earth Observation Data Exploitation Platforms

    Science.gov (United States)

    Romeo, A.; Pinto, S.; Loekken, S.; Marin, A.

    2017-12-01

    In the last few years data produced daily by several private and public Earth Observation (EO) satellites reached the order of tens of Terabytes, representing for scientists and commercial application developers both a big opportunity for their exploitation and a challenge for their management. New IT technologies, such as Big Data and cloud computing, enable the creation of web-accessible data exploitation platforms, which offer to scientists and application developers the means to access and use EO data in a quick and cost effective way. RHEA Group is particularly active in this sector, supporting the European Space Agency (ESA) in the Exploitation Platforms (EP) initiative, developing technology to build multi cloud platforms for the processing and analysis of Earth Observation data, and collaborating with larger European initiatives such as the European Plate Observing System (EPOS) and the European Open Science Cloud (EOSC). An EP is a virtual workspace, providing a user community with access to (i) large volume of data, (ii) algorithm development and integration environment, (iii) processing software and services (e.g. toolboxes, visualization routines), (iv) computing resources, (v) collaboration tools (e.g. forums, wiki, etc.). When an EP is dedicated to a specific Theme, it becomes a Thematic Exploitation Platform (TEP). Currently, ESA has seven TEPs in a pre-operational phase dedicated to geo-hazards monitoring and prevention, costal zones, forestry areas, hydrology, polar regions, urban areas and food security. On the technology development side, solutions like the multi cloud EO data processing platform provides the technology to integrate ICT resources and EO data from different vendors in a single platform. In particular it offers (i) Multi-cloud data discovery, (ii) Multi-cloud data management and access and (iii) Multi-cloud application deployment. This platform has been demonstrated with the EGI Federated Cloud, Innovation Platform Testbed Poland

  16. Heisenberg's heirs exploit loopholes in his law

    International Nuclear Information System (INIS)

    Taubes, G.

    1994-01-01

    This article describes research into Heisenberg's Uncertainty Principle. Loopholes in the principle have led to a series of experiments using sophisticated optical techniques to extract information from a quantum system without disturbing the variable being measured. The experiments are based on a technique called back-action evasion, which exploits the possibility of channeling all the uncertainty generated by measuring one quantum variable (e.g. laser beam intensity) onto a related variable known as the conjugate observable (beam phase). These experiments and others are described

  17. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars

    2010-01-01

    an overview of current strategies for improving the different stages of liposomal cancer therapy, which involve transporting drug-loaded liposomes through the bloodstream, increasing tumor accumulation, and improving drug release and cancer cell uptake after accumulation at the tumor target site. What...... the reader will gain: The review focuses on strategies that exploit characteristic features of solid tumors, such as abnormal vasculature, overexpression of receptors and enzymes, as well as acidic and thiolytic characteristics of the tumor microenvironment. Take home message: It is concluded that the design...

  18. Pilot plant for exploitation of geothermal waters

    Directory of Open Access Journals (Sweden)

    Stojiljković Dragan T.

    2006-01-01

    Full Text Available In Sijarinska spa, there are some 15 mineral and thermomineral springs, that are already being used for therapeutic purposes. For the exploitation of heat energy boring B-4 is very interesting. It is a boring of a closed type, with the water temperature of about 78°C and a flow rate of about 33 l/s. Waters with the flow rate of about 6 l/s are currently used for heating of the Gejzer hotel, and waters of the flow rate of about 0,121 l/s for the pilot drying plant. The paper presents this pilot plant. .

  19. Exploiting Redundancy in an OFDM SDR Receiver

    Directory of Open Access Journals (Sweden)

    Tomas Palenik

    2009-01-01

    Full Text Available Common OFDM system contains redundancy necessary to mitigate interblock interference and allows computationally effective single-tap frequency domain equalization in receiver. Assuming the system implements an outer error correcting code and channel state information is available in the receiver, we show that it is possible to understand the cyclic prefix insertion as a weak inner ECC encoding and exploit the introduced redundancy to slightly improve error performance of such a system. In this paper, an easy way to implement modification to an existing SDR OFDM receiver is presented. This modification enables the utilization of prefix redundancy, while preserving full compatibility with existing OFDM-based communication standards.

  20. Geothermal resources: exploration and exploitation. A bibliography

    Energy Technology Data Exchange (ETDEWEB)

    1976-07-01

    This comprehensive bibliography contains 5476 citations of foreign and domestic research reports, journal articles, patents, conference proceedings, and books concerned with the exploration and exploitation of geothermal resources. The coverage dates back as far as useful references could be obtained and extends through June 1976. References are arranged in broad subject categories and are made up of complete bibliographic citations. These are followed by a listing of subject descriptors used to describe the subject content of each reference. Four indexes are included: Corporate, Personal Author, Subject, and Report Number. Also included is a list of journals from which articles were selected. (LBS)

  1. Algorithms exploiting ultrasonic sensors for subject classification

    Science.gov (United States)

    Desai, Sachi; Quoraishee, Shafik

    2009-09-01

    Proposed here is a series of techniques exploiting micro-Doppler ultrasonic sensors capable of characterizing various detected mammalian targets based on their physiological movements captured a series of robust features. Employed is a combination of unique and conventional digital signal processing techniques arranged in such a manner they become capable of classifying a series of walkers. These processes for feature extraction develops a robust feature space capable of providing discrimination of various movements generated from bipeds and quadrupeds and further subdivided into large or small. These movements can be exploited to provide specific information of a given signature dividing it in a series of subset signatures exploiting wavelets to generate start/stop times. After viewing a series spectrograms of the signature we are able to see distinct differences and utilizing kurtosis, we generate an envelope detector capable of isolating each of the corresponding step cycles generated during a walk. The walk cycle is defined as one complete sequence of walking/running from the foot pushing off the ground and concluding when returning to the ground. This time information segments the events that are readily seen in the spectrogram but obstructed in the temporal domain into individual walk sequences. This walking sequence is then subsequently translated into a three dimensional waterfall plot defining the expected energy value associated with the motion at particular instance of time and frequency. The value is capable of being repeatable for each particular class and employable to discriminate the events. Highly reliable classification is realized exploiting a classifier trained on a candidate sample space derived from the associated gyrations created by motion from actors of interest. The classifier developed herein provides a capability to classify events as an adult humans, children humans, horses, and dogs at potentially high rates based on the tested sample

  2. Augmented reality enabling intelligence exploitation at the edge

    Science.gov (United States)

    Kase, Sue E.; Roy, Heather; Bowman, Elizabeth K.; Patton, Debra

    2015-05-01

    Today's Warfighters need to make quick decisions while interacting in densely populated environments comprised of friendly, hostile, and neutral host nation locals. However, there is a gap in the real-time processing of big data streams for edge intelligence. We introduce a big data processing pipeline called ARTEA that ingests, monitors, and performs a variety of analytics including noise reduction, pattern identification, and trend and event detection in the context of an area of operations (AOR). Results of the analytics are presented to the Soldier via an augmented reality (AR) device Google Glass (Glass). Non-intrusive AR devices such as Glass can visually communicate contextually relevant alerts to the Soldier based on the current mission objectives, time, location, and observed or sensed activities. This real-time processing and AR presentation approach to knowledge discovery flattens the intelligence hierarchy enabling the edge Soldier to act as a vital and active participant in the analysis process. We report preliminary observations testing ARTEA and Glass in a document exploitation and person of interest scenario simulating edge Soldier participation in the intelligence process in disconnected deployment conditions.

  3. Host age modulates within-host parasite competition.

    Science.gov (United States)

    Izhar, Rony; Routtu, Jarkko; Ben-Ami, Frida

    2015-05-01

    In many host populations, one of the most striking differences among hosts is their age. While parasite prevalence differences in relation to host age are well known, little is known on how host age impacts ecological and evolutionary dynamics of diseases. Using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa, we examined how host age at exposure influences within-host parasite competition and virulence. We found that multiply-exposed hosts were more susceptible to infection and suffered higher mortality than singly-exposed hosts. Hosts oldest at exposure were least often infected and vice versa. Furthermore, we found that in young multiply-exposed hosts competition was weak, allowing coexistence and transmission of both parasite clones, whereas in older multiply-exposed hosts competitive exclusion was observed. Thus, age-dependent parasite exposure and host demography (age structure) could together play an important role in mediating parasite evolution. At the individual level, our results demonstrate a previously unnoticed interaction of the host's immune system with host age, suggesting that the specificity of immune function changes as hosts mature. Therefore, evolutionary models of parasite virulence might benefit from incorporating age-dependent epidemiological parameters. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  4. Competing Discourses about Youth Sexual Exploitation in Canadian News Media.

    Science.gov (United States)

    Saewyc, Elizabeth M; Miller, Bonnie B; Rivers, Robert; Matthews, Jennifer; Hilario, Carla; Hirakata, Pam

    2013-10-01

    Media holds the power to create, maintain, or break down stigmatizing attitudes, which affect policies, funding, and services. To understand how Canadian news media depicts the commercial sexual exploitation of children and youth, we examined 835 Canadian newspaper articles from 1989-2008 using a mixed methods critical discourse analysis approach, comparing representations to existing research about sexually exploited youth. Despite research evidence that equal rates of boys and girls experience exploitation, Canadian news media depicted exploited youth predominantly as heterosexual girls, and described them alternately as victims or workers in a trade, often both in the same story. News media mentioned exploiters far less often than victims, and portrayed them almost exclusively as male, most often called 'customers' or 'consumers,' and occasionally 'predators'; in contrast, research has documented the majority of sexually exploited boys report female exploiters. Few news stories over the past two decades portrayed the diversity of victims, perpetrators, and venues of exploitation reported in research. The focus on victims but not exploiters helps perpetuate stereotypes of sexual exploitation as business or a 'victimless crime,' maintains the status quo, and blurs responsibility for protecting youth under the UN Convention on the Rights of the Child. Health care providers and researchers can be advocates for accuracy in media coverage about sexual exploitation; news reporters and editors should focus on exploiters more than victims, draw on existing research evidence to avoid perpetuating stereotypes, and use accurate terms, such as commercial sexual exploitation, rather than terms related to business or trade.

  5. ROUNDTABLE - SESSION 2 EXPLOITATION, CONSERVATION AND LEGISLATION

    Directory of Open Access Journals (Sweden)

    EDSMAN L.

    2004-01-01

    Full Text Available The link between socioeconomics and conservation and the role of legislation in conservation work was discussed in the group with participants from nine European countries. Interest and knowledge among the general public, stakeholders and managers is the key to successful conservation of native crayfish species. Exploitation and conservation do not necessarily exclude each other. A controlled fishery, where it can be sustained, may be an essential tool for conservation by increasing the general awareness and involving more people in the task of protecting the native crayfish species. This strategy is mainly possible for the noble crayfish in the northern part of its distribution, where strong traditions connected to crayfish also exist. A balance between utilisation and overexploitation has to be found and local guidelines for sustainable exploitation produced. Media, the Internet and educational material aimed at schools and stakeholders are excellent ways of reaching a wide audience with information. Universal objectives, rules and regulations at the European level are desirable and the noble crayfish and the stone crayfish should be included in Annex II of the Habitat Directive. Based on this framework detailed regulations are best worked out at the national level, considering the specific crayfish situation in the country. Information about the legislation, the purpose of the legislation and the consequences when not obeying it should be distributed. Stricter regulation of the trade with live alien crayfish is vital because of the associated risk of introducing new diseases and species.

  6. Uncovering Indicators of Commercial Sexual Exploitation.

    Science.gov (United States)

    Bounds, Dawn; Delaney, Kathleen R; Julion, Wrenetha; Breitenstein, Susan

    2017-07-01

    It is estimated that annually 100,000 to 300,000 youth are at risk for sex trafficking; a commercial sex act induced by force, fraud, or coercion, or any such act where the person induced to perform such an act is younger than 18 years of age. Increasingly, such transactions are occurring online via Internet-based sites that serve the commercial sex industry. Commercial sex transactions involving trafficking are illegal; thus, Internet discussions between those involved must be veiled. Even so, transactions around sex trafficking do occur. Within these transactions are innuendos that provide one avenue for detecting potential activity. The purpose of this study is to identify linguistic indicators of potential commercial sexual exploitation within the online comments of men posted on an Internet site. Six hundred sixty-six posts from five Midwest cities and 363 unique members were analyzed via content analysis. Three main indicators were found: the presence of youth or desire for youthfulness, presence of pimps, and awareness of vulnerability. These findings begin a much-needed dialogue on uncovering online risks of commercial sexual exploitation and support the need for further research on Internet indicators of sex trafficking.

  7. Large size space construction for space exploitation

    Science.gov (United States)

    Kondyurin, Alexey

    2016-07-01

    Space exploitation is impossible without large space structures. We need to make sufficient large volume of pressurized protecting frames for crew, passengers, space processing equipment, & etc. We have to be unlimited in space. Now the size and mass of space constructions are limited by possibility of a launch vehicle. It limits our future in exploitation of space by humans and in development of space industry. Large-size space construction can be made with using of the curing technology of the fibers-filled composites and a reactionable matrix applied directly in free space. For curing the fabric impregnated with a liquid matrix (prepreg) is prepared in terrestrial conditions and shipped in a container to orbit. In due time the prepreg is unfolded by inflating. After polymerization reaction, the durable construction can be fitted out with air, apparatus and life support systems. Our experimental studies of the curing processes in the simulated free space environment showed that the curing of composite in free space is possible. The large-size space construction can be developed. A project of space station, Moon base, Mars base, mining station, interplanet space ship, telecommunication station, space observatory, space factory, antenna dish, radiation shield, solar sail is proposed and overviewed. The study was supported by Humboldt Foundation, ESA (contract 17083/03/NL/SFe), NASA program of the stratospheric balloons and RFBR grants (05-08-18277, 12-08-00970 and 14-08-96011).

  8. PROBA-V Mission Exploitation Platform

    Directory of Open Access Journals (Sweden)

    Erwin Goor

    2016-07-01

    Full Text Available As an extension of the PROBA-Vegetation (PROBA-V user segment, the European Space Agency (ESA, de Vlaamse Instelling voor Technologisch Onderzoek (VITO, and partners TRASYS and Spacebel developed an operational Mission Exploitation Platform (MEP to drastically improve the exploitation of the PROBA-V Earth Observation (EO data archive, the archive from the historical SPOT-VEGETATION mission, and derived products by researchers, service providers, and thematic users. The analysis of the time series of data (petabyte range is addressed, as well as the large scale on-demand processing of the complete archive, including near real-time data. The platform consists of a private cloud environment, a Hadoop-based processing environment and a data manager. Several applications are released to the users, e.g., a full resolution viewing service, a time series viewer, pre-defined on-demand processing chains, and virtual machines with powerful tools and access to the data. After an initial release in January 2016 a research platform was deployed gradually, allowing users to design, debug, and test applications on the platform. From the PROBA-V MEP, access to, e.g., Sentinel-2 and Sentinel-3 data will be addressed as well.

  9. Host specialist clownfishes are environmental niche generalists

    Science.gov (United States)

    Litsios, Glenn; Kostikova, Anna; Salamin, Nicolas

    2014-01-01

    Why generalist and specialist species coexist in nature is a question that has interested evolutionary biologists for a long time. While the coexistence of specialists and generalists exploiting resources on a single ecological dimension has been theoretically and empirically explored, biological systems with multiple resource dimensions (e.g. trophic, ecological) are less well understood. Yet, such systems may provide an alternative to the classical theory of stable evolutionary coexistence of generalist and specialist species on a single resource dimension. We explore such systems and the potential trade-offs between different resource dimensions in clownfishes. All species of this iconic clade are obligate mutualists with sea anemones yet show interspecific variation in anemone host specificity. Moreover, clownfishes developed variable environmental specialization across their distribution. In this study, we test for the existence of a relationship between host-specificity (number of anemones associated with a clownfish species) and environmental-specificity (expressed as the size of the ecological niche breadth across climatic gradients). We find a negative correlation between host range and environmental specificities in temperature, salinity and pH, probably indicating a trade-off between both types of specialization forcing species to specialize only in a single direction. Trade-offs in a multi-dimensional resource space could be a novel way of explaining the coexistence of generalist and specialists. PMID:25274370

  10. Detecting peripheral-based attacks on the host memory

    CERN Document Server

    Stewin, Patrick

    2015-01-01

    This work addresses stealthy peripheral-based attacks on host computers and presents a new approach to detecting them. Peripherals can be regarded as separate systems that have a dedicated processor and dedicated runtime memory to handle their tasks. The book addresses the problem that peripherals generally communicate with the host via the host’s main memory, storing cryptographic keys, passwords, opened files and other sensitive data in the process – an aspect attackers are quick to exploit.  Here, stealthy malicious software based on isolated micro-controllers is implemented to conduct an attack analysis, the results of which provide the basis for developing a novel runtime detector. The detector reveals stealthy peripheral-based attacks on the host’s main memory by exploiting certain hardware properties, while a permanent and resource-efficient measurement strategy ensures that the detector is also capable of detecting transient attacks, which can otherwise succeed when the applied strategy only me...

  11. Testing local host adaptation and phenotypic plasticity in a herbivore when alternative related host plants occur sympatrically.

    Directory of Open Access Journals (Sweden)

    Lorena Ruiz-Montoya

    Full Text Available Host race formation in phytophagous insects can be an early stage of adaptive speciation. However, the evolution of phenotypic plasticity in host use is another possible outcome. Using a reciprocal transplant experiment we tested the hypothesis of local adaptation in the aphid Brevicoryne brassicae. Aphid genotypes derived from two sympatric host plants, Brassica oleracea and B. campestris, were assessed in order to measure the extent of phenotypic plasticity in morphological and life history traits in relation to the host plants. We obtained an index of phenotypic plasticity for each genotype. Morphological variation of aphids was summarized by principal components analysis. Significant effects of recipient host on morphological variation and life history traits (establishment, age at first reproduction, number of nymphs, and intrinsic growth rate were detected. We did not detected genotype × host plant interaction; in general the genotypes developed better on B. campestris, independent of the host plant species from which they were collected. Therefore, there was no evidence to suggest local adaptation. Regarding plasticity, significant differences among genotypes in the index of plasticity were detected. Furthermore, significant selection on PC1 (general aphid body size on B. campestris, and on PC1 and PC2 (body length relative to body size on B. oleracea was detected. The elevation of the reaction norm of PC1 and the slope of the reaction norm for PC2 (i.e., plasticity were under directional selection. Thus, host plant species constitute distinct selective environments for B. brassicae. Aphid genotypes expressed different phenotypes in response to the host plant with low or nil fitness costs. Phenotypic plasticity and gene flow limits natural selection for host specialization promoting the maintenance of genetic variation in host exploitation.

  12. Born in an alien nest: how do social parasite male offspring escape from host aggression?

    Directory of Open Access Journals (Sweden)

    Patrick Lhomme

    Full Text Available Social parasites exploit the colony resources of social insects. Some of them exploit the host colony as a food resource or as a shelter whereas other species also exploit the brood care behavior of their social host. Some of these species have even lost the worker caste and rely completely on the host's worker force to rear their offspring. To avoid host defenses and bypass their recognition code, these social parasites have developed several sophisticated chemical infiltration strategies. These infiltration strategies have been highly studied in several hymenopterans. Once a social parasite has successfully entered a host nest and integrated its social system, its emerging offspring still face the same challenge of avoiding host recognition. However, the strategy used by the offspring to survive within the host nest without being killed is still poorly documented. In cuckoo bumblebees, the parasite males completely lack the morphological and chemical adaptations to social parasitism that the females possess. Moreover, young parasite males exhibit an early production of species-specific cephalic secretions, used as sexual pheromones. Host workers might thus be able to recognize them. Here we used a bumblebee host-social parasite system to test the hypothesis that social parasite male offspring exhibit a chemical defense strategy to escape from host aggression during their intranidal life. Using behavioral assays, we showed that extracts from the heads of young cuckoo bumblebee males contain a repellent odor that prevents parasite males from being attacked by host workers. We also show that social parasitism reduces host worker aggressiveness and helps parasite offspring acceptance.

  13. zero day exploits and national readiness for cyber-warfare

    African Journals Online (AJOL)

    HOD

    A zero day vulnerability is an unknown exploit that divulges security flaws in software before such a flaw is publicly ... Keywords: exploits, zero day, vulnerability, cyberspace, cyber-warfare. 1. ..... industries and companies across the globe. The.

  14. Immunohistochemical analysis of EGFR and hyaluronan in tongue cancer and the development of regional recurrence in patients initially diagnosed N0.

    Science.gov (United States)

    Lindell Jonsson, Eva; Nylander, Karin; Hallén, Lars; Laurell, Göran

    2017-08-01

    To investigate whether the extent of expression of hyaluronan (HA) and epidermal growth factor receptor (EGFR) in squamous cell carcinoma of the mobile tongue can predict the risk of cervical metastasis and survival. Retrospective histopathologic study. Surgical specimens from 64 patients who had undergone surgery for squamous cell carcinoma of the mobile tongue were assessed using immunohistochemistry to investigate the expression of HA and EGFR in the primary tumours, and the data were then correlated to cervical metastasis and survival. There was a significant correlation between the intensity of HA staining and patient survival (p .024), and a weak correlation between the staining proportion of EGFR and the risk for regional recurrence (AUC 66). This study indicates that immunoscoring using HA could be used to provide prognostic tools for tongue cancer, and that it might be of interest to study the prognostic properties of EGFR further concerning the risk for regional recurrence after the primary treatment.

  15. Host phylogeny determines viral persistence and replication in novel hosts.

    Directory of Open Access Journals (Sweden)

    Ben Longdon

    2011-09-01

    Full Text Available Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

  16. Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

    Science.gov (United States)

    Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

    2011-01-01

    Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

  17. The Theory of Exploitation as the Unequal Exchange of Labour

    OpenAIRE

    Veneziani, Roberto; Yoshihara, Naoki

    2016-01-01

    This paper analyses the normative and positive foundations of the theory of exploitation as the unequal exchange of labour (UEL). The key intuitions behind all of the main approaches to UEL exploitation are explicitly analysed as a series of formal claims in a general economic environment. It is then argued that these intuitions can be captured by one fundamental axiom - called Labour Exploitation - which defines the basic domain of all UEL exploitation forms and identifies the formal and the...

  18. The theory of exploitation as the unequal exchange of labour

    OpenAIRE

    Veneziani, Roberto; Yoshihara, Naoki

    2017-01-01

    This paper analyses the normative and positive foundations of the theory of exploitation as the unequal exchange of labour (UEL). The key intuitions behind all of the main approaches to UEL exploitation are explicitly analysed as a series of formal claims in a general economic environment. It is then argued that these intuitions can be captured by one fundamental axiom - called Labour Exploitation - which defines the basic domain of all UEL exploitation forms and identifies the formal and the...

  19. Total exploitation of an ornamental granite quarry

    Directory of Open Access Journals (Sweden)

    Taboada, J.

