Science.gov

Sample records for adam melhem alishia

  1. What's an Adam's Apple?

    MedlinePlus

    ... Help White House Lunch Recipes What's an Adam's Apple? KidsHealth > For Kids > What's an Adam's Apple? Print A A A Text Size You're ... the throat. This is what's called an Adam's apple. Everyone's larynx grows during puberty, but a girl's ...

  2. Ansel Adams: early works

    NASA Astrophysics Data System (ADS)

    Throckmorton, Jodi

    2010-02-01

    Ansel Adams (1902-1984), photographer, musician, naturalist, explorer, critic, and teacher, was a giant in the field of landscape photography. In his images of the unspoiled Western landscape, he strove to capture the sublime: the transcendentalist concept that nature can generate the experience of awe for the viewer. Many viewers are familiar with the heroic, high-contrast prints on high-gloss paper that Adams made to order beginning in the 1970s; much less well known are the intimate prints that the artist crafted earlier in his career. This exhibition focuses on these masterful small prints from the 1920s into the 1950s. During this time period, Adams's printing style changed dramatically. The painterly, soft-focus, warm-toned style of the Parmelian Prints of the High Sierras from the 1920s evolved into the sharp-focus style of the f/64 school of photography that Adams co-founded in the 1930s with Edward Weston and Imogen Cunningham. After World War II, Adams opted for a cooler, higher-contrast look for his prints. Throughout the various styles in which he chose to work, Adams explored the power of nature and succeeded in establishing landscape photography as a legitimate form of modern art.

  3. Was Adam a Real Person?

    ERIC Educational Resources Information Center

    Lamoureux, Denis O.

    2011-01-01

    Belief in the historicity of Adam has been held firmly throughout the history of the church. In the light of modern biblical criticism and the evolutionary sciences, some conservative Christians are now questioning whether or not Adam was a real person. This paper argues that the existence of Adam in the opening chapters of scripture reflects an…

  4. The Adams Family

    ERIC Educational Resources Information Center

    Douven, Igor; Verbrugge, Sara

    2010-01-01

    According to Adams's Thesis, the acceptability of an indicative conditional sentence goes by the conditional probability of its consequent given its antecedent. We test, for the first time, whether this thesis is descriptively correct and show that it is not; in particular, we show that it yields the wrong predictions for people's judgments of the…

  5. ADAM Proteases and Gastrointestinal Function.

    PubMed

    Jones, Jennifer C; Rustagi, Shelly; Dempsey, Peter J

    2016-01-01

    A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment. ADAM10 and ADAM17 are the most studied members of the ADAM family in the gastrointestinal tract. ADAMs regulate many cellular processes associated with intestinal development, cell fate specification, and the maintenance of intestinal stem cell/progenitor populations. Several signaling pathway molecules that undergo ectodomain shedding by ADAMs [e.g., ligands and receptors from epidermal growth factor receptor (EGFR)/ErbB and tumor necrosis factor α (TNFα) receptor (TNFR) families] help drive and control intestinal inflammation and injury/repair responses. Dysregulation of these processes through aberrant ADAM expression or sustained ADAM activity is linked to chronic inflammation, inflammation-associated cancer, and tumorigenesis.

  6. ADAM Proteases and Gastrointestinal Function

    PubMed Central

    Jones, Jennifer C.; Rustagi, Shelly; Dempsey, Peter J.

    2016-01-01

    A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment. ADAM10 and ADAM17 are the most studied members of the ADAM family in the gastrointestinal tract. ADAMs regulate many cellular processes associated with intestinal development, cell fate specification, and the maintenance of intestinal stem cell/progenitor populations. Several signaling pathway molecules that undergo ectodomain shedding by ADAMs [e.g., ligands and receptors from epidermal growth factor receptor (EGFR)/ErbB and tumor necrosis factor α (TNFα) receptor (TNFR) families] help drive and control intestinal inflammation and injury/repair responses. Dysregulation of these processes through aberrant ADAM expression or sustained ADAM activity is linked to chronic inflammation, inflammation-associated cancer, and tumorigenesis. PMID:26667078

  7. [Hakim-Adams syndrome].

    PubMed

    Shamov, I A

    2015-01-01

    Hakim-Adams syndrome is little known, although quite common disease. The etiology is not fully clear. Pathogenetic mechanisms included the blockage of cerebrospinal fluid outflow along the upper lateral surface of the brain, development of hydrocephalus with the expansion of the brain ventricles while maintaining normotensive cerebrospinal fluid (CSF). Main manifestations are ataxia, apraxia, symptoms of dementia and urinary disturbances, up to incontinence. Diagnosis is based on clinical symptoms, exploratory lumbar and neuroimaging. Main treatment is ventriculoperitoneal (stomach) shunt placement for fluid drainage. Timely surgical intervention gives good results and improves quality of life of patients. PMID:26525816

  8. New Mathematical Dimensions: Adam's Story

    ERIC Educational Resources Information Center

    Manizade, Agida

    2009-01-01

    Adam, an 11th grader, was identified as gifted and accepted into a two week summer enrichment program. He signed up for "Geometry with Flash Programming." He had no prior programming experience but had a strong and healthy self-image as mathematics student. Although Adam had a positive attitude toward mathematics and saw himself as a successful…

  9. Changing Perceptions in "Adam Bede."

    ERIC Educational Resources Information Center

    Loges, Max L.

    From the very beginning of "Adam Bede," the idea of sight or perception is emphasized. Indeed by reference to a quotation from Wordsworth, George Eliot announces the purpose of the novel: to reveal clearly, to remove from the shade. While most of the characters in "Adam Bede" do not perceive events clearly and must have their erroneous opinions…

  10. The disintegrin-metalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer.

    PubMed

    Carl-McGrath, Stacy; Lendeckel, Uwe; Ebert, Matthias; Roessner, Albert; Röcken, Christoph

    2005-01-01

    The ADAMs (A disintegrin and metalloproteinase) are a family of cell-surface membrane glycoproteins, whose multidomain structure enables diverse roles in a wide range of cellular processes. Accumulating evidence associates an increased expression of individual ADAM family members with various types of cancer, and we investigated the possible involvement of ADAM9, 12 and 15 in the pathogenesis of gastric cancer (GC). Using immunohistochemistry and quantitative RT-PCR, we examined the transcription and expression pattern of ADAM9, 12, and 15 in GCs and the corresponding non-tumor tissue, and in GC cell lines (AGS, MKN45, MKN28, NCI-N87, KATOIII). All three ADAMs were found to be significantly upregulated in GC compared to non-neoplastic foveolar epithelium, with ADAM12 expression being higher in intestinal- than in diffuse-type tumors. In vitro proliferation assays were used to evaluate the effects of ADAM-specific antibodies on the growth of GC cell lines. The administration of anti-ADAM9 and anti-ADAM15 antibodies inhibited cell growth, whereas anti-ADAM12 enhanced the proliferation of the GC cell lines. ADAM9, 12 and 15 are implicated in the malignant growth of GC cells, perhaps via the interaction with adhesion molecules, or the proteolytic 'shedding' of signaling molecules and the consequent transactivation of their receptors, such as the epithelial growth factor receptor and its ligands. The resultant modulation of the tumor-host interface may contribute to the pathogenesis, development or progression of gastric cancer. PMID:15586220

  11. Evolution of Vertebrate Adam Genes; Duplication of Testicular Adams from Ancient Adam9/9-like Loci.

    PubMed

    Bahudhanapati, Harinath; Bhattacharya, Shashwati; Wei, Shuo

    2015-01-01

    Members of the disintegrin metalloproteinase (ADAM) family have important functions in regulating cell-cell and cell-matrix interactions as well as cell signaling. There are two major types of ADAMs: the somatic ADAMs (sADAMs) that have a significant presence in somatic tissues, and the testicular ADAMs (tADAMs) that are expressed predominantly in the testis. Genes encoding tADAMs can be further divided into two groups: group I (intronless) and group II (intron-containing). To date, tAdams have only been reported in placental mammals, and their evolutionary origin and relationship to sAdams remain largely unknown. Using phylogenetic and syntenic tools, we analyzed the Adam genes in various vertebrates ranging from fishes to placental mammals. Our analyses reveal duplication and loss of some sAdams in certain vertebrate species. In particular, there exists an Adam9-like gene in non-mammalian vertebrates but not mammals. We also identified putative group I and group II tAdams in all amniote species that have been examined. These tAdam homologues are more closely related to Adams 9 and 9-like than to other sAdams. In all amniote species examined, group II tAdams lie in close vicinity to Adam9 and hence likely arose from tandem duplication, whereas group I tAdams likely originated through retroposition because of their lack of introns. Clusters of multiple group I tAdams are also common, suggesting tandem duplication after retroposition. Therefore, Adam9/9-like and some of the derived tAdam loci are likely preferred targets for tandem duplication and/or retroposition. Consistent with this hypothesis, we identified a young retroposed gene that duplicated recently from Adam9 in the opossum. As a result of gene duplication, some tAdams were pseudogenized in certain species, whereas others acquired new expression patterns and functions. The rapid duplication of Adam genes has a major contribution to the diversity of ADAMs in various vertebrate species. PMID:26308360

  12. Evolution of Vertebrate Adam Genes; Duplication of Testicular Adams from Ancient Adam9/9-like Loci

    PubMed Central

    Wei, Shuo

    2015-01-01

    Members of the disintegrin metalloproteinase (ADAM) family have important functions in regulating cell-cell and cell-matrix interactions as well as cell signaling. There are two major types of ADAMs: the somatic ADAMs (sADAMs) that have a significant presence in somatic tissues, and the testicular ADAMs (tADAMs) that are expressed predominantly in the testis. Genes encoding tADAMs can be further divided into two groups: group I (intronless) and group II (intron-containing). To date, tAdams have only been reported in placental mammals, and their evolutionary origin and relationship to sAdams remain largely unknown. Using phylogenetic and syntenic tools, we analyzed the Adam genes in various vertebrates ranging from fishes to placental mammals. Our analyses reveal duplication and loss of some sAdams in certain vertebrate species. In particular, there exists an Adam9-like gene in non-mammalian vertebrates but not mammals. We also identified putative group I and group II tAdams in all amniote species that have been examined. These tAdam homologues are more closely related to Adams 9 and 9-like than to other sAdams. In all amniote species examined, group II tAdams lie in close vicinity to Adam9 and hence likely arose from tandem duplication, whereas group I tAdams likely originated through retroposition because of their lack of introns. Clusters of multiple group I tAdams are also common, suggesting tandem duplication after retroposition. Therefore, Adam9/9-like and some of the derived tAdam loci are likely preferred targets for tandem duplication and/or retroposition. Consistent with this hypothesis, we identified a young retroposed gene that duplicated recently from Adam9 in the opossum. As a result of gene duplication, some tAdams were pseudogenized in certain species, whereas others acquired new expression patterns and functions. The rapid duplication of Adam genes has a major contribution to the diversity of ADAMs in various vertebrate species. PMID:26308360

  13. Adam Smith and dependency.

    PubMed

    Ozler, Sule

    2012-06-01

    The focus of this paper is the works and life of Adam Smith, who is widely recognized as the father and founder of contemporary economics. Latent content analysis is applied to his seminal text in economics, An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The results reveal that Smith considers dependence on others a problem and sees the solution to this problem in impersonalized interdependence. In addition, his views on social dependency and personal dependency, reflected in his Lectures on Jurisprudence (1963) and The Theory of Moral Sentiments (1759), are analyzed. This analysis suggests a central tension between dependence and independence in Smith's writings. The personal dependency patterns he exhibited in his life, which also suggest a tension between dependence and independence, are identified through a reading of his biographies. Based on insights from psychoanalytic literature, this paper proposes that developing the ideas in the Wealth of Nations was part of Smith's creative solution to this tension. In particular, his solution to one individual's dependence on another was through a system of impersonalized interdependence. In other words, Smith defended against his personal dependence through his economic theorizing. PMID:22712591

  14. Adam Smith and dependency.

    PubMed

    Ozler, Sule

    2012-06-01

    The focus of this paper is the works and life of Adam Smith, who is widely recognized as the father and founder of contemporary economics. Latent content analysis is applied to his seminal text in economics, An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The results reveal that Smith considers dependence on others a problem and sees the solution to this problem in impersonalized interdependence. In addition, his views on social dependency and personal dependency, reflected in his Lectures on Jurisprudence (1963) and The Theory of Moral Sentiments (1759), are analyzed. This analysis suggests a central tension between dependence and independence in Smith's writings. The personal dependency patterns he exhibited in his life, which also suggest a tension between dependence and independence, are identified through a reading of his biographies. Based on insights from psychoanalytic literature, this paper proposes that developing the ideas in the Wealth of Nations was part of Smith's creative solution to this tension. In particular, his solution to one individual's dependence on another was through a system of impersonalized interdependence. In other words, Smith defended against his personal dependence through his economic theorizing.

  15. The ADAM environment and transputers

    NASA Technical Reports Server (NTRS)

    Kelly, B. D.; Stewart, J. M.; Mcnally, B. V.

    1992-01-01

    The ADAM environment is both used for data analysis by Starlink and for data acquisition by the UK-involved observatories in Australia, Hawaii, and the Canary Islands. ADAM was originally hosted under VAX/VMS but is now at an advanced stage of a Unix port. ADAM comprises a parameter system, hierarchical data system, noticeboard system, error handling system, and other components. Originally a multi-tasking single processor environment, it has been enhanced to a multiprocessor environment using local or wide area networking. The Royal Observatory Edinburgh is producing a transputer version of the ADAM kernel to allow instruments which make use of transputers for data acquisition/control to integrate more closely with the ADAM software running at the telescopes. Communication into the transputer system is based on Ethernet carrying TCP/IP, which eases development toward a network of mixed VMS/Unix/transputer Telescope systems. The transputer system is being applied to instruments under development for the UKIRT and JCMT telescopes.

  16. Franklin-Adams, John (1843-1912)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    English businessman and amateur astronomer; compiled the Franklin-Adams Photographic Atlas of Star Positions (1913). The Franklin-Adams camera was a 25 cm aperture, 10 degree field telescope, later re-erected in Johannesburg....

  17. ADAMS executive and operating system

    NASA Technical Reports Server (NTRS)

    Pittman, W. D.

    1981-01-01

    The ADAMS Executive and Operating System, a multitasking environment under which a variety of data reduction, display and utility programs are executed, a system which provides a high level of isolation between programs allowing them to be developed and modified independently, is described. The Airborne Data Analysis/Monitor System (ADAMS) was developed to provide a real time data monitoring and analysis capability onboard Boeing commercial airplanes during flight testing. It inputs sensor data from an airplane performance data by applying transforms to the collected sensor data, and presents this data to test personnel via various display media. Current utilization and future development are addressed.

  18. Children's Literature. Adams State College.

    ERIC Educational Resources Information Center

    Myers, Susan L.

    This is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The dual purpose of these modules is stated as follows: trying to understand children and their needs and becoming familiar with and developing criteria for evaluating children's literature. The objectives of the modules, which are…

  19. John Couch Adams, the astronomer.

    NASA Astrophysics Data System (ADS)

    Foster, N.

    1989-03-01

    The planet Neptune was discovered more than 140 years ago. The circumstances of the discovery gave rise to great controversy, and very nearly led to an international incident between Britain and France, but this was only one of John Couch Adams' many contributions to astronomical science.

  20. ADAM 12: A Putative Marker of Oligodendrogliomas?

    PubMed Central

    Kanakis, Dimitrios; Lendeckel, Uwe; Theodosiou, Paraskevi; Dobrowolny, Henrik; Mawrin, Christian; Keilhoff, Gerburg; Bukowska, Alicia; Dietzmann, Knut; Bogerts, Bernhard; Bernstein, Hans-Gert

    2013-01-01

    ADAM 12 (meltrin alpha) belongs to a large family of molecules, consisting of members with both disintegrin and metalloproteinase properties. ADAMs have been implicated in several cell physiological processes including cell adhesion, cell fusion, proteolysis and signalling. ADAM 12 is widely expressed, including skeletal muscle, testis, bone, intestine, heart and kidney. In addition, a variety of tumours show elevated expression of ADAM12; among them being breast-, colon-, gastric- and lung-carcinoma. As to the brain, ADAM 12 has been shown previously to be expressed in rat and human oligodendrocytes. However, little is known about the expression of this protease in brain tumours. This study demonstrates the presence of ADAM 12 in non-neoplastic oligodendroglial cells of normal human brain as well as in neoplastic oligodendroglia and minigemistocytes arising from four pure oligodendrogliomas and three mixed oligoastrocytomas. Double stainings revealed a notable preference of ADAM 12 for the oligodendroglial over astroglial components. The results of immunohistochemistry are in accordance with the results obtained from the RT-PCR, which further demonstrated a mild difference concerning the mRNA concentration of ADAM 12 between similar grades of eight astrocytomas and eight oligodendrogliomas (namely four astrocytomas grade II versus four oligodendrogliomas grade II and four astrocytomas grade III versus four oligodendrogliomas grade III). Both cellular immunostaining for ADAM 12 and ADAM 12 mRNA content decrease with higher histologic grade of the tumour. Surprisingly, the latter parameter (ADAM12 mRNA) showed a significant opposite correlation to the degree of histologic tumour malignancy. From our data showing that ADAM 12 is highly expressed in, but not restricted to, oligodendrogliomas, we conclude that ADAM 12 immunohistochemistry may be a helpful tool in the diagnosis of brain tumours. PMID:23324579

  1. ADAM 12: a putative marker of oligodendrogliomas?

    PubMed

    Kanakis, Dimitrios; Lendeckel, Uwe; Theodosiou, Paraskevi; Dobrowolny, Henrik; Mawrin, Christian; Keilhoff, Gerburg; Bukowska, Alicia; Dietzmann, Knut; Bogerts, Bernhard; Bernstein, Hans-Gert

    2013-01-01

    ADAM 12 (meltrin alpha) belongs to a large family of molecules, consisting of members with both disintegrin and metalloproteinase properties. ADAMs have been implicated in several cell physiological processes including cell adhesion, cell fusion, proteolysis and signalling. ADAM 12 is widely expressed, including skeletal muscle, testis, bone, intestine, heart and kidney. In addition, a variety of tumours show elevated expression of ADAM12; among them being breast-, colon-, gastric- and lung-carcinoma. As to the brain, ADAM 12 has been shown previously to be expressed in rat and human oligodendrocytes. However, little is known about the expression of this protease in brain tumours. This study demonstrates the presence of ADAM 12 in non-neoplastic oligodendroglial cells of normal human brain as well as in neoplastic oligodendroglia and minigemistocytes arising from four pure oligodendrogliomas and three mixed oligoastrocytomas. Double stainings revealed a notable preference of ADAM 12 for the oligodendroglial over astroglial components. The results of immunohistochemistry are in accordance with the results obtained from the RT-PCR, which further demonstrated a mild difference concerning the mRNA concentration of ADAM 12 between similar grades of eight astrocytomas and eight oligodendrogliomas (namely four astrocytomas grade II versus four oligodendrogliomas grade II and four astrocytomas grade III versus four oligodendrogliomas grade III). Both cellular immunostaining for ADAM 12 and ADAM 12 mRNA content decrease with higher histologic grade of the tumour. Surprisingly, the latter parameter (ADAM12 mRNA) showed a significant opposite correlation to the degree of histologic tumour malignancy. From our data showing that ADAM 12 is highly expressed in, but not restricted to, oligodendrogliomas, we conclude that ADAM 12 immunohistochemistry may be a helpful tool in the diagnosis of brain tumours.

  2. ADAM17, shedding, TACE as therapeutic targets.

    PubMed

    Rose-John, Stefan

    2013-05-01

    ADAM17 has been molecularly cloned as the enzyme responsible for cleavage of the transmembrane protein TNFα (TNFα converting enzyme, TACE). Later it was realized that ADAM17 was also responsible for the processing of cell adhesion proteins, cytokine and growth factor receptors and many ligands of the EGF receptor. Since TNFα is a target of anti-inflammatory therapies, it was speculated that inhibition of ADAM17 might be a therapeutic strategy in the treatment of inflammation or inflammation associated cancer. Meanwhile it has been recognized that ADAM17 governs many vital functions in the body and loss of ADAM17 leads to severe defects in the skin and to high susceptibility of the intestine to inflammation. Here I summarize data on the physiologic role of ADAM17 and the feasibility of specific blockade of this enzyme.

  3. ADAMS: AIRLAB data management system user's guide

    NASA Technical Reports Server (NTRS)

    Conrad, C. L.; Ingogly, W. F.; Lauterbach, L. A.

    1986-01-01

    The AIRLAB Data Management System (ADAMS) is an online environment that supports research at NASA's AIRLAB. ADAMS provides an easy to use interactive interface that eases the task of documenting and managing information about experiments and improves communication among project members. Data managed by ADAMS includes information about experiments, data sets produced, software and hardware available in AIRLAB as well as that used in a particular experiment, and an on-line engineer's notebook. The User's Guide provides an overview of the ADAMS system as well as details of the operations available within ADAMS. A tutorial section takes the user step-by-step through a typical ADAMS session. ADAMS runs under the VAX/VMS operating system and uses the ORACLE database management system and DEC/FMS (the Forms Management System). ADAMS can be run from any VAX connected via DECnet to the ORACLE host VAX. The ADAMS system is designed for simplicity, so interactions within the underlying data management system and communications network are hidden from the user.

  4. Adam receives Fred Whipple Award

    NASA Astrophysics Data System (ADS)

    McCord, Thomas B.; Adams, John B.

    John B. Adams was presented with the Fred Whipple Award at the AGU Fall Meeting in December in San Francisco, California. The award, established in 1989 by the Planetary Sciences Section, is presented to an individual who makes an outstanding contribution to the field of planetary science.In the beginning, scientists including Galileo studied the solar system by staring through a tube with glass elements called a telescope. This panchromatic instrument demonstrated existence and motion of objects and revealed features such as craters and clouds. However, it required approximately another 400 years to develop the physics and technology necessary to determine remotely the composition of these objects.

  5. ADAMs family and relatives in cardiovascular physiology and pathology.

    PubMed

    Zhang, Pu; Shen, Mengcheng; Fernandez-Patron, Carlos; Kassiri, Zamaneh

    2016-04-01

    A disintegrin and metalloproteinases (ADAMs) are a family of membrane-bound proteases. ADAM-TSs (ADAMs with thrombospondin domains) are a close relative of ADAMs that are present in soluble form in the extracellular space. Dysregulated production or function of these enzymes has been associated with pathologies such as cancer, asthma, Alzheimer's and cardiovascular diseases. ADAMs contribute to angiogenesis, hypertrophy and apoptosis in a stimulus- and cell type-dependent manner. Among the ADAMs identified so far (34 in mouse, 21 in human), ADAMs 8, 9, 10, 12, 17 and 19 have been shown to be involved in cardiovascular development or cardiomyopathies; and among the 19 ADAM-TSs, ADAM-TS1, 5, 7 and 9 are important in development of the cardiovascular system, while ADAM-TS13 can contribute to vascular disorders. Meanwhile, there remain a number of ADAMs and ADAM-TSs whose function in the cardiovascular system has not been yet explored. The current knowledge about the role of ADAMs and ADAM-TSs in the cardiovascular pathologies is still quite limited. The most detailed studies have been performed in other cell types (e.g. cancer cells) and organs (nervous system) which can provide valuable insight into the potential functions of ADAMs and ADAM-TSs, their mechanism of action and therapeutic potentials in cardiomyopathies. Here, we review what is currently known about the structure and function of ADAMs and ADAM-TSs, and their roles in development, physiology and pathology of the cardiovascular system.

  6. Asteroid shape modelling with ADAM

    NASA Astrophysics Data System (ADS)

    Viikinkoski, Matti; Kaasalainen, Mikko; Durech, Josef

    2015-08-01

    Technological advancements have made it possible to obtain highly detailed images of asteroids, yet 3-D shape reconstruction remains a challenge. Shape inversion is an ill-posed inverse problem as systematic errors, shadowing effects due to non-convex features, and the limitations of the imaging systems render the direct inversion impossible. Moreover, the coverage of one observation session alone is seldom sufficient for 3-D reconstruction, necessitating a method for the integration of widely different, complementary data sources into a coherent shape solution.We present a new 3-D shape reconstruction method for asteroid models. ADAM, an acronym for all-data asteroid modelling, is a general procedure for combining disk-resolved observational data into a shape model. ADAM handles all disk-resolved data in a uniform manner via 2-D Fourier Transform. Almost all disk-resolved data sources are supported: adaptive optics and other images, range-Doppler radar data, and thermal infrared interferometry.As case studies, we examine the shape of (41) Daphne using the adaptive optics images and photometry, and create a model of the asteroid 2000 ET70 from the range-Doppler radar images. Finally, we combine ALMA science verification data, adaptive optics images, occultations, and lightcurve data to study the shape of the large main-belt asteroid (3) Juno.

  7. Differential regional expression of multiple ADAMs during feather bud formation.

    PubMed

    Lin, Juntang; Luo, Jiankai; Redies, Christoph

    2011-09-01

    The expression of seven members of the ADAM family was investigated by in situ hybridization in the developing feather buds of chicken. The expression profiles of the ADAMs in the cells and tissues of the feather buds differ from each other. ADAM9, ADAM10, and ADAM17 are expressed in the epidermis of the feather bud, whereas ADAM23 expression is restricted to the bud crest, with a distribution similar to that of sonic hedgehog. ADAM13 is not only expressed in the epidermis, but also in restricted regions of the dermis. Both ADAM12 and ADAM22 are expressed in the dermis of the feather bud, with an opposite mediolateral and anteroposterior polarity. Furthermore, the mRNAs of all investigated ADAMs show regional differences in their expression, for example, in the neck and in the roots of the leg and wing. These results suggest that ADAMs play a variety of roles during avian feather bud formation.

  8. Cleavage Site Localization Differentially Controls Interleukin-6 Receptor Proteolysis by ADAM10 and ADAM17

    PubMed Central

    Riethmueller, Steffen; Ehlers, Johanna C.; Lokau, Juliane; Düsterhöft, Stefan; Knittler, Katharina; Dombrowsky, Gregor; Grötzinger, Joachim; Rabe, Björn; Rose-John, Stefan; Garbers, Christoph

    2016-01-01

    Limited proteolysis of the Interleukin-6 Receptor (IL-6R) leads to the release of the IL-6R ectodomain. Binding of the cytokine IL-6 to the soluble IL-6R (sIL-6R) results in an agonistic IL-6/sIL-6R complex, which activates cells via gp130 irrespective of whether the cells express the IL-6R itself. This signaling pathway has been termed trans-signaling and is thought to mainly account for the pro-inflammatory properties of IL-6. A Disintegrin And Metalloprotease 10 (ADAM10) and ADAM17 are the major proteases that cleave the IL-6R. We have previously shown that deletion of a ten amino acid long stretch within the stalk region including the cleavage site prevents ADAM17-mediated cleavage, whereas the receptor retained its full biological activity. In the present study, we show that deletion of a triple serine (3S) motif (Ser-359 to Ser-361) adjacent to the cleavage site is sufficient to prevent IL-6R cleavage by ADAM17, but not ADAM10. We find that the impaired shedding is caused by the reduced distance between the cleavage site and the plasma membrane. Positioning of the cleavage site in greater distance towards the plasma membrane abrogates ADAM17-mediated shedding and reveals a novel cleavage site of ADAM10. Our findings underline functional differences in IL-6R proteolysis by ADAM10 and ADAM17. PMID:27151651

  9. John Quincy Adams's rhetorical crusade for astronomy.

    PubMed

    Portolano, M

    2000-09-01

    Astronomy thrived in Europe during the early nineteenth century, but in the United States a utilitarian mind-set opposed it. John Quincy Adams's oratory in support of American astronomical discovery reached its peak during congressional debate over the Smithsonian Institution (1838-1846). During this debate Adams countered proposals to found a university with plans for an observatory. His addresses to congressional and public audiences about observatories and astronomy were intended to foster interest in the science and encourage the growing astronomical community in America. Although the U.S. Naval Observatory in Washington, D.C., was established before the Smithsonian debate ended, many considered Adams its political father. Adams composed his speeches on astronomy in a systematic manner, following neoclassical principles of rhetoric that he had taught at Harvard University. His speeches both in and outside of Congress show evidence of the rhetorical principles he conscientiously used in the service of astronomy.

  10. John Quincy Adams's rhetorical crusade for astronomy.

    PubMed

    Portolano, M

    2000-09-01

    Astronomy thrived in Europe during the early nineteenth century, but in the United States a utilitarian mind-set opposed it. John Quincy Adams's oratory in support of American astronomical discovery reached its peak during congressional debate over the Smithsonian Institution (1838-1846). During this debate Adams countered proposals to found a university with plans for an observatory. His addresses to congressional and public audiences about observatories and astronomy were intended to foster interest in the science and encourage the growing astronomical community in America. Although the U.S. Naval Observatory in Washington, D.C., was established before the Smithsonian debate ended, many considered Adams its political father. Adams composed his speeches on astronomy in a systematic manner, following neoclassical principles of rhetoric that he had taught at Harvard University. His speeches both in and outside of Congress show evidence of the rhetorical principles he conscientiously used in the service of astronomy. PMID:11143785

  11. ADAM: All-Data Asteroid Modeling

    NASA Astrophysics Data System (ADS)

    Viikinkoski, Matti; Kaasalainen, Mikko; Durech, Josef

    2015-02-01

    ADAM (All-Data Asteroid Modeling) models asteroid shape reconstruction from observations. Developed in MATLAB with core routines in C, its features include general nonconvex and non-starlike parametric 3D shape supports and reconstruction of asteroid shape from any combination of lightcurves, adaptive optics images, HST/FGS data, disk-resolved thermal images, interferometry, and range-Doppler radar images. ADAM does not require boundary contour extraction for reconstruction and can be run in parallel.

  12. PROTEOLYTIC PROCESSING OF DELTA-LIKE 1 BY ADAM PROTEASES*

    PubMed Central

    Dyczynska, Emilia; Sun, Danqiong; Yi, Haiqing; Sehara-Fujisawa, Atsuko; Blobel, Carl P.; Zolkiewska, Anna

    2009-01-01

    Delta-like 1 (Dll1) is a mammalian ligand for Notch receptors. Interactions between Dll1 and Notch in trans activate the Notch pathway, whereas Dll1 binding to Notch in cis inhibits Notch signaling. Dll1 undergoes proteolytic processing in its extracellular domain by ADAM10. In this work, we demonstrate that Dll1 represents a substrate for several other members of the ADAM family. In co-transfected cells, Dll1 is constitutively cleaved by ADAM12, and the N-terminal fragment of Dll1 is released to medium. ADAM12-mediated cleavage of Dll1 is cell density-dependent, takes place in cis orientation, and does not require the presence of the cytoplasmic domain of ADAM12. Full length Dll1, but not its N- or C-terminal proteolytic fragment, co-immunoprecipitates with ADAM12. By using a Notch reporter construct, we show that Dll1 processing by ADAM12 increases Notch signaling in a cell-autonomous manner. Furthermore, ADAM9 and ADAM17 have the ability to process Dll1. In contrast, ADAM15 does not cleave Dll1, although the two proteins still co-immunoprecipitate with each other. Asn353 present in the catalytic motif of ADAM12 and other Dll1-processing ADAMs, but absent in ADAM15, is necessary for Dll1 cleavage. Dll1 cleavage is reduced in ADAM9/12/15−/− mouse embryonic fibroblasts (MEFs), suggesting that the endogenous ADAM9 and/or ADAM12 present in wild type MEFs contribute to Dll1 processing. Finally, the endogenous Dll1 present in primary mouse myoblasts undergoes cleavage in confluent, differentiating myoblast cultures and this cleavage is decreased by ADAM12 siRNAs. Our findings expand the role of ADAM proteins in the regulation of Notch signaling. PMID:17107962

  13. A Conversation with Adam Heller.

    PubMed

    Heller, Adam; Cairns, Elton J

    2015-01-01

    Adam Heller, Ernest Cockrell Sr. Chair in Engineering Emeritus of the John J. McKetta Department of Chemical Engineering at The University of Texas at Austin, recalls his childhood in the Holocaust and his contributions to science and technology that earned him the US National Medal of Technology and Innovation in a conversation with Elton J. Cairns, Professor of Chemical and Biomolecular Engineering at the University of California, Berkeley. Dr. Heller, born in 1933, describes the enslavement of his father by Hungarians in 1942; the confiscation of his family's home, business, and all its belongings in 1944; and his incarceration in a brick factory with 18,000 Jews who were shipped by the Hungarians to be gassed by Germans in Auschwitz. Dr. Heller and his immediate family survived the Holocaust and arrived in Israel in 1945. He studied under Ernst David Bergmann at the Hebrew University, and then worked at Bell Laboratories and GTE Laboratories, where he headed Bell Lab's Electronic Materials Research Department. At GTE Laboratories, he built in 1966 the first neodymium liquid lasers and in 1973 with Jim Auborn conceived and engineered the lithium thionyl chloride battery, one of the first to be manufactured lithium batteries, which is still in use. After joining the faculty of engineering of The University of Texas at Austin, he cofounded with his son Ephraim Heller TheraSense, now a major part of Abbott Diabetes Care, which produced a microcoulometer that made the monitoring of glucose painless by accurately measuring the blood glucose concentration in 300 nL of blood. He also describes the electrical wiring of enzymes, the basis for Abbott's state-of-the-art continuous glucose monitoring system. He discusses his perspective of reducing the risk of catastrophic global warming in a wealth-accumulating, more-energy-consuming world and provides advice for students entering careers in science or engineering.

  14. A Conversation with Adam Heller.

    PubMed

    Heller, Adam; Cairns, Elton J

    2015-01-01

    Adam Heller, Ernest Cockrell Sr. Chair in Engineering Emeritus of the John J. McKetta Department of Chemical Engineering at The University of Texas at Austin, recalls his childhood in the Holocaust and his contributions to science and technology that earned him the US National Medal of Technology and Innovation in a conversation with Elton J. Cairns, Professor of Chemical and Biomolecular Engineering at the University of California, Berkeley. Dr. Heller, born in 1933, describes the enslavement of his father by Hungarians in 1942; the confiscation of his family's home, business, and all its belongings in 1944; and his incarceration in a brick factory with 18,000 Jews who were shipped by the Hungarians to be gassed by Germans in Auschwitz. Dr. Heller and his immediate family survived the Holocaust and arrived in Israel in 1945. He studied under Ernst David Bergmann at the Hebrew University, and then worked at Bell Laboratories and GTE Laboratories, where he headed Bell Lab's Electronic Materials Research Department. At GTE Laboratories, he built in 1966 the first neodymium liquid lasers and in 1973 with Jim Auborn conceived and engineered the lithium thionyl chloride battery, one of the first to be manufactured lithium batteries, which is still in use. After joining the faculty of engineering of The University of Texas at Austin, he cofounded with his son Ephraim Heller TheraSense, now a major part of Abbott Diabetes Care, which produced a microcoulometer that made the monitoring of glucose painless by accurately measuring the blood glucose concentration in 300 nL of blood. He also describes the electrical wiring of enzymes, the basis for Abbott's state-of-the-art continuous glucose monitoring system. He discusses his perspective of reducing the risk of catastrophic global warming in a wealth-accumulating, more-energy-consuming world and provides advice for students entering careers in science or engineering. PMID:26247288

  15. Epithelial cell ADAM17 activation by Helicobacter pylori: role of ADAM17 C-terminus and Threonine-735 phosphorylation.

    PubMed

    McClurg, Urszula L; Danjo, Kazuma; King, Harry O; Scott, Gina B; Robinson, Philip A; Crabtree, Jean E

    2015-03-01

    Helicobacter pylori transactivates the epidermal growth factor receptor (EGFR) on gastric epithelial cells via a signalling cascade involving a disintegrin and metalloprotease 17 (ADAM17) cleavage of membrane bound heparin binding-epidermal growth factor (HB-EGF). The effects of H. pylori on ADAM17 C-terminus in epithelial cells have been examined. Total cellular ADAM17 and surface expression of ADAM17 were significantly increased by H. pylori in AGS gastric epithelial cells. These changes were associated with ADAM17 C-terminal phosphorylation at T375 and S791. AGS cells lacking the ADAM17 C-terminal domain induced significantly attenuated cleavage of HB-EGF and were also unable to upregulate HB-EGF and EGFR transcripts to the same extent as cells expressing full length ADAM17. In mitotic unstimulated AGS and ADAM17 over-expressing AGS cells, ADAM17 was highly T735 phosphorylated indicating ADAM17 T735 phosphorylation is modified during the cell cycle. In conclusion, H. pylori induced ADAM17 C-terminal T735 and/or S791 phosphorylation in gastric epithelial cells are likely to be an important trigger inducing ADAM17 activation and shedding of HB-EGF leading to EGFR transactivation. ADAM17 over-expression in gastric cancer represents a potential target for therapeutic intervention.

  16. Women in History--Abigail Adams: Life, Accomplishments, and Ideas

    ERIC Educational Resources Information Center

    Kenan, Sharon K.

    2008-01-01

    This article profiles the life, accomplishments, and ideas of Abigail Adams. Born in 1944, Adams lacked a formal education, but she more than made up for that shortcoming with her love of reading, especially literature, and her interests in politics and events surrounding the young colonies. Adams was supportive of the advancement of women. She…

  17. Paraprofessional of the Year 2009: Tina Adams

    ERIC Educational Resources Information Center

    Berry, John N., III

    2009-01-01

    There is no doubt among the staff and managers at North Carolina State University (NCSU) Libraries, Raleigh, that advanced library technician Tina Adams deserves to be the winner of the "Library Journal's "Paraprofessional of the Year Award for 2009." "Certainly this library has never seen anyone like her before, not in my nine years on staff,"…

  18. Adam Smith and the Rhetoric of Style.

    ERIC Educational Resources Information Center

    Moran, Michael G.

    Historians of rhetoric have generally accepted the view that Adam Smith rejected the principles of classical rhetoric. However, while there can be no doubt that Smith greatly truncated the five classical arts of rhetoric (invention, arrangement, style, memory, and delivery) by reducing his concerns largely to style and arrangement, he did not…

  19. Adam Smith, Religion, and Tuition Tax Credits.

    ERIC Educational Resources Information Center

    Alexander, Kern

    1983-01-01

    Examines tuition tax credit programs in framework of Adam Smith's ideas on the economic impact of established churches. Finds that tuition tax credits would amount to state expenditures to relieve the financial burden of parochial school parents and would allow churches to invest commercially to maintain their charitable functions. (JW)

  20. ADAM "sequence" part II: hypothesis and speculation.

    PubMed

    Opitz, John M; Johnson, Dennis R; Gilbert-Barness, Enid F

    2015-03-01

    Noted for centuries in humans, a relatively hairless mammal [e.g., Hallero, 1766; Hohl, 1828 in Klunker, 2003], the so-called amniotic deformities, adhesions, mutilations (ADAM) sequence remains causally and pathogenetically incognito. In 1930 Streeter stated " apodictically" that no evidence has been found that intra-uterine amputation is due to amniotic bands or adhesions …" and that his 16 cases provided (histological) evidence for a "germinal origin." He concluded that an amniotic cord was "not an adhesion or inflammatory product but … an anomalous developmental structure and present from the outset." In survivors the "traces" of damaged limb-buds "reveal the scars of poor germ-plasm." In 1958, Willis, in dismissing the amniotic origin of the ADAM defects (or "Streeter" or "Simonart" bands) quoted Keith [1940] to the effect that "(a)mniotic adhesions … are always produced by … the fetus – as a result of dysplasia in foetal tissues. They are the result, not the cause, of foetal malformations." Streeter [1930] mentions a potential familial case (56-year-old man and his mother), not controlled by photographs or other records and concluded "that the (ADAM) deformity is not easily transmissible," but "due to the constitution of the germ-plasm." Torpin [1968] concluded, as apodictically as Streeter and Willis, that "… proof of amnion rupture without damage to the chorionic sac is no longer "in question." Considering Torpin's decades-long study of the ADAM phenomenon and review of 494 references (missing many) it is surprising that he does not discuss the relationship between the apparent ADAM defects and other, internal anomalies that maybe present in an affected fetus or infant not evidently caused by the amniotic disruptions, adhesions or mutilations, unless his mind was made up. Our review of these internal and other presumed primary malformations in ADAM is ongoing. However, on a preliminary basis, it seems likely to us that: (1) there is an increased

  1. ADAM "sequence" part II: hypothesis and speculation.

    PubMed

    Opitz, John M; Johnson, Dennis R; Gilbert-Barness, Enid F

    2015-03-01

    Noted for centuries in humans, a relatively hairless mammal [e.g., Hallero, 1766; Hohl, 1828 in Klunker, 2003], the so-called amniotic deformities, adhesions, mutilations (ADAM) sequence remains causally and pathogenetically incognito. In 1930 Streeter stated " apodictically" that no evidence has been found that intra-uterine amputation is due to amniotic bands or adhesions …" and that his 16 cases provided (histological) evidence for a "germinal origin." He concluded that an amniotic cord was "not an adhesion or inflammatory product but … an anomalous developmental structure and present from the outset." In survivors the "traces" of damaged limb-buds "reveal the scars of poor germ-plasm." In 1958, Willis, in dismissing the amniotic origin of the ADAM defects (or "Streeter" or "Simonart" bands) quoted Keith [1940] to the effect that "(a)mniotic adhesions … are always produced by … the fetus – as a result of dysplasia in foetal tissues. They are the result, not the cause, of foetal malformations." Streeter [1930] mentions a potential familial case (56-year-old man and his mother), not controlled by photographs or other records and concluded "that the (ADAM) deformity is not easily transmissible," but "due to the constitution of the germ-plasm." Torpin [1968] concluded, as apodictically as Streeter and Willis, that "… proof of amnion rupture without damage to the chorionic sac is no longer "in question." Considering Torpin's decades-long study of the ADAM phenomenon and review of 494 references (missing many) it is surprising that he does not discuss the relationship between the apparent ADAM defects and other, internal anomalies that maybe present in an affected fetus or infant not evidently caused by the amniotic disruptions, adhesions or mutilations, unless his mind was made up. Our review of these internal and other presumed primary malformations in ADAM is ongoing. However, on a preliminary basis, it seems likely to us that: (1) there is an increased

  2. Illnesses of the brain in John Quincy Adams.

    PubMed

    Paulson, George

    2004-12-01

    John Quincy Adams, the sixth and perhaps most scholarly American president, served courageously despite familial essential tremor, depression, and cerebrovascular disease. His cousin Samuel Adams and his father John Adams also had essential tremor, which the later called "quiveration". Alcoholism and depression affected several members of J.Q. Adams's family. Following his own time as president, J.Q. Adams returned to duty as the congressman who most assiduously fought slavery, a fight he continued even after he had suffered a major left hemispheric stroke. His fatal collapse in Congress, protesting the Mexican War, is legendary among the final illnesses of American statesmen. PMID:15545105

  3. Illnesses of the brain in John Quincy Adams.

    PubMed

    Paulson, George

    2004-12-01

    John Quincy Adams, the sixth and perhaps most scholarly American president, served courageously despite familial essential tremor, depression, and cerebrovascular disease. His cousin Samuel Adams and his father John Adams also had essential tremor, which the later called "quiveration". Alcoholism and depression affected several members of J.Q. Adams's family. Following his own time as president, J.Q. Adams returned to duty as the congressman who most assiduously fought slavery, a fight he continued even after he had suffered a major left hemispheric stroke. His fatal collapse in Congress, protesting the Mexican War, is legendary among the final illnesses of American statesmen.

  4. Non-MacAdam color discrimination ellipses

    NASA Astrophysics Data System (ADS)

    Goldstein, Peter

    2012-10-01

    MacAdam ellipses and the 1976 u'v' chromaticity space are commonly used in the illumination and LED industries. Delta E 2000 (ΔE) is the most up-to-date color difference metric endorsed by CIE and is more reliable than earlier metrics. This paper shows how the ΔE 2000 standard can be used to derive ellipses to be plotted in the well-known 1931 xy color space and examines the validity of MacAdam ellipses and the 1976 u'v' chromaticity space in terms of this metric. The 1976 u'v' chromaticity space is found, in quantitative terms, to be less uniform than the 1931 xy chromaticity space based on ΔE 2000. This paper recommends ΔE calculations as a quantitative tool, the proposed ellipses as a descriptive tool, and the total abandonment of the 1976 u'v' color space.

  5. Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain

    NASA Astrophysics Data System (ADS)

    Miller, Miles A.; Moss, Marcia L.; Powell, Gary; Petrovich, Robert; Edwards, Lori; Meyer, Aaron S.; Griffith, Linda G.; Lauffenburger, Douglas A.

    2015-10-01

    Dysregulation of ErbB-family signaling underlies numerous pathologies and has been therapeutically targeted through inhibiting ErbB-receptors themselves or their cognate ligands. For the latter, “decoy” antibodies have been developed to sequester ligands including heparin-binding epidermal growth factor (HB-EGF); however, demonstrating sufficient efficacy has been difficult. Here, we hypothesized that this strategy depends on properties such as ligand-receptor binding affinity, which varies widely across the known ErbB-family ligands. Guided by computational modeling, we found that high-affinity ligands such as HB-EGF are more difficult to target with decoy antibodies compared to low-affinity ligands such as amphiregulin (AREG). To address this issue, we developed an alternative method for inhibiting HB-EGF activity by targeting its cleavage from the cell surface. In a model of the invasive disease endometriosis, we identified A Disintegrin and Metalloproteinase 12 (ADAM12) as a protease implicated in HB-EGF shedding. We designed a specific inhibitor of ADAM12 based on its recombinant prodomain (PA12), which selectively inhibits ADAM12 but not ADAM10 or ADAM17. In endometriotic cells, PA12 significantly reduced HB-EGF shedding and resultant cellular migration. Overall, specific inhibition of ligand shedding represents a possible alternative to decoy antibodies, especially for ligands such as HB-EGF that exhibit high binding affinity and localized signaling.

  6. The dental health of President John Adams.

    PubMed

    Ring, Malvin E

    2004-01-01

    The oral health of George Washington has been widely studied and written about. Not so, however, with our second president, John Adams, whose dental health was apparently poor throughout his life. His pernicious habit of inducing vomiting to treat various bodily ills, coupled with a great love of sweets, led to the loss of his teeth, which he stubbornly refused to replace with dentures. When he was older, this led to his speech being so badly affected, that he could barely be understood.

  7. Shedding of collagen XVII/BP180 in skin depends on both ADAM10 and ADAM9.

    PubMed

    Franzke, Claus-Werner; Bruckner-Tuderman, Leena; Blobel, Carl P

    2009-08-28

    Collagen XVII is a transmembrane collagen and the major autoantigen of the autoimmune skin blistering disease bullous pemphigoid. Collagen XVII is proteolytically released from the membrane, and the pathogenic epitope harbors the cleavage site for its ectodomain shedding, suggesting that proteolysis has an important role in regulating the function of collagen XVII in skin homeostasis. Previous studies identified ADAMs 9, 10, and 17 as candidate collagen XVII sheddases and suggested that ADAM17 is a major sheddase. Here we show that ADAM17 only indirectly affects collagen XVII shedding and that ADAMs 9 and 10 are the most prominent collagen XVII sheddases in primary keratinocytes because (a) collagen XVII shedding was not stimulated by phorbol esters, known activators of ADAM17, (b) constitutive and calcium influx-stimulated shedding was sensitive to the ADAM10-selective inhibitor GI254023X and was strongly reduced in Adam10(-/-) cells, (c) there was a 55% decrease in constitutive collagen XVII ectodomain shedding from Adam9(-/-) keratinocytes, and (d) H(2)O(2) enhanced ADAM9 expression and stimulated collagen XVII shedding in skin and keratinocytes of wild type mice but not of Adam9(-/-) mice. We conclude that ADAM9 and ADAM10 can both contribute to collagen XVII shedding in skin with an enhanced relative contribution of ADAM9 in the presence of reactive oxygen species. These results provide critical new insights into the identity and regulation of the major sheddases for collagen XVII in keratinocytes and skin and have implications for the treatment of blistering diseases of the skin.

  8. The good, the bad and the ugly substrates for ADAM10 and ADAM17 in brain pathology, inflammation and cancer.

    PubMed

    Pruessmeyer, Jessica; Ludwig, Andreas

    2009-04-01

    Various surface molecules undergo regulated cleavage by the disintegrin and metalloproteinases ADAM10 and ADAM17. The list of substrates includes molecules involved in brain pathology, inflammation and cancer. In the brain both proteases mediate neuroprotective cleavage events such as inactivation of amyloid precursor protein. In inflammatory settings signaling of cytokines including TNFalpha and IL-6 is triggered by proteolytic release of soluble agonists and leukocyte recruitment is controlled by the cleavage of adhesion molecules. Moreover, in tumors, ADAM10- and ADAM17-mediated shedding events trigger proliferative signaling via activation of growth factors including ErbB family members. Concepts of either increasing ADAM10- or ADAM17-activity to limit neurodegeneration or suppressing their activity to block inflammation or tumor growth have to be carefully scrutinized for their potential side effects in various tissues and pathologies. PMID:18951988

  9. From Adam Swift to Adam Smith: How the "Invisible Hand" Overcomes Middle Class Hypocrisy

    ERIC Educational Resources Information Center

    Tooley, James

    2007-01-01

    This paper challenges Richard Pring's suggestion that parents using private education may be undermining the desire for social justice and equality, using recent arguments of Adam Swift as a springboard. Swift's position on the banning of private schools, which uses a Rawlsian "veil of ignorance" argument, is explored, and it is suggested that, if…

  10. Connective tissue growth factor is a substrate of ADAM28

    SciTech Connect

    Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki; Onuma, Junko; Fujii, Yutaka; Jinno, Hiromitsu; Okada, Yasunori

    2010-11-26

    Research highlights: {yields} The hyper-variable region in the cysteine-rich domain of ADAM28 binds to C-terminal domain of CTGF. {yields} ADAM28 cleaves CTGF alone and CTGF in the CTGF/VEGF{sub 165} complex. {yields} CTGF digestion by ADAM28 releases biologically active VEGF{sub 165} from the complex. {yields} ADAM28, CTGF and VEGF{sub 165} are commonly co-expressed by carcinoma cells in human breast carcinoma tissues. {yields} These suggest that ADAM28 promotes VEGF{sub 165}-induced angiogenesis in the breast carcinomas by selective CTGF digestion in the CTGF/VEGF{sub 165} complex. -- Abstract: ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinoma cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala{sup 181}-Tyr{sup 182} and Asp{sup 191}-Pro{sup 192} bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor{sub 165} (VEGF{sub 165}), releasing biologically active VEGF{sub 165} from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF{sub 165}-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF{sub 165} complex.

  11. ADAM12 and ADAM17 gene expression in laser-capture microdissected and non-microdissected breast tumors.

    PubMed

    Narita, Diana; Seclaman, Edward; Ilina, Razvan; Cireap, Natalia; Ursoniu, Sorin; Anghel, Andrei

    2011-06-01

    ADAM (a disintegrin and metalloprotease)12 and ADAM17 are multidomain transmembrane proteins involved in ectodomain shedding of cytokines, growth factors and adhesion molecules, with pivotal activities in the tumor microenvironment. The aim of this study was to confirm the up-regulation of ADAM17 and ADAM12 gene splicing variants in breast tumors and to delineate their expression between laser-capture microdissected (LCM) and non-microdissected breast tumors. The gene expression was analyzed by quantitative-reverse transcription-PCR in a total sample of 109 breast tumors paired with corresponding non-neoplastic breast tissues. ADAM12 and 17 proteins expression for corresponding tissue samples was confirmed by immunohistochemistry. ADAM12S, 12L and 17 genes were significantly up-regulated in either malign or benign LCM samples when compared to non-tumor controls. For non-LCM samples, it was obtained also an increased expression for ADAM12 and 17 genes in cancers, while in benign tumors only ADAM12 variants were significantly up-regulated compared to controls. When benign versus malignant tumors were compared, in LCM samples all investigated genes displayed a higher expression in cancers, whereas in non-LCM, ADAM12 variants were overexpressed in benign samples. The increased expression of ADAM12 protein in the tumor cells and stroma of benign breast diseases was immunohistochemically confirmed. These differences between LCM and non-LCM samples were explained by the contribution of the stroma to the expression of this marker. This study underlines the accuracy conferred by homogenous LCM samples on gene expression profiles and confers further evidence regarding the role of ADAM12 and 17 in the breast tumorigenesis and progression.

  12. ADAM8 as a drug target in Pancreatic Cancer

    PubMed Central

    Schlomann, Uwe; Koller, Garrit; Conrad, Catharina; Ferdous, Taheera; Golfi, Panagiota; Garcia, Adolfo Molejon; Höfling, Sabrina; Parsons, Maddy; Costa, Patricia; Soper, Robin; Bossard, Maud; Hagemann, Thorsten; Roshani, Rozita; Sewald, Norbert; Ketchem, Randal R.; Moss, Marcia L.; Rasmussen, Fred H.; Miller, Miles A.; Lauffenburger, Douglas A.; Tuveson, David A.; Nimsky, Christopher; Bartsch, Jörg W.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a grim prognosis with less than 5% survivors after 5 years. High expression levels of ADAM8, a metalloprotease-disintegrin, are correlated with poor clinical outcome. We show that ADAM8 expression is associated with increased migration and invasiveness of PDAC cells caused by activation of ERK 1/2 and higher MMP activities. For biological function, ADAM8 requires multimerisation and associates with β1-integrin on the cell surface. A peptidomimetic ADAM8 inhibitor, BK-1361, designed by structural modelling of the disintegrin domain, prevents ADAM8 multimerisation. In PDAC cells, BK-1361 affects ADAM8 function leading to reduced invasiveness, and less ERK 1/2 and MMP activation. BK-1361 application in mice decreased tumour burden and metastasis of implanted pancreatic tumour cells and provides improved metrics of clinical symptoms and survival in a KrasG12D-driven mouse model of PDAC. Thus, our data integrate ADAM8 in pancreatic cancer signalling and validate ADAM8 as a target for PDAC therapy. PMID:25629724

  13. "Adam of the Road" by Elizabeth Janet Gray. Literature Unit.

    ERIC Educational Resources Information Center

    Robbins, Mari Lu

    Intended as an aid to classroom teachers, this 48-page handbook presents a literature unit based on the children's book, "Adam of the Road" by Elizabeth Janet Gray. It begins with sample lesson plans, pre-reading activities, author information, a book summary, and vocabulary lists and suggested vocabulary activities. Next, chapters of "Adam of the…

  14. ADAM8 as a drug target in pancreatic cancer.

    PubMed

    Schlomann, Uwe; Koller, Garrit; Conrad, Catharina; Ferdous, Taheera; Golfi, Panagiota; Garcia, Adolfo Molejon; Höfling, Sabrina; Parsons, Maddy; Costa, Patricia; Soper, Robin; Bossard, Maud; Hagemann, Thorsten; Roshani, Rozita; Sewald, Norbert; Ketchem, Randal R; Moss, Marcia L; Rasmussen, Fred H; Miller, Miles A; Lauffenburger, Douglas A; Tuveson, David A; Nimsky, Christopher; Bartsch, Jörg W

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a grim prognosis with <5% survivors after 5 years. High expression levels of ADAM8, a metalloprotease disintegrin, are correlated with poor clinical outcome. We show that ADAM8 expression is associated with increased migration and invasiveness of PDAC cells caused by activation of ERK1/2 and higher MMP activities. For biological function, ADAM8 requires multimerization and associates with β1 integrin on the cell surface. A peptidomimetic ADAM8 inhibitor, BK-1361, designed by structural modelling of the disintegrin domain, prevents ADAM8 multimerization. In PDAC cells, BK-1361 affects ADAM8 function leading to reduced invasiveness, and less ERK1/2 and MMP activation. BK-1361 application in mice decreased tumour burden and metastasis of implanted pancreatic tumour cells and provides improved metrics of clinical symptoms and survival in a Kras(G12D)-driven mouse model of PDAC. Thus, our data integrate ADAM8 in pancreatic cancer signalling and validate ADAM8 as a target for PDAC therapy.

  15. The Failed Educations of John Stuart Mill and Henry Adams.

    ERIC Educational Resources Information Center

    Crossley, Robert

    1979-01-01

    Analyzes and contrasts Mill's "Autobiography" and Adams'"The Education of Henry Adams" in order to present two approaches to the nature of education and of failure. Maintains that their perspectives may serve as catalysts and cautions for contemporary theories of education and its utility and relevance. (CAM)

  16. Helping Eve overcome ADAM: G-quadruplexes in the ADAM-15 promoter as new molecular targets for breast cancer therapeutics.

    PubMed

    Brown, Robert V; Gaerig, Vanessa C; Simmons, Taesha; Brooks, Tracy A

    2013-12-05

    ADAM-15, with known zymogen, secretase, and disintegrin activities, is a catalytically active member of the ADAM family normally expressed in early embryonic development and aberrantly expressed in various cancers, including breast, prostate and lung. ADAM-15 promotes extracellular shedding of E-cadherin, a soluble ligand for the HER2/neu receptor, leading to activation, increased motility, and proliferation. Targeted downregulation of both ADAM-15 and HER2/neu function synergistically kills breast cancer cells, but to date there are no therapeutic options for decreasing ADAM-15 function or expression. In this vein, we have examined a unique string of guanine-rich DNA within the critical core promoter of ADAM-15. This region of DNA consists of seven contiguous runs of three or more consecutive guanines, which, under superhelical stress, can relax from duplex DNA to form an intrastrand secondary G-quadruplex (G4) structure. Using biophysical and biological techniques, we have examined the G4 formation within the entire and various truncated regions of the ADAM-15 promoter, and demonstrate strong intrastrand G4 formation serving to function as a biological silencer element. Characterization of the predominant G4 species formed within the ADAM-15 promoter will allow for specific drug targeting and stabilization, and the further development of novel, targeted therapeutics.

  17. A Disintegrin and Metalloproteinase10 (ADAM10) Regulates NOTCH Signaling during Early Retinal Development

    PubMed Central

    Toonen, Joseph A.; Ronchetti, Adam; Sidjanin, D. J.

    2016-01-01

    ADAM10 and ADAM17 are two closely related members of the ADAM (a disintegrin and metalloprotease) family of membrane-bound sheddases, which proteolytically cleave surface membrane proteins. Both ADAM10 and ADAM17 have been implicated in the proteolytic cleavage of NOTCH receptors and as such regulators of NOTCH signaling. During retinal development, NOTCH signaling facilitates retinal neurogenesis by maintaining progenitor cells in a proliferative state and by mediating retinal cell fates. However, the roles of ADAM10 and ADAM17 in the retina are not well defined. In this study, we set out to clarify the roles of ADAM10 and ADAM17 during early retinal development. The retinal phenotype of conditionally abated Adam17 retinae (Adam17 CKO) did not differ from the controls whereas conditionally ablated Adam10 retinae (Adam10 CKO) exhibited abnormal morphogenesis characterized by the formation of rosettes and a loss of retinal laminae phenotypically similar to morphological abnormalities identified in mice with retinal NOTCH signaling deficiency. Additionally, Adam10 CKO retinae exhibited abnormal neurogenesis characterized by fewer proliferating progenitor cells and greater differentiation of early photoreceptors and retinal ganglion cells. Moreover, constitutive activation of the NOTCH1-intracellular domain (N1-ICD) rescued Adam10 CKO abnormal neurogenesis, as well as abnormal retinal morphology by maintaining retinal cells in the progenitor state. Collectively these findings provide in vivo genetic evidence that ADAM10, and not ADAM17, is indispensable for proper retinal development as a regulator of NOTCH signaling. PMID:27224017

  18. Human and Murine Interleukin 23 Receptors Are Novel Substrates for A Disintegrin and Metalloproteases ADAM10 and ADAM17.

    PubMed

    Franke, Manuel; Schröder, Jutta; Monhasery, Niloufar; Ackfeld, Theresa; Hummel, Thorben M; Rabe, Björn; Garbers, Christoph; Becker-Pauly, Christoph; Floss, Doreen M; Scheller, Jürgen

    2016-05-13

    IL-23 (interleukin 23) regulates immune responses against pathogens and plays a major role in the differentiation and maintenance of TH17 cells and the development of autoimmune diseases and cancer. The IL-23 receptor (IL-23R) complex consists of the unique IL-23R and the common IL-12 receptor β1 (IL-12Rβ1). Differential splicing generates antagonistic soluble IL-23R (sIL-23R) variants, which might limit IL-23-mediated immune responses. Here, ectodomain shedding of human and murine IL-23R was identified as an alternative pathway for the generation of sIL-23R. Importantly, proteolytically released sIL-23R has IL-23 binding activity. Shedding of IL-23R was induced by stimulation with the phorbol ester phorbol 12-myristate 13-acetate (PMA), but not by ionomycin. PMA-induced shedding was abrogated by an ADAM (A disintegrin and metalloprotease) 10 and 17 selective inhibitor, but not by an ADAM10 selective inhibitor. ADAM17-deficient but not ADAM10-deficient HEK293 cells failed to shed IL-23R after PMA stimulation, demonstrating that ADAM17 but not ADAM10 cleaves the IL-23R. Constitutive shedding was, however, inhibited by an ADAM10 selective inhibitor. Using deletions and specific amino acid residue exchanges, we identified critical determinants of ectodomain shedding within the stalk region of the IL-23R. Finally, interaction studies identified domains 1 and 3 of the IL-23R as the main ADAM17 binding sites. In summary, we describe human and murine IL-23R as novel targets for protein ectodomain shedding by ADAM10 and ADAM17.

  19. Luhmann Receives 2007 John Adam Fleming Medal

    NASA Astrophysics Data System (ADS)

    Russell, Christopher T.; Luhmann, Janet G.

    2008-02-01

    This year's John Adam Fleming medalist quickly established a reputation as an innovative and productive scientist with a broad range of interests. She made early and seminal contributions to aeronomy, cosmic rays, and magnetospheric and planetary physics. She contributed importantly to the understanding of the interaction of the solar wind with the atmosphere and magnetic fields of Mercury, Venus, Earth, and Mars. She has examined the behavior of planetary rings, the interaction of interstellar neutrals with heliospheric plasmas, as well as the interaction of planetary neutrals with the heliosphere. She has led in the study of the interaction of the moon Titan with the Saturn magnetosphere, and most recently she developed a vigorous solar physics effort, leading the implementation of the IMPACT particle and field package on the twin STEREO mission, now entering its second year of successful operation.

  20. Adam Paulsen, a Pioneer in Auroral Research

    NASA Astrophysics Data System (ADS)

    Jørgensen, Torben S.; Rasmussen, Ole

    2006-02-01

    The 20 to 30 years following the first International Polar Year in 1882-1883 was a period of quickly advancing knowledge and understanding of auroral phenomena. This was the time when hypotheses of aurora being due to, for example, reflections of fires from the interior of the Earth or sunlight from ice particles were abandoned and replaced by the mechanism of precipitating electrons. One of the auroral researchers at that time was the Dane Adam Frederik Wivet Paulsen (1833-1907). However, when reading literature about auroral history, his ideas and work do not seem to have attracted much interest outside his own and neighboring countries. For example, in his sweeping historical account Majestic Lights: The Aurora in Science, History, and the Arts [1980], author Robert Eather only referred to Paulsen in a couple of lines.

  1. John Adams and CERN: Personal Recollections

    NASA Astrophysics Data System (ADS)

    Brianti, G.; Plane, D. E.

    2014-02-01

    By any standards, John Adams had a most remarkable career. He was involved in three important, emerging technologies, radar, particle accelerators and controlled fusion, and had an outstanding impact on the last two. Without a university education, he attained hierarchical positions of the highest level in prestigious national and international organizations. This article covers the CERN part of his career, by offering some personal insights into the different facets of his contributions to major accelerator projects, from the first strong-focusing synchrotron, the PS, to the SPS and its conversion to a proton--antiproton collider. In particular, it outlines his abilities as a leader of an international collaboration, which has served as an example for international initiatives in other disciplines.

  2. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    SciTech Connect

    Ungerer, Christopher; Doberstein, Kai; Boehm, Beate; Pfeilschifter, Josef; Mihic-Probst, Daniela; Gutwein, Paul

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  3. TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization.

    PubMed

    Jouannet, Stéphanie; Saint-Pol, Julien; Fernandez, Laurent; Nguyen, Viet; Charrin, Stéphanie; Boucheix, Claude; Brou, Christel; Milhiet, Pierre-Emmanuel; Rubinstein, Eric

    2016-05-01

    The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N-cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co-immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization. PMID:26686862

  4. Adams v. Bennett and Women's Equity Action League v. Bennett.

    ERIC Educational Resources Information Center

    Pratt, John H.

    1988-01-01

    Responding to requests to appeal Adams v. Bennett and Women's Equity Action League v. Bennett, both dealing with alleged illegal granting of federal funds, Judge Pratt decided that the plaintiffs in both cases lacked standing to continue their litigation. (BJV)

  5. 7. Historic American Buildings Survey, C. C. Adams, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Historic American Buildings Survey, C. C. Adams, Photographer August 1931, SEED PACKING ROOM, Gift of New York State Department of Education. - Shaker North Family Washhouse (first), Shaker Road, New Lebanon, Columbia County, NY

  6. ADAM17 substrate release in proximal tubule drives kidney fibrosis

    PubMed Central

    Kefaloyianni, Eirini; Muthu, Muthu Lakshmi; Kaeppler, Jakob; Sun, Xiaoming; Sabbisetti, Venkata; Chalaris, Athena; Rose-John, Stefan; Wong, Eitan; Sagi, Irit; Waikar, Sushrut S.; Rennke, Helmut; Bonventre, Joseph V.

    2016-01-01

    Kidney fibrosis following kidney injury is an unresolved health problem and causes significant morbidity and mortality worldwide. In a study into its molecular mechanism, we identified essential causative features. Acute or chronic kidney injury causes sustained elevation of a disintegrin and metalloprotease 17 (ADAM17); of its cleavage-activated proligand substrates, in particular of pro-TNFα and the EGFR ligand amphiregulin (pro-AREG); and of the substrates’ receptors. As a consequence, EGFR is persistently activated and triggers the synthesis and release of proinflammatory and profibrotic factors, resulting in macrophage/neutrophil ingress and fibrosis. ADAM17 hypomorphic mice, specific ADAM17 inhibitor–treated WT mice, or mice with inducible KO of ADAM17 in proximal tubule (Slc34a1-Cre) were significantly protected against these effects. In vitro, in proximal tubule cells, we show that AREG has unique profibrotic actions that are potentiated by TNFα-induced AREG cleavage. In vivo, in acute kidney injury (AKI) and chronic kidney disease (CKD, fibrosis) patients, soluble AREG is indeed highly upregulated in human urine, and both ADAM17 and AREG expression show strong positive correlation with fibrosis markers in related kidney biopsies. Our results indicate that targeting of the ADAM17 pathway represents a therapeutic target for human kidney fibrosis. PMID:27642633

  7. The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity

    PubMed Central

    Abbruzzese, Genevieve; Gorny, Anne-Kathrin; Kaufmann, Lilian T.; Cousin, Hélène; Kleino, Iivari; Steinbeisser, Herbert; Alfandari, Dominique

    2015-01-01

    ABSTRACT Cranial neural crest (CNC) cells are a transient population of stem cells that originate at the border of the neural plate and the epidermis, and migrate ventrally to contribute to most of the facial structures including bones, cartilage, muscles and ganglia. ADAM13 is a cell surface metalloprotease that is essential for CNC cell migration. Here, we show in Xenopus laevis embryos that the Wnt receptor Fz4 binds to the cysteine-rich domain of ADAM13 and negatively regulates its proteolytic activity in vivo. Gain of Fz4 function inhibits CNC cell migration and can be rescued by gain of ADAM13 function. Loss of Fz4 function also inhibits CNC cell migration and induces a reduction of mature ADAM13, together with an increase in the ADAM13 cytoplasmic fragment that is known to translocate into the nucleus to regulate gene expression. We propose that Fz4 associates with ADAM13 during its transport to the plasma membrane to regulate its proteolytic activity. PMID:25616895

  8. ADAM17 substrate release in proximal tubule drives kidney fibrosis

    PubMed Central

    Kefaloyianni, Eirini; Muthu, Muthu Lakshmi; Kaeppler, Jakob; Sun, Xiaoming; Sabbisetti, Venkata; Chalaris, Athena; Rose-John, Stefan; Wong, Eitan; Sagi, Irit; Waikar, Sushrut S.; Rennke, Helmut; Humphreys, Benjamin D.; Bonventre, Joseph V.; Herrlich, Andreas

    2016-01-01

    Kidney fibrosis following kidney injury is an unresolved health problem and causes significant morbidity and mortality worldwide. In a study into its molecular mechanism, we identified essential causative features. Acute or chronic kidney injury causes sustained elevation of a disintegrin and metalloprotease 17 (ADAM17); of its cleavage-activated proligand substrates, in particular of pro-TNFα and the EGFR ligand amphiregulin (pro-AREG); and of the substrates’ receptors. As a consequence, EGFR is persistently activated and triggers the synthesis and release of proinflammatory and profibrotic factors, resulting in macrophage/neutrophil ingress and fibrosis. ADAM17 hypomorphic mice, specific ADAM17 inhibitor–treated WT mice, or mice with inducible KO of ADAM17 in proximal tubule (Slc34a1-Cre) were significantly protected against these effects. In vitro, in proximal tubule cells, we show that AREG has unique profibrotic actions that are potentiated by TNFα-induced AREG cleavage. In vivo, in acute kidney injury (AKI) and chronic kidney disease (CKD, fibrosis) patients, soluble AREG is indeed highly upregulated in human urine, and both ADAM17 and AREG expression show strong positive correlation with fibrosis markers in related kidney biopsies. Our results indicate that targeting of the ADAM17 pathway represents a therapeutic target for human kidney fibrosis.

  9. ADAM10 as a target for anti-cancer therapy.

    PubMed

    Moss, Marcia L; Stoeck, Alexander; Yan, Wenbo; Dempsey, Peter J

    2008-02-01

    There is a great unmet medical need in the area of cancer treatment. A potential therapeutic target for intervention in cancer is ADAM10. ADAM10 is a disintegrin-metalloproteinase that processes membrane bound proteins from the cell surface to yield soluble forms. Pharmaceutical companies are actively seeking out inhibitors of ADAM10 for treatments in cancer as the enzyme is known to release the ErbB receptor, HER2/ErbB2 from the cell membrane, an event that is necessary for HER2 positive tumor cells to proliferate. ADAM10 is also capable of processing betacellulin indicating that an inhibitor could be used against EGFR/ErbB1 and/or HER4/ErbB4 receptor positive tumor cells that are betacellulin-dependent. ADAM10 is the principle sheddase for several other molecules associated with cancer proliferation, differentiation, adhesion and migration such as Notch, E-cadherin, CD44 and L1 adhesion molecule indicating that targeting ADAM10 with specific inhibitors could be beneficial.

  10. Adam Politzer-Father of Modern Otology.

    PubMed

    Dhungat, J V Pai; Gore, Geeta

    2015-09-01

    Adam Politzer (1835-1920) was born in Alberti near the city of Budapest in Hungary. He studied medicine at the University of Vienna and obtained his Doctorate degree in 1859. Some of his teachers belonged to the famous second "Vienna School" such as Joseph Skoda, Karl Rokitansky, Von Hebra, Josef Hyrtil, Johann Von Oppolzer and famous physiologist Carl Ludwig -who took special interest in him and was influential in his subsequent career. Politzer showed unusual interest in diseases of the ear and started to work in Carl Ludwig's laboratory. His interest at that time was mainly the physics of the auditory system. He studied the innervations of the intrinsic muscles of the ear There he was the first to demonstrate that the innervations of the tensor tympani muscle was by trigeminal nerve and that of the stapedial muscle was by facial nerve. He studied the air movement in the Eustachian tube and variation of air pressure in the tympanic cavity by connecting two manometers- one placed in the external auditory canal meatus, and another in the pharynx. He showed valve near the opening into the middle ear which controls the process. It is usually closed to keep the bacteria and other things away from the mouth and nose. PMID:27608882

  11. TACE (ADAM17) inhibits Schwann cell myelination.

    PubMed

    La Marca, Rosa; Cerri, Federica; Horiuchi, Keisuke; Bachi, Angela; Feltri, M Laura; Wrabetz, Lawrence; Blobel, Carl P; Quattrini, Angelo; Salzer, James L; Taveggia, Carla

    2011-06-12

    Tumor necrosis factor-α-converting enzyme (TACE; also known as ADAM17) is a proteolytic sheddase that is responsible for the cleavage of several membrane-bound molecules. We report that TACE cleaves neuregulin-1 (NRG1) type III in the epidermal growth factor domain, probably inactivating it (as assessed by deficient activation of the phosphatidylinositol-3-OH kinase pathway), and thereby negatively regulating peripheral nervous system (PNS) myelination. Lentivirus-mediated knockdown of TACE in vitro in dorsal root ganglia neurons accelerates the onset of myelination and results in hypermyelination. In agreement, motor neurons of conditional knockout mice lacking TACE specifically in these cells are significantly hypermyelinated, and small-caliber fibers are aberrantly myelinated. Further, reduced TACE activity rescues hypomyelination in NRG1 type III haploinsufficient mice in vivo. We also show that the inhibitory effect of TACE is neuron-autonomous, as Schwann cells lacking TACE elaborate myelin of normal thickness. Thus, TACE is a modulator of NRG1 type III activity and is a negative regulator of myelination in the PNS.

  12. ADAM12 induces estrogen-independence in breast cancer cells.

    PubMed

    Roy, Roopali; Moses, Marsha A

    2012-02-01

    Antiestrogen therapy has been used successfully to prolong disease-free and overall survival of ER positive breast cancer patients. However, 50% of patients with ER+ tumors fail to respond to such therapy or eventually acquire resistance to endocrine therapy, resulting in tumor progression and mortality. It is imperative, therefore, to understand the mechanisms that lead to hormone refractory breast cancer in order to develop therapeutics that can modulate the resistance to antiestrogen therapy. The protease, ADAM12, can be detected in the urine of breast cancer patients and its levels correlate with disease status, stage, and cancer risk. Within the context of this study, the authors have investigated the role of the two distinct isoforms of ADAM12 in breast tumor cell proliferation and as potential mediators of endocrine resistance. Using stable clones of ADAM12-overexpressing MCF-7 cells, the authors analyzed proliferation rates of these ER+ breast tumor cells both in estrogen-depleted medium and in the presence of the antiestrogens, tamoxifen, and ICI 182,780. Acquired estrogen resistance in these cells was analyzed using phospho-RTK analysis. Upregulation and phosphorylation of proteins were detected via immunoprecipitation and immunoblotting. EGFR and MAPK inhibitors were used to explore the mechanism of acquired estrogen resistance in breast tumor cells. It was observed that overexpression of the two isoforms, transmembrane ADAM12-L, and secreted ADAM12-S, in breast tumor cells promoted estrogen-independent proliferation. In ADAM12-L-expressing cells, estrogen-independence was a direct result of increased EGFR expression and MAPK activation, whereas, the mechanism in ADAM12-S-expressing cells may be enhanced IGF-1R signaling. The importance of the EGFR signaling pathway in the estrogen-independent growth of ADAM12-L expressing cells was highlighted by the effect of EGFR inhibitors AG1478 and PD15035 or MAPK inhibitor U0126, each of which abolished the

  13. Taking Charge: Walter Sydney Adams and the Mount Wilson Observatory

    NASA Astrophysics Data System (ADS)

    Brashear, R.

    2004-12-01

    The growing preeminence of American observational astronomy in the first half of the 20th century is a well-known story and much credit is given to George Ellery Hale and his skill as an observatory-building entrepreneur. But a key figure who has yet to be discussed in great detail is Walter Sydney Adams (1876-1956), Hale's Assistant Director at Mount Wilson Observatory. Due to Hale's illnesses, Adams was Acting Director for much of Hale's tenure, and he became the second Director of Mount Wilson from 1923 to 1946. Behind his New England reserve Adams was instrumental in the growth of Mount Wilson and thus American astronomy in general. Adams was hand-picked by Hale to take charge of stellar spectroscopy work at Yerkes and Mount Wilson and the younger astronomer showed tremendous loyalty to Hale and Hale's vision throughout his career. As Adams assumed the leadership role at Mount Wilson he concentrated on making the observatory a place where researchers worked with great freedom but maintain a high level of cooperation. This paper will concentrate on Adams's early years and look at his growing relationship with Hale and how he came to be the central figure in the early history of Mount Wilson as both a solar and stellar observatory. His education, his years at Dartmouth and Yerkes (including his unfortunate encounter with epsilon Leonis), and his formative years on Mount Wilson are all important in learning how he shaped the direction of Mount Wilson and the development of American astronomy in the first half of the 20th century. This latter history cannot be complete until we bring Adams into better focus.

  14. Characterization of Mammalian ADAM2 and Its Absence from Human Sperm

    PubMed Central

    Choi, Heejin; Jin, Sora; Kwon, Jun Tae; Kim, Jihye; Jeong, Juri; Kim, Jaehwan; Jeon, Suyeon; Park, Zee Yong; Jung, Kang-Jin; Park, Kwangsung; Cho, Chunghee

    2016-01-01

    The members of the ADAM (a disintegrin and metalloprotease) family are membrane-anchored multi-domain proteins that play prominent roles in male reproduction. ADAM2, which was one of the first identified ADAMs, is the best studied ADAM in reproduction. In the male germ cells of mice, ADAM2 and other ADAMs form complexes that contribute to sperm-sperm adhesion, sperm-egg interactions, and the migration of sperm in the female reproductive tract. Here, we generated specific antibodies against mouse and human ADAM2, and investigated various features of ADAM2 in mice, monkeys and humans. We found that the cytoplasmic domain of ADAM2 might enable the differential association of this protein with other ADAMs in mice. Western blot analysis with the anti-human ADAM2 antibodies showed that ADAM2 is present in the testis and sperm of monkeys. Monkey ADAM2 was found to associate with chaperone proteins in testis. In humans, we identified ADAM2 as a 100-kDa protein in the testis, but failed to detect it in sperm. This is surprising given the results in mice and monkeys, but it is consistent with the failure of ADAM2 identification in the previous proteomic analyses of human sperm. These findings suggest that the reproductive functions of ADAM2 differ between humans and mice. Our protein analysis showed the presence of potential ADAM2 complexes involving yet-unknown proteins in human testis. Taken together, our results provide new information regarding the characteristics of ADAM2 in mammalian species, including humans. PMID:27341348

  15. FAST{_}AD Code Verification: A Comparison to ADAMS

    SciTech Connect

    Buhl, M.L.; Wright, A.D.; Pierce, K.G.

    2001-02-15

    The National Renewable Energy Laboratory's National Wind Technology Center (NWTC) has refocused its wind turbine design-code comparison effort to verify FAST{_}AD with ADAMS. FAST{_}AD is a wind turbine structural-response code developed by Oregon State University for the NWTC. ADAMS is a commercial, general-purpose, multibody-dynamics code developed by Mechanical Dynamics, Inc. ADAMS, which is used in many industries, has been rigorously tested. Both ADAMS and FAST{_}AD use the AeroDyn subroutine package for calculating aerodynamic forces. The University of Utah developed AeroDyn for the NWTC. To compare FAST{_}AD to ADAMS, we modeled a rough approximation of the AWT-27 P4 turbine, using the same properties for both simulators. The AWT-27 is a 275-kilowatt (kW), two-bladed wind turbine. We also created three-bladed versions of the turbine models to verify FAST{_}AD for three-bladed turbines. In this paper, we list the aerodynamic features used in the comparison. We also explain how the programs model the turbine structure, describe the degrees of freedom (DOFs) used for this study, and present simulation comparisons that show very good agreement.

  16. Phosphatidylserine exposure is required for ADAM17 sheddase function

    PubMed Central

    Sommer, Anselm; Kordowski, Felix; Büch, Joscha; Maretzky, Thorsten; Evers, Astrid; Andrä, Jörg; Düsterhöft, Stefan; Michalek, Matthias; Lorenzen, Inken; Somasundaram, Prasath; Tholey, Andreas; Sönnichsen, Frank D.; Kunzelmann, Karl; Heinbockel, Lena; Nehls, Christian; Gutsmann, Thomas; Grötzinger, Joachim; Bhakdi, Sucharit; Reiss, Karina

    2016-01-01

    ADAM17, a prominent member of the ‘Disintegrin and Metalloproteinase' (ADAM) family, controls vital cellular functions through cleavage of transmembrane substrates. Here we present evidence that surface exposure of phosphatidylserine (PS) is pivotal for ADAM17 to exert sheddase activity. PS exposure is tightly coupled to substrate shedding provoked by diverse ADAM17 activators. PS dependency is demonstrated in the following: (a) in Raji cells undergoing apoptosis; (b) in mutant PSA-3 cells with manipulatable PS content; and (c) in Scott syndrome lymphocytes genetically defunct in their capacity to externalize PS in response to intracellular Ca2+ elevation. Soluble phosphorylserine but not phosphorylcholine inhibits substrate cleavage. The isolated membrane proximal domain (MPD) of ADAM17 binds to PS but not to phosphatidylcholine liposomes. A cationic PS-binding motif is identified in this domain, replacement of which abrogates liposome-binding and renders the protease incapable of cleaving its substrates in cells. We speculate that surface-exposed PS directs the protease to its targets where it then executes its shedding function. PMID:27161080

  17. Structural Characterization of the Ectodomain of a Disintegrin and Metalloproteinase-22 (ADAM22), a Neural Adhesion Receptor Instead of Metalloproteinase INSIGHTS ON ADAM FUNCTION

    SciTech Connect

    Liu, Heli; Shim, Ann H.R.; He, Xiaolin

    2009-12-01

    ADAMs (adisintegrin and metalloproteinases) are a family of multidomain transmembrane glycoproteins with diverse roles in physiology and diseases, with several members being drug targets for cancer and inflammation therapies. The spatial organization of the ADAM extracellular segment and its influence on the function of ADAMs have been unclear. Although most members of the ADAM family are active zinc metalloproteinases, 8 of 21 ADAMs lack functional metalloproteinase domains and are implicated in protein-protein interactions instead of membrane protein ectodomain shedding. One of such non-proteinase ADAMs, ADAM22, acts as a receptor on the surface of the postsynaptic neuron to regulate synaptic signal transmission. The crystal structure of the full ectodomain of mature human ADAM22 shows that it is a compact four-leaf clover with the metalloproteinase-like domain held in the concave face of a rigid module formed by the disintegrin, cysteine-rich, and epidermal growth factor-like domains. The loss of metalloproteinase activity is ensured by the absence of critical catalytic residues, the filling of the substrate groove, and the steric hindrance by the cysteine-rich domain. The structure, combined with calorimetric experiments, suggests distinct roles of three putative calcium ions bound to ADAM22, with one in the metalloproteinase-like domain being regulatory and two in the disintegrin domain being structural. The metalloproteinase-like domain contacts the rest of ADAM22 with discontinuous, hydrophilic, and poorly complemented interactions, suggesting the possibility of modular movement of ADAM22 and other ADAMs. The ADAM22 structure provides a framework for understanding how different ADAMs exert their adhesive function and shedding activities.

  18. Disturbed follicular architecture in B cell ADAM10 knockouts is mediated by compensatory increases in ADAM17 and TNFα shedding1

    PubMed Central

    Folgosa, Lauren; Zellner, Hannah B.; Shikh, Mohey Eldin El; Conrad, Daniel H.

    2013-01-01

    B cell ADAM10 is required for the development and maintenance of proper secondary lymphoid tissue architecture; however, the underlying mechanism remains unclear. In this study, we show disturbances in naïve lymph node architecture from B cell specific ADAM10 deficient mice (ADAM10B−/−) including loss of B/T compartmentalization, attenuation of FDC reticula, excessive collagen deposition, and increased HEV formation. Because TNFα signaling is critical for secondary lymphoid tissue architecture, we examined compensatory changes in ADAM17 and TNFα in ADAM10B−/− B cells. Surprisingly, defective follicular development in these mice was associated with increased rather than decreased TNFα expression. Here, we describe an increase in TNFα message, mRNA stability, soluble protein release, and membrane expression in ADAM10B−/− B cells compared to WT, which coincides with increased ADAM17 message and protein. To assess the mechanistic contribution of excessive TNFα to abnormal lymphoid architecture in ADAM10B−/− mice, we performed a bone marrow reconstitution study. Rectification of WT architecture was noted only in irradiated WT mice reconstituted with ADAM10B−/− + TNFKO bone marrow due to normalization of TNFα levels not seen in ADAM10B−/− alone. We conclude that ADAM17 overcompensation causes excessive TNFα shedding and further upregulation of TNFα expression, creating an aberrant signaling environment within B cell cortical regions of ADAM10B−/− lymph nodes, highlighting a key interplay between B cell ADAM10 and ADAM17 with respect to TNFα homeostasis. PMID:24227779

  19. The Adam language: Ada extended with support for multiway activities

    NASA Technical Reports Server (NTRS)

    Charlesworth, Arthur

    1993-01-01

    The Adam language is an extension of Ada that supports multiway activities, which are cooperative activities involving two or more processes. This support is provided by three new constructs: diva procedures, meet statements, and multiway accept statements. Diva procedures are recursive generic procedures having a particular restrictive syntax that facilitates translation for parallel computers. Meet statements and multiway accept statements provide two ways to express a multiway rendezvous, which is an n-way rendezvous generalizing Ada's 2-way rendezvous. While meet statements tend to have simpler rules than multiway accept statements, the latter approach is a more straightforward extension of Ada. The only nonnull statements permitted within meet statements and multiway accept statements are calls on instantiated diva procedures. A call on an instantiated diva procedure is also permitted outside a multiway rendezvous; thus sequential Adam programs using diva procedures can be written. Adam programs are translated into Ada programs appropriate for use on parallel computers.

  20. Aberrant ADAM10 expression correlates with osteosarcoma progression

    PubMed Central

    2014-01-01

    Background Osteosarcoma is the most common type of bone cancer and is notorious for its rapid progression. The Notch signaling pathway has recently been shown to be involved in osteosarcoma. As a major sheddase of Notch receptors, ADAM10 has been implicated in many types of cancers, but its role in osteosarcoma has not been investigated. Previous studies have shown that the expression of CD31 was significantly elevated in metastatic osteosarcoma; however, its expression in nonmetastatic groups is not known. In addition, the mysterious multinucleated giant cell in giant cell-rich osteosarcoma was previously regarded as an osteoclast-like cell, but its exact identity is unclear. Method Tissue chip samples from 40 cases of nonmetastatic osteosarcoma were stained for cytoplasmic ADAM10, activated Notch1 and CD31. Osteoclasts in tumor sections were also stained for tartrate-resistant acid phosphatase (TRAP). Results Immunofluorescence staining revealed that ADAM10 expression significantly increased with the progression of osteosarcoma as well as in osteoblastic osteosarcoma, whereas the expression of the Notch intracellular domain (NICD) and CD31 was not significantly altered between different pathological stages. In addition, multinucleated giant cells in giant cell-rich osteosarcoma were also found to coexpress CD31, ADAM10 and NICD, but were negative for TRAP staining. Conclusions Our results highlight the importance of ADAM10 in the progression of osteosarcoma and suggest that the protein might be a potential therapeutic target in osteosarcoma treatment. This study also demonstrates that the multinucleated giant cell is an angiogenic tumor cell, rather than an osteoclast, and involves ADAM10/Notch1 signaling activation. PMID:24548763

  1. 77 FR 60004 - Culturally Significant Object Imported for Exhibition Determinations: “Wtewael's Adam and Eve”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Culturally Significant Object Imported for Exhibition Determinations: ``Wtewael's Adam and Eve'' SUMMARY... object to be included in the exhibition ``Wtewael's Adam and Eve,'' imported from abroad for...

  2. Jefferson and Adams on the mind-body problem.

    PubMed

    Robinson, Daniel N

    2003-08-01

    Amidst the voluminous correspondence between Thomas Jefferson and John Adams are several letters pertaining to the material basis of mental life. These reveal in a most suggestive way the substantial differences between them. Well informed on prevailing scientific and philosophical perspectives, Jefferson and Adams used the issue to express their positions on the nature and limits of knowledge, the relative authority of scientific methods and speculations, and the larger question of human perfectibility. At the same time, their exchanges illuminate the prevailing and divergent perspectives on human psychology adopted by major leaders of thought in the New World.

  3. John Adams High School First Year Report, 1969-1970.

    ERIC Educational Resources Information Center

    Adams High School, Portland, OR.

    This report is an assessment of the events of the first year of operation of John Adams High School, Portland, Oregon. The primary goal of the school was to provide an educational experience relevant to the needs and interests of all adolescents, regardless of their intentions about pursuing further formal education. The report is oriented toward…

  4. What Ever Happened to . . . John Adams High School?

    ERIC Educational Resources Information Center

    Doremus, Richard R.

    1981-01-01

    First in a series, this article describes the rise and fall of John Adams High School, an experimental school in Portland (Oregon) that was recently closed after 12 years of operation. The experiences of those who tried to make the experiment work may help others interested in educational innovation. (WD)

  5. Research and Evaluation at John Adams High School.

    ERIC Educational Resources Information Center

    Adams High School, Portland, OR.

    We at Adams have committed ourselves (1) to search for new ways to make the inquiry into our own activities and the evaluation of our programs relevant and consistent with our notions of humanistic and personal education, and (2) to seek a mechanism for using research and evaluation to improve the operation of the school at every level and for…

  6. 3. Aerial view southeast, State Route 92 bottom left, Adams ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Aerial view southeast, State Route 92 bottom left, Adams Dam Road center, Brandywine Creek State Park and J. Chandler Farm in center left, duck pond bottom right and reservoir bottom left. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

  7. 4. Aerial view southwest, Adams Dam Road bottom left, State ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Aerial view southwest, Adams Dam Road bottom left, State Route 100 center, back gates to Winterthur and Wilmington Country Club upper center, duck pond and reservoir bottom right and center, and State Route 92 center bottom. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

  8. 5. Aerial view west, Adams Dam Road bottom center, State ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Aerial view west, Adams Dam Road bottom center, State Route 100 center, duck pond and reservoir center, State Route 100 center right, State Route 92 below center right, Brandywine Creek State Park center bottom. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

  9. An Informal Report on Collegiate Successes with "The Adams Chronicles."

    ERIC Educational Resources Information Center

    Goldsberry, Gary G.

    In the spring of 1976, "The Adams Chronicles", a bicentennial television course developed by Coast Community College District and the University of California at San Diego, was distributed to colleges nationwide at no charge with the understanding that each college would return information regarding promotion, enrollment, and form of offering this…

  10. Adam Smith and the Teaching of English Literature.

    ERIC Educational Resources Information Center

    Court, Franklin E.

    1985-01-01

    Adam Smith used selections from English literature in his classroom during the eighteenth century because he believed that vernacular literature could provide a ready context for the teaching of ideological, social, and moral lessons. He believed that higher education should prepare students for the real business of the real world. (RM)

  11. Adam Smith and the Moral Economy of the Classroom System.

    ERIC Educational Resources Information Center

    Hamilton, D.

    1980-01-01

    Traces the development of mass schooling to its origins in 19th-century Glasgow. Its importance as an intellectual and economic center enabled Glasgow to invent a solution to the problem of urban schooling, while the association of scholars like Adam Smith with Glasgow University made Scottish educational theories acceptable around the world. (DB)

  12. ADAM: A Collaborative Effort To Prepare Future Administrators.

    ERIC Educational Resources Information Center

    Richardson, Michael D.; And Others

    ADAM (Administrative Development and Management), an administrator preparation partnership between Greenwood (South Carolina) School District 50 and Clemson University, is described in this paper. The program uses practicing administrators in collaboration with college faculty to train prospective school administrators. The purpose is to provide…

  13. The ADaptation and Anticipation Model (ADAM) of sensorimotor synchronization

    PubMed Central

    van der Steen, M. C. (Marieke); Keller, Peter E.

    2013-01-01

    A constantly changing environment requires precise yet flexible timing of movements. Sensorimotor synchronization (SMS)—the temporal coordination of an action with events in a predictable external rhythm—is a fundamental human skill that contributes to optimal sensory-motor control in daily life. A large body of research related to SMS has focused on adaptive error correction mechanisms that support the synchronization of periodic movements (e.g., finger taps) with events in regular pacing sequences. The results of recent studies additionally highlight the importance of anticipatory mechanisms that support temporal prediction in the context of SMS with sequences that contain tempo changes. To investigate the role of adaptation and anticipatory mechanisms in SMS we introduce ADAM: an ADaptation and Anticipation Model. ADAM combines reactive error correction processes (adaptation) with predictive temporal extrapolation processes (anticipation) inspired by the computational neuroscience concept of internal models. The combination of simulations and experimental manipulations based on ADAM creates a novel and promising approach for exploring adaptation and anticipation in SMS. The current paper describes the conceptual basis and architecture of ADAM. PMID:23772211

  14. Father Knows Best: Using Adam Smith to Teach Transactions Costs

    ERIC Educational Resources Information Center

    Dupont, Brandon

    2014-01-01

    Adam Smith's moral philosophy can be used to introduce economics students to the important idea of transactions costs. The author provides a brief background in this article to Smith's moral philosophy and connects it to the costs of transacting in a way that fits easily into the standard principles of microeconomics classroom. By doing…

  15. Cloning and expression of ADAM related metalloproteases in Equine Laminitis

    PubMed Central

    Coyne, Michael J.; Cousin, Hélène; Loftus, John P.; Johnson, Philip J.; Belknap, James K.; Gradil, Carlos M.; Black, Samuel J.; Alfandari, Dominique

    2010-01-01

    Equine laminitis is a debilitating disease affecting the digital laminae that suspends the distal phalanx within the hoof. While the clinical progression of the disease has been well documented, the molecular events associated with its pathogenesis remain largely unknown. We have investigated the expression of genes coding for proteins containing a Disintegrin and Metalloprotease domain (ADAM), as well as genes encoding the natural inhibitors of these enzymes (Tissue Inhibitor of MetalloProtease; TIMP) in horses with naturally acquired (acute, chronic and aggravated chronic cases collected in clinic) or experimentally-induced (black walnut extract and starch gruel models) laminitis using real time quantitative RT-PCR. Changes in expression of these enzymes and regulators may underlie the pathologic remodeling of lamellar tissue in laminitis. Genes encoding ADAMs involved in inflammation (ADAM-10 and ADAM-17), as well as those implicated in arthritis (ADAMTS-1, ADAMTS-4 and ADAMTS-5) were cloned, and the sequences used to generate specific oligonucleotide primers for the RT-qPCR experiments. Our results show that genes encoding ADAM-10 and 17 were not induced in most laminitic animals whereas ADAMTS-4 gene expression was strongly upregulated in practically all cases of experimentally induced and naturally acquired laminitis. The expression of MMP-9 and ADAMTS-5 was also increased in many of the laminitic horses. In addition, TIMP-2 gene expression was decreased in most laminitic horses, whereas expression of genes encoding other TIMPs, namely TIMP-1 and TIMP-3 was randomly increased or decreased in the various models. We conclude that elevated expression of lamellar ADAMTS-4 is a common feature of laminitis consistent with a central role of the gene product in the pathophysiology of laminitis. PMID:19131116

  16. Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice.

    PubMed

    Cooley, Lauren Folgosa; Martin, Rebecca K; Zellner, Hannah B; Irani, Anne-Marie; Uram-Tuculescu, Cora; El Shikh, Mohey Eldin; Conrad, Daniel H

    2015-01-01

    ADAM10, as the sheddase of the low affinity IgE receptor (CD23), promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J). While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone) WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J) compared to Th1 prone controls. To further understand this regulation, ADAM17 and TNF were studied in C57Bl/6 and Balb/c mice deficient in ADAM10. C57-ADAM10B-/- were more adept at increasing ADAM17 levels and thus TNF cleavage resulting in excess follicular TNF levels and abnormal secondary lymphoid tissue architecture not noted in Balb-ADAM10B-/-. Moreover, the level of B cell ADAM10 as well as Th context is critical for determining IgE production potential. Using a murine house dust mite airway hypersensitivity model, we describe that high B cell ADAM10 level in a Th2 context (Balb/c WT) is optimal for disease induction including bronchoconstriction, goblet cell metaplasia, mucus, inflammatory cellular infiltration, and IgE production. Balb/c mice deficient in B cell ADAM10 have attenuated lung and airway symptoms compared to Balb WT and are actually most similar to C57 WT (Th1 prone). C57-ADAM10B-/- have even further reduced symptomology. Taken together, it is critical to consider both innate B cell levels of ADAM10 and ADAM17 as well as Th context when determining host susceptibility to allergic disease. High B cell ADAM10 and low ADAM17 levels would help diagnostically in predicting Th2 disease susceptibility; and, we provide support for the use ADAM10 inhibitors in treating Th2 disease.

  17. Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis.

    PubMed

    De Savi, Chris; Pape, Andrew; Sawyer, Yvonne; Milne, David; Davies, Chris; Cumming, John G; Ting, Attilla; Lamont, Scott; Smith, Peter D; Tart, Jonathon; Page, Ken; Moore, Peter

    2011-06-01

    A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics.

  18. Secretion-Positive LGI1 Mutations Linked to Lateral Temporal Epilepsy Impair Binding to ADAM22 and ADAM23 Receptors

    PubMed Central

    Dazzo, Emanuela; Belluzzi, Elisa; Malacrida, Sandro; Vitiello, Libero; Greggio, Elisa; Tosatto, Silvio C. E.

    2016-01-01

    Autosomal dominant lateral temporal epilepsy (ADTLE) is a focal epilepsy syndrome caused by mutations in the LGI1 gene, which encodes a secreted protein. Most ADLTE-causing mutations inhibit LGI1 protein secretion, and only a few secretion-positive missense mutations have been reported. Here we describe the effects of four disease-causing nonsynonymous LGI1 mutations, T380A, R407C, S473L, and R474Q, on protein secretion and extracellular interactions. Expression of LGI1 mutant proteins in cultured cells shows that these mutations do not inhibit protein secretion. This finding likely results from the lack of effects of these mutations on LGI1 protein folding, as suggested by 3D protein modelling. In addition, immunofluorescence and co-immunoprecipitation experiments reveal that all four mutations significantly impair interaction of LGI1 with the ADAM22 and ADAM23 receptors on the cell surface. These results support the existence of a second mechanism, alternative to inhibition of protein secretion, by which ADLTE-causing LGI1 mutations exert their loss-of-function effect extracellularly, and suggest that interactions of LGI1 with both ADAM22 and ADAM23 play an important role in the molecular mechanisms leading to ADLTE. PMID:27760137

  19. A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis

    PubMed Central

    Köhn-Gaone, Julia; Chalupsky, Karel; Lüllmann-Rauch, Renate; Barikbin, Roja; Bergmann, Juri; Wöhner, Birte; Zbodakova, Olga; Leuschner, Ivo; Martin, Gregor; Tiegs, Gisa; Rose-John, Stefan; Sedlacek, Radislav; Tirnitz-Parker, Janina E.E.; Saftig, Paul; Schmidt-Arras, Dirk

    2016-01-01

    A Disintegrin And Metalloprotease (ADAM) 10 exerts essential roles during organ development and tissue integrity in different organs, mainly through activation of the Notch pathway. However, only little is known about its implication in liver tissue physiology. Here we show that in contrast to its role in other tissues, ADAM10 is dispensable for the Notch2-dependent biliary tree formation. However, we demonstrate that expression of bile acid transporters is dependent on ADAM10. Consequently, mice deficient for Adam10 in hepatocytes, cholangiocytes and liver progenitor cells develop spontaneous hepatocyte necrosis and concomitant liver fibrosis. We furthermore observed a strongly augmented ductular reaction in 15-week old ADAM10Δhep/Δch mice and demonstrate that c-Met dependent liver progenitor cell activation is enhanced. Additionally, liver progenitor cells are primed to hepatocyte differentiation in the absence of ADAM10. These findings show that ADAM10 is a novel central node controlling liver tissue homeostasis. Highlights: Loss of ADAM10 in murine liver results in hepatocyte necrosis and concomitant liver fibrosis. ADAM10 directly regulates expression of bile acid transporters but is dispensable for Notch2-dependent formation of the biliary system. Activation of liver progenitor cells is enhanced through increased c-Met signalling, in the absence of ADAM10. Differentiation of liver progenitor cells to hepatocytes is augmented in the absence of ADAM10. PMID:26942887

  20. Role of ADAM33 gene and associated single nucleotide polymorphisms in asthma.

    PubMed

    Sharma, Neeraj; Tripathi, Priya; Awasthi, Shally

    2011-04-01

    Asthma is a multifactorial disorder, primarily resulting from interactions between genetic and environmental factors. ADAM33 gene (located on chromosome 20p13) has been reported to play an important role in asthma. This review article is intended to include all of the publications, to date, which have assessed the association of ADAM33 gene polymorphisms as well as have shown the role of ADAM33 gene in airway remodeling and their expression with asthma. A PubMed search was performed for studies published between 1990 and 2010. The terms "ADAM33," "ADAM33 gene and asthma," and "ADAM33 gene polymorphisms" were used as search criteria. Based on available literature we can only speculate its role in the morphogenesis and functions of the lung. Fourteen studies conducted in different populations were found showing an association of ADAM33 gene polymorphisms with asthma. However, none of the single nucleotide polymorphisms (SNPs) of ADAM33 gene had found association with asthma across all ethnic groups. Because higher expression of ADAM33 is found in the fibroblast and smooth muscle cells of the lung, over- or underexpression of ADAM33 gene may result in alterations in airway remodeling and repair processes. However, no SNP of ADAM33 gene showed significant associations with asthma across all ethnic groups; the causative polymorphism, if any, still has to be identified.

  1. ADAM17 Silencing in Mouse Colon Carcinoma Cells: The Effect on Tumoricidal Cytokines and Angiogenesis

    PubMed Central

    Das, Sudipta; Czarnek, Maria; Bzowska, Monika; Mężyk-Kopeć, Renata; Stalińska, Krystyna; Wyroba, Barbara; Sroka, Jolanta; Jucha, Jarosław; Deneka, Dawid; Stokłosa, Paulina; Ogonek, Justyna; Swartz, Melody A.; Madeja, Zbigniew; Bereta, Joanna

    2012-01-01

    ADAM17 (a disintegrin and metalloprotease 17) is a major sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules and is often overexpressed in malignant cells. It is generally accepted that ADAM17 promotes tumor development via activating growth factors from the EGF family, thus facilitating autocrine stimulation of tumor cell proliferation and migration. Here we show, using MC38CEA murine colon carcinoma model, that ADAM17 also regulates tumor angiogenesis and cytokine profile. When ADAM17 was silenced in MC38CEA cells, in vivo tumor growth and in vitro cell motility were significantly diminished, but no effect was seen on in vitro cell proliferation. ADAM17-silencing was accompanied by decreased in vitro expression of vascular endothelial growth factor-A and matrix metalloprotease-9, which was consistent with the limited angiogenesis and slower growth seen in ADAM17-silenced tumors. Among the growth factors susceptible to shedding by ADAM17, neuregulin-1 was the only candidate to mediate the effects of ADAM17 on MC38CEA motility and tumor angiogenesis. Concentrations of TNF and IFNγ, cytokines that synergistically induced proapoptotic effects on MC38CEA cells, were significantly elevated in the lysates of ADAM17-silenced tumors compared to mock transfected controls, suggesting a possible role for ADAM17 in host immune suppression. These results introduce new, complex roles of ADAM17 in tumor progression, including its impact on the anti-tumor immune response. PMID:23251384

  2. ADAM17 silencing in mouse colon carcinoma cells: the effect on tumoricidal cytokines and angiogenesis.

    PubMed

    Das, Sudipta; Czarnek, Maria; Bzowska, Monika; Mężyk-Kopeć, Renata; Stalińska, Krystyna; Wyroba, Barbara; Sroka, Jolanta; Jucha, Jarosław; Deneka, Dawid; Stokłosa, Paulina; Ogonek, Justyna; Swartz, Melody A; Madeja, Zbigniew; Bereta, Joanna

    2012-01-01

    ADAM17 (a disintegrin and metalloprotease 17) is a major sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules and is often overexpressed in malignant cells. It is generally accepted that ADAM17 promotes tumor development via activating growth factors from the EGF family, thus facilitating autocrine stimulation of tumor cell proliferation and migration. Here we show, using MC38CEA murine colon carcinoma model, that ADAM17 also regulates tumor angiogenesis and cytokine profile. When ADAM17 was silenced in MC38CEA cells, in vivo tumor growth and in vitro cell motility were significantly diminished, but no effect was seen on in vitro cell proliferation. ADAM17-silencing was accompanied by decreased in vitro expression of vascular endothelial growth factor-A and matrix metalloprotease-9, which was consistent with the limited angiogenesis and slower growth seen in ADAM17-silenced tumors. Among the growth factors susceptible to shedding by ADAM17, neuregulin-1 was the only candidate to mediate the effects of ADAM17 on MC38CEA motility and tumor angiogenesis. Concentrations of TNF and IFNγ, cytokines that synergistically induced proapoptotic effects on MC38CEA cells, were significantly elevated in the lysates of ADAM17-silenced tumors compared to mock transfected controls, suggesting a possible role for ADAM17 in host immune suppression. These results introduce new, complex roles of ADAM17 in tumor progression, including its impact on the anti-tumor immune response.

  3. High Glucose Up-regulates ADAM17 through HIF-1α in Mesangial Cells.

    PubMed

    Li, Renzhong; Uttarwar, Lalita; Gao, Bo; Charbonneau, Martine; Shi, Yixuan; Chan, John S D; Dubois, Claire M; Krepinsky, Joan C

    2015-08-28

    We previously showed that ADAM17 mediates high glucose-induced matrix production by kidney mesangial cells. ADAM17 expression is increased in diabetic kidneys, suggesting that its up-regulation may augment high glucose profibrotic responses. We thus studied the effects of high glucose on ADAM17 gene regulation. Primary rat mesangial cells were treated with high glucose (30 mm) or mannitol as osmotic control. High glucose dose-dependently increased ADAM17 promoter activity, transcript, and protein levels. This correlated with augmented ADAM17 activity after 24 h versus 1 h of high glucose. We tested involvement of transcription factors shown in other settings to regulate ADAM17 transcription. Promoter activation was not affected by NF-κB or Sp1 inhibitors, but was blocked by hypoxia-inducible factor-1α (HIF-1α) inhibition or down-regulation. This also prevented ADAM17 transcript and protein increases. HIF-1α activation by high glucose was shown by its increased nuclear translocation and activation of the HIF-responsive hypoxia-response element (HRE)-luciferase reporter construct. Assessment of ADAM17 promoter deletion constructs coupled with mutation analysis and ChIP studies identified HIF-1α binding to its consensus element at -607 as critical for the high glucose response. Finally, inhibitors of epidermal growth factor receptor (EGFR) and downstream PI3K/Akt, or ADAM17 itself, prevented high glucose-induced HIF-1α activation and ADAM17 up-regulation. Thus, high glucose induces ADAM17 transcriptional up-regulation in mesangial cells, which is associated with augmentation of its activity. This is mediated by HIF-1α and requires EGFR/ADAM17 signaling, demonstrating the potentiation by ADAM17 of its own up-regulation. ADAM17 inhibition thus provides a potential novel therapeutic strategy for the treatment of diabetic nephropathy.

  4. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    PubMed

    Mężyk-Kopeć, Renata; Wyroba, Barbara; Stalińska, Krystyna; Próchnicki, Tomasz; Wiatrowska, Karolina; Kilarski, Witold W; Swartz, Melody A; Bereta, Joanna

    2015-01-01

    Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy. PMID:26176220

  5. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells

    PubMed Central

    Stalińska, Krystyna; Próchnicki, Tomasz; Wiatrowska, Karolina; Kilarski, Witold W.; Swartz, Melody A.; Bereta, Joanna

    2015-01-01

    Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy. PMID:26176220

  6. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    PubMed

    Mężyk-Kopeć, Renata; Wyroba, Barbara; Stalińska, Krystyna; Próchnicki, Tomasz; Wiatrowska, Karolina; Kilarski, Witold W; Swartz, Melody A; Bereta, Joanna

    2015-01-01

    Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy.

  7. Adam8 Limits the Development of Allergic Airway Inflammation in Mice

    PubMed Central

    Knolle, Martin D.; Nakajima, Takahiro; Hergrueter, Anja; Gupta, Kushagra; Polverino, Francesca; Craig, Vanessa J.; Fyfe, Susanne E.; Zahid, Muhammad; Permaul, Perdita; Cernadas, Manuela; Montano, Gilbert; Tesfaigzi, Yohannes; Sholl, Lynette; Kobzik, Lester; Israel, Elliot; Owen, Caroline A.

    2013-01-01

    To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8 limited AAI and AHR in mice by reducing leukocyte survival because: 1) Adam8−/− mice with AAI had fewer apoptotic eosinophils and macrophages in their airways than WT mice with AAI; and 2) Adam8−/− macrophages and eosinophils had reduced rates of apoptosis compared with WT leukocytes when the intrinsic (but not the extrinsic) apoptosis pathway was triggered in the cells in vitro. ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients but, surprisingly, airway macrophages had less ADAM8 staining than airway eosinophils. Thus, ADAM8 has anti-inflammatory activities during AAI in mice by activating the intrinsic apoptosis pathway in myeloid leukocytes. Strategies that increase ADAM8 levels in myeloid leukocytes may have therapeutic efficacy in asthma. PMID:23670189

  8. Adams-Based Rover Terramechanics and Mobility Simulator - ARTEMIS

    NASA Technical Reports Server (NTRS)

    Trease, Brian P.; Lindeman, Randel A.; Arvidson, Raymond E.; Bennett, Keith; VanDyke, Lauren P.; Zhou, Feng; Iagnemma, Karl; Senatore, Carmine

    2013-01-01

    The Mars Exploration Rovers (MERs), Spirit and Opportunity, far exceeded their original drive distance expectations and have traveled, at the time of this reporting, a combined 29 kilometers across the surface of Mars. The Rover Sequencing and Visualization Program (RSVP), the current program used to plan drives for MERs, is only a kinematic simulator of rover movement. Therefore, rover response to various terrains and soil types cannot be modeled. Although sandbox experiments attempt to model rover-terrain interaction, these experiments are time-intensive and costly, and they cannot be used within the tactical timeline of rover driving. Imaging techniques and hazard avoidance features on MER help to prevent the rover from traveling over dangerous terrains, but mobility issues have shown that these methods are not always sufficient. ARTEMIS, a dynamic modeling tool for MER, allows planned drives to be simulated before commands are sent to the rover. The deformable soils component of this model allows rover-terrain interactions to be simulated to determine if a particular drive path would take the rover over terrain that would induce hazardous levels of slip or sink. When used in the rover drive planning process, dynamic modeling reduces the likelihood of future mobility issues because high-risk areas could be identified before drive commands are sent to the rover, and drives planned over these areas could be rerouted. The ARTEMIS software consists of several components. These include a preprocessor, Digital Elevation Models (DEMs), Adams rover model, wheel and soil parameter files, MSC Adams GUI (commercial), MSC Adams dynamics solver (commercial), terramechanics subroutines (FORTRAN), a contact detection engine, a soil modification engine, and output DEMs of deformed soil. The preprocessor is used to define the terrain (from a DEM) and define the soil parameters for the terrain file. The Adams rover model is placed in this terrain. Wheel and soil parameter files

  9. Adams-Oliver Syndrome: A Case with Full Expression

    PubMed Central

    Dehdashtian, Amir; Dehdashtian, Masoud

    2016-01-01

    Adams-Oliver syndrome (AOS) is characterized by the combination of congenital scalp defects (aplasia cutis congenita) and terminal transverse limb defects of variable severity. It is believed that Adams-Oliver syndrome without major organ abnormalities does not necessarily alter the normal lifespan. We present a case without detectable major organ abnormality contrary to life but with poor weight gain. A male infant with scalp and skin cutis aplasia, generalized cutis aplasia, dilated veins over scalp and trunk, hypoplastic toes and nails of feet, glaucoma, poor feeding and poor weight gain. This report shows a case of AOS without major multiple organ abnormalities but with poor feeding and abnormal weight gain that may be alter the normal lifespan. PMID:27433307

  10. Empathy's purity, sympathy's complexities; De Waal, Darwin and Adam Smith.

    PubMed

    van der Weele, Cor

    2011-07-01

    Frans de Waal's view that empathy is at the basis of morality directly seems to build on Darwin, who considered sympathy as the crucial instinct. Yet when we look closer, their understanding of the central social instinct differs considerably. De Waal sees our deeply ingrained tendency to sympathize (or rather: empathize) with others as the good side of our morally dualistic nature. For Darwin, sympathizing was not the whole story of the "workings of sympathy"; the (selfish) need to receive sympathy played just as central a role in the complex roads from sympathy to morality. Darwin's understanding of sympathy stems from Adam Smith, who argued that the presence of morally impure motives should not be a reason for cynicism about morality. I suggest that De Waal's approach could benefit from a more thorough alignment with the analysis of the workings of sympathy in the work of Darwin and Adam Smith.