    2005-09-01

    Full Text Available In this paper we propose a methodology to estimate the recovery percentage for each of the products which can be obtained from the exploitation of an ornamental granite quarry: block, semiblock, masonry-transverse stone, and the smaller materials that can be used to obtain construction aggregates. This methodology ensures that quarry exploitation is exhaustive, thereby minimising the production of spoils and the consequent negative impact on the environment. The analysis is based on a detailed and exhaustive compilation of discontinuity data from the research fronts, which are then interpreted statistically and projected over the three weakness planes that are a particular feature of ornamental granite deposits. Using this information, and bearing in mind the minimum commercially viable sizes for each kind of granite, the corresponding recovery rates are calculated for each material in each plane. The results are then integrated using spatial techniques, and the result is an evaluation of quarry contents with a view to total exploitation. This methodology was applied to a quarry in the opening phase in order to carry out an a priori assessment of the economic feasibility of the quarry.

    En este trabajo se propone una metodología para estimar el porcentaje de recuperación de cada uno de los productos que se pueden obtener en la explotación de una cantera de granito ornamental: bloque, semibloque, manpostería y per piaños, y material restante destinado a la obtención de áridos. De esta manera se logra un aprovechamiento integral de la cantera, evitándose la generación de estériles y el subsiguiente impacto ambiental producido por éstos. La metodología de análisis se basa en la recopilación detallada y exhaustiva de datos de discontinuidades en los frentes de investigación, que se interpretan estadísticamente y se proyectan sobre los tres planos de debilidad propios del granito ornamental. Con esta información, y las

  20. Membrane rafts: a potential gateway for bacterial entry into host cells.

    Science.gov (United States)

    Hartlova, Anetta; Cerveny, Lukas; Hubalek, Martin; Krocova, Zuzana; Stulik, Jiri

    2010-04-01

    Pathogenic bacteria have developed various mechanisms to evade host immune defense systems. Invasion of pathogenic bacteria requires interaction of the pathogen with host receptors, followed by activation of signal transduction pathways and rearrangement of the cytoskeleton to facilitate bacterial entry. Numerous bacteria exploit specialized plasma membrane microdomains, commonly called membrane rafts, which are rich in cholesterol, sphingolipids and a special set of signaling molecules which allow entry to host cells and establishment of a protected niche within the host. This review focuses on the current understanding of the raft hypothesis and the means by which pathogenic bacteria subvert membrane microdomains to promote infection.

  1. Use of habitat odour by host-seeking insects.

    Science.gov (United States)

    Webster, Ben; Cardé, Ring T

    2017-05-01

    Locating suitable feeding or oviposition sites is essential for insect survival. Understanding how insects achieve this is crucial, not only for understanding the ecology and evolution of insect-host interactions, but also for the development of sustainable pest-control strategies that exploit insects' host-seeking behaviours. Volatile chemical cues are used by foraging insects to locate and recognise potential hosts but in nature these resources usually are patchily distributed, making chance encounters with host odour plumes rare over distances greater than tens of metres. The majority of studies on insect host-seeking have focussed on short-range orientation to easily detectable cues and it is only recently that we have begun to understand how insects overcome this challenge. Recent advances show that insects from a wide range of feeding guilds make use of 'habitat cues', volatile chemical cues released over a relatively large area that indicate a locale where more specific host cues are most likely to be found. Habitat cues differ from host cues in that they tend to be released in larger quantities, are more easily detectable over longer distances, and may lack specificity, yet provide an effective way for insects to maximise their chances of subsequently encountering specific host cues. This review brings together recent advances in this area, discussing key examples and similarities in strategies used by haematophagous insects, soil-dwelling insects and insects that forage around plants. We also propose and provide evidence for a new theory that general and non-host plant volatiles can be used by foraging herbivores to locate patches of vegetation at a distance in the absence of more specific host cues, explaining some of the many discrepancies between laboratory and field trials that attempt to make use of plant-derived repellents for controlling insect pests. © 2016 Cambridge Philosophical Society.

  2. Environmental effects of geothermal energy exploitation

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, H [Japan Metals and Chemicals Co., Ltd., Japan

    1975-01-01

    The environmental effects of geothermal power generation which cause air and water pollution and destruction of natural areas are reviewed. The production of steam and hot water affect existing hot springs sources and can cause ground subsidence. Harmful gas can be released onto the atmosphere from fumarolic gas and hot springs. Hydrothermal geothermal fields occasionally contain harmful substances such as arsenic in the hot water. Serious environmental effects can result from geothermal exploitation activities such as the felling of trees for road construction, well drilling, and plant construction. Once geothermal power generation has begun, the release of H/sub 2/S into the atmosphere and the reinjection of hot water are conducted continuously and sufficient countermeasures can be taken. One problem is the effects of plant construction and operation on natural parks. It is important to reach a compromise between development and protection of natural senic areas. Two figures, two tables, and 13 references are provided.

  3. CHARACTERISTICS OF HYDROCARBON EXPLOITATION IN ARCTIC CIRCLE

    Directory of Open Access Journals (Sweden)

    Vanja Lež

    2013-12-01

    Full Text Available The existence of large quantities of hydrocarbons is supposed within the Arctic Circle. Assumed quantities are 25% of the total undiscovered hydrocarbon reserves on Earth, mostly natural gas. Over 500 major and minor gas accumulations within the Arctic Circle were discovered so far, but apart from Snøhvit gas field, there is no commercial exploitation of natural gas from these fields. Arctic gas projects are complicated, technically hard to accomplish, and pose a great threat to the return of investment, safety of people and equipment and for the ecosystem. Russia is a country that is closest to the realization of the Arctic gas projects that are based on the giant gas fields. The most extreme weather conditions in the seas around Greenland are the reason why this Arctic region is the least explored and furthest from the realization of any gas project (the paper is published in Croatian .

  4. Protocol to Exploit Waiting Resources for UASNs

    Directory of Open Access Journals (Sweden)

    Li-Ling Hung

    2016-03-01

    Full Text Available The transmission speed of acoustic waves in water is much slower than that of radio waves in terrestrial wireless sensor networks. Thus, the propagation delay in underwater acoustic sensor networks (UASN is much greater. Longer propagation delay leads to complicated communication and collision problems. To solve collision problems, some studies have proposed waiting mechanisms; however, long waiting mechanisms result in low bandwidth utilization. To improve throughput, this study proposes a slotted medium access control protocol to enhance bandwidth utilization in UASNs. The proposed mechanism increases communication by exploiting temporal and spatial resources that are typically idle in order to protect communication against interference. By reducing wait time, network performance and energy consumption can be improved. A performance evaluation demonstrates that when the data packets are large or sensor deployment is dense, the energy consumption of proposed protocol is less than that of existing protocols as well as the throughput is higher than that of existing protocols.

  5. Exploitation of heterogeneous resources for ATLAS Computing

    CERN Document Server

    Chudoba, Jiri; The ATLAS collaboration

    2018-01-01

    LHC experiments require significant computational resources for Monte Carlo simulations and real data processing and the ATLAS experiment is not an exception. In 2017, ATLAS exploited steadily almost 3M HS06 units, which corresponds to about 300 000 standard CPU cores. The total disk and tape capacity managed by the Rucio data management system exceeded 350 PB. Resources are provided mostly by Grid computing centers distributed in geographically separated locations and connected by the Grid middleware. The ATLAS collaboration developed several systems to manage computational jobs, data files and network transfers. ATLAS solutions for job and data management (PanDA and Rucio) were generalized and now are used also by other collaborations. More components are needed to include new resources such as private and public clouds, volunteers' desktop computers and primarily supercomputers in major HPC centers. Workflows and data flows significantly differ for these less traditional resources and extensive software re...

  6. Geometric saliency to characterize radar exploitation performance

    Science.gov (United States)

    Nolan, Adam; Keserich, Brad; Lingg, Andrew; Goley, Steve

    2014-06-01

    Based on the fundamental scattering mechanisms of facetized computer-aided design (CAD) models, we are able to define expected contributions (EC) to the radar signature. The net result of this analysis is the prediction of the salient aspects and contributing vehicle morphology based on the aspect. Although this approach does not provide the fidelity of an asymptotic electromagnetic (EM) simulation, it does provide very fast estimates of the unique scattering that can be consumed by a signature exploitation algorithm. The speed of this approach is particularly relevant when considering the high dimensionality of target configuration variability due to articulating parts which are computationally burdensome to predict. The key scattering phenomena considered in this work are the specular response from a single bounce interaction with surfaces and dihedral response formed between the ground plane and vehicle. Results of this analysis are demonstrated for a set of civilian target models.

  7. Exploitation and use of coal field gas

    Energy Technology Data Exchange (ETDEWEB)

    Wang, K; Li, Z; Sun, Q

    1982-04-25

    There are slightly more than 440 mine shafts in the world from which gas is pumped at the same time coal is being mined, the volume pumped being 3.125 billion cubic meters. All the countries of the world today widely use gas as a fuel and as a raw material for the chemical industry. In China 40 percent of the total number of mine shafts are high gas mine shafts. In China, gas is used largely as fuel by the people, to fire boilers, to make formaldehyde, and to make carbon ink. Prospects are good for the exploitation of mine shaft gas that is produced in association with coal. Mine shaft gas is a top quality energy source with an extraction life that is longer than coals. (DP)

  8. Liking and hyperlinking: Community detection in online child sexual exploitation networks.

    Science.gov (United States)

    Westlake, Bryce G; Bouchard, Martin

    2016-09-01

    The online sexual exploitation of children is facilitated by websites that form virtual communities, via hyperlinks, to distribute images, videos, and other material. However, how these communities form, are structured, and evolve over time is unknown. Collected using a custom-designed webcrawler, we begin from known child sexual exploitation (CE) seed websites and follow hyperlinks to connected, related, websites. Using a repeated measure design we analyze 10 networks of 300 + websites each - over 4.8 million unique webpages in total, over a period of 60 weeks. Community detection techniques reveal that CE-related networks were dominated by two large communities hosting varied material -not necessarily matching the seed website. Community stability, over 60 weeks, varied across networks. Reciprocity in hyperlinking between community members was substantially higher than within the full network, however, websites were not more likely to connect to homogeneous-content websites. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. A multicriteria approach to identify investment opportunities for the exploitation of the clean development mechanism

    International Nuclear Information System (INIS)

    Diakoulaki, D.; Georgiou, P.; Tourkolias, C.; Georgopoulou, E.; Lalas, D.; Mirasgedis, S.; Sarafidis, Y.

    2007-01-01

    The aim of the present paper is to investigate the prospects for the exploitation of the Kyoto Protocol's Clean Development Mechanism (CDM) in Greece. The paper is addressing 3 questions: in which country, what kind of investment, with which economic and environmental return? The proposed approach is based on a multicriteria analysis for identifying priority countries and interesting investment opportunities in each priority country. These opportunities are then evaluated through a conventional financial analysis in order to assess their economic and environmental attractiveness. To this purpose, the IRR of a typical project in each investment category is calculated by taking into account country-specific parameters, such as baseline emission factors, load factors, costs, energy prices etc. The results reveal substantial differences in the economic and environmental return of different types of projects in different host-countries and show that for the full exploitation of the CDM a multifaceted approach to decision-making is necessary

  10. Exploiting Unique Structural and Functional Properties of Malarial Glycolytic Enzymes for Antimalarial Drug Development

    Directory of Open Access Journals (Sweden)

    Asrar Alam

    2014-01-01

    Full Text Available Metabolic enzymes have been known to carry out a variety of functions besides their normal housekeeping roles known as “moonlighting functions.” These functionalities arise from structural changes induced by posttranslational modifications and/or binding of interacting proteins. Glycolysis is the sole source of energy generation for malaria parasite Plasmodium falciparum, hence a potential pathway for therapeutic intervention. Crystal structures of several P. falciparum glycolytic enzymes have been solved, revealing that they exhibit unique structural differences from the respective host enzymes, which could be exploited for their selective targeting. In addition, these enzymes carry out many parasite-specific functions, which could be of potential interest to control parasite development and transmission. This review focuses on the moonlighting functions of P. falciparum glycolytic enzymes and unique structural differences and functional features of the parasite enzymes, which could be exploited for therapeutic and transmission blocking interventions against malaria.

  11. Summary of radiation protection in exploitation

    International Nuclear Information System (INIS)

    Garcier, Yves; Guers, Rene; Bidard, Francoise; Colson, Philippe; Gonin, Michele; Delabre, Herve; Hemidy, Pierre-Yves; Corgnet, Bruno; Perrin, Marie-Claire; Phan Hoang, Long; Abela, Gonzague; Crepieux, Virginie; Guyot, Pierre; Haranger, Didier; Warembourg, Philippe

    2004-01-01

    This document proposes a large and detailed overview of notions and practices regarding radiation protection in relationship with an NPP exploitation framework. It presents the main notions: matter structure, radioactivity, interactions between matter and radiations, types of ionizing radiation, magnitudes and measurement units, exposure modes, main principles of radiation protection, means of protection against internal and external exposures. The second part proposes an overview of the origin of radiological risks in a nuclear power plant. This origin can be found in fission products, activation products, actinides, designed protections, or circuit contaminations. These radiological risks are more precisely identified and described in terms of detection and prevention (internal exposure risk, contamination risk, iodine-related risk, alpha radiation-related risk, access to the reactor building). The next part addresses the medical and radiological follow-up of exposed workers by a special medical control, by an individual exposure control, by a specific control of female personnel, and by attention to exceptional exposures. Measurement means are presented (detection principles, installation continuous control, workspaces control, personnel contamination control, follow-up of individual dose) as well as collective and individual protection means. The management of radiation protection is addressed through a presentation of decision and management structures for radiation protection, and of EDF objectives and ambitions in this domain. The organization of radiation protection during exploitation is described: responsibilities for radiation protection in a nuclear power station, requirements for workers, preparation of interventions in controlled zone, work execution in controlled zone, zone controls and radiological cleanness of installations. The two last chapters address issues and practices of radiation protection in the case of deconstruction or dismantling, and

  12. Ceramic Hosts for Fission Products Immobilization

    Energy Technology Data Exchange (ETDEWEB)

    Peter C Kong

    2010-07-01

    Natural spinel, perovskite and zirconolite rank among the most leach resistant of mineral forms. They also have a strong affinity for a large number of other elements and including actinides. Specimens of natural perovskite and zirconolite were radioisotope dated and found to have survived at least 2 billion years of natural process while still remain their loading of uranium and thorium . Developers of the Synroc waste form recognized and exploited the capability of these minerals to securely immobilize TRU elements in high-level waste . However, the Synroc process requires a relatively uniform input and hot pressing equipment to produce the waste form. It is desirable to develop alternative approaches to fabricate these durable waste forms to immobilize the radioactive elements. One approach is using a high temperature process to synthesize these mineral host phases to incorporate the fission products in their crystalline structures. These mineral assemblages with immobilized fission products are then isolated in a durable high temperature glass for periods measured on a geologic time scale. This is a long term research concept and will begin with the laboratory synthesis of the pure spinel (MgAl2O4), perovskite (CaTiO3) and zirconolite (CaZrTi2O7) from their constituent oxides. High temperature furnace and/or thermal plasma will be used for the synthesis of these ceramic host phases. Nonradioactive strontium oxide will be doped into these ceramic phases to investigate the development of substitutional phases such as Mg1-xSrxAl2O4, Ca1-xSrxTiO3 and Ca1-xSrxZrTi2O7. X-ray diffraction will be used to establish the crystalline structures of the pure ceramic hosts and the substitution phases. Scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDX) will be performed for product morphology and fission product surrogates distribution in the crystalline hosts. The range of strontium doping is planned to reach the full substitution of the divalent

  13. Fatty acid-producing hosts

    Science.gov (United States)

    Pfleger, Brian F; Lennen, Rebecca M

    2013-12-31

    Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fatty acid product comprising culturing such hosts at 37.degree. C. are also described.

  14. Exploiting tRNAs to Boost Virulence

    Directory of Open Access Journals (Sweden)

    Suki Albers

    2016-01-01

    Full Text Available Transfer RNAs (tRNAs are powerful small RNA entities that are used to translate nucleotide language of genes into the amino acid language of proteins. Their near-uniform length and tertiary structure as well as their high nucleotide similarity and post-transcriptional modifications have made it difficult to characterize individual species quantitatively. However, due to the central role of the tRNA pool in protein biosynthesis as well as newly emerging roles played by tRNAs, their quantitative assessment yields important information, particularly relevant for virus research. Viruses which depend on the host protein expression machinery have evolved various strategies to optimize tRNA usage—either by adapting to the host codon usage or encoding their own tRNAs. Additionally, several viruses bear tRNA-like elements (TLE in the 5′- and 3′-UTR of their mRNAs. There are different hypotheses concerning the manner in which such structures boost viral protein expression. Furthermore, retroviruses use special tRNAs for packaging and initiating reverse transcription of their genetic material. Since there is a strong specificity of different viruses towards certain tRNAs, different strategies for recruitment are employed. Interestingly, modifications on tRNAs strongly impact their functionality in viruses. Here, we review those intersection points between virus and tRNA research and describe methods for assessing the tRNA pool in terms of concentration, aminoacylation and modification.

  15. Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways

    Directory of Open Access Journals (Sweden)

    Peter Wimmer

    2015-08-01

    Full Text Available Posttranslational modifications (PTMs of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub and small ubiquitin-like modifier (SUMO moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways.

  16. Mission Exploitation Platform PROBA-V

    Science.gov (United States)

    Goor, Erwin

    2016-04-01

    VITO and partners developed an end-to-end solution to drastically improve the exploitation of the PROBA-V EO-data archive (http://proba-v.vgt.vito.be/), the past mission SPOT-VEGETATION and derived vegetation parameters by researchers, service providers and end-users. The analysis of time series of data (+1PB) is addressed, as well as the large scale on-demand processing of near real-time data. From November 2015 an operational Mission Exploitation Platform (MEP) PROBA-V, as an ESA pathfinder project, will be gradually deployed at the VITO data center with direct access to the complete data archive. Several applications will be released to the users, e.g. - A time series viewer, showing the evolution of PROBA-V bands and derived vegetation parameters for any area of interest. - Full-resolution viewing services for the complete data archive. - On-demand processing chains e.g. for the calculation of N-daily composites. - A Virtual Machine will be provided with access to the data archive and tools to work with this data, e.g. various toolboxes and support for R and Python. After an initial release in January 2016, a research platform will gradually be deployed allowing users to design, debug and test applications on the platform. From the MEP PROBA-V, access to Sentinel-2 and landsat data will be addressed as well, e.g. to support the Cal/Val activities of the users. Users can make use of powerful Web based tools and can self-manage virtual machines to perform their work on the infrastructure at VITO with access to the complete data archive. To realise this, private cloud technology (openStack) is used and a distributed processing environment is built based on Hadoop. The Hadoop ecosystem offers a lot of technologies (Spark, Yarn, Accumulo, etc.) which we integrate with several open-source components. The impact of this MEP on the user community will be high and will completely change the way of working with the data and hence open the large time series to a larger

  17. Sex-specific effects of a parasite evolving in a female-biased host population.

    Science.gov (United States)

    Duneau, David; Luijckx, Pepijn; Ruder, Ludwig F; Ebert, Dieter

    2012-12-18

    Males and females differ in many ways and might present different opportunities and challenges to their parasites. In the same way that parasites adapt to the most common host type, they may adapt to the characteristics of the host sex they encounter most often. To explore this hypothesis, we characterized host sex-specific effects of the parasite Pasteuria ramosa, a bacterium evolving in naturally, strongly, female-biased populations of its host Daphnia magna. We show that the parasite proliferates more successfully in female hosts than in male hosts, even though males and females are genetically identical. In addition, when exposure occurred when hosts expressed a sexual dimorphism, females were more infected. In both host sexes, the parasite causes a similar reduction in longevity and leads to some level of castration. However, only in females does parasite-induced castration result in the gigantism that increases the carrying capacity for the proliferating parasite. We show that mature male and female Daphnia represent different environments and reveal one parasite-induced symptom (host castration), which leads to increased carrying capacity for parasite proliferation in female but not male hosts. We propose that parasite induced host castration is a property of parasites that evolved as an adaptation to specifically exploit female hosts.

  18. Sex-specific effects of a parasite evolving in a female-biased host population

    Directory of Open Access Journals (Sweden)

    Duneau David

    2012-12-01

    Full Text Available Abstract Background Males and females differ in many ways and might present different opportunities and challenges to their parasites. In the same way that parasites adapt to the most common host type, they may adapt to the characteristics of the host sex they encounter most often. To explore this hypothesis, we characterized host sex-specific effects of the parasite Pasteuria ramosa, a bacterium evolving in naturally, strongly, female-biased populations of its host Daphnia magna. Results We show that the parasite proliferates more successfully in female hosts than in male hosts, even though males and females are genetically identical. In addition, when exposure occurred when hosts expressed a sexual dimorphism, females were more infected. In both host sexes, the parasite causes a similar reduction in longevity and leads to some level of castration. However, only in females does parasite-induced castration result in the gigantism that increases the carrying capacity for the proliferating parasite. Conclusions We show that mature male and female Daphnia represent different environments and reveal one parasite-induced symptom (host castration, which leads to increased carrying capacity for parasite proliferation in female but not male hosts. We propose that parasite induced host castration is a property of parasites that evolved as an adaptation to specifically exploit female hosts.

  19. Has Sarcocystis neurona Dubey et al., 1991 (Sporozoa: Apicomplexa: Sarcocystidae) cospeciated with its intermediate hosts?

    Science.gov (United States)

    Elsheikha, Hany M

    2009-08-26

    The question of how Sarcocystis neurona is able to overcome species barrier and adapt to new hosts is central to the understanding of both the evolutionary origin of S. neurona and the prediction of its field host range. Therefore, it is worth reviewing current knowledge on S. neurona host specificity. The available host range data for S. neurona are discussed in relation to a subject of evolutionary importance-specialist or generalist and its implications to understand the strategies of host adaptation. Current evidences demonstrate that a wide range of hosts exists for S. neurona. This parasite tends to be highly specific for its definitive host but much less so for its intermediate host (I.H.). The unique specificity of S. neurona for its definitive host may be mediated by a probable long coevolutionary relationship of the parasite and carnivores in a restricted ecological niche 'New World'. This might be taken as evidence that carnivores are the 'original' host group for S. neurona. Rather, the capacity of S. neurona to exploit an unusually large number of I.H. species probably indicates that S. neurona maintains non-specificity to its I.H. as an adaptive response to insure the survival of the parasite in areas in which the 'preferred' host is not available. This review concludes with the view that adaptation of S. neurona to a new host is a complex interplay that involves a large number of determinants.

  20. Sex-specific effects of a parasite evolving in a female-biased host population

    Science.gov (United States)

    2012-01-01

    Background Males and females differ in many ways and might present different opportunities and challenges to their parasites. In the same way that parasites adapt to the most common host type, they may adapt to the characteristics of the host sex they encounter most often. To explore this hypothesis, we characterized host sex-specific effects of the parasite Pasteuria ramosa, a bacterium evolving in naturally, strongly, female-biased populations of its host Daphnia magna. Results We show that the parasite proliferates more successfully in female hosts than in male hosts, even though males and females are genetically identical. In addition, when exposure occurred when hosts expressed a sexual dimorphism, females were more infected. In both host sexes, the parasite causes a similar reduction in longevity and leads to some level of castration. However, only in females does parasite-induced castration result in the gigantism that increases the carrying capacity for the proliferating parasite. Conclusions We show that mature male and female Daphnia represent different environments and reveal one parasite-induced symptom (host castration), which leads to increased carrying capacity for parasite proliferation in female but not male hosts. We propose that parasite induced host castration is a property of parasites that evolved as an adaptation to specifically exploit female hosts. PMID:23249484

  1. Guidelines for Hosted Payload Integration

    Science.gov (United States)

    2014-06-06

    reduces risk. Need to consider mass simulator to protect host launch window. Average Payload Power Both BOL and EOL . Host must consider orbit...acceptance testing. Peak Payload Power Both BOL and EOL . Host must consider orbit constraints. Typically driven by Payload operations but must...post-retirement failure might cause damage to the Spacecraft Host or its payloads. Safe conditions at EOL should consider thermal and radiation

  2. HostPhinder: A Phage Host Prediction Tool

    Directory of Open Access Journals (Sweden)

    Julia Villarroel

    2016-05-01

    Full Text Available The current dramatic increase of antibiotic resistant bacteria has revitalised the interest in bacteriophages as alternative antibacterial treatment. Meanwhile, the development of bioinformatics methods for analysing genomic data places high-throughput approaches for phage characterization within reach. Here, we present HostPhinder, a tool aimed at predicting the bacterial host of phages by examining the phage genome sequence. Using a reference database of 2196 phages with known hosts, HostPhinder predicts the host species of a query phage as the host of the most genomically similar reference phages. As a measure of genomic similarity the number of co-occurring k-mers (DNA sequences of length k is used. Using an independent evaluation set, HostPhinder was able to correctly predict host genus and species for 81% and 74% of the phages respectively, giving predictions for more phages than BLAST and significantly outperforming BLAST on phages for which both had predictions. HostPhinder predictions on phage draft genomes from the INTESTI phage cocktail corresponded well with the advertised targets of the cocktail. Our study indicates that for most phages genomic similarity correlates well with related bacterial hosts. HostPhinder is available as an interactive web service [1] and as a stand alone download from the Docker registry [2].

  3. Relationship between exploitation, oscillation, MSY and extinction.

    Science.gov (United States)

    Ghosh, Bapan; Kar, T K; Legovic, T

    2014-10-01

    We give answers to two important problems arising in current fisheries: (i) how maximum sustainable yield (MSY) policy is influenced by the initial population level, and (ii) how harvesting, oscillation and MSY are related to each other in prey-predator systems. To examine the impact of initial population on exploitation, we analyze a single species model with strong Allee effect. It is found that even when the MSY exists, the dynamic solution may not converge to the equilibrium stock if the initial population level is higher but near the critical threshold level. In a prey-predator system with Allee effect in the prey species, the initial population does not have such important impact neither on MSY nor on maximum sustainable total yield (MSTY). However, harvesting the top predator may cause extinction of all species if odd number of trophic levels exist in the ecosystem. With regard to the second problem, we study two prey-predator models and establish that increasing harvesting effort either on prey, predator or both prey and predator destroys previously existing oscillation. Moreover, equilibrium stock both at MSY and MSTY level is stable. We also discuss the validity of found results to other prey-predator systems. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Exploiting Virtualization and Cloud Computing in ATLAS

    International Nuclear Information System (INIS)

    Harald Barreiro Megino, Fernando; Van der Ster, Daniel; Benjamin, Doug; De, Kaushik; Gable, Ian; Paterson, Michael; Taylor, Ryan; Hendrix, Val; Vitillo, Roberto A; Panitkin, Sergey; De Silva, Asoka; Walker, Rod

    2012-01-01

    The ATLAS Computing Model was designed around the concept of grid computing; since the start of data-taking, this model has proven very successful in the federated operation of more than one hundred Worldwide LHC Computing Grid (WLCG) sites for offline data distribution, storage, processing and analysis. However, new paradigms in computing, namely virtualization and cloud computing, present improved strategies for managing and provisioning IT resources that could allow ATLAS to more flexibly adapt and scale its storage and processing workloads on varied underlying resources. In particular, ATLAS is developing a “grid-of-clouds” infrastructure in order to utilize WLCG sites that make resources available via a cloud API. This work will present the current status of the Virtualization and Cloud Computing R and D project in ATLAS Distributed Computing. First, strategies for deploying PanDA queues on cloud sites will be discussed, including the introduction of a “cloud factory” for managing cloud VM instances. Next, performance results when running on virtualized/cloud resources at CERN LxCloud, StratusLab, and elsewhere will be presented. Finally, we will present the ATLAS strategies for exploiting cloud-based storage, including remote XROOTD access to input data, management of EC2-based files, and the deployment of cloud-resident LCG storage elements.

  5. Exploiting intrinsic fluctuations to identify model parameters.

    Science.gov (United States)

    Zimmer, Christoph; Sahle, Sven; Pahle, Jürgen

    2015-04-01

    Parameterisation of kinetic models plays a central role in computational systems biology. Besides the lack of experimental data of high enough quality, some of the biggest challenges here are identification issues. Model parameters can be structurally non-identifiable because of functional relationships. Noise in measured data is usually considered to be a nuisance for parameter estimation. However, it turns out that intrinsic fluctuations in particle numbers can make parameters identifiable that were previously non-identifiable. The authors present a method to identify model parameters that are structurally non-identifiable in a deterministic framework. The method takes time course recordings of biochemical systems in steady state or transient state as input. Often a functional relationship between parameters presents itself by a one-dimensional manifold in parameter space containing parameter sets of optimal goodness. Although the system's behaviour cannot be distinguished on this manifold in a deterministic framework it might be distinguishable in a stochastic modelling framework. Their method exploits this by using an objective function that includes a measure for fluctuations in particle numbers. They show on three example models, immigration-death, gene expression and Epo-EpoReceptor interaction, that this resolves the non-identifiability even in the case of measurement noise with known amplitude. The method is applied to partially observed recordings of biochemical systems with measurement noise. It is simple to implement and it is usually very fast to compute. This optimisation can be realised in a classical or Bayesian fashion.

  6. Fostering the Exploitation of Open Educational Resources

    Directory of Open Access Journals (Sweden)

    Thomas Richter

    2014-07-01

    Full Text Available The central concept behind Open Educational Resources (OER is opening up the access to educational resources for stakeholders who are not the usual target user group. This concept must be perceived as innovative because it describes a general economic and social paradigm shift: Education, which formerly was limited to a specific group of learners, now, is promoted as a public good. However, despite very good intentions, internationally agreed quality standards, and the availability of the required technological infrastructure, the critical threshold is not yet met. Due to several reasons, the usefulness of OER is often limited to the originally targeted context. Questions arise if the existing quality standards for Technology Enhanced Learning (TEL actually meet the specific requirements within the OER value chain, if the existing quality standards are applicable to OER in a meaningful way, and under which conditions related standards generally could support the exploitation of OER.We analyze quality standards for TEL and contrast the life cycle model of commercial learning resources against the life cycle model of OER. We investigate special demands on quality from the context of OER and, taking the former results into account, derive emergent quality criteria for OER. The paper concludes with recommendations for the design of OER and a future standard development.

  7. Exploiting Genetic Interference for Antiviral Therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Tanner

    2016-05-01

    Full Text Available Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus's inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles-the evolution of drug resistance and targeting therapy to high-risk populations-both of which impede treatment in resource-poor settings.

  8. Radiation protection in exploitation of uranium ores

    International Nuclear Information System (INIS)

    Pavlov, I.V.; Shalaev, I.L.

    1976-01-01

    The results are analyzed of the study of the radiation conditions in uranium mines, design and testing of protection means, improvement of methods and equipment for the dosimetric control in different countries since 1968 to 1975. There are outlined radiation hazards and their role in the formation of the radiation situation in mines, dispersive composition of aerosols of short-living daughter products of Rn(DPR) in the mine atmosphere. Among means of the radiation protection the following are dealt with: ventilation including the calculation of air requirements, design of ventilation systems, ventilation practices in working mines; lowering of the release of radon into the mine atmosphere by isolating non-exploited pits, application of gas-proof covers to cofferdams in faces of jointing zones, intensification of mining works in dangerous zones. Methods of air cleaning to remove Rn are suggested in brief. Apparatus are described for the individual control of the level of latent energy in the zone of miners' respiration: track dosimeters, thermoluminescent crystalls (TLC), photographic films, semiconductor systems and biophysical methods of the control for uranium mines. The efficient use of existing protection means provides the normal radiation situation in mines without significant additional investments

  9. Accelerating Large Data Analysis By Exploiting Regularities

    Science.gov (United States)

    Moran, Patrick J.; Ellsworth, David

    2003-01-01

    We present techniques for discovering and exploiting regularity in large curvilinear data sets. The data can be based on a single mesh or a mesh composed of multiple submeshes (also known as zones). Multi-zone data are typical to Computational Fluid Dynamics (CFD) simulations. Regularities include axis-aligned rectilinear and cylindrical meshes as well as cases where one zone is equivalent to a rigid-body transformation of another. Our algorithms can also discover rigid-body motion of meshes in time-series data. Next, we describe a data model where we can utilize the results from the discovery process in order to accelerate large data visualizations. Where possible, we replace general curvilinear zones with rectilinear or cylindrical zones. In rigid-body motion cases we replace a time-series of meshes with a transformed mesh object where a reference mesh is dynamically transformed based on a given time value in order to satisfy geometry requests, on demand. The data model enables us to make these substitutions and dynamic transformations transparently with respect to the visualization algorithms. We present results with large data sets where we combine our mesh replacement and transformation techniques with out-of-core paging in order to achieve significant speed-ups in analysis.

  10. Entomopathogenic Fungi: New Insights into Host-Pathogen Interactions.

    Science.gov (United States)

    Butt, T M; Coates, C J; Dubovskiy, I M; Ratcliffe, N A

    2016-01-01

    Although many insects successfully live in dangerous environments exposed to diverse communities of microbes, they are often exploited and killed by specialist pathogens. Studies of host-pathogen interactions (HPI) provide valuable insights into the dynamics of the highly aggressive coevolutionary arms race between entomopathogenic fungi (EPF) and their arthropod hosts. The host defenses are designed to exclude the pathogen or mitigate the damage inflicted while the pathogen responds with immune evasion and utilization of host resources. EPF neutralize their immediate surroundings on the insect integument and benefit from the physiochemical properties of the cuticle and its compounds that exclude competing microbes. EPF also exhibit adaptations aimed at minimizing trauma that can be deleterious to both host and pathogen (eg, melanization of hemolymph), form narrow penetration pegs that alleviate host dehydration and produce blastospores that lack immunogenic sugars/enzymes but facilitate rapid assimilation of hemolymph nutrients. In response, insects deploy an extensive armory of hemocytes and macromolecules, such as lectins and phenoloxidase, that repel, immobilize, and kill EPF. New evidence suggests that immune bioactives work synergistically (eg, lysozyme with antimicrobial peptides) to combat infections. Some proteins, including transferrin and apolipophorin III, also demonstrate multifunctional properties, participating in metabolism, homeostasis, and pathogen recognition. This review discusses the molecular intricacies of these HPI, highlighting the interplay between immunity, stress management, and metabolism. Increased knowledge in this area could enhance the efficacy of EPF, ensuring their future in integrated pest management programs. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Host species and developmental stage, but not host social structure, affects bacterial community structure in socially polymorphic bees.

    Science.gov (United States)

    McFrederick, Quinn S; Wcislo, William T; Hout, Michael C; Mueller, Ulrich G

    2014-05-01

    Social transmission and host developmental stage are thought to profoundly affect the structure of bacterial communities associated with honey bees and bumble bees, but these ideas have not been explored in other bee species. The halictid bees Megalopta centralis and M. genalis exhibit intrapopulation social polymorphism, which we exploit to test whether bacterial communities differ by host social structure, developmental stage, or host species. We collected social and solitary Megalopta nests and sampled bees and nest contents from all stages of host development. To survey these bacterial communities, we used 16S rRNA gene 454 pyrosequencing. We found no effect of social structure, but found differences by host species and developmental stage. Wolbachia prevalence differed between the two host species. Bacterial communities associated with different developmental stages appeared to be driven by environmentally acquired bacteria. A Lactobacillus kunkeei clade bacterium that is consistently associated with other bee species was dominant in pollen provisions and larval samples, but less abundant in mature larvae and pupae. Foraging adults appeared to often reacquire L. kunkeei clade bacteria, likely while foraging at flowers. Environmental transmission appears to be more important than social transmission for Megalopta bees at the cusp between social and solitary behavior. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  12. Toxoplasma gondii sequesters lysosomes from mammalian hosts in the vacuolar space.

    Science.gov (United States)

    Coppens, Isabelle; Dunn, Joe Dan; Romano, Julia D; Pypaert, Marc; Zhang, Hui; Boothroyd, John C; Joiner, Keith A

    2006-04-21

    The intracellular compartment harboring Toxoplasma gondii satisfies the parasite's nutritional needs for rapid growth in mammalian cells. We demonstrate that the parasitophorous vacuole (PV) of T. gondii accumulates material coming from the host mammalian cell via the exploitation of the host endo-lysosomal system. The parasite actively recruits host microtubules, resulting in selective attraction of endo-lysosomes to the PV. Microtubule-based invaginations of the PV membrane serve as conduits for the delivery of host endo-lysosomes within the PV. These tubular conduits are decorated by a parasite coat, including the tubulogenic protein GRA7, which acts like a garrote that sequesters host endocytic organelles in the vacuolar space. These data define an unanticipated process allowing the parasite intimate and concentrated access to a diverse range of low molecular weight components produced by the endo-lysosomal system. More generally, they identify a unique mechanism for unidirectional transport and sequestration of host organelles.

  13. Main principles of developing exploitation models of semiconductor devices

    Science.gov (United States)

    Gradoboev, A. V.; Simonova, A. V.

    2018-05-01

    The paper represents primary tasks, solutions of which allow to develop the exploitation modes of semiconductor devices taking into account complex and combined influence of ionizing irradiation and operation factors. The structure of the exploitation model of the semiconductor device is presented, which is based on radiation and reliability models. Furthermore, it was shown that the exploitation model should take into account complex and combine influence of various ionizing irradiation types and operation factors. The algorithm of developing the exploitation model of the semiconductor devices is proposed. The possibility of creating the radiation model of Schottky barrier diode, Schottky field-effect transistor and Gunn diode is shown based on the available experimental data. The basic exploitation model of IR-LEDs based upon double AlGaAs heterostructures is represented. The practical application of the exploitation models will allow to output the electronic products with guaranteed operational properties.

  14. Transnational gestational surrogacy: does it have to be exploitative?

    Science.gov (United States)

    Kirby, Jeffrey

    2014-01-01

    This article explores the controversial practice of transnational gestational surrogacy and poses a provocative question: Does it have to be exploitative? Various existing models of exploitation are considered and a novel exploitation-evaluation heuristic is introduced to assist in the analysis of the potentially exploitative dimensions/elements of complex health-related practices. On the basis of application of the heuristic, I conclude that transnational gestational surrogacy, as currently practiced in low-income country settings (such as rural, western India), is exploitative of surrogate women. Arising out of consideration of the heuristic's exploitation conditions, a set of public education and enabled choice, enhanced protections, and empowerment reforms to transnational gestational surrogacy practice is proposed that, if incorporated into a national regulatory framework and actualized within a low income country, could possibly render such practice nonexploitative.

  15. The Drosophila melanogaster host model

    Science.gov (United States)

    Igboin, Christina O.; Griffen, Ann L.; Leys, Eugene J.

    2012-01-01

    The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed. PMID:22368770

  16. The Drosophila melanogaster host model

    Directory of Open Access Journals (Sweden)

    Christina O. Igboin

    2012-02-01

    Full Text Available The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed.

  17. The Drosophila melanogaster host model.

    Science.gov (United States)

    Igboin, Christina O; Griffen, Ann L; Leys, Eugene J

    2012-01-01

    The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen-host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial-host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis-host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed.

  18. Exploiting Untapped Information Resources in Earth Science

    Science.gov (United States)

    Ramachandran, R.; Fox, P. A.; Kempler, S.; Maskey, M.

    2015-12-01

    One of the continuing challenges in any Earth science investigation is the amount of time and effort required for data preparation before analysis can begin. Current Earth science data and information systems have their own shortcomings. For example, the current data search systems are designed with the assumption that researchers find data primarily by metadata searches on instrument or geophysical keywords, assuming that users have sufficient knowledge of the domain vocabulary to be able to effectively utilize the search catalogs. These systems lack support for new or interdisciplinary researchers who may be unfamiliar with the domain vocabulary or the breadth of relevant data available. There is clearly a need to innovate and evolve current data and information systems in order to improve data discovery and exploration capabilities to substantially reduce the data preparation time and effort. We assert that Earth science metadata assets are dark resources, information resources that organizations collect, process, and store for regular business or operational activities but fail to utilize for other purposes. The challenge for any organization is to recognize, identify and effectively utilize the dark data stores in their institutional repositories to better serve their stakeholders. NASA Earth science metadata catalogs contain dark resources consisting of structured information, free form descriptions of data and pre-generated images. With the addition of emerging semantic technologies, such catalogs can be fully utilized beyond their original design intent of supporting current search functionality. In this presentation, we will describe our approach of exploiting these information resources to provide novel data discovery and exploration pathways to science and education communities

  19. Postural Hand Synergies during Environmental Constraint Exploitation

    Directory of Open Access Journals (Sweden)

    Cosimo Della Santina

    2017-08-01

    Full Text Available Humans are able to intuitively exploit the shape of an object and environmental constraints to achieve stable grasps and perform dexterous manipulations. In doing that, a vast range of kinematic strategies can be observed. However, in this work we formulate the hypothesis that such ability can be described in terms of a synergistic behavior in the generation of hand postures, i.e., using a reduced set of commonly used kinematic patterns. This is in analogy with previous studies showing the presence of such behavior in different tasks, such as grasping. We investigated this hypothesis in experiments performed by six subjects, who were asked to grasp objects from a flat surface. We quantitatively characterized hand posture behavior from a kinematic perspective, i.e., the hand joint angles, in both pre-shaping and during the interaction with the environment. To determine the role of tactile feedback, we repeated the same experiments but with subjects wearing a rigid shell on the fingertips to reduce cutaneous afferent inputs. Results show the persistence of at least two postural synergies in all the considered experimental conditions and phases. Tactile impairment does not alter significantly the first two synergies, and contact with the environment generates a change only for higher order Principal Components. A good match also arises between the first synergy found in our analysis and the first synergy of grasping as quantified by previous work. The present study is motivated by the interest of learning from the human example, extracting lessons that can be applied in robot design and control. Thus, we conclude with a discussion on implications for robotics of our findings.

  20. Exploiting core knowledge for visual object recognition.

    Science.gov (United States)

    Schurgin, Mark W; Flombaum, Jonathan I

    2017-03-01

    Humans recognize thousands of objects, and with relative tolerance to variable retinal inputs. The acquisition of this ability is not fully understood, and it remains an area in which artificial systems have yet to surpass people. We sought to investigate the memory process that supports object recognition. Specifically, we investigated the association of inputs that co-occur over short periods of time. We tested the hypothesis that human perception exploits expectations about object kinematics to limit the scope of association to inputs that are likely to have the same token as a source. In several experiments we exposed participants to images of objects, and we then tested recognition sensitivity. Using motion, we manipulated whether successive encounters with an image took place through kinematics that implied the same or a different token as the source of those encounters. Images were injected with noise, or shown at varying orientations, and we included 2 manipulations of motion kinematics. Across all experiments, memory performance was better for images that had been previously encountered with kinematics that implied a single token. A model-based analysis similarly showed greater memory strength when images were shown via kinematics that implied a single token. These results suggest that constraints from physics are built into the mechanisms that support memory about objects. Such constraints-often characterized as 'Core Knowledge'-are known to support perception and cognition broadly, even in young infants. But they have never been considered as a mechanism for memory with respect to recognition. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Host genetics affect microbial ecosystems via host immunity.

    Science.gov (United States)

    El Kafsi, Hela; Gorochov, Guy; Larsen, Martin

    2016-10-01

    Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity. Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics. We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.

  2. Thermal Property Engineering: Exploiting the Properties of Ceramic Nanocomposites

    Science.gov (United States)

    2018-03-01

    ARL-TR-8308 ● MAR 2018 US Army Research Laboratory Thermal Property Engineering : Exploiting the Properties of Ceramic...return it to the originator. ARL-TR-8308 ● MAR 2018 US Army Research Laboratory Thermal Property Engineering : Exploiting the...2015 – Dec 31 2017 4. TITLE AND SUBTITLE Thermal Property Engineering : Exploiting the Properties of Ceramic Nanocomposites 5a. CONTRACT NUMBER 5b

  3. Targeting Host Factors to Treat West Nile and Dengue Viral Infections

    Directory of Open Access Journals (Sweden)

    Manoj N. Krishnan

    2014-02-01

    Full Text Available West Nile (WNV and Dengue (DENV viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

  4. Targeting host factors to treat West Nile and dengue viral infections.

    Science.gov (United States)

    Krishnan, Manoj N; Garcia-Blanco, Mariano A

    2014-02-10

    West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

  5. Departure mechanisms for host search on high-density patches by the Meteorus pulchricornis.

    Science.gov (United States)

    Sheng, Sheng; Feng, Sufang; Meng, Ling; Li, Baoping

    2014-01-01

    Less attention has been paid to the parasitoid-host system in which the host occurs in considerably high density with a hierarchical patch structure in studies on time allocation strategies of parasitoids. This study used the parasitoid Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae) and the Oriental leafworm, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) as the parasitoids-host model system to investigate patch-leaving mechanisms as affected by the high-host density, hierarchical patch structure, and foraging behaviors on both former and current patches. The results showed that three out of eight covariates tested had significant effects on the patch-leaving tendency, including the host density, ovipositor insertion, and host rejection on the current patch. The parasitoid paid more visits to the patch with high-density hosts. While the patch with higher host densities decreased the leaving tendency, the spatial distribution of hosts examined had no effect on the leaving tendency. Both oviposition and host rejection decreased the patch-leaving tendency. The variables associated with the former patch, such as the host density and number of ovipositor insertions, however, did not have an effect on the leaving tendency. Our study suggested that M. pulchricornis females may use an incremental mechanism to exploit high-density patches to the fullest. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

  6. Exploiting Laboratory and Heliophysics Plasma Synergies

    Directory of Open Access Journals (Sweden)

    Jill Dahlburg

    2010-05-01

    Full Text Available Recent advances in space-based heliospheric observations, laboratory experimentation, and plasma simulation codes are creating an exciting new cross-disciplinary opportunity for understanding fast energy release and transport mechanisms in heliophysics and laboratory plasma dynamics, which had not been previously accessible. This article provides an overview of some new observational, experimental, and computational assets, and discusses current and near-term activities towards exploitation of synergies involving those assets. This overview does not claim to be comprehensive, but instead covers mainly activities closely associated with the authors’ interests and reearch. Heliospheric observations reviewed include the Sun Earth Connection Coronal and Heliospheric Investigation (SECCHI on the National Aeronautics and Space Administration (NASA Solar Terrestrial Relations Observatory (STEREO mission, the first instrument to provide remote sensing imagery observations with spatial continuity extending from the Sun to the Earth, and the Extreme-ultraviolet Imaging Spectrometer (EIS on the Japanese Hinode spacecraft that is measuring spectroscopically physical parameters of the solar atmosphere towards obtaining plasma temperatures, densities, and mass motions. The Solar Dynamics Observatory (SDO and the upcoming Solar Orbiter with the Heliospheric Imager (SoloHI on-board will also be discussed. Laboratory plasma experiments surveyed include the line-tied magnetic reconnection experiments at University of Wisconsin (relevant to coronal heating magnetic flux tube observations and simulations, and a dynamo facility under construction there; the Space Plasma Simulation Chamber at the Naval Research Laboratory that currently produces plasmas scalable to ionospheric and magnetospheric conditions and in the future also will be suited to study the physics of the solar corona; the Versatile Toroidal Facility at the Massachusetts Institute of Technology that

  7. Simulated population responses of common carp to commercial exploitation

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Michael J.; Hennen, Matthew J.; Brown, Michael L.