  11. Automatic Dynamic Aircraft Modeler (ADAM) for the Computer Program NASTRAN

    NASA Technical Reports Server (NTRS)

    Griffis, H.

    1985-01-01

    Large general purpose finite element programs require users to develop large quantities of input data. General purpose pre-processors are used to decrease the effort required to develop structural models. Further reduction of effort can be achieved by specific application pre-processors. Automatic Dynamic Aircraft Modeler (ADAM) is one such application specific pre-processor. General purpose pre-processors use points, lines and surfaces to describe geometric shapes. Specifying that ADAM is used only for aircraft structures allows generic structural sections, wing boxes and bodies, to be pre-defined. Hence with only gross dimensions, thicknesses, material properties and pre-defined boundary conditions a complete model of an aircraft can be created.

  12. Empathy's purity, sympathy's complexities; De Waal, Darwin and Adam Smith.

    PubMed

    van der Weele, Cor

    2011-07-01

    Frans de Waal's view that empathy is at the basis of morality directly seems to build on Darwin, who considered sympathy as the crucial instinct. Yet when we look closer, their understanding of the central social instinct differs considerably. De Waal sees our deeply ingrained tendency to sympathize (or rather: empathize) with others as the good side of our morally dualistic nature. For Darwin, sympathizing was not the whole story of the "workings of sympathy"; the (selfish) need to receive sympathy played just as central a role in the complex roads from sympathy to morality. Darwin's understanding of sympathy stems from Adam Smith, who argued that the presence of morally impure motives should not be a reason for cynicism about morality. I suggest that De Waal's approach could benefit from a more thorough alignment with the analysis of the workings of sympathy in the work of Darwin and Adam Smith. PMID:21765569

  13. ADAM: An Axisymmetric Duct Aeroacoustic Modeling system. [aircraft turbofan engines

    NASA Technical Reports Server (NTRS)

    Abrahamson, A. L.

    1983-01-01

    An interconnected system of computer programs for analyzing the propagation and attenuation of sound in aeroengine ducts containing realistic compressible subsonic mean flows, ADAM was developed primarily for research directed towards the reduction of noise emitted from turbofan aircraft engines. The two basic components are a streamtube curvature program for determination of the mean flow, and a finite element code for solution of the acoustic propagation problem. The system, which has been specifically tailored for ease of use, is presently installed at NASA Langley Reseach Center on a Control Data Cyber 175 Computer under the NOS Operating system employing a Tektronix terminal for interactive graphics. The scope and organization of the ADAM system is described. A users guide, examples of input data, and results for selected cases are included.

  14. Application of the ADAMS program to deployable space truss structures

    NASA Technical Reports Server (NTRS)

    Calleson, R. E.

    1985-01-01

    The need for a computer program to perform kinematic and dynamic analyses of large truss structures while deploying from a packaged configuration in space led to the evaluation of several existing programs. ADAMS (automatic dynamic analysis of mechanical systems), a generalized program from performing the dynamic simulation of mechanical systems undergoing large displacements, is applied to two concepts of deployable space antenna units. One concept is a one cube folding unit of Martin Marietta's Box Truss Antenna and the other is a tetrahedral truss unit of a Tetrahedral Truss Antenna. Adequate evaluation of dynamic forces during member latch-up into the deployed configuration is not yet available from the present version of ADAMS since it is limited to the assembly of rigid bodies. Included is a method for estimating the maximum bending stress in a surface member at latch-up. Results include member displacement and velocity responses during extension and an example of member bending stresses at latch-up.

  15. Control of ADAM17 activity by regulation of its cellular localisation

    PubMed Central

    Lorenzen, Inken; Lokau, Juliane; Korpys, Yvonne; Oldefest, Mirja; Flynn, Charlotte M.; Künzel, Ulrike; Garbers, Christoph; Freeman, Matthew; Grötzinger, Joachim; Düsterhöft, Stefan

    2016-01-01

    An important, irreversible step in many signalling pathways is the shedding of membrane-anchored proteins. A Disintegrin And Metalloproteinase (ADAM) 17 is one of the major sheddases involved in a variety of physiological and pathophysiological processes including regeneration, differentiation, and cancer progression. This central role in signalling implies that ADAM17 activity has to be tightly regulated, including at the level of localisation. Most mature ADAM17 is localised intracellularly, with only a small amount at the cell surface. We found that ADAM17 is constitutively internalised by clathrin-coated pits and that physiological stimulators such as GPCR ligands induce ADAM17-mediated shedding, but do not alter the cell-surface abundance of the protease. In contrast, the PKC-activating phorbol ester PMA, often used as a strong inducer of ADAM17, causes not only proteolysis by ADAM17 but also a rapid increase of the mature protease at the cell surface. This is followed by internalisation and subsequent degradation of the protease. Eventually, this leads to a substantial downregulation of mature ADAM17. Our results therefore imply that physiological activation of ADAM17 does not rely on its relocalisation, but that PMA-induced PKC activity drastically dysregulates the localisation of ADAM17. PMID:27731361

  16. ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression

    PubMed Central

    Fritzsche, Florian R; Wassermann, Kirsten; Jung, Monika; Tölle, Angelika; Kristiansen, Ilka; Lein, Michael; Johannsen, Manfred; Dietel, Manfred; Jung, Klaus; Kristiansen, Glen

    2008-01-01

    Background A Disintegrin And Metalloprotease (ADAM) 9 has been implicated in tumour progression of various solid tumours, however, little is known about its role in renal cell carcinoma. We evaluated the expression of ADAM9 on protein and transcript level in a clinico-pathologically characterized renal cell cancer cohort. Methods 108 renal cancer cases were immunostained for ADAM9 on a tissue-micro-array. For 30 additional cases, ADAM9 mRNA of microdissected tumour and normal tissue was analyzed via quantitative RT-PCR. SPSS 14.0 was used to apply crosstables (Fisher's exact test and χ2-test), correlations and univariate as well as multivariate survival analyses. Results ADAM9 was significantly up-regulated in renal cancer in comparison to the adjacent normal tissue on mRNA level. On protein level, ADAM9 was significantly associated with higher tumour grade, positive nodal status and distant metastasis. Furthermore, ADAM9 protein expression was significantly associated with shortened patient survival in the univariate analysis. Conclusion ADAM9 is strongly expressed in a large proportion of renal cell cancers, concordant with findings in other tumour entities. Additionally, ADAM9 expression is significantly associated with markers of unfavourable prognosis. Whether the demonstrated prognostic value of ADAM9 is independent from other tumour parameters will have to be verified in larger study cohorts. PMID:18582378

  17. ADAM-mediated amphiregulin shedding and EGFR transactivation

    PubMed Central

    Kasina, S.; Scherle, P. A.; Hall, C. L.; Macoska, J. A.

    2011-01-01

    Introduction The ectodomain shedding of epidermal growth factor receptor (EGFR) ligands, such as amphiregulin (AREG), by ADAMs (A Disintegrin And Metalloproteases) can be stimulated by G protein-coupled receptor (GPCR) agonists. Interactions between the CXCR4 GPCR and the CXCL12 chemokine have been shown to mediate gene transcription and cellular proliferation in non-transformed and transformed prostate epithelial cells, as well as motility/invasiveness in transformed cells. Objectives In this report, we investigated the ability of CXCL12 to stimulate amphiregulin ectodomain shedding in non-transformed and transformed prostate epithelial cells that respond proliferatively to sub-nanomolar levels of CXCL12 and amphiregulin. Materials and Methods Non-transformed N15C6 and transformed PC3 prostate epithelial cells were assessed for amphiregulin shedding, ADAM activation, Src phosphorylation and EGFR activation using ELISA, immunoblot, and immunoprecipitation techniques, and for proliferation using cell counting after stimulation with CXCL12 or vehicle. Results The results of these studies identify CXCL12 as a novel inducer of amphiregulin ectodomain shedding and show that both basal and CXCL12-mediated amphiregulin shedding are ADAM10- and Src kinase-dependent in non-transformed N15C6 cells. In contrast, amphiregulin shedding is not amplified subsequent to stimulation with exogenous CXCL12, and is not reduced subsequent to metalloprotease- or Src kinase-inhibition, in highly aggressive PC3 prostate cancer cells. These data also show that CXCL12-mediated cellular proliferation requires EGFR transactivation in a Src-and ADAM-dependent manner in non-transformed prostate epithelial cells. However, these same mechanisms are dysfunctional in highly transformed prostate cancer cells, which secrete amphiregulin in an autocrine manner that cannot be repressed through metalloprotease- or Src kinase inhibition. Conclusion These findings show that non-transformed and transformed

  18. Evaluation of ADAM/1 model for advanced coal extraction concepts

    NASA Technical Reports Server (NTRS)

    Deshpande, G. K.; Gangal, M. D.

    1982-01-01

    Several existing computer programs for estimating life cycle cost of mining systems were evaluated. A commercially available program, ADAM/1 was found to be satisfactory in relation to the needs of the advanced coal extraction project. Two test cases were run to confirm the ability of the program to handle nonconventional mining equipment and procedures. The results were satisfactory. The model, therefore, is recommended to the project team for evaluation of their conceptual designs.

  19. ADAMS GAP AND SHINBONE CREEK ROADLESS AREAS, ALABAMA.

    USGS Publications Warehouse

    Klein, T.L.; Harrison, Donald K.

    1984-01-01

    The Adams Gap and Shinbone Creek Roadless Areas in Alabama were evaluated for their mineral potential. The only resource within the established boundary of the roadless area is quartzite suitable for crushed rock or refractory-grade aggregate. The quartzite contains deleterious impurities and is found in abundance outside the areas. Natural gas or petroleum may exist at depth. Detailed seismic studies and deep drilling tests are needed before a reasonable estimate of hydrocarbon potential can be made.

  20. iRhoms 1 and 2 are essential upstream regulators of ADAM17-dependent EGFR signaling

    PubMed Central

    Li, Xue; Maretzky, Thorsten; Weskamp, Gisela; Monette, Sébastien; Qing, Xiaoping; Issuree, Priya Darshinee A.; Crawford, Howard C.; McIlwain, David R.; Mak, Tak W.; Salmon, Jane E.; Blobel, Carl P.

    2015-01-01

    The metalloproteinase ADAM17 (a disintegrin and metalloprotease 17) controls EGF receptor (EGFR) signaling by liberating EGFR ligands from their membrane anchor. Consequently, a patient lacking ADAM17 has skin and intestinal barrier defects that are likely caused by lack of EGFR signaling, and Adam17−/− mice die perinatally with open eyes, like Egfr−/− mice. A hallmark feature of ADAM17-dependent EGFR ligand shedding is that it can be rapidly and posttranslationally activated in a manner that requires its transmembrane domain but not its cytoplasmic domain. This suggests that ADAM17 is regulated by other integral membrane proteins, although much remains to be learned about the underlying mechanism. Recently, inactive Rhomboid 2 (iRhom2), which has seven transmembrane domains, emerged as a molecule that controls the maturation and function of ADAM17 in myeloid cells. However, iRhom2−/− mice appear normal, raising questions about how ADAM17 is regulated in other tissues. Here we report that iRhom1/2−/− double knockout mice resemble Adam17−/− and Egfr−/− mice in that they die perinatally with open eyes, misshapen heart valves, and growth plate defects. Mechanistically, we show lack of mature ADAM17 and strongly reduced EGFR phosphorylation in iRhom1/2−/− tissues. Finally, we demonstrate that iRhom1 is not essential for mouse development but regulates ADAM17 maturation in the brain, except in microglia, where ADAM17 is controlled by iRhom2. These results provide genetic, cell biological, and biochemical evidence that a principal function of iRhoms1/2 during mouse development is to regulate ADAM17-dependent EGFR signaling, suggesting that iRhoms1/2 could emerge as novel targets for treatment of ADAM17/EGFR-dependent pathologies. PMID:25918388

  1. The alpha secretase ADAM10: A metalloprotease with multiple functions in the brain.

    PubMed

    Saftig, Paul; Lichtenthaler, Stefan F

    2015-12-01

    Proteins belonging to the 'A Disintegrin And Metalloproteinase' (ADAM) family are membrane-anchored proteases that are able to cleave the extracellular domains of several membrane-bound proteins in a process known as 'ectodomain shedding'. In the central nervous system, ADAM10 has attracted the most attention, since it was described as the amyloid precursor protein α-secretase over ten years ago. Despite the excitement over the potential of ADAM10 as a novel drug target in Alzheimer disease, the physiological functions of ADAM10 in the brain are not yet well understood. This is largely because of the embryonic lethality of ADAM10-deficient mice, which results from the loss of cleavage and signaling of the Notch receptor, another ADAM10 substrate. However, the recent generation of conditional ADAM10-deficient mice and the identification of further ADAM10 substrates in the brain has revealed surprisingly numerous and fundamental functions of ADAM10 in the development of the embryonic brain and also in the homeostasis of adult neuronal networks. Mechanistically, ADAM10 controls these functions by utilizing unique postsynaptic substrates in the central nervous system, in particular synaptic cell adhesion molecules, such as neuroligin-1, N-cadherin, NCAM, Ephrin A2 and A5. Consequently, a dysregulation of ADAM10 activity is linked to psychiatric and neurological diseases, such as epilepsy, fragile X syndrome and Huntington disease. This review highlights the recent progress in understanding the substrates and function as well as the regulation and cell biology of ADAM10 in the central nervous system and discusses the value of ADAM10 as a drug target in brain diseases.

  2. Dr. Lytle Adams' incendiary "bat bomb" of World War II.

    PubMed

    Christen, Arden G; Christen, Joan A

    2004-11-01

    On December 7, 1941, a 60-year old dentist from Irwin, Pennsylvania, Dr. Lytle S. Adams, was driving home from a vacation at Carlsbad Caverns in New Mexico. Hours earlier, he had been gripped with amazement as he witnessed millions of bats exiting the caves of Carlsbad. Listening to his car radio on his return trip, he was shocked to hear that Japan had just attacked Pearl Harbor. Dr. Adams, outraged over this travesty, began to mentally construct a plan for U.S. retaliation. As his thoughts returned to the countless bats that had awed him, he formed a tentative plan: millions of these small, flying mammals could be connected to tiny, time-fused incendiary bombs, and then released to land on the flimsily constructed structures which dotted the cities of Japan. Within a few minutes, the bombs would explode and enflame the entire urban areas. He postulated that these immeasurable numbers of fires, spreading their devastation over such vast areas within Japanese cities would result in the enemy's speedy surrender. This article documents the futile efforts of Dr. Adams, his team and the U.S. government to develop and employ an effective, incendiary bat bomb. The recently developed atom bomb, a far more deadly weapon was used in its place. PMID:15666497

  3. Dr. Lytle Adams' incendiary "bat bomb" of World War II.

    PubMed

    Christen, Arden G; Christen, Joan A

    2004-11-01

    On December 7, 1941, a 60-year old dentist from Irwin, Pennsylvania, Dr. Lytle S. Adams, was driving home from a vacation at Carlsbad Caverns in New Mexico. Hours earlier, he had been gripped with amazement as he witnessed millions of bats exiting the caves of Carlsbad. Listening to his car radio on his return trip, he was shocked to hear that Japan had just attacked Pearl Harbor. Dr. Adams, outraged over this travesty, began to mentally construct a plan for U.S. retaliation. As his thoughts returned to the countless bats that had awed him, he formed a tentative plan: millions of these small, flying mammals could be connected to tiny, time-fused incendiary bombs, and then released to land on the flimsily constructed structures which dotted the cities of Japan. Within a few minutes, the bombs would explode and enflame the entire urban areas. He postulated that these immeasurable numbers of fires, spreading their devastation over such vast areas within Japanese cities would result in the enemy's speedy surrender. This article documents the futile efforts of Dr. Adams, his team and the U.S. government to develop and employ an effective, incendiary bat bomb. The recently developed atom bomb, a far more deadly weapon was used in its place.

  4. Dissecting the role of ADAM10 as a mediator of Staphylococcus aureus α-toxin action.

    PubMed

    von Hoven, Gisela; Rivas, Amable J; Neukirch, Claudia; Klein, Stefan; Hamm, Christian; Qin, Qianqian; Meyenburg, Martina; Füser, Sabine; Saftig, Paul; Hellmann, Nadja; Postina, Rolf; Husmann, Matthias

    2016-07-01

    Staphylococcus aureus is a leading cause of bacterial infections in humans, including life-threatening diseases such as pneumonia and sepsis. Its small membrane-pore-forming α-toxin is considered an important virulence factor. By destroying cell-cell contacts through cleavage of cadherins, the metalloproteinase ADAM10 (a disintegrin and metalloproteinase 10) critically contributes to α-toxin-dependent pathology of experimental S. aureus infections in mice. Moreover, ADAM10 was proposed to be a receptor for α-toxin. However, it is unclear whether the catalytic activity or specific domains of ADAM10 are involved in mediating binding and/or subsequent cytotoxicity of α-toxin. Also, it is not known how α-toxin triggers ADAM10's enzymatic activity, and whether ADAM10 is invariably required for all α-toxin action on cells. In the present study, we show that efficient cleavage of the ADAM10 substrate epithelial cadherin (E-cadherin) requires supra-cytotoxic concentrations of α-toxin, leading to significant increases in intracellular [Ca(2+)]; the fall in cellular ATP levels, typically following membrane perforation, became observable at far lower concentrations. Surprisingly, ADAM10 was dispensable for α-toxin-dependent xenophagic targeting of S. aureus, whereas a role for α-toxin attack on the plasma membrane was confirmed. The catalytic site of ADAM10, furin cleavage site, cysteine switch and intracellular domain of ADAM10 were not required for α-toxin binding and subsequent cytotoxicity. In contrast, an essential role for the disintegrin domain and the prodomain emerged. Thus, co-expression of the prodomain with prodomain-deficient ADAM10 reconstituted binding of α-toxin and susceptibility of ADAM10-deficient cells. The results of the present study may help to inform structural analyses of α-toxin-ADAM10 interactions and to design novel strategies to counteract S. aureus α-toxin action.

  5. ADAM22, A KV1 CHANNEL INTERACTING PROTEIN, RECRUITS MAGUKS TO JUXTAPARANODES OF MYELINATED AXONS

    PubMed Central

    Ogawa, Yasuhiro; Oses-Prieto, Juan; Kim, Moon Young; Horresh, Ido; Peles, Elior; Burlingame, Alma L.; Trimmer, James S.; Meijer, Dies; Rasband, Matthew N.

    2009-01-01

    Clustered Kv1 K+ channels regulate neuronal excitability at juxtaparanodes of myelinated axons, axon initial segments (AIS), and cerebellar basket cell terminals (BCTs). These channels are part of a larger protein complex that includes cell adhesion molecules and scaffolding proteins. To identify proteins that regulate assembly, clustering, and/or maintenance of axonal Kv1 channel protein complexes, we immunoprecipitated Kv1.2 α subunits, then used mass-spectrometry to identify interacting proteins. We found that ADAM22 (A Disintegrin And Metalloproteinase 22) is a component of the Kv1 channel complex, and that ADAM22 co-immunoprecipitates Kv1.2 and the MAGUKs PSD-93 and PSD-95. When co-expressed with MAGUKs in heterologous cells, ADAM22 and Kv1 channels are recruited into membrane surface clusters. However, co-expression of Kv1.2 with ADAM22 and MAGUKs does not alter channel properties. Among all the known Kv1 channel interacting proteins, only ADAM22 is found at every site where Kv1 channels are clustered. Analysis of Caspr-null mice showed that like other previously described juxtaparanodal proteins, disruption of the paranodal junction resulted in redistribution of ADAM22 into paranodal zones. Analysis of Caspr2-, PSD-93-, PSD-95-, and double PSD-93/PSD-95-null mice showed ADAM22 clustering at BCTs requires PSD-95, but ADAM22 clustering at juxtaparanodes requires neither PSD-93 nor PSD-95. In direct contrast, analysis of ADAM22-null mice demonstrated juxtaparanodal clustering of PSD-93 and PSD-95 requires ADAM22, whereas Kv1.2 and Caspr2 clustering is normal in ADAM22-null mice. Thus, ADAM22 is an axonal component of the Kv1 K+ channel complex that recruits MAGUKs to juxtaparanodes. PMID:20089912

  6. [Cloning of mouse adam10 gene promoter and construction and identification of dual luciferase reporter system].

    PubMed

    Chen, Wei; Chen, Chong; Zhang, Huan-Xin; Cao, Jiang; Sang, Wei; Wu, Qing-Yun; Zhao, Kai; Zang, Yu; Zeng, Ling-Yu; Xu, Kai-Lin

    2012-06-01

    This study was aimed to clone mouse adam10 gene promoter and construct its dual luciferase report vector, and to investigate its transcriptional activity. Total DNA was extracted from mouse brain and used for amplifying the fragment containing adam10 gene promoter by PCR. The amplified product was inserted into pGL-4.10 vector to construct pGL4.10-adam10. The pGL4.10-adam10 and control plasmid pGL4.74 were co-transfected into HEK293 FT cells by lipofectamine 2000. The activity of adam10 gene promoter was assayed by luciferase system. The results showed that the recombinant plasmid pGL4.10-adam10 containing promoter of mouse adam10 was correctly constructed. The method was optimized by changing ratio of two plasmids. Moreover, the transcriptional activity of pGL4.10-adam10 stimulated by ionomycin increased. It is concluded that the dual luciferase reporter system is successfully established, which is useful in bioluminescence imaging technology in vitro. The effect of ionomycin can enhance the transcriptional activity of adam10 gene promoter.

  7. ADAM10 Is Involved in Cell Junction Assembly in Early Porcine Embryo Development.

    PubMed

    Kwon, Jeongwoo; Jeong, Sung-min; Choi, Inchul; Kim, Nam-Hyung

    2016-01-01

    ADAM10 (A Disintegrin and Metalloprotease domain-containing protein 10) is a cell surface protein with a unique structure possessing both potential adhesion and protease domains. However, the role of ADAM10 in preimplantation stage embryos is not clear. In this study, we examined the expression patterns and functional roles of ADAM10 in porcine parthenotes during preimplantation development. The transcription level of ADAM10 dramatically increased from the morula stage onward. Immunostaining revealed that ADAM10 was present in both the nucleus and cytoplasm in early cleavage stage embryos, and localized to the apical region of the outer cells in morula and blastocyst embryos. Knockdown (KD) of ADAM10 using double strand RNA did not alter preimplantation embryo development until morula stage, but resulted in significantly reduced development to blastocyst stage. Moreover, the KD blastocyst showed a decrease in gene expression of adherens and tight junction (AJ/TJ), and an increase in trophectoderm TJ permeability by disrupting TJ assembly. Treatment with an ADAM10 specific chemical inhibitor, GI254023X, at the morula stage also inhibited blastocyst development and led to disruption of TJ assembly. An in situ proximity ligation assay demonstrated direct interaction of ADAM10 with coxsackie virus and adenovirus receptor (CXADR), supporting the involvement of ADAM10 in TJ assembly. In conclusion, our findings strongly suggest that ADADM10 is important for blastocyst formation rather than compaction, particularly for TJ assembly and stabilization in preimplantation porcine parthenogenetic development. PMID:27043020

  8. ADAM10 Is Involved in Cell Junction Assembly in Early Porcine Embryo Development

    PubMed Central

    Kwon, Jeongwoo; Jeong, Sung-min; Choi, Inchul; Kim, Nam-Hyung

    2016-01-01

    ADAM10 (A Disintegrin and Metalloprotease domain-containing protein 10) is a cell surface protein with a unique structure possessing both potential adhesion and protease domains. However, the role of ADAM10 in preimplantation stage embryos is not clear. In this study, we examined the expression patterns and functional roles of ADAM10 in porcine parthenotes during preimplantation development. The transcription level of ADAM10 dramatically increased from the morula stage onward. Immunostaining revealed that ADAM10 was present in both the nucleus and cytoplasm in early cleavage stage embryos, and localized to the apical region of the outer cells in morula and blastocyst embryos. Knockdown (KD) of ADAM10 using double strand RNA did not alter preimplantation embryo development until morula stage, but resulted in significantly reduced development to blastocyst stage. Moreover, the KD blastocyst showed a decrease in gene expression of adherens and tight junction (AJ/TJ), and an increase in trophectoderm TJ permeability by disrupting TJ assembly. Treatment with an ADAM10 specific chemical inhibitor, GI254023X, at the morula stage also inhibited blastocyst development and led to disruption of TJ assembly. An in situ proximity ligation assay demonstrated direct interaction of ADAM10 with coxsackie virus and adenovirus receptor (CXADR), supporting the involvement of ADAM10 in TJ assembly. In conclusion, our findings strongly suggest that ADADM10 is important for blastocyst formation rather than compaction, particularly for TJ assembly and stabilization in preimplantation porcine parthenogenetic development. PMID:27043020

  9. Recent eruptions of Mount Adams, Washington Cascades, USA

    USGS Publications Warehouse

    Hildreth, Wes; Fierstein, Judy

    1997-01-01

    The postglacial eruption rate for the Mount Adams volcanic field is ∼0.1 km3/k.y., four to seven times smaller than the average rate for the past 520 k.y. Ten vents have been active since the last main deglaciation ∼15 ka. Seven high flank vents (at 2100-2600 m) and the central summit vent of the 3742-m stratocone produced varied andesites, and two peripheral vents (at 2100 and 1200 m) produced mildly alkalic basalt. Eruptive ages of most of these units are bracketed with respect to regional tephra layers from Mount Mazama and Mount St. Helens. The basaltic lavas and scoria cones north and south of Mount Adams and a 13-km-long andesitic lava flow on its east flank are of early postglacial age. The three most extensive andesitic lava-flow complexes were emplaced in the mid-Holocene (7-4 ka). Ages of three smaller Holocene andesite units are less well constrained. A phreatomagmatic ejecta cone and associated andesite lavas that together cap the summit may be of latest Pleistocene age. but a thin layer of mid-Holocene tephra appears to have erupted there as well. An alpine-meadow section on the southeast flank contains 24 locally derived Holocene andesitic ash layers intercalated with several silicic tephras from Mazama and St. Helens. Microprobe analyses of phenocrysts from the ash layers and postglacial lavas suggest a few correlations and refine some age constraints. Approximately 6 ka, a 0.07-km3 debris avalanche from the southwest face of Mount Adams gen-erated a clay-rich debris flow that devastated >30 km2 south of the volcano. A gravitationally metastable 2-to 3-km3 reservoir of hydrothermally altered fragmental andesite remains on the ice-capped summit and, towering 3 km above the surrounding lowlands, represents a greater hazard than an eruptive recurrence in the style of the last 15 k.y.

  10. Simulation of Naval Guns' Breechblock System Dynamics Based on ADAMS

    NASA Astrophysics Data System (ADS)

    Tan, Bo; Liu, Hui-Min; Liu, Kai

    In order to study the dynamical characteristics of the breechblock system during gun firing, a virtual prototype model was established based on ADAMS, in which motion and force transmission among mechanisms are realized by collision. By simulation, kinematics and dynamics properties of main components are obtained, and the relationships between the motion of breechblock and the position of breechblock opening plate are analyzed. According to the simulation results, the collision among the breechblock opening plate and the roller is discontinuous, which may make the breechblock system fail to hitch the breechblock reliably. And within allowable scope of the structure, the breechblock opening template should be installed near the upside as much as possible.

  11. Lance–Adams syndrome: A special case of a mother

    PubMed Central

    Nigam, Gaurav Bhaskar; Babu, Sachin Suresh; Peter, C. Sudhir; Peter, C. Shobhna

    2016-01-01

    Predicting the neurological outcome in survivors of cardiorespiratory arrest is difficult. A distinction has been made between acute and chronic posthypoxic myoclonus, called myoclonic status epilepticus and Lance–Adams syndrome (LAS), respectively, with the acute condition carrying a bad prognosis. Here, we report a case of a 37-year-old female who developed seizures after a successful cardiopulmonary resuscitation. The available literature on such cases is very rare and has generally mentioned a poor outcome. However, our patient was successfully managed and showed clinical features of LAS. Thus, making an early diagnosis and proper management of hypoxic brain insults is positively related to improving the patient's functional outcome.

  12. The "delivery" of Adam: a medical interpretation of Michelangelo.

    PubMed

    Di Bella, Stefano; Taglietti, Fabrizio; Iacobuzio, Andrea; Johnson, Emma; Baiocchini, Andrea; Petrosillo, Nicola

    2015-04-01

    This article describes what we believe to be the key to interpreting the concept represented by Michelangelo's painting the Creation of Adam. This fresco, one of his most famous masterpieces, is situated in the heart of the Sistine Chapel and is viewed by millions of people every year. A man of many talents, Michelangelo's proficiency in anatomical dissection is reflected in his artwork. As such, analyses of hidden meanings in this fresco have been ascribed, including the concept of the "Brain-God." However, we see a postpartum uterus and adjacent anatomy, justifying our interpretation that Michelangelo was depicting something far more fundamental: the birth of mankind. PMID:25841253

  13. Lance-Adams syndrome: A special case of a mother.

    PubMed

    Nigam, Gaurav Bhaskar; Babu, Sachin Suresh; Peter, C Sudhir; Peter, C Shobhna

    2016-09-01

    Predicting the neurological outcome in survivors of cardiorespiratory arrest is difficult. A distinction has been made between acute and chronic posthypoxic myoclonus, called myoclonic status epilepticus and Lance-Adams syndrome (LAS), respectively, with the acute condition carrying a bad prognosis. Here, we report a case of a 37-year-old female who developed seizures after a successful cardiopulmonary resuscitation. The available literature on such cases is very rare and has generally mentioned a poor outcome. However, our patient was successfully managed and showed clinical features of LAS. Thus, making an early diagnosis and proper management of hypoxic brain insults is positively related to improving the patient's functional outcome. PMID:27688633

  14. ADAM15 Is Functionally Associated with the Metastatic Progression of Human Bladder Cancer

    PubMed Central

    Rubin, John R.; Hayward, Alexandra; Cates, Angelica L.; Day, Kathleen C.; El-Sawy, Layla; Kunju, L. Priya; Daignault, Stephanie; Lee, Cheryl T.; Liebert, Monica; Hussain, Maha; Day, Mark L.

    2016-01-01

    ADAM15 is a member of a family of catalytically active disintegrin membrane metalloproteinases that function as molecular signaling switches, shed membrane bound growth factors and/or cleave and inactivate cell adhesion molecules. Aberrant metalloproteinase function of ADAM15 may contribute to tumor progression through the release of growth factors or disruption of cell adhesion. In this study, we utilized human bladder cancer tissues and cell lines to evaluate the expression and function of ADAM15 in the progression of human bladder cancer. Examination of genome and transcriptome databases revealed that ADAM15 ranked in the top 5% of amplified genes and its mRNA was significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. Immunostaining of a bladder tumor tissue array designed to evaluate disease progression revealed increased ADAM15 immunoreactivity associated with increasing cancer stage and exhibited significantly stronger staining in metastatic samples. About half of the invasive tumors and the majority of the metastatic cases exhibited high ADAM15 staining index, while all low grade and noninvasive cases exhibited negative or low staining. The knockdown of ADAM15 mRNA expression significantly inhibited bladder tumor cell migration and reduced the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibited tumor growth by 45% compared to controls. Structural modeling of the catalytic domain led to the design of a novel ADAM15-specific sulfonamide inhibitor that demonstrated bioactivity and significantly reduced the viability of bladder cancer cells in vitro and in human bladder cancer xenografts. Taken together, the results revealed an undescribed role of ADAM15 in the invasion of human bladder cancer and suggested that the ADAM15 catalytic domain may represent a viable therapeutic target in

  15. 77 FR 75207 - The Adams Express Company and Petroleum & Resources Corporation; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ... COMMISSION The Adams Express Company and Petroleum & Resources Corporation; Notice of Application December 13... and Petroleum & Resources Corporation (the ``Funds''). DATES: Filing Dates: The application was filed..., 2012, The Adams Express Company held approximately 8.5% of the outstanding shares of...

  16. ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease.

    PubMed

    Letronne, Florent; Laumet, Geoffroy; Ayral, Anne-Marie; Chapuis, Julien; Demiautte, Florie; Laga, Mathias; Vandenberghe, Michel E; Malmanche, Nicolas; Leroux, Florence; Eysert, Fanny; Sottejeau, Yoann; Chami, Linda; Flaig, Amandine; Bauer, Charlotte; Dourlen, Pierre; Lesaffre, Marie; Delay, Charlotte; Huot, Ludovic; Dumont, Julie; Werkmeister, Elisabeth; Lafont, Franck; Mendes, Tiago; Hansmannel, Franck; Dermaut, Bart; Deprez, Benoit; Hérard, Anne-Sophie; Dhenain, Marc; Souedet, Nicolas; Pasquier, Florence; Tulasne, David; Berr, Claudine; Hauw, Jean-Jacques; Lemoine, Yves; Amouyel, Philippe; Mann, David; Déprez, Rebecca; Checler, Frédéric; Hot, David; Delzescaux, Thierry; Gevaert, Kris; Lambert, Jean-Charles

    2016-07-01

    Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30(mut)) did not affect Aβ secretion. Proteomics/cell-based experiments showed that ADAM30-dependent regulation of APP metabolism required both cathepsin D (CTSD) activation and APP sorting to lysosomes. Accordingly, in Alzheimer-like transgenic mice, neuronal ADAM30 over-expression lowered Aβ42 secretion in neuron primary cultures, soluble Aβ42 and amyloid plaque load levels in the brain and concomitantly enhanced CTSD activity and finally rescued long term potentiation alterations. Our data thus indicate that lowering ADAM30 expression may favor Aβ production, thereby contributing to Alzheimer's disease development. PMID:27333034

  17. ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease.

    PubMed

    Letronne, Florent; Laumet, Geoffroy; Ayral, Anne-Marie; Chapuis, Julien; Demiautte, Florie; Laga, Mathias; Vandenberghe, Michel E; Malmanche, Nicolas; Leroux, Florence; Eysert, Fanny; Sottejeau, Yoann; Chami, Linda; Flaig, Amandine; Bauer, Charlotte; Dourlen, Pierre; Lesaffre, Marie; Delay, Charlotte; Huot, Ludovic; Dumont, Julie; Werkmeister, Elisabeth; Lafont, Franck; Mendes, Tiago; Hansmannel, Franck; Dermaut, Bart; Deprez, Benoit; Hérard, Anne-Sophie; Dhenain, Marc; Souedet, Nicolas; Pasquier, Florence; Tulasne, David; Berr, Claudine; Hauw, Jean-Jacques; Lemoine, Yves; Amouyel, Philippe; Mann, David; Déprez, Rebecca; Checler, Frédéric; Hot, David; Delzescaux, Thierry; Gevaert, Kris; Lambert, Jean-Charles

    2016-07-01

    Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30(mut)) did not affect Aβ secretion. Proteomics/cell-based experiments showed that ADAM30-dependent regulation of APP metabolism required both cathepsin D (CTSD) activation and APP sorting to lysosomes. Accordingly, in Alzheimer-like transgenic mice, neuronal ADAM30 over-expression lowered Aβ42 secretion in neuron primary cultures, soluble Aβ42 and amyloid plaque load levels in the brain and concomitantly enhanced CTSD activity and finally rescued long term potentiation alterations. Our data thus indicate that lowering ADAM30 expression may favor Aβ production, thereby contributing to Alzheimer's disease development.

  18. African American Faculty at Traditionally White Institutions: The Impact of the "Adams" Case on Hiring Practices.

    ERIC Educational Resources Information Center

    Silver, Joseph H., Sr.

    1990-01-01

    The "Adams v. Richardson" case required states to redress inequalities in employment opportunities for African American faculty at traditionally White institutions (TWIs). Studies the impact of the litigation in nine states affected by "Adams" and finds evidence of some positive effect. Calls for greater court oversight of TWI faculty hiring. (AF)

  19. DEVELOPMENT OF THE HUMAN LUNG MEASURED BY AEROSOL-DERIVED AIRWAY MORPHEMETRY (ADAM).

    EPA Science Inventory

    We measured, in vivo, the airspace calibers of the small airways and alveoli by ADAM in the lungs of children of ages 6 to 18 years and adults aged 18 to 80 years. ADAM utilizes the gravitational settling time of inhaled monodisperse particles to infer the vertical distance to th...

  20. 75 FR 51519 - Regional Transportation District-Acquisition Exemption-Union Pacific Railroad Company in Adams...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... Railroad Company in Adams, Denver, and Jefferson Counties, CO Regional Transportation District (RTD) \\1... Subdivision extending approximately 8.96 miles, from milepost 628.50, in Adams County, CO., to milepost 637.46... operations as a result of this transaction will not result in the creation of a Class II or Class I...

  1. The futility of utility: how market dynamics marginalize Adam Smith

    NASA Astrophysics Data System (ADS)

    McCauley, Joseph L.

    2000-10-01

    Economic theorizing is based on the postulated, nonempiric notion of utility. Economists assume that prices, dynamics, and market equilibria are supposed to be derived from utility. The results are supposed to represent mathematically the stabilizing action of Adam Smith's invisible hand. In deterministic excess demand dynamics I show the following. A utility function generally does not exist mathematically due to nonintegrable dynamics when production/investment are accounted for, resolving Mirowski's thesis. Price as a function of demand does not exist mathematically either. All equilibria are unstable. I then explain how deterministic chaos can be distinguished from random noise at short times. In the generalization to liquid markets and finance theory described by stochastic excess demand dynamics, I also show the following. Market price distributions cannot be rescaled to describe price movements as ‘equilibrium’ fluctuations about a systematic drift in price. Utility maximization does not describe equilibrium. Maximization of the Gibbs entropy of the observed price distribution of an asset would describe equilibrium, if equilibrium could be achieved, but equilibrium does not describe real, liquid markets (stocks, bonds, foreign exchange). There are three inconsistent definitions of equilibrium used in economics and finance, only one of which is correct. Prices in unregulated free markets are unstable against both noise and rising or falling expectations: Adam Smith's stabilizing invisible hand does not exist, either in mathematical models of liquid market data, or in real market data.

  2. ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

    PubMed

    Xu, Qin; Ying, Mingang; Chen, Guilin; Lin, Ang; Xie, Yunqing; Ohara, Noriyuki; Zhou, Dongmei

    2014-08-01

    Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P < 0.05). Strong expression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P < 0.05). Overexpression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P < 0.05). Multivariate analysis suggested that lymph node metastasis, parametrium invasion, and ADAM17 expression were independent prognostic indicators for cervical cancer. ADAM17 RNAi decreased EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a

  3. The role of CXCL16 and its processing metalloproteinases ADAM10 and ADAM17 in the proliferation and migration of human mesangial cells

    SciTech Connect

    Schramme, Anja; Abdel-Bakky, Mohamed Sadek; Kaempfer-Kolb, Nicole; Pfeilschifter, Josef

    2008-05-30

    In this study, we analyzed the regulation and functional role of CXCL16 in human mesangial cells (hMCs). We can show, that CXCL16 is constitutively expressed in hMCs and is further up-regulated by cytokine mix (IFN{gamma}, TNF{alpha}, and IL1{beta}). The constitutive release of CXCL16 from hMCs was rapidly induced by the stimulation with cytokines. We identified ADAM10 and ADAM17 as being responsible for the cytokine-induced shedding of CXCL16. Notably, targeting ADAM10 and ADAM17 in hMCs decreased the chemotaxis of T-Jurkat cells, whereas the inhibition of CXCL16 had no significant influence. This suggests that both proteases are important players in the recruitment of immune cells into the glomerulus, but other substrates than CXCL16 are involved in this process. Finally, we could show that the inhibition of CXCL16, ADAM10, and ADAM17 led to a strong reduction of cell proliferation and migration of hMCs. This finding could be important to develop novel diagnostic and therapeutic strategies to treat mesangial proliferative kidney diseases.

  4. Identification of novel interaction between ADAM17 (a disintegrin and metalloprotease 17) and thioredoxin-1.

    PubMed

    Aragão, Annelize Z B; Nogueira, Maria Luiza C; Granato, Daniela C; Simabuco, Fernando M; Honorato, Rodrigo V; Hoffman, Zaira; Yokoo, Sami; Laurindo, Francisco R M; Squina, Fabio M; Zeri, Ana Carolina M; Oliveira, Paulo S L; Sherman, Nicholas E; Paes Leme, Adriana F

    2012-12-14

    ADAM17, which is also known as TNFα-converting enzyme, is the major sheddase for the EGF receptor ligands and is considered to be one of the main proteases responsible for the ectodomain shedding of surface proteins. How a membrane-anchored proteinase with an extracellular catalytic domain can be activated by inside-out regulation is not completely understood. We characterized thioredoxin-1 (Trx-1) as a partner of the ADAM17 cytoplasmic domain that could be involved in the regulation of ADAM17 activity. We induced the overexpression of the ADAM17 cytoplasmic domain in HEK293 cells, and ligands able to bind this domain were identified by MS after protein immunoprecipitation. Trx-1 was also validated as a ligand of the ADAM17 cytoplasmic domain and full-length ADAM17 recombinant proteins by immunoblotting, immunolocalization, and solid phase binding assay. In addition, using nuclear magnetic resonance, it was shown in vitro that the titration of the ADAM17 cytoplasmic domain promotes changes in the conformation of Trx-1. The MS analysis of the cross-linked complexes showed cross-linking between the two proteins by lysine residues. To further evaluate the functional role of Trx-1, we used a heparin-binding EGF shedding cell model and observed that the overexpression of Trx-1 in HEK293 cells could decrease the activity of ADAM17, activated by either phorbol 12-myristate 13-acetate or EGF. This study identifies Trx-1 as a novel interaction partner of the ADAM17 cytoplasmic domain and suggests that Trx-1 is a potential candidate that could be involved in ADAM17 activity regulation.

  5. A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma

    PubMed Central

    Kanzaki, Hiroyuki; Shinohara, Fumiaki; Suzuki, Maiko; Wada, Satoshi; Miyamoto, Yutaka; Yamaguchi, Yuuki; Katsumata, Yuta; Makihira, Seicho; Kawai, Toshi; Taubman, Martin A.; Nakamura, Yoshiki

    2016-01-01

    Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases. PMID:27573075

  6. A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma.

    PubMed

    Kanzaki, Hiroyuki; Shinohara, Fumiaki; Suzuki, Maiko; Wada, Satoshi; Miyamoto, Yutaka; Yamaguchi, Yuuki; Katsumata, Yuta; Makihira, Seicho; Kawai, Toshi; Taubman, Martin A; Nakamura, Yoshiki

    2016-01-01

    Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases. PMID:27573075

  7. A new species of Spiroberotha Adams 1989 (Neuroptera: Berothidae) and the first record of the genus in Brazil.

    PubMed

    Machado, Renato Jose Pires; Krolow, Tiago Kütter

    2016-01-01

    The genus Spiroberotha Adams, 1989 is classified in Berothidae (Neuroptera) with two described species: S. fernandezi Adams, 1989 from Venezuela and S. sanctarosae Adams, 1989 from Colombia, Costa Rica and Venezuela. Here we describe a new species, S. tocantinensis n. sp., from Palmas, Tocantins, Brazil. This is the first record of the genus in Brazil, extending its geographical distribution. PMID:27394485

  8. Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

    SciTech Connect

    Endsley, Mark A.; Somasunderam, Anoma D.; Li, Guangyu; Oezguen, Numan; Thiviyanathan, Varatharasa; Murray, James L.; Rubin, Donald H.; Hodge, Thomas W.; and others

    2014-04-15

    Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4{sup +} T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizes with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry. - Highlights: • Nuclear trafficking of the HIV-1 pre-integration complex depends on ADAM10. • ADAM10 associates with HIV-1 integrase in the pre-integration complex. • HIV-1 replication depends on the expression of ADAM15 and γ-secretase. • Silencing ADAM15 or γ-secretase expression inhibits nuclear import of viral cDNA. • ADAM10 is important for HIV-1 replication in human macrophages and CD4{sup +} T lymphocytes.

  9. Econophysical visualization of Adam Smith’s invisible hand

    NASA Astrophysics Data System (ADS)

    Cohen, Morrel H.; Eliazar, Iddo I.

    2013-02-01

    Consider a complex system whose macrostate is statistically observable, but yet whose operating mechanism is an unknown black-box. In this paper we address the problem of inferring, from the system’s macrostate statistics, the system’s intrinsic force yielding the observed statistics. The inference is established via two diametrically opposite approaches which result in the very same intrinsic force: a top-down approach based on the notion of entropy, and a bottom-up approach based on the notion of Langevin dynamics. The general results established are applied to the problem of visualizing the intrinsic socioeconomic force-Adam Smith’s invisible hand-shaping the distribution of wealth in human societies. Our analysis yields quantitative econophysical representations of figurative socioeconomic forces, quantitative definitions of “poor” and “rich”, and a quantitative characterization of the “poor-get-poorer” and the “rich-get-richer” phenomena.

  10. Defenses and morality: Adam Smith, Sigmund Freud, and contemporary psychoanalysis.

    PubMed

    Gabrinetti, Paul A; Özler, Sule

    2014-10-01

    In this paper we follow the development and transmission of moral learning from Adam Smith's impartial spectator to Sigmund Freud's superego and then to contemporary psychoanalysis. We argue that defenses are an integral component in the acquisition of any moral system. Elaborating on this argument, we assert that there is a progression from defensive systems that are "closed" to defensive systems that are "open," as defined in a recent work by Novick and Novick. The former system is "static, avoids reality, and is characterized by power dynamics, sadomasochism, and omnipotent defense." The latter, on the other hand, is a system that allows for "joy, creativity, spontaneity, love and it is attuned to reality." Furthermore, while Smith and Freud's systems are more one-person systems of defense, contemporary psychoanalysis has moved to more of a two-person system.

  11. Defenses and morality: Adam Smith, Sigmund Freud, and contemporary psychoanalysis.

    PubMed

    Gabrinetti, Paul A; Özler, Sule

    2014-10-01

    In this paper we follow the development and transmission of moral learning from Adam Smith's impartial spectator to Sigmund Freud's superego and then to contemporary psychoanalysis. We argue that defenses are an integral component in the acquisition of any moral system. Elaborating on this argument, we assert that there is a progression from defensive systems that are "closed" to defensive systems that are "open," as defined in a recent work by Novick and Novick. The former system is "static, avoids reality, and is characterized by power dynamics, sadomasochism, and omnipotent defense." The latter, on the other hand, is a system that allows for "joy, creativity, spontaneity, love and it is attuned to reality." Furthermore, while Smith and Freud's systems are more one-person systems of defense, contemporary psychoanalysis has moved to more of a two-person system. PMID:25247288

  12. A Disintegrin and Metalloprotease (ADAM): Historical Overview of Their Functions

    PubMed Central

    Giebeler, Nives; Zigrino, Paola

    2016-01-01

    Since the discovery of the first disintegrin protein from snake venom and the following identification of a mammalian membrane-anchored metalloprotease-disintegrin implicated in fertilization, almost three decades of studies have identified additional members of these families and several biochemical mechanisms regulating their expression and activity in the cell. Most importantly, new in vivo functions have been recognized for these proteins including cell partitioning during development, modulation of inflammatory reactions, and development of cancers. In this review, we will overview the a disintegrin and metalloprotease (ADAM) family of proteases highlighting some of the major research achievements in the analysis of ADAMs’ function that have underscored the importance of these proteins in physiological and pathological processes over the years. PMID:27120619

  13. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life

    PubMed Central

    Davies, Elizabeth R.; Kelly, Joanne F.C.; Howarth, Peter H.; Wilson, David I.; Holgate, Stephen T.; Davies, Donna E.; Whitsett, Jeffrey A.

    2016-01-01

    Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma. PMID:27489884

  14. The ADAMs family of proteases as targets for the treatment of cancer.

    PubMed

    Mullooly, Maeve; McGowan, Patricia M; Crown, John; Duffy, Michael J

    2016-08-01

    The ADAMs (a disintegrin and metalloproteases) are transmembrane multidomain proteins implicated in multiple biological processes including proteolysis, cell adhesion, cell fusion, cell proliferation and cell migration. Of these varied activities, the best studied is their role in proteolysis. However, of the 22 ADAMs believed to be functional in humans, only approximately a half possess matrix metalloproteinase (MMP)-like protease activity. In contrast to MMPs which are mostly implicated in the degradation of extracellular matrix proteins, the main ADAM substrates are the ectodomains of type I and type II transmembrane proteins. These include growth factor/cytokine precursors, growth factor/cytokine receptors and adhesion proteins. Recently, several different ADAMs, especially ADAM17, have been shown to play a role in the development and progression of multiple cancer types. Consistent with this role in cancer, targeting ADAM17 with either low molecular weight inhibitors or monoclonal antibodies was shown to have anti-cancer activity in multiple preclinical systems. Although early phase clinical trials have shown no serious side effects with a dual ADAM10/17 low molecular weight inhibitor, the consequences of long-term treatment with these agents is unknown. Furthermore, efficacy in clinical trials remains to be shown.

  15. SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation

    PubMed Central

    Saraceno, C; Marcello, E; Di Marino, D; Borroni, B; Claeysen, S; Perroy, J; Padovani, A; Tramontano, A; Gardoni, F; Di Luca, M

    2014-01-01

    A disintegrin and metalloproteinase 10 (ADAM10) is the major α-secretase that catalyzes the amyloid precursor protein (APP) ectodomain shedding in the brain and prevents amyloid formation. Its activity depends on correct intracellular trafficking and on synaptic membrane insertion. Here, we describe that in hippocampal neurons the synapse-associated protein-97 (SAP97), an excitatory synapse scaffolding element, governs ADAM10 trafficking from dendritic Golgi outposts to synaptic membranes. This process is mediated by a previously uncharacterized protein kinase C phosphosite in SAP97 SRC homology 3 domain that modulates SAP97 association with ADAM10. Such mechanism is essential for ADAM10 trafficking from the Golgi outposts to the synapse, but does not affect ADAM10 transport from the endoplasmic reticulum. Notably, this process is altered in Alzheimer's disease brains. These results help in understanding the mechanism responsible for the modulation of ADAM10 intracellular path, and can constitute an innovative therapeutic strategy to finely tune ADAM10 shedding activity towards APP. PMID:25429624

  16. Neptune's Discovery: Le Verrier, Adams, and the Assignment of Credit

    NASA Astrophysics Data System (ADS)

    Sheehan, William

    2011-01-01

    As one of the most significant achievements of 19th century astronomy, the discovery of Neptune has been the subject of a vast literature. A large part of this literature--beginning with the period immediately after the optical discovery in Berlin--has been the obsession with assigning credit to the two men who attempted to calculate the planet's position (and initially this played out against the international rivalry between France and England). Le Verrier and Adams occupied much different positions in the Scientific Establishments of their respective countries; had markedly different personalities; and approached the investigation using different methods. A psychiatrist and historian of astronomy tries to provide some new contexts to the familiar story of the discovery of Neptune, and argues that the personalities of these two men played crucial roles in their approaches to the problem they set themselves and the way others reacted to their stimuli. Adams had features of high-functioning autism, while Le Verrier's domineering, obsessive, orderly personality--though it allowed him to be immensely productive--eventually led to serious difficulties with his peers (and an outright revolt). Though it took extraordinary smarts to calculate the position of Neptune, the discovery required social skills that these men lacked--and thus the process to discovery was more bumbling and adventitious than it might have been. The discovery of Neptune occurred at a moment when astronomy was changing from that of heroic individuals to team collaborations involving multiple experts, and remains an object lesson in the sociological aspects of scientific endeavor.

  17. Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17

    PubMed Central

    Klingener, Michael; Raines, Elaine W.; Crawford, Howard C.

    2015-01-01

    The identification of the molecular network that supports oligodendrocyte (OL) regeneration under demyelinating conditions has been a primary goal for regenerative medicine in demyelinating disorders. We recently described an essential function for TACE/ADAM17 in regulating oligodendrogenesis during postnatal myelination, but it is unknown whether this protein also plays a role in OL regeneration and remyelination under demyelinating conditions. By using genetic mouse models to achieve selective gain- or loss-of-function of TACE or EGFR in OL lineage cells in vivo, we found that TACE is critical for EGFR activation in OLs following demyelination, and therefore, for sustaining OL regeneration and CNS remyelination. TACE deficiency in oligodendrocyte progenitor cells following demyelination disturbs OL lineage cell expansion and survival, leading to a delay in the remyelination process. EGFR overexpression in TACE deficient OLs in vivo restores OL development and postnatal CNS myelination, but also OL regeneration and CNS remyelination following demyelination. Our study reveals an essential function of TACE in supporting OL regeneration and CNS remyelination that may contribute to the design of new strategies for therapeutic intervention in demyelinating disorders by promoting oligodendrocyte regeneration and myelin repair. SIGNIFICANCE STATEMENT Oligodendrocyte (OL) regeneration has emerged as a promising new approach for the treatment of demyelinating disorders. By using genetic mouse models to selectively delete TACE expression in oligodendrocyte progenitors cells (OPs), we found that TACE/ADAM17 is required for supporting OL regeneration following demyelination. TACE genetic depletion in OPs abrogates EGFR activation in OL lineage cells, and perturbs cell expansion and survival, blunting the process of CNS remyelination. Moreover, EGFR overexpression in TACE-deficient OPs in vivo overcomes the defects in OL development during postnatal development but also OL

  18. ADAM12-directed ectodomain shedding of E-cadherin potentiates trophoblast fusion.

    PubMed

    Aghababaei, M; Hogg, K; Perdu, S; Robinson, W P; Beristain, A G

    2015-12-01

    Trophoblasts, placental cells of epithelial lineage, undergo extensive differentiation to form the cellular components of the placenta. Trophoblast progenitor cell differentiation into the multinucleated syncytiotrophoblast is a key developmental process required for placental function, where defects in syncytiotrophoblast formation and turnover associate with placental pathologies and link to poor pregnancy outcomes. The cellular and molecular processes governing syncytiotrophoblast formation are poorly understood, but require the activation of pathways that direct cell fusion. The protease, A Disintegrin and Metalloproteinase 12 (ADAM12), controls cell fusion in myoblasts and is highly expressed in the placenta localizing to multiple trophoblast populations. However, the importance of ADAM12 in regulating trophoblast fusion is unknown. Here, we describe a function for ADAM12 in regulating trophoblast fusion. Using two distinct trophoblast models of cell fusion, we show that ADAM12 is dynamically upregulated and is under the transcriptional control of protein kinase A. siRNA-directed loss of ADAM12 impedes spontaneous fusion of primary cytotrophoblasts, whereas overexpression of the secreted variant, ADAM12S, potentiates cell fusion in the Bewo trophoblast cell line. Mechanistically, both ectopic and endogenous levels of ADAM12 were shown to control trophoblast fusion through E-cadherin ectodomain shedding and remodeling of intercellular boundaries. This study describes a novel role for ADAM12 in placental development, specifically highlighting its importance in controlling the differentiation of villous cytotrophoblasts into multinucleated cellular structures. Moreover, this work identifies E-cadherin as a novel ADAM12 substrate, and highlights the significance that cell adhesion molecule ectodomain shedding has in normal development.

  19. Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

    PubMed

    Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

    2015-10-01

    Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness.

  20. Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

    PubMed Central

    Kuhn, Peer-Hendrik; Colombo, Alessio Vittorio; Schusser, Benjamin; Dreymueller, Daniela; Wetzel, Sebastian; Schepers, Ute; Herber, Julia; Ludwig, Andreas; Kremmer, Elisabeth; Montag, Dirk; Müller, Ulrike; Schweizer, Michaela; Saftig, Paul; Bräse, Stefan; Lichtenthaler, Stefan F

    2016-01-01

    Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain. DOI: http://dx.doi.org/10.7554/eLife.12748.001 PMID:26802628

  1. The Role of SnoN in Transforming Growth Factor β1-induced Expression of Metalloprotease-Disintegrin ADAM12*

    PubMed Central

    Solomon, Emilia; Li, Hui; Duhachek Muggy, Sara; Syta, Emilia; Zolkiewska, Anna

    2010-01-01

    Increased expression of metalloprotease-disintegrin ADAM12 is a hallmark of several pathological conditions, including cancer, cardiovascular disease, and certain inflammatory diseases of the central nervous system or the muscoskeletal system. We show that transforming growth factor β1 (TGFβ1) is a potent inducer of ADAM12 mRNA and protein in mouse fibroblasts and in mouse and human mammary epithelial cells. Induction of ADAM12 is detected within 2 h of treatment with TGFβ1, is Smad2/Smad3-dependent, and is a result of derepression of the Adam12 gene. SnoN, a negative regulator of the TGFβ signaling pathway, is a master regulator of ADAM12 expression in response to TGFβ1 stimulation. Overexpression of SnoN in NIH3T3 cells reduces the magnitude of ADAM12 induction by TGFβ1 treatment. Down-regulation of SnoN expression by short hairpin RNA enhances TGFβ1-induced expression of ADAM12. In a panel of TGFβ1-responsive cancer cell lines with high expression of SnoN, induction of ADAM12 by TGFβ1 is significantly impaired, suggesting that the endogenous SnoN plays a role in regulating ADAM12 expression in response to TGFβ1. Identification of SnoN as a repressor of the ADAM12 gene should contribute to advances in the studies on the role of ADAM12 in tumor progression and in the development of other pathologies. PMID:20457602

  2. iRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding

    PubMed Central

    Maretzky, Thorsten; McIlwain, David R.; Issuree, Priya Darshinee A.; Li, Xue; Malapeira, Jordi; Amin, Sadaf; Lang, Philipp A.; Mak, Tak W.; Blobel, Carl P.