    2011-12-01

    Common carp Cyprinus carpio is a widespread invasive species that can become highly abundant and impose deleterious ecosystem effects. Thus, aquatic resource managers are interested in controlling common carp populations. Control of invasive common carp populations is difficult, due in part to the inherent uncertainty of how populations respond to exploitation. To understand how common carp populations respond to exploitation, we evaluated common carp population dynamics (recruitment, growth, and mortality) in three natural lakes in eastern South Dakota. Common carp exhibited similar population dynamics across these three systems that were characterized by consistent recruitment (ages 3 to 15 years present), fast growth (K = 0.37 to 0.59), and low mortality (A = 1 to 7%). We then modeled the effects of commercial exploitation on size structure, abundance, and egg production to determine its utility as a management tool to control populations. All three populations responded similarly to exploitation simulations with a 575-mm length restriction, representing commercial gear selectivity. Simulated common carp size structure modestly declined (9 to 37%) in all simulations. Abundance of common carp declined dramatically (28 to 56%) at low levels of exploitation (0 to 20%) but exploitation >40% had little additive effect and populations were only reduced by 49 to 79% despite high exploitation (>90%). Maximum lifetime egg production was reduced from 77 to 89% at a moderate level of exploitation (40%), indicating the potential for recruitment overfishing. Exploitation further reduced common carp size structure, abundance, and egg production when simulations were not size selective. Our results provide insights to how common carp populations may respond to exploitation. Although commercial exploitation may be able to partially control populations, an integrated removal approach that removes all sizes of common carp has a greater chance of controlling population abundance

  8. Exploiting for medical and biological applications

    Science.gov (United States)

    Giano, Michael C.

    Biotherapeutics are an emerging class of drug composed of molecules ranging in sizes from peptides to large proteins. Due to their poor stability and mucosal membrane permeability, biotherapeutics are administered by a parenteral method (i.e., syringe, intravenous or intramuscular). Therapeutics delivered systemically often experience short half-lives. While, local administration may involve invasive surgical procedures and suffer from poor retention at the site of application. To compensate, the patient receives frequent doses of highly concentrated therapeutic. Unfortunately, the off-target side effects and discomfort associated with multiple injections results in poor patient compliance. Therefore, new delivery methods which can improve therapeutic retention, reduce the frequency of administration and may aid in decreasing the off-target side effects is a necessity. Hydrogels are a class of biomaterials that are gaining interests for tissue engineering and drug delivery applications. Hydrogel materials are defined as porous, 3-dimensional networks that are primarily composed of water. Generally, they are mechanically rigid, cytocompatible and easily chemically functionalized. Collectively, these properties make hydrogels fantastic candidates to perform as drug delivery depots. Current hydrogel delivery systems physically entrap the target therapeutic which is then subsequently released over time at the site of administration. The swelling and degradation of the material effect the diffusion of the therapy from the hydrogel, and therefore should be controlled. Although these strategies provide some regulation over therapeutic release, full control of the delivery is not achieved. Newer approaches are focused on designing hydrogels that exploit known interactions, covalently attach the therapy or respond to an external stimulus in an effort to gain improved control over the therapy's release. Unfortunately, the biotherapeutic is typically required to be chemically

  9. Early Sexual Exploitation as an Influence in Prostitution.

    Science.gov (United States)

    Silbert, Mimi H.; Pines, Ayala M.

    1983-01-01

    Surveyed 200 female street prostitutes to determine whether they were sexually exploited during childhood. Results showed 60 percent of the subjects were sexually exploited. The few girls who discussed their abuse with others were met with shame and most often inaction. Only 10 percent were abused by strangers. (JAC)

  10. A Descriptive Study on Sexually Exploited Children in Residential Treatment

    Science.gov (United States)

    Twill, Sarah E.; Green, Denise M.; Traylor, Amy

    2010-01-01

    Sexual exploitation and prostitution of children and adolescents is a multibillion dollar industry in the United States (Estes and Weiner in "Medical, legal & social science aspects of child sexual exploitation: A comprehensive review of pornography, prostitution, and internet crimes, vol I," G.W. Medical Publishing, Inc, St Louis,…

  11. Exploiting opportunities at all cost? Entrepreneurial intent and externalities

    NARCIS (Netherlands)

    Urbig, D.; Weitzel, G.U.; Rosenkranz, S.; van Witteloostuijn, A.

    2011-01-01

    they exploit welfare-enhancing opportunities as it is assumed in several normative models? Do we need to prevent potential entrepreneurs from being destructive or are there intrinsic limits to harm others? We experimentally investigate how people with different entrepreneurial intent exploit risky

  12. Exploitation program of ''Adamow'' quarry up to 2015

    International Nuclear Information System (INIS)

    Hadlaw, A.

    1994-01-01

    The brown coal deposits exploited by the quarry ''Adamow'' located in Central Poland are shortly described and the prognosis of their exploitation up to 2015 is given. The basis data on the perspective deposits in the quarry's area are also presented. All deposits are shown on the map. 3 ills, 2 tabs

  13. Panel discussion on exploitation of geothermal resources in thermal zones

    Energy Technology Data Exchange (ETDEWEB)

    Viramonte, J G; Mange, J; Stefani, G

    1978-03-01

    The topics discussed include the major known geothermal resources, varying ways of exploiting geothermal resources, technical and economic difficulties in the exploitation, the place of geothermal energy in the total energy policy of a given country, advanced exploration techniques, and indications of needed areas of study. The panelists represented most of the South American countries, Mexico, and Italy. (JSR)

  14. Host-selective toxins of Pyrenophora tritici-repentis induce common responses associated with host susceptibility.

    Directory of Open Access Journals (Sweden)

    Iovanna Pandelova

    Full Text Available Pyrenophora tritici-repentis (Ptr, a necrotrophic fungus and the causal agent of tan spot of wheat, produces one or a combination of host-selective toxins (HSTs necessary for disease development. The two most studied toxins produced by Ptr, Ptr ToxA (ToxA and Ptr ToxB (ToxB, are proteins that cause necrotic or chlorotic symptoms respectively. Investigation of host responses induced by HSTs provides better insight into the nature of the host susceptibility. Microarray analysis of ToxA has provided evidence that it can elicit responses similar to those associated with defense. In order to evaluate whether there are consistent host responses associated with susceptibility, a similar analysis of ToxB-induced changes in the same sensitive cultivar was conducted. Comparative analysis of ToxA- and ToxB-induced transcriptional changes showed that similar groups of genes encoding WRKY transcription factors, RLKs, PRs, components of the phenylpropanoid and jasmonic acid pathways are activated. ROS accumulation and photosystem dysfunction proved to be common mechanism-of-action for these toxins. Despite similarities in defense responses, transcriptional and biochemical responses as well as symptom development occur more rapidly for ToxA compared to ToxB, which could be explained by differences in perception as well as by differences in activation of a specific process, for example, ethylene biosynthesis in ToxA treatment. Results of this study suggest that perception of HSTs will result in activation of defense responses as part of a susceptible interaction and further supports the hypothesis that necrotrophic fungi exploit defense responses in order to induce cell death.

  15. Hijacking of the Host Ubiquitin Network by Legionella pneumophila

    Directory of Open Access Journals (Sweden)

    Jiazhang Qiu

    2017-12-01

    Full Text Available Protein ubiquitination is critical for regulation of numerous eukaryotic cellular processes such as protein homeostasis, cell cycle progression, immune response, DNA repair, and vesicular trafficking. Ubiquitination often leads to the alteration of protein stability, subcellular localization, or interaction with other proteins. Given the importance of ubiquitination in the regulation of host immunity, it is not surprising that many infectious agents have evolved strategies to interfere with the ubiquitination network with sophisticated mechanisms such as functional mimicry. The facultative intracellular pathogen Legionella pneumophila is the causative agent of Legionnaires' disease. L. pneumophila is phagocytosed by macrophages and is able to replicate within a niche called Legionella-containing vacuole (LCV. The biogenesis of LCV is dependent upon the Dot/Icm type IV secretion system which delivers more than 330 effector proteins into host cytosol. The optimal intracellular replication of L. pneumophila requires the host ubiquitin-proteasome system. Furthermore, membranes of the bacterial phagosome are enriched with ubiquitinated proteins in a way that requires its Dot/Icm type IV secretion system, suggesting the involvement of effectors in the manipulation of the host ubiquitination machinery. Here we summarize recent advances in our understanding of mechanisms exploited by L. pneumophila effector proteins to hijack the host ubiquitination pathway.

  16. A Legionella Effector Disrupts Host Cytoskeletal Structure by Cleaving Actin.

    Directory of Open Access Journals (Sweden)

    Yao Liu

    2017-01-01

    Full Text Available Legionella pneumophila, the etiological agent of Legionnaires' disease, replicates intracellularly in protozoan and human hosts. Successful colonization and replication of this pathogen in host cells requires the Dot/Icm type IVB secretion system, which translocates approximately 300 effector proteins into the host cell to modulate various cellular processes. In this study, we identified RavK as a Dot/Icm substrate that targets the host cytoskeleton and reduces actin filament abundance in mammalian cells upon ectopic expression. RavK harbors an H95EXXH99 motif associated with diverse metalloproteases, which is essential for the inhibition of yeast growth and for the induction of cell rounding in HEK293T cells. We demonstrate that the actin protein itself is the cellular target of RavK and that this effector cleaves actin at a site between residues Thr351 and Phe352. Importantly, RavK-mediated actin cleavage also occurs during L. pneumophila infection. Cleavage by RavK abolishes the ability of actin to form polymers. Furthermore, an F352A mutation renders actin resistant to RavK-mediated cleavage; expression of the mutant in mammalian cells suppresses the cell rounding phenotype caused by RavK, further establishing that actin is the physiological substrate of RavK. Thus, L. pneumophila exploits components of the host cytoskeleton by multiple effectors with distinct mechanisms, highlighting the importance of modulating cellular processes governed by the actin cytoskeleton in the intracellular life cycle of this pathogen.

  17. Host Factors in Ebola Infection.

    Science.gov (United States)

    Rasmussen, Angela L

    2016-08-31

    Ebola virus (EBOV) emerged in West Africa in 2014 to devastating effect, and demonstrated that infection can cause a broad range of severe disease manifestations. As the virus itself was genetically similar to other Zaire ebolaviruses, the spectrum of pathology likely resulted from variable responses to infection in a large and genetically diverse population. This review comprehensively summarizes current knowledge of the host response to EBOV infection, including pathways hijacked by the virus to facilitate replication, host processes that contribute directly to pathogenesis, and host-pathogen interactions involved in subverting or antagonizing host antiviral immunity.

  18. [Ecotourism exploitation model in Bita Lake Natural Reserve of Yunnan].

    Science.gov (United States)

    Yang, G; Wang, Y; Zhong, L

    2000-12-01

    Bita lake provincial natural reserve is located in Shangri-La region of North-western Yunnan, and was set as a demonstrating area for ecotourism exploitation in 1998. After a year's exploitation construction and half a year's operation as a branch of the 99' Kunming International Horticulture Exposition to accept tourists, it was proved that the ecotourism demonstrating area attained four integrated functions of ecotourism, i.e., tourism, protection, poverty clearing and environment education. Five exploitation and management models including function zoned exploitation model, featured tourism communication model signs system designing model, local Tibetan family reception model and environmental monitoring model, were also successful, which were demonstrated and spreaded to the whole province. Bita lake provincial natural reserve could be a good sample for the ecotourism exploitation natural reserves of the whole country.

  19. HostPhinder: A Phage Host Prediction Tool

    DEFF Research Database (Denmark)

    Villarroel, Julia; Kleinheinz, Kortine Annina; Jurtz, Vanessa Isabell

    2016-01-01

    The current dramatic increase of antibiotic resistant bacteria has revitalised the interest in bacteriophages as alternative antibacterial treatment. Meanwhile, the development of bioinformatics methods for analysing genomic data places high-throughput approaches for phage characterization within...... bacterial hosts. HostPhinder is available as an interactive web service [1] and as a stand alone download from the Docker registry [2]....

  20. HOST liner cyclic facilities

    Science.gov (United States)

    Schultz, D.

    1983-01-01

    The HOST Liner Cyclic Program is utilizing two types of test apparatus, rectangular box rigs and a full annular rig. To date two quartz lamp cyclic box rigs have been tested and a third is to begin testing in late October 1983. The box rigs are used to evaluate 5x8 inch rectangular linear samples. A 21 inch diameter outer liner simulator is also being built up for testing beginning in April 1984. All rigs are atmospheric rigs. The first box rig, a three 6-kVA lamp installation, was operated under adverse conditions to determine feasibility of using quartz lamps for cyclic testing. This work was done in December 1981 and looked promising. The second box rig, again using three 6-kVA lamps, was operated to obtain instrumentation durability information and initial data input to a Finite Element Model. This limited test program was conducted in August 1983. Five test plates were run. Instrumentation consisted of strain gages, thermocouples and thermal paint. The strain gages were found to fail at 1200 F as expected though plates were heated to 1700 F. The third box rig, containing four 6-kVA lamps, is in build up for testing to begin in late October 1983. In addition to 33 percent greater power input, this rig has provision for 400 F backside line cooling air and a viewing port suitable for IR camera viewing. The casing is also water cooled for extended durability.

  1. Biomechanical and histologic evaluation of tissue engineered ligaments using chitosan and hyaluronan hybrid polymer fibers: a rabbit medial collateral ligament reconstruction model.

    Science.gov (United States)

    Irie, Toru; Majima, Tokifumi; Sawaguchi, Naohiro; Funakoshi, Tadanao; Nishimura, Shin-Ichiro; Minami, Akio

    2011-05-01

    In this study, we used a rabbit medial collateral ligament reconstruction model to evaluate a novel chitosan-based hyaluronan hybrid polymer fiber scaffold for ligament tissue engineering and to examine whether mechanical forces exerted in an in vivo model increased extracellular matrix production by seeded fibroblasts. Scaffolds were used 2 weeks after incubation with fibroblasts obtained from the same rabbit in a cell-seeded scaffold (CSS) group and without cells in a noncell-seeded scaffold (NCSS) group. At 3, 6, and 12 weeks after surgery, the failure loads of the engineered ligaments in the CSS groups were significantly greater than those in the NCSS groups. At 6 weeks after surgery, the reconstructed tissue of the CSS group was positive for type I collagen, whereas that in the NCSS group was negative for type I collagen. At 12 weeks after surgery, the reconstructed tissue stained positive for type I collagen in the CSS group, but negative in the NCSS group. Our results indicate that the scaffold material enhanced the production of type I collagen and led to improved mechanical strength in the engineered ligament in vivo. Copyright © 2011 Wiley Periodicals, Inc.

  2. Corneal protection with high-molecular-weight hyaluronan against in vitro and in vivo sodium lauryl sulfate-induced toxic effects.

    Science.gov (United States)

    Pauloin, Thierry; Dutot, Mélody; Liang, Hong; Chavinier, Emilie; Warnet, Jean-Michel; Rat, Patrice

    2009-10-01

    The aim of this study was to investigate high-molecular-weight hyaluronan (HA-HMW) corneal protection against sodium lauryl sulfate (SLS)-induced toxic effects with in vitro and in vivo experimental approaches. In vitro experiments consisted of a human corneal epithelial cell line incubated with HA-HMW, rinsed, and incubated with SLS. Cell viability, oxidative stress, chromatin condensation, caspase-3, -8, -9, and P2X7 cell death receptor activation, interleukin-6, and interleukin-8 production were investigated. In vivo experiments consisted of 36 New Zealand white rabbits treated for 3 days, 3 times per day, with HA-HMW or phosphate-buffered salt solution. At day 4, eyes were treated with SLS. Clinical observation and in vivo confocal microscopy using the Rostock Cornea Module of the Heidelberg Retina Tomograph-II were performed to evaluate and to compare SLS-induced toxicity between eyes treated with HA-HMW and eyes treated with phosphate-buffered salt solution. In vitro data indicate that exposure of human corneal epithelial cells to HA-HMW significantly decreased SLS-induced oxidative stress, apoptosis, and inflammation cytokine production. In vivo data indicate that SLS cornea injuries, characterized by damaged corneal epithelium, damaged anterior stroma, and inflammatory infiltrations, were attenuated with HA-HMW treatment. A good correlation was seen between in vitro and in vivo findings showing that HA-HMW decreases SLS-induced toxic effects and protects cornea.

  3. A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force

    Science.gov (United States)

    Bano, Fouzia; Banerji, Suneale; Howarth, Mark; Jackson, David G.; Richter, Ralf P.

    2016-09-01

    Glycosaminoglycans (GAGs), a category of linear, anionic polysaccharides, are ubiquitous in the extracellular space, and important extrinsic regulators of cell function. Despite the recognized significance of mechanical stimuli in cellular communication, however, only few single molecule methods are currently available to study how monovalent and multivalent GAG·protein bonds respond to directed mechanical forces. Here, we have devised such a method, by combining purpose-designed surfaces that afford immobilization of GAGs and receptors at controlled nanoscale organizations with single molecule force spectroscopy (SMFS). We apply the method to study the interaction of the GAG polymer hyaluronan (HA) with CD44, its receptor in vascular endothelium. Individual bonds between HA and CD44 are remarkably resistant to rupture under force in comparison to their low binding affinity. Multiple bonds along a single HA chain rupture sequentially and independently under load. We also demonstrate how strong non-covalent bonds, which are versatile for controlled protein and GAG immobilization, can be effectively used as molecular anchors in SMFS. We thus establish a versatile method for analyzing the nanomechanics of GAG·protein interactions at the level of single GAG chains, which provides new molecular-level insight into the role of mechanical forces in the assembly and function of GAG-rich extracellular matrices.

  4. Quantitative proteomics reveals altered expression of extracellular matrix related proteins of human primary dermal fibroblasts in response to sulfated hyaluronan and collagen applied as artificial extracellular matrix.

    Science.gov (United States)

    Müller, Stephan A; van der Smissen, Anja; von Feilitzsch, Margarete; Anderegg, Ulf; Kalkhof, Stefan; von Bergen, Martin

    2012-12-01

    Fibroblasts are the main matrix producing cells of the dermis and are also strongly regulated by their matrix environment which can be used to improve and guide skin wound healing processes. Here, we systematically investigated the molecular effects on primary dermal fibroblasts in response to high-sulfated hyaluronan [HA] (hsHA) by quantitative proteomics. The comparison of non- and high-sulfated HA revealed regulation of 84 of more than 1,200 quantified proteins. Based on gene enrichment we found that sulfation of HA alters extracellular matrix remodeling. The collagen degrading enzymes cathepsin K, matrix metalloproteinases-2 and -14 were found to be down-regulated on hsHA. Additionally protein expression of thrombospondin-1, decorin, collagen types I and XII were reduced, whereas the expression of trophoblast glycoprotein and collagen type VI were slightly increased. This study demonstrates that global proteomics provides a valuable tool for revealing proteins involved in molecular effects of growth substrates for further material optimization.

  5. Dual pH/redox responsive and CD44 receptor targeting hybrid nano-chrysalis based on new oligosaccharides of hyaluronan conjugates.

    Science.gov (United States)

    Chen, Daquan; Dong, Xue; Qi, Mengjiao; Song, Xiaoyan; Sun, Jingfang

    2017-02-10

    A smart hybrid microenvironment-mediated dual pH/redox-responsive polymeric nanoparticles combined with inorganic calcium phosphate (CaP) was fabricated, which we term as armored nano-chrysalis inspired by butterfly pupa. The nano-chrysalis has an inner core composed of specially designed oligosaccharides of hyaluronan (oHA) targeting CD44 receptor. The inner core has two functions, i.e., the dual pH/redox responsive polymeric conjugate and the fluorescent curcumin-prodrug function. The prepared nano-chrysalis possessed a smaller size (102.5±4.6nm) than the unarmored nano-chrysalis (122.5±6.6nm). Interestingly, while the nano-chrysalis were stable under pH 7.4, when incubated under the tumor acidic conditions (pH 6.5) the outer CaP armor would dissolve in a pH-dependent, sustained manner. Moreover, nano-chrysalis was demonstrated to present the most effective antitumor efficacy than other formulations. This study provides a promising smart nano-carrier platform to enhance the stability, decrease the side effects, and improve the therapeutic efficacy of anticancer drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. [Tuberculosis in compromised hosts].