    2013-01-01

    Protein ectodomain shedding by ADAM17 (a disintegrin and metalloprotease 17), a principal regulator of EGF-receptor signaling and TNFα release, is rapidly and posttranslationally activated by a variety of signaling pathways, and yet little is known about the underlying mechanism. Here, we report that inactive rhomboid protein 2 (iRhom2), recently identified as essential for the maturation of ADAM17 in hematopoietic cells, is crucial for the rapid activation of the shedding of some, but not all substrates of ADAM17. Mature ADAM17 is present in mouse embryonic fibroblasts (mEFs) lacking iRhom2, and yet ADAM17 is unable to support stimulated shedding of several of its substrates, including heparin-binding EGF and Kit ligand 2 in this context. Stimulated shedding of other ADAM17 substrates, such as TGFα, is not affected in iRhom2−/− mEFs but can be strongly reduced by treating iRhom2−/− mEFs with siRNA against iRhom1. Activation of heparin-binding EGF or Kit ligand 2 shedding by ADAM17 in iRhom2−/− mEFs can be rescued by wild-type iRhom2 but not by iRhom2 lacking its N-terminal cytoplasmic domain. The requirement for the cytoplasmic domain of iRhom2 for stimulated shedding by ADAM17 may help explain why the cytoplasmic domain of ADAM17 is not required for stimulated shedding. The functional relevance of iRhom2 in regulating shedding of EGF receptor (EGFR) ligands is established by a lack of lysophasphatidic acid/ADAM17/EGFR-dependent crosstalk with ERK1/2 in iRhom2−/− mEFs, and a significant reduction of FGF7/ADAM17/EGFR-stimulated migration of iRhom2−/− keratinocytes. Taken together, these findings uncover functions for iRhom2 in the regulation of EGFR signaling and in controlling the activation and substrate selectivity of ADAM17-dependent shedding events. PMID:23801765

  3. Highlighting High Performance: Adam Joseph Lewis Center for Environmental Studies, Oberlin College, Oberlin, Ohio

    SciTech Connect

    2002-11-01

    Oberlin College’s Adam Joseph Lewis Center for Environmental Studies is a high-performance building featuring an expansive photovoltaic system and a closed-loop groundwater heat pump system. Designers incorporated energy-efficient components and materials

  4. CCD Photometry and Lightcurve Analysis of 1730 Marceline and 1996 Adams from Observatori Carmelita in Tiana

    NASA Astrophysics Data System (ADS)

    Aymami, Josep Maria

    2011-01-01

    Analysis of observations carried out during 2010 September and October determined the synodic periods of 1730 Marceline (1936 UA) and 1996 Adams (1961 UA). For main-belt asteroid 1730 Marceline, a period of 3.837 ± 0.001 h was found. For 1996 Adams, also an MBA, a period of 3.311 ± 0.001 h was determined. This differs from the period of 3.56 h found by Alvarez-Candal et al. (2004).

  5. MicroRNA-147b Regulates Vascular Endothelial Barrier Function by Targeting ADAM15 Expression

    PubMed Central

    Chatterjee, Victor; Beard, Richard S.; Reynolds, Jason J.; Haines, Ricci; Guo, Mingzhang; Rubin, Matthew; Guido, Jenny; Wu, Mack H.; Yuan, Sarah Y.

    2014-01-01

    A disintegrin and metalloproteinase15 (ADAM15) has been shown to be upregulated and mediate endothelial hyperpermeability during inflammation and sepsis. This molecule contains multiple functional domains with the ability to modulate diverse cellular processes including cell adhesion, extracellular matrix degradation, and ectodomain shedding of transmembrane proteins. These characteristics make ADAM15 an attractive therapeutic target in various diseases. The lack of pharmacological inhibitors specific to ADAM15 prompted our efforts to identify biological or molecular tools to alter its expression for further studying its function and therapeutic implications. The goal of this study was to determine if ADAM15-targeting microRNAs altered ADAM15-induced endothelial barrier dysfunction during septic challenge by bacterial lipopolysaccharide (LPS). An in silico analysis followed by luciferase reporter assay in human vascular endothelial cells identified miR-147b with the ability to target the 3′ UTR of ADAM15. Transfection with a miR-147b mimic led to decreased total, as well as cell surface expression of ADAM15 in endothelial cells, while miR-147b antagomir produced an opposite effect. Functionally, LPS-induced endothelial barrier dysfunction, evidenced by a reduction in transendothelial electric resistance and increase in albumin flux across endothelial monolayers, was attenuated in cells treated with miR-147b mimics. In contrast, miR-147b antagomir exerted a permeability-increasing effect in vascular endothelial cells similar to that caused by LPS. Taken together, these data suggest the potential role of miR147b in regulating endothelial barrier function by targeting ADAM15 expression. PMID:25333931

  6. Adams-Oliver syndrome associated with cutis marmorata telangiectatica congenita and congenital cataract: a case report.

    PubMed

    Fayol, Laurence; Garcia, Patricia; Denis, Danièle; Philip, Nicole; Simeoni, Umberto

    2006-04-01

    A female infant presented with Adams-Oliver syndrome (AOS), intrauterine growth retardation, severe cutis marmorata telangiectatica congenita, bilateral congenital cataract, and periventricular lesions. The here-reported association of bilateral congenital cataract with AOS is original. Adams-Oliver syndrome is a genetic defect that causes a vasculopathy and leads to a variety of phenotypes. This observation further supports the current understanding of the physiopathology of AOS. PMID:16586236

  7. ADAM17 Inhibitors Attenuate Corneal Epithelial Detachment Induced by Mustard Exposure

    PubMed Central

    DeSantis-Rodrigues, Andrea; Chang, Yoke-Chen; A. Hahn, Rita; P. Po, Iris; Zhou, Peihong; Lacey, C. Jeffrey; Pillai, Abhilash; C. Young, Sherri; A. Flowers II, Robert; A. Gallo, Michael; D. Laskin, Jeffrey; R. Gerecke, Donald; K. H. Svoboda, Kathy; D. Heindel, Ned; Gordon, Marion K.

    2016-01-01

    Purpose Sulfur mustard, nitrogen mustard (NM), and 2-chloroethyl ethyl sulfide all cause corneal injury with epithelial–stromal separation, differing only by degree. Injury can resolve in a few weeks or develop into chronic corneal problems. These vesicants induce microbullae at the epithelial–stromal junction, which is partially caused by cleavage of transmembranous hemidesmosomal collagen XVII, a component anchoring the epithelium to the stroma. ADAM17 is an enzyme involved in wound healing and is able to cleave collagen XVII. The activity of ADAM17 was inhibited in vesicant-exposed corneas by four different hydroxamates, to evaluate their therapeutic potential when applied 2 hours after exposure, thereby allowing ADAM17 to perform its early steps in wound healing. Methods Rabbit corneal organ cultures exposed to NM for 2 hours were washed, then incubated at 37°C for 22 hours, with or without one of the four hydroxamates (dose range, 0.3–100 nmol in 20 μL, applied four times). Corneas were analyzed by light and immunofluorescence microscopy, and ADAM17 activity assays. Results Nitrogen mustard–induced corneal injury showed significant activation of ADAM17 levels accompanying epithelial–stromal detachment. Corneas treated with hydroxamates starting 2 hours post exposure showed a dose-dependent ADAM17 activity inhibition up to concentrations of 3 nmol. Of the four hydroxamates, NDH4417 (N-octyl-N-hydroxy-2-[4-hydroxy-3-methoxyphenyl] acetamide) was most effective for inhibiting ADAM17 and retaining epithelial–stromal attachment. Conclusions Mustard exposure leads to corneal epithelial sloughing caused, in part, by the activation of ADAM17 at the epithelial–stromal junction. Select hydroxamate compounds applied 2 hours after NM exposure mitigated epithelial–stromal separation. PMID:27058125

  8. A novel peptide ADAM8 inhibitor attenuates bronchial hyperresponsiveness and Th2 cytokine mediated inflammation of murine asthmatic models

    PubMed Central

    Chen, Jun; Deng, Linhong; Dreymüller, Daniela; Jiang, Xuemei; Long, Jiaoyue; Duan, Yiyuan; Wang, Yue; Luo, Mingzhi; Lin, Feng; Mao, Lizhen; Müller, Bernd; Koller, Garrit; Bartsch, Jörg W.

    2016-01-01

    A disintegrin and metalloproteinase 8 (ADAM8) has been identified as a signature gene associated with moderate and severe asthma. Studies in mice have demonstrated that the severity of asthma can be reduced by either transgenic knock-out or by antibodies blocking ADAM8 function, highlighting ADAM8 as potential drug target for asthma therapy. Here, we examined the therapeutic effect of an ADAM8 inhibitor peptide (BK-1361) that specifically blocks cellular ADAM8 activity in ovalbumin-sensitized and challenged Balb/c mice. We found that BK-1361 (25 μg/g body weight) attenuated airway responsiveness to methacholine stimulation by up to 42%, concomitantly reduced tissue remodeling by 50%, and decreased inflammatory cells (e.g. eosinophils down by 54%)/inflammatory factors (e.g. sCD23 down by 50%)/TH2 cytokines (e.g. IL-5 down by 70%)/ADAM8-positive eosinophils (down by 60%) in the lung. We further verified that BK-1361 specifically targets ADAM8 in vivo as the peptide caused significantly reduced levels of soluble CD23 in wild-type but not in ADAM8-deficient mice. These findings suggest that BK-1361 blocks ADAM8-dependent asthma effects in vivo by inhibiting infiltration of eosinophils and TH2 lymphocytes, thus leading to reduction of TH2-mediated inflammation, tissue remodeling and bronchial hyperresponsiveness. Taken together, pharmacological ADAM8 inhibition appears as promising novel therapeutic strategy for the treatment of asthma. PMID:27458083

  9. Geologic map and geothermal assessment of the Mount Adams volcanic field, Cascade Range of southern Washington

    USGS Publications Warehouse

    Hildreth, Wes; Fierstein, Judy

    1990-01-01

    More than 60 Quaternary vents make up the basalt-to-rhyodacite Mount Adams volcanic field and have erupted scoriae and lavas with a total volume of >370 km3. The Mount Adams andesite-dacite stratocone itself is a compound edifice that includes the high cone above 2300 m (20-10 ka), remnants of at least two earlier andesite-dacite cones as old as 0.5 Ma, and 7 Holocene flank vents. Four other Holocene vents and tens of vents contemporaneous with Mount Adams are peripheral to the stratocone. All of these vents, including Mount Adams, lie within a N-S eruptive zone 55 km long and 5 km wide. The age of all known Mount Adams silicic products (>100 ka) and the heterogeneous mafic compositions of the summit cone and Holocene lavas make it unlikely that the stratocone is underlain by an upper-crustal reservoir. Rather, the stratocone at the focus is built up of fractionated hybrid magmas that rise from MASH zones (melting-assimilation-storage-homogenization). The pyroclastic core of breccia and scoria at Mount Adams has undergone acid-sulfate leaching and deposition of alunite, kaolinite, silica, gypsum, sulfur, and Fe-oxides and has been a constant source of avalanches and debris flows. Most heat supplied from depth to the fumarolically altered core is dispersed by the high precipitation rate and high permeability of the rubbly lava flows so that a hydrothermal convection pattern is not maintained. Summit-restricted fumaroles are weak and diffuse.

  10. The Low Affinity IgE Receptor (CD23) Is Cleaved by the Metalloproteinase ADAM10*

    PubMed Central

    Lemieux, George A.; Blumenkron, Fernando; Yeung, Nolan; Zhou, Pei; Williams, Jason; Grammer, Amrie C.; Petrovich, Robert; Lipsky, Peter E.; Moss, Marcia L.; Werb, Zena

    2008-01-01

    The low affinity IgE receptor, Fc∊RII (CD23), is both a positive and negative regulator of IgE synthesis. The proteinase activity that converts the membrane-bound form of CD23 into a soluble species (sCD23) is an important regulator of the function of CD23 and may be an important therapeutic target for the control of allergy and inflammation. We have characterized the catalytic activity of ADAM (a disintegrin and metalloproteinase) 10 toward human CD23. We found that ADAM10 efficiently catalyzes the cleavage of peptides derived from two distinct cleavage sites in the CD23 backbone. Tissue inhibitors of metalloproteinases and a specific prodomain-based inhibitor of ADAM10 perturb the release of endogenously produced CD23 from human leukemia cell lines as well as primary cultures of human B-cells. Expression of a mutant metalloproteinase-deficient construct of ADAM10 partially inhibited the production of sCD23. Similarly, small inhibitory RNA knockdown of ADAM10 partially inhibited CD23 release and resulted in the accumulation of the membrane-bound form of CD23 on the cells. ADAM10 contributes to CD23 shedding and thus could be considered a potential therapeutic target for the treatment of allergic disease. PMID:17389606

  11. The low affinity IgE receptor (CD23) is cleaved by the metalloproteinase ADAM10.

    PubMed

    Lemieux, George A; Blumenkron, Fernando; Yeung, Nolan; Zhou, Pei; Williams, Jason; Grammer, Amrie C; Petrovich, Robert; Lipsky, Peter E; Moss, Marcia L; Werb, Zena

    2007-05-18

    The low affinity IgE receptor, FcepsilonRII (CD23), is both a positive and negative regulator of IgE synthesis. The proteinase activity that converts the membrane-bound form of CD23 into a soluble species (sCD23) is an important regulator of the function of CD23 and may be an important therapeutic target for the control of allergy and inflammation. We have characterized the catalytic activity of ADAM (a disintegrin and metalloproteinase) 10 toward human CD23. We found that ADAM10 efficiently catalyzes the cleavage of peptides derived from two distinct cleavage sites in the CD23 backbone. Tissue inhibitors of metalloproteinases and a specific prodomain-based inhibitor of ADAM10 perturb the release of endogenously produced CD23 from human leukemia cell lines as well as primary cultures of human B-cells. Expression of a mutant metalloproteinase-deficient construct of ADAM10 partially inhibited the production of sCD23. Similarly, small inhibitory RNA knockdown of ADAM10 partially inhibited CD23 release and resulted in the accumulation of the membrane-bound form of CD23 on the cells. ADAM10 contributes to CD23 shedding and thus could be considered a potential therapeutic target for the treatment of allergic disease.

  12. Lrig2 Negatively Regulates Ectodomain Shedding of Axon Guidance Receptors by ADAM Proteases.

    PubMed

    van Erp, Susan; van den Heuvel, Dianne M A; Fujita, Yuki; Robinson, Ross A; Hellemons, Anita J C G M; Adolfs, Youri; Van Battum, Eljo Y; Blokhuis, Anna M; Kuijpers, Marijn; Demmers, Jeroen A A; Hedman, Håkan; Hoogenraad, Casper C; Siebold, Christian; Yamashita, Toshihide; Pasterkamp, R Jeroen

    2015-12-01

    Many guidance receptors are proteolytically cleaved by membrane-associated metalloproteases of the ADAM family, leading to the shedding of their ectodomains. Ectodomain shedding is crucial for receptor signaling and function, but how this process is controlled in neurons remains poorly understood. Here, we show that the transmembrane protein Lrig2 negatively regulates ADAM-mediated guidance receptor proteolysis in neurons. Lrig2 binds Neogenin, a receptor for repulsive guidance molecules (RGMs), and prevents premature Neogenin shedding by ADAM17 (TACE). RGMa reduces Lrig2-Neogenin interactions, providing ADAM17 access to Neogenin and allowing this protease to induce ectodomain shedding. Regulation of ADAM17-mediated Neogenin cleavage by Lrig2 is required for neurite growth inhibition by RGMa in vitro and for cortical neuron migration in vivo. Furthermore, knockdown of Lrig2 significantly improves CNS axon regeneration. Together, our data identify a unique ligand-gated mechanism to control receptor shedding by ADAMs and reveal functions for Lrigs in neuron migration and regenerative failure. PMID:26651291

  13. ADAMS/WT advanced development - version 1.4 and beyond

    SciTech Connect

    Elliott, A.S.; Depauw, T.R.

    1996-12-31

    ADAMS/WT is an wind-turbine-specific shell for the general-purpose mechanical system simulation package ADAMS5. It was developed under the guidance of the National Renewable Energy Laboratory to give engineers and analysts in the wind turbine community access to the analytical power of ADAMS, without having to become expert in its particular technology. The 1.4 version of ADAMS/WT is the most recent upgrade to the package, incorporating the most up-to-date version of the AeroDyn aerodynamic forcing subroutines from the University of Utah. It is also the first version to be made available on the Windows/NT platform. In version 1.4, ADAMS/WT has been significantly improved throughout and runs much faster. Automatic generation of standardized output has been added. The documentation has been extensively augmented with more detailed descriptions, more figures and more examples. ADAMS/WT remains the most powerful analytical tool available for horizontal-axis wind turbine development. 10 figs.

  14. ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview

    PubMed Central

    Takeda, Soichi

    2016-01-01

    A disintegrin and metalloproteinase (ADAM) family proteins constitute a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell-surface protein ectodomains, including the latent forms of growth factors, cytokines, receptors and other molecules. Snake venom metalloproteinases (SVMPs) are major components in most viper venoms. SVMPs are primarily responsible for hemorrhagic activity and may also interfere with the hemostatic system in envenomed animals. SVMPs are phylogenetically most closely related to ADAMs and, together with ADAMs and related ADAM with thrombospondin motifs (ADAMTS) family proteinases, constitute adamalysins/reprolysins or the M12B clan (MEROPS database) of metalloproteinases. Although the catalytic domain structure is topologically similar to that of other metalloproteinases such as matrix metalloproteinases, the M12B proteinases have a modular structure with multiple non-catalytic ancillary domains that are not found in other proteinases. Notably, crystallographic studies revealed that, in addition to the conserved metalloproteinase domain, M12B members share a hallmark cysteine-rich domain designated as the “ADAM_CR” domain. Despite their name, ADAMTSs lack disintegrin-like structures and instead comprise two ADAM_CR domains. This review highlights the current state of our knowledge on the three-dimensional structures of M12B proteinases, focusing on their unique domains that may collaboratively participate in directing these proteinases to specific substrates. PMID:27196928

  15. A-Disintegrin-And-Metalloproteinase (ADAM) 10 Activity on Resting and Activated Platelets.

    PubMed

    Facey, Adam; Pinar, Isaac; Arthur, Jane F; Qiao, Jianlin; Jing, Jing; Mado, Belden; Carberry, Josie; Andrews, Robert K; Gardiner, Elizabeth E

    2016-03-01

    The primary platelet collagen receptor, glycoprotein VI (GPVI), plays an important role in platelet activation and thrombosis. The ectodomain of human GPVI (sGPVI) is proteolytically shed from human platelets by a-disintegrin-and-metalloproteinase 10 (ADAM10). In this study, we used a novel ADAM10-sensitive fluorescence resonance energy transfer sensor to analyze ADAM10-mediated shedding of GPVI from human platelets in response to the exposure of GPVI ligands collagen-related peptide (10 μg/mL), collagen (10 μg/mL), and convulxin (0.1 μg/mL) to shear stress (1000-10000 s(-1), 5 min), or a generic activator of metalloproteinases, N-ethylmaleimide (NEM, 5 mM). Elevated shear, NEM, or ligand engagement of GPVI all induced shedding of GPVI, as detected by release of sGPVI; however, only shear or NEM significantly increased ADAM10 enzyme activity. ADAM10 activity was also detectable on the surface of thrombi formed on a collagen-coated surface under flow conditions. Our findings indicate different mechanisms regulate shear- and ligand-induced shedding and shear forces found within the vasculature can regulate ADAM10 activity. PMID:26840909

  16. IL-1beta signals through the EGF receptor and activates Egr-1 through MMP-ADAM.

    PubMed

    Sanchez-Guerrero, Estella; Chen, Elya; Kockx, Maaike; An, Si-Wei; Chong, Beng H; Khachigian, Levon M

    2012-01-01

    The immediate-early gene Egr-1 controls the inducible expression of many genes implicated in the pathogenesis of a range of vascular disorders, yet our understanding of the mechanisms controlling the rapid expression of this prototypic zinc finger transcription factor is poor. Here we show that Egr-1 expression induced by IL-1beta is dependent on metalloproteinases (MMP) and a disintegrin and a metalloproteinase (ADAM). Pharmacologic MMP/ADAM inhibitors and siRNA knockdown prevent IL-1beta induction of Egr-1. Further, IL-1beta activates Egr-1 via the epidermal growth factor receptor (EGFR). This is blocked by EGFR tyrosine kinase inhibition and EGFR knockdown. IL-1beta induction of Egr-1 expression is reduced in murine embryonic fibroblasts (mEFs) deficient in ADAM17 despite unbiased expression of EGFR and IL-1RI in ADAM17-deficient and wild-type mEFs. Finally, we show that IL-1beta-inducible wound repair after mechanical injury requires both EGFR and MMP/ADAM. This study reports for the first time that Egr-1 induction by IL-1beta involves EGFR and MMP/ADAM-dependent EGFR phosphorylation. PMID:22792188

  17. MT5-MMP, ADAM-10, and N-Cadherin Act in Concert To Facilitate Synapse Reorganization after Traumatic Brain Injury

    PubMed Central

    Warren, Kelly M.; Reeves, Thomas M.

    2012-01-01

    Abstract Matrix metalloproteinases (MMPs) influence synaptic recovery following traumatic brain injury (TBI). Membrane type 5-matrix metalloproteinase (MT5-MMP) and a distintegrin and metalloproteinase-10 (ADAM-10) are membrane-bound MMPs that cleave N-cadherin, a protein critical to synapse stabilization. This study examined protein and mRNA expression of MT5-MMP, ADAM-10, and N-cadherin after TBI, contrasting adaptive and maladaptive synaptogenesis. The effect of MMP inhibition on MT5-MMP, ADAM-10, and N-cadherin was assessed during maladaptive plasticity and correlated with synaptic function. Rats were subjected to adaptive unilateral entorhinal cortical lesion (UEC) or maladaptive fluid percussion TBI+bilateral entorhinal cortical lesion (TBI+BEC). Hippocampal MT5-MMP and ADAM-10 protein was significantly elevated 2 and 7 days post-injury. At 15 days after UEC, each MMP returned to control level, while TBI+BEC ADAM-10 remained elevated. At 2 and 7 days, N-cadherin protein was below control. By the 15-day synapse stabilization phase, UEC N-cadherin rose above control, a shift not seen for TBI+BEC. At 7 days, increased TBI+BEC ADAM-10 transcript correlated with protein elevation. UEC ADAM-10 mRNA did not change, and no differences in MT5-MMP or N-cadherin mRNA were detected. Confocal imaging showed MT5-MMP, ADAM-10, and N-cadherin localization within reactive astrocytes. MMP inhibition attenuated ADAM-10 protein 15 days after TBI+BEC and increased N-cadherin. This inhibition partially restored long-term potentiation induction, but did not affect paired-pulse facilitation. Our results confirm time- and injury-dependent expression of MT5-MMP, ADAM-10, and N-cadherin during reactive synaptogenesis. Persistent ADAM-10 expression was correlated with attenuated N-cadherin level and reduced functional recovery. MMP inhibition shifted ADAM-10 and N-cadherin toward adaptive expression and improved synaptic function. PMID:22489706

  18. ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated guanylate kinases to juxtaparanodes of myelinated axons.

    PubMed

    Ogawa, Yasuhiro; Oses-Prieto, Juan; Kim, Moon Young; Horresh, Ido; Peles, Elior; Burlingame, Alma L; Trimmer, James S; Meijer, Dies; Rasband, Matthew N

    2010-01-20

    Clustered Kv1 K(+) channels regulate neuronal excitability at juxtaparanodes of myelinated axons, axon initial segments, and cerebellar basket cell terminals (BCTs). These channels are part of a larger protein complex that includes cell adhesion molecules and scaffolding proteins. To identify proteins that regulate assembly, clustering, and/or maintenance of axonal Kv1 channel protein complexes, we immunoprecipitated Kv1.2 alpha subunits, and then used mass spectrometry to identify interacting proteins. We found that a disintegrin and metalloproteinase 22 (ADAM22) is a component of the Kv1 channel complex and that ADAM22 coimmunoprecipitates Kv1.2 and the membrane-associated guanylate kinases (MAGUKs) PSD-93 and PSD-95. When coexpressed with MAGUKs in heterologous cells, ADAM22 and Kv1 channels are recruited into membrane surface clusters. However, coexpression of Kv1.2 with ADAM22 and MAGUKs does not alter channel properties. Among all the known Kv1 channel-interacting proteins, only ADAM22 is found at every site where Kv1 channels are clustered. Analysis of Caspr-null mice showed that, like other previously described juxtaparanodal proteins, disruption of the paranodal junction resulted in redistribution of ADAM22 into paranodal zones. Analysis of Caspr2-, PSD-93-, PSD-95-, and double PSD-93/PSD-95-null mice showed ADAM22 clustering at BCTs requires PSD-95, but ADAM22 clustering at juxtaparanodes requires neither PSD-93 nor PSD-95. In direct contrast, analysis of ADAM22-null mice demonstrated juxtaparanodal clustering of PSD-93 and PSD-95 requires ADAM22, whereas Kv1.2 and Caspr2 clustering is normal in ADAM22-null mice. Thus, ADAM22 is an axonal component of the Kv1 K(+) channel complex that recruits MAGUKs to juxtaparanodes. PMID:20089912

  19. Monocyte ADAM17 promotes diapedesis during transendothelial migration: Identification of steps and substrates targeted by metalloproteinases

    PubMed Central

    Tsubota, Yoshiaki; Frey, Jeremy M.; Tai, Phillip W.L.; Welikson, Robert E.; Raines, Elaine W.

    2013-01-01

    Despite expanded definition of the leukocyte adhesion cascade and mechanisms underlying individual steps, very little is known about regulatory mechanisms controlling sequential shifts between steps. We tested the hypothesis that metalloproteinases provide a mechanism to rapidly transition monocytes between different steps. Our study identifies diapedesis as a step targeted by metalloproteinase activity. Time-lapse video microscopy shows that the presence of a metalloproteinase inhibitor results in a doubling of the time required for human monocytes to complete diapedesis on unactivated or inflamed human endothelium, under both static and physiological-flow conditions. Thus, diapedesis is promoted by metalloproteinase activity. In contrast, neither adhesion of monocytes nor their locomotion over the endothelium is altered by metalloproteinase inhibition. We further demonstrate that metalloproteinase inhibition significantly elevates monocyte cell-surface levels of integrins CD11b/CD18 (Mac-1) specifically during transendothelial migration. Interestingly, such alterations are not detected for other endothelial- and monocyte-adhesion molecules that are presumed metalloproteinase substrates. Two major transmembrane metalloproteinases, ADAM17 and ADAM10, are identified as enzymes that control constitutive cleavage of Mac-1. We further establish that knockdown of monocyte ADAM17, but not endothelial ADAM10 or ADAM17, or monocyte ADAM10, reproduces the diapedesis delay observed with metalloproteinase inhibition. Therefore, we conclude that monocyte ADAM17 facilitates the completion of transendothelial migration by accelerating the rate of diapedesis. We propose that the progression of diapedesis may be regulated by spatial and temporal cleavage of Mac-1, which is triggered upon interaction with endothelium. PMID:23479224

  20. Fendiline inhibits proliferation and invasion of pancreatic cancer cells by interfering with ADAM10 activation and β-catenin signaling

    PubMed Central

    Woods, Neha; Trevino, Jose; Coppola, Domenico; Chellappan, Srikumar; Yang, Shengyu; Padmanabhan, Jaya

    2015-01-01

    ADAM10 (A Disintegrin and Metalloprotease Domain 10) affects the pathophysiology of various cancers, and we had shown that inhibition of ADAM10 sensitizes pancreatic cancer cells to gemcitabine. ADAM10 is activated in response to calcium influx, and here we examined if calcium channel blockers (CCB) would impede ADAM10 activation and affect biology of pancreatic cancer cells. We find that the CCB, fendiline, significantly reduces proliferation, migration, invasion, and anchorage independent growth of pancreatic cancer cells. This was associated with ADAM10 inhibition and its localization at the actin-rich membrane protrusions. Further, fendiline-treated cells formed cadherin-catenin positive tight adherens junctions and elicited defective protein trafficking and recycling. Furthermore, the expression of β-catenin target genes, cyclinD1, c-Myc and CD44, were significantly decreased, suggesting that fendiline might prevent cell proliferation and migration by inhibiting ADAM10 function, cadherin proteolysis and stabilization of cadherin-catenin interaction at the plasma membrane. This will subsequently diminish β-catenin intracellular signaling and repress TCF/LEF target gene expression. Supporting this notion, RNAi-directed downregulation of ADAM10 in cancer cells decreased the expression of cyclinD1, c-Myc and CD44. Furthermore, analysis of human pancreatic tumor tissue microarrays and lysates showed elevated levels of ADAM10, suggesting that aberrant activation of ADAM10 plays a fundamental role in growth and metastasis of PDACs and inhibiting this pathway might be a viable strategy to combat PDACs. PMID:26440150

  1. Effect of a dominant-negative form of ADAM10 in a mouse model of Alzheimer's disease.

    PubMed

    Schroeder, Anja; Fahrenholz, Falk; Schmitt, Ulrich

    2009-01-01

    The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid-beta protein precursor (AbetaPP) within the region of the amyloid-beta peptides to prevent their formation and aggregation in the brain. Members of the ADAM family (a disintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. We recently demonstrated that overexpression of ADAM10 in mice transgenic for human AbetaPP (ADAM10 x APP[V717I]) alleviated functional deficits related to Alzheimer's disease. To further demonstrate that this is due to the specific activity of alpha-secretase, we characterized mice overexpressing an inactive form of ADAM10 (ADAM10[E384A]; ADAM10-dn). Three lines of mice (controls (C57Bl/6 x FVB), APP[V717I[ transgenics and ADAM10-dn x APP[V717I] double-transgenics) were investigated with respect to learning and memory in the Morris water maze. Double-transgenic mice overexpressing ADAM10-dn behaved similar to APP[V717I] overexpressing mice. This provides further evidence that ADAM10 in vivo by its enzymatic activity is able to counteract cognitive deficits. Stimulation of alpha-secretase activity might thus be a suitable approach to study treatment strategies of Alzheimer's disease.

  2. Analysis of mixed model in gear transmission based on ADAMS

    NASA Astrophysics Data System (ADS)

    Li, Xiufeng; Wang, Yabin

    2012-09-01

    The traditional method of mechanical gear driving simulation includes gear pair method and solid to solid contact method. The former has higher solving efficiency but lower results accuracy; the latter usually obtains higher precision of results while the calculation process is complex, also it is not easy to converge. Currently, most of the researches are focused on the description of geometric models and the definition of boundary conditions. However, none of them can solve the problems fundamentally. To improve the simulation efficiency while ensure the results with high accuracy, a mixed model method which uses gear tooth profiles to take the place of the solid gear to simulate gear movement is presented under these circumstances. In the process of modeling, build the solid models of the mechanism in the SolidWorks firstly; Then collect the point coordinates of outline curves of the gear using SolidWorks API and create fit curves in Adams based on the point coordinates; Next, adjust the position of those fitting curves according to the position of the contact area; Finally, define the loading conditions, boundary conditions and simulation parameters. The method provides gear shape information by tooth profile curves; simulates the mesh process through tooth profile curve to curve contact and offer mass as well as inertia data via solid gear models. This simulation process combines the two models to complete the gear driving analysis. In order to verify the validity of the method presented, both theoretical derivation and numerical simulation on a runaway escapement are conducted. The results show that the computational efficiency of the mixed model method is 1.4 times over the traditional method which contains solid to solid contact. Meanwhile, the simulation results are more closely to theoretical calculations. Consequently, mixed model method has a high application value regarding to the study of the dynamics of gear mechanism.

  3. Mutations in NOTCH1 cause Adams-Oliver syndrome.

    PubMed

    Stittrich, Anna-Barbara; Lehman, Anna; Bodian, Dale L; Ashworth, Justin; Zong, Zheyuan; Li, Hong; Lam, Patricia; Khromykh, Alina; Iyer, Ramaswamy K; Vockley, Joseph G; Baveja, Rajiv; Silva, Ermelinda Santos; Dixon, Joanne; Leon, Eyby L; Solomon, Benjamin D; Glusman, Gustavo; Niederhuber, John E; Roach, Jared C; Patel, Millan S

    2014-09-01

    Notch signaling determines and reinforces cell fate in bilaterally symmetric multicellular eukaryotes. Despite the involvement of Notch in many key developmental systems, human mutations in Notch signaling components have mainly been described in disorders with vascular and bone effects. Here, we report five heterozygous NOTCH1 variants in unrelated individuals with Adams-Oliver syndrome (AOS), a rare disease with major features of aplasia cutis of the scalp and terminal transverse limb defects. Using whole-genome sequencing in a cohort of 11 families lacking mutations in the four genes with known roles in AOS pathology (ARHGAP31, RBPJ, DOCK6, and EOGT), we found a heterozygous de novo 85 kb deletion spanning the NOTCH1 5' region and three coding variants (c.1285T>C [p.Cys429Arg], c.4487G>A [p.Cys1496Tyr], and c.5965G>A [p.Asp1989Asn]), two of which are de novo, in four unrelated probands. In a fifth family, we identified a heterozygous canonical splice-site variant (c.743-1 G>T) in an affected father and daughter. These variants were not present in 5,077 in-house control genomes or in public databases. In keeping with the prominent developmental role described for Notch1 in mouse vasculature, we observed cardiac and multiple vascular defects in four of the five families. We propose that the limb and scalp defects might also be due to a vasculopathy in NOTCH1-related AOS. Our results suggest that mutations in NOTCH1 are the most common cause of AOS and add to a growing list of human diseases that have a vascular and/or bony component and are caused by alterations in the Notch signaling pathway. PMID:25132448

  4. Role of integrins, tetraspanins, and ADAM proteins during the development of apoptotic bodies by spermatogenic cells.

    PubMed

    Kierszenbaum, Abraham L; Rosselot, Carolina; Rivkin, Eugene; Tres, Laura L

    2006-07-01

    We have previously reported that Sertoli cell geometric changes induced by a Fas (CD95) agonist or by restricting Sertoli cell spreading can trigger spermatogenic cell detachment from Sertoli cell surfaces and initiate a programmed cell death sequence. Here, we have focused on ADAM proteins, tetraspanins CD9 and CD81, and the integrin beta1 subunit, which is co-expressed in testis with integrin alpha3 and integrin alpha6 subunits, to understand how these molecules may stabilize spermatogenic cell attachment to Sertoli cell surfaces. Like ADAM proteins, integrin beta1, alpha3, and alpha6 subunits, and CD9 and CD81 transcripts are expressed in the fetal testis and throughout testicular maturation, as well as, in Sertoli-spermatogenic cell co-cultures. Prespermatogonia (gonocytes) display CD9 and CD81 immunoreactive sites. Integrin alpha6 subunit transcripts have unusual developmental characteristics: fetal testis expresses the integrin alpha6B isoform exclusively. In contrast, the integrin alpha6B isoform co-exists with the integrin alpha6A isoform in prepubertal testes and Sertoli-spermatogenic cell co-cultures. A blocking anti body targeting the extracellular domain (N-terminal) of the integrin beta1 subunit causes rapid contraction of Sertoli cells leading to the gradual detachment of associated spermatogenic cells. In contrast, predicted active site peptides targeting the disintegrin domain of ADAM 1, ADAM 2, ADAM 3 (cyritestin), ADAM 4, ADAM 5, ADAM 6, and ADAM 15 (metragidin) do not disturb significantly the attachment of spermatogenic cells to Sertoli cell surfaces. Spermatogenic cells dislodged from their attachment sites by the integrin beta1 subunit blocking antibody display annexin V immunoreactivity, a sign of early apoptosis. Time-lapse videomicroscopy demonstrates that the removal by apoptosis of a single member of a spermatogenic cell cohort inter-connected by cytoplasmic bridges does not affect the remaining members of the cohort. During spermatogenic

  5. Regulated ADAM17-dependent EGF family ligand release by substrate-selecting signaling pathways.

    PubMed

    Dang, Michelle; Armbruster, Nicole; Miller, Miles A; Cermeno, Efrain; Hartmann, Monika; Bell, George W; Root, David E; Lauffenburger, Douglas A; Lodish, Harvey F; Herrlich, Andreas

    2013-06-11

    Ectodomain cleavage of cell-surface proteins by A disintegrin and metalloproteinases (ADAMs) is highly regulated, and its dysregulation has been linked to many diseases. ADAM10 and ADAM17 cleave most disease-relevant substrates. Broad-spectrum metalloprotease inhibitors have failed clinically, and targeting the cleavage of a specific substrate has remained impossible. It is therefore necessary to identify signaling intermediates that determine substrate specificity of cleavage. We show here that phorbol ester or angiotensin II-induced proteolytic release of EGF family members may not require a significant increase in ADAM17 protease activity. Rather, inducers activate a signaling pathway using PKC-α and the PKC-regulated protein phosphatase 1 inhibitor 14D that is required for ADAM17 cleavage of TGF-α, heparin-binding EGF, and amphiregulin. A second pathway involving PKC-δ is required for neuregulin (NRG) cleavage, and, indeed, PKC-δ phosphorylation of serine 286 in the NRG cytosolic domain is essential for induced NRG cleavage. Thus, signaling-mediated substrate selection is clearly distinct from regulation of enzyme activity, an important mechanism that offers itself for application in disease.

  6. ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors.

    PubMed

    Becker, Amy M; Walcheck, Bruce; Bhattacharya, Deepta

    2015-01-01

    All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17(-/-) ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17(-/-) ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential.

  7. The ADAM17-amphiregulin-EGFR axis in mammary development and cancer.

    PubMed

    Sternlicht, Mark D; Sunnarborg, Susan W

    2008-06-01

    In order to fulfill its function of producing and delivering sufficient milk to newborn mammalian offspring, the mammary gland first has to form an extensive ductal network. As in all phases of mammary development, hormonal cues elicit local intra- and inter-cellular signaling cascades that regulate ductal growth and differentiation. Among other things, ductal development requires the epidermal growth factor receptor (EGFR), its ligand amphiregulin (AREG), and the transmembrane metalloproteinase ADAM17, which can cleave and release AREG from the cell surface so that it may interact with its receptor. Tissue recombination and transplantation studies demonstrate that EGFR phosphorylation and ductal development proceed only when ADAM17 and AREG are expressed on mammary epithelial cells and EGFR is present on stromal cells, and that local administration of soluble AREG can rescue the development of ADAM17-deficient transplants. Thus proper mammary morphogenesis requires the ADAM17-mediated release of AREG from ductal epithelial cells, the subsequent activation of EGFR on stromal cells, and EGFR-dependent stromal responses that in return elicit a new set of epithelial responses, all culminating in the formation of a fully functional ductal tree. This, however, raises new issues concerning what may act upstream, downstream or in parallel with the ADAM17-AREG-EGFR axis, how it may become hijacked or corrupted during the onset and evolution of cancer, and how such ill effects may be confronted.

  8. ADAM10 as a biomarker for Alzheimer's disease: a study with Brazilian elderly.

    PubMed

    Manzine, Patricia Regina; de França Bram, Jessyka Maria; Barham, Elisabeth Joan; do Vale, Francisco de Assis Carvalho; Selistre-de-Araújo, Heloisa Sobreiro; Cominetti, Márcia Regina; Iost Pavarini, Sofia Cristina

    2013-01-01

    Alzheimer's disease (AD) is the most common cause of dementia in people above age 65. Platelet studies with ADAM10 have shown that its expression is reduced in AD patients. The aim of this research was to compare the platelet levels of ADAM10 protein in two Brazilian elderly groups, considering the stages of the disease. The SDS-PAGE technique followed by Western blotting was used. Data were analyzed using comparison, correlation and association statistical methods. The results showed reduced platelet ADAM10 levels in AD elderly compared to non-AD subjects. The disease progression intensified this reduction. ADAM10 was the only statistically significant variable (p = 0.01) to increase the AD occurrence probability. The cutoff value of 0.4212 in the receiver operating characteristic curve captured sensitivity and specificity of 70 and 80.77%, respectively. Together with other clinical criteria, ADAM10 seems to be a relevant biomarker tool for early and accurate AD diagnosis. PMID:23306532

  9. ADAM17 in tumor associated leukocytes regulates inflammatory mediators and promotes mammary tumor formation

    PubMed Central

    Chuntova, Pavlina; Brady, Nicholas J.; Witschen, Patrice M.; Kemp, Sarah E.; Nelson, Andrew C.; Walcheck, Bruce; Schwertfeger, Kathryn L.

    2016-01-01

    The presence of inflammatory cells within the tumor microenvironment has been tightly linked to mammary tumor formation and progression. Specifically, interactions between tumor cells and infiltrating macrophages can contribute to the generation of a pro-tumorigenic microenvironment. Understanding the complex mechanisms that drive tumor cell-macrophage cross-talk will ultimately lead to the development of approaches to prevent or treat early stage breast cancers. As described here, we demonstrate that the cell surface protease a disintegrin and metalloproteinase 17 (ADAM17) is expressed by macrophages in mammary tumors and contributes to regulating the expression of pro-inflammatory mediators, including inflammatory cytokines and the inflammatory mediator cyclooxygenase-2 (Cox-2). Furthermore, we demonstrate that ADAM17 is expressed on leukocytes, including macrophages, within polyoma middle T (PyMT)-derived mammary tumors. Genetic deletion of ADAM17 in leukocytes resulted in decreased onset of mammary tumor growth, which was associated with reduced expression of the Cox-2 within the tumor. These findings demonstrate that ADAM17 regulates key inflammatory mediators in macrophages and that leukocyte-specific ADAM17 is an important promoter of mammary tumor initiation. Understanding the mechanisms associated with early stage tumorigenesis has implications for the development of preventive and/or treatment strategies for early stage breast cancers.

  10. Pyrococcus Furiosus Genome Supplementary Data from the Adams Laboratory at the University of Georgia

    DOE Data Explorer

    Adams, Michael W.W.; Weinberg, Michael V.; Schut, Gerrit J.; Brehm, Scott; Datta, Susmitta; Zhou, J.

    The research in the Adams Laboratory focuses on the physiology of hyperthermophilic organisms with an emphasis on metal-containing enzymes in the hyperthermophilic marine archaeon Pyrococcus furiosus. Three of the many articles from this University of Georgia lab have supplementary materials that are available on the Adams Lab website. All three sets of data are Open Reading Frames (ORFs) used for DNA microarray experiments and the changes in signal intensities. The full citations for the three articles are: 1) Weinberg, M. V., Schut, G. J., Brehm, S., Datta, S. and Adams, M. W. W. (2005) Cold shock of a hyperthermophilic archaeon: Pyrococcus furiosus exhibits multiple responses to a suboptimal growth temperature with a key role for membrane-bound glycoproteins. J Bacteriol. 187, 336-348; 2) Schut, G. J., Brehm, S. D., Datta, S. and Adams, M. W. W. (2003) "Whole genome DNA microarray analysis of a hyperthermophile and an archaeon: Pyrococcus furiosus grown on carbohydrates or peptides" J. Bacteriol. 185, 3935-3947; Schut, G. J., Zhou, J. and Adams, M. W. W. (2001) "DNA microarray analysis of the hyperthermophilic archaeon Pyrococcus furiosus evidence for a new type of sulfur-reducing enzyme" J. Bacteriol. 183, 7027-7036. Note that these articles are copyrighted by the Journal of Bacteriology.

  11. ADAM binding protein Eve-1 is required for ectodomain shedding of epidermal growth factor receptor ligands.

    PubMed

    Tanaka, Motonari; Nanba, Daisuke; Mori, Seiji; Shiba, Fumio; Ishiguro, Hiroshi; Yoshino, Koichiro; Matsuura, Nariaki; Higashiyama, Shigeki

    2004-10-01

    A disintegrin and metalloproteases (ADAMs) are implicated in the ectodomain shedding of epidermal growth factor receptor (EGFR) ligands in EGFR transactivation. However, the activation mechanisms of ADAMs remain elusive. To analyze the regulatory mechanisms of ADAM activation, we performed yeast two-hybrid screening using the cytoplasmic domain of ADAM12 as bait, and identified a protein that we designated Eve-1. Two cDNAs were cloned and characterized. They encode alternatively spliced isoforms of Eve-1, called Eve-1a and Eve-1b, that have four and five tandem Src homology 3 (SH3) domains in the carboxyl-terminal region, respectively, and seven proline-rich SH3 domain binding motifs in the amino-terminal region. The short forms of Eve-1, Eve-1c and Eve-1d, translated at Met-371 are human counterparts of mouse Sh3d19. Northern blot analysis demonstrated that Eve-1 is abundantly expressed in skeletal muscle and heart. Western blot analysis revealed the dominant production of Eve-1c in human cancer cell lines. Knockdown of Eve-1 by small interfering RNA in HT1080 cells reduced the shedding of proHB-EGF induced by angiotensin II and 12-O-tetradecanoylphorbol-13-acetate, as well as the shedding of pro-transforming growth factor-alpha, promphiregulin, and proepiregulin by 12-O-tetradecanoylphorbol-13-acetate, suggesting that Eve-1 plays a role in positively regulating the activity of ADAMs in the signaling of EGFR-ligand shedding.

  12. 50th anniversary of the discovery of ibuprofen: an interview with Dr Stewart Adams.

    PubMed

    Halford, Gayle M; Lordkipanidzé, Marie; Watson, Steve P

    2012-01-01

    2011 marks the 50th anniversary of the discovery of ibuprofen. This article is a focus on the personal reflections and career of Dr Stewart Adams OBE, the scientist whose research lead to the discovery of the cyclooxygenase inhibitor. When Dr Adams discovered ibuprofen, he was working as a pharmacologist in the Research Department for the Boots Pure Drug Company Ltd. Dr Adams was assigned to work on rheumatoid arthritis (RA) and chose in 1953 to search for a drug that would be effective in RA but would not be a corticosteroid. He was one of the first workers in this field that later became known as NSAIDs (Non-Steroidal Anti Inflammatory Drugs). In 1961, Dr Adams with John Nicholson, the organic chemist, filed a patent for the compound 2-(4-isobutylphenyl) propionic acid, later to become one of the most successful NSAIDs in the modern world, ibuprofen. In this article, Dr Adams gives his modest insight into the early stages and initial observations which led to this world-wide success.

  13. Inverse regulation of the ADAM-family members, decysin and MADDAM/ADAM19 during monocyte differentiation

    PubMed Central

    Fritsche, Jana; Müller, Alexandra; Hausmann, Martin; Rogler, Gerhard; Andreesen, Reinhard; Kreutz, Marina

    2003-01-01

    Two members of the ADAM (a disintegrin and metalloprotease)-family, MADDAM and decysin, were described as dendritic cell (DC) maturation markers. We are interested in monocyte differentiation and investigated in particular the expression pattern of both genes during the differentiation of human monocytes into DC and macrophages (MAC). Both genes are weakly expressed in freshly isolated monocytes. In immature DC decysin mRNA was absent, even after induction of the terminal differentiation of DC by CD40L or tumour necrosis factor-α (TNF-α). Only in DC maturated by lipopolysaccharide (LPS) strong signals of decysin mRNA were detected. However, MADDAM mRNA was expressed in immature DC and the expression was markedly increased after induction of the terminal DC differentiation by various stimuli. In contrast, MAC showed a high constitutive decysin mRNA expression, but expressed no MADDAM mRNA. On protein level similar results of MADDAM expression were obtained. Stimulation of MAC by LPS did not induce MADDAM mRNA expression, while decysin mRNA expression was strongly increased. Further investigations revealed that the well-known inducer of MAC differentiation, 1α,25-dihydroxyvitamin D3 up-regulated decysin mRNA expression during the differentiation of primary monocytes and myelomonocytic THP-1 cells into MAC. In vivo decysin mRNA expression was only detected in human colon, but not in other tissues we examined. Accordingly, isolated intestinal MAC expressed decysin mRNA. In conclusion, decysin and MADDAM mRNA expression were regulated in an opposite way during monocyte differentiation: MADDAM mRNA and protein was mainly detected in DC, whereas decysin mRNA expression was mainly found in MAC. Therefore only MADDAM, but not decysin is a suitable marker for human monocyte-derived DC. PMID:14632642

  14. Activity of ADAM17 (a Disintegrin and Metalloprotease 17) Is Regulated by Its Noncatalytic Domains and Secondary Structure of its Substrates*

    PubMed Central

    Stawikowska, Roma; Cudic, Mare; Giulianotti, Marc; Houghten, Richard A.; Fields, Gregg B.; Minond, Dmitriy

    2013-01-01

    ADAM proteases are implicated in multiple diseases, but no drugs based on ADAM inhibition exist. Most of the ADAM inhibitors developed to date feature zinc-binding moieties that target the active site zinc, which leads to a lack of selectivity and off target toxicity. Targeting secondary substrate binding sites (exosites) can potentially work as an alternative strategy for drug discovery; however, there are only a few reports of potential exosites in ADAM protease structures. In the study presented here, we utilized a series of TNFα-based substrates to probe ADAM10 and 17 interactions with its canonical substrate to identify the structural features that determine ADAM protease substrate specificity. We found that noncatalytic domains of ADAM17 did not directly bind the substrates used in the study but affected the binding nevertheless, most likely because of steric hindrance. Additionally, noncatalytic domains of ADAM17 affected the size/shape of the carbohydrate-binding pocket contained within the catalytic domain of ADAM17. This suggests that noncatalytic domains of ADAM17 play a role in substrate specificity and might help explain differences in substrate repertoires of ADAM17 and its closest homologue, ADAM10. We also addressed the question of which substrate features can affect ADAM protease specificity. We found that all ADAM proteases tested (i.e., ADAM10, 12, and 17) significantly decreased activity when the TNFα-derived sequence was induced into α-helical conformation, suggesting that conformation plays a role in determining ADAM protease substrate specificity. These findings can help in the discovery of ADAM isoform- and substrate-specific inhibitors. PMID:23779109

  15. Analysis of a two-bladed, teetering-hub turbine using the ADAMS (tm) software

    NASA Astrophysics Data System (ADS)

    Wright, A. D.; Osgood, R. O.; Malcolm, D. J.

    1994-05-01

    A major goal of the federal wind energy program is the rapid development and validation of structural models to determine loads and response for a wide variety of different wind turbine configurations operating under extreme conditions. Such codes are crucial to the successful design of future advanced wind turbines. In cooperation with R. Lynette & Associates the Wind Technology Division at NREL has developed a full system dynamics model of the AWT-26 Pl machine, using the Automatic Dynamic analysis of Mechanical Systems (ADAMS) software from Mechanical Dynamics, Inc. In this paper, we show validation of sub-models by comparisons with modal test data. We describe the most important system modes involved in this structure and demonstrate how the ADAMS model can be used to tune the structure to avoid interactions. We also identify questions that remain unanswered by ADAMS in modeling this turbine and recommend future directions that DOE code development activities should take.

  16. [An important son of Aub: the military surgeon and ophthalmologist Johann Adam Schmidt (1759-1809)].

    PubMed

    Krogmann, Frank; Vollmuth, Ralf

    2009-01-01

    The following article gives you a review to the life and work of the military surgeon and ophthalmologist Johann Adam Schmidt who was born in Aub/Lower Franconia on the 12th of October 1759. He had got his surgical education in Würzburg and had worked as an Unterchirurgus in the War of the Bavarian succession. Later on he completed his education in Vienna where he, by joining different work places, had been appointed to a professorship at the Medico-Surgical Joseph's Academy and became a leading figure of the Austrian military medical service. Also as an ophthalmologist Johann Adam Schmidt obtained high credit for his practical activity and his academic work. Johann Adam Schmidt died on the 19th of February 1809 and left a multiplicity of publications. He got not least publicity as the doctor of Beethoven, who dedicated the trio for piano, clarinet or violin and violoncello (Es-major) Opus 38 to Schmidt.

  17. Lytle S. Adams, DDS (1883-1970): Nonstop Airmail Pick-up inventor.

    PubMed

    Christen, Arden G; Christen, Joan A

    2005-11-01

    Between 1923 and 1940, a restless, optimistic, self-styled, inventor, Lytle S. Adams, DDS (1883-1970) was tirelessly working to develop a nonstop, airmail delivery and pick-up system. He believed that his invention would enable air postal services to serve those smaller, more isolated communities that would otherwise be bypassed due to economic and operational reasons. For 17 years, Adams vigorously promoted his pick-up system in both public and private arenas, and he even obtained congressional support for his ideas. However, he was unable to arrange for long-term, hardheaded financial and engineering support. Consequently, the once promising Adams Nonstop Airmail Pick-up System had only temporary and limited success. His endeavor, like others which came before and after, initially appeared to be a sound idea in search of inspired realization.

  18. PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells.

    PubMed

    Marchesi, Nicoletta; Amadio, Marialaura; Colombrita, Claudia; Govoni, Stefano; Ratti, Antonia; Pascale, Alessia

    2016-09-01

    Neuronal ELAV/Hu (nELAV) are RNA-binding proteins that mainly regulate gene expression by increasing the stability and/or translation rate of target mRNAs bearing ARE (adenine and uracil-rich elements) sequences. Among nELAV target transcripts there is ADAM10, an α-secretase involved in the non-amyloidogenic processing of the amyloid-β protein precursor (AβPP) which leads to the production of the neuroprotective sAβPPα peptide. The aim of this study was to evaluate if nELAV depletion affects ADAM10 expression in human SH-SY5Y neuroblastoma cells. We also studied the effects of Bryostatin-1, a molecule able to activate nELAV protein cascade. The specific HuD/nELAV gene silencing decreased both nELAV and ADAM10 protein contents; similar results were obtained by Aβ40 treatment in wild-type SH-SY5Y cells. In HuD-silenced cells, the exposure to Bryostatin-1 counteracted both nELAV and ADAM10 proteins downregulation, by restoring nELAV/ADAM10 basal levels. We also found that sAβPPα release, which seemed not to be compromised by Aβ40 challenge or HuD-silencing, was favored by Bryostatin-1. Overall, these findings strongly suggest that a deficiency in nELAV content negatively affects ADAM10 expression and may play a role in neurodegenerative diseases, which may benefit by molecules activating ELAV cascade.

  19. PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells.

    PubMed

    Marchesi, Nicoletta; Amadio, Marialaura; Colombrita, Claudia; Govoni, Stefano; Ratti, Antonia; Pascale, Alessia

    2016-09-01

    Neuronal ELAV/Hu (nELAV) are RNA-binding proteins that mainly regulate gene expression by increasing the stability and/or translation rate of target mRNAs bearing ARE (adenine and uracil-rich elements) sequences. Among nELAV target transcripts there is ADAM10, an α-secretase involved in the non-amyloidogenic processing of the amyloid-β protein precursor (AβPP) which leads to the production of the neuroprotective sAβPPα peptide. The aim of this study was to evaluate if nELAV depletion affects ADAM10 expression in human SH-SY5Y neuroblastoma cells. We also studied the effects of Bryostatin-1, a molecule able to activate nELAV protein cascade. The specific HuD/nELAV gene silencing decreased both nELAV and ADAM10 protein contents; similar results were obtained by Aβ40 treatment in wild-type SH-SY5Y cells. In HuD-silenced cells, the exposure to Bryostatin-1 counteracted both nELAV and ADAM10 proteins downregulation, by restoring nELAV/ADAM10 basal levels. We also found that sAβPPα release, which seemed not to be compromised by Aβ40 challenge or HuD-silencing, was favored by Bryostatin-1. Overall, these findings strongly suggest that a deficiency in nELAV content negatively affects ADAM10 expression and may play a role in neurodegenerative diseases, which may benefit by molecules activating ELAV cascade. PMID:27472877

  20. A Reader Response to File and Adams's "The Reality, Robustness, and Possible Superiority of Incidental Vocabulary Acquisition"

    ERIC Educational Resources Information Center

    Mason, Beniko; Krashen, Stephen

    2010-01-01

    File and Adams (2010) conclude that their data confirm the superiority of form-focused vocabulary instruction over incidental acquisition. The authors of this response argue that File and Adams's data actually confirm the reality, robustness, and possible superiority of incidental acquisition. Their subjects heard two passages read to them that…

  1. Problems with McAdams and Pals's (2006) Proposal of a Framework for an Integrative Theory of Personality

    ERIC Educational Resources Information Center

    Epstein, Seymour

    2007-01-01

    Comments on the original article "A New Big Five: Fundamental Principles for an Integrative Science of Personality," by Dan P. McAdams and Jennifer L. Pals (see record 2006-03947-002). Here, the current author begins with a critique of McAdams and Pals's (April 2006) five principles for a framework for an integrative theory of personality. The…

  2. 77 FR 25229 - Adams-Warnock Railway, Inc.-Lease and Operation Exemption-Norfolk Southern Railway Company

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Surface Transportation Board Adams-Warnock Railway, Inc.--Lease and Operation Exemption-- Norfolk Southern Railway Company Adams--Warnock Railway, Inc. (AWRY), a noncarrier, has filed a verified notice...

  3. 78 FR 37791 - In the Matter of: Jose Guadalupe Reyes-Martinez, Inmate Number #85993-279, CI Adams County...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ... by successive Presidential Notices, the most recent being that of August 15, 2012 (77 FR 49699..., CI Adams County, Correctional Institution, P.O. Box 1600, Washington, MS 39190; Order Denying Export... Adams County, Correctional Institution, P.O. Box 1600, Washington, MS 39190, and when acting for or...

  4. 77 FR 5291 - The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... published in the Federal Register. Dated: January 20, 2012. Hillary Rodham Clinton, Secretary of State... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known as Abu Adam...

  5. Adam M. Reid: APA/APAGS Award for Distinguished Graduate Student in Professional Psychology.

    PubMed

    2015-11-01

    The APA/APAGS Award for Distinguished Graduate Student in Professional Psychology is awarded on an annual basis by the APA Board of Professional Affairs (BPA) and the American Psychological Association of Graduate Students (APAGS) to a graduate student who has demonstrated outstanding practice and application of psychology. One of the 2015 award winners is Adam M. Reid, who received this award "for his community service, in which he has integrated the highest standards of professional psychological clinical practice and science." Adam's award citation, biography, and a selected bibliography are presented here.

  6. ADAM17 is critical for multipolar exit and radial migration of neuronal intermediate progenitor cells in mice cerebral cortex.

    PubMed

    Li, Qingyu; Zhang, Zhengyu; Li, Zengmin; Zhou, Mei; Liu, Bin; Pan, Le; Ma, Zhixing; Zheng, Yufang

    2013-01-01

    The radial migration of neuronal progenitor cells is critical for the development of cerebral cortex layers. They go through a critical step transforming from multipolar to bipolar before outward migration. A Disintegrin and Metalloprotease 17 (ADAM17) is a transmembrane protease which can process many substrates involved in cell-cell interaction, including Notch, ligands of EGFR, and some cell adhesion molecules. In this study, we used in utero electroporation to knock down or overexpress ADAM17 at embryonic day 14.5 (E14.5) in neuronal progenitor cells to examine the role of ADAM17 in cortical embryonic neurogenesis. Our results showed that the radial migration of ADAM17-knocked down cells were normal till E16.5 and reached the intermediate zone (IZ). Then most transfected cells stopped migration and stayed at the IZ to inner cortical plate (CP) layer at E18.5, and there was higher percentage of multipolar cells at IZ layer in the ADAM17-knocked down group compared to the cells in control group. Marker staining revealed that those ADAM17-knocked down cells differentiated normally from neural stem cells (NSCs) to neuronal intermediate progenitor cells (nIPCs) but did not differentiate into mature neurons. The migration and multipolar exit defects caused by ADAM17 knockdown could be partially rescued by over-expressing an shRNA resistant ADAM17, while overexpressing ADAM17 alone did not affect the radial migration. Taken together, our results showed for the first time that, ADAM17 is critical in regulating the multipolar-stage exit and radial migration of the nIPCs during telencephalon cortex development in mice. PMID:23755270

  7. ADAM17 is critical for multipolar exit and radial migration of neuronal intermediate progenitor cells in mice cerebral cortex.

    PubMed

    Li, Qingyu; Zhang, Zhengyu; Li, Zengmin; Zhou, Mei; Liu, Bin; Pan, Le; Ma, Zhixing; Zheng, Yufang

    2013-01-01

    The radial migration of neuronal progenitor cells is critical for the development of cerebral cortex layers. They go through a critical step transforming from multipolar to bipolar before outward migration. A Disintegrin and Metalloprotease 17 (ADAM17) is a transmembrane protease which can process many substrates involved in cell-cell interaction, including Notch, ligands of EGFR, and some cell adhesion molecules. In this study, we used in utero electroporation to knock down or overexpress ADAM17 at embryonic day 14.5 (E14.5) in neuronal progenitor cells to examine the role of ADAM17 in cortical embryonic neurogenesis. Our results showed that the radial migration of ADAM17-knocked down cells were normal till E16.5 and reached the intermediate zone (IZ). Then most transfected cells stopped migration and stayed at the IZ to inner cortical plate (CP) layer at E18.5, and there was higher percentage of multipolar cells at IZ layer in the ADAM17-knocked down group compared to the cells in control group. Marker staining revealed that those ADAM17-knocked down cells differentiated normally from neural stem cells (NSCs) to neuronal intermediate progenitor cells (nIPCs) but did not differentiate into mature neurons. The migration and multipolar exit defects caused by ADAM17 knockdown could be partially rescued by over-expressing an shRNA resistant ADAM17, while overexpressing ADAM17 alone did not affect the radial migration. Taken together, our results showed for the first time that, ADAM17 is critical in regulating the multipolar-stage exit and radial migration of the nIPCs during telencephalon cortex development in mice.

  8. Rethinking Equality of Opportunity: Comment on Adam Swift's "How Not to Be a Hypocrite"

    ERIC Educational Resources Information Center

    Anderson, Elizabeth

    2004-01-01

    Adam Swift objects to private schools on the grounds of equal opportunity and efficiency, and to both private and selective public schools on the grounds of solidarity and improving the academic achievement of less advantaged students. I argue that private schools are not inefficient, and that a meritocratic ideal of equality of opportunity in…

  9. VizieR Online Data Catalog: ADAM: 3D asteroid shape reconstruction code (Viikinkoski+, 2015)

    NASA Astrophysics Data System (ADS)

    Viikinkoski, M.; Kaasalainen, M.; Durech, J.

    2015-02-01

    About the code: ADAM is a collection of routines for 3D asteroid shape reconstruction from disk-resolved observations. Any combination of lightcurves, adaptive optics images, HST/FGS data, range-Doppler radar images and disk-resolved thermal images may be used as data sources. The routines are implemented in a combination of MATLAB and C. (2 data files).

  10. Adam Smith and the Educative Critique: A Response to My Commentators

    ERIC Educational Resources Information Center

    Weinstein, Jack Russell

    2015-01-01

    This paper is both a response to the four reviewers in a special symposium on my book Adam Smith's Pluralism and a substantive discussion of philosophy of education. In it, I introduce what I call "the educative critique," a mode of analysis similar to Marxist, feminist, or postcolonial critiques, but focusing on the educative role of a…

  11. THE E.O.A. BASIC EDUCATION COMMUNITY IN JOHN ADAMS ADULT SCHOOL, 1965-1966.

    ERIC Educational Resources Information Center

    EDMINSTER, HOWARD

    DATA FROM THE DEPARTMENT OF SOCIAL SERVICES AND SCHOOL FILES ARE PRESENTED ON 99 STUDENTS (90 PERCENT) REFERRED BY THE AGENCY TO THE BASIC EDUCATION PROGRAM AT THE JOHN ADAMS ADULT SCHOOL. OVER 60 PERCENT WERE NEGROES, WITH WHITES, MEXICANS, AND AMERICAN INDIANS ALSO REPRESENTED. THE MAJORITY WERE FROM SOUTHERN STATES, 37 PERCENT WERE DIVORCED OR…

  12. Music for Elementary Teachers; Self-Help Guide (MUS 370). Adams State College.

    ERIC Educational Resources Information Center

    Stokes, Cloyce

    This self-help guide for the music teacher is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The guide itself consists of 11 modules, the first five of which focus on the mathematical and scientific aspects of music--pitch, tempo, furation, time, and key. These five modules are…

  13. Keywords and Vocabulary Acquisition: Some Words of Caution about Johnson, Adams, and Bruning (1985).

    ERIC Educational Resources Information Center

    Pressley, Michael; Levin, Joel R.

    1985-01-01

    The mnemonic keyword study of Johnson, Adams, and Bruning (1985) on effectiveness of the keyword method for second-language vocabulary acquisition is critiqued. Of particular concern are literature currency vis-a-vis the authors' stated rationale for conducting the study, and methodological issues associated with the study's implementation.…

  14. Every Day Is Earth Day: A Resource List from the James P. Adams Library.

    ERIC Educational Resources Information Center

    Brennan, Patricia B. M.; And Others

    This is an extensive interdisciplinary bibliography of environmentally-related resources from the shelves of the James P. Adams Library at Rhode Island College. It is noted that the list is selective rather than comprehensive, and that the regional (United States, New England, or Rhode Island) has been emphasized when possible. The bibliography…

  15. Award for Distinguished Scientific Early Career Contributions to Psychology: Adam K. Anderson

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Adam K. Anderson, recipient of the Award for Distinguished Scientific Early Career Contributions to Psychology, is cited for his outstanding contribution to understanding the representation of emotion and its influence on cognition. By combining psychological and neuroscience techniques with rigorous and creative experimental designs, Anderson has…

  16. Boundary Value Technique for Initial Value Problems Based on Adams-Type Second Derivative Methods

    ERIC Educational Resources Information Center

    Jator, S. N.; Sahi, R. K.

    2010-01-01

    In this article, we propose a family of second derivative Adams-type methods (SDAMs) of order up to 2k + 2 ("k" is the step number) for initial value problems. The methods are constructed through a continuous approximation of the SDAM which is obtained by multistep collocation. The continuous approximation is used to obtain initial value methods,…

  17. Back to Beginnings: Credentialism, Productivity, and Adam Smith's Division of Labour.

    ERIC Educational Resources Information Center

    Davis, Denis J.

    1981-01-01

    The foundation of factional pressures for upgrading educational credentials in the labor market is examined through a review of human capital and screening theories. The writings of Adam Smith are referenced to show that the claims of the beneficial effects of educational upgrading have been questioned for 200 years. (Author/MLW)

  18. Rhetorical Studies: A Reassessment of Adam Smith's Lectures on Rhetoric and Belles Lettres.

    ERIC Educational Resources Information Center

    Purcell, William M.

    1986-01-01

    Offers a dissenting interpretation of Adam Smith's Lectures on Rhetoric and Belles Lettres and a more conservative perspective on Smith's significance to the history of rhetorical theory. Views the lectures as an historical commentary on literature and rhetoric from the perspective of an eighteenth-century lecturer. (JD)

  19. How To Survive in Postindustrial Environments: Adam Smith's Advice for Today's Colleges and Universities.

    ERIC Educational Resources Information Center

    Ortmann, Andreas

    1997-01-01

    Adam Smith's discussion of the payment modes of teachers and resulting consequences for the quality of teaching and process of curricular innovation are reviewed through the conceptual lens of modern agency theory. Smith's analysis of higher education in his day (eighteenth century) sheds light on faculty incentive and assessment problems that…

  20. Two Rival Conceptions of Vocational Education: Adam Smith and Friedrich List.

    ERIC Educational Resources Information Center

    Winch, Christopher

    1998-01-01

    Examines and discusses two views of political economy: (1) the classical model of Adam Smith; and (2) the social capitalist model associated with Friedrich List. Explores two varieties of vocational education and training that emerge from a comparison of Smith's and List's ideas. (CMK)

  1. Comparing Adam Smith's Wealth of Nations to James Madison's Federalist #10.

    ERIC Educational Resources Information Center

    Mundell, Jean

    1987-01-01

    Presents a lesson which calls upon students to compare Adam Smith's WEALTH OF NATIONS to James Madison's FEDERALIST #10 to see how the ancient concept of individual rights and liberties was used to describe both economic and governmental systems. Presents questions to provide the basis for comparison. (GEA)

  2. Implementation of Distributed ADAMS Over Legion Using a Component DBMS Design. Final Report

    SciTech Connect

    Pfaltz, John L.; Orlandic, Ratko

    2002-11-26

    There were four primary research areas reported in the final report for the original funding period They are: implementation of high dimensional data spaces; knowledge discovery in scientific databases; and mismatch between implementing components; demonstrate the utility of ADAMS in a specific domain science.

  3. The sheddase ADAM10 is a potent modulator of prion disease

    PubMed Central

    Altmeppen, Hermann C; Prox, Johannes; Krasemann, Susanne; Puig, Berta; Kruszewski, Katharina; Dohler, Frank; Bernreuther, Christian; Hoxha, Ana; Linsenmeier, Luise; Sikorska, Beata; Liberski, Pawel P; Bartsch, Udo; Saftig, Paul; Glatzel, Markus

    2015-01-01

    The prion protein (PrPC) is highly expressed in the nervous system and critically involved in prion diseases where it misfolds into pathogenic PrPSc. Moreover, it has been suggested as a receptor mediating neurotoxicity in common neurodegenerative proteinopathies such as Alzheimer's disease. PrPC is shed at the plasma membrane by the metalloprotease ADAM10, yet the impact of this on prion disease remains enigmatic. Employing conditional knockout mice, we show that depletion of ADAM10 in forebrain neurons leads to posttranslational increase of PrPC levels. Upon prion infection of these mice, clinical, biochemical, and morphological data reveal that lack of ADAM10 significantly reduces incubation times and increases PrPSc formation. In contrast, spatiotemporal analysis indicates that absence of shedding impairs spread of prion pathology. Our data support a dual role for ADAM10-mediated shedding and highlight the role of proteolytic processing in prion disease. DOI: http://dx.doi.org/10.7554/eLife.04260.001 PMID:25654651

  4. Springs, streams, and gas vent on and near Mount Adams volcano, Washington

    USGS Publications Warehouse

    Nathenson, Manuel; Mariner, Robert H.

    2013-01-01

    Springs and some streams on Mount Adams volcano have been sampled for chemistry and light stable isotopes of water. Spring temperatures are generally cooler than air temperatures from weather stations at the same elevation. Spring chemistry generally reflects weathering of volcanic rock from dissolved carbon dioxide. Water in some springs and streams has either dissolved hydrothermal minerals or has reacted with them to add sulfate to the water. Some samples appear to have obtained their sulfate from dissolution of gypsum while some probably involve reaction with sulfide minerals such as pyrite. Light stable isotope data for water from springs follow a local meteoric water line, and the variation of isotopes with elevation indicate that some springs have very local recharge and others have water from elevations a few hundred meters higher. No evidence was found for thermal or slightly thermal springs on Mount Adams. A sample from a seeping gas vent on Mount Adams was at ambient temperature, but the gas is similar to that found on other Cascade volcanoes. Helium isotopes are 4.4 times the value in air, indicating that there is a significant component of mantle helium. The lack of fumaroles on Mount Adams and the ambient temperature of the gas indicates that the gas is from a hydrothermal system that is no longer active.

  5. Highlighting High Performance Buildings: Adam Joseph Lewis Center for Environmental Studies

    SciTech Connect

    2002-11-01

    Oberlin College's Adam Joseph Lewis Center for Environmental Studies is a high-performance building featuring an expansive photovoltaic system and a closed-loop groundwater heat pump system. Designers incorporated energy-efficient components and materials that are local, non-toxic, and durable.

  6. Financial Assistance to Black Doctoral Students in Two "Adams" States: A Policy Analysis.

    ERIC Educational Resources Information Center

    Upton, James N.; Pruitt, Anne S.

    The context for financial aid policy affecting black doctoral students in Oklahoma and Florida was studied using the case study method. Attention was focused on environmental and organizational variables affecting the implementation of financial aid policy. Historical patterns surrounding race relations in both states before the 1973 "Adams"…

  7. Serendipity in the Theater: Maude Adams as James M. Barrie's American Muse.

    ERIC Educational Resources Information Center

    Diaz de Chumaceiro, Cora L.

    2003-01-01

    This essay discusses how Maude Adams influenced James M. Barrie's creative process and became his inspiration. Set change theory is underscored as a cognitive explanation for Barrie's illumination. The psychoanalytic theory of transference is proposed as an underlying mechanism for facilitating the change of mental set during the incubation stage.…

  8. Working for the People? Mrs Bridges Adams and the London School Board, 1897-1904.

    ERIC Educational Resources Information Center

    Martin, Jane

    2000-01-01

    Focuses on Mrs. Bridges Adams who was a supporter of state maintenance committed to educational opportunity for workers' children. Focuses on her political recruitment, her contribution to the work of the London School Board (England), and her role in the struggle to save the school board system. (CMK)

  9. Higher Education Financing in the Fifty States: Significance for the 'Adams' States.

    ERIC Educational Resources Information Center

    Budig, Jeanne E.; Khan, Anwar

    Findings of a study on higher education financing in the states are summarized with specific reference for the states covered by the 1977 Adams versus Richardson decision. The study, "Higher Education Financing in the Fifty States: Interstate Comparisons" (Marilyn McCoy, D. Kent Halstead), was jointly issued by the National Center for Higher…

  10. Black Faculty in Traditionally White Institutions in Selected "Adams" States: Characteristics, Experiences and Perceptions.

    ERIC Educational Resources Information Center

    Silver, John H.; And Others

    This document provides an empirical analysis of the hiring, promotion/advancement, and retention of black faculty in traditionally white public institutions of higher education in the 10 states affected by the Adams v. Richardson case. The underrepresentation of black scholars on the faculties of the nation's colleges and universities remains a…

  11. Achieving Social Justice: An Examination of Oklahoma's Response to "Adams v. Richardson."

    ERIC Educational Resources Information Center

    Olson, Carol; Hagy, Joe

    1990-01-01

    Reviews the efforts of Oklahoma to comply with the 1969 Supreme Court decision, "Adams v Richardson," which required states to desegregate traditionally White educational institutions. Concludes that Oklahoma has failed to increase the number of minority students in institutions of higher education but has institutionalized the principles of…

  12. The Quest To Define Collegiate Desegregation: Black Colleges, Title VI Compliance, and Post-Adams Litigation.

    ERIC Educational Resources Information Center

    Brown, M. Christopher, II

    This book outlines and explains the statutory and legal foundations of desegregation in higher education. It traces the historical development of college desegregation and analyzes the history of compliance and enforcement litigation in the aftermath of "Adams v. Richardson" (1972). The chapters are: (1) "Black Colleges and Desegregation"; (2)…

  13. Fractional Adams-Bashforth/Moulton methods: An application to the fractional Keller-Segel chemotaxis system

    NASA Astrophysics Data System (ADS)

    Zayernouri, Mohsen; Matzavinos, Anastasios

    2016-07-01

    We first formulate a fractional class of explicit Adams-Bashforth (A-B) and implicit Adams-Moulton (A-M) methods of first- and second-order accuracy for the time-integration of 0 CD t τ u (x , t) = g (t ; u), τ ∈ (0 , 1 ], where 0 CD t τ denotes the fractional derivative in the Caputo sense. In this fractional setting and in contrast to the standard Adams methods, an extra history load term emerges and the associated weight coefficients are τ-dependent. However when τ = 1, the developed schemes reduce to the well-known A-B and A-M methods with standard coefficients. Hence, in terms of scientific computing, our approach constitutes a minimal modification of the existing Adams libraries. Next, we develop an implicit-explicit (IMEX) splitting scheme for linear and nonlinear fractional PDEs of a general advection-reaction-diffusion type, and we apply our scheme to the time-space fractional Keller-Segel chemotaxis system. In this context, we evaluate the nonlinear advection term explicitly, employing the fractional A-B method in the prediction step, and we treat the corresponding diffusion term implicitly in the correction step using the fractional A-M scheme. Moreover, we perform the corresponding spatial discretization by employing an efficient and spectrally-accurate fractional spectral collocation method. Our numerical experiments exhibit the efficiency of the proposed IMEX scheme in solving nonlinear fractional PDEs.

  14. "Beginning To Read: Thinking and Learning about Print" by Marilyn Jager Adams. A Summary.

    ERIC Educational Resources Information Center

    Stahl, Steven A.; And Others

    Prepared for teachers, school administrators, parents, and other members of the interested public, this summary of Marilyn Jager Adams'"Beginning to Read: Thinking and Learning about Print" selects from the complex and extensive body of research in the book to present a more direct but much less detailed account of useful, research-based…

  15. The emerging role of matrix metalloproteases of the ADAM family in male germ cell apoptosis

    PubMed Central

    Urriola-Muñoz, Paulina; Lagos-Cabré, Raúl

    2011-01-01

    Constitutive germ cell apoptosis during mammalian spermatogenesis is a key process for controlling sperm output and to eliminate damaged or unwanted cells. An increase or decrease in the apoptosis rate has deleterious consequences and leads to low sperm production. Apoptosis in spermatogenesis has been widely studied, but the mechanism by which it is induced under physiological or pathological conditions has not been clarified. We have recently identified the metalloprotease ADAM17 (TACE) as a putative physiological inducer of germ cell apoptosis. The mechanisms involved in regulating the shedding of the ADAM17 extracellular domain are still far from being understood, although they are important in order to understand cell-cell communications. Here, we review the available data regarding apoptosis during mammalian spermatogenesis and the localization of ADAM proteins in the male reproductive tract. We propose an integrative working model where ADAM17, p38 MAPK, protein kinase C (PKC) and the tyrosine kinase c-Abl participate in the physiological signalling cascade inducing apoptosis in germ cells. In our model, we also propose a role for the Sertoli cell in regulating the Fas/FasL system in order to induce the extrinsic pathway of apoptosis in germ cells. This working model could be applied to further understand constitutive apoptosis in spermatogenesis and in pathological conditions (e.g., varicocele) or following environmental toxicants exposure (e.g., genotoxicity or xenoestrogens). PMID:22319668

  16. The Life and Times of John Couch Adams, from 1819 to 1847

    NASA Astrophysics Data System (ADS)

    Sheen, Brian M.

    2011-01-01

    John Couch Adams was born in 1819 in the middle of Cornwall, the most remote and isolated county in England. How he progressed from there to Cambridge University to become one of the finest mathematicians of the nineteenth century fills everyone who studies him with awe. Tragically what should have been his greatest triumph - the discovery of a new planet - was marred by mishap, controversy and unanswered questions. This presentation examines one of the first of these questions and provides new answers based on recently revealed evidence. The Astronomer Royal of the day was attempting to support Adams and as part of that support asked if his analysis took into account changes in radius vector of Uranus. Adams did not reply and the rest as they say is history. However there is far more to the question than a non-existent letter - this in itself turns out to be not exactly true. Further analysis of the orbits and a letter in French - not been translated before reveals Adams had a more profound understanding of the situation than some later authors have given him credit.

  17. Making Socialists: Mary Bridges Adams and the Fight for Knowledge and Power, 1855-1939

    ERIC Educational Resources Information Center

    Weiler, Kathleen

    2012-01-01

    This article presents a review of "Making socialists: Mary Bridges Adams and the fight for knowledge and power, 1855-1939," by Jane Martin. Jane Martin has explored the history of late-nineteenth-century and early-twentieth century-British women educational activists in numerous publications over the past two decades. Her first book, "Women and…

  18. Comparison of different order Adams-Bashforth methods in an atmospheric general circulation model

    NASA Astrophysics Data System (ADS)

    Zhao, Bin; Zhang, Bo

    2011-12-01

    The Asselin-Robert time filter used in the leapfrog scheme does degrade the accuracy of calculations. As an attractive alternative to leapfrog time differencing, the second-order Adams-Bashforth method is not subject to time splitting instability and keeps excellent calculation accuracy. A second-order Adams-Bashforth model has been developed, which represents better stability, excellent convergence and improved simulation of prognostic variables. Based on these results, the higher-order Adams-Bashforth methods are developed on the basis of NCAR (National Center for Atmospheric Research) CAM 3.1 (Community Atmosphere Model 3.1) and the characteristics of dynamical cores are analyzed in this paper. By using Lorenz nonlinear convective equations, the filtered leapfrog scheme shows an excellent pattern for eliminating 2Δ t wave solutions after 20 steps but represents less computational solution accuracy. The fourth-order Adams-Bashforth method is closely converged to the exact solution and provides a reference against which other methods may be compared. Thus, the Adams-Bashforth methods produce more accurate and convergent solution with differencing order increasing. The Held-Suarez idealized test is carried out to demonstrate that all methods have similar climate states to the results of many other global models for long-term integration. Besides, higher-order methods perform better in mass conservation and exhibit improvement in simulating tropospheric westerly jets, which is likely equivalent to the advantages of increasing horizontal resolutions. Based on the idealized baroclinic wave test, a better capability of the higher-order method in maintaining simulation stability is convinced. Furthermore, after the baroclinic wave is triggered through overlaying the steady-state initial conditions with the zonal perturbation, the higher-order method has a better ability in the simulation of baroclinic wave perturbation.

  19. Dysfunctional ADAM22 implicated in progressive encephalopathy with cortical atrophy and epilepsy

    PubMed Central

    Muona, Mikko; Fukata, Yuko; Anttonen, Anna-Kaisa; Laari, Anni; Palotie, Aarno; Pihko, Helena; Lönnqvist, Tuula; Valanne, Leena; Somer, Mirja; Fukata, Masaki

    2016-01-01

    Objective: To identify the molecular genetic basis of a syndrome characterized by rapidly progressing cerebral atrophy, intractable seizures, and intellectual disability. Methods: We performed exome sequencing in the proband and whole-genome single nucleotide polymorphism genotyping (copy number variant analysis) in the proband-parent trio. We used heterologous expression systems to study the functional consequences of identified mutations. Results: The search for potentially deleterious recessive or de novo variants yielded compound heterozygous missense (c.1202G>A, p.Cys401Tyr) and frameshift deletion (c.2396delG, p.Ser799IlefsTer96) mutations in ADAM22, which encodes a postsynaptic receptor for LGI1. The deleterious effect of the mutations was observed in cell surface binding and immunoprecipitation assays, which revealed that both mutant proteins failed to bind to LGI1. Furthermore, immunoprecipitation assays showed that the frameshift mutant ADAM22 also did not bind to the postsynaptic scaffolding protein PSD-95. Conclusions: The mutations identified abolish the LGI1-ADAM22 ligand-receptor complex and are thus a likely primary cause of the proband's epilepsy syndrome, which is characterized by unusually rapidly progressing cortical atrophy starting at 3–4 months of age. These findings are in line with the implicated role of the LGI1-ADAM22 complex as a key player in nervous system development, specifically in functional maturation of postnatal synapses. Because the frameshift mutation affects an alternatively spliced exon with highest expression in postnatal brain, the combined effect of the mutations is likely to be hypomorphic rather than complete loss of function. This is compatible with the longer survival of the patient compared to Lgi1−/− and Adam22−/− mice, which develop lethal seizures during the first postnatal weeks. PMID:27066583

  20. Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

    NASA Technical Reports Server (NTRS)

    Humphreys, B. T.; Thompson, W. K.; Lewandowski, B. E.; Cadwell, E. E.; Newby, N. J.; Fincke, R. S.; Sheehan, C.; Mulugeta, L.

    2012-01-01

    NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the

  1. Association of ADAM33 gene polymorphisms with COPD in a northeastern Chinese population

    PubMed Central

    2009-01-01

    Background Chronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors. ADAM33 (a disintegrin and metalloproteinase 33) has been one of the most exciting candidate genes for asthma since its first association with the disease in Caucasian populations. Recently, ADAM33 was shown to be associated with excessive decline of lung function and COPD. The aim of this study was to evaluate the potential relationship between polymorphisms of ADAM33 and COPD in a Han population in northeastern China. Methods A total of 312 COPD patients and a control group of 319 healthy volunteers were recruited for this study. Eight polymorphic loci (V4, T+1, T2, T1, S2, S1, Q-1, and F+1) of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results Statistically significant differences in the distributions of the T2G, T1G, S2C, and Q-1G alleles between patients and controls were observed (P < 0.001, odds ratio (OR) = 2.81, 95% confidence interval (CI) = 2.19-3.61; P < 0.001, OR = 2.60, 95% CI = 2.06-3.30; P = 0.03, OR = 1.31, 95% CI = 1.02-1.69; and P < 0.001, OR = 1.93, 95% CI = 1.50-2.50, respectively). Haplotype analysis showed that the frequencies of the CGGGGAGC, CGGGGAGT, CGGGCAGC, and CGGGGGGC haplotypes were significantly higher in the case group than in the control group (P = 0.0002, 0.0001, 0.0005, and 0.0074, respectively). In contrast, the haplotype CGAAGAGC was more common in the control group than in the case group (P < 0.0001). Conclusion These preliminary results suggest an association between ADAM33 polymorphisms and COPD in a Chinese Han population. PMID:20003279

  2. An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth.

    PubMed

    Atapattu, Lakmali; Saha, Nayanendu; Chheang, Chanly; Eissman, Moritz F; Xu, Kai; Vail, Mary E; Hii, Linda; Llerena, Carmen; Liu, Zhanqi; Horvay, Katja; Abud, Helen E; Kusebauch, Ulrike; Moritz, Robert L; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M; Nikolov, Dimitar B; Lackmann, Martin; Janes, Peter W

    2016-08-22

    The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. PMID:27503072

  3. MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targeting ADAM19

    SciTech Connect

    Shan, Nianxi; Shen, Liangfang; Wang, Jun; He, Dan; Duan, Chaojun

    2015-01-02

    Highlights: • Decreased miR-153 and up-regulated ADAM19 are correlated with NSCLC pathology. • MiR-153 inhibits the proliferation and migration and invasion of NSCLC cells in vitro. • ADAM19 is a direct target of miR-153. • ADAM19 is involved in miR-153-suppressed migration and invasion of NSCLC cells. - Abstract: MiR-153 was reported to be dysregulated in some human cancers. However, the function and mechanism of miR-153 in lung cancer cells remains unknown. In this study, we investigated the role of miR-153 in human non-small-cell lung cancer (NSCLC). Using qRT-PCR, we demonstrated that miR-153 was significantly decreased in clinical NSCLC tissues and cell lines, and downregulation of miR-153 was significantly correlated with lymph node status. We further found that ectopic expression of miR-153 significantly inhibited the proliferation and migration and invasion of NSCLC cells in vitro, suggesting that miR-153 may be a novel tumor suppressor in NSCLC. Further integrated analysis revealed that ADAM19 is as a direct and functional target of miR-153. Luciferase reporter assay demonstrated that miR-153 directly targeted 3′UTR of ADAM19, and correlation analysis revealed an inverse correlation between miR-153 and ADAM19 mRNA levels in clinical NSCLC tissues. Knockdown of ADAM19 inhibited migration and invasion of NSCLC cells which was similar with effects of overexpression of miR-153, while overexpression of ADAM19 attenuated the function of miR-153 in NSCLC cells. Taken together, our results highlight the significance of miR-153 and ADAM19 in the development and progression of NSCLC.

  4. Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II.

    PubMed

    Takayanagi, Takehiko; Forrester, Steven J; Kawai, Tatsuo; Obama, Takashi; Tsuji, Toshiyuki; Elliott, Katherine J; Nuti, Elisa; Rossello, Armando; Kwok, Hang Fai; Scalia, Rosario; Rizzo, Victor; Eguchi, Satoru

    2016-10-01

    Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which AngII elevates blood pressure and enhances cardiovascular remodeling and damage may be distinct. However, the signal transduction cascade by which AngII specifically initiates cardiovascular remodeling, such as hypertrophy and fibrosis, remains insufficiently understood. In vascular smooth muscle cells, a metalloproteinase ADAM17 mediates epidermal growth factor receptor transactivation, which may be responsible for cardiovascular remodeling but not hypertension induced by AngII. Thus, the objective of this study was to test the hypothesis that activation of vascular ADAM17 is indispensable for vascular remodeling but not for hypertension induced by AngII. Vascular ADAM17-deficient mice and control mice were infused with AngII for 2 weeks. Control mice infused with AngII showed cardiac hypertrophy, vascular medial hypertrophy, and perivascular fibrosis. These phenotypes were prevented in vascular ADAM17-deficient mice independent of blood pressure alteration. AngII infusion enhanced ADAM17 expression, epidermal growth factor receptor activation, and endoplasmic reticulum stress in the vasculature, which were diminished in ADAM17-deficient mice. Treatment with a human cross-reactive ADAM17 inhibitory antibody also prevented cardiovascular remodeling and endoplasmic reticulum stress but not hypertension in C57Bl/6 mice infused with AngII. In vitro data further supported these findings. In conclusion, vascular ADAM17 mediates AngII-induced cardiovascular remodeling via epidermal growth factor receptor activation independent of blood pressure regulation. ADAM17 seems to be a unique therapeutic target for the prevention of hypertensive complications.

  5. Src plays a key role in ADAM28 expression in v-src-transformed epithelial cells and human carcinoma cells.

    PubMed

    Abe, Hitoshi; Mochizuki, Satsuki; Ohara, Kentaro; Ueno, Mari; Ochiai, Hiroki; Kitagawa, Yuko; Hino, Okio; Sato, Hiroshi; Okada, Yasunori

    2013-11-01

    ADAM28, a disintegrin and metalloproteinase 28, is overexpressed by carcinoma cells with direct correlations with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, the molecular mechanisms of ADAM28 gene expression in carcinoma cells remain elusive. Herein, we investigated the expression of ADAM28 in Madin-Darby canine kidney epithelial cells transformed by oncogenes, including v-src, LMP1, ErbB2, Ha-Ras, and c-Fos, and found that v-src transformants selectively induce ADAM28. Implantation of the v-src transformants showed a progressively growing tumor, which was significantly suppressed by local injections of anti-ADAM28 antibody. ADAM28 expression in v-src transformants was partially inhibited by treatment with inhibitors to Src kinase, mitogen-activated protein kinase kinase (MEK), phosphatidylinositol 3-kinase (PI3K), or mammalian target of rapamycin, and abrogated by v-Src kinase inhibitor, radicicol, or a mixture of MEK and PI3K inhibitors. Human carcinoma cell lines of the lung, breast, ovary, kidney, and colon showed ADAM28 expression, which was correlated with phosphorylation of c-Src and suppressed by the inhibitors in a similar way to v-src transformants. IHC of the human tumor tissues demonstrated co-expression of ADAM28 and phosphorylated Src in neoplastic cells of the breast, lung, and colon carcinomas and some adenomas of the colon, but not in nonneoplastic colon mucosa. Our data provide, to the best of our knowledge, the first evidence that Src is an inducer of ADAM28 gene expression through the MEK/extracellular signal-regulated kinase and PI3K/mammalian target of rapamycin pathways. PMID:24007880

  6. Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II.

    PubMed

    Takayanagi, Takehiko; Forrester, Steven J; Kawai, Tatsuo; Obama, Takashi; Tsuji, Toshiyuki; Elliott, Katherine J; Nuti, Elisa; Rossello, Armando; Kwok, Hang Fai; Scalia, Rosario; Rizzo, Victor; Eguchi, Satoru

    2016-10-01

    Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which AngII elevates blood pressure and enhances cardiovascular remodeling and damage may be distinct. However, the signal transduction cascade by which AngII specifically initiates cardiovascular remodeling, such as hypertrophy and fibrosis, remains insufficiently understood. In vascular smooth muscle cells, a metalloproteinase ADAM17 mediates epidermal growth factor receptor transactivation, which may be responsible for cardiovascular remodeling but not hypertension induced by AngII. Thus, the objective of this study was to test the hypothesis that activation of vascular ADAM17 is indispensable for vascular remodeling but not for hypertension induced by AngII. Vascular ADAM17-deficient mice and control mice were infused with AngII for 2 weeks. Control mice infused with AngII showed cardiac hypertrophy, vascular medial hypertrophy, and perivascular fibrosis. These phenotypes were prevented in vascular ADAM17-deficient mice independent of blood pressure alteration. AngII infusion enhanced ADAM17 expression, epidermal growth factor receptor activation, and endoplasmic reticulum stress in the vasculature, which were diminished in ADAM17-deficient mice. Treatment with a human cross-reactive ADAM17 inhibitory antibody also prevented cardiovascular remodeling and endoplasmic reticulum stress but not hypertension in C57Bl/6 mice infused with AngII. In vitro data further supported these findings. In conclusion, vascular ADAM17 mediates AngII-induced cardiovascular remodeling via epidermal growth factor receptor activation independent of blood pressure regulation. ADAM17 seems to be a unique therapeutic target for the prevention of hypertensive complications. PMID:27480833

  7. Extraction and Separation Modeling of Orion Test Vehicles with ADAMS Simulation

    NASA Technical Reports Server (NTRS)

    Fraire, Usbaldo, Jr.; Anderson, Keith; Cuthbert, Peter A.

    2013-01-01

    The Capsule Parachute Assembly System (CPAS) project has increased efforts to demonstrate the performance of fully integrated parachute systems at both higher dynamic pressures and in the presence of wake fields using a Parachute Compartment Drop Test Vehicle (PCDTV) and a Parachute Test Vehicle (PTV), respectively. Modeling the extraction and separation events has proven challenging and an understanding of the physics is required to reduce the risk of separation malfunctions. The need for extraction and separation modeling is critical to a successful CPAS test campaign. Current PTV-alone simulations, such as Decelerator System Simulation (DSS), require accurate initial conditions (ICs) drawn from a separation model. Automatic Dynamic Analysis of Mechanical Systems (ADAMS), a Commercial off the Shelf (COTS) tool, was employed to provide insight into the multi-body six degree of freedom (DOF) interaction between parachute test hardware and external and internal forces. Components of the model include a composite extraction parachute, primary vehicle (PTV or PCDTV), platform cradle, a release mechanism, aircraft ramp, and a programmer parachute with attach points. Independent aerodynamic forces were applied to the mated test vehicle/platform cradle and the separated test vehicle and platform cradle. The aero coefficients were determined from real time lookup tables which were functions of both angle of attack ( ) and sideslip ( ). The atmospheric properties were also determined from a real time lookup table characteristic of the Yuma Proving Grounds (YPG) atmosphere relative to the planned test month. Representative geometries were constructed in ADAMS with measured mass properties generated for each independent vehicle. Derived smart separation parameters were included in ADAMS as sensors with defined pitch and pitch rate criteria used to refine inputs to analogous avionics systems for optimal separation conditions. Key design variables were dispersed in a Monte

  8. Fibronectin fragments and the cleaving enzyme ADAM-8 in the degenerative human intervertebral disc

    PubMed Central

    Ruel, Nancy; Markova, Dessislava Z.; Adams, Sherrill L.; Scanzello, Carla; Cs-Szabo, Gabriella; Gerard, David; Shi, Peng; Anderson, D. Greg; Zack, Marc; An, Howard S.; Chen, Di; Zhang, Yejia

    2014-01-01

    Study Design The presence fibronectin fragments (FN-fs) and the cleaving enzyme, A disintegrin and metalloproteinase domain-containing protein (ADAM)-8 were examined in human intervertebral disc (IVD) tissue in vitro. Objective To investigate the presence and pathophysiological concentration of FN-fs and their cleaving enzyme, ADAM-8, in the human IVD tissue. Summary of Background Data The 29kDa FN-f has been shown to result in extracellular matrix loss in rabbit IVDs. However, the concentration of this biologically active fragment in the degenerative human IVD tissue has previously not been determined. Further, it is critical to identify the enzyme(s) responsible for FN cleavage in the IVD. Methods Human degenerative IVD tissues were removed during spinal surgery. A normal appearing young adult and an infant human cadaveric sample were obtained as controls. Soluble proteins were extracted, and analyzed by Western blotting utilizing antibodies specific for the human FN neoepitope VRAA271. A purified 29 kDa FN-f was used to allow estimation of the concentration of FN-fs in the tissues. ADAM-8, a FN-cleaving enzyme, was analyzed by Western blotting and immunostaining. Results All adult IVD tissues contain many FN-f species, but these species were absent from the infant disc tissue. Moderately degenerative discs contained the highest amount of FN-fs; the concentration was estimated to be in the nanomolar range per gram of tissue. ADAM-8, known to cleave FN resulting in the VRAA271 neoepitope, was present in the human disc. ADAM-8 primarily localized in the pericellular matrix of the nucleus pulposus (NP) tissue, as determined by immunostaining. Conclusion This is the first report that N-terminal FN-fs are consistently present in IVD tissues from adult subjects. The pathophysiological concentration of these fragments is estimated to be at nanomolar range per gram of IVD tissue. Further, ADAM-8, known to cleave FN, is present at the pericellular matrix of disc cells

  9. The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis.

    PubMed

    De Savi, Chris; Pape, Andrew; Cumming, John G; Ting, Attilla; Smith, Peter D; Burrows, Jeremy N; Mills, Mark; Davies, Chris; Lamont, Scott; Milne, David; Cook, Calum; Moore, Peter; Sawyer, Yvonne; Gerhardt, Stefan

    2011-03-01

    Two series of N-hydroxyformamide inhibitors of ADAM-TS4 were identified from screening compounds previously synthesised as inhibitors of matrix metalloproteinase-13 (collagenase-3). Understanding of the binding mode of this class of compound using ADAM-TS1 as a structural surrogate has led to the discovery of potent and very selective inhibitors with favourable DMPK properties. Synthesis, structure-activity relationships, and strategies to improve selectivity and lower in vivo metabolic clearance are described.

  10. ADaM: augmenting existing approximate fast matching algorithms with efficient and exact range queries

    PubMed Central

    2014-01-01

    Background Drug discovery, disease detection, and personalized medicine are fast-growing areas of genomic research. With the advancement of next-generation sequencing techniques, researchers can obtain an abundance of data for many different biological assays in a short period of time. When this data is error-free, the result is a high-quality base-pair resolution picture of the genome. However, when the data is lossy the heuristic algorithms currently used when aligning next-generation sequences causes the corresponding accuracy to drop. Results This paper describes a program, ADaM (APF DNA Mapper) which significantly increases final alignment accuracy. ADaM works by first using an existing program to align "easy" sequences, and then using an algorithm with accuracy guarantees (the APF) to align the remaining sequences. The final result is a technique that increases the mapping accuracy from only 60% to over 90% for harder-to-align sequences. PMID:25079667

  11. Adam M. Grant: Award for Distinguished Scientific Early Career Contributions to Psychology.

    PubMed

    2011-11-01

    Presents Adam M. Grant, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "For extensive, elegant, and programmatic research on the power of relational job design in enhancing employee motivation, productivity, and satisfaction; for creative and rigorous studies documenting the profound and surprising effects of connecting employees to their impact on others; for highlighting prosocial motivation, not only extrinsic and intrinsic motivations, as a key force behind employee behavior; and for demonstrating by example the feasibility and benefits of conducting field experiments, yielding studies rich in internal validity, external validity, and practical impact. In addition to his accomplishments, Adam M. Grant is known for his generosity as a scholar, teacher, and colleague." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID:22082387

  12. Geochemical survey of the Adams Gap and Shinbone Creek Roadless Areas, Clay County, Alabama

    USGS Publications Warehouse

    Robinson, G.R.; Klein, T.L.; Lesure, F.G.; Hanley, J.T.

    1984-01-01

    Reports covering the mineral resources of Clay County and vicinity include Brewer (1896) and Adams (1930) on gold, Prouty (1923) on graphite, and Heinrich and Olson (1953) on mica. The mineral resources of the Talladega National Forest were evaluated by Gilbert and Smith (1973). The mineral resource potential of the two roadless areas is detailed in Robinson and others (1983) and an accompanying geologic report is given in Robinson and others (in press).

  13. Rival ecologies of global commerce: Adam Smith and the natural historians.

    PubMed

    Jonsson, Fredrik Albritton

    2010-01-01

    This essay explores how the defense of global commerce pioneered in the Enlightenment was tied to the improvement of the natural order. Two rival ecologies, one made by natural historians and the other developed by Adam Smith and his liberal successors, vied for intellectual precedence as well as for practical application in the metropole and the colonies. Together they constitute the beginnings of an ongoing quarrel over the environmental foundation of capitalism.

  14. Promoter Variants of the ADAM10 Gene and Their Roles in Temporal Lobe Epilepsy

    PubMed Central

    Tao, Hua; Zhao, Jianghao; Zhou, Xu; Ma, Zhonghua; Chen, Ying; Sun, Fuhai; Cui, Lili; Zhou, Haihong; Cai, Yujie; Chen, Yanyan; Zhao, Shu; Yao, Lifen; Zhao, Bin; Li, Keshen

    2016-01-01

    Previous evidence has indicated that downregulated ADAM10 gives rise to epileptic seizures in Alzheimer’s disease, and this study investigated the association of ADAM10 with temporal lobe epilepsy (TLE) from a genetic perspective. A total of 496 TLE patients and 528 healthy individuals were enrolled and genotyped for ADAM10 promoter variants (rs653765 G > A and rs514049 A > C). The alleles, genotypes, and haplotypes were then compared with clarify the association of these variants with TLE and their impacts upon age at onset, initial seizure types before treatments, and responses to drug treatments. In cohorts I, II, and I + II, the frequencies of the A allele and AA genotype at rs514049 were consistently increased in the cases compared with the controls (p = 0.020 and p = 0.009; p = 0.008 and p = 0.009; p = 0.000 and p = 0.000; q = 0.003 and q = 0.002, respectively). In contrast, the frequency of the AC haplotype (rs653765–rs514049) decreased in cohorts I + II (p = 0.013). Further analyses of the TLE patients indicated that the AA genotype functioned as a predisposing factor to drug-resistant TLE and the AC haplotype as a protective factor against generalized tonic–clonic seizures (GTCS) and drug-resistant TLE. This study is the first to demonstrate an association of the ADAM10 promoter variants with TLE. In particular, the AA genotype and AC haplotype showed their effects upon GTCS and drug-resistant TLE. PMID:27445971

  15. Museum Quality: A New Museum and Recharged College Bring Creative Energy to North Adams, Massachusetts

    ERIC Educational Resources Information Center

    Grant, Mary

    2005-01-01

    Nestled in the valley between the Berkshire hills and the Taconic range, North Adams, Massachusetts, in many ways is typical of old New England mill towns working hard to create a new identity in the global economy. When Sprague Electric left town in 1985, the city of 16,000 reeled from the loss of 4,000 blue-collar jobs. This article describes…

  16. INSULIN INDUCED EPIDERMAL GROWTH FACTOR ACTIVATION IN VASCULAR SMOOTH MUSCLE CELLS IS ADAM-DEPENDENT

    PubMed Central

    Roztocil, Elisa; Nicholl, Suzanne M.; Davies, Mark G.

    2008-01-01

    Background With the rise in metabolic syndrome, understanding the role of insulin signaling within the cells of vasculature has become more important but yet remains poorly defined. The study examines the role of insulin actions on a pivotal cross-talk receptor, Epidermal Growth Factor Receptor (EGFR). EGFR is transactivated by both G-protein-coupled receptors and receptor linked tyrosine kinases and is key to many of their responses. Objective To determine the pathway of EGFR transactivation by insulin in human coronary smooth muscle cells (VSMC) Methods VSMC were cultured in vitro. Assays of EGFR phosphorylation were examined in response to insulin in the presence and absence of the plasmin inhibitors (e-aminocaproic acid and aprotinin) matrix metalloprotease (MMP) inhibitor GM6001, the ADAM (A Disintegrin And Metalloproteinase Domain) inhibitors TAPI-0 and TAPI-1, Heparin binding epidermal growth factor (HB-EGF) inhibitor, CRM197, HB-EGF inhibitory antibodies, EGF inhibitory antibodies and the EGFR inhibitor AG1478. Results Insulin induced time-dependent EGFR phosphorylation, which was inhibited by AG1478 in a concentration dependent manner. Application of the plasmin inhibitors did not block the response. EGFR phosphorylation by insulin was blocked by inhibition of MMP activity and the ligand HB-EGF. The presence of the ADAM inhibitors, TAPI-0 and TAPI-1 significantly decreased EGFR activation. EGFR phosphorylation by EGF was not interrupted by inhibition of plasmin, MMPs TAPIs, or HB-EGF. Direct blockade of the EGFR prevented activation by both insulin and EGF. Conclusion Insulin can induce transactivation of EGFR by an ADAM-mediated, HB-EGF dependent process. This is the first description of crosstalk via ADAM between insulin and EGFR in vascular SMC. Targeting a pivotal cross-talk receptor such as EGFR, which can be transactivated by both G-protein-coupled receptors and receptor tyrosine kinases is an attractive molecular target. PMID:18656632

  17. Recombinant disintegrin domain of human ADAM9 inhibits migration and invasion of DU145 prostate tumor cells

    PubMed Central

    Martin, Ana Carolina Baptista Moreno; Cardoso, Ana Carolina Ferreira; Selistre-de-Araujo, Heloisa Sobreiro; Cominetti, Márcia Regina

    2015-01-01

    One of the most important features of malignant cells is their capacity to invade adjacent tissues and metastasize to distant organs. This process involves the creation, by tumor and stroma cells, of a specific microenvironment, suitable for proliferation, migration and invasion of tumor cells. The ADAM family of proteins has been involved in these processes. This work aimed to investigate the role of the recombinant disintegrin domain of the human ADAM9 (rADAM9D) on the adhesive and mobility properties of DU145 prostate tumor cells. rADAM9D was able to support DU145 cell adhesion, inhibit the migration of DU145 cells, as well as the invasion of this cell line through matrigel in vitro. Overall this work demonstrates that rADAM9D induces specific cellular migratory properties when compared with different constructs having additional domains, specially those of metalloproteinase and cysteine-rich domains. Furthermore, we showed that rADAM9D was able to inhibit cell adhesion, migration and invasion mainly through interacting with α6β1 in DU145 tumor cell line. These results may contribute to the development of new therapeutic strategies for prostate cancer. PMID:26211476

  18. IL-1β and ADAM17 are central regulators of β-defensin expression in Candida esophagitis.

    PubMed

    Pahl, Rene; Brunke, Gabriele; Steubesand, Nadine; Schubert, Sabine; Böttner, Martina; Wedel, Thilo; Jürgensen, Christian; Hampe, Jochen; Schäfer, Heiner; Zeissig, Sebastian; Schreiber, Stefan; Rosenstiel, Philip; Reiss, Karina; Arlt, Alexander

    2011-04-01

    Candida albicans resides on epithelial surfaces as part of the physiological microflora. However, under certain conditions, it may cause life-threatening infections, including Candida sepsis. We have recently shown that human β-defensins (hBDs) hBD-2 and hBD-3 are upregulated in Candida esophagitis and that this antifungal host response is distinctly regulated by NF-κB and MAPK/activator protein-1 (AP-1) pathways. Here, we show that C. albicans induces hBD-2 through an autocrine IL-1β loop and that activation of the epidermal growth factor receptor (EGFR) by endogenous transforming growth factor-α (TGF-α) is a crucial event in the induction of hBD-3. To further dissect upstream signaling events, we investigated expression of the central sheddases for EGFR ligands ADAM10 and ADAM17 in the healthy and infected esophagus. Next, we used pharmaceutical inhibitors and small-interfering RNA-mediated knock down of ADAM10 and ADAM17 to reveal that ADAM17-induced shedding of TGF-α is a crucial step in the induction of hBD-3 expression in response to Candida infection. In conclusion, we describe for the first time an autocrine IL-1β loop responsible for the induction of hBD-2 expression and an ADAM17-TGF-α-EGFR-MAPK/AP-1 pathway leading to hBD-3 upregulation in the course of a Candida infection of the esophagus. PMID:21233274

  19. Endostatin and irradiation modifies the activity of ADAM10 and neprilysin in breast cancer cells.

    PubMed

    Aydemir, Esra Arslan; Şimşek, Ece; Korcum, Aylin Fidan; Fişkin, Kayahan

    2016-09-01

    Angiogenesis, the formation of new blood vessels, is regarded as a key cancer cell property. Endostatin (ES) is a potential antiangiogenic agent and it may be useful when implemented in combination with other cancer therapeutic strategies. The present study investigated the in vitro effects of ES, radiotherapy (RT) or combination therapy (ES + RT) on two important proteases, a disintegrin and metalloproteinase domain‑containing protein 10 (ADAM10) and neprilysin (NEP) in 4T1 mouse breast cancer cells and the more metastatic phenotype of 4THMpc breast cancer cells. 4T1 and 4THMpc cells were treated with recombinant murine ES (4 µg/ml) alone, RT (45 Gy) alone or with ES + RT. ADAM10 enzyme activity was determined using a tumor necrosis factor‑α converting enzyme (α‑secretase) activity assay kit, and NEP enzyme activity was measured with a fluorometric assay based on the generation of free dansyl‑D‑Ala‑Gly from N-dansyl-Ala-Gly-D-nitro-Phe-Gly, the substrate of NEP. Western blotting analysis was performed to determine whether the altered enzyme activity levels of the two cell lines occurred due to changes in expression level. These data indicate that ES independently potentiates the activity of ADAM10 and NEP enzymes in 4T1 and 4THMpc breast cancer cells. PMID:27430992

  20. iRHOM2-dependent regulation of ADAM17 in cutaneous disease and epidermal barrier function.

    PubMed

    Brooke, Matthew A; Etheridge, Sarah L; Kaplan, Nihal; Simpson, Charlotte; O'Toole, Edel A; Ishida-Yamamoto, Akemi; Marches, Olivier; Getsios, Spiro; Kelsell, David P

    2014-08-01

    iRHOM2 is a highly conserved, catalytically inactive member of the Rhomboid family, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 (TACE) in macrophages. Dominant iRHOM2 mutations are the cause of the inherited cutaneous and oesophageal cancer-susceptibility syndrome tylosis with oesophageal cancer (TOC), suggesting a role for this protein in epithelial cells. Here, using tissues derived from TOC patients, we demonstrate that TOC-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes, resulting in significantly upregulated shedding of ADAM17 substrates, including EGF-family growth factors and pro-inflammatory cytokines. This activity is accompanied by increased EGFR activity, increased desmosome processing and the presence of immature epidermal desmosomes, upregulated epidermal transglutaminase activity and heightened resistance to Staphylococcal infection in TOC keratinocytes. Many of these features are consistent with the presence of a constitutive wound-healing-like phenotype in TOC epidermis, which may shed light on a novel pathway in skin repair, regeneration and inflammation.

  1. The LGI1-ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function.

    PubMed

    Lovero, Kathryn L; Fukata, Yuko; Granger, Adam J; Fukata, Masaki; Nicoll, Roger A

    2015-07-28

    Synapse development is coordinated by a number of transmembrane and secreted proteins that come together to form synaptic organizing complexes. Whereas a variety of synaptogenic proteins have been characterized, much less is understood about the molecular networks that support the maintenance and functional maturation of nascent synapses. Here, we demonstrate that leucine-rich, glioma-inactivated protein 1 (LGI1), a secreted protein previously shown to modulate synaptic AMPA receptors, is a paracrine signal released from pre- and postsynaptic neurons that acts specifically through a disintegrin and metalloproteinase protein 22 (ADAM22) to set postsynaptic strength. We go on to describe a novel role for ADAM22 in maintaining excitatory synapses through PSD-95/Dlg1/zo-1 (PDZ) domain interactions. Finally, we show that in the absence of LGI1, the mature synapse scaffolding protein PSD-95, but not the immature synapse scaffolding protein SAP102, is unable to modulate synaptic transmission. These results indicate that LGI1 and ADAM22 form an essential synaptic organizing complex that coordinates the maturation of excitatory synapses by regulating the functional incorporation of PSD-95.