    Science.gov (United States)

    2003-11-01

    Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

  7. Nonintegrated Host Association of Myrmecophilus tetramorii, a Specialist Myrmecophilous Ant Cricket (Orthoptera: Myrmecophilidae

    Directory of Open Access Journals (Sweden)

    Takashi Komatsu

    2013-01-01

    Full Text Available Myrmecophilus ant crickets (Orthoptera: Myrmecophilidae are typical ant guests. In Japan, about 10 species are recognized on the basis of morphological and molecular phylogenetic frameworks. Some of these species have restricted host ranges and behave intimately toward their host ant species (i.e., they are host specialist. We focused on one species, M. tetramorii, which uses the myrmicine ant Tetramorium tsushimae as its main host. All but one M. tetramorii individuals were collected specifically from nests of T. tsushimae in the field. However, behavioral observation showed that all individuals used in the experiment received hostile reactions from the host ants. There were no signs of intimate behaviors such as grooming of hosts or receipt of mouth-to-mouth feeding from hosts, which are seen in some host-specialist Myrmecophilus species among obligate host-ant species. Therefore, it may be that M. tetramorii is the species that is specialized to exploit the host by means other than chemical integration.

  8. Host-associated populations in the lettuce root aphid, Pemphigus bursarius (L.).

    Science.gov (United States)

    Miller, N J; Kift, N B; Tatchell, G M

    2005-05-01

    Pemphigus bursarius is a host-alternating aphid in which annual rounds of sexual reproduction on its primary host, Populus nigra, are interspersed with parthenogenesis on a range of secondary hosts. Evidence was sought for the existence of genetically distinct populations, associated with different secondary hosts, in P. bursarius. Microsatellite markers revealed that genetically distinct populations were present on three different secondary host species. Microsatellites were also used, in conjunction with mitochondrial DNA sequence variation, to investigate the relationships between aphids on Populus, following sexual reproduction, and those on the secondary hosts. Evidence was found for a distinct, cyclically parthenogenetic population that exploited Lactuca sativa as its secondary host. In contrast, populations associated with Matricaria inodora appeared to be largely composed of obligate parthenogens or may even have been another species of Pemphigus. Populations on Lapsana communis appeared to be a mixture of cyclical and obligate parthenogens and were more genetically heterogeneous than those on other secondary hosts, possibly due to founder effects. Experiments to measure the performance of P. bursarius clones on different secondary hosts were inconclusive, failing to demonstrate either the presence or absence of adaptations to secondary hosts.

  9. Differential recognition and hydrolysis of host carbohydrate antigens by Streptococcus pneumoniae family 98 glycoside hydrolases.

    Science.gov (United States)

    Higgins, Melanie A; Whitworth, Garrett E; El Warry, Nahida; Randriantsoa, Mialy; Samain, Eric; Burke, Robert D; Vocadlo, David J; Boraston, Alisdair B

    2009-09-18

    The presence of a fucose utilization operon in the Streptococcus pneumoniae genome and its established importance in virulence indicates a reliance of this bacterium on the harvesting of host fucose-containing glycans. The identities of these glycans, however, and how they are harvested is presently unknown. The biochemical and high resolution x-ray crystallographic analysis of two family 98 glycoside hydrolases (GH98s) from distinctive forms of the fucose utilization operon that originate from different S. pneumoniae strains reveal that one enzyme, the predominant type among pneumococcal isolates, has a unique endo-beta-galactosidase activity on the LewisY antigen. Altered active site topography in the other species of GH98 enzyme tune its endo-beta-galactosidase activity to the blood group A and B antigens. Despite their different specificities, these enzymes, and by extension all family 98 glycoside hydrolases, use an inverting catalytic mechanism. Many bacterial and viral pathogens exploit host carbohydrate antigens for adherence as a precursor to colonization or infection. However, this is the first evidence of bacterial endoglycosidase enzymes that are known to play a role in virulence and are specific for distinct host carbohydrate antigens. The strain-specific distribution of two distinct types of GH98 enzymes further suggests that S. pneumoniae strains may specialize to exploit host-specific antigens that vary from host to host, a factor that may feature in whether a strain is capable of colonizing a host or establishing an invasive infection.

  10. Exploitation of manipulators: 'hitch-hiking' as a parasite transmission strategy.

    Science.gov (United States)

    Thomas; Renaud; Poulin

    1998-07-01

    For many parasites with complex life cycles, manipulation of host behaviour is an adaptation to increase the probability of successful transmission. Since manipulation is likely to be costly, other parasites may exploit hosts already manipulated so as to ensure their transmission without investing in manipulation. Such a cheating strategy, called 'hitch-hiking', could be adaptive in a range of situations. We first propose and discuss criteria that should be met by any parasite to be considered a hitch-hiker. Then, to understand the evolution of the hitch-hiking strategy, we use simple mathematical models to analyse the influence of several variables on the potential benefits for a nonmanipulative parasite of actively seeking a ride to the definitive host with a manipulative parasite. The models suggest that the prevalence or abundance of manipulative parasites will be a key determinant of whether hitch-hiking can be an advantageous option for other parasites. Copyright 1998 The Association for the Study of Animal Behaviour.

  11. Host factors in nidovirus replication

    NARCIS (Netherlands)

    Wilde, Adriaan Hugo de

    2013-01-01

    The interplay between nidoviruses and the infected host cell was investigated. Arterivirus RNA-synthesising activity was shown to depend on intact membranes and on a cytosolic host protein which does not cosediment with the RTC. Furthermore, the immunosuppressant drug cyclosporin A (CsA) blocks

  12. Larval helminths in intermediate hosts

    DEFF Research Database (Denmark)

    Fredensborg, Brian Lund; Poulin, R

    2005-01-01

    Density-dependent effects on parasite fitness have been documented from adult helminths in their definitive hosts. There have, however, been no studies on the cost of sharing an intermediate host with other parasites in terms of reduced adult parasite fecundity. Even if larval parasites suffer a ...

  13. Host Adaptation of Staphylococcal Leukocidins

    NARCIS (Netherlands)

    Vrieling, M

    2016-01-01

    Staphylococcus aureus is a human and animal pathogen of global importance and has the capacity to cause disease in distinct host populations, using a large arsenal of secreted proteins to evade the host immune response. Amongst the immune evasion proteins of S. aureus, secreted cytotoxins play a

  14. Rationalising predictors of child sexual exploitation and sex-trading.

    Science.gov (United States)

    Klatt, Thimna; Cavner, Della; Egan, Vincent

    2014-02-01

    Although there is evidence for specific risk factors leading to child sexual exploitation and prostitution, these influences overlap and have rarely been examined concurrently. The present study examined case files for 175 young persons who attended a voluntary organization in Leicester, United Kingdom, which supports people who are sexually exploited or at risk of sexual exploitation. Based on the case files, the presence or absence of known risk factors for becoming a sex worker was coded. Data were analyzed using t-test, logistic regression, and smallest space analysis. Users of the voluntary organization's services who had been sexually exploited exhibited a significantly greater number of risk factors than service users who had not been victims of sexual exploitation. The logistic regression produced a significant model fit. However, of the 14 potential predictors--many of which were associated with each other--only four variables significantly predicted actual sexual exploitation: running away, poverty, drug and/or alcohol use, and having friends or family members in prostitution. Surprisingly, running away was found to significantly decrease the odds of becoming involved in sexual exploitation. Smallest space analysis of the data revealed 5 clusters of risk factors. Two of the clusters, which reflected a desperation and need construct and immature or out-of-control lifestyles, were significantly associated with sexual exploitation. Our research suggests that some risk factors (e.g. physical and emotional abuse, early delinquency, and homelessness) for becoming involved in sexual exploitation are common but are part of the problematic milieu of the individuals affected and not directly associated with sex trading itself. Our results also indicate that it is important to engage with the families and associates of young persons at risk of becoming (or remaining) a sex worker if one wants to reduce the numbers of persons who engage in this activity. Copyright

  15. Meaning, function and methods of the recultivation in mining exploitation

    OpenAIRE

    Dambov, Risto; Ljatifi, Ejup

    2015-01-01

    With the exploitation of mineral resources is performed degradation and deformation of the relief and the general part of surface of the Earth's crust. Depending on the type of open pit mine, this degradation can be expressed to a lesser or greater extent, and sometimes in several square kilometers. The exploitation of mineral resources is with unbreakable link with the environment. Very often it is said that mining is „enemy No. 1“ for environment. With exploitation comes to degradation of h...

  16. The possibilities of exploitation of Serbian thermomineral waters

    International Nuclear Information System (INIS)

    Jovanovic, L.

    2002-01-01

    Global ecological problem of petrol resources deficit caused an intensive search of alternative energy sources. Deficit of conventional energy fluids in Yugoslavia requires serious efforts to create a program of alternative energy sources exploitation. Geothermal energy represents an important energetic source for the countries with poor energy resources. Geothermal energy can become the basis for economic development. At present these geothermal resources are not being exploited in Yugoslavia. The possibilities of effective exploitation of thermal and thermomineral water resources in Yugoslavia are presented in this paper

  17. Imouraren mining exploitation : Complementary studies Synthetic report Volum B - Mines

    International Nuclear Information System (INIS)

    1980-01-01

    The object of the current study is to determine the main technical characteristics of the reference project of a mine that can supply the necessary ore quantity at a production of 3000 tonnes uranium per year, along 10 years. The project is one of the possible solutions for exploiting the mine. The current study permits to establish : investment and functioning cost estimation, overall project of the mining exploitation program, necessary strength estimation, average ore grades evaluation and variations of these grades, utilities needs, production vizing program, main exploitation methods and necessary materials. Reference project study of the mine serves as base to the economics studies and studies optimization [fr

  18. Cuticular Hydrocarbons of Tribolium confusum Larvae Mediate Trail Following and Host Recognition in the Ectoparasitoid Holepyris sylvanidis.

    Science.gov (United States)

    Fürstenau, Benjamin; Hilker, Monika

    2017-09-01

    Parasitic wasps which attack insects infesting processed stored food need to locate their hosts hidden inside these products. Their host search is well-known to be guided by host kairomones, perceived via olfaction or contact. Among contact kairomones, host cuticular hydrocarbons (CHCs) may provide reliable information for a parasitoid. However, the chemistry of CHC profiles of hosts living in processed stored food products is largely unknown. Here we showed that the ectoparasitoid Holepyris sylvanidis uses CHCs of its host Tribolium confusum, a worldwide stored product pest, as kairomones for host location and recognition at short range. Chemical analysis of T. confusum larval extracts by gas chromatography coupled with mass spectrometry revealed a rich blend of long-chain (C25-C30) hydrocarbons, including n-alkanes, mono-, and dimethylalkanes. We further studied whether host larvae leave sufficient CHCs on a substrate where they walk along, thus allowing parasitoids to perceive a CHC trail and follow it to their host larvae. We detected 18 CHCs on a substrate that had been exposed to host larvae. These compounds were also found in crude extracts of host larvae and made up about a fifth of the CHC amount extracted. Behavioral assays showed that trails of host CHCs were followed by the parasitoids and reduced their searching time until successful host recognition. Host CHC trails deposited on different substrates were persistent for about a day. Hence, the parasitoid H. sylvanidis exploits CHCs of T. confusum larvae for host finding by following host CHC trails and for host recognition by direct contact with host larvae.

  19. Inhibiting host-pathogen interactions using membrane-based nanostructures.

    Science.gov (United States)

    Bricarello, Daniel A; Patel, Mira A; Parikh, Atul N

    2012-06-01

    Virulent strains of bacteria and viruses recognize host cells by their plasma membrane receptors and often exploit the native translocation machinery to invade the cell. A promising therapeutic concept for early interruption of pathogen infection is to subvert this pathogenic trickery using exogenously introduced decoys that present high-affinity mimics of cellular receptors. This review highlights emerging applications of molecularly engineered lipid-bilayer-based nanostructures, namely (i) functionalized liposomes, (ii) supported colloidal bilayers or protocells and (iii) reconstituted lipoproteins, which display functional cellular receptors in optimized conformational and aggregative states. These decoys outcompete host cell receptors by preferentially binding to and neutralizing virulence factors of both bacteria and viruses, thereby promising a new approach to antipathogenic therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. The Battle of RNA Synthesis: Virus versus Host.

    Science.gov (United States)

    Harwig, Alex; Landick, Robert; Berkhout, Ben

    2017-10-21

    Transcription control is the foundation of gene regulation. Whereas a cell is fully equipped for this task, viruses often depend on the host to supply tools for their transcription program. Over the course of evolution and adaptation, viruses have found diverse ways to optimally exploit cellular host processes such as transcription to their own benefit. Just as cells are increasingly understood to employ nascent RNAs in transcription regulation, recent discoveries are revealing how viruses use nascent RNAs to benefit their own gene expression. In this review, we first outline the two different transcription programs used by viruses, i.e., transcription (DNA-dependent) and RNA-dependent RNA synthesis. Subsequently, we use the distinct stages (initiation, elongation, termination) to describe the latest insights into nascent RNA-mediated regulation in the context of each relevant stage.

  1. Host-guest supramolecular nanosystems for cancer diagnostics and therapeutics.

    Science.gov (United States)

    Wang, Lei; Li, Li-li; Fan, Yun-shan; Wang, Hao

    2013-07-26

    Extensive efforts have been devoted to the construction of functional supramolecular nanosystems for applications in catalysis, energy conversion, sensing and biomedicine. The applications of supramolecular nanosystems such as liposomes, micelles, inorganic nanoparticles, carbon materials for cancer diagnostics and therapeutics have been reviewed by other groups. Here, we will focus on the recent momentous advances in the implementation of typical supramolecular hosts (i.e., cyclodextrins, calixarenes, cucurbiturils and metallo-hosts) and their nanosystems in cancer diagnostics and therapeutics. We discuss the evolutive process of supramolecular nanosystems from the structural control and characterization to their diagnostic and therapeutic function exploitation and even the future potentials for clinical translation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Ebola virus host cell entry.

    Science.gov (United States)

    Sakurai, Yasuteru

    2015-01-01

    Ebola virus is an enveloped virus with filamentous structure and causes a severe hemorrhagic fever in human and nonhuman primates. Host cell entry is the first essential step in the viral life cycle, which has been extensively studied as one of the therapeutic targets. A virus factor of cell entry is a surface glycoprotein (GP), which is an only essential viral protein in the step, as well as the unique particle structure. The virus also interacts with a lot of host factors to successfully enter host cells. Ebola virus at first binds to cell surface proteins and internalizes into cells, followed by trafficking through endosomal vesicles to intracellular acidic compartments. There, host proteases process GPs, which can interact with an intracellular receptor. Then, under an appropriate circumstance, viral and endosomal membranes are fused, which is enhanced by major structural changes of GPs, to complete host cell entry. Recently the basic research of Ebola virus infection mechanism has markedly progressed, largely contributed by identification of host factors and detailed structural analyses of GPs. This article highlights the mechanism of Ebola virus host cell entry, including recent findings.

  3. Conflicts Related to Natural Resources Exploitation: A Case Study of ...

    African Journals Online (AJOL)

    Conflicts Related to Natural Resources Exploitation: A Case Study of Oil Crisis in Nigeria's Niger Delta Region and its Socio-Political and Economic Implications. ... on the environment leading to pollution of land, rivers, creeks and waterways.

  4. Exploitation of unconventional protein sources in the feed of weaner ...

    African Journals Online (AJOL)

    Exploitation of unconventional protein sources in the feed of weaner rabbits ... as protein sources for feeding ruminants but rarely considered as feed for micro ... 26.88 g/100g DM in Centrosema pubescens and Moringa oleifera, respectively.

  5. Exploiting Formation Flying for Fuel Saving Supersonic Oblique Wing Aircraft

    Science.gov (United States)

    2007-07-01

    used and developed during recent wing / winglet / morphing design programmes (Refs.13-14). By exploiting this method, we have assessed the aerodynamics ...parameters, Propulsion Issues, Size Issues, Aero-elastic effects 15. SUBJECT TERMS EOARD, Control System, Aerodynamics 16...

  6. Human trafficking and exploitation: A global health concern.

    Science.gov (United States)

    Zimmerman, Cathy; Kiss, Ligia

    2017-11-01

    In this collection review, Cathy Zimmerman and colleague introduce the PLOS Medicine Collection on Human Trafficking, Exploitation and Health, laying out the magnitude of the global trafficking problem and offering a public health policy framework to guide responses to trafficking.

  7. Uncertainty avoidance and the exploration-exploitation trade-off

    NARCIS (Netherlands)

    Broekhuizen, Thijs; Giarratana, Marco S.; Torres, Anna

    2017-01-01

    Purpose - This study aims to investigate how a firm's uncertainty avoidance - as indicated by the headquarters' national culture - impacts firm performance by affecting exploratory (product innovation) and exploitative (brand trademark protection) activities. It aims to show that firms characterized

  8. Enhanced surrogate models for statistical design exploiting space mapping technology

    DEFF Research Database (Denmark)

    Koziel, Slawek; Bandler, John W.; Mohamed, Achmed S.

    2005-01-01

    We present advances in microwave and RF device modeling exploiting Space Mapping (SM) technology. We propose new SM modeling formulations utilizing input mappings, output mappings, frequency scaling and quadratic approximations. Our aim is to enhance circuit models for statistical analysis...

  9. Trajectories and cycles of sexual exploitation and trafficking for sexual exploitation of women in the Peruvian Amazon

    OpenAIRE

    Mujica, Jaris

    2015-01-01

    The commercial sexual exploitation is a constant activity in the Peruvian Amazon. Around the river port of Pucallpa in ucayali region, the practice appears systematically: teenage attend taverns around the port, and those dedicated to the work of cooking camps logging, are victims of constant exploitation and many also of trafficking. this article aims to reconstruct the path of life and reproductive cycle of the forms of exploitation in a sample of 20 women, and focuses on: (i) evidence of s...

  10. Escaping from the exploitation trap by shaping the digital future

    OpenAIRE

    Füzes, Péter; Gódor, Zoltán; Szabó, Zsolt Roland

    2017-01-01

    Even Fortune 500 firms can disappear quickly, because many of them falls into an exploitation trap. Examples show that certain organizations – that manifest ambidextrous features – can avoid the exploitation trap. But, how can they do it? Authors tracked the digital transformation of a Fortune 500 company in order to understand the strategic and organizational challenges and solutions to become resilient and prosperous. A cutting edge example is shown in the paper about how an industry leader...

  11. The concept of exploitation in international human trafficking law

    OpenAIRE

    von der Pütten, Tuija Kaarina

    2017-01-01

    Human trafficking is commonly known as a criminal practice that takes place in the framework of sex trade: women and children are trafficked within a state, or from one state to another, for the purpose of sexual exploitation. Similarly, the early 20th century international conventions aimed to tackle ‘white slave traffic’, trafficking of women and children for sexual exploitation. However, it is misleading to see trafficking only within this context. People are trafficked so that they can be...

  12. Echinococcus-Host Interactions at Cellular and Molecular Levels.

    Science.gov (United States)

    Brehm, K; Koziol, U

    2017-01-01

    The potentially lethal zoonotic diseases alveolar and cystic echinococcosis are caused by the metacestode larval stages of the tapeworms Echinococcus multilocularis and Echinococcus granulosus, respectively. In both cases, metacestode growth and proliferation occurs within the inner organs of mammalian hosts, which is associated with complex molecular host-parasite interactions that regulate nutrient uptake by the parasite as well as metacestode persistence and development. Using in vitro cultivation systems for parasite larvae, and informed by recently released, comprehensive genome and transcriptome data for both parasites, these molecular host-parasite interactions have been subject to significant research during recent years. In this review, we discuss progress in this field, with emphasis on parasite development and proliferation. We review host-parasite interaction mechanisms that occur early during an infection, when the invading oncosphere stage undergoes a metamorphosis towards the metacestode, and outline the decisive role of parasite stem cells during this process. We also discuss special features of metacestode morphology, and how this parasite stage takes up nutrients from the host, utilizing newly evolved or expanded gene families. We comprehensively review mechanisms of host-parasite cross-communication via evolutionarily conserved signalling systems and how the parasite signalling systems might be exploited for the development of novel chemotherapeutics. Finally, we point to an urgent need for the development of functional genomic techniques in this parasite, which will be imperative for hypothesis-driven analyses into Echinococcus stem cell biology, developmental mechanisms and immunomodulatory activities, which are all highly relevant for the development of anti-infective measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Digbeth hosts the Big Bang

    CERN Multimedia

    2002-01-01

    Birminham museum of science and discovery, Thinktank, is hosting 'Building The Universe', a free exhibition about the work undertaken at the European Laboratory for Particle Physics, in Geneva (3 paragraphs).

  14. Asymmetrical floating point array processors, their application to exploration and exploitation

    Energy Technology Data Exchange (ETDEWEB)

    Geriepy, B L

    1983-01-01

    An asymmetrical floating point array processor is a special-purpose scientific computer which operates under asymmetrical control of a host computer. Although an array processor can receive fixed point input and produce fixed point output, its primary mode of operation is floating point. The first generation of array processors was oriented towards time series information. The next generation of array processors has proved much more versatile and their applicability ranges from petroleum reservoir simulation to speech syntheses. Array processors are becoming commonplace in mining, the primary usage being construction of grids-by usual methods or by kriging. The Australian mining community is among the world's leaders in regard to computer-assisted exploration and exploitation systems. Part of this leadership role must be providing guidance to computer vendors in regard to current and future requirements.

  15. Direct exploitation of a top 500 Supercomputer for Analysis of CMS Data

    International Nuclear Information System (INIS)

    Cabrillo, I; Cabellos, L; Marco, J; Fernandez, J; Gonzalez, I

    2014-01-01

    The Altamira Supercomputer hosted at the Instituto de Fisica de Cantatbria (IFCA) entered in operation in summer 2012. Its last generation FDR Infiniband network used (for message passing) in parallel jobs, supports the connection to General Parallel File System (GPFS) servers, enabling an efficient simultaneous processing of multiple data demanding jobs. Sharing a common GPFS system and a single LDAP-based identification with the existing Grid clusters at IFCA allows CMS researchers to exploit the large instantaneous capacity of this supercomputer to execute analysis jobs. The detailed experience describing this opportunistic use for skimming and final analysis of CMS 2012 data for a specific physics channel, resulting in an order of magnitude reduction of the waiting time, is presented.

  16. From Exploitation to Industry: Definitions, Risks, and Consequences of Domestic Sexual Exploitation and Sex Work Among Women and Girls

    OpenAIRE

    Gerassi, Lara

    2015-01-01

    In the last 15 years, terms such as prostitution, sex trafficking, sexual exploitation, modern-day slavery, and sex work have elicited much confusion and debate as to their definitions. Consequently several challenges have emerged for both law enforcement in the prosecution of criminals and practitioners in service provision. This article reviews the state of the literature with regard to domestic, sexual exploitation among women and girls in the United States and seeks to (1) provide definit...

  17. The interaction between LYVE-1 with hyaluronan on the cell surface may play a role in the diversity of adhesion to cancer cells.