  2. ADAM: a general method for using various data types in asteroid reconstruction

    NASA Astrophysics Data System (ADS)

    Viikinkoski, Matti; Kaasalainen, Mikko; Durech, Josef

    2015-04-01

    We introduce ADAM, the All-Data Asteroid Modelling algorithm. ADAM is simple and universal since it handles all disk-resolved data types (adaptive optics or other images, interferometry, and range-Doppler radar data) in a uniform manner via the 2D Fourier transform, enabling fast convergence in model optimization. The resolved data can be combined with disk-integrated data (photometry). In the reconstruction process, the difference between each data type is only a few code lines defining the particular generalized projection from 3D onto a 2D image plane. Occultation timings can be included as sparse silhouettes, and thermal infrared data are efficiently handled with an approximate algorithm that is sufficient in practice because of the dominance of the high-contrast (boundary) pixels over the low-contrast (interior) pixels. This is of particular importance to the raw ALMA data that can be directly handled by ADAM without having to construct the standard image. We study the reliability of the inversion, using the independent shape supports of function series and control-point surfaces. When other data are lacking, one can carry out fast non-convex lightcurve-only inversions, but any shape models resulting from it should only be taken as illustrative large-scale models. The code is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/576/A8

  3. An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin.

    PubMed

    Lo Sardo, Valentina; Zuccato, Chiara; Gaudenzi, Germano; Vitali, Barbara; Ramos, Catarina; Tartari, Marzia; Myre, Michael A; Walker, James A; Pistocchi, Anna; Conti, Luciano; Valenza, Marta; Drung, Binia; Schmidt, Boris; Gusella, James; Zeitlin, Scott; Cotelli, Franco; Cattaneo, Elena

    2012-05-01

    The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure. We studied neurulation in htt-null embryonic stem cells and htt-morpholino zebrafish embryos and found a previously unknown, evolutionarily recent function for this ancient protein. We found that htt was essential for homotypic interactions between neuroepithelial cells; it permitted neurulation and rosette formation by regulating metalloprotease ADAM10 activity and Ncadherin cleavage. This function was embedded in the N terminus of htt and was phenocopied by treatment of htt knockdown zebrafish with an ADAM10 inhibitor. Notably, in htt-null cells, reversion of the rosetteless phenotype occurred only with expression of evolutionarily recent htt heterologues from deuterostome organisms. Conversely, all of the heterologues that we tested, including htt from Drosophila melanogaster and Dictyostelium discoideum, exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one of htt’s ancestral function(s), but, in deuterostomes, htt evolved to acquire a unique regulatory activity for controlling neural adhesion via ADAM10-Ncadherin, with implications for brain evolution and development.

  4. An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin.

    PubMed

    Lo Sardo, Valentina; Zuccato, Chiara; Gaudenzi, Germano; Vitali, Barbara; Ramos, Catarina; Tartari, Marzia; Myre, Michael A; Walker, James A; Pistocchi, Anna; Conti, Luciano; Valenza, Marta; Drung, Binia; Schmidt, Boris; Gusella, James; Zeitlin, Scott; Cotelli, Franco; Cattaneo, Elena

    2012-05-01

    The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure. We studied neurulation in htt-null embryonic stem cells and htt-morpholino zebrafish embryos and found a previously unknown, evolutionarily recent function for this ancient protein. We found that htt was essential for homotypic interactions between neuroepithelial cells; it permitted neurulation and rosette formation by regulating metalloprotease ADAM10 activity and Ncadherin cleavage. This function was embedded in the N terminus of htt and was phenocopied by treatment of htt knockdown zebrafish with an ADAM10 inhibitor. Notably, in htt-null cells, reversion of the rosetteless phenotype occurred only with expression of evolutionarily recent htt heterologues from deuterostome organisms. Conversely, all of the heterologues that we tested, including htt from Drosophila melanogaster and Dictyostelium discoideum, exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one of htt’s ancestral function(s), but, in deuterostomes, htt evolved to acquire a unique regulatory activity for controlling neural adhesion via ADAM10-Ncadherin, with implications for brain evolution and development. PMID:22466506

  5. Reliability evaluation of I-123 ADAM SPECT imaging using SPM software and AAL ROI methods

    NASA Astrophysics Data System (ADS)

    Yang, Bang-Hung; Tsai, Sung-Yi; Wang, Shyh-Jen; Su, Tung-Ping; Chou, Yuan-Hwa; Chen, Chia-Chieh; Chen, Jyh-Cheng

    2011-08-01

    The level of serotonin was regulated by serotonin transporter (SERT), which is a decisive protein in regulation of serotonin neurotransmission system. Many psychiatric disorders and therapies were also related to concentration of cerebral serotonin. I-123 ADAM was the novel radiopharmaceutical to image SERT in brain. The aim of this study was to measure reliability of SERT densities of healthy volunteers by automated anatomical labeling (AAL) method. Furthermore, we also used statistic parametric mapping (SPM) on a voxel by voxel analysis to find difference of cortex between test and retest of I-123 ADAM single photon emission computed tomography (SPECT) images.Twenty-one healthy volunteers were scanned twice with SPECT at 4 h after intravenous administration of 185 MBq of 123I-ADAM. The image matrix size was 128×128 and pixel size was 3.9 mm. All images were obtained through filtered back-projection (FBP) reconstruction algorithm. Region of interest (ROI) definition was performed based on the AAL brain template in PMOD version 2.95 software package. ROI demarcations were placed on midbrain, pons, striatum, and cerebellum. All images were spatially normalized to the SPECT MNI (Montreal Neurological Institute) templates supplied with SPM2. And each image was transformed into standard stereotactic space, which was matched to the Talairach and Tournoux atlas. Then differences across scans were statistically estimated on a voxel by voxel analysis using paired t-test (population main effect: 2 cond's, 1 scan/cond.), which was applied to compare concentration of SERT between the test and retest cerebral scans.The average of specific uptake ratio (SUR: target/cerebellum-1) of 123I-ADAM binding to SERT in midbrain was 1.78±0.27, pons was 1.21±0.53, and striatum was 0.79±0.13. The cronbach's α of intra-class correlation coefficient (ICC) was 0.92. Besides, there was also no significant statistical finding in cerebral area using SPM2 analysis. This finding might help us

  6. The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining.

    PubMed

    Guo, Zhi-Bao; Su, Ying-Ying; Wang, Yi-Hui; Wang, Wei; Guo, Da-Zhi

    2016-09-01

    ADAM10 (a disintegrin and metalloprotease 10) is a member of the ADAMs family, which is key in the development of the nervous system, by regulating proliferation, migration, differentiation and survival of various cells, including axonal growth and myelination. Previous studies have investigated the embryonic or postnatal expression of ADAM10, however, detailed information regarding its cellular distribution in the adult stage, to the best of our knowledge, is not available. The present study investigated the expression pattern of the ADAM10 gene in the adult mouse central nervous system (CNS) using an ADAM10 complementary RNA probe for in situ hybridization (ISH). Immunohistochemical staining was used to identify the type of the ISH staining‑positive cells with neuron‑ or astrocyte‑specific antibodies. The results of the current study demonstrated that the ADAM10 gene was predominantly expressed in the neurons of the cerebral cortex, hippocampus, thalamus and cerebellar granular cells in adult mouse CNS. PMID:27431484

  7. The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining

    PubMed Central

    Guo, Zhi-Bao; Su, Ying-Ying; Wang, Yi-Hui; Wang, Wei; Guo, Da-Zhi

    2016-01-01

    ADAM10 (a disintegrin and metalloprotease 10) is a member of the ADAMs family, which is key in the development of the nervous system, by regulating proliferation, migration, differentiation and survival of various cells, including axonal growth and myelination. Previous studies have investigated the embryonic or postnatal expression of ADAM10, however, detailed information regarding its cellular distribution in the adult stage, to the best of our knowledge, is not available. The present study investigated the expression pattern of the ADAM10 gene in the adult mouse central nervous system (CNS) using an ADAM10 complementary RNA probe for in situ hybridization (ISH). Immunohistochemical staining was used to identify the type of the ISH staining-positive cells with neuron- or astrocyte-specific antibodies. The results of the current study demonstrated that the ADAM10 gene was predominantly expressed in the neurons of the cerebral cortex, hippocampus, thalamus and cerebellar granular cells in adult mouse CNS. PMID:27431484

  8. Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain-8 expression and cranial neural crest cell migration

    PubMed Central

    Cousin, Hélène; Abbruzzese, Genevieve; Kerdavid, Erin; Gaultier, Alban; Alfandari, Dominique

    2011-01-01

    Summary ADAMs are transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. The cytoplasmic domain of ADAMs can regulate the proteolytic activity by controlling the subcellular localization and/or the activation of the protease domain. Here we show that the cytoplasmic domain of ADAM13 is cleaved and translocates into the nucleus. Preventing this translocation renders the protein incapable of promoting cranial neural crest (CNC) cell migration in vivo, without affecting its proteolytic activity. In addition, the cytoplasmic domain of ADAM13 regulates the expression of multiple genes in CNC, including the protease Calpain8-a. Restoring the expression of Calpain8-a is sufficient to rescue CNC migration in the absence of the ADAM13 cytoplasmic domain. This study shows that the cytoplasmic domain of ADAM metalloproteases can perform essential functions in the nucleus of cells and may contribute substantially to the overall function of the protein. PMID:21316592

  9. Springs, streams, and gas vent on and near Mount Adams volcano, Washington

    NASA Astrophysics Data System (ADS)

    Nathenson, M.; Mariner, R. H.

    2013-12-01

    The construction of the Mount Adams stratovolcano in southwestern Washington started at about 520 ka (see review in Nathenson and Mariner, 2013). The volume rate of eruption has varied episodically, with the most recent period of high production having built the current central edifice during the period 35 to 10 ka. Eruptions have continued into the Holocene, but the rate of eruption has not been large. An extensive area and volume of hydrothermal alteration estimated from geologic and geophysical mapping indicates that there has been a significant hydrothermal system in the past. Oxidation of hydrogen sulfide produced elemental sulfur and sulfuric acid that interacted with andesite to produce kaolinite, alunite, gypsum, and silica. Springs and some streams on Mount Adams volcano have been sampled for chemistry and light stable isotopes of water (Nathenson and Mariner, 2013). No evidence was found for thermal or slightly thermal springs on Mount Adams. Spring temperatures are generally cooler than air temperatures from weather stations at the same elevation. Spring chemistry generally reflects weathering of volcanic rock from dissolved carbon dioxide. Water in some springs and streams has either dissolved hydrothermal minerals or has reacted with them to add sulfate to the water. Some samples appear to have obtained their sulfate from dissolution of gypsum while some probably involve reaction with sulfide minerals such as pyrite. Light stable isotope data for water from springs follow a local meteoric water line, and the variation of isotopes with elevation indicates that some springs have very local recharge and others have water from elevations a few hundred meters higher. A sample from a seeping gas vent on Mount Adams at an elevation of 3,609 m was at ambient temperature, but the gas is similar to that found on other Cascade volcanoes and appears to originate from a high-temperature (200°-300 °C) hydrothermal system. Helium isotopes are 4.4 times the value in

  10. Development of an advanced system identification technique for comparing ADAMS analytical results with modal test data for a MICON 65/13 wind turbine

    NASA Astrophysics Data System (ADS)

    Bialasiewicz, J. T.

    1995-07-01

    This work uses the theory developed in NREL/TP-442-7110 to analyze simulated data from an ADAMS (Automated Dynamic Analysis of Mechanical Systems) model of the MICON 65/13 wind turbine. The Observer/Kalman Filter identification approach is expanded to use input-output time histories from ADAMS simulations or structural test data. A step by step outline is offered on how the tools developed in this research, can be used for validation of the ADAMS model.

  11. Development of an advanced system identification technique for comparing ADAMS analytical results with modal test data for a MICON 65/13 wind turbine

    SciTech Connect

    Bialasiewicz, J.T.

    1995-07-01

    This work uses the theory developed in NREL/TP--442-7110 to analyze simulated data from an ADAMS (Automated Dynamic Analysis of Mechanical Systems) model of the MICON 65/13 wind turbine. The Observer/Kalman Filter identification approach is expanded to use input-output time histories from ADAMS simulations or structural test data. A step by step outline is offered on how the tools developed in this research, can be used for validation of the ADAMS model.

  12. Genetic variants of Adam17 differentially regulate TGFβ signaling to modify vascular pathology in mice and humans

    PubMed Central

    Kawasaki, Kyoko; Freimuth, Julia; Meyer, Dominique S.; Lee, Marie M.; Tochimoto-Okamoto, Akiko; Benzinou, Michael; Clermont, Frederic F.; Wu, Gloria; Roy, Ritu; Letteboer, Tom G. W.; Ploos van Amstel, Johannes Kristian; Giraud, Sophie; Dupuis-Girod, Sophie; Lesca, Gaeten; Westermann, Cornelius J. J.; Coffey, Robert J.; Akhurst, Rosemary J.

    2014-01-01

    Outcome of TGFβ1 signaling is context dependent and differs between individuals due to germ-line genetic variation. To explore innate genetic variants that determine differential outcome of reduced TGFβ1 signaling, we dissected the modifier locus Tgfbm3, on mouse chromosome 12. On a NIH/OlaHsd genetic background, the Tgfbm3bC57 haplotype suppresses prenatal lethality of Tgfb1−/− embryos and enhances nuclear accumulation of mothers against decapentaplegic homolog 2 (Smad2) in embryonic cells. Amino acid polymorphisms within a disintegrin and metalloprotease 17 (Adam17) can account, at least in part, for this Tgfbm3b effect. ADAM17 is known to down-regulate Smad2 signaling by shedding the extracellular domain of TGFβRI, and we show that the C57 variant is hypomorphic for down-regulation of Smad2/3-driven transcription. Genetic variation at Tgfbm3 or pharmacological inhibition of ADAM17, modulates postnatal circulating endothelial progenitor cell (CEPC) numbers via effects on TGFβRI activity. Because CEPC numbers correlate with angiogenic potential, this suggests that variant Adam17 is an innate modifier of adult angiogenesis, acting through TGFβR1. To determine whether human ADAM17 is also polymorphic and interacts with TGFβ signaling in human vascular disease, we investigated hereditary hemorrhagic telangiectasia (HHT), which is caused by mutations in TGFβ/bone morphogenetic protein receptor genes, ENG, encoding endoglin (HHT1), or ACVRL1 encoding ALK1 (HHT2), and considered a disease of excessive abnormal angiogenesis. HHT manifests highly variable incidence and severity of clinical features, ranging from small mucocutaneous telangiectases to life-threatening visceral and cerebral arteriovenous malformations (AVMs). We show that ADAM17 SNPs associate with the presence of pulmonary AVM in HHT1 but not HHT2, indicating genetic variation in ADAM17 can potentiate a TGFβ-regulated vascular disease. PMID:24812125

  13. SAR Studies of Exosite-Binding Substrate-Selective Inhibitors of A Disintegrin And Metalloprotease 17 (ADAM17) and Application as Selective in Vitro Probes.

    PubMed

    Knapinska, Anna M; Dreymuller, Daniela; Ludwig, Andreas; Smith, Lyndsay; Golubkov, Vladislav; Sohail, Anjum; Fridman, Rafael; Giulianotti, Marc; LaVoi, Travis M; Houghten, Richard A; Fields, Gregg B; Minond, Dmitriy

    2015-08-13

    ADAM17 is implicated in several debilitating diseases. However, drug discovery efforts targeting ADAM17 have failed due to the utilization of zinc-binding inhibitors. We previously reported discovery of highly selective nonzinc-binding exosite-targeting inhibitors of ADAM17 that exhibited not only enzyme isoform selectivity but synthetic substrate selectivity as well ( J. Biol. Chem. 2013, 288, 22871). As a result of SAR studies presented herein, we obtained several highly selective ADAM17 inhibitors, six of which were further characterized in biochemical and cell-based assays. Lead compounds exhibited low cellular toxicity and high potency and selectivity for ADAM17. In addition, several of the leads inhibited ADAM17 in a substrate-selective manner, which has not been previously documented for inhibitors of the ADAM family. These findings suggest that targeting exosites of ADAM17 can be used to obtain highly desirable substrate-selective inhibitors. Additionally, current inhibitors can be used as probes of biological activity of ADAM17 in various in vitro and, potentially, in vivo systems.

  14. ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeutic target in breast, ovarian and prostate cancers

    PubMed Central

    Sinnathamby, G; Zerfass, J; Hafner, J; Block, P; Nickens, Z; Hobeika, A; Secord, A A; Lyerly, H K; Morse, M A; Philip, R

    2011-01-01

    Selection of suitable antigens is critical for the development of cancer vaccines. Most desirable are over-expressed cell surface proteins that may serve as targets for both antibodies and T cells, thus maximizing a concerted immune response. Towards this goal, we characterized the relevance of tumour necrosis factor-α-converting enzyme (ADAM17) for such targeted therapeutics. ADAM17 is one of the several metalloproteinases that play a key role in epidermal growth factor receptor (EGFR) signalling and has recently emerged as a new therapeutic target in several tumour types. In the present study, we analysed the expression profile of ADAM17 in a variety of normal and cancer cells of human origin and found that this protein is over-expressed on the surface of several types of cancer cells compared to the normal counterparts. Furthermore, we analysed the presentation of a human leucocyte antigen (HLA)-A2-restricted epitope from ADAM17 protein to specific T cells established from normal donors as well as ovarian cancer patients. Our analysis revealed that the HLA-A2-restricted epitope is processed efficiently and presented by various cancer cells and not by normal cells. Tumour-specific T cell activation results in the secretion of both interferon-γ and granzyme B that can be blocked by HLA-A2 specific antibodies. Collectively, our data present evidence that ADAM17 can be a potential target antigen to devise novel immunotherapeutic strategies against ovarian, breast and prostate cancer. PMID:21175594

  15. ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeutic target in breast, ovarian and prostate cancers.

    PubMed

    Sinnathamby, G; Zerfass, J; Hafner, J; Block, P; Nickens, Z; Hobeika, A; Secord, A A; Lyerly, H K; Morse, M A; Philip, R

    2011-03-01

    Selection of suitable antigens is critical for the development of cancer vaccines. Most desirable are over-expressed cell surface proteins that may serve as targets for both antibodies and T cells, thus maximizing a concerted immune response. Towards this goal, we characterized the relevance of tumour necrosis factor-α-converting enzyme (ADAM17) for such targeted therapeutics. ADAM17 is one of the several metalloproteinases that play a key role in epidermal growth factor receptor (EGFR) signalling and has recently emerged as a new therapeutic target in several tumour types. In the present study, we analysed the expression profile of ADAM17 in a variety of normal and cancer cells of human origin and found that this protein is over-expressed on the surface of several types of cancer cells compared to the normal counterparts. Furthermore, we analysed the presentation of a human leucocyte antigen (HLA)-A2-restricted epitope from ADAM17 protein to specific T cells established from normal donors as well as ovarian cancer patients. Our analysis revealed that the HLA-A2-restricted epitope is processed efficiently and presented by various cancer cells and not by normal cells. Tumour-specific T cell activation results in the secretion of both interferon-γ and granzyme B that can be blocked by HLA-A2 specific antibodies. Collectively, our data present evidence that ADAM17 can be a potential target antigen to devise novel immunotherapeutic strategies against ovarian, breast and prostate cancer. PMID:21175594

  16. Helicopter magnetic and electromagnetic surveys at Mounts Adams, Baker and Rainier, Washington: implications for debris flow hazards and volcano hydrology

    USGS Publications Warehouse

    Finn, Carol A.; Deszcz-Pan, Maria

    2011-01-01

    High‐resolution helicopter magnetic and electromagnetic (HEM) data flown over the rugged, ice‐covered Mt. Adams, Mt. Baker and Mt. Rainier volcanoes (Washington), reveal the distribution of alteration, water and ice thickness essential to evaluating volcanic landslide hazards. These data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses (>500 m) of water‐saturated hydrothermally altered rock west of the modern summit of Mount Rainier in the Sunset Amphitheater region and in the central core of Mount Adams north of the summit. Alteration at Mount Baker is restricted to thinner (<300 m) zones beneath Sherman Crater and the Dorr Fumarole Fields. The EM data identified water‐saturated rocks from the surface to the detection limit (100–200 m) in discreet zones at Mt. Rainier and Mt Adams and over the entire summit region at Mt. Baker. The best estimates for ice thickness are obtained over relatively low resistivity (<800 ohm‐m) ground for the main ice cap on Mt. Adams and over most of the summit of Mt. Baker. The modeled distribution of alteration, pore fluids and partial ice volumes on the volcanoes helps identify likely sources for future alteration‐related debris flows, including the Sunset Amphitheater region at Mt. Rainier, steep cliffs at the western edge of the central altered zone at Mount Adams and eastern flanks of Mt. Baker.

  17. A systematic study of modulation of ADAM-mediated ectodomain shedding by site-specific O-glycosylation

    PubMed Central

    Goth, Christoffer K.; Halim, Adnan; Khetarpal, Sumeet A.; Rader, Daniel J.; Clausen, Henrik; Schjoldager, Katrine T.-B. G.

    2015-01-01

    Regulated shedding of the ectodomain of cell membrane proteins by proteases is a common process that releases the extracellular domain from the cell and activates cell signaling. Ectodomain shedding occurs in the immediate extracellular juxtamembrane region, which is also where O-glycosylation is often found and examples of crosstalk between shedding and O-glycosylation have been reported. Here, we systematically investigated the potential of site-specific O-glycosylation mediated by distinct polypeptide GalNAc-transferase (GalNAc-T) isoforms to coregulate ectodomain shedding mediated by the A Disintegrin And Metalloproteinase (ADAM) subfamily of proteases and in particular ADAM17. We analyzed 25 membrane proteins that are known to undergo ADAM17 shedding and where the processing sites included Ser/Thr residues within ± 4 residues that could represent O-glycosites. We used in vitro GalNAc-T enzyme and ADAM cleavage assays to demonstrate that shedding of at least 12 of these proteins are potentially coregulated by O-glycosylation. Using TNF-α as an example, we confirmed that shedding mediated by ADAM17 is coregulated by O-glycosylation controlled by the GalNAc-T2 isoform both ex vivo in isogenic cell models and in vivo in mouse Galnt2 knockouts. The study provides compelling evidence for a wider role of site-specific O-glycosylation in ectodomain shedding. PMID:26554003

  18. A systematic study of modulation of ADAM-mediated ectodomain shedding by site-specific O-glycosylation.

    PubMed

    Goth, Christoffer K; Halim, Adnan; Khetarpal, Sumeet A; Rader, Daniel J; Clausen, Henrik; Schjoldager, Katrine T-B G

    2015-11-24

    Regulated shedding of the ectodomain of cell membrane proteins by proteases is a common process that releases the extracellular domain from the cell and activates cell signaling. Ectodomain shedding occurs in the immediate extracellular juxtamembrane region, which is also where O-glycosylation is often found and examples of crosstalk between shedding and O-glycosylation have been reported. Here, we systematically investigated the potential of site-specific O-glycosylation mediated by distinct polypeptide GalNAc-transferase (GalNAc-T) isoforms to coregulate ectodomain shedding mediated by the A Disintegrin And Metalloproteinase (ADAM) subfamily of proteases and in particular ADAM17. We analyzed 25 membrane proteins that are known to undergo ADAM17 shedding and where the processing sites included Ser/Thr residues within ± 4 residues that could represent O-glycosites. We used in vitro GalNAc-T enzyme and ADAM cleavage assays to demonstrate that shedding of at least 12 of these proteins are potentially coregulated by O-glycosylation. Using TNF-α as an example, we confirmed that shedding mediated by ADAM17 is coregulated by O-glycosylation controlled by the GalNAc-T2 isoform both ex vivo in isogenic cell models and in vivo in mouse Galnt2 knockouts. The study provides compelling evidence for a wider role of site-specific O-glycosylation in ectodomain shedding. PMID:26554003

  19. Role of ADAM17 in invasion and migration of CD133-expressing liver cancer stem cells after irradiation

    PubMed Central

    Hong, Sung Woo; Hur, Wonhee; Choi, Jung Eun; Kim, Jung-Hee; Hwang, Daehee; Yoon, Seung Kew

    2016-01-01

    We investigated the biological role of CD133-expressing liver cancer stem cells (CSCs) enriched after irradiation of Huh7 cells in cell invasion and migration. We also explored whether a disintegrin and metalloproteinase-17 (ADAM17) influences the metastatic potential of CSC-enriched hepatocellular carcinoma (HCC) cells after irradiation. A CD133-expressing Huh7 cell subpopulation showed greater resistance to sublethal irradiation and specifically enhanced cell invasion and migration capabilities. We also demonstrated that the radiation-induced MMP-2 and MMP-9 enzyme activities as well as the secretion of vascular endothelial growth factor were increased more predominantly in Huh7CD133+ cell subpopulations than Huh7CD133− cell subpopulations. Furthermore, we showed that silencing ADAM17 significantly inhibited the migration and invasiveness of enriched Huh7CD133+ cells after irradiation; moreover, Notch signaling was significantly reduced in irradiated CD133-expressing liver CSCs following stable knockdown of the ADAM17 gene. In conclusion, our findings indicate that CD133-expressing liver CSCs have considerable metastatic capabilities after irradiation of HCC cells, and their metastatic capabilities might be maintained by ADAM17. Therefore, suppression of ADAM17 shows promise for improving the efficiency of current radiotherapies and reducing the metastatic potential of liver CSCs during HCC treatment. PMID:26993601

  20. Association of ADAM33 gene polymorphisms with adult allergic asthma and rhinitis in a Chinese Han population

    PubMed Central

    Su, Dongju; Zhang, Ximei; Sui, Hong; Lü, Fuzhen; Jin, Lianhong; Zhang, Jing

    2008-01-01

    Background Rhinitis and asthma are very common diseases involving genetic and environmental factors. Most patients with asthma also have rhinitis, which suggests the concept of 'one airway, one disease.' A disintegrin and metalloproteinase 33 (ADAM33) is the first asthma-susceptible gene to be discovered by positional cloning. To evaluate the potential influence of ADAM33 gene polymorphisms on allergic rhinitis (AR) and allergic asthma (AS), a case-control study was conducted on the Han population of northeast China. Methods Six polymorphic sites (V4, T+1, T2, T1, S1, and Q-1) were genotyped in 128 patients with AR, 181 patients with AS, and 151 healthy controls (CTR). Genotypes were determined by the polymerase chain restriction fragment length polymorphism (PCR-RFLP) method. Data were analyzed using the chi-square test with Haploview software. Results The single nucleotide polymorphisms (SNPs), V4 G/C, T+1 A/G, and T1 G/A, of the ADAM33 gene may be the causal variants in AR, whereas ADAM33 V4 G/C, T2 A/G, T1 G/A, and Q-1A/G may participate in the susceptibility of AS. Conclusion These results suggest that polymorphisms of the ADAM33 gene may modify individual susceptibility to AR and AS in a Chinese Han population. PMID:18778489

  1. ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

    PubMed Central

    2011-01-01

    Background Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. Results We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Conclusions Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on

  2. The Co-simulation of Humanoid Robot Based on Solidworks, ADAMS and Simulink

    NASA Astrophysics Data System (ADS)

    Song, Dalei; Zheng, Lidan; Wang, Li; Qi, Weiwei; Li, Yanli

    A simulation method of adaptive controller is proposed for the humanoid robot system based on co-simulation of Solidworks, ADAMS and Simulink. A complex mathematical modeling process is avoided by this method, and the real time dynamic simulating function of Simulink would be exerted adequately. This method could be generalized to other complicated control system. This method is adopted to build and analyse the model of humanoid robot. The trajectory tracking and adaptive controller design also proceed based on it. The effect of trajectory tracking is evaluated by fitting-curve theory of least squares method. The anti-interference capability of the robot is improved a lot through comparative analysis.

  3. [Professor Adam Nowosławski (1925-2012)--founder of the Polish School of Immunopathology].

    PubMed

    Madaliński, Kazimierz

    2012-01-01

    Professor dr med. Adam Nowosławski, has died at age of 87, on February 3, 2012, the founder of the Polish school of immunopathology, member of Polish Academy of Sciences and of Polish Academy of Art and Sciences. Professor was born on April 30, 1925 in Rzeszów (SE Poland). During the Second World War he took part in the anti-nazi resistance movement; he was the soldier of the 'Baszta' regiment of the Home Army. Subsequently, he was imprisoned in the Pawiak and concentration camps: Majdanek and Buchenwald. The medical studies he has completed at Warsaw Medical Academy between 1946-1951. The degree of doctor of medicine Prof. Adam Nowosławski has obtained in 1963, habilitation degree in the field of immunopathology--in 1966; the title of Professor he has obtained in 1980. His scientific achievements consist of 170 publications, including 101 original papers. His publications were quoted in several American books for students and physicians. Topics of his early papers concerned the immunopatogenesis ofPneumocystis carinii--induced pneumonia in premature babies, immunopatogenesis of rheumatoid arthritis, and the origin of rheumatoid factor. The enormous role in the field of hepatology played research on the virus of hepatitis B. These studies dealt with the discovery of HB core antigen which had the cellular localization different from HB surface antigen and with the parameters of the immune response to infection. Papers published on this topic were the mostly quoted in the literature and earned him national awards. The activity of Prof. Adam Nowosławski in the field of HIV/AIDS prevention was honored by the special prize of the Minister of Health. Professor was the honorary member of the two Societies: Polish Society of Pathologists and Polish Society of Hepatology. He was also the member of International Association for the Study of the Liver and International Academy of Pathology. Prof. Adam Nowosławski received the national medals: Polonia Restituta Crosses

  4. A Mechanism of Male Germ Cell Apoptosis Induced by Bisphenol-A and Nonylphenol Involving ADAM17 and p38 MAPK Activation

    PubMed Central

    Moreno, Ricardo D.

    2014-01-01

    Germ cell apoptosis regulation is pivotal in order to maintain proper daily sperm production. Several reports have shown that endocrine disruptors such as Bisphenol-A (BPA) and Nonylphenol (NP) induce germ cell apoptosis along with a decrease in sperm production. Given their ubiquitous distribution in plastic products used by humans it is important to clarify their mechanism of action. TACE/ADAM17 is a widely distributed extracellular metalloprotease and participates in the physiological apoptosis of germ cells during spermatogenesis. The aims of this work were: 1) to determine whether BPA and NP induce ADAM17 activation; and 2) to study whether ADAM17 and/or ADAM10 are involved in germ cell apoptosis induced by BPA and NP in the pubertal rat testis. A single dose of BPA or NP (50 mg/kg) induces germ cell apoptosis in 21-day-old male rats, which was prevented by a pharmacological inhibitor of ADAM17, but not by an inhibitor of ADAM10. In vitro, we showed that BPA and NP, at similar concentrations to those found in human samples, induce the shedding of exogenous and endogenous (TNF-α) ADAM17 substrates in primary rat Sertoli cell cultures and TM4 cell line. In addition, pharmacological inhibitors of metalloproteases and genetic silencing of ADAM17 prevent the shedding induced in vitro by BPA and NP. Finally, we showed that in vivo BPA and NP induced early activation (phosphorylation) of p38 MAPK and translocation of ADAM17 to the cell surface. Interestingly, the inhibition of p38 MAPK prevents germ cell apoptosis and translocation of ADAM17 to the cell surface. These results show for the first time that xenoestrogens can induce activation of ADAM17 at concentrations similar to those found in human samples, suggesting a mechanism by which they could imbalance para/juxtacrine cell-to-cell-communication and induce germ cell apoptosis. PMID:25474107

  5. The Cysteine-Rich Domain of Human Adam 12 Supports Cell Adhesion through Syndecans and Triggers Signaling Events That Lead to β1 Integrin–Dependent Cell Spreading

    PubMed Central

    Iba, Kousuke; Albrechtsen, Reidar; Gilpin, Brent; Fröhlich, Camilla; Loechel, Frosty; Zolkiewska, Anna; Ishiguro, Kazuhiro; Kojima, Tetsuhito; Liu, Wei; Langford, J. Kevin; Sanderson, Ralph D.; Brakebusch, Cord; Fässler, Reinhard; Wewer, Ulla M.

    2000-01-01

    The ADAMs (a disintegrin and metalloprotease) family of proteins is involved in a variety of cellular interactions, including cell adhesion and ecto- domain shedding. Here we show that ADAM 12 binds to cell surface syndecans. Three forms of recombinant ADAM 12 were used in these experiments: the cys-teine-rich domain made in Escherichia coli (rADAM 12-cys), the disintegrin-like and cysteine-rich domain made in insect cells (rADAM 12-DC), and full-length human ADAM 12-S tagged with green fluorescent protein made in mammalian cells (rADAM 12-GFP). Mesenchymal cells specifically and in a dose-dependent manner attach to ADAM 12 via members of the syndecan family. After binding to syndecans, mesenchymal cells spread and form focal adhesions and actin stress fibers. Integrin β1 was responsible for cell spreading because function-blocking monoclonal antibodies completely inhibited cell spreading, and chondroblasts lacking β1 integrin attached but did not spread. These data suggest that mesenchymal cells use syndecans as the initial receptor for the ADAM 12 cysteine-rich domain–mediated cell adhesion, and then the β1 integrin to induce cell spreading. Interestingly, carcinoma cells attached but did not spread on ADAM 12. However, spreading could be efficiently induced by the addition of either 1 mM Mn2+ or the β1 integrin–activating monoclonal antibody 12G10, suggesting that in these carcinoma cells, the ADAM 12–syndecan complex fails to modulate the function of β1 integrin. PMID:10831617

  6. Analysis of a two-bladed, teetering-hub turbine using the ADAMS{reg_sign} software

    SciTech Connect

    Wright, A D; Osgood, R O; Malcolm, D J

    1994-05-01

    A major goal of the federal wind energy program is the rapid development and validation of structural models to determine loads and response for a wide variety of different wind turbine configurations operating under extreme conditions. Such codes are crucial to the successful design of future advanced wind turbines. In cooperation with R. Lynette & Associates the Wind Technology Division at NREL has developed a full system dynamics model of the AWT-26 Pl machine, using the Automatic Dynamic analysis of Mechanical Systems (ADAMS) software from Mechanical Dynamics, Inc. In this paper, we show validation of sub-models by comparisons with modal test data. We describe the most important system modes involved in this structure and demonstrate how the ADAMS model can be used to tune the structure to avoid interactions. We also identify questions that remain unanswered by ADAMS in modeling this turbine and recommend future directions that DOE code development activities should take.

  7. Neptune: towards understanding how Adams's upbringing enabled him to predict, then miss the discovery of the century

    NASA Astrophysics Data System (ADS)

    Sheen, B.

    2013-03-01

    The story of John Couch Adams the great Cornish astronomer of the nineteenth century is well known and this paper will not revisit old ground. However, many questions remain unanswered and in this paper I propose to indicate some of them as section headings, and seek to address them. In this way Adams's early life is examined, and its effect on his academic life during the time of the Neptune discovery. The row that followed discovery is high-lighted together with the equally contentious issue of the new planet's name. Although it is usually believed that Adams graciously accepted the failure of the Cambridge University Observatory to find his planet, examination of his later work which is often highly critical of French astronomers sheds a different light on that theory.

  8. ADAM10 overexpression shifts lympho- and myelopoiesis by dysregulating site 2/site 3 cleavage products of Notch.

    PubMed

    Gibb, David R; Saleem, Sheinei J; Kang, Dae-Joong; Subler, Mark A; Conrad, Daniel H

    2011-04-01

    Although the physiological consequences of Notch signaling in hematopoiesis have been extensively studied, the differential effects of individual notch cleavage products remain to be elucidated. Given that ADAM10 is a critical regulator of Notch and that its deletion is embryonically lethal, we generated mice that overexpress ADAM10 (ADAM10 transgenic [A10Tg]) at early stages of lympho- and myeloid development. Transgene expression resulted in abrogated B cell development, delayed T cell development in the thymus, and unexpected systemic expansion of CD11b(+)Gr-1(+) cells, also known as myeloid-derived suppressor cells. Mixed bone marrow reconstitution assays demonstrated that transgene expression altered hematopoiesis via a cell-intrinsic mechanism. Consistent with previously reported observations, we hypothesized that ADAM10 overexpression dysregulated Notch by uncoupling the highly regulated proteolysis of Notch receptors. This was confirmed using an in vitro model of hematopoiesis via culturing A10Tg hematopoietic Lineage(-)Sca-1(+)c-Kit(+) cells with OP-9 stromal cells in the presence or absence of Delta-like 1, a primary ligand for Notch. Blockade of the site 2 (S2) and site 3 (S3) cleavage of the Notch receptor demonstrated differential effects on hematopoiesis. OP9-DL1 cultures containing the ADAM10 inhibitor (S2 cleavage site) enhanced and rescued B cell development from wild-type and A10Tg Lineage(-)Sca-1(+)c-Kit(+) cells, respectively. In contrast, blockade of γ-secretase at the S3 cleavage site induced accumulation of the S2 product and consequently prevented B cell development and resulted in myeloid cell accumulation. Collectively, these findings indicate that the differential cleavage of Notch into S2 and S3 products regulated by ADAM10 is critical to hematopoietic cell-fate determination.

  9. Dynamic change of Adamalysin 19 (ADAM19) in human placentas and its effects on cell invasion and adhesion in human trophoblastic cells.

    PubMed

    Zhao, MeiRong; Qiu, Wei; Li, YuXia; Sang, QingXiang Amy; Wang, YanLing

    2009-08-01

    Human ADAM19 is a recently identified member of the ADAM family. It is highly expressed in human placentas, but its dynamic change and function at the human feto-maternal interface during placentation remain to be elucidated. In this present study, the spatial and temporal expression and cellular localization of ADAM19 in normal human placentas were first demonstrated, and the effects of ADAM19 on trophoblast cell adhesion and invasion were further investigated by using a human choriocarcinoma cell line (JEG-3) as an in vitro model. The data demonstrated that ADAM19 was widely distributed in villous cytotrophoblast cells, syncytiotrophoblast cells, column trophoblasts, and villous capillary endothelial cells during early pregnancy. The mRNA and protein level of ADAM19 in placentas was high at gestational weeks 8-9, but diminished significantly at mid- and term pregnancy. In JEG-3 cells, the overexpression of ADAM19 led to diminished cell invasion, as well as increases in cell adhesiveness and the expression of E-cadherin, with no changes in beta-catenin expression observed. These data indicate that ADAM19 may participate in the coordinated regulation of human trophoblast cell behaviors during the process of placentation.

  10. Skin Barrier Defects Caused by Keratinocyte-Specific Deletion of ADAM17 or EGFR Are Based on Highly Similar Proteome and Degradome Alterations.

    PubMed

    Tholen, Stefan; Wolf, Cristina; Mayer, Bettina; Knopf, Julia D; Löffek, Stefanie; Qian, Yawen; Kizhakkedathu, Jayachandran N; Biniossek, Martin L; Franzke, Claus-Werner; Schilling, Oliver

    2016-05-01

    Keratinocyte-specific deletion of ADAM17 in mice impairs terminal differentiation of keratinocytes leading to severe epidermal barrier defects. Mice deficient for ADAM17 in keratinocytes phenocopy mice with a keratinocyte-specific deletion of epidermal growth factor receptor (EGFR), which highlights the role of ADAM17 as a "ligand sheddase" of EGFR ligands. In this study, we aim for the first proteomic/degradomic approach to characterize the disruption of the ADAM17-EGFR signaling axis and its consequences for epidermal barrier formation. Proteomic profiling of the epidermal proteome of mice deficient for either ADAM17 or EGFR in keratinocytes at postnatal days 3 and 10 revealed highly similar protein alterations for ADAM17 and EGFR deficiency. These include massive proteome alterations of structural and regulatory components important for barrier formation such as transglutaminases, involucrin, filaggrin, and filaggrin-2. Cleavage site analysis using terminal amine isotopic labeling of substrates revealed increased proteolytic processing of S100 fused-type proteins including filaggrin-2. Alterations in proteolytic processing are supported by altered abundance of numerous proteases upon keratinocyte-specific Adam17 or Egfr deletion, among them kallikreins, cathepsins, and their inhibitors. This study highlights the essential role of proteolytic processing for maintenance of a functional epidermal barrier. Furthermore, it suggests that most defects in formation of the postnatal epidermal barrier upon keratinocyte-specific ADAM17 deletion are mediated via EGFR.

  11. Towards the "Informed Use" of Information and Communication Technology in Education: A Response to Adams' "Powerpoint, Habits of Mind, and Classroom Culture"

    ERIC Educational Resources Information Center

    Vallance, Michael; Towndrow, Phillip A.

    2007-01-01

    PowerPoint, the widely-used slide-show software package, is finding increasing currency in lecture halls and classrooms as the preferred method of communicating and presenting information. But, as Adams [Adams, C. (2006) "PowerPoint, habits of mind, and classroom culture." "Journal of Curriculum Studies," 38(4), 389-411] attempts to show, users…

  12. ADAM10 Cell Surface Expression but Not Activity Is Critical for Staphylococcus aureus α-Hemolysin-Mediated Activation of the NLRP3 Inflammasome in Human Monocytes

    PubMed Central

    Ezekwe, Ejiofor A.D.; Weng, Chengyu; Duncan, Joseph A.

    2016-01-01

    The Staphylococcus aureus toxin, α-hemolysin, is an important and well-studied virulence factor in staphylococcal infection. It is a soluble monomeric protein that, once secreted by the bacterium, forms a heptameric pore in the membrane of a broad range of host cell types. Hemolysin was recently discovered to bind and activate a disintegrin and metalloprotease 10 (ADAM10). In epithelial and endothelial cells, ADAM10 activation is required for the toxin’s activity against these cells. In host monocytic cells, α-hemolysin activates the nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 (NLRP3) inflammasome leading to production of pro-inflammatory cytokines and cell death. We now show that ADAM10 is critical for α-hemolysin-mediated activation of the NLRP3 inflammasome in human monocytes as siRNA knockdown or chemical blockade of ADAM10-α-hemolysin interaction leads to diminished inflammasome activation and cell death by reducing the available ADAM10 on the cell surface. Unlike epithelial cell and endothelial cell damage, which requires α-hemolysin induced ADAM10 activation, ADAM10 protease activity was not required for NLRP3 inflammasome activation. This work confirms the importance of ADAM10 in immune activation by α-hemolysin, but indicates that host cell signal induction by the toxin is different between host cell types. PMID:27043625

  13. Postglacial lahars and potential hazards in the White Salmon River system on the southwest flank of Mount Adams, Washington

    USGS Publications Warehouse

    Vallance, James W.

    1999-01-01

    Mount Adams, a stratovolcano in southwestern Washington State, formed during Pleistocene time and reached roughly its present size before the end of the Fraser glaciation, which occurred between 25,000 and 12,000 years ago. Since the last glaciation, Mount Adams has erupted at least nine times, producing eight peripheral lava flows and a cinder cone at the summit but no pyroclastic flows. No stratigraphic evidence was found for the occurrence of lahars concurrently with eruptions; in fact, at least one lahar and one debris avalanche occurred during apparently dormant intervals.

  14. Isotopic and trace element constraints on the petrogenesis of lavas from the Mount Adams volcanic field, Washington

    USGS Publications Warehouse

    Jicha, B.R.; Hart, G.L.; Johnson, C.M.; Hildreth, W.; Beard, B.L.; Shirey, S.B.; Valley, J.W.

    2009-01-01

    Strontium, Nd, Pb, Hf, Os, and O isotope compositions for 30 Quaternary lava flows from the Mount Adams stratovolcano and its basaltic periphery in the Cascade arc, southern Washington, USA indicate a major component from intraplate mantle sources, a relatively small subduction component, and interaction with young mafic crust at depth. Major- and trace-element patterns for Mount Adams lavas are distinct from the rear-arc Simcoe volcanic field and other nearby volcanic centers in the Cascade arc such as Mount St. Helens. Radiogenic isotope (Sr, Nd, Pb, and Hf) compositions do not correlate with geochemical indicators of slab-fluids such as (Sr/P)n and Ba/Nb. Mass-balance modeling calculations, coupled with trace-element and isotopic data, indicate that although the mantle source for the calc-alkaline Adams basalts has been modified with a fluid derived from subducted sediment, the extent of modification is significantly less than what is documented in the southern Cascades. The isotopic and trace-element compositions of most Mount Adams lavas require the presence of enriched and depleted mantle sources, and based on volume-weighted chemical and isotopic compositions for Mount Adams lavas through time, an intraplate mantle source contributed the major magmatic mass of the system. Generation of basaltic andesites to dacites at Mount Adams occurred by assimilation and fractional crystallization in the lower crust, but wholesale crustal melting did not occur. Most lavas have Tb/Yb ratios that are significantly higher than those of MORB, which is consistent with partial melting of the mantle in the presence of residual garnet. ??18O values for olivine phenocrysts in Mount Adams lavas are within the range of typical upper mantle peridotites, precluding involvement of upper crustal sedimentary material or accreted terrane during magma ascent. The restricted Nd and Hf isotope compositions of Mount Adams lavas indicate that these isotope systems are insensitive to crustal

  15. Isotopic and trace element constraints on the petrogenesis of lavas from the Mount Adams volcanic field, Washington

    NASA Astrophysics Data System (ADS)

    Jicha, Brian R.; Hart, Garret L.; Johnson, Clark M.; Hildreth, Wes; Beard, Brian L.; Shirey, Steven B.; Valley, John W.

    2009-02-01

    Strontium, Nd, Pb, Hf, Os, and O isotope compositions for 30 Quaternary lava flows from the Mount Adams stratovolcano and its basaltic periphery in the Cascade arc, southern Washington, USA indicate a major component from intraplate mantle sources, a relatively small subduction component, and interaction with young mafic crust at depth. Major- and trace-element patterns for Mount Adams lavas are distinct from the rear-arc Simcoe volcanic field and other nearby volcanic centers in the Cascade arc such as Mount St. Helens. Radiogenic isotope (Sr, Nd, Pb, and Hf) compositions do not correlate with geochemical indicators of slab-fluids such as (Sr/P) n and Ba/Nb. Mass-balance modeling calculations, coupled with trace-element and isotopic data, indicate that although the mantle source for the calc-alkaline Adams basalts has been modified with a fluid derived from subducted sediment, the extent of modification is significantly less than what is documented in the southern Cascades. The isotopic and trace-element compositions of most Mount Adams lavas require the presence of enriched and depleted mantle sources, and based on volume-weighted chemical and isotopic compositions for Mount Adams lavas through time, an intraplate mantle source contributed the major magmatic mass of the system. Generation of basaltic andesites to dacites at Mount Adams occurred by assimilation and fractional crystallization in the lower crust, but wholesale crustal melting did not occur. Most lavas have Tb/Yb ratios that are significantly higher than those of MORB, which is consistent with partial melting of the mantle in the presence of residual garnet. δ 18O values for olivine phenocrysts in Mount Adams lavas are within the range of typical upper mantle peridotites, precluding involvement of upper crustal sedimentary material or accreted terrane during magma ascent. The restricted Nd and Hf isotope compositions of Mount Adams lavas indicate that these isotope systems are insensitive to crustal

  16. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

    PubMed Central

    Kashef, Jubin; Alfandari, Dominique

    2015-01-01

    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell–cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. PMID:26206614

  17. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.

    PubMed

    Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique

    2016-07-15

    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo.

  18. ADAM10-mediated release of heregulin confers resistance to trastuzumab by activating HER3

    PubMed Central

    Ebbing, Eva A.; Medema, Jan Paul; Damhofer, Helene; Meijer, Sybren L.; Krishnadath, Kausilia K.; van Berge Henegouwen, Mark I.

    2016-01-01

    Receptor tyrosine kinases of the HER-family are involved in the development and progression of multiple epithelial tumors, and have consequently become widely used targets for new anti-cancer therapies. Trastuzumab, an antibody against HER2, has shown potent growth inhibitory effects on HER2 overexpressing tumors, including gastro-esophageal cancer, however, resistance to this therapy is inevitable. Unfortunately, a paucity of data on the cellular mechanisms of resistance to targeted therapeutic agents exists in esophageal adenocarcinoma. Using primary established HER2-overexpressing cultures and patient-derived xenograft models, we now reveal a novel resistance mechanism to trastuzumab in esophageal cancer: In response to trastuzumab, both HER3 and the metalloprotease ADAM10 are simultaneously upregulated. The proteolytic activity of the latter then releases the HER3 ligand heregulin from the cell surface to activate HER3 and confer resistance to trastuzumab by inducing compensatory growth factor receptor signaling. Blocking either HER3 or ADAM10 effectively reverts the acquired resistance to trastuzumab. Our data thus provide strategies to inhibit this signaling and circumvent resistance to trastuzumab. PMID:26863569

  19. John G.C. Adams: father of Dental Public Health in Canada.

    PubMed

    Kenny, David J; Dale, Anne C; Wencer, David G

    2014-01-01

    John Gennings Curtis Adams (1839-1922), Canada's first resident dental missionary, was the father of Dental Public Health in Canada. He established, personally funded and operated the first free dental hospital in North America for poor children and their mothers in Toronto from 1872, three years before the founding of The Hospital for Sick Children; he later became their first dentist of record. He was a visionary zealot for prevention of decay, dental education, and treatment over extraction. Dr. Adams understood that neither parents (rich or poor) nor physicians were aware of the extent of pathosis present in children's mouths. He petitioned individuals, lobbied politicians and unions and pressured dental organizations on the importance of twice-annual school inspections to demonstrate disease so that parents would seek care for their children. He wanted government-funded dental hospitals like his own to treat those who could not afford care. He realized his objectives and his reforms to prevent suffering, as Toronto school inspections began in 1911 and Toronto's first publicly-funded free dental clinic opened in 1913. He was Canada's first dental philanthropist and a visionary for preventive dentistry.

  20. John G.C. Adams: father of Dental Public Health in Canada.

    PubMed

    Kenny, David J; Dale, Anne C; Wencer, David G

    2014-01-01

    John Gennings Curtis Adams (1839-1922), Canada's first resident dental missionary, was the father of Dental Public Health in Canada. He established, personally funded and operated the first free dental hospital in North America for poor children and their mothers in Toronto from 1872, three years before the founding of The Hospital for Sick Children; he later became their first dentist of record. He was a visionary zealot for prevention of decay, dental education, and treatment over extraction. Dr. Adams understood that neither parents (rich or poor) nor physicians were aware of the extent of pathosis present in children's mouths. He petitioned individuals, lobbied politicians and unions and pressured dental organizations on the importance of twice-annual school inspections to demonstrate disease so that parents would seek care for their children. He wanted government-funded dental hospitals like his own to treat those who could not afford care. He realized his objectives and his reforms to prevent suffering, as Toronto school inspections began in 1911 and Toronto's first publicly-funded free dental clinic opened in 1913. He was Canada's first dental philanthropist and a visionary for preventive dentistry. PMID:25549402

  1. TACE/ADAM17 is essential for oligodendrocyte development and CNS myelination.

    PubMed

    Palazuelos, Javier; Crawford, Howard C; Klingener, Michael; Sun, Bingru; Karelis, Jason; Raines, Elaine W; Aguirre, Adan

    2014-09-01

    Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGFα and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPs in vivo leads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination.

  2. TACE/ADAM17 Is Essential for Oligodendrocyte Development and CNS Myelination

    PubMed Central

    Palazuelos, Javier; Crawford, Howard C.; Klingener, Michael; Sun, Bingru; Karelis, Jason; Raines, Elaine W.

    2014-01-01

    Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGFα and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPs in vivo leads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination. PMID:25186737

  3. Adam's Dream

    ERIC Educational Resources Information Center

    Piacenti, Alexandria

    2011-01-01

    Growing up as a young girl, summer camp was a typical affair. Packed lunches kept cold with frozen freezer packs, seemingly endless slip n' slides, activities, games, contests. Every morning, the author was eager to wake up and head off to hours and hours of fun with friends and counselors. However, one may think the camping experience could not…

  4. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

    PubMed

    Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

    2016-05-01

    ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. PMID:26918856

  5. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

    PubMed

    Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

    2016-05-01

    ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells.

  6. Spatially heterogeneous dynamics and the Adam-Gibbs relation in the Dzugutov liquid.

    PubMed

    Gebremichael, Yeshitila; Vogel, Michael; Bergroth, Magnus N J; Starr, Francis W; Glotzer, Sharon C

    2005-08-11

    We perform molecular dynamics simulations of a one-component glass-forming liquid and use the inherent structure formalism to test the predictions of the Adam-Gibbs (AG) theory and to explore the possible connection between these predictions and spatially heterogeneous dynamics. We calculate the temperature dependence of the average potential energy of the equilibrium liquid and show that it obeys the Rosenfeld-Tarazona T(3/5) law for low temperature T, while the average inherent structure energy is found to be inversely proportional to temperature at low T, consistent with a Gaussian distribution of potential energy minima. We investigate the shape of the basins around the local minima in configuration space via the average basin vibrational frequency and show that the basins become slightly broader upon cooling. We evaluate the configurational entropy S(conf), a measure of the multiplicity of potential energy minima sampled by the system, and test the validity of the AG relation between S(conf) and the bulk dynamics. We quantify the dynamically heterogeneous motion by analyzing the motion of particles that are mobile on short and intermediate time scales relative to the characteristic bulk relaxation time. These mobile particles move in one-dimensional "strings", and these strings form clusters with a well-defined average cluster size. The AG approach predicts that the minimum size of cooperatively rearranging regions (CRR) of molecules is inversely proportional to S(conf), and recently (Phys. Rev. Lett. 2003, 90, 085506) it has been shown that the mobile-particle clusters are consistent with the CRR envisaged by Adam and Gibbs. We test the possibility that the mobile-particle strings, rather than clusters, may describe the CRR of the Adam-Gibbs approach. We find that the strings also follow a nearly inverse relation with S(conf). We further show that the logarithm of the time when the strings and clusters are maximum, which occurs in the late

  7. A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease

    PubMed Central

    Hao, Jingcan; Wang, Wenyu; Wen, Yan; Xiao, Xiao; He, Awen; Guo, Xiong; Yang, Tielin; Liu, Xiaogang; Shen, Hui; Chen, Xiangding; Tian, Qing; Deng, Hong-Wen; Zhang, Feng

    2016-01-01

    Kashin-Beck disease (KBD) is a chronic osteoarthropathy, which manifests as joint deformities and growth retardation. Only a few genetic studies of growth retardation associated with the KBD have been carried out by now. In this study, we conducted a two-stage bivariate genome-wide association study (BGWAS) of the KBD using joint deformities and body height as study phenotypes, totally involving 2,417 study subjects. Articular cartilage specimens from 8 subjects were collected for immunohistochemistry. In the BGWAS, ADAM12 gene achieved the most significant association (rs1278300 p-value = 9.25 × 10−9) with the KBD. Replication study observed significant association signal at rs1278300 (p-value = 0.007) and rs1710287 (p-value = 0.002) of ADAM12 after Bonferroni correction. Immunohistochemistry revealed significantly decreased expression level of ADAM12 protein in the KBD articular cartilage (average positive chondrocyte rate = 47.59 ± 7.79%) compared to healthy articular cartilage (average positive chondrocyte rate = 64.73 ± 5.05%). Our results suggest that ADAM12 gene is a novel susceptibility gene underlying both joint destruction and growth retardation of the KBD. PMID:27545300

  8. Lightweight robotic mobility: template-based modeling for dynamics and controls using ADAMS/car and MATLAB

    NASA Astrophysics Data System (ADS)

    Adamczyk, Peter G.; Gorsich, David J.; Hudas, Greg R.; Overholt, James

    2003-09-01

    The U.S. Army is seeking to develop autonomous off-road mobile robots to perform tasks in the field such as supply delivery and reconnaissance in dangerous territory. A key problem to be solved with these robots is off-road mobility, to ensure that the robots can accomplish their tasks without loss or damage. We have developed a computer model of one such concept robot, the small-scale "T-1" omnidirectional vehicle (ODV), to study the effects of different control strategies on the robot's mobility in off-road settings. We built the dynamic model in ADAMS/Car and the control system in Matlab/Simulink. This paper presents the template-based method used to construct the ADAMS model of the T-1 ODV. It discusses the strengths and weaknesses of ADAMS/Car software in such an application, and describes the benefits and challenges of the approach as a whole. The paper also addresses effective linking of ADAMS/Car and Matlab for complete control system development. Finally, this paper includes a section describing the extension of the T-1 templates to other similar ODV concepts for rapid development.

  9. The Feasibility of Consolidating the Schools of Mount Joy Township, Adams County, Pennsylvania. Bulletin, 1920, No. 9

    ERIC Educational Resources Information Center

    Cook, Katherine M.; Deffenbaugh, W. S.

    1920-01-01

    Mount Joy Township is located in southeastern Pennsylvania, in Adams County. It is immediately adjacent to the historic battlefield and town of Gettysburg. Though irregular in shape, it averages about 5 miles from north to south and 41 miles from east to west, and contains approximately 36 square miles. The population of the township in 1910 was…

  10. Estrogen upregulates MICA/B expression in human non-small cell lung cancer through the regulation of ADAM17.

    PubMed

    Ren, Jing; Nie, Yunzhong; Lv, Mingming; Shen, Sunan; Tang, Ruijing; Xu, Yujun; Hou, Yayi; Zhao, Shuli; Wang, Tingting

    2015-11-01

    Estrogen is involved in promoting lung cancer cell division and metastasis. MICA and MICB function as ligands for NKG2D, an important immunoreceptor expressed on natural killer (NK) cells. However, whether estrogen regulates MICA/B expression and affects tumor immune escape remains unknown. In this study, we measured the mRNA levels of MICA, MICB and ADAM17in non-small cell lung cancer (NSCLC) cell lines treated with estrogen. Surface expression of MICA/B on LTEP-a2 and A549 was detected using flow cytometry. We demonstrate that both mRNA and secretory protein levels of MICA/B in lung adenocarcinoma cell lines were upregulated by estradiol. Estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. This secretion of MICA/B downregulated the NKG2D receptor on the surface of NK92 cells and impaired the cytotoxic activity of NK cells. Estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. Furthermore, a significant correlation between the concentration of estradiol and the expression of MICA was found in tumor tissues of NSCLC patients. Therefore, we conclude that estrogen can regulate the expression and secretion of MICA/B through ADAM17, which helps lung cancer cells escape NKG2D-mediated immune surveillance.

  11. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Response from Adam C. Maloof

    NASA Astrophysics Data System (ADS)

    Maloof, Adam C.

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist."

  12. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Citation for Adam C. Maloof

    NASA Astrophysics Data System (ADS)

    Hoffman, Paul F.

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist."

  13. Heightened cleavage of Axl receptor tyrosine kinase by ADAM metalloproteases may contribute to disease pathogenesis in SLE.

    PubMed

    Orme, Jacob J; Du, Yong; Vanarsa, Kamala; Mayeux, Jessica; Li, Li; Mutwally, Azza; Arriens, Cristina; Min, Soyoun; Hutcheson, Jack; Davis, Laurie S; Chong, Benjamin F; Satterthwaite, Anne B; Wu, Tianfu; Mohan, Chandra

    2016-08-01

    Systemic lupus erythematosus (SLE) is characterized by antibody-mediated chronic inflammation in the kidney, lung, skin, and other organs to cause inflammation and damage. Several inflammatory pathways are dysregulated in SLE, and understanding these pathways may improve diagnosis and treatment. In one such pathway, Axl tyrosine kinase receptor responds to Gas6 ligand to block inflammation in leukocytes. A soluble form of the Axl receptor ectodomain (sAxl) is elevated in serum from patients with SLE and lupus-prone mice. We hypothesized that sAxl in SLE serum originates from the surface of leukocytes and that the loss of leukocyte Axl contributes to the disease. We determined that macrophages and B cells are a source of sAxl in SLE and in lupus-prone mice. Shedding of the Axl ectodomain from the leukocytes of lupus-prone mice is mediated by the matrix metalloproteases ADAM10 and TACE (ADAM17). Loss of Axl from lupus-prone macrophages renders them unresponsive to Gas6-induced anti-inflammatory signaling in vitro. This phenotype is rescued by combined ADAM10/TACE inhibition. Mice with Axl-deficient macrophages develop worse disease than controls when challenged with anti-glomerular basement membrane (anti-GBM) sera in an induced model of nephritis. ADAM10 and TACE also mediate human SLE PBMC Axl cleavage. Collectively, these studies indicate that increased metalloprotease-mediated cleavage of leukocyte Axl may contribute to end organ disease in lupus. They further suggest dual ADAM10/TACE inhibition as a potential therapeutic modality in SLE.

  14. Adam Smith's invisible hand is unstable: physics and dynamics reasoning applied to economic theorizing

    NASA Astrophysics Data System (ADS)

    McCauley, Joseph L.

    2002-11-01

    Neo-classical economic theory is based on the postulated, nonempiric notion of utility. Neo-classical economists assume that prices, dynamics, and market equilibria are supposed to be derived from utility. The results are supposed to represent mathematically the stabilizing action of Adam Smith's invisible hand. In deterministic excess demand dynamics, however, a utility function generally does not exist mathematically due to nonintegrability. Price as a function of demand does not exist and all equilibria are unstable. Qualitatively, and empirically, the neo-classical prediction of price as a function of demand describes neither consumer nor trader demand. We also discuss five inconsistent definitions of equilibrium used in economics and finance, only one of which is correct, and then explain the fallacy in the economists’ notion of ‘temporary price equilibria’.

  15. Enthalpies of Mixing in Sodium Silicate Glasses and Relevance to Adam-Gibbs Theory

    NASA Astrophysics Data System (ADS)

    Hovis, G.; Jarry, P.; Toplis, M.; Richet, P.

    2003-12-01

    Solution calorimetric measurements have been made in 20.1 wt % hydrofluoric acid at 50° C on binary Na2O-SiO2 glasses ranging in composition from 0 to 50 mol % Na2O. The initial calorimetric data for compositions between 20 and 50 mol % Na2O were highly variable, determined later to be due to the development of Na carbonate on the glass surfaces. However, additional measurements using minimally-ground specimens that had been remelted shortly before the calorimetric dissolutions produced highly reproducible results. After adjustment of the data for glass transition temperature (Richet et al., 1984, J. Amer. Ceram. Soc.), the results show nearly linear ("ideal") behavior of the heats of solution between 50 % Na2O and 30-35 % Na2O. However, positive enthalpies of mixing (Hex) are evident in the compositional region between 0 and 30-35 mol % Na2O, with maximum magnitudes of Hex on the order of 5 kJ/mol relative to 0 and 35 % Na2O end members. Within the framework of the Adam-Gibbs theory of structural relaxation, viscosity and heat capacity data may be combined to determine configurational entropies of silicate glasses. When applied to sodium silicate glasses (Toplis, 2001, Chemical Geology), positive entropies of mixing (Sex) are calculated for compositions between 0 and 30 mole % Na2O, a compositional region where liquid immiscibility also is known to occur (Haller et al., 1974, J. Amer. Ceram. Soc.) and where Gibbs free energies of mixing (Gex) therefore must be positive. Because positive entropies of mixing contribute negatively (-TSex) to Gex, the observed immiscibility requires positive enthalpies of mixing (Hex) in the silicic part of the compositional range. The present study confirms such positive enthalpies of mixing and supports the usefulness of Adam-Gibbs theory for the prediction of viscosity/entropy behavior of silicate glasses and liquids.

  16. Adams-Harbertson protein precipitation-based wine tannin method found invalid.

    PubMed

    Brooks, Larry; McCloskey, Leo; McKesson, Doug; Sylvan, Marshall

    2008-01-01

    The poor precision of the Adams-Harbertson wine tannin assay which was proposed for commercial winemaking, thereby creating the real possibility of quality control problems, is documented. The method is a version of the Hagerman and Butler protein precipitation-based tannin method. An extensive invalidation of the assay results with luxury wine data shows that the assay cannot distinguish bottled wine with reasonable accuracy. Five laboratories used Adams-Harbertson to assay 9 replicates each, of 3 bottled wines (n = 135) found in California supermarkets, with tannin concentrations of nominally 500 and 1000 ppm by high-performance liquid chromatography (HPLC). Reliability exceeded the +/-5% industry requirement by nominally 5 times (z-score based on 5% distribution). Coefficient of variation was +/-27%, making the standard deviation range 54% for Pinot Noir, 34% for Merlot, and 44% for Cabernet Sauvignon. Validity exceeded the 100% requirement. Intralaboratory validity recovery was 55-63%. Interwinery validity was 71-178% of the mean for Pinot Noir, 81-144% for Merlot, and 83-164% for Cabernet Sauvignon. Range as a function of the mean was 89% for Pinot Noir, 55% for Merlot, and 67% for Cabernet Sauvignon. Expect intermethod validity to be nominally 50%, i.e., percent recovery to HPLC. These statistically significant errors were predicted by the literature. First-order error is related to the tannin-protein equilibrium constant (Ka), as suggested by the original author, Hagerman, and the protein equivalence point error as suggested by Silber. This does not obviate second-order errors for tannin-protein analytical chemistry. Winemakers using the measurements risk making wines that are relatively more tannic than the measurements report. PMID:18980123

  17. [Adam hammer (1818 - 1878) - remarks on a forgotten pioneer of ether anaesthesia in obstetrics].

    PubMed

    Goerig, M; Streckfuss, W

    2004-05-01

    Adam Hammer, born in 1818, and working as a doctor for the poor since 1847 in Mannheim, was the first person in the German speaking world to use ether for pain relief during labor on February 18th 1847. He took part in the abortive April 1848 Revolution in Mannheim - a pinnacle of German liberalism and later of political radicalism, which attented to abolish the Monarchy and introduce a democratic Republic. After the revolution was put down, Hammer emigrated to the United States and settled down in St. Louis, Missouri. Remaining politically active, he joined the Republican Party, founded in 1854 and served as a military surgeon in the Union Army during the American Civil War. Even before the war, he was engaged in efforts to improve the level of medical training in America and was involved with the foundation of High Schools which offered training courses along the lines of German universities. His ideas and innovations were not introduced immediately, but had a significant impact on medical training methology later on in the US. During a visit in Europe in 1876, he was the first to diagnose a coronary thombosis as the cause of a heart attack on a live patient. The diagnosis was later confirmed by post-morten autopsy on the patient. In 1877 he returned to Germany and died one year later. The biography of Adam Hammer mirrows that of many other German-Americans whose emigration proved to be a gain for America but a loss for Germany. This story was destinated to be repeated in terrible circumstances some decades later. PMID:15156417

  18. ADAM10 controls collagen signaling and cell migration on collagen by shedding the ectodomain of discoidin domain receptor 1 (DDR1)

    PubMed Central

    Shitomi, Yasuyuki; Thøgersen, Ida B.; Ito, Noriko; Leitinger, Birgit; Enghild, Jan J.; Itoh, Yoshifumi

    2015-01-01

    Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and transmits signals from various collagens in epithelial cells. However, how DDR1–dependent signaling is regulated has not been understood. Here we report that collagen binding induces ADAM10-dependent ectodomain shedding of DDR1. DDR1 shedding is not a result of an activation of its signaling pathway, since DDR1 mutants defective in signaling were shed in an efficient manner. DDR1 and ADAM10 were found to be in a complex on the cell surface, but shedding did not occur unless collagen bound to DDR1. Using a shedding-resistant DDR1 mutant, we found that ADAM10-dependent DDR1 shedding regulates the half-life of collagen-induced phosphorylation of the receptor. Our data also revealed that ADAM10 plays an important role in regulating DDR1-mediated cell adhesion to achieve efficient cell migration on collagen matrices. PMID:25540428

  19. Inversion of Electromagnetic Data to Obtain Ice Thicknesses at Mts. Adams, Baker and Rainier, Washington

    NASA Astrophysics Data System (ADS)

    Deszcz-Pan, M.; Finn, C. A.; Anderson, E.

    2008-12-01

    Helicopter electromagnetic (HEM) data over Mt. Adams, Mt. Baker and Mt. Rainier volcanoes were originally collected to map altered zones for volcano hazards assessments but also can be used to obtain the thickness of ice by a numerical inverse process that includes magnetic susceptibility and dielectric properties of rocks in addition to the standard resistivity and thickness parameters. The multifrequency electromagnetic system used 5 coplanar (106400, 25400, 6121, 1515 and 388 Hz) and one coaxial (3315 Hz) coil. Transmitter and receiver coils in the electromagnetic sensor detected the electromagnetic response of the exposed and ice-covered ground at different frequencies to obtain information from different depths. A one- dimensional (1-D) program using analytic Jacobians was used to invert HEM data. The final three- dimensional model was stitched together from a series of 1-D inversions. Sensitivity tests of the responses to simple two-layer resistivity models representing volcano structure were calculated to guide the inverse process. The tests and practical noise levels showed that ppm response for a 10 ohm-m bottom layer, representing wet and altered rocks, below a very resistive, 1 M ohm-m layer, representing ice, is above the 40 ppm noise limit for up to depths of ~100 m. The results also showed that basement resistivities exceeding 1000 ohm-m below 30 m ice will not be well resolved. The effect of magnetic susceptibility on the measured Hz fields was evaluated for the case of a 30-m-thick top layer overlying a 1000 ohm-m bottom layer. The susceptibility of 0.025 SI strongly influences the in-phase component by lowering its value by a few ppm along the complete spectrum of frequencies. The in-phase and quadrature responses of the Hz component for varying relative dielectric permittivity were calculated for the same model and show that only the highest frequencies, above 10 kHz, are influenced by the dielectric properties of the model, and only for the case

  20. ADAM9 Expression Is Associate with Glioma Tumor Grade and Histological Type, and Acts as a Prognostic Factor in Lower-Grade Gliomas

    PubMed Central

    Fan, Xing; Wang, Yongheng; Zhang, Chuanbao; Liu, Li; Yang, Sen; Wang, Yinyan; Liu, Xing; Qian, Zenghui; Fang, Shengyu; Qiao, Hui; Jiang, Tao

    2016-01-01

    The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p < 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p < 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p < 0.001 and p < 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients. PMID:27571068

  1. EphrinB2 affects apical constriction in Xenopus embryos and is regulated by ADAM10 and flotillin-1

    NASA Astrophysics Data System (ADS)

    Ji, Yon Ju; Hwang, Yoo-Seok; Mood, Kathleen; Cho, Hee-Jun; Lee, Hyun-Shik; Winterbottom, Emily; Cousin, Hélène; Daar, Ira O.

    2014-03-01

    The Eph/ephrin signalling pathways have a critical function in cell adhesion and repulsion, and thus play key roles in various morphogenetic events during development. Here we show that a decrease in ephrinB2 protein causes neural tube closure defects during Xenopus laevis embryogenesis. Such a decrease in ephrinB2 protein levels is observed on the loss of flotillin-1 scaffold protein, a newly identified ephrinB2-binding partner. This dramatic decline in ephrinB2 protein levels on the absence of flotillin-1 expression is specific, and is partly the result of an increased susceptibility to cleavage by the metalloprotease ADAM10. These findings indicate that flotillin-1 regulates ephrinB2 protein levels through ADAM10, and is required for appropriate neural tube morphogenesis in the Xenopus embryo.

  2. An ADAM9 mutation in canine cone-rod dystrophy 3 establishes homology with human cone-rod dystrophy 9

    PubMed Central

    Goldstein, Orly; Mezey, Jason G.; Boyko, Adam R.; Gao, Chuan; Wang, Wei; Bustamante, Carlos D.; Anguish, Lynne J.; Jordan, Julie Ann; Pearce-Kelling, Susan E.; Aguirre, Gustavo D.

    2010-01-01

    Purpose To identify the causative mutation in a canine cone-rod dystrophy (crd3) that segregates as an adult onset disorder in the Glen of Imaal Terrier breed of dog. Methods Glen of Imaal Terriers were ascertained for crd3 phenotype by clinical ophthalmoscopic examination, and in selected cases by electroretinography. Blood samples from affected cases and non-affected controls were collected and used, after DNA extraction, to undertake a genome-wide association study using Affymetrix Version 2 Canine single nucleotide polymorphism chips and 250K Sty Assay protocol. Positional candidate gene analysis was undertaken for genes identified within the peak-association signal region. Retinal morphology of selected crd3-affected dogs was evaluated by light and electron microscopy. Results A peak association signal exceeding genome-wide significance was identified on canine chromosome 16. Evaluation of genes in this region suggested A Disintegrin And Metalloprotease domain, family member 9 (ADAM9), identified concurrently elsewhere as the cause of human cone-rod dystrophy 9 (CORD9), as a strong positional candidate for canine crd3. Sequence analysis identified a large genomic deletion (over 20 kb) that removed exons 15 and 16 from the ADAM9 transcript, introduced a premature stop, and would remove critical domains from the encoded protein. Light and electron microscopy established that, as in ADAM9 knockout mice, the primary lesion in crd3 appears to be a failure of the apical microvilli of the retinal pigment epithelium to appropriately invest photoreceptor outer segments. By electroretinography, retinal function appears normal in very young crd3-affected dogs, but by 15 months of age, cone dysfunction is present. Subsequently, both rod and cone function degenerate. Conclusions Identification of this ADAM9 deletion in crd3-affected dogs establishes this canine disease as orthologous to CORD9 in humans, and offers opportunities for further characterization of the disease

  3. A disintegrin and metalloprotease 33 (ADAM33) gene polymorphisms and the risk of asthma: a meta-analysis.

    PubMed

    Liang, Siqiao; Wei, Xuan; Gong, Chen; Wei, Jinmei; Chen, Zhangrong; Deng, Jingmin

    2013-05-01

    Polymorphisms in the ADAM33 gene have been associated with asthma, but the data are controversial. Therefore, we reviewed the related studies and quantitatively summarized the associations between ADAM33 polymorphisms and asthma risk using meta-analysis. A dominant model (AA+Aa vs. aa), recessive model (AA vs. Aa+aa), additive model (AA vs. aa) and allelic model (A vs. a) were used to estimate the association between ADAM33 polymorphism and asthma risk. A total of 29 case-control studies referring to 14 SNPs were identified: rs2280091(T1), rs2787094(V4), rs528557(S2), rs2280090(T2), rs511898(F+1), rs44707(ST+4), rs3918396(S1), rs543749(V-1), rs574174(ST+7), rs597980(ST+5), rs2853209(S+1), rs2280089(T+1), rs612709(Q-1), and rs3746631(V5). The results indicated that S1, V-1, V5, S+1, S2, ST+4, ST+7, ST+5, and Q-1 were not associated with asthma. Significant associations were found with the T1, V4, F+1 and T+1 polymorphisms in the overall population. In the subgroup analysis by ethnicity, a positive result was only found for the T1, V4, F+1 and T2 polymorphisms in Asia but not in Europe or Latin America. This meta-analysis provides evidence that the T1, V4, F+1, T2, and T+1 polymorphisms in the ADAM33 gene are risk factors for asthma, especially in the Asian population. PMID:23380143

  4. Detrital zircon geochronology of the Adams Argillite and Nation River Formation, east-central Alaska, U.S.A

    USGS Publications Warehouse

    Gehrels, G.E.; Johnsson, M.J.; Howell, D.G.

    1999-01-01

    The Cambrian Adams Argillite and the Devonian Nation River Formation are two sandstone-bearing units within a remarkably complete Paleozoic stratigraphic section in east-central Alaska. These strata, now foreshortened and fault-bounded, were originally contiguous with miogeoclinal strata to the east that formed as a passive-margin sequence along the northwestern margin of the North American continent. Seventy-five detrital zircon grains from the Adams Argillite and the Nation River Formation were analyzed in an effort to provide constraints on the original sources of the grains, and to generate a detrital zircon reference for miogeoclinal strata in the northern Cordillera. Thirty-five single zircon grains from a quartzite in the Adams Argillite yield dominant age clusters of 1047-1094 (n = 6), 1801-1868 (n = 10), and 2564-2687 (n = 5) Ma. Forty zircons extracted from a sandstone in the Nation River Formation yield clusters primarily of 424-434 (n = 6), 1815-1838 (n = 6), 1874-1921 (n = 7), and 2653-2771 (n = 4) Ma. The Early Proterozoic and Archean grains in both units probably originated in basement rocks in a broad region of the Canadian Shield. In contrast, the original igneous sources for mid-Protcrozoic grains in the Adams Argillite and ??? 430 Ma grains in the Nation River Formation are more difficult to identify. Possible original sources for the mid-Proterozoic grains include: (1) the Grenville Province of eastern Laurentia, (2) the Pearya terrane along the Arctic margin, and (3) mid-Proterozoic igneous rocks that may have been widespread along or outboard of the Cordilleran margin. The ??? 430 Ma grains may have originated in: (1) arc-type sources along the Cordilleran margin, (2) the Caledonian orogen, or (3) a landmass, such as Pearya, Siberia, or crustal fragments now in northern Asia, that resided outboard of the Innuitian orogen during mid-Paleozoic time. Copyright ?? 1999, SEPM (Society for Sedimentary Geology).

  5. Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell–derived ADAM9

    PubMed Central

    Mammadova-Bach, Elmina; Zigrino, Paola; Brucker, Camille; Bourdon, Catherine; Freund, Monique; Abrams, Scott I.; Orend, Gertaud; Gachet, Christian

    2016-01-01

    Metastatic dissemination of cancer cells, which accounts for 90% of cancer mortality, is the ultimate hallmark of malignancy. Growing evidence suggests that blood platelets have a predominant role in tumor metastasis; however, the molecular mechanisms involved remain elusive. Here, we demonstrate that genetic deficiency of integrin α6β1 on platelets markedly decreases experimental and spontaneous lung metastasis. In vitro and in vivo assays reveal that human and mouse platelet α6β1 supports platelet adhesion to various types of cancer cells. Using a knockdown approach, we identified ADAM9 as the major counter receptor of α6β1 on both human and mouse tumor cells. Static and flow-based adhesion assays of platelets binding to DC-9, a recombinant protein covering the disintegrin-cysteine domain of ADAM9, demonstrated that this receptor directly binds to platelet α6β1. In vivo studies showed that the interplay between platelet α6β1 and tumor cell–expressed ADAM9 promotes efficient lung metastasis. The integrin α6β1–dependent platelet-tumor cell interaction induces platelet activation and favors the extravasation process of tumor cells. Finally, we demonstrate that a pharmacological approach targeting α6β1 efficiently impairs tumor metastasis through a platelet-dependent mechanism. Our study reveals a mechanism by which platelets promote tumor metastasis and suggests that integrin α6β1 represents a promising target for antimetastatic therapies. PMID:27699237

  6. Mid-trimester maternal ADAM12 levels differ according to fetal gender in pregnancies complicated by preeclampsia.

    PubMed

    Myers, Jenny E; Thomas, Grégoire; Tuytten, Robin; Van Herrewege, Yven; Djiokep, Raoul O; Roberts, Claire T; Kenny, Louise C; Simpson, Nigel A B; North, Robyn A; Baker, Philip N

    2015-02-01

    An overrepresentation of adverse pregnancy outcomes has been observed in pregnancies associated with a male fetus. We investigated the association between fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy Endpoints (SCOPE) study (preeclampsia n = 150; no preeclampsia n = 450). In contrast to placental growth factor, soluble endoglin, and insulin-like growth factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20 weeks were dependent on fetal gender in pregnancies complicated by preeclampsia, for male (n = 73) fetuses the multiples of the median (MoM; interquartile range [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n = 75) MoM was 1.1 (1.0-1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for pregnancies associated with a male fetus (area under receiver-operator curve [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus (AUC 0.62 [0.55-0.70]); P = .03. The data presented here fit a contemporary hypothesis that there is a difference between the genders in response to an adverse maternal environment and suggest that an alteration in ADAM12 may reflect an altered placental response in pregnancies subsequently complicated by preeclampsia. PMID:24899472

  7. Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell–derived ADAM9

    PubMed Central

    Mammadova-Bach, Elmina; Zigrino, Paola; Brucker, Camille; Bourdon, Catherine; Freund, Monique; Abrams, Scott I.; Orend, Gertaud; Gachet, Christian

    2016-01-01

    Metastatic dissemination of cancer cells, which accounts for 90% of cancer mortality, is the ultimate hallmark of malignancy. Growing evidence suggests that blood platelets have a predominant role in tumor metastasis; however, the molecular mechanisms involved remain elusive. Here, we demonstrate that genetic deficiency of integrin α6β1 on platelets markedly decreases experimental and spontaneous lung metastasis. In vitro and in vivo assays reveal that human and mouse platelet α6β1 supports platelet adhesion to various types of cancer cells. Using a knockdown approach, we identified ADAM9 as the major counter receptor of α6β1 on both human and mouse tumor cells. Static and flow-based adhesion assays of platelets binding to DC-9, a recombinant protein covering the disintegrin-cysteine domain of ADAM9, demonstrated that this receptor directly binds to platelet α6β1. In vivo studies showed that the interplay between platelet α6β1 and tumor cell–expressed ADAM9 promotes efficient lung metastasis. The integrin α6β1–dependent platelet-tumor cell interaction induces platelet activation and favors the extravasation process of tumor cells. Finally, we demonstrate that a pharmacological approach targeting α6β1 efficiently impairs tumor metastasis through a platelet-dependent mechanism. Our study reveals a mechanism by which platelets promote tumor metastasis and suggests that integrin α6β1 represents a promising target for antimetastatic therapies.

  8. Mid-trimester maternal ADAM12 levels differ according to fetal gender in pregnancies complicated by preeclampsia.

    PubMed

    Myers, Jenny E; Thomas, Grégoire; Tuytten, Robin; Van Herrewege, Yven; Djiokep, Raoul O; Roberts, Claire T; Kenny, Louise C; Simpson, Nigel A B; North, Robyn A; Baker, Philip N

    2015-02-01

    An overrepresentation of adverse pregnancy outcomes has been observed in pregnancies associated with a male fetus. We investigated the association between fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy Endpoints (SCOPE) study (preeclampsia n = 150; no preeclampsia n = 450). In contrast to placental growth factor, soluble endoglin, and insulin-like growth factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20 weeks were dependent on fetal gender in pregnancies complicated by preeclampsia, for male (n = 73) fetuses the multiples of the median (MoM; interquartile range [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n = 75) MoM was 1.1 (1.0-1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for pregnancies associated with a male fetus (area under receiver-operator curve [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus (AUC 0.62 [0.55-0.70]); P = .03. The data presented here fit a contemporary hypothesis that there is a difference between the genders in response to an adverse maternal environment and suggest that an alteration in ADAM12 may reflect an altered placental response in pregnancies subsequently complicated by preeclampsia.

  9. Fisetin suppresses ADAM9 expression and inhibits invasion of glioma cancer cells through increased phosphorylation of ERK1/2.

    PubMed

    Chen, Chien-Min; Hsieh, Yi-Hsien; Hwang, Jin-Ming; Jan, Hsun-Jin; Hsieh, Shu-Ching; Lin, Shin-Huey; Lai, Chung-Yu

    2015-05-01

    Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid which is widely distributed in plants. It has been reported to possess some anticancer and anti-invasive capabilities. We set out to explore the effects of fisetin on antimetastatic and its mechanism of action in GBM8401 cells. The results indicated that fisetin exhibited effective inhibition of cell migration and inhibited the invasion of GBM8401 cells under non-cytotoxic concentrations. To identify the potential targets of fisetin, human proteinase antibody array analysis was performed, and the results indicated that the fisetin treatment inhibited the expression of ADAM9 protein and mRNA, which are known to contribute to the progression of glioma cancer. Our results showed that fisetin phosphorylated ERK1/2 in a sustained way that contributed to the inhibited ADAM9 protein and mRNA expression determined by Western blot and RT-PCR. Moreover, inhibition of ERK1/2 by U0126 or transfection with the siERK plasmid significantly abolished the fisetin-inhibited migration and invasion through activation of the ERK1/2 pathway. In summary, our results suggest that fisetin might be a potential therapeutic agent against human glioma cells based on its capacity to activate ERK1/2 and to inhibit ADAM9 expression.

  10. The Ansel Adams zone system: HDR capture and range compression by chemical processing

    NASA Astrophysics Data System (ADS)

    McCann, John J.

    2010-02-01

    We tend to think of digital imaging and the tools of PhotoshopTM as a new phenomenon in imaging. We are also familiar with multiple-exposure HDR techniques intended to capture a wider range of scene information, than conventional film photography. We know about tone-scale adjustments to make better pictures. We tend to think of everyday, consumer, silver-halide photography as a fixed window of scene capture with a limited, standard range of response. This description of photography is certainly true, between 1950 and 2000, for instant films and negatives processed at the drugstore. These systems had fixed dynamic range and fixed tone-scale response to light. All pixels in the film have the same response to light, so the same light exposure from different pixels was rendered as the same film density. Ansel Adams, along with Fred Archer, formulated the Zone System, staring in 1940. It was earlier than the trillions of consumer photos in the second half of the 20th century, yet it was much more sophisticated than today's digital techniques. This talk will describe the chemical mechanisms of the zone system in the parlance of digital image processing. It will describe the Zone System's chemical techniques for image synthesis. It also discusses dodging and burning techniques to fit the HDR scene into the LDR print. Although current HDR imaging shares some of the Zone System's achievements, it usually does not achieve all of them.

  11. Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17

    PubMed Central

    Guinea-Viniegra, Juan; Zenz, Rainer; Scheuch, Harald; Jiménez, María; Bakiri, Latifa; Petzelbauer, Peter; Wagner, Erwin F.

    2012-01-01

    Squamous cell carcinomas (SCCs) are heterogeneous and aggressive skin tumors for which innovative, targeted therapies are needed. Here, we identify a p53/TACE pathway that is negatively regulated by FOS and show that the FOS/p53/TACE axis suppresses SCC by inducing differentiation. We found that epidermal Fos deletion in mouse tumor models or pharmacological FOS/AP-1 inhibition in human SCC cell lines induced p53 expression. Epidermal cell differentiation and skin tumor suppression were caused by a p53-dependent transcriptional activation of the metalloprotease TACE/ADAM17 (TNF-α–converting enzyme), a previously unknown p53 target gene that was required for NOTCH1 activation. Although half of cutaneous human SCCs display p53-inactivating mutations, restoring p53/TACE activity in mouse and human skin SCCs induced tumor cell differentiation independently of the p53 status. We propose FOS/AP-1 inhibition or p53/TACE reactivating strategies as differentiation-inducing therapies for SCCs. PMID:22772468

  12. Angular Distribution of Charged Particles in the Atmosphere- Results of the ADAM Experiment on BEXUS 19

    NASA Astrophysics Data System (ADS)

    Martensen, S.; Brudern, M.; Christiansen, F.; Koberle, M.; Trautwein, D.; Wraase, S.; Bottcher, S.; Burmeister, S.; Heber, B.; Wimmer-Schweingruber, R.

    2015-09-01

    Particle showers, which produce a large number of secondary particles, are generated by the interaction of high-energy cosmic ray particles with the Earth's atmosphere. The Team ADAM (Angular Distribution of charged partides - Atmosphere Measurement) has flown an experiment to measure the altitude- dependent angular distribution of secondary charged particles on a stratospheric balloon within the REXUS/BEXUS programme in October 2014. We designed a sensor head consisting of 16 planar silicon semi-conductor detectors (SSDs), which allowed us to determine the zenith-angle of individual particles by coincidence measurements. After a year of development and testing, on October 9th the instrument performed measurements for 4 hours in an altitude of 27 km in northern Sweden. In this contribution measurements performed during the flight in comparison to ones obtained on ground will be presented. On the one hand we focus on the count and dose rate profiles as functions of residual pressure, on the other hand we discuss the angular distribution below and above the PFOTZERMaximum.

  13. Number of discernible colors for color-deficient observers estimated from the MacAdam limits.

    PubMed

    Perales, Esther; Martínez-Verdú, Francisco Miguel; Linhares, João Manuel Maciel; Nascimento, Sérgio Miguel Cardoso

    2010-10-01

    We estimated the number of colors perceived by color normal and color-deficient observers when looking at the theoretic limits of object-color stimuli. These limits, the optimal color stimuli, were computed for a color normal observer and CIE standard illuminant D65, and the resultant colors were expressed in the CIELAB and DIN99d color spaces. The corresponding color volumes for abnormal color vision were computed using models simulating for normal trichromatic observers the appearance for dichromats and anomalous trichomats. The number of colors perceived in each case was then computed from the color volumes enclosed by the optimal colors also known as MacAdam limits. It was estimated that dichromats perceive less than 1% of the colors perceived by normal trichromats and that anomalous trichromats perceive 50%-60% for anomalies in the medium-wavelength-sensitive and 60%-70% for anomalies in the long-wavelength-sensitive cones. Complementary estimates obtained similarly for the spectral locus of monochromatic stimuli suggest less impairment for color-deficient observers, a fact that is explained by the two-dimensional nature of the locus. PMID:20922000

  14. Desperately seeking social approval: Adam Smith, Thorstein Veblen and the moral limits of capitalist culture.

    PubMed

    Watson, Matthew

    2012-09-01

    Adam Smith and Thorstein Veblen shared much in matters of economic ontology. Both dismissed the very notion of an autonomous economic self and instead investigated the processes through which self and other are mutually constituted under changing cultural traditions of individual aspiration. Their strikingly similar critiques of status-oriented consumption and concern for the moral basis of the market economy are established in this manner. However, the political implications of their analyses point in different directions, with Veblen being the more radical. The Smithian individual can always use spectatorial insights to assert through genuinely praiseworthy behaviour personal moral distance from social norms of status-oriented consumption. The Veblenian individual, by contrast, has no such capacity for elevating abstract moral principles above socially-situated conduct, as mind and environment co-evolve in line with changing material circumstances of life. For Veblen, the rise of status-oriented consumption itself acted as a form of moral self-education that more deeply entrenched the social norms of ownership out of which it arose, thus the impossibility of an autonomous economic self was matched by the impossibility of an autonomous moral self. To his way of thinking, moral degradation in conspicuous consumption was irredeemably inscribed into the whole cultural structure of capitalism. PMID:22950465

  15. Desperately seeking social approval: Adam Smith, Thorstein Veblen and the moral limits of capitalist culture.

    PubMed

    Watson, Matthew

    2012-09-01

    Adam Smith and Thorstein Veblen shared much in matters of economic ontology. Both dismissed the very notion of an autonomous economic self and instead investigated the processes through which self and other are mutually constituted under changing cultural traditions of individual aspiration. Their strikingly similar critiques of status-oriented consumption and concern for the moral basis of the market economy are established in this manner. However, the political implications of their analyses point in different directions, with Veblen being the more radical. The Smithian individual can always use spectatorial insights to assert through genuinely praiseworthy behaviour personal moral distance from social norms of status-oriented consumption. The Veblenian individual, by contrast, has no such capacity for elevating abstract moral principles above socially-situated conduct, as mind and environment co-evolve in line with changing material circumstances of life. For Veblen, the rise of status-oriented consumption itself acted as a form of moral self-education that more deeply entrenched the social norms of ownership out of which it arose, thus the impossibility of an autonomous economic self was matched by the impossibility of an autonomous moral self. To his way of thinking, moral degradation in conspicuous consumption was irredeemably inscribed into the whole cultural structure of capitalism.

  16. SIVA/DIVA- INITIAL VALUE ORDINARY DIFFERENTIAL EQUATION SOLUTION VIA A VARIABLE ORDER ADAMS METHOD

    NASA Technical Reports Server (NTRS)

    Krogh, F. T.

    1994-01-01

    The SIVA/DIVA package is a collection of subroutines for the solution of ordinary differential equations. There are versions for single precision and double precision arithmetic. These solutions are applicable to stiff or nonstiff differential equations of first or second order. SIVA/DIVA requires fewer evaluations of derivatives than other variable order Adams predictor-corrector methods. There is an option for the direct integration of second order equations which can make integration of trajectory problems significantly more efficient. Other capabilities of SIVA/DIVA include: monitoring a user supplied function which can be separate from the derivative; dynamically controlling the step size; displaying or not displaying output at initial, final, and step size change points; saving the estimated local error; and reverse communication where subroutines return to the user for output or computation of derivatives instead of automatically performing calculations. The user must supply SIVA/DIVA with: 1) the number of equations; 2) initial values for the dependent and independent variables, integration stepsize, error tolerance, etc.; and 3) the driver program and operational parameters necessary for subroutine execution. SIVA/DIVA contains an extensive diagnostic message library should errors occur during execution. SIVA/DIVA is written in FORTRAN 77 for batch execution and is machine independent. It has a central memory requirement of approximately 120K of 8 bit bytes. This program was developed in 1983 and last updated in 1987.

  17. Distribution of melt beneath Mount St Helens and Mount Adams inferred from magnetotelluric data

    USGS Publications Warehouse

    Hill, G.J.; Caldwell, T.G.; Heise, W.; Chertkoff, D.G.; Bibby, H.M.; Burgess, M.K.; Cull, J.P.; Cas, Ray A.F.

    2009-01-01

    Three prominent volcanoes that form part of the Cascade mountain range in Washington State (USA)Mounts StHelens, Adams and Rainierare located on the margins of a mid-crustal zone of high electrical conductivity1,5. Interconnected melt can increase the bulk conductivity of the region containing the melt6,7, which leads us to propose that the anomalous conductivity in this region is due to partial melt associated with the volcanism. Here we test this hypothesis by using magnetotelluric data recorded at a network of 85 locations in the area of the high-conductivity anomaly. Our data reveal that a localized zone of high conductivity beneath thisvolcano extends downwards to join the mid-crustal conductor. As our measurements were made during the recent period of lava extrusion at Mount St Helens, we infer that the conductivity anomaly associated with the localized zone, and by extension with the mid-crustal conductor, is caused by the presence of partial melt. Our interpretation is consistent with the crustal origin of silicic magmas erupting from Mount St Helens8, and explains the distribution of seismicity observed at the time of the catastrophic eruption in 1980 (refs9, 10). ?? 2009 Macmillan Publishers Limited. All rights reserved.

  18. Number of discernible colors for color-deficient observers estimated from the MacAdam limits.

    PubMed

    Perales, Esther; Martínez-Verdú, Francisco Miguel; Linhares, João Manuel Maciel; Nascimento, Sérgio Miguel Cardoso

    2010-10-01

    We estimated the number of colors perceived by color normal and color-deficient observers when looking at the theoretic limits of object-color stimuli. These limits, the optimal color stimuli, were computed for a color normal observer and CIE standard illuminant D65, and the resultant colors were expressed in the CIELAB and DIN99d color spaces. The corresponding color volumes for abnormal color vision were computed using models simulating for normal trichromatic observers the appearance for dichromats and anomalous trichomats. The number of colors perceived in each case was then computed from the color volumes enclosed by the optimal colors also known as MacAdam limits. It was estimated that dichromats perceive less than 1% of the colors perceived by normal trichromats and that anomalous trichromats perceive 50%-60% for anomalies in the medium-wavelength-sensitive and 60%-70% for anomalies in the long-wavelength-sensitive cones. Complementary estimates obtained similarly for the spectral locus of monochromatic stimuli suggest less impairment for color-deficient observers, a fact that is explained by the two-dimensional nature of the locus.

  19. Evaluation of ADAM/1 model for advanced coal-extraction concepts

    SciTech Connect

    Deshpande, G. K.; Gangal, M. D.

    1982-01-15

    The Advanced Coal Extraction Project is sponsored by the Department of Energy at the Jet Propulsion Laboratory to define and develop advanced underground coal extraction systems which: (1) are suitable for significant remaining resources after the year 2000, and (2) promise a significant improvement in production cost and miner safety, with no degradation in miner health, environmental quality and resource recovery. System requirements in the five performance areas have been defined by Goldsmith and Lavin (1980). Several existing computer programs for estimating life-cycle cost of mining systems have been evaluated. A commercially available program ADAM/1 was found to be satisfactory in relation to the needs of the Advanced Coal Extraction Project. Two test cases were run to confirm the ability of the program to handle non-conventional mining equipment and procedures. The results were satisfactory. The model, therefore, is recommended to the project team for evaluation of their conceptual designs. Since the model is commercially available, data preparation instructions are not reproduced in this document; instead the reader is referred to the original documents for this information.

  20. EphrinA/EphA-induced ectodomain shedding of neural cell adhesion molecule regulates growth cone repulsion through ADAM10 metalloprotease.

    PubMed

    Brennaman, Leann H; Moss, Marcia L; Maness, Patricia F

    2014-01-01

    EphrinA/EphA-dependent axon repulsion is crucial for synaptic targeting in developing neurons but downstream molecular mechanisms remain obscure. Here, it is shown that ephrinA5/EphA3 triggers proteolysis of the neural cell adhesion molecule (NCAM) by the metalloprotease a disintegrin and metalloprotease (ADAM)10 to promote growth cone collapse in neurons from mouse neocortex. EphrinA5 induced ADAM10 activity to promote ectodomain shedding of polysialic acid-NCAM in cortical neuron cultures, releasing a ~ 250 kDa soluble fragment consisting of most of its extracellular region. NCAM shedding was dependent on ADAM10 and EphA3 kinase activity as shown in HEK293T cells transfected with dominant negative ADAM10 and kinase-inactive EphA3 (K653R) mutants. Purified ADAM10 cleaved NCAM at a sequence within the E-F loop of the second fibronectin type III domain (Leu(671) -Lys(672) /Ser(673) -Leu(674) ) identified by mass spectrometry. Mutations of NCAM within the ADAM10 cleavage sequence prevented EphA3-induced shedding of NCAM in HEK293T cells. EphrinA5-induced growth cone collapse was dependent on ADAM10 activity, was inhibited in cortical cultures from NCAM null mice, and was rescued by WT but not ADAM10 cleavage site mutants of NCAM. Regulated proteolysis of NCAM through the ephrin5/EphA3/ADAM10 mechanism likely impacts synapse development, and may lead to excess NCAM shedding when disrupted, as implicated in neurodevelopmental disorders such as schizophrenia. PSA-NCAM and ephrinA/EphA3 coordinately regulate inhibitory synapse development. Here, we have found that ephrinA5 stimulates EphA3 kinase and ADAM10 activity to promote PSA-NCAM cleavage at a site in its second FNIII repeat, which regulates ephrinA5-induced growth cone collapse in GABAergic and non-GABAergic neurons. These findings identify a new regulatory mechanism which may contribute to inhibitory connectivity.

  1. Estimates of Asian dust deposition over the Asian region by using ADAM2 in 2007.

    PubMed

    Park, Soon-Ung; Choe, Anna; Park, Moon-Soo

    2010-05-01

    The Asian Dust Aerosol Model 2 (ADAM2) with the MM5 meteorological model has been employed to estimate the dust concentration, and wet and dry depositions of dust in the Asian region for the year of 2007. It is found that the model simulates quite reasonably the dust (PM(10)) concentrations both in the dust source region (100-110 degrees E and 37-43 degrees N) and the downstream region of Korea. The starting and ending times of most of dust events and their peak concentration occurring times are well simulated. The annual average dust (PM(10)) concentration near the surface is found to be 171microgm(-3) over the dust source area, 39microgm(-3) over the Yellow Sea, 25microgm(-3) over the Korean peninsula and 17microgm(-3) over the East Sea. It is also found that the annual total deposition of dust is about 118.1tkm(-2) (dry deposition, 101.4tkm(-2); wet deposition, 16.7tkm(-2)) in the dust source region, 19.0tkm(-2) (dry deposition, 7.8tkm(-2); wet deposition, 11.2tkm(-2)) in the Yellow Sea, 12.6tkm(-2) (dry deposition, 6.5tkm(-2); wet deposition, 6.1tkm(-2)) in the Korean peninsula and 10.7tkm(-2) (dry deposition, 2.1tkm(-2); wet deposition, 8.6tkm(-2)) in the East Sea. Their ratios of wet deposition to total deposition of dust in the respective regions are 14%, 59%, 48% and 80%. This clearly indicates that the main dust removal mechanism from the atmosphere is dry deposition over the source region whereas wet deposition predominates in the downstream region of the sea. The estimated dust deposition could adversely impact the eco-environmental system in the downstream regions of the dust source region significantly.

  2. A Computational Model of the LGI1 Protein Suggests a Common Binding Site for ADAM Proteins

    PubMed Central

    Leonardi, Emanuela; Andreazza, Simonetta; Vanin, Stefano; Busolin, Giorgia; Nobile, Carlo; Tosatto, Silvio C. E.

    2011-01-01

    Mutations of human leucine-rich glioma inactivated (LGI1) gene encoding the epitempin protein cause autosomal dominant temporal lateral epilepsy (ADTLE), a rare familial partial epileptic syndrome. The LGI1 gene seems to have a role on the transmission of neuronal messages but the exact molecular mechanism remains unclear. In contrast to other genes involved in epileptic disorders, epitempin shows no homology with known ion channel genes but contains two domains, composed of repeated structural units, known to mediate protein-protein interactions. A three dimensional in silico model of the two epitempin domains was built to predict the structure-function relationship and propose a functional model integrating previous experimental findings. Conserved and electrostatic charged regions of the model surface suggest a possible arrangement between the two domains and identifies a possible ADAM protein binding site in the β-propeller domain and another protein binding site in the leucine-rich repeat domain. The functional model indicates that epitempin could mediate the interaction between proteins localized to different synaptic sides in a static way, by forming a dimer, or in a dynamic way, by binding proteins at different times. The model was also used to predict effects of known disease-causing missense mutations. Most of the variants are predicted to alter protein folding while several other map to functional surface regions. In agreement with experimental evidence, this suggests that non-secreted LGI1 mutants could be retained within the cell by quality control mechanisms or by altering interactions required for the secretion process. PMID:21479274

  3. Atmospheric Deposition And MediterraneAN sea water productiviTy (Thales - ADAMANT) An overview

    NASA Astrophysics Data System (ADS)

    Christodoulaki, Sylvia; Petihakis, George; Triantafyllou, George; Pitta, Paraskevi; Papadimitriou, Vassileios; Tsiaras, Konstantinos; Mihalopoulos, Nikolaos; Kanakidou, Maria

    2015-04-01

    In the marine environment the salinity and biological pumps sequester atmospheric carbon dioxide. The biological pump is directly related to marine primary production which is controlled by nutrient availability mainly of iron, nitrogen and phosphorus. The Mediterranean Sea, especially the eastern basin is one of the most oligotrophic seas. The nitrogen (N) to phosphorus (P) ratio is unusually high, especially in the eastern basin (28:1) and primary production is limited by phosphorus availability. ADAMANT project contributes to new knowledge into how nutrients enter the marine environment through atmospheric deposition, how they are assimilated by organisms and how this influences carbon and nutrient fluxes. Experimental work has been combined with atmospheric and marine models. Important knowledge is obtained on nutrients deposition through mesocosm experiments on their uptake by the marine systems and their effects on the marine carbon cycle and food chain. Kinetic parameters of adsorption of acidic and organic volatile compounds in atmospheric samples of dust and marine salts are estimated in conjunction with solubility of N and P in mixtures contained in dust. Atmospheric and oceanographic models are coupled to create a system that is able to holistically simulate the effects of atmospheric deposition on the marine environment over time, beginning from the pre-industrial era until the future years (hind cast, present and forecast simulations). This research has been co-financed by the European Union (European Social Fund) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework - Research Funding Program: THALES, Investing in knowledge society through European Social Fund.

  4. Plasma Ang2 and ADAM17 levels are elevated during clinical malaria; Ang2 level correlates with severity and expression of EPCR-binding PfEMP1

    PubMed Central

    Petersen, Jens E. V.; Mkumbaye, Sixbert I.; Vaaben, Anna V.; Manjurano, Alphaxard; Lyimo, Eric; Kavishe, Reginald A.; Mwakalinga, Steven B.; Mosha, Jacklin; Minja, Daniel T. R.; Lusingu, John P. A.; Theander, Thor G.; Lavstsen, Thomas; Wang, Christian W.

    2016-01-01

    The pathogenesis of Plasmodium falciparum malaria involves a complex interplay between parasite adhesion and inflammatory response that includes release of cytokines and activation of the endothelium with accompanying release of Angiopoitin 2 (Ang2) to the plasma. A-disintegrin and metalloproteinase 17 (ADAM17) is a protein responsible for releasing cytokines, including Tumor Necrosis Factor α (TNFα), and shedding of adhesion proteins. In this study, we show that plasma levels of ADAM17 are increased in Tanzanian children hospitalized with a malaria infection compared with asymptomatic children but similar to children hospitalized with other infectious diseases. The plasma levels of ADAM17 decreased during recovery after an acute malaria episode. Plasma levels of Ang2 were associated with markers of malaria severity and levels of var transcripts encoding P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) containing Cysteine Rich Inter Domain Region α1 (CIDRα1) domains predicted to bind Endothelial Protein C receptor (EPCR). ADAM17 levels were not associated with expression of var genes encoding different PfEMP1 types when controlling for age. These data are the first to report ADAM17 plasma levels in malaria-exposed individuals, and support the notion that parasite sequestration mediated by EPCR-binding PfEMP1 is associated with endothelial activation and pathology in severe paediatric malaria. PMID:27784899

  5. The interleukin-6 receptor Asp358Ala single nucleotide polymorphism rs2228145 confers increased proteolytic conversion rates by ADAM proteases.

    PubMed

    Garbers, Christoph; Monhasery, Niloufar; Aparicio-Siegmund, Samadhi; Lokau, Juliane; Baran, Paul; Nowell, Mari A; Jones, Simon A; Rose-John, Stefan; Scheller, Jürgen

    2014-09-01

    The pleiotropic activities of Interleukin (IL-)6 are controlled by membrane-bound and soluble forms of the IL-6 receptor (IL-6R) in processes called classic and trans-signaling, respectively. The coding single nucleotide polymorphism (SNP) rs2228145 of the Interleukin 6 receptor (IL-6R Asp358Ala variant) is associated with a 2-fold increase in soluble IL-6R (sIL-6R) serum levels resulting in reduced IL-6-induced C-reactive protein (CRP) production and a reduced risk for coronary heart disease. It was suggested that the increased sIL-6R level leads to decreased IL-6 classic or increased IL-6 trans-signaling. Irrespective of the functional outcome of increased sIL-6R serum level, it is still under debate, whether the increased sIL-6R serum levels emerged from differential splicing or ectodomain shedding. Here we show that increased proteolytic ectodomain shedding mediated by the A Disintegrin and metalloproteinase domain (ADAM) proteases ADAM10 and ADAM17 caused increased sIL-6R serum level in vitro as well as in healthy volunteers homozygous for the IL-6R Asp358Ala allele. Differential splicing of the IL-6R appears to have only a minor effect on sIL-6R level. Increased ectodomain shedding resulted in reduced cell-surface expression of the IL-6R Asp358Ala variant compared to the common IL-6R variant. In conclusion, increased IL-6R ectodomain shedding is a mechanistic explanation for the increased serum IL-6R levels found in persons homozygous for the rs2228145 IL-6R Asp358Ala variant.

  6. Octyl Gallate Markedly Promotes Anti-Amyloidogenic Processing of APP through Estrogen Receptor-Mediated ADAM10 Activation

    PubMed Central

    Zhang, She-Qing; Sawmiller, Darrell; Li, Song; Rezai-Zadeh, Kavon; Hou, Huayan; Zhou, Shufeng; Shytle, Douglas; Giunta, Brian; Fernandez, Frank; Mori, Takashi; Tan, Jun

    2013-01-01

    Our previous studies showed that the green tea-derived polyphenolic compound (−)-epigallocatechin-3 gallate (EGCG) reduces amyloid-β (Aβ) production in both neuronal and mouse Alzheimer’s disease (AD) models in concert with activation of estrogen receptor-α/phosphatidylinositide 3-kinase/protein kinase B (ERα/PI3K/Akt) signaling and anti-amyloidogenic amyloid precursor protein (APP) α-secretase (a disintegrin and metallopeptidase domain-10, ADAM10) processing. Since the gallate moiety in EGCG may correspond to the 7α position of estrogen, thereby facilitating ER binding, we extensively screened the effect of other gallate containing phenolic compounds on APP anti-amyloidogenic processing. Octyl gallate (OG; 10 µM), drastically decreased Aβ generation, in concert with increased APP α-proteolysis, in murine neuron-like cells transfected with human wild-type APP or “Swedish” mutant APP. OG markedly increased production of the neuroprotective amino-terminal APP cleavage product, soluble APP-α (sAPPα). In accord with our previous study, these cleavage events were associated with increased ADAM10 maturation and reduced by blockade of ERα/PI3k/Akt signaling. To validate these findings in vivo, we treated Aβ-overproducing Tg2576 mice with OG daily for one week by intracerebroventricular injection and found decreased Aβ levels associated with increased sAPPα. These data indicate that OG increases anti-amyloidogenic APP α-secretase processing by activation of ERα/PI3k/Akt signaling and ADAM10, suggesting that this compound may be an effective treatment for AD. PMID:23977176

  7. The Development of Airborne Data for Assessing Models (ADAM) - A central repository of airborne field campaign data archives

    NASA Astrophysics Data System (ADS)

    Chen, G.; Kleb, M. M.; Aknan, A. A.; Brown, C. C.; Mangosing, D. C.; Thornhill, A.; Rinsland, P. L.

    2010-12-01

    NASA, NOAA, and NSF have conducted over 30 airborne campaigns during the past three decades aimed at gaining an understanding of the tropospheric chemical and physical processes related to climate change and air-quality issues. In recent years, the scientific value of this accumulated airborne data has been increasingly recognized for use in satellite validation and model assessment and evaluation activities. In addition to the high spatial-temporal resolutions, the airborne data, especially from the more recent studies, offers a comprehensive view of the atmosphere through a large suite of the simultaneously observed atmospheric species/parameters, ranging from photochemical precursors to products as well as particle chemical, microphysical, and optical properties. To better facilitate the model assessment and evaluation activities, we are actively engaged in the development of a web-based central airborne data archive: ADAM (Airborne Data for Assessing Models). This effort is sponsored by the NASA MEaSUREs program and is intended to archive data from tropospheric chemistry airborne field campaign since the 1980s. The principal design philosophy of the ADAM web site is to provide an intuitive user interface that allows users to browse, visualize, subset (both spatially and temporally), merge, and download the airborne data, as well as providing adequate metadata associated with the data archive. A working version of the web site which shows the ADAM user interface and functionalities will be presented. Also presented are conventions to establish common names for the atmospheric variables which are often observed during airborne campaigns as well as the approaches to handle missing data and limit of detections. This presentation is intended to serve the purpose of getting feedback from the broad atmospheric community, including both modelers and measurement experts.

  8. Genetic Variants in IL6R and ADAM19 are Associated with COPD Severity in a Mexican Mestizo Population.

    PubMed

    Pérez-Rubio, Gloria; Silva-Zolezzi, Irma; Fernández-López, Juan Carlos; Camarena, Ángel; Velázquez-Uncal, Mónica; Morales-Mandujano, Fabiola; Hernández-Zenteno, Rafael De Jesús; Flores-Trujillo, Fernando; Sánchez-Romero, Candelaria; Velázquez-Montero, Alejandra; Espinosa de Los Monteros, Carlos; Sansores, Raúl H; Ramírez-Venegas, Alejandra; Falfán-Valencia, Ramcés

    2016-10-01

    Chronic obstructive pulmonary disease (COPD) is a complex and multifactorial disease with a strong genetic component. Our objective is to identify the genetic variants associated with COPD risk and its severity in Mexican Mestizo population. We evaluated 1285 single-nucleotide polymorphisms (SNPs) of candidate genes in 299 smokers with COPD (COPD-S) and 531 smokers without COPD (SWOC) using an Illumina GoldenGate genotyping microarray. In addition, 251 ancestry informative markers were included. Allele A of rs2545771 in CYP2F2P is associated with a lower risk of COPD (p = 4.02E-10, odds ratio [OR] = 0.104, confidence interval [CI] 95% 0.05-0.18). When the COPD group was stratified by severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD; levels III + IV vs. I + II), 3 SNPs (rs4329505 and rs4845626 in interleukin 6 receptor [IL6R] and rs1422794 in a disintegrin and metalloproteinase domain 19 [ADAM19]) were associated with a lower risk of suffering the most severe stages of the disease. rs2819096 in the surfactant protein D (SFTPD) gene was associated with a higher risk of COPD GOLD III + IV (p = 7.79E-03, OR = 1.80, CI 95% 1.16-2.79). Finally, the haplotype in IL6R was associated with a lower risk of suffering from more severe COPD, whereas the haplotype in ADAM19 was associated with a higher risk (p = 7.40E-03, OR = 2.83, CI 95% 1.20-6.86) of suffering from the severe stages of the disease. Our data suggest that there are alleles and haplotypes in the IL6R, ADAM19, and SFTPD genes associated with different severity stages of COPD; in CYP2F2P, rs25455771 is associated with a lower risk of COPD.

  9. Brain serotonin transporter binding of [123I]ADAM: within-subject variation between summer and winter data.

    PubMed

    Koskela, Anu; Kauppinen, Tomi; Keski-Rahkonen, Anna; Sihvola, Elina; Kaprio, Jaakko; Rissanen, Aila; Ahonen, Aapo

    2008-09-01

    The neurotransmitter serotonin (5-HT) controls several physiological functions, and a disturbance of the 5-HT system is implicated in many psychiatric conditions. Seasonal variation has been suggested in the 5-HT system. We investigated within-subject seasonal variation in brain serotonin transporter (SERT) binding with the SERT-ligand [(123)I]ADAM and single photon emission computed tomography (SPECT) in 12 healthy individuals. No systematic variation was found in the midbrain or thalamus areas between scans done in summer and winter. Our results suggest that factors other than season are more important in causing within-subject variation of brain SERT binding between summer and winter.