    Science.gov (United States)

    Du, Yan; Liu, Hua; He, Yiqing; Liu, Yiwen; Yang, Cuixia; Zhou, Muqing; Wang, Wenjuan; Cui, Lian; Hu, Jiajie; Gao, Feng

    2013-01-01

    Hyaluronan (HA), a simple disaccharide unit, can polymerize and is considered a primary component of the extracellular matrix, which has a wide range of biological functions. In recent years, HA was found on the surface of tumor cells. According to previous reports, differing HA content on the cell surface of tumor cells is closely related to lymph node metastases, but the mechanisms mediating this process remained unclear. This research intended to study the surface content of HA on tumor cells and analyze cell adhesive changes caused by the interaction between HA and its lymphatic endothelial receptor (LYVE-1). We screened and observed high HA content on HS-578T breast cells and low HA content on MCF-7 breast cells through particle exclusion, immunofluorescence and flow cytometry experiments. The expression of LYVE-1, the lymph-vessel specific HA receptor, was consistent with our previous report and enhanced the adhesion of HA(high)-HS-578T cells to COS-7(LYVE-1(+)) through HA in cell static adhesion and dynamic parallel plate flow chamber experiments. MCF-7 breast cells contain little HA on the surface; however, our results showed little adhesion difference between MCF-7 cells and COS-7(LYVE-1(+)) and COS-7(LYVE-1(-)) cells. Similar results were observed concerning the adhesion of HS-578T cells or MCF-7 cells to SVEC4-10 cells. Furthermore, we observed for the first time that the cell surface HA content of high transfer tumor cells was rich, and we visualized the cross-linking of HA cable structures, which may activate LYVE-1 on lymphatic endothelial cells, promoting tumor adhesion. In summary, high-low cell surface HA content of tumor cells through the interaction with LYVE-1 leads to adhesion differences.

  18. pH-Amplified multilayer films based on hyaluronan: influence of HA molecular weight and concentration on film growth and stability.

    Science.gov (United States)

    Shen, Liyan; Chaudouet, Patrick; Ji, Jian; Picart, Catherine

    2011-04-11

    In this study, we investigate the growth and internal properties of polyelectrolyte multilayer films made of poly(l-lysine) and hyaluronan (PLL/HA) under pH-amplified conditions, that is, by alternate deposition of PLL at high pH and HA at low pH. We focus especially on the influence of the molecular weight of HA in this process as well as on its concentration in solution. Film growth was followed by quartz crystal microbalance and by infrared spectroscopy to quantify the deposited mass and to characterize the internal properties of the films, including the presence of hydrogen bonds and the ionization degree of HA in the films. Film growth was significantly faster for HA of high molecular weight (1300 kDa) as compared with 400 and 200 kDa. PLL was found to exhibit a random structure once deposited in the films. Furthermore, we found that PLL-ending films are more stable when they are placed in PBS than their HA counterparts. This was explained on the basis of more cohesive interactions in the films for PLL-ending films. Finally, we quantified PLL(FITC) diffusion into the films and observed that PLL diffusion is enhanced when PLL is paired with the HA of high MW. All together, these results suggest that besides purely physicochemical parameters such as variation in pH, the molecular weight of HA, its concentration in solution, and the possibility to form intermolecular HA association play important roles in film growth, internal cohesion, and stability.

  19. Effect of long-term culture of mouse embryonic stem cells under low oxygen concentration as well as on glycosaminoglycan hyaluronan on cell proliferation and differentiation.

    Science.gov (United States)

    Ramírez, M Á; Pericuesta, E; Yáñez-Mó, M; Palasz, A; Gutiérrez-Adán, A

    2011-02-01

    Maintaining undifferentiated stem cells in defined conditions is of critical importance to improve their in vitro culture. We have evaluated the effects of culturing mouse stem (mES) cells under physiological oxygen concentration as well as by replacing fibroblast feeder layer (mEF) with gelatin or glycosaminoglycan hyaluronan (HA), on cell proliferation and differentiation. After 3 days culture or after long-term cell culture under different conditions, levels of apoptotic cell death were determined by cell cycle and TUNEL (TdT-mediated dUTP nick end labelling) assays and levels of cell proliferation by CFSE (5-(and-6)-carboxyfluorescein diacetate succinimidyl ester) labelling. We assessed spontaneous differentiation into cardiomyocytes and mRNA expression of pluripotency and differentiation biomarkers. After 3 days culture under hypoxic conditions, levels of proliferation and apoptosis of mES cells were higher, in correlation with increase in intracellular reactive oxygen species. However, when cells were continuously grown for 1 month under those conditions, the level of apoptosis was, in all cases, under 4%. Hypoxia reduced spontaneous differentiation of mES into cardiomyocytes. Long-term culture on HA was more effective in maintaining the pluripotent state of the mES cells when compared to that on gelatin. Level of terminal differentiation was highest on mEF, intermediate on HA and lowest on gelatin. Our data suggest that hypoxia is not necessary for maintaining pluripotency of mES cells and appeared to be detrimental during ES differentiation. Moreover, HA may offer a valuable alternative for long-term culture of mES cells in vitro. © 2010 Blackwell Publishing Ltd.

  20. Sequencing of chondroitin sulfate oligosaccharides using a novel exolyase from a marine bacterium that degrades hyaluronan and chondroitin sulfate/dermatan sulfate.

    Science.gov (United States)

    Wang, Wenshuang; Cai, Xiaojuan; Han, Naihan; Han, Wenjun; Sugahara, Kazuyuki; Li, Fuchuan

    2017-11-09

    Glycosaminoglycans (GAGs) are a family of chemically heterogeneous polysaccharides that play important roles in physiological and pathological processes. Owing to the structural complexity of GAGs, their sophisticated chemical structures and biological functions have not been extensively studied. Lyases that cleave GAGs are important tools for structural analysis. Although various GAG lyases have been identified, exolytic lyases with unique enzymatic property are urgently needed for GAG sequencing. In the present study, a putative exolytic GAG lyase from a marine bacterium was recombinantly expressed and characterized in detail. Since it showed exolytic lyase activity toward hyaluronan (HA), chondroitin sulfate (CS), and dermatan sulfate (DS), it was designated as HCDLase. This novel exolyase exhibited the highest activity in Tris-HCl buffer (pH 7.0) at 30°C. Especially, it showed a specific activity that released 2-aminobenzamide (2-AB)-labeled disaccharides from the reducing end of 2-AB-labeled CS oligosaccharides, which suggest that HCDLase is not only a novel exolytic lyase that can split disaccharide residues from the reducing termini of sugar chains but also a useful tool for the sequencing of CS chains. Notably, HCDLase could not digest 2-AB-labeled oligosaccharides from HA, DS, or unsulfated chondroitin, which indicated that sulfates and bond types affect the catalytic activity of HCDLase. Finally, this enzyme combined with CSase ABC was successfully applied for the sequencing of several CS hexa- and octasaccharides with complex structures. The identification of HCDLase provides a useful tool for CS-related research and applications. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  1. Acquisition of epithelial-mesenchymal transition and cancer stem-like phenotypes within chitosan-hyaluronan membrane-derived 3D tumor spheroids.

    Science.gov (United States)

    Huang, Yen-Jang; Hsu, Shan-Hui

    2014-12-01

    Cancer drug development has to go through rigorous testing and evaluation processes during pre-clinical in vitro studies. However, the conventional two-dimensional (2D) in vitro culture is often discounted by the insufficiency to present a more typical tumor microenvironment. The multicellular tumor spheroids have been a valuable model to provide more comprehensive assessment of tumor in response to therapeutic strategies. Here, we applied chitosan-hyaluronan (HA) membranes as a platform to promote three-dimensional (3D) tumor spheroid formation. The biological features of tumor spheroids of human non-small cell lung cancer (NSCLC) cells on chitosan-HA membranes were compared to those of 2D cultured cells in vitro. The cells in tumor spheroids cultured on chitosan-HA membranes showed higher levels of stem-like properties and epithelial-mesenchymal transition (EMT) markers, such as NANOG, SOX2, CD44, CD133, N-cadherin, and vimentin, than 2D cultured cells. Moreover, they exhibited enhanced invasive activities and multidrug resistance by the upregulation of MMP2, MMP9, BCRC5, BCL2, MDR1, and ABCG2 as compared with 2D cultured cells. The grafting densities of HA affected the tumor sphere size and mRNA levels of genes on the substrates. These evidences suggest that chitosan-HA membranes may offer a simple and valuable biomaterial platform for rapid generation of tumor spheroids in vitro as well as for further applications in cancer stem cell research and cancer drug screening. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Rational Exploitation and Utilizing of Groundwater in Jiangsu Coastal Area

    Science.gov (United States)

    Kang, B.; Lin, X.

    2017-12-01

    Jiangsu coastal area is located in the southeast coast of China, where is a new industrial base and an important coastal and Land Resources Development Zone of China. In the areas with strong human exploitation activities, regional groundwater evolution is obviously affected by human activities. In order to solve the environmental geological problems caused by groundwater exploitation fundamentally, we must find out the forming conditions of regional groundwater hydrodynamic field, and the impact of human activities on groundwater hydrodynamic field evolution and hydrogeochemical evolition. Based on these results, scientific management and reasonable exploitation of the regional groundwater resources can be provided for the utilization. Taking the coastal area of Jiangsu as the research area, we investigate and analyze of the regional hydrogeological conditions. The numerical simulation model of groundwater flow was established according to the water power, chemical and isotopic methods, the conditions of water flow and the influence of hydrodynamic field on the water chemical field. We predict the evolution of regional groundwater dynamics under the influence of human activities and climate change and evaluate the influence of groundwater dynamic field evolution on the environmental geological problems caused by groundwater exploitation under various conditions. We get the following conclusions: Three groundwater exploitation optimal schemes were established. The groundwater salinization was taken as the primary control condition. The substitution model was proposed to model groundwater exploitation and water level changes by BP network method.Then genetic algorithm was used to solve the optimization solution. Three groundwater exploitation optimal schemes were submit to local water resource management. The first sheme was used to solve the groundwater salinization problem. The second sheme focused on dual water supply. The third sheme concerned on emergency water

  3. Patterns of resource exploitation in four coexisting globeflower fly species ( Chiastocheta sp.)

    Science.gov (United States)

    Pompanon, François; Pettex, Emeline; Després, Laurence

    2006-03-01

    Life history and spatio-temporal patterns of resource utilisation were characterised in four Chiastocheta (Diptera: Anthomyiidae) species, whose larvae compete as seed predators on Trollius europaeus fruits. Interspecific co-occurrence was observed in 80% of the resource patches (= Trollius fruits) in the two communities studied. Isolated larvae from all species had a similar food intake, but differed in development time and size at emergence. Different species exhibit contrasting resource exploitation strategies with specific mining patterns and a partial temporal shift. Two species exhibited particularly singular strategies. C. rotundiventris escaped from strong interactions with other species because it was the first species to develop and the only one to exploit the central pith of Trollius fruits. The key role of this species as the main pollinator of the host-plant appears to be a by-product of constraints imposed by occupying a restricted niche. Although the resource is ephemeral due to seed dispersal, C. dentifera, the last species to oviposit, is not disadvantaged because it has a short development time and rapid food intake. The different patterns can partly explain the stability of Chiastocheta communities, but do not prevent competition to occur at high larval densities.

  4. Exploitation and Utilization of Oilfield Geothermal Resources in China

    Directory of Open Access Journals (Sweden)

    Shejiao Wang

    2016-09-01

    Full Text Available Geothermal energy is a clean, green renewable resource, which can be utilized for power generation, heating, cooling, and could effectively replace oil, gas, and coal. In recent years, oil companies have put more efforts into exploiting and utilizing geothermal energy with advanced technologies for heat-tracing oil gathering and transportation, central heating, etc., which has not only reduced resource waste, but also improved large-scale and industrial resource utilization levels, and has achieved remarkable economic and social benefits. Based on the analysis of oilfield geothermal energy development status, resource potential, and exploitation and utilization modes, the advantages and disadvantages of harnessing oilfield geothermal resource have been discussed. Oilfield geothermal energy exploitation and utilization have advantages in resources, technical personnel, technology, and a large number of abandoned wells that could be reconstructed and utilized. Due to the high heat demand in oilfields, geothermal energy exploitation and utilization can effectively replace oil, gas, coal, and other fossil fuels, and has bright prospects. The key factors limiting oilfield geothermal energy exploitation and utilization are also pointed out in this paper, including immature technologies, lack of overall planning, lack of standards in resource assessment, and economic assessment, lack of incentive policies, etc.

  5. Two different strategies of host manipulation allow parasites to persist in intermediate-definitive host systems

    NARCIS (Netherlands)

    Vries, de L.J.; Langevelde, van F.

    2018-01-01

    Trophically transmitted parasites start their development in an intermediate host, before they finish the development in their definitive host when the definitive host preys on the intermediate host. In intermediate-definitive host systems, two strategies of host manipulation have been evolved:

  6. Rotaxane and catenane host structures for sensing charged guest species.

    Science.gov (United States)

    Langton, Matthew J; Beer, Paul D

    2014-07-15

    CONSPECTUS: The promise of mechanically interlocked architectures, such as rotaxanes and catenanes, as prototypical molecular switches and shuttles for nanotechnological applications, has stimulated an ever increasing interest in their synthesis and function. The elaborate host cavities of interlocked structures, however, can also offer a novel approach toward molecular recognition: this Account describes the use of rotaxane and catenane host systems for binding charged guest species, and for providing sensing capability through an integrated optical or electrochemical reporter group. Particular attention is drawn to the exploitation of the unusual dynamic properties of interlocked molecules, such as guest-induced shuttling or conformational switching, as a sophisticated means of achieving a selective and functional sensor response. We initially survey interlocked host systems capable of sensing cationic guests, before focusing on our accomplishments in synthesizing rotaxanes and catenanes designed for the more challenging task of selective anion sensing. In our group, we have developed the use of discrete anionic templation to prepare mechanically interlocked structures for anion recognition applications. Removal of the anion template reveals an interlocked host system, possessing a unique three-dimensional geometrically restrained binding cavity formed between the interlocked components, which exhibits impressive selectivity toward complementary anionic guest species. By incorporating reporter groups within such systems, we have developed both electrochemical and optical anion sensors which can achieve highly selective sensing of anionic guests. Transition metals, lanthanides, and organic fluorophores integrated within the mechanically bonded structural framework of the receptor are perturbed by the binding of the guest, with a concomitant change in the emission profile. We have also exploited the unique dynamics of interlocked hosts by demonstrating that an

  7. Sexual exploitation and labor during adolescence: A case study

    Directory of Open Access Journals (Sweden)

    Luciana Dutra-Thomé

    2011-09-01

    Full Text Available The present article focused on the perception of sexual exploitation as a job, using a single case study design. The aim of the study was to investigate the case of a 14 year-old girl, involved in commercial sexual exploitation, who considered this situation as her labor activity. A content analysis showed protective and risk factors as categories, especially related to her labor activities. The girl perceived the sexual exploitation activity as a job that provided autonomy, subsistence, and survival. The study revealed that the negative effects of working during adolescence may bring consequences to health and development. Youth work may be defined as a risk factor, especially when the labour conditions are not adequate and protected.

  8. Information source exploitation/exploration and NPD decision-making

    DEFF Research Database (Denmark)

    Jespersen, Kristina Risom

    different Scandinavian companies. Data was analyzed using hierarchical regression models across decision criteria dimensions and NPD stages as well as analyzing the combination of selected information sources. Rather than forwarding one optimal search behavior for the entire NPD process, we find optimal...... information search behavior at either end of the exploitation/exploration continuum. Additionally, we find that overexploitation and overexploration is caused by managerial bias. This creates managerial misbehavior at gate decision-points of the NPD process.......The purpose of this study is to examine how the exploration/exploitation continuum is applied by decision-makers in new product gate decision-making. Specifically, we analyze at gate decision-points how the evaluation of a new product project is affected by the information source exploitation...

  9. The ALARA project of the EDF nuclear park exploitation

    International Nuclear Information System (INIS)

    Potoczek, J.

    1998-01-01

    To bring the exploitation of the nuclear park of EDF at the level of the best exploiters in the world in matter of collective and individual dosimetry, the ALARA principle coordinates numerous actions: to associate the temporary societies, to define common language, methods and tools for the whole park to organize a level effect in this area, to optimize the maintenance that is expansive in radiation doses, to make the different levels of management responsible on dosimetric stakes, to reduce the singular sources of exposure, to assure the organisation and exploitation of the experience back in this field and adapt consequently the system of information. The results are cheerful and the objectives for 2000 are: less than 1.2 h.Sv by year and by reactor, no intervener whom annual radiation dose is upper than 20 mSv (out of exceptional case). (N.C.)

  10. The exploitation of swamp plants for dewatering liquid sewage sludge

    Directory of Open Access Journals (Sweden)

    Jiří Šálek

    2006-01-01

    Full Text Available The operators of little rural wastewater treatment plants have been interested in economic exploitation of sewage sludge in local conditions. The chance is searching simply and natural ways of processing and exploitation stabilized sewage sludge in agriculture. Manure substrate have been obtained by composting waterless sewage sludge including rest plant biomass after closing 6–8 years period of filling liquid sewage sludge to the basin. Main attention was focused on exploitation of swamp plants for dewatering liquid sewage sludge and determination of influence sewage sludge on plants, intensity and course of evapotranspiration and design and setting of drying beds. On the base of determined ability of swamp plants evapotranspiration were edited suggestion solutions of design and operation sludge bed facilities in the conditions of small rural wastewater treatment plant.

  11. Cultural Work as a Site of Struggle: Freelancers and Exploitation

    Directory of Open Access Journals (Sweden)

    Nicole S. Cohen

    2012-05-01

    Full Text Available This paper argues that Marxist political economy is a useful framework for understanding contemporary conditions of cultural work. Drawing on Karl Marx’s foundational concepts, labour process theory, and a case study of freelance writers, I argue that the debate over autonomy and control in cultural work ignores exploitation in labour-capital relationships, which is a crucial process shaping cultural work. To demonstrate the benefits of this approach, I discuss two methods media firms use to extract surplus value from freelance writers: exploitation of unpaid labour time and exploitation of intellectual property through aggressive copyright regimes. I argue that a Marxist perspective can uncover the dynamics that are transforming cultural industries and workers’ experiences. From this perspective, cultural work is understood as a site of struggle.

  12. How a retrotransposon exploits the plant's heat stress response for its activation.

    Directory of Open Access Journals (Sweden)

    Vladimir V Cavrak

    2014-01-01

    Full Text Available Retrotransposons are major components of plant and animal genomes. They amplify by reverse transcription and reintegration into the host genome but their activity is usually epigenetically silenced. In plants, genomic copies of retrotransposons are typically associated with repressive chromatin modifications installed and maintained by RNA-directed DNA methylation. To escape this tight control, retrotransposons employ various strategies to avoid epigenetic silencing. Here we describe the mechanism developed by ONSEN, an LTR-copia type retrotransposon in Arabidopsis thaliana. ONSEN has acquired a heat-responsive element recognized by plant-derived heat stress defense factors, resulting in transcription and production of full length extrachromosomal DNA under elevated temperatures. Further, the ONSEN promoter is free of CG and CHG sites, and the reduction of DNA methylation at the CHH sites is not sufficient to activate the element. Since dividing cells have a more pronounced heat response, the extrachromosomal ONSEN DNA, capable of reintegrating into the genome, accumulates preferentially in the meristematic tissue of the shoot. The recruitment of a major plant heat shock transcription factor in periods of heat stress exploits the plant's heat stress response to achieve the transposon's activation, making it impossible for the host to respond appropriately to stress without losing control over the invader.

  13. Exploiting Thread Parallelism for Ocean Modeling on Cray XC Supercomputers

    Energy Technology Data Exchange (ETDEWEB)

    Sarje, Abhinav [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Jacobsen, Douglas W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Williams, Samuel W. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Ringler, Todd [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Oliker, Leonid [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-05-01

    The incorporation of increasing core counts in modern processors used to build state-of-the-art supercomputers is driving application development towards exploitation of thread parallelism, in addition to distributed memory parallelism, with the goal of delivering efficient high-performance codes. In this work we describe the exploitation of threading and our experiences with it with respect to a real-world ocean modeling application code, MPAS-Ocean. We present detailed performance analysis and comparisons of various approaches and configurations for threading on the Cray XC series supercomputers.

  14. Influence of Machine Exploitation Effectiveness on Furniture Production Quality Level

    Directory of Open Access Journals (Sweden)

    Stasiak-Betlejewska Renata

    2015-12-01

    Full Text Available One of the most important factors determining the company‘s capacity to produce high quality products is the level of machinery operation effectiveness. Companies having modern machinery are characterized by high productivity. To obtain a high quality product, the equipment should be properly used, without any failure, which contributes significantly to the exploitation level increase. The modernity level and the exploitation effectiveness level for chosen machine producing furniture components in relation to the product quality level were analysed in the paper. As a result of the research findings analysis, proposals for corrective actions with regard to machinery maintenance and production processes were presented.

  15. On species preservation and Non-Cooperative Exploiters

    DEFF Research Database (Denmark)

    Kronbak, Lone Grønbæk; Lindroos, Marko

    cases where several non-cooperative exploiters are involved in mixed fisheries. This paper is targeting biodiversity preservation by setting up a two species model with the aim of ensuring both species survive harvesting of exploiters adapting a non-cooperative behaviour. The model starts out as a multi......-species model without biological dependency and is then modified to include also biological dependency. We contribute to the literature by analytically finding the limits on the number of players preserving both species including the conditions to be satisfied. For visual purposes we simulate a two species...

  16. Final Report, “Exploiting Global View for Resilience”

    Energy Technology Data Exchange (ETDEWEB)

    Chien, Andrew [Univ. of Chicago, IL (United States)

    2017-03-29

    Final technical report for the "Exploiting Global View for Resilience" project. The GVR project aims to create a new approach to portable, resilient applications. The GVR approach builds on a global view data model,, adding versioning (multi-version), user control of timing and rate (multi-stream), and flexible cross layer error signalling and recovery. With a versioned array as a portable abstraction, GVR enables application programmers to exploit deep scientific and application code insights to manage resilience (and its overhead) in a flexible, portable fashion.

  17. Fishery Development and Exploitation in South East Australia

    Directory of Open Access Journals (Sweden)

    Camilla Novaglio

    2018-04-01

    Full Text Available Understanding the full extent of past ecological changes in human-influenced marine systems is needed to inform present management policies, but is often hampered by the scarcity of information about exploitation practices and population status over the entire history of fishing. The history of commercial fishing in South East Australia is relatively recent and thus easier to document. Our aim is to reconstruct such history and to use this information to understand general patterns and consequences of fishing exploitation. Intense exploitation of marine resources arrived in South East Australia with European colonization in the early 1800s, and unregulated sealing, whaling and oyster dredging resulted in the first documented significant impact on local marine populations. Exploitation extended to demersal resources in 1915 when the trawl fishery developed. Between the early 1800s and the 1980s, some of the exploited stocks collapsed, but fishing moved further offshore and in deeper waters as technology improved and new resources became available or were discovered. This phase of fisheries expansion masked the unsustainable nature of some fishing industries, such as trawling and whaling, and postponed the need for management regulations. From the 1990s onward, an increasing awareness of the depleted nature of some fisheries led to the establishment of management strategies aiming at a more sustainable exploitation of target stocks and, from the mid-2000s onwards, management strategies were revised and improved to better address the effect of fishing on multiple components of marine ecosystems. This led to the recovery of some depleted populations and to increased habitat protection. The relatively short history of fishing exploitation and the small scale of the fishing industry in South East Australia played a significant role in limiting the magnitude of fishing impacts on local populations and helped to achieve recoveries when fisheries

  18. The Inflammasome in Host Defense

    Directory of Open Access Journals (Sweden)

    Gang Chen

    2009-12-01

    Full Text Available Nod-like receptors have emerged as an important family of sensors in host defense. These receptors are expressed in macrophages, dendritic cells and monocytes and play an important role in microbial immunity. Some Nod-like receptors form the inflammasome, a protein complex that activates caspase-1 in response to several stimuli. Caspase-1 activation leads to processing and secretion of pro-inflammatory cytokines such as interleukin (IL-1β and IL-18. Here, we discuss recent advances in the inflammasome field with an emphasis on host defense. We also compare differential requirements for inflammasome activation in dendritic cells, macrophages and monocytes.

  19. Host factors influencing viral persistence

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Nansen, A; Ørding Andreasen, Susanne

    2000-01-01

    host were used. Our results reveal that very different outcomes may be observed depending on virus strain and immunocompetence of the host. Thus while CD4+ cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4+ cells, B cells or CD40 ligand...... replication, mice lacking the ability to produce interferon-gamma may develop either a severe, mostly fatal, T-cell mediated wasting syndrome or a chronic infection characterized by long-term coexistence of antiviral cytotoxic T lymphocytes and infectious virus. Mathematical modelling indicates...

  20. From Exploitation to Industry: Definitions, Risks, and Consequences of Domestic Sexual Exploitation and Sex Work Among Women and Girls.

    Science.gov (United States)

    Gerassi, Lara

    In the last 15 years, terms such as prostitution, sex trafficking, sexual exploitation, modern-day slavery, and sex work have elicited much confusion and debate as to their definitions. Consequently several challenges have emerged for both law enforcement in the prosecution of criminals and practitioners in service provision. This article reviews the state of the literature with regard to domestic, sexual exploitation among women and girls in the United States and seeks to (1) provide definitions and describe the complexity of all terms relating to domestic sexual exploitation of women and girls in the United States, (2) explore available national prevalence data according to the definitions provided, and (3) review the evidence of mental health, social, and structural risk factors at the micro-, mezzo-, and macrolevels.

  1. From Exploitation to Industry: Definitions, Risks, and Consequences of Domestic Sexual Exploitation and Sex Work Among Women and Girls

    Science.gov (United States)

    Gerassi, Lara

    2015-01-01

    In the last 15 years, terms such as prostitution, sex trafficking, sexual exploitation, modern-day slavery, and sex work have elicited much confusion and debate as to their definitions. Consequently several challenges have emerged for both law enforcement in the prosecution of criminals and practitioners in service provision. This article reviews the state of the literature with regard to domestic, sexual exploitation among women and girls in the United States and seeks to (1) provide definitions and describe the complexity of all terms relating to domestic sexual exploitation of women and girls in the United States, (2) explore available national prevalence data according to the definitions provided, and (3) review the evidence of mental health, social, and structural risk factors at the micro-, mezzo-, and macrolevels. PMID:26726289

  2. Myxozoan infections of caecilians demonstrate broad host specificity and indicate a link with human activity.

    Science.gov (United States)

    Hartigan, Ashlie; Wilkinson, Mark; Gower, David J; Streicher, Jeffrey W; Holzer, Astrid S; Okamura, Beth

    2016-05-01

    Myxozoans are parasitic cnidarians that infect a wide variety of hosts. Vertebrates typically serve as intermediate hosts whereas definitive hosts are invertebrates, including annelids and bryozoans. Myxozoans are known to exploit species in two of the three extant amphibian orders (Anura: frogs and toads; Caudata: newts and salamanders). Here we use museum collections to determine, to our knowledge for the first time, whether myxozoans also exploit the third amphibian order (Gymnophiona: caecilians). Caecilians are a poorly known group of limbless amphibians, the ecologies of which range from aquatic to fully terrestrial. We examined 12 caecilian species in seven families (148 individuals total) characterised by a diversity of ecologies and life histories. Using morphological and molecular surveys, we discovered the presence of the myxozoan Cystodiscus axonis in two South American species (one of seven examined families) of aquatic caecilians - Typhlonectes natans and Typhlonectes compressicauda. All infected caecilians had been maintained in captivity in the United Kingdom prior to their preservation. Cystodiscus axonis is known from several Australian frog species and its presence in caecilians indicates a capacity for infecting highly divergent amphibian hosts. This first known report of myxozoan infections in caecilians provides evidence of a broad geographic and host range. However, the source of these infections remains unknown and could be related to exposure in South America, the U.K. or to conditions in captivity. Copyright © 2016 Australian Society for Parasitology Inc. All rights reserved.

  3. Wideband Low Noise Amplifiers Exploiting Thermal Noise Cancellation

    NARCIS (Netherlands)

    Bruccoleri, F.; Klumperink, Eric A.M.; Nauta, Bram

    2005-01-01

    Low Noise Amplifiers (LNAs) are commonly used to amplify signals that are too weak for direct processing for example in radio or cable receivers. Traditionally, low noise amplifiers are implemented via tuned amplifiers, exploiting inductors and capacitors in resonating LC-circuits. This can render

  4. Human trafficking for labour exploitation: Interpreting the crime

    NARCIS (Netherlands)

    Coster van Voorhout, J.E.B.

    2007-01-01

    The definition of human trafficking for labour exploitation, as follows from the European Council Framework Decision, proves to be unclear. Literal interpretation does not suffice, because it does not clarify all elements of what is deemed to be criminal behaviour, and hermeneutical interpretation

  5. Efficient Depth Map Compression Exploiting Segmented Color Data

    DEFF Research Database (Denmark)

    Milani, Simone; Zanuttigh, Pietro; Zamarin, Marco

    2011-01-01

    performances is still an open research issue. This paper presents a novel compression scheme that exploits a segmentation of the color data to predict the shape of the different surfaces in the depth map. Then each segment is approximated with a parameterized plane. In case the approximation is sufficiently...

  6. Bats track and exploit changes in insect pest populations

    Science.gov (United States)

    The role of bats or any generalist predator in suppressing prey populations depends on the predator’s ability to exploit available prey in space and time. Using a qPCR faecal DNA assay, we document significant association between numbers of Brazilian free-tailed bats (Tadarida brasiliensis) consumin...

  7. Describing Data Format Exploits Using Bitstream Segment Graphs

    NARCIS (Netherlands)

    Hartle, Michael; Schumann, Daniel; Botchak, Arsene; Tews, Erik; Mühlhäuser, Max

    2008-01-01

    Exploits based on data processing bugs are delivered through crafted data that seems to follow a data format, yet is altered in some way to trigger a specific bug during processing, eg. in order to execute contained malicious code. Decomposing crafted data according to the purported data format and

  8. Exploiting Patient Labour at Kew Cottages, Australia, 1887-1950

    Science.gov (United States)

    Monk, Lee-Ann

    2010-01-01

    This article examines the exploitation of patient labour at Kew Cottages, Australia's first purpose-built state institution for people with learning disabilities. Analysing historical evidence for the period 1887-1950 shows that unpaid patient labour contributed significantly to the economy of the Cottages and so to the government department of…

  9. Exploiting serological data to understand the epidemiology of foot ...

    African Journals Online (AJOL)

    Exploiting serological data to understand the epidemiology of foot-and-mouth disease virus serotypes circulating in Libya. Ibrahim Eldaghayes, Abdunaser Dayhum, Abdulwahab Kammon, Monier Sharif, Giancarlo Ferrari, Christianus Bartels, Keith Sumption, Donald P. King, Santina Grazioli, Emiliana Brocchi ...

  10. Open pit coal exploitation viability. Margarita mine. Case of study

    International Nuclear Information System (INIS)

    Veloza, Julia; Molina, Jorge; Mejia, Humberto

    2006-01-01

    This paper provides an analysis of financial viability, planning and design for the new coal open pit exploitation for La Margarita mine, with coal-resources estimated on 440.139,7 ton. Dimension, design and economic evaluation were possible by three exploitation methods: (multiple bench, open cast contour, and terraces). Net present values (NVP) were calculated: $c 817,5; $c 518,5 and $c 645,2 respectively for each method (given in million current Colombian pesos $. $c 2380 are equivalent to $us 1) and rate of return (ROR) 78,33%; 34,0% and 38,62% respectively for each method. These indicators served as a parameter to choose the multiple bench method, which should be recalculated because it was necessary to work jointly with two pits and making feasible the project. in addition a general environmental evaluation was done, which is vital for the exploitation. Important impacts on the flower, animals, air, water were found, and measures of control, prevention and mitigation were stated. it is expected that this paper can be useful as a technical-economical support for the development of the open pit exploitation in the margarita mine

  11. Exploiting wild relatives of S. lycopersicum for quality traits

    NARCIS (Netherlands)

    Víquez Zamora, A.M.

    2015-01-01

    Exploiting wild relatives of S. lycopersicum for quality traits Ana Marcela Víquez Zamora Tomatoes are consumed worldwide and became a model for crop plant research. A part of the research aims at expanding genetic diversity in tomato; this can be done by incorporating

  12. Geographical aspects of exploitation of nuclear energy in Europe

    International Nuclear Information System (INIS)

    Kurucova, S.

    2007-05-01

    The topic of exploitation of nuclear energy is becoming increasingly actual in the present time in connection with frequently discussed question of 'renaissance of nuclear energetics'. The work is aimed at research of geographical aspects of exploitation of nuclear energy for military and civil purposes on the territory of Europe. The base of work represents the analysis of theoretical aspects of research of energy, mainly of nuclear energy. The work examines the historical development of exploitation of nuclear energy since its discovery, through development of military nuclear industry in Europe, big attention is paid to spreading of nuclear energetics on the territory of Europe from its beginnings up to the present time. The main part of the work represents the analysis of the present situation of exploitation of nuclear energy for civil purposes in Europe. The attention is paid to so-called nuclear fuel cycle as complex chain of several reciprocally interconnected operations of nuclear fuel treatment. The monitoring of spatial relations among individual countries within their nuclear fuel cycles is emphasised. The analysis of historical development and of the present state of nuclear energetics finished up in the outline of the perspectives of its further development in Europe. The analysis of the tendencies of evolution of world energetic economy mentions on the trend of growth of energy consumption in the world and Europe, as well as on the important position of nuclear energy in the structure of energy sources. Summary in English language is included. (author)

  13. Exploitation of Free Markets and Globalization to Finance Terrorists

    Science.gov (United States)

    2008-09-01

    is their capability to exploit the black market peso exchange or the international foreign exchange arbitrage . Under the scenario of a weak U.S...appears legitimate. By using intermediaries or legitimate businesses, the financial markets are wide open for terrorists to hedge funds and

  14. Exploitation of commercial remote sensing images: reality ignored?

    Science.gov (United States)

    Allen, Paul C.

    1999-12-01

    The remote sensing market is on the verge of being awash in commercial high-resolution images. Market estimates are based on the growing numbers of planned commercial remote sensing electro-optical, radar, and hyperspectral satellites and aircraft. EarthWatch, Space Imaging, SPOT, and RDL among others are all working towards launch and service of one to five meter panchromatic or radar-imaging satellites. Additionally, new advances in digital air surveillance and reconnaissance systems, both manned and unmanned, are also expected to expand the geospatial customer base. Regardless of platform, image type, or location, each system promises images with some combination of increased resolution, greater spectral coverage, reduced turn-around time (request-to- delivery), and/or reduced image cost. For the most part, however, market estimates for these new sources focus on the raw digital images (from collection to the ground station) while ignoring the requirements for a processing and exploitation infrastructure comprised of exploitation tools, exploitation training, library systems, and image management systems. From this it would appear the commercial imaging community has failed to learn the hard lessons of national government experience choosing instead to ignore reality and replicate the bias of collection over processing and exploitation. While this trend may be not impact the small quantity users that exist today it will certainly adversely affect the mid- to large-sized users of the future.

  15. Human trafficking and exploitation: A global health concern.

    Directory of Open Access Journals (Sweden)

    Cathy Zimmerman

    2017-11-01

    Full Text Available In this collection review, Cathy Zimmerman and colleague introduce the PLOS Medicine Collection on Human Trafficking, Exploitation and Health, laying out the magnitude of the global trafficking problem and offering a public health policy framework to guide responses to trafficking.

  16. Six scenarios of exploiting an ontology based, mobilized learning environment

    NARCIS (Netherlands)

    Kismihók, G.; Szabó, I.; Vas, R.

    2012-01-01

    In this article, six different exploitation possibilities of an educational ontology based, mobilized learning management system are presented. The focal point of this system is the educational ontology model. The first version of this educational ontology model serves as a foundation for curriculum

  17. Risk assessment by dynamic representation of vulnerability, exploitation, and impact

    Science.gov (United States)

    Cam, Hasan

    2015-05-01

    Assessing and quantifying cyber risk accurately in real-time is essential to providing security and mission assurance in any system and network. This paper presents a modeling and dynamic analysis approach to assessing cyber risk of a network in real-time by representing dynamically its vulnerabilities, exploitations, and impact using integrated Bayesian network and Markov models. Given the set of vulnerabilities detected by a vulnerability scanner in a network, this paper addresses how its risk can be assessed by estimating in real-time the exploit likelihood and impact of vulnerability exploitation on the network, based on real-time observations and measurements over the network. The dynamic representation of the network in terms of its vulnerabilities, sensor measurements, and observations is constructed dynamically using the integrated Bayesian network and Markov models. The transition rates of outgoing and incoming links of states in hidden Markov models are used in determining exploit likelihood and impact of attacks, whereas emission rates help quantify the attack states of vulnerabilities. Simulation results show the quantification and evolving risk scores over time for individual and aggregated vulnerabilities of a network.

  18. Indicators of Nuclear safety and exploitation in ANAV

    International Nuclear Information System (INIS)

    Quintana Prieto, M.; Jorda Alcove, M.

    2013-01-01

    The use of indicators by ANAV plants, aims to be a tool to facilitate the assessment of the behaviour of the plants nuclear over a specific time period. The following are and are they explain those related to Nuclear safety and exploitation.

  19. Exploiting Elementary Landscapes for TSP, Vehicle Routing and Scheduling

    Science.gov (United States)

    2015-09-03

    similar mathematical foundation to enable gradient descent methods for discrete combinatorial optimization problems. We are also generalizing our prior...research has exploited statistical and mathematical properties of elementary landscapes to develop new gradient methods for combinatorial optimization... mathematically methods to more automatically identify elementary landscapes. If a combinatorial optimization problem is a superposition of elemen

  20. 77 FR 36491 - Request for Information Regarding Senior Financial Exploitation

    Science.gov (United States)

    2012-06-19

    ... BUREAU OF CONSUMER FINANCIAL PROTECTION [Docket CFPB-2012-0018] Request for Information Regarding Senior Financial Exploitation AGENCY: Bureau of Consumer Financial Protection. ACTION: Request for Information. SUMMARY: Section 1013(g)(1) of the Dodd-Frank Wall Street Reform and Consumer Protection Act of...

  1. Features for Exploiting Black-Box Optimization Problem Structure

    DEFF Research Database (Denmark)

    Tierney, Kevin; Malitsky, Yuri; Abell, Tinus

    2013-01-01

    landscape of BBO problems and show how an algorithm portfolio approach can exploit these general, problem indepen- dent features and outperform the utilization of any single minimization search strategy. We test our methodology on data from the GECCO Workshop on BBO Benchmarking 2012, which contains 21...

  2. Assisting children born of sexual exploitation and abuse

    Directory of Open Access Journals (Sweden)

    Lauren Rumble

    2007-01-01

    Full Text Available The UN Secretary-General has issued a strategy tosupport victims of sexual exploitation and abuse by UNstaff. It includes a controversial proposal to introduceDNA sampling for all UN staff. Unless this suggestionis adopted, an important opportunity to implementa truly survivor-centred approach may be lost.

  3. Beyond the Bravado: Sex Roles and the Exploitive Male.

    Science.gov (United States)

    Taubman, Stan

    1986-01-01

    Examines the tendency of men to engage in domestic violence and sexual exploitation and presents male sex-role acquisition as a process of psychosocial violence against young boys, which creates a sense of shame, powerlessness, self-alienation, isolation from others, and retaliatory rage and inhibits capacities for intimacy and mutuality.…

  4. Grooming Cybervictims: The Psychosocial Effects of Online Exploitation for Youth.

    Science.gov (United States)

    Berson, Ilene R.

    2003-01-01

    Presents an overview of the benefits and risks of Web-based interactions for youth. Discusses, as an illustrative example, the psychosocial effects of online "grooming" practices that are designed to lure and exploit children by enticing them, typically in a nonsexual way, toward a sexual encounter. Suggests constructive solutions and a…

  5. A Randomized Controlled Trial on the Efficacy and Safety of a New Crosslinked Hyaluronan Gel in Reducing Adhesions after Gynecologic Laparoscopic Surgeries.

    Science.gov (United States)

    Liu, Chongdong; Lu, Qi; Zhang, Zhiqiang; Xue, Min; Zhang, Youzhong; Zhang, Yi; Wang, Huilan; Li, Huajun; Zhou, Yingfang; Zhang, Zhenyu; Li, Wei

    2015-01-01

    To evaluate the safety and efficacy of a new crosslinked hyaluronan (NCH) gel in reducing postoperative adhesions. Randomized controlled trial (Canadian Task Force classification I). Seven departments of obstetrics and gynecology in China. A total of 216 women scheduled for gynecologic laparoscopic surgery for primary removal of adhesions, myomas, ovarian cysts, or endometriotic cysts. Patients were randomized to receive either NCH gel or saline with 1:1 allocation. All patients were evaluated using a modified American Fertility Society (mAFS) scoring system for the incidence, extent, and severity of pre-existing and postoperative adhesions at the 10 anatomic sites of ovaries/tubes and at the expanded 23 or 24 anatomic sites throughout the abdominopelvic cavity by laparoscopy. A total of 215 randomized patients were treated with either saline solution (108 of 108) or NCH gel (107 of 108), composing the full analysis set (FAS), and 196 patients (94 of 108 in the saline control group and 102 of 108 in the NCH gel group) completed the entire study, composing the per protocol set (PPS). The postoperative incidence of moderate or severe adhesions evaluated at the 10 sites (the primary endpoint for efficacy) was 27.7% in the control group and 9.8% in the NCH gel group, a difference of 14.4% (95% confidence interval [CI], 2.6%-20.6%) in the PPS, and 37.0% in the control group and 14.0% in the NCH gel group, a difference of 20.0% (95% CI, 8.9%-26.8%) in the FAS. The postoperative incidence of moderate or severe adhesions evaluated at the 24 sites was also significantly lower in the NCH gel group compared with the control group (5.9% vs 14.9%; p = .036) in the PPS. Also in the PPS, the NCH gel group had significantly lower postoperative adhesion scores of severity, extent, and mAFS: 60.0%, 50.8%, and 76.9%, respectively (median scores of the 10 sites; p = .002) and 48.5%, 50.0%, and 72.2% (median scores of the 24 sites; p = .001) lower than those recorded in the control

  6. Host Defence to Pulmonary Mycosis

    Directory of Open Access Journals (Sweden)

    Christopher H Mody

    1999-01-01

    Full Text Available OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease.

  7. Intercultural Competence in Host Students?

    DEFF Research Database (Denmark)

    Egekvist, Ulla Egidiussen; Lyngdorf, Niels Erik; Du, Xiangyun

    2016-01-01

    Although substantial work in intercultural education has been done on the intercultural competences of mobile students engaging in international study visits, there is a need to explore intercultural competences in host students. This chapter seeks to answer questions about the challenges...

  8. Host Event Based Network Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Jonathan Chugg

    2013-01-01

    The purpose of INL’s research on this project is to demonstrate the feasibility of a host event based network monitoring tool and the effects on host performance. Current host based network monitoring tools work on polling which can miss activity if it occurs between polls. Instead of polling, a tool could be developed that makes use of event APIs in the operating system to receive asynchronous notifications of network activity. Analysis and logging of these events will allow the tool to construct the complete real-time and historical network configuration of the host while the tool is running. This research focused on three major operating systems commonly used by SCADA systems: Linux, WindowsXP, and Windows7. Windows 7 offers two paths that have minimal impact on the system and should be seriously considered. First is the new Windows Event Logging API, and, second, Windows 7 offers the ALE API within WFP. Any future work should focus on these methods.

  9. Visualization of Host-Polerovirus Interaction Topologies Using Protein Interaction Reporter Technology.

    Science.gov (United States)

    DeBlasio, Stacy L; Chavez, Juan D; Alexander, Mariko M; Ramsey, John; Eng, Jimmy K; Mahoney, Jaclyn; Gray, Stewart M; Bruce, James E; Cilia, Michelle

    2016-02-15

    reporter (PIR) technology to illustrate how viruses exploit host proteins during plant infection. PIR technology enabled our team to precisely describe the sites of functional virus-virus, virus-host, and host-host protein interactions using a mass spectrometry analysis that takes just a few hours. Applications of PIR technology in host-pathogen interactions will enable researchers studying recalcitrant pathogens, such as animal pathogens where host proteins are incorporated directly into the infectious agents, to investigate how proteins interact during infection and transmission as well as develop new tools for interdiction and therapy. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Disentangling the influence of parasite genotype, host genotype and maternal environment on different stages of bacterial infection in Daphnia magna.

    Science.gov (United States)

    Hall, Matthew D; Ebert, Dieter

    2012-08-22

    Individuals naturally vary in the severity of infectious disease when exposed to a parasite. Dissecting this variation into genetic and environmental components can reveal whether or not this variation depends on the host genotype, parasite genotype or a range of environmental conditions. Complicating this task, however, is that the symptoms of disease result from the combined effect of a series of events, from the initial encounter between a host and parasite, through to the activation of the host immune system and the exploitation of host resources. Here, we use the crustacean Daphnia magna and its parasite Pasteuria ramosa to show how disentangling genetic and environmental factors at different stages of infection improves our understanding of the processes shaping infectious disease. Using compatible host-parasite combinations, we experimentally exclude variation in the ability of a parasite to penetrate the host, from measures of parasite clearance, the reduction in host fecundity and the proliferation of the parasite. We show how parasite resistance consists of two components that vary in environmental sensitivity, how the maternal environment influences all measured aspects of the within-host infection process and how host-parasite interactions following the penetration of the parasite into the host have a distinct temporal component.

  11. Escalation of a coevolutionary arms race through host rejection of brood parasitic young.

    Science.gov (United States)

    Langmore, Naomi E; Hunt, Sarah; Kilner, Rebecca M

    2003-03-13

    Cuckoo nestlings that evict all other young from the nest soon after hatching impose a high reproductive cost on their hosts. In defence, hosts have coevolved strategies to prevent brood parasitism. Puzzlingly, they do not extend beyond the egg stage. Thus, hosts adept at recognizing foreign eggs remain vulnerable to exploitation by cuckoo nestlings. Here we show that the breach of host egg defences by cuckoos creates a new stage in the coevolutionary cycle. We found that defences used during the egg-laying period by host superb fairy-wrens (Malurus cyaneus) are easily evaded by the Horsfield's bronze-cuckoo (Chrysococcyx basalis), a specialist fairy-wren brood parasite. However, although hosts never deserted their own broods, they later abandoned 40% of nests containing a lone Horsfield's bronze-cuckoo nestling, and 100% of nests with a lone shining bronze-cuckoo nestling (Chrysococcyx lucidus), an occasional fairy-wren brood parasite. Our experiments demonstrate that host discrimination against evictor-cuckoo nestlings is possible, and suggest that it has selected for the evolution of nestling mimicry in bronze-cuckoos.

  12. Location of Host and Host Habitat by Fruit Fly Parasitoids

    Directory of Open Access Journals (Sweden)

    Pascal Rousse

    2012-11-01

    Full Text Available Augmentative releases of parasitoids may be a useful tool for the area-wide management of tephritid pests. The latter are parasitized by many wasp species, though only a few of them are relevant for augmentative biocontrol purposes. To date, nearly all the actual or potential biocontrol agents for such programs are egg or larval Opiinae parasitoids (Hymenoptera: Braconidae. Here, we review the literature published on their habitat and host location behavior, as well as the factors that modulate this behavior, which is assumed to be sequential; parasitoids forage first for the host habitat and then for the host itself. Parasitoids rely on chemical, visual, and mechanical stimuli, often strongly related to their ecology. Behavioral modulation factors include biotic and abiotic factors including learning, climatic conditions and physiological state of the insect. Finally, conclusions and perspectives for future research are briefly highlighted. A detailed knowledge of this behavior may be very useful for selecting the release sites for both inundative/augmentative releases of mass-reared parasitoids and inoculative releases for classical biocontrol.

  13. Endophytes: exploitation as a tool in plant protection

    Directory of Open Access Journals (Sweden)

    Devanushi Dutta

    2014-10-01

    Full Text Available Endophytes are symptomless fungal or bacterial microorganisms found in almost all living plant species reported so far. They are the plant-associated microbes that form symbiotic association with their host plants by colonizing the internal tissues, which has made them valuable for agriculture as a tool in improving crop performance. Many fungal endophytes produce secondary metabolites such as auxin, gibberellin etc that helps in growth and development of the host plant. Some of these compounds are antibiotics having antifungal, antibacterial and insecticidal properties, which strongly inhibit the growth of other microorganisms, including plant pathogens. This article reviews the endophyte isolated from different plants, mode of endophytic infection and benefits derived by the host plant as a result of endophytism.

  14. Hosting the first EDRS payload

    Science.gov (United States)

    Poncet, D.; Glynn, S.; Heine, F.

    2017-11-01

    The European Data Relay System (EDRS) will provide optical and microwave data relay services between Low Earth Orbit (LEO) satellites at altitudes up to 2000 km and the ground through geostationary (GEO) satellite nodes. Currently, two such nodes have been procured as part of a Public Private Partnership (PPP) between Astrium (now Airbus Defence and Space) and ESA. The first node (EDRS-A) is a hosted payload embarked upon the Eutelsat 9B satellite and scheduled for launch in early 2015.

  15. Host thin films incorporating nanoparticles

    Science.gov (United States)

    Qureshi, Uzma

    The focus of this research project was the investigation of the functional properties of thin films that incorporate a secondary nanoparticulate phase. In particular to assess if the secondary nanoparticulate material enhanced a functional property of the coating on glass. In order to achieve this, new thin film deposition methods were developed, namely use of nanopowder precursors, an aerosol assisted transport technique and an aerosol into atmospheric pressure chemical vapour deposition system. Aerosol assisted chemical vapour deposition (AACVD) was used to deposit 8 series of thin films on glass. Five different nanoparticles silver, gold, ceria, tungsten oxide and zinc oxide were tested and shown to successfully deposit thin films incorporating nanoparticles within a host matrix. Silver nanoparticles were synthesised and doped within a titania film by AACVD. This improved solar control properties. A unique aerosol assisted chemical vapour deposition (AACVD) into atmospheric pressure chemical vapour deposition (APCVD) system was used to deposit films of Au nanoparticles and thin films of gold nanoparticles incorporated within a host titania matrix. Incorporation of high refractive index contrast metal oxide particles within a host film altered the film colour. The key goal was to test the potential of nanopowder forms and transfer the suspended nanopowder via an aerosol to a substrate in order to deposit a thin film. Discrete tungsten oxide nanoparticles or ceria nanoparticles within a titanium dioxide thin film enhanced the self-cleaning and photo-induced super-hydrophilicity. The nanopowder precursor study was extended by deposition of zinc oxide thin films incorporating Au nanoparticles and also ZnO films deposited from a ZnO nanopowder precursor. Incorporation of Au nanoparticles within a VO: host matrix improved the thermochromic response, optical and colour properties. Composite VC/TiC and Au nanoparticle/V02/Ti02 thin films displayed three useful

  16. Annexe 3. Constitution d'une exploitation à Homs

    OpenAIRE

    2015-01-01

    ‘Abd al-Laṭīf, né en 1925, est jardinier à Horns. Il exploite avec son fils aîné et l'aide de deux de ses petits-fils un jardin de quelques 35 dunum (3,5 hectares) situé dans le zūr al-Ǧdīdeh, secteur central de la zone agricole. Cette grande exploitation, constituée de plusieurs parcelles ayant différents statuts, est en partie le produit d'une histoire familiale dont je voudrais présenter ici brièvement les principaux aspects. Figure 50 – Alliances matrimoniales entre la lignée de ‘Abbās e...

  17. Design and Exploitation Problems of Drill String in Directional Drilling

    Directory of Open Access Journals (Sweden)

    Bednarz Stanislaw

    2004-09-01

    Full Text Available Drill string design for directional drilling requires accounting for a number of factors. First, types and expected values of loads should be determined. Then, elements of the drill string should be so selected as to enable realization of the plan at specified loads. Some of additional factors, e. g. purchase, exploitation cost, geological conditions in the bore-hole, washing of the bore-hole, stability, trajectory, rig parameters, accuracy of gauges, pumps parameters remain in conflict. Drill pipes are made of rolled pipes, upset and welded with tool joints to 9,5 m long; the shorter ones can be made of hot forged rods. Exploitation requirements, being a result of practical experience supported by theoretical and laboratory analyses should be a part of syllabuses of technical staff educational programs. Apart from designing the string, it is also vital to lower the risk of a drilling failure. The significance of these aspects seems to be unquestionable.

  18. Environmental Impacts of Sand Exploitation. Analysis of Sand Market

    Directory of Open Access Journals (Sweden)

    Marius Dan Gavriletea

    2017-06-01

    Full Text Available Sand is an indispensable natural resource for any society. Despite society’s increasing dependence on sand, there are major challenges that this industry needs to deal with: limited sand resources, illegal mining, and environmental impact of sand mining. The purpose of this paper is twofold: to present an overview of the sand market, highlighting the main trends and actors for production, export and import, and to review the main environmental impacts associated with sand exploitation process. Based on these findings, we recommend different measures to be followed to reduce negative impacts. Sand mining should be done in a way that limits environmental damage during exploitation and restores the land after mining operations are completed.

  19. Analysis Of Damage Arising From Exploitation Of The Aircraft

    Directory of Open Access Journals (Sweden)

    Woźny Piotr

    2014-12-01

    Full Text Available During exploitation, due to a variety of reasons, aircrafts are damaged or suffer from different failures. In the process of operation, using appropriate methods of diagnosis, failure, damage, and relative deregulation of individual elements or units can be detected. For this purpose, one can apply a number of indirect diagnostic methods with the use of recorded diagnostic signals or a direct diagnosis with the use of non-destructive methods. The proper identification of the technical condition allows to determine the causes of irregularities and take actions aimed at preventing their occurrence. The article presents the types of exploitation damage of a multi-purpose aircraft. In addition, the criteria for the division of damage and research methods of the causes of damage are presented. Furthermore, an analysis of the scope of activities to be performed during the research of causes of damage to the aircraft is made.

  20. Target Localization with a Single Antenna via Directional Multipath Exploitation

    Directory of Open Access Journals (Sweden)

    Ali H. Muqaibel

    2015-01-01

    Full Text Available Target localization in urban sensing can benefit from angle dependency of the pulse shape at a radar receiver antenna. We propose a localization approach that utilizes the embedded directivity in ultra-wideband (UWB antennas to estimate target positions. A single radar unit sensing operation of indoor targets surrounded by interior walls is considered, where interior wall multipaths are exploited to provide target cross-range. This exploitation assumes resolvability of the multipath components, which is made possible by the virtue of using UWB radar signals. The proposed approach is most attractive when only few multipaths are detectable due to propagation obstructions or owing to low signal-to-noise ratios. Both simulated and experimental data are used to demonstrate the effectiveness of the proposed approach.

  1. Exploring, exploiting and evolving diversity of aquatic ecosystem models

    DEFF Research Database (Denmark)

    Janssen, Annette B G; Arhonditsis, George B.; Beusen, Arthur

    2015-01-01

    Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality...... management. In this spirit, numerous models have been developed since the 1970s. We set off to explore model diversity by making an inventory among 42 aquatic ecosystem modellers, by categorizing the resulting set of models and by analysing them for diversity. We then focus on how to exploit model diversity...... available through open-source policies, to standardize documentation and technical implementation of models, and to compare models through ensemble modelling and interdisciplinary approaches. We end with our perspective on how the field of aquatic ecosystem modelling might develop in the next 5–10 years...

  2. Exploiting Social Media Sensor Networks through Novel Data Fusion Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Kouri, Tina [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-11-01

    Unprecedented amounts of data are continuously being generated by sensors (“hard” data) and by humans (“soft” data), and this data needs to be exploited to its full potential. The first step in exploiting this data is determine how the hard and soft data are related to each other. In this project we fuse hard and soft data, using the attributes of each (e.g., time and space), to gain more information about interesting events. Next, we attempt to use social networking textual data to predict the present (i.e., predict that an interesting event is occurring and details about the event) using data mining, machine learning, natural language processing, and text analysis techniques.

  3. Do singing rock hyraxes exploit conspecific calls to gain attention?

    Directory of Open Access Journals (Sweden)

    Amiyaal Ilany

    Full Text Available Signal detection theory predicts that signals directed at distant or busy receivers in noisy backgrounds will begin with an alert component, in order to draw attention. Instead of an alert component, however, animals could get the same effect by using an external stimulus. Here we combined observations of free-living rock hyraxes (Procavia capensis with playback experiments to elucidate the circumstances under which males begin singing. We show that males sing following hyrax pup screams, which elicit a strong response from hyraxes within hearing distance, which are potential receivers. We hypothesize that singers enhance their singing display by exploiting the rarely emitted pup screams. To our knowledge, our findings are the first indication that animals may enhance signal reception by exploiting conspecifics' signals and the differential attention to these signals. We suggest that the utilization of external stimuli by signalers may be widespread, as an adaptive strategy for communication in complex environments.

  4. Exploitation of Natural Resources and the Public Sector in Greenland

    DEFF Research Database (Denmark)

    Nielsen, Søren Bo

    This paper considers the role of the public sector in future exploitation of non-renewable resources, especially minerals, in Greenland. The focus is on fiscal sustainability, principles for public sector involvement and the form of government take from mining activities. At present, the public...... budget in Greenland is nearly in balance, but at unchanged policies and standards public expenditures relative to GDP are bound to increase dramatically over the next decades due to population ageing. At the same time, the freezing of the block grant from Denmark implies a decrease in revenues relative...... to GDP. Hence, fiscal policy is quite far from being sustainable. Apart from a need for reforms, these facts also constrain the possible role of the public sector in future resource exploitation. In any case, the government should preferably adhere to strict principles when developing the mineral sector...

  5. Evaluating Maximum Wind Energy Exploitation in Active Distribution Networks

    DEFF Research Database (Denmark)

    Siano, Pierluigi; Chen, Peiyuan; Chen, Zhe

    2010-01-01

    The increased spreading of distributed and renewable generation requires moving towards active management of distribution networks. In this paper, in order to evaluate maximum wind energy exploitation in active distribution networks, a method based on a multi-period optimal power flow (OPF......) analysis is proposed. Active network management schemes such as coordinated voltage control, energy curtailment and power factor control are integrated in the method in order to investigate their impacts on the maximization of wind energy exploitation. Some case studies, using real data from a Danish...... distribution system, confirmed the effectiveness of the proposed method in evaluating the optimal applications of active management schemes to increase wind energy harvesting without costly network reinforcement for the connection of wind generation....

  6. Exploitation of the Virtual Worlds in Tourism and Tourism Education

    Directory of Open Access Journals (Sweden)

    Zejda Pavel

    2016-12-01

    Full Text Available Academics perceive a great potential of virtual worlds in various areas, including tourism and education. Efforts adapting the virtual worlds in practice are, however, still marginal. There is no clear definition of the virtual world. Therefore the author of this article attempts to provide one. The paper also focuses on the barriers of a wider exploitation of the virtual worlds and discusses the principles that might help to increase their potential in tourism area. One of the principles – gamification – favours a wider adaptation of the virtual worlds in tourism. Applying gamification principles provides visitors with some unique experiences while serving as a powerful marketing tool for institutions. The benefits of implementing tourism education activities based on cooperative principles set in an immersive environment of the virtual worlds are depicted afterwards. Finally, this paper includes successful case studies, which show advantages and drawbacks of some approaches in exploiting the virtual worlds in tourism and tourism education.

  7. The ESA Scientific Exploitation of Operational Missions element

    Science.gov (United States)

    Desnos, Yves-Louis; Regner, Peter; Delwart, Steven; Benveniste, Jerome; Engdahl, Marcus; Zehner, Claus; Mathieu, Pierre-Philippe; Bojkov, Bojan; Gascon, Ferran; Donlon, Craig; Davidson, Malcolm; Goryl, Philippe; Pinnock, Simon

    2015-04-01

    SEOM is a program element within the fourth period (2013-2017) of ESA's Earth Observation Envelope Programme (http://seom.esa.int/). The prime objective is to federate, support and expand the international research community that the ERS,ENVISAT and the Envelope programmes have built up over the last 25 years. It aims to further strengthen the leadership of the European Earth Observation research community by enabling them to extensively exploit future European operational EO missions. SEOM will enable the science community to address new scientific research that are opened by free and open access to data from operational EO missions. Based on community-wide recommendations for actions on key research issues, gathered through a series of international thematic workshops and scientific user consultation meetings, a work plan has been established and is approved every year by ESA Members States. The 2015 SEOM work plan is covering the organisation of three Science users consultation workshops for Sentinel1/3/5P , the launch of new R&D studies for scientific exploitation of the Sentinels, the development of open-source multi-mission scientific toolboxes, the organisation of advanced international training courses, summer schools and educational materials, as well as activities for promoting the scientific use of EO data. The first SEOM projects have been tendered since 2013 including the development of Sentinel toolboxes, advanced INSAR algorithms for Sentinel-1 TOPS data exploitation, Improved Atmospheric Spectroscopic data-base (IAS), as well as grouped studies for Sentinel-1, -2, and -3 land and ocean applications and studies for exploiting the synergy between the Sentinels. The status and first results from these SEOM projects will be presented and an outlook for upcoming SEOM studies will be given.

  8. Exploitation of the Virtual Worlds in Tourism and Tourism Education

    OpenAIRE

    Zejda Pavel; Zejda David

    2016-01-01

    Academics perceive a great potential of virtual worlds in various areas, including tourism and education. Efforts adapting the virtual worlds in practice are, however, still marginal. There is no clear definition of the virtual world. Therefore the author of this article attempts to provide one. The paper also focuses on the barriers of a wider exploitation of the virtual worlds and discusses the principles that might help to increase their potential in tourism area. One of the principles – g...

  9. Exploration and Exploitation of Victorian Science in Darwin's Reading Notebooks

    OpenAIRE

    Murdock, Jaimie; Allen, Colin; DeDeo, Simon

    2015-01-01

    Search in an environment with an uncertain distribution of resources involves a trade-off between exploitation of past discoveries and further exploration. This extends to information foraging, where a knowledge-seeker shifts between reading in depth and studying new domains. To study this decision-making process, we examine the reading choices made by one of the most celebrated scientists of the modern era: Charles Darwin. From the full-text of books listed in his chronologically-organized r...

  10. Exploiting Lexical Regularities in Designing Natural Language Systems.

    Science.gov (United States)

    1988-04-01

    ELEMENT. PROJECT. TASKN Artificial Inteligence Laboratory A1A4WR NTumet 0) 545 Technology Square Cambridge, MA 02139 Ln *t- CONTROLLING OFFICE NAME AND...RO-RI95 922 EXPLOITING LEXICAL REGULARITIES IN DESIGNING NATURAL 1/1 LANGUAGE SYSTENS(U) MASSACHUSETTS INST OF TECH CAMBRIDGE ARTIFICIAL INTELLIGENCE...oes.ary and ftdou.Ip hr Nl wow" L,2This paper presents the lexical component of the START Question Answering system developed at the MIT Artificial

  11. Television production, Funding Models and Exploitation of Content

    OpenAIRE

    Doyle, Gillian

    2016-01-01

    The rise of digital platforms has transformative implications for strategies of financing media production and for exploitation of the economic value in creative content. In the television industry, changes in technologies for distribution and the emergence of SVOD services such as Netflix are gradually shifting audiences and financial power away from broadcasters while at the same time creating unprecedented opportunities for programme-makers.  Drawing on findings from recent RCUK-funded res...

  12. Exploitation and Utilization of Oilfield Geothermal Resources in China

    OpenAIRE

    Shejiao Wang; Jiahong Yan; Feng Li; Junwen Hu; Kewen Li

    2016-01-01

    Geothermal energy is a clean, green renewable resource, which can be utilized for power generation, heating, cooling, and could effectively replace oil, gas, and coal. In recent years, oil companies have put more efforts into exploiting and utilizing geothermal energy with advanced technologies for heat-tracing oil gathering and transportation, central heating, etc., which has not only reduced resource waste, but also improved large-scale and industrial resource utilization levels, and has ac...

  13. Low-Level Exploitation Mitigation by Diverse Microservices

    OpenAIRE

    Otterstad , Christian; Yarygina , Tetiana

    2017-01-01

    Part 2: Microservices and Containers; International audience; This paper discusses a combination of isolatable microservices and software diversity as a mitigation technique against low-level exploitation; the effectiveness and benefits of such an architecture are substantiated. We argue that the core security benefit of microservices with diversity is increased control flow isolation. Additionally, a new microservices mitigation technique leveraging a security monitor service is introduced t...

  14. Organizational Ambidexterity : Balancing Exploitation and Exploration in Organizations

    OpenAIRE

    Yigit, Mert

    2013-01-01

    Purpose: This paper aims to investigate necessity of ambidexterity for organizations. The main interest of this thesis is to investigate why organizations should be ambidextrous and how organizations can reach ambidexterity under the pressure of limited resources and competitive market condition. Findings: This thesis explored relations and tensions between exploitation and exploration in organizational and individual aspects. Findings in the research show that communication skill of the subu...

  15. Exploiting Child-Robot Aesthetic Interaction for a Social Robot

    OpenAIRE

    Lee, Jae-Joon; Kim, Dae-Won; Kang, Bo-Yeong

    2012-01-01

    A social robot interacts and communicates with humans by using the embodied knowledge gained from interactions with its social environment. In recent years, emotion has emerged as a popular concept for designing social robots. Several studies on social robots reported an increase in robot sociability through emotional imitative interactions between the robot and humans. In this paper conventional emotional interactions are extended by exploiting the aesthetic theories that the sociability of ...

  16. Preventing Exploits Against Software of Uncertain Provenance (PEASOUP)

    Science.gov (United States)

    2015-05-01

    two common synchronization idioms: conditional variables (e.g., pthread_cond_wait()) and semaphores that count up and are used for signaling...delay prior to certain synchronization operations. The operations include thread creation, the first lock of each mutex (or decrement of a semaphore ...permissions are shared by all threads in the same process. • Synchronization Primitives . To exploit the race condition, two attacker-controlled

  17. Endangered Species and Natural Resource Exploitation: Extinction vs. Coexistence

    OpenAIRE

    Tsur, Yacov; Zemel, Amos

    1994-01-01

    The threat on the survival of animal species due to intensive use of natural resources is incorporated within resource management models, paying special attention to uncertainty regarding the conditions that lead to extinction. The manner in which the potential benefits forgone due to the species extinction (denoted extinction penalty) induce more conservative exploitation policies is studied in detail. When the extinction penalty is ignored, the optimal policy is to drive the resource stock ...

  18. An Equity Centered Management Approach to Exploiting Sport Employee Productivity

    OpenAIRE

    Schneider, Robert C.

    2017-01-01

    A primary goal ofsport organizations is to exploit employees’ abilities to their fullestcapacities. Sport managers who successfully maximize employee productivity willgreatly increase the chances of achieving the organization’s goals andobjectives. The full potential of sport employees’ abilities can be realizedthrough the application of the equity component grounded in Adam’s EquityTheory (Adams, 1963). Centered on the premise that the relationship betweensport manager and employer must be o...

  19. Exploiting GPUs in Virtual Machine for BioCloud

    OpenAIRE

    Jo, Heeseung; Jeong, Jinkyu; Lee, Myoungho; Choi, Dong Hoon

    2013-01-01

    Recently, biological applications start to be reimplemented into the applications which exploit many cores of GPUs for better computation performance. Therefore, by providing virtualized GPUs to VMs in cloud computing environment, many biological applications will willingly move into cloud environment to enhance their computation performance and utilize infinite cloud computing resource while reducing expenses for computations. In this paper, we propose a BioCloud system architecture that ena...

  20. Exploiting Innocuous Activity for Correlating Users Across Sites

    OpenAIRE

    Goga , Oana; Lei , Howard; Parthasarathi , Sree Hari Krishnan; Friedland , Gerald; Sommer , Robin; Teixeira , Renata

    2013-01-01

    International audience; We study how potential attackers can identify accounts on different social network sites that all belong to the same user, exploiting only innocuous activity that inherently comes with posted content. We examine three specific features on Yelp, Flickr, and Twitter: the geo-location attached to a user's posts, the timestamp of posts, and the user's writing style as captured by language models. We show that among these three features the location of posts is the most powe...