  10. oxLDL-induced lipid accumulation in glomerular podocytes: role of IFN-γ, CXCL16, and ADAM10.

    PubMed

    Wang, Li; Sun, Shuzhen; Zhou, Aihua; Yao, Xiujun; Wang, Yulin

    2014-09-01

    Previous studies have shown that lipid accumulation plays an important role in the pathogenesis and development of glomerular sclerosis. oxLDL caused damage in renal mesangial cells, endothelial cells, and podocytes, and podocytes might be the major victim of oxLDL insult. However, the regulatory mechanism of how oxLDL induces the damage of podocytes remains to be elucidated. In this study, oil red staining was used to investigate the lipid accumulation in podocytes. Moreover, the effects of CXCL16 antibody, IFN-γ, and ADAM10 inhibitor on oxLDL intake and CXCL16 expression were also explored to elucidate the regulatory factors of lipid accumulation in podocytes.

  11. Analyses of geochemical samples and descriptions of rock samples, Adams Gap and Shinbone Creek Roadless Areas, Clay County, Alabama

    USGS Publications Warehouse

    Erickson, M.S.; Hanley, J.T.; Kelley, D.L.; Sherlock, L.J.

    1983-01-01

    Semiquantitative spectrographic analyses for 31 elements on 105 rocks, 47 stream-sediment, and 70 soil samples from the Adams Gap and Shinbone Creek Roadless Areas and vicinity, Talladega National Forest, Clay County, Alabama are reported here in detail. Atomic-absorption analyses for zinc in all samples and for gold in 5 selected rock samples are also reported. Localities for all sables are given in Universal Transverse Mercator (UTM) coordinates. A brief description of each rock sample is included. Rocks analyzed include quartzite, phyllite, vein quartz, and schist.

  12. EGCG functions through estrogen receptor-mediated activation of ADAM10 in the promotion of non-amyloidogenic processing of APP

    PubMed Central

    Fernandez, Jamie Winderbaum; Rezai-Zadeh, Kavon; Obregon, Demian; Tan, Jun

    2010-01-01

    Estrogen depletion following menopause has been correlated with an increased risk of developing Alzheimer’s disease (AD). We previously explored the beneficial effect of (-)-epigallocatechin-3-gallate (EGCG) on AD mice and found increased non-amyloidogenic processing of amyloid precursor protein (APP) through the α-secretase a-disintegrin-and-metallopeptidase-domain 10 (ADAM10). Our results in this study suggest that EGCG-mediated enhancement of non-amyloidogenic processing of APP is mediated by the maturation of ADAM10 via an estrogen receptor-α (ERα)/PI3K/Akt dependent mechanism, independent of furin-mediated ADAM10 activation. These data support prior assertions that central selective estrogen receptor modulation could be a therapeutic target for AD and support the use of EGCG as a well-tolerated alternative to estrogen therapy in the prophylaxis and treatment of this disease. PMID:20849853

  13. Yakama Nation Housing Authority, Adams View: System Retrofit Research Report and Case Study Summary; 23 February 2004--15 January 2005

    SciTech Connect

    CARB

    2005-11-01

    The Yakama Nation is the largest tribe in the Pacific Northwest. The Yakama Nation Housing Authority (YNHA) is working to rehabilitate single family homes (two to four bedrooms) in its Adams View project using public and tax credit financing. It is in need of a major rehabilitation as a result of wear and tear after many years of use and overcrowding. The scope for the current CARB ''gut rehab'' project is 25 of the 40 homes in the Adams View development, but the proposed strategies could be replicated for the remaining 15 homes as well as for several other similar developments of the YNHA. On a larger scale, the system rehabilitation strategy developed for the Adam's View project should be replicable for most of the more than 4,300 housing units that were constructed in the Northwest (Washington, Oregon, and Idaho) under the US Department of Housing and Urban Development (HUD) Housing Act of 1937.

  14. Digitization Procedures of Analogue Seismograms from the Adam Dziewonski Observatory (HRV) at Harvard, MA

    NASA Astrophysics Data System (ADS)

    Torpey, M.; Ishii, M.

    2010-12-01

    This project explores methods of digitization of analogue seismic recordings for better preservation and to facilitate data distribution to the community. Different techniques are investigated using seismograms from one particular station, the Adam Dziewonski Observatory (HRV) at Harvard, Massachusetts. This seismological station, still in operation as a part of the Global Seismographic Network today, is one of the oldest stations in the United States. The station was built in 1933, and since its installation, the station has produced approximately 16,000 analogue seismograms. The majority of these recordings were taken between 1933 and 1953, with some intermittent recordings between 1962 and 1998 after digital seismometers had become a standard. These analogue seismograms have the potential of expanding the database for seismological research such as identification of events previously not catalogued. Due to poor storage environment at the station, some of the records, especially those on regular type of paper, are damaged beyond repair. Nevertheless, many of the records on photographic paper are in better condition, and we have focused on a subset of these recordings that are least damaged. Even these seismograms require cleaning and, in consultation with the Weissman Preservation Center of Harvard Library, preparation techniques for the photographic records are examined. After the seismograms are cleaned and flattened, three different equipments are investigated for digitization, i.e., a copy machine, scanner, and camera. These instruments allow different imaging resolutions, ranging from 200 dots per inch (dpi) to 800 dpi. The image resolution and the bit depth have a wide range of implications that are closely linked to the digitization program one chooses to convert the image to time series. We explore three different software for this conversion, SeisDig (Bromirski and Chuang, 2003), Teseo2 (Pintore and Quintiliani, 2008), and NeuraLog (www

  15. The ADAM project: a generic web interface for retrieval and display of ATLAS TDAQ information

    NASA Astrophysics Data System (ADS)

    Harwood, A.; Lehmann Miotto, G.; Magnoni, L.; Vandelli, W.; Savu, D.

    2012-06-01

    This paper describes a new approach to the visualization of information about the operation of the ATLAS Trigger and Data Acquisition system. ATLAS is one of the two general purpose detectors positioned along the Large Hadron Collider at CERN. Its data acquisition system consists of several thousand computers interconnected via multiple gigabit Ethernet networks, that are constantly monitored via different tools. Operational parameters ranging from the temperature of the computers to the network utilization are stored in several databases for later analysis. Although the ability to view these data-sets individually is already in place, currently there is no way to view this data together, in a uniform format, from one location. The ADAM project has been launched in order to overcome this limitation. It defines a uniform web interface to collect data from multiple providers that have different structures. It is capable of aggregating and correlating the data according to user defined criteria. Finally, it visualizes the collected data using a flexible and interactive front-end web system. Structurally, the project comprises of 3 main levels of the data collection cycle: The Level 0 represents the information sources within ATLAS. These providers do not store information in a uniform fashion. The first step of the project was to define a common interface with which to expose stored data. The interface designed for the project originates from the Google Data Protocol API. The idea is to allow read-only access to data providers, through HTTP requests similar in format to the SQL query structure. This provides a standardized way to access this different information sources within ATLAS. The Level 1 can be considered the engine of the system. The primary task of the Level 1 is to gather data from multiple data sources via the common interface, to correlate this data together, or over a defined time series, and expose the combined data as a whole to the Level 2 web

  16. Autoantibodies to Epilepsy-Related LGI1 in Limbic Encephalitis Neutralize LGI1-ADAM22 Interaction and Reduce Synaptic AMPA Receptors

    PubMed Central

    Ohkawa, Toshika; Fukata, Yuko; Yamasaki, Miwako; Miyazaki, Taisuke; Yokoi, Norihiko; Takashima, Hiroshi; Watanabe, Masahiko; Watanabe, Osamu

    2013-01-01

    More than 30 mutations in LGI1, a secreted neuronal protein, have been reported with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although LGI1 haploinsufficiency is thought to cause ADLTE, the underlying molecular mechanism that results in abnormal brain excitability remains mysterious. Here, we focused on a mode of action of LGI1 autoantibodies associated with limbic encephalitis (LE), which is one of acquired epileptic disorders characterized by subacute onset of amnesia and seizures. We comprehensively screened human sera from patients with immune-mediated neurological disorders for LGI1 autoantibodies, which also uncovered novel autoantibodies against six cell surface antigens including DCC, DPP10, and ADAM23. Our developed ELISA arrays revealed a specific role for LGI1 antibodies in LE and concomitant involvement of multiple antibodies, including LGI1 antibodies in neuromyotonia, a peripheral nerve disorder. LGI1 antibodies associated with LE specifically inhibited the ligand-receptor interaction between LGI1 and ADAM22/23 by targeting the EPTP repeat domain of LGI1 and reversibly reduced synaptic AMPA receptor clusters in rat hippocampal neurons. Furthermore, we found that disruption of LGI1-ADAM22 interaction by soluble extracellular domain of ADAM22 was sufficient to reduce synaptic AMPA receptors in rat hippocampal neurons and that levels of AMPA receptor were greatly reduced in the hippocampal dentate gyrus in the epileptic LGI1 knock-out mouse. Therefore, either genetic or acquired loss of the LGI1-ADAM22 interaction reduces the AMPA receptor function, causing epileptic disorders. These results suggest that by finely regulating the synaptic AMPA receptors, the LGI1-ADAM22 interaction maintains physiological brain excitability throughout life. PMID:24227725

  17. Deletions in the cytoplasmic domain of iRhom1 and iRhom2 promote shedding of the TNF receptor by the protease ADAM17.

    PubMed

    Maney, Sathish K; McIlwain, David R; Polz, Robin; Pandyra, Aleksandra A; Sundaram, Balamurugan; Wolff, Dorit; Ohishi, Kazuhito; Maretzky, Thorsten; Brooke, Matthew A; Evers, Astrid; Vasudevan, Ananda A Jaguva; Aghaeepour, Nima; Scheller, Jürgen; Münk, Carsten; Häussinger, Dieter; Mak, Tak W; Nolan, Garry P; Kelsell, David P; Blobel, Carl P; Lang, Karl S; Lang, Philipp A

    2015-11-01

    The protease ADAM17 (a disintegrin and metalloproteinase 17) catalyzes the shedding of various transmembrane proteins from the surface of cells, including tumor necrosis factor (TNF) and its receptors. Liberation of TNF receptors (TNFRs) from cell surfaces can dampen the cellular response to TNF, a cytokine that is critical in the innate immune response and promotes programmed cell death but can also promote sepsis. Catalytically inactive members of the rhomboid family of proteases, iRhom1 and iRhom2, mediate the intracellular transport and maturation of ADAM17. Using a genetic screen, we found that the presence of either iRhom1 or iRhom2 lacking part of their extended amino-terminal cytoplasmic domain (herein referred to as ΔN) increases ADAM17 activity, TNFR shedding, and resistance to TNF-induced cell death in fibrosarcoma cells. Inhibitors of ADAM17, but not of other ADAM family members, prevented the effects of iRhom-ΔN expression. iRhom1 and iRhom2 were functionally redundant, suggesting a conserved role for the iRhom amino termini. Cells from patients with a dominantly inherited cancer susceptibility syndrome called tylosis with esophageal cancer (TOC) have amino-terminal mutations in iRhom2. Keratinocytes from TOC patients exhibited increased TNFR1 shedding compared with cells from healthy donors. Our results explain how loss of the amino terminus in iRhom1 and iRhom2 impairs TNF signaling, despite enhancing ADAM17 activity, and may explain how mutations in the amino-terminal region contribute to the cancer predisposition syndrome TOC. PMID:26535007

  18. Selective Loss of Presynaptic Potassium Channel Clusters at the Cerebellar Basket Cell Terminal Pinceau in Adam11 Mutants Reveals Their Role in Ephaptic Control of Purkinje Cell Firing

    PubMed Central

    Kole, Matthew J.; Qian, Jing; Waase, Marc P.; Klassen, Tara L.; Chen, Tim T.; Augustine, George J.

    2015-01-01

    A specialized axonal ending, the basket cell “pinceau,” encapsulates the Purkinje cell axon initial segment (AIS), exerting final inhibitory control over the integrated outflow of the cerebellar cortex. This nonconventional axo-axonic contact extends beyond the perisomatic chemical GABAergic synaptic boutons to the distal AIS, lacks both sodium channels and local exocytotic machinery, and yet contains a dense cluster of voltage-gated potassium channels whose functional contribution is unknown. Here, we show that ADAM11, a transmembrane noncatalytic disintegrin, is the first reported Kv1-interacting protein essential for localizing Kv1.1 and Kv1.2 subunit complexes to the distal terminal. Selective absence of these channels at the pinceau due to mutation of ADAM11 spares spontaneous GABA release from basket cells at the perisomatic synapse yet eliminates ultrarapid ephaptic inhibitory synchronization of Purkinje cell firing. Our findings identify a critical role for presynaptic K+ channels at the pinceau in ephaptic control over the speed and stability of spike rate coding at the Purkinje cell AIS in mice. SIGNIFICANCE STATEMENT This study identifies ADAM11 as the first essential molecule for the proper localization of potassium ion channels at presynaptic nerve terminals, where they modulate excitability and the release of neural transmitters. Genetic truncation of the transmembrane disintegrin and metalloproteinase protein ADAM11 resulted in the absence of Kv1 channels that are normally densely clustered at the terminals of basket cell axons in the cerebellar cortex. These specialized terminals are responsible for the release of the neurotransmitter GABA onto Purkinje cells and also display electrical signaling. In the ADAM11 mutant, GABAergic release was not altered, but the ultrarapid electrical signal was absent, demonstrating that the dense presynaptic cluster of Kv1 ion channels at these terminals mediate electrical transmission. Therefore, ADAM11 plays a

  19. ADAM17_i33780A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the genetics of lipid lowering drugs and diet network study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes, and elevated levels of expression have been linked to obesity and insulin resistance. This study evaluated the association of six ADAM17 single nucleotide polymorphi...

  20. HIV-Nef and ADAM17-Containing Plasma Extracellular Vesicles Induce and Correlate with Immune Pathogenesis in Chronic HIV Infection

    PubMed Central

    Lee, Jung-Hyun; Schierer, Stephan; Blume, Katja; Dindorf, Jochen; Wittki, Sebastian; Xiang, Wei; Ostalecki, Christian; Koliha, Nina; Wild, Stefan; Schuler, Gerold; Fackler, Oliver T.; Saksela, Kalle; Harrer, Thomas; Baur, Andreas S.

    2016-01-01

    Antiretroviral therapy (ART) efficiently suppresses HIV replication but immune activation and low CD4 T cell counts often persist. The underlying mechanism of this ART-resistant pathogenesis is not clear. We observed that levels of plasma extracellular vesicles (pEV) are strongly elevated in HIV infection and do not decline during ART. Surprisingly, these vesicles contained the viral accessory proteins Nef and Vpu, which are assumed to be not expressed under efficient ART, as well as pro-inflammatory effectors, including activated ADAM17. HIV pEV were characterized by the presence of activated αvβ3 and absence of CD81 and Tsg101. Correlating with immune activation, peripheral monocytes ingested large amounts of pEV, giving rise to an increased population of CD1c+ CD14+ cells that secreted inflammatory cytokines. Importantly, the pro-inflammatory content, particularly ADAM17 activity, correlated with low T cell counts. Preliminary evidence suggested that HIV pEV derived from peripheral mononuclear cells and from an unknown myeloid cell population. In summary we propose an important role of pro-inflammatory pEV in chronic HIV infection due to ongoing viral Nef activity. PMID:27211553

  1. INTERNATIONAL UNION OF OPERATING ENGINEERS NATIONAL HAZMAT PROGRAM - ADAMANT CIRCULAR SAW OENHP{number_sign}: 2001-05, VERSION A

    SciTech Connect

    Unknown

    2002-01-01

    Florida International University's (FIU) Hemispheric Center for Environmental Technology (HCET) evaluated five saws for their effectiveness in cutting up specially prepared fiberglass-reinforced plywood crates. These crates were built as surrogates for crates that presently hold radioactive contaminated glove boxes at the Department of Energy's (DOE) Los Alamos facility. The Adamant circular saw was assessed on August 14, 2001. During the FIU test of efficacy, a team from the Operating Engineers National Hazmat Program (OENHP) evaluated the occupational safety and health issues associated with this technology. The Adamant was only used during a limited ''test'' on a regular plywood crate due to safety considerations of the tool for this application. The Adamant circular saw, a counter-rotating twin-cutter, constructed with blades that work differently than conventional cutting wheels with twin blades, each rotating in opposite directions. It is used to cut wood and metals. Each blade is approximately 8 3/4 inches in diameter with a maximum cutting depth of 2 1/2 inches. The machine has two rotation speeds: 1,900 and 2,900 rotations per minute (rpm). The saw is operated with an interlocked, guarded trigger switch located at the end of the saw opposite the cutting blades. To operate the saw, the safety interlock must be depressed prior to powering the saw with the trigger control. The saw is supported by a handle at the front of the saw near the cutting blades. The top part of the blades is guarded near the handle, with approximately three-fourths of the face of the blades exposed. The Adamant circular saw is an innovative technology used to cut metals and wood. Its safety features include: interlocking switch for powering the saw, overload indicator and shutoff, and an electronic brake that stops the engine immediately when the start button is released. The top part of the blades is guarded near the motor. With approximately three-fourths of the face of the blades

  2. Testimony of Gina Adams, Senior Fellow, Urban Institute. Before the Early Childhood, Elementary, and Secondary Education Subcommittee Hearing on "Improving Early Childhood Development Policies and Practices"

    ERIC Educational Resources Information Center

    Adams, Gina

    2009-01-01

    This paper presents the testimony of Gina Adams before the Early Childhood, Elementary, and Secondary Education Subcommittee Hearing on "Improving Early Childhood Development Policies and Practices." This testimony was presented to the House Committee on Education and Labor, U.S. House of Representatives last March 19, 2009. She talks about how…

  3. What Is Essential in Standard Setting and Construct Maps? Commentary on Adam E. Wyse's "Construct Maps as a Foundation for Standard Setting"

    ERIC Educational Resources Information Center

    Schulz, E. Matthew

    2013-01-01

    In this article, E. Matthew Schulz responds to Adam Wyse's article, "Construct Maps as a Foundation for Standard Setting." In doing so, he asserts that one of the most important ideas in Wyse's work is that information used in standard setting needs to be better represented through the use of graphics. However, he's not…

  4. miR-203 suppresses the proliferation and metastasis of hepatocellular carcinoma by targeting oncogene ADAM9 and oncogenic long non-coding RNA HULC.

    PubMed

    Wan, Daiwei; Shen, Shunli; Fu, Shunjun; Preston, Burnley; Brandon, Coder; He, Songbing; Shen, Chenglong; Wu, Jian; Wang, Sutong; Xie, Wenxuan; Chen, Bin; Liya, A; Guo, Yixing; Zheng, Dingcheng; Zhi, Qiaoming; Peng, Baogang

    2016-01-01

    MicroRNAs (miRNAs) have been integrated into tumorigenic programs by regulating genes at post-transcriptional level. Long non-coding RNAs (lncRNAs) are novel targets for miRNAs. Here, we reported that miR-203 down-regulation was closely linked to advanced clinical features and poor overall survival (OS) of patients with hepatocellular carcinoma. We also confirmed that miR-203 and oncogene ADAM9 (a disintegrin and metalloproteinase 9)/oncogenic long non-coding RNA HULC (highly up-regulated in liver cancer) were inversely expressed in hepatocellular carcinoma (HCC) tissues or cell lines. More intriguingly, up-regulation of miR-203 diminished the expression of ADAM9 and HULC in HCC cancer cells. Over-expression of miR-203 could markedly inhibit cell proliferation, invasion and induce cell apoptosis. Furthermore, we identified that miR-203 modulated ADAM9 and HULC in a novel post-transcriptional regulatory mechanism. Over-expression of HULC partly rescued the miR-203-mediated antitumor effects. These results suggested that miR-203 played tumor suppressive roles by downregulating ADAM9 and HULC and indicated its potential application in cancer treatment.

  5. Superfund record of decision (EPA Region 3), Westinghouse Elevator Company Plant, Operable Unit 2, Cumberland Township, Adams County, Gettysburg, PA, March 31, 1995

    SciTech Connect

    1995-04-01

    This Record of Decision (ROD) presents the selected remedial action for Operable Unit 2 (Soils) at the Westinghouse Elevator Company Plant Site in Adams County, Pennsylvania. The selected remedy for the soils at the Westinghouse Elevator Plant is No Additional Action for this Operable Unit. The other alternatives evaluated would produce little or no environmental benefit at substantial cost.

  6. Fidelia Adams Johnson: Ingenious Daughter of the Founder of Grambling State University. From Voices of Inspiration Series, an Oral History Project.

    ERIC Educational Resources Information Center

    Grambling State Univ., LA. Dept. of History and Philosophy.

    In this brief oral history, the life of Fidelia Adams Johnson is recounted with sections devoted to her family background, formative years, college experience, working life and retirement years as a black woman of influence. Her grandfather helped establish Tuskegee Institute and her father founded Louisiana's Grambling State College. Fidelia…

  7. 77 FR 38126 - In the Matter of the Designation of Abubakar Adam Kambar, Also Known as Abu Yasir, Also Known as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-26

    .... Dated: June 18, 2012. Hillary Rodham Clinton, Secretary of State. BILLING CODE 4710-10-P ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE In the Matter of the Designation of Abubakar Adam Kambar, Also Known as Abu Yasir, Also Known as Abubakar...

  8. The Earliest Reference to ADHD in the Medical Literature? Melchior Adam Weikard's Description in 1775 of "Attention Deficit" (Mangel der Aufmerksamkeit, Attentio Volubilis)

    ERIC Educational Resources Information Center

    Barkley, Russell A.; Peters, Helmut

    2012-01-01

    Objective: The present article reports on the discovery and translation of a chapter in a 1775 medical textbook by the German physician, Melchior Adam Weikard, which describes attention disorders. This article is believed to be the earliest reference to the syndrome that today is known as attention deficit hyperactivity disorder, or ADHD. Method:…

  9. Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling

    PubMed Central

    Chang, Mei-Chi; Chan, Chiu-Po; Chen, Yi-Jane; Hsien, Hsiang-Chi; Chang, Ya-Ching; Yeung, Sin-Yuet; Jeng, Po-Yuan; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

    2016-01-01

    Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production. ANE-induced EGF production was inhibited by catalase. Addition of anti-EGF neutralizing antibody attenuated ANE-induced cyclooxygenase-2 (COX-2), mature ADAM9 expression and PGE2 and 8-isoprostane production. ANE-induced IL-1α production was inhibited by catalase, anti-EGF antibody, PD153035 (EGF receptor antagonist) and U0126 (MEK inhibitor) but not by α-naphthoflavone (cytochrome p450-1A1 inhibitor). ANE-induced ADAM17 production was inhibited by pp2 (Src inhibitor), U0126, α-naphthoflavone and aspirin. AG490 (JAK inhibitor) prevented ANE-stimulated ADAM17, IL-1α, PGE2 production, COX-2 expression, ADAM9 maturation, and the ANE-induced decline in keratin 5 and 14, but showed little effect on cdc2 expression and EGF production. Moreover, ANE-induced 8-isoprostane production by GKs was inhibited by catalase, anti-EGF antibody, AG490, pp2, U0126, α-naphthoflavone, Zinc protoporphyrin (ZnPP) and aspirin. These results indicate that AN components may involve in BQ-induced oral cancer by induction of reactive oxygen species, EGF/EGFR, IL-1α, ADAMs, JAK, Src, MEK/ERK, CYP1A1, and COX signaling pathways, and the aberration of cell cycle and differentiation. Various blockers against ROS, EGF, IL-1α, ADAM, JAK, Src, MEK, CYP1A1, and COX can be used for prevention or treatment of BQ chewing-related diseases. PMID:26919242

  10. Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling.

    PubMed

    Chang, Mei-Chi; Chan, Chiu-Po; Chen, Yi-Jane; Hsien, Hsiang-Chi; Chang, Ya-Ching; Yeung, Sin-Yuet; Jeng, Po-Yuan; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

    2016-03-29

    Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production. ANE-induced EGF production was inhibited by catalase. Addition of anti-EGF neutralizing antibody attenuated ANE-induced cyclooxygenase-2 (COX-2), mature ADAM9 expression and PGE2 and 8-isoprostane production. ANE-induced IL-1α production was inhibited by catalase, anti-EGF antibody, PD153035 (EGF receptor antagonist) and U0126 (MEK inhibitor) but not by α-naphthoflavone (cytochrome p450-1A1 inhibitor). ANE-induced ADAM17 production was inhibited by pp2 (Src inhibitor), U0126, α-naphthoflavone and aspirin. AG490 (JAK inhibitor) prevented ANE-stimulated ADAM17, IL-1α, PGE2 production, COX-2 expression, ADAM9 maturation, and the ANE-induced decline in keratin 5 and 14, but showed little effect on cdc2 expression and EGF production. Moreover, ANE-induced 8-isoprostane production by GKs was inhibited by catalase, anti-EGF antibody, AG490, pp2, U0126, α-naphthoflavone, Zinc protoporphyrin (ZnPP) and aspirin. These results indicate that AN components may involve in BQ-induced oral cancer by induction of reactive oxygen species, EGF/EGFR, IL-1α, ADAMs, JAK, Src, MEK/ERK, CYP1A1, and COX signaling pathways, and the aberration of cell cycle and differentiation. Various blockers against ROS, EGF, IL-1α, ADAM, JAK, Src, MEK, CYP1A1, and COX can be used for prevention or treatment of BQ chewing-related diseases. PMID:26919242

  11. An ADAM33 Polymorphism Associates with Progression of Preschool Wheeze into Childhood Asthma: A Prospective Case-Control Study with Replication in a Birth Cohort Study

    PubMed Central

    Klaassen, Ester M. M.; Penders, John; Jöbsis, Quirijn; van de Kant, Kim D. G.; Thijs, Carel; Mommers, Monique; van Schayck, Constant P.; van Eys, Guillaume; Koppelman, Gerard H.; Dompeling, Edward

    2015-01-01

    Background The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined. Objective To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma. Materials and Methods In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis). Results In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze. Conclusion Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma. PMID:25768087

  12. Epidermal growth factor (EGF) ligand release by substrate-specific a disintegrin and metalloproteases (ADAMs) involves different protein kinase C (PKC) isoenzymes depending on the stimulus.

    PubMed

    Dang, Michelle; Dubbin, Karen; D'Aiello, Antonio; Hartmann, Monika; Lodish, Harvey; Herrlich, Andreas

    2011-05-20

    The dysregulation of EGF family ligand cleavage has severe consequences for the developing as well as the adult organism. Therefore, their production is highly regulated. The limiting step is the ectodomain cleavage of membrane-bound precursors by one of several a disintegrin and metalloprotease (ADAM) metalloproteases, and understanding the regulation of cleavage is an important goal of current research. We have previously reported that in mouse lung epithelial cells, the pro-EGF ligands TGFα, neuregulin 1β (NRG), and heparin-binding EGF are differentially cleaved depending on the cleavage stimulus (Herrlich, A., Klinman, E., Fu, J., Sadegh, C., and Lodish, H. (2008) FASEB J.). In this study in mouse embryonic fibroblasts that lack different ADAMs, we show that induced cleavage of EGF ligands can involve the same substrate-specific metalloprotease but does require different stimulus-dependent signaling pathways. Cleavage was stimulated by phorbol ester (12-O-tetradecanoylphorbol-13-acetate (TPA), a mimic of diacylglycerol and PKC activator), hypertonic stress, lysophosphatidic acid (LPA)-induced G protein-coupled receptor activation, or by ionomycin-induced intracellular calcium release. Although ADAMs showed substrate preference (ADAM17, TGFα and heparin-binding EGF; and ADAM9, NRG), substrate cleavage differed substantially with the stimulus, and cleavage of the same substrate depended on the presence of different, sometimes multiple, PKC isoforms. For instance, classical PKC was required for TPA-induced but not hypertonic stress-induced cleavage of all EGF family ligands. Inhibition of PKCζ enhanced NRG release upon TPA stimulation, but it blocked NRG release in response to hypertonic stress. Our results suggest a model in which substantial regulation of ectodomain cleavage occurs not only on the metalloprotease level but also on the level of the substrate or of a third protein.

  13. Caveolin-1-dependent activation of the metalloprotease TACE/ADAM17 by TGF-β in hepatocytes requires activation of Src and the NADPH oxidase NOX1.

    PubMed

    Moreno-Càceres, Joaquim; Mainez, Jèssica; Mayoral, Rafael; Martín-Sanz, Paloma; Egea, Gustavo; Fabregat, Isabel

    2016-04-01

    Transforming growth factor-β (TGF-β) plays a dual role in hepatocytes, inducing both pro- and anti-apoptotic responses, the balance between which decides cell fate. Survival signals are mediated by the epidermal growth factor receptor (EGFR) pathway, which is activated by TGF-β. We have previously shown that caveolin-1 (CAV1) is required for activation of the metalloprotease tumour necrosis factor (TNF)-α-converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17), and hence transactivation of the EGFR pathway. The specific mechanism by which TACE/ADAM17 is activated has not yet been determined. Here we show that TGF-β induces phosphorylation of sarcoma kinase (Src) in hepatocytes, a process that is impaired in Cav1(-/-) hepatocytes, coincident with a decrease in phosphorylated Src in detergent-resistant membrane fractions. TGF-β-induced activation of TACE/ADAM17 and EGFR phosphorylation were blocked using the Src inhibitor PP2. Cav1(+/+) hepatocytes showed early production of reactive oxygen species (ROS) induced by TGF-β, which was not seen in Cav1(-/-) cells. Production of ROS was inhibited by both the NADPH oxidase 1 (NOX1) inhibitor STK301831 and NOX1 knock-down, which also impaired TACE/ADAM17 activation and thus EGFR phosphorylation. Finally, neither STK301831 nor NOX1 silencing impaired Src phosphorylation, but PP2 blocked early ROS production, showing that Src is involved in NOX1 activation. As expected, inhibition of Src or NOX1 increased TGF-β-induced cell death in Cav1(+/+) cells. In conclusion, CAV1 is required for TGF-β-mediated activation of TACE/ADAM17 through a mechanism that involves phosphorylation of Src and NOX1-mediated ROS production.

  14. 123I-ADAM SPECT imaging of serotonin transporter binding in patients with night eating syndrome: a preliminary report.

    PubMed

    Lundgren, Jennifer D; Newberg, Andrew B; Allison, Kelly C; Wintering, Nancy A; Ploessl, Karl; Stunkard, Albert J

    2008-04-15

    Night eating syndrome (NES) represents a delay in the circadian pattern of food intake, manifested by evening hyperphagia and/or nocturnal awakenings accompanied by ingestions of food. A neurobiological marker of NES has been implicated with the recently discovered therapeutic response to the selective serotonin reuptake inhibitor (SSRI) sertraline. This pilot SPECT (single photon emission computed tomography) study compared the serotonin transporter (SERT) uptake ratios of night eaters with those of healthy controls. Six night eaters underwent SPECT imaging using the radiopharmaceutical (123)I-ADAM. Uptake, compared with that of the cerebellum, was obtained for the midbrain, basal ganglia, and temporal lobes; uptake ratios in night eaters were compared with those of six healthy controls. Night eaters had significantly greater SERT uptake ratios in the midbrain than healthy controls. These findings, in conjunction with the therapeutic response of NES to sertraline, indicate that the serotonin system is involved in the pathophysiology of NES.

  15. Understanding Influence within the Context of Nursing: Development of the Adams Influence Model Using Practice, Research, and Theory.

    PubMed

    Adams, Jeffrey M; Natarajan, Sudha

    2016-01-01

    Acquiring influence, and knowing how to use it, is a required competency for nurse leaders, yet the concept of influence and how it works is not well described in the nursing literature. In this article, the authors examine what is known about influence and present an influence model specific to nurse leaders. The Adams Influence Model was developed through an iterative process and is based on a comprehensive review of the influence literature, expert commentary, multiple pilot studies, evaluation of nursing theories, and validation by an external data source. Rather than defining "how to" influence, the model serves as a guide for personal reflection, helping nurse leaders understand and reflect on the influence process and factors, tactics, and strategies they can use when seeking to influence others. PMID:27490886

  16. Understanding Influence within the Context of Nursing: Development of the Adams Influence Model Using Practice, Research, and Theory.

    PubMed

    Adams, Jeffrey M; Natarajan, Sudha

    2016-01-01

    Acquiring influence, and knowing how to use it, is a required competency for nurse leaders, yet the concept of influence and how it works is not well described in the nursing literature. In this article, the authors examine what is known about influence and present an influence model specific to nurse leaders. The Adams Influence Model was developed through an iterative process and is based on a comprehensive review of the influence literature, expert commentary, multiple pilot studies, evaluation of nursing theories, and validation by an external data source. Rather than defining "how to" influence, the model serves as a guide for personal reflection, helping nurse leaders understand and reflect on the influence process and factors, tactics, and strategies they can use when seeking to influence others.

  17. 123I-ADAM SPECT imaging of serotonin transporter binding in patients with night eating syndrome: a preliminary report.

    PubMed

    Lundgren, Jennifer D; Newberg, Andrew B; Allison, Kelly C; Wintering, Nancy A; Ploessl, Karl; Stunkard, Albert J

    2008-04-15

    Night eating syndrome (NES) represents a delay in the circadian pattern of food intake, manifested by evening hyperphagia and/or nocturnal awakenings accompanied by ingestions of food. A neurobiological marker of NES has been implicated with the recently discovered therapeutic response to the selective serotonin reuptake inhibitor (SSRI) sertraline. This pilot SPECT (single photon emission computed tomography) study compared the serotonin transporter (SERT) uptake ratios of night eaters with those of healthy controls. Six night eaters underwent SPECT imaging using the radiopharmaceutical (123)I-ADAM. Uptake, compared with that of the cerebellum, was obtained for the midbrain, basal ganglia, and temporal lobes; uptake ratios in night eaters were compared with those of six healthy controls. Night eaters had significantly greater SERT uptake ratios in the midbrain than healthy controls. These findings, in conjunction with the therapeutic response of NES to sertraline, indicate that the serotonin system is involved in the pathophysiology of NES. PMID:18281200

  18. More than a neuroanatomical representation in The Creation of Adam by Michelangelo Buonarroti, a representation of the Golden Ratio.

    PubMed

    de Campos, Deivis; Malysz, Tais; Bonatto-Costa, João Antonio; Jotz, Geraldo Pereira; de Oliveira Junior, Lino Pinto; da Rocha, Andrea Oxley

    2015-09-01

    Michelangelo Buonarroti (1475-1564) was a master anatomist as well as an artistic genius. He dissected numerous cadavers and developed a profound understanding of human anatomy. Among his best-known artworks are the frescoes painted on the ceiling of the Sistine Chapel (1508-1512), in Rome. Currently, there is some debate over whether the frescoes merely represent the teachings of the Catholic Church at the time or if there are other meanings hidden in the images. In addition, there is speculation regarding the image of the brain embedded in the fresco known as "The Creation of Adam," which contains anatomic features of the midsagittal and lateral surfaces of the brain. Within this context, we report our use of Image Pro Plus Software 6.0 to demonstrate mathematical evidence that Michelangelo painted "The Creation of Adam" using the Divine Proportion/Golden Ratio (GR) (1.6). The GR is classically associated with greater structural efficiency and is found in biological structures and works of art by renowned artists. Thus, according to the evidence shown in this article, we can suppose that the beauty and harmony recognized in all Michelangelo's works may not be based solely on his knowledge of human anatomical proportions, but that the artist also probably knew anatomical structures that conform to the GR display greater structural efficiency. It is hoped that this report will at least stimulate further scientific and scholarly contributions to this fascinating topic, as the study of these works of art is essential for the knowledge of the history of Anatomy.

  19. Structure, function and latency regulation of a bacterial enterotoxin potentially derived from a mammalian adamalysin/ADAM xenolog

    PubMed Central

    Goulas, Theodoros; Arolas, Joan L.; Gomis-Rüth, F. Xavier

    2011-01-01

    Enterotoxigenic Bacteroides fragilis is the most frequent disease-causing anaerobe in the intestinal tract of humans and livestock and its specific virulence factor is fragilysin, also known as B. fragilis toxin. This is a 21-kDa zinc-dependent metallopeptidase existing in three closely related isoforms that hydrolyze E-cadherin and contribute to secretory diarrhea, and possibly to inflammatory bowel disease and colorectal cancer. Here we studied the function and zymogenic structure of fragilysin-3 and found that its activity is repressed by a ∼170-residue prodomain, which is the largest hitherto structurally characterized for a metallopeptidase. This prodomain plays a role in both the latency and folding stability of the catalytic domain and it has no significant sequence similarity to any known protein. The prodomain adopts a novel fold and inhibits the protease domain via an aspartate-switch mechanism. The catalytic fragilysin-3 moiety is active against several protein substrates and its structure reveals a new family prototype within the metzincin clan of metallopeptidases. It shows high structural similarity despite negligible sequence identity to adamalysins/ADAMs, which have only been described in eukaryotes. Because no similar protein has been found outside enterotoxigenic B. fragilis, our findings support that fragilysins derived from a mammalian adamalysin/ADAM xenolog that was co-opted by B. fragilis through a rare case of horizontal gene transfer from a eukaryotic cell to a bacterial cell. Subsequently, this co-opted peptidase was provided with a unique chaperone and latency maintainer in the time course of evolution to render a robust and dedicated toxin to compromise the intestinal epithelium of mammalian hosts. PMID:21233422

  20. Extraction-Separation Performance and Dynamic Modeling of Orion Test Vehicles with Adams Simulation: 2nd Edition

    NASA Technical Reports Server (NTRS)

    Fraire, Usbaldo, Jr.; Anderson, Keith; Varela, Jose G.; Bernatovich, Michael A.

    2015-01-01

    NASA's Orion Capsule Parachute Assembly System (CPAS) project has advanced into the third generation of its parachute test campaign and requires technically comprehensive modeling capabilities to simulate multi-body dynamics (MBD) of test articles released from a C-17. Safely extracting a 30,000 lbm mated test article from a C-17 and performing stable mid-air separation maneuvers requires an understanding of the interaction between elements in the test configuration and how they are influenced by extraction parachute performance, aircraft dynamics, aerodynamics, separation dynamics, and kinetic energy experienced by the system. During the real-time extraction and deployment sequences, these influences can be highly unsteady and difficult to bound. An avionics logic window based on time, pitch, and pitch rate is used to account for these effects and target a favorable separation state in real time. The Adams simulation has been employed to fine-tune this window, as well as predict and reconstruct the coupled dynamics of the Parachute Test Vehicle (PTV) and Cradle Platform Separation System (CPSS) from aircraft extraction through the mid-air separation event. The test-technique for the extraction of CPAS test articles has evolved with increased complexity and requires new modeling concepts to ensure the test article is delivered to a stable test condition for the programmer phase. Prompted by unexpected dynamics and hardware malfunctions in drop tests, these modeling improvements provide a more accurate loads prediction by incorporating a spring-damper line-model derived from the material properties. The qualification phase of CPAS testing is on the horizon and modeling increasingly complex test-techniques with Adams is vital to successfully qualify the Orion parachute system for human spaceflight.

  1. Three-dimensional geophysical mapping of rock alteration and water content at Mount Adams, Washington: Implications for lahar hazards

    USGS Publications Warehouse

    Finn, C.A.; Deszcz-Pan, M.; Anderson, E.D.; John, D.A.

    2007-01-01

    Hydrothermally altered rocks, particularly if water saturated, can weaken stratovolcanoes, thereby increasing the potential for catastrophic sector collapses that can lead to far-traveled, destructive debris flows. Evaluating the hazards associated with such alteration is difficult because alteration has been mapped on few active volcanoes and the distribution and intensity of subsurface alteration are largely unknown on any active volcano. At Mount Adams, some Holocene debris flows contain abundant hydrothermal minerals derived from collapse of the altered, edifice. Intense hydrothermal alteration significantly reduces the resistivity and magnetization of volcanic rock, and therefore hydrothermally altered rocks can be identified with helicopter electromagnetic and magnetic measurements. Electromagnetic and magnetic data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses of hydrothermally altered rock in the central core of Mount Adams north of the summit. We identify steep cliffs at the western edge of this zone as the likely source for future large debris flows. In addition, the electromagnetic data identified water in the brecciated core of the upper 100-200 m of the volcano. Water helps alter the rocks, reduces the effective stress, thereby increasing the potential for slope failure, and acts, with entrained melting ice, as a lubricant to transform debris avalanches into lahars. Therefore knowing the distribution of water is also important for hazard assessments. Our results demonstrate that high-resolution geophysical and geological observations can yield unprecedented views of the three-dimensional distribution of altered rock and shallow pore water aiding evaluation of the debris avalanche hazard.

  2. More than a neuroanatomical representation in The Creation of Adam by Michelangelo Buonarroti, a representation of the Golden Ratio.

    PubMed

    de Campos, Deivis; Malysz, Tais; Bonatto-Costa, João Antonio; Jotz, Geraldo Pereira; de Oliveira Junior, Lino Pinto; da Rocha, Andrea Oxley

    2015-09-01

    Michelangelo Buonarroti (1475-1564) was a master anatomist as well as an artistic genius. He dissected numerous cadavers and developed a profound understanding of human anatomy. Among his best-known artworks are the frescoes painted on the ceiling of the Sistine Chapel (1508-1512), in Rome. Currently, there is some debate over whether the frescoes merely represent the teachings of the Catholic Church at the time or if there are other meanings hidden in the images. In addition, there is speculation regarding the image of the brain embedded in the fresco known as "The Creation of Adam," which contains anatomic features of the midsagittal and lateral surfaces of the brain. Within this context, we report our use of Image Pro Plus Software 6.0 to demonstrate mathematical evidence that Michelangelo painted "The Creation of Adam" using the Divine Proportion/Golden Ratio (GR) (1.6). The GR is classically associated with greater structural efficiency and is found in biological structures and works of art by renowned artists. Thus, according to the evidence shown in this article, we can suppose that the beauty and harmony recognized in all Michelangelo's works may not be based solely on his knowledge of human anatomical proportions, but that the artist also probably knew anatomical structures that conform to the GR display greater structural efficiency. It is hoped that this report will at least stimulate further scientific and scholarly contributions to this fascinating topic, as the study of these works of art is essential for the knowledge of the history of Anatomy. PMID:26182895

  3. Summary of hydrogeologic and ground-water-quality data and hydrogeologic framework at selected well sites, Adams County, Pennsylvania

    USGS Publications Warehouse

    Low, Dennis J.; Dugas, Diana L.

    1999-01-01

    Rapid population growth in Adams County has increased the demand for ground water and led Adams County planning officials to undertake an effort to evaluate the capabilities of existing community water systems to meet future, projected growth and to begin wellhead-protection programs for public-supply wells. As part of this effort, this report summarizes ground-water data on a countywide scale and provides hydrogeologic information needed to delineate wellheadprotection areas in three hydrogeologic units (Gettysburg Lowland, Blue Ridge, and Piedmont Lowland). Reported yields, specific capacities, well depths, and reported overburden thickness can vary by hydrogeologic unit, geologic formation, water use (domestic and nondomestic), and topographic setting. The reported yields of domestic wells drilled in the Gettysburg Lowland (median reported yield of 10 gallons per minute) are significantly greater than the reported yields from the Blue Ridge, Piedmont Lowland, and Piedmont Upland (median reported yields of 7.0, 8.0, and 7.0 gallons per minute, respectively). Reported yields of domestic wells completed in the diabase and the New Oxford Formation of the Gettysburg Lowland, and in the metarhyolite and metabasalt of the Blue Ridge, are significantly lower than reported yields of wells completed in the Gettysburg Formation. For nondomestic wells, reported yields from the Conestoga Formation of the Piedmont Lowland are significantly greater than in the diabase. Reported yields of nondomestic wells drilled in the Gettysburg, New Oxford, and Conestoga Formations, and the metarhyolite are significantly greater than those for domestic wells drilled in the respective geologic formations. Specific capacities of nondomestic wells in the Conestoga and Gettysburg Formations are significantly greater than their domestic counterparts. Specific capacities of nondomestic wells in the Conestoga Formation are significantly greater than the specific capacities of nondomestic wells in

  4. Two Single-Nucleotide Polymorphisms in ADAM12 Gene Are Associated with Early and Late Radiographic Knee Osteoarthritis in Estonian Population.

    PubMed

    Kerna, Irina; Kisand, Kalle; Tamm, Ann E; Kumm, Jaanika; Tamm, Agu O

    2013-01-01

    Objectives. To investigate associations of selected single-nucleotide polymorphisms (SNPs) in ADAM12 gene with radiographic knee osteoarthritis (rKOA) in Estonian population. Methods. The rs3740199, rs1871054, rs1278279, and rs1044122 SNPs in ADAM12 gene were genotyped in 438 subjects (303 women) from population-based cohort, aged 32 to 57 (mean 45.4). The rKOA features were evaluated in the tibiofemoral joint (TFJ) and patellofemoral joint. Results. The early rKOA was found in 51.4% of investigated subjects (72% women) and 12.3% of participants (63% women) had advanced stage of diseases. The A allele of synonymous SNP rs1044122 was associated with early rKOA in TFJ, predominantly with the presence of osteophytes in females (OR 1.57; 95% CI 1.08-2.29, P = 0.018). The C allele of intron polymorphism rs1871054 carried risk for advanced rKOA, mostly to osteophyte formation in TFJ in males (OR 3.03; 95% CI 1.11-7.53, P = 0.018). Also the CCAA haplotype of ADAM12 was associated with osteophytosis, again mostly in TFJ in males (P = 0.014). For rs3740199 and rs1278279, no statistically significant associations were observed. Conclusion.  ADAM12 gene variants are related to rKOA risk during the early and late stages of diseases. The genetic risk seems to be predominantly associated with the appearance of osteophytes-a marker of bone remodelling and neochondrogenesis.

  5. Loss of ADAM17-Mediated Tumor Necrosis Factor Alpha Signaling in Intestinal Cells Attenuates Mucosal Atrophy in a Mouse Model of Parenteral Nutrition.

    PubMed

    Feng, Yongjia; Tsai, Yu-Hwai; Xiao, Weidong; Ralls, Matthew W; Stoeck, Alex; Wilson, Carole L; Raines, Elaine W; Teitelbaum, Daniel H; Dempsey, Peter J

    2015-11-01

    Total parenteral nutrition (TPN) is commonly used clinically to sustain patients; however, TPN is associated with profound mucosal atrophy, which may adversely affect clinical outcomes. Using a mouse TPN model, removing enteral nutrition leads to decreased crypt proliferation, increased intestinal epithelial cell (IEC) apoptosis and increased mucosal tumor necrosis factor alpha (TNF-α) expression that ultimately produces mucosal atrophy. Upregulation of TNF-α signaling plays a central role in mediating TPN-induced mucosal atrophy without intact epidermal growth factor receptor (EGFR) signaling. Currently, the mechanism and the tissue-specific contributions of TNF-α signaling to TPN-induced mucosal atrophy remain unclear. ADAM17 is an ectodomain sheddase that can modulate the signaling activity of several cytokine/growth factor receptor families, including the TNF-α/TNF receptor and ErbB ligand/EGFR pathways. Using TPN-treated IEC-specific ADAM17-deficient mice, the present study demonstrates that a loss of soluble TNF-α signaling from IECs attenuates TPN-induced mucosal atrophy. Importantly, this response remains dependent on the maintenance of functional EGFR signaling in IECs. TNF-α blockade in wild-type mice receiving TPN confirmed that soluble TNF-α signaling is responsible for downregulation of EGFR signaling in IECs. These results demonstrate that ADAM17-mediated TNF-α signaling from IECs has a significant role in the development of the proinflammatory state and mucosal atrophy observed in TPN-treated mice.

  6. Systematic evaluation of methyl ester bioisosteres in the context of developing alkenyldiarylmethanes (ADAMs) as non-nucleoside reverse transcriptase inhibitors (NNRTIs) for anti-HIV-1 chemotherapy.

    PubMed

    Hoshi, Ayako; Sakamoto, Takeshi; Takayama, Jun; Xuan, Meiyan; Okazaki, Mari; Hartman, Tracy L; Buckheit, Robert W; Pannecouque, Christophe; Cushman, Mark

    2016-07-01

    The alkenyldiarylmethanes (ADAMs) are a class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) targeting HIV-1. Four chemically and metabolically stabilized ADAMs incorporating N-methoxyimidoyl halide replacements of the methyl esters of the lead compound were previously reported. In this study, twenty-five new ADAMs were synthesized in order to investigate the biological consequences of installing nine different methyl ester bioisosteres at three different locations. Attempts to define a universal rank order of methyl ester bioisosteres and discover the 'best' one in terms of inhibitory activity versus HIV-1 reverse transcriptase (RT) led to the realization that the potencies are critically dependent on the surrounding structure at each location, and therefore the definition of universal rank order is impossible. This investigation produced several new non-nucleoside reverse transcriptase inhibitors in which all three of the three methyl esters of the lead compound were replaced by methyl ester bioisosteres, resulting in compounds that are more potent as HIV-1 RT inhibitors and antiviral agents than the lead compound itself and are expected to also be more metabolically stable than the lead compound. PMID:27234889

  7. The Elsevier Trophoblast Research Award Lecture: Importance of metzincin proteases in trophoblast biology and placental development: a focus on ADAM12.

    PubMed

    Aghababaei, Mahroo; Beristain, Alexander G

    2015-04-01

    Placental development is a highly regulated process requiring signals from both fetal and maternal uterine compartments. Within this complex system, trophoblasts, placental cells of epithelial lineage, form the maternal-fetal interface controlling nutrient, gas and waste exchange. The commitment of progenitor villous cytotrophoblasts to differentiate into diverse trophoblast subsets is a fundamental process in placental development. Differentiation of trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential for uterine arterial remodeling and placental function. Inadequate placentation, characterized by defects in trophoblast differentiation, may underlie the earliest cellular events driving pregnancy disorders such as preeclampsia and fetal growth restriction. Molecularly, invasive trophoblasts acquire characteristics defined by profound alterations in cell-cell and cell-matrix adhesion, cytoskeletal reorganization and production of proteolytic factors. To date, most studies have investigated the importance of the matrix metalloproteinases (MMPs) and their ability to efficiently remodel components of the extracellular matrix (ECM). However, it is now becoming clear that besides MMPs, other related proteases regulate trophoblast invasion via mechanisms other than ECM turnover. In this review, we will summarize the current knowledge on the regulation of trophoblast invasion by members of the metzincin family of metalloproteinases. Specifically, we will discuss the emerging roles that A Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a particular focus on the ADAM subtype, ADAM12.

  8. The Elsevier Trophoblast Research Award Lecture: Importance of metzincin proteases in trophoblast biology and placental development: a focus on ADAM12.

    PubMed

    Aghababaei, Mahroo; Beristain, Alexander G

    2015-04-01

    Placental development is a highly regulated process requiring signals from both fetal and maternal uterine compartments. Within this complex system, trophoblasts, placental cells of epithelial lineage, form the maternal-fetal interface controlling nutrient, gas and waste exchange. The commitment of progenitor villous cytotrophoblasts to differentiate into diverse trophoblast subsets is a fundamental process in placental development. Differentiation of trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential for uterine arterial remodeling and placental function. Inadequate placentation, characterized by defects in trophoblast differentiation, may underlie the earliest cellular events driving pregnancy disorders such as preeclampsia and fetal growth restriction. Molecularly, invasive trophoblasts acquire characteristics defined by profound alterations in cell-cell and cell-matrix adhesion, cytoskeletal reorganization and production of proteolytic factors. To date, most studies have investigated the importance of the matrix metalloproteinases (MMPs) and their ability to efficiently remodel components of the extracellular matrix (ECM). However, it is now becoming clear that besides MMPs, other related proteases regulate trophoblast invasion via mechanisms other than ECM turnover. In this review, we will summarize the current knowledge on the regulation of trophoblast invasion by members of the metzincin family of metalloproteinases. Specifically, we will discuss the emerging roles that A Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a particular focus on the ADAM subtype, ADAM12. PMID:25589360

  9. Loss of ADAM17-Mediated Tumor Necrosis Factor Alpha Signaling in Intestinal Cells Attenuates Mucosal Atrophy in a Mouse Model of Parenteral Nutrition

    PubMed Central

    Feng, Yongjia; Tsai, Yu-Hwai; Xiao, Weidong; Ralls, Matthew W.; Stoeck, Alex; Wilson, Carole L.; Raines, Elaine W.

    2015-01-01

    Total parenteral nutrition (TPN) is commonly used clinically to sustain patients; however, TPN is associated with profound mucosal atrophy, which may adversely affect clinical outcomes. Using a mouse TPN model, removing enteral nutrition leads to decreased crypt proliferation, increased intestinal epithelial cell (IEC) apoptosis and increased mucosal tumor necrosis factor alpha (TNF-α) expression that ultimately produces mucosal atrophy. Upregulation of TNF-α signaling plays a central role in mediating TPN-induced mucosal atrophy without intact epidermal growth factor receptor (EGFR) signaling. Currently, the mechanism and the tissue-specific contributions of TNF-α signaling to TPN-induced mucosal atrophy remain unclear. ADAM17 is an ectodomain sheddase that can modulate the signaling activity of several cytokine/growth factor receptor families, including the TNF-α/TNF receptor and ErbB ligand/EGFR pathways. Using TPN-treated IEC-specific ADAM17-deficient mice, the present study demonstrates that a loss of soluble TNF-α signaling from IECs attenuates TPN-induced mucosal atrophy. Importantly, this response remains dependent on the maintenance of functional EGFR signaling in IECs. TNF-α blockade in wild-type mice receiving TPN confirmed that soluble TNF-α signaling is responsible for downregulation of EGFR signaling in IECs. These results demonstrate that ADAM17-mediated TNF-α signaling from IECs has a significant role in the development of the proinflammatory state and mucosal atrophy observed in TPN-treated mice. PMID:26283731

  10. C6 Glioma-Secreted NGF and FGF2 Regulate Neuronal APP Processing Through Up-Regulation of ADAM10 and Down-Regulation of BACE1, Respectively.

    PubMed

    Xie, Huiping; Xiao, Zhimin; Huang, Jian

    2016-07-01

    Excessive accumulation of amyloid-β (Aβ) caused by cleavage of amyloid precursor protein (APP) is thought to be the primary cause of Alzheimer's disease (AD). Two key enzymes ADAM10 and BACE1 are involved in the initial cleavage of APP, resulting in the onset of two pathways, the amyloidogenic pathway and the non-amyloidogenic pathway, respectively. Altering APP metabolism towards the non-amyloidogenic pathway is thought to reduce Aβ production. It has been reported that, in vivo, exogenous neurotrophic factors make APP apt to entering the non-amyloidogenic pathway. Since astrocytes secrete a battery of neurotrophic factors, we investigated the role of astrocyte-derived factors in the dynamics of Aβ generation in neural cells. Results show that C6 glioma cell-conditioned medium (GCM), obtained from cultured astrocyte-derived C6 glioma cells, inhibit Aβ1-42 production and shift APP processing towards the non-amyloidogenic pathway in APPswe-HEK293 cells. Such effect is attributed to two key APP cleavage enzymes, ADAM10 and BACE1. Two neurotrophic factors in the GCM, nerve growth factor and fibroblast growth factor 2, are responsible for the up-regulation of ADAM10 and down-regulation of BACE1, respectively. Our findings enhance our understanding of the relationship between astrocytes and Aβ generation, indicating that stimulation of astrocytic neurotrophic factors could slow AD progression. PMID:26614345

  11. Variability of the needle essential oils of Juniperus deltoides R.P.ADAMS from different populations in Serbia and Croatia.

    PubMed

    Rajčević, Nemanja; Janaćković, Peđa; Bojović, Srđan; Tešević, Vele; Marin, Petar D

    2013-01-01

    The essential-oil compositions of one Croatian and three Serbian populations of Juniperus deltoides R.P.ADAMS have been determined by GC/MS analysis. In total, 147 compounds were identified, representing 97.3-98.3% of the oil composition. The oils were dominated by monoterpenes, which are characteristic components for the species of the section Juniperus. Two monoterpenes, α-pinene and limonene, were the dominant constituents, with a summed-up average content of 49.45%. Statistical methods were used to determine the diversity of the terpene classes and the common terpenes between the newly described J. deltoides populations from Serbia and Croatia. Only reports on several specimens from this species have been reported so far, and there are no studies that treat population diversity. Cluster analysis of the oil contents of 21 terpenes showed high correlation with the geographical distribution of the populations, separating the Croatian from the Serbian populations. The comparison of the essential-oil compositions obtained in the present study with literature data, showed the separation of J. deltoides and J. oxycedrus ssp. oxycedrus from the western Mediterranean region.

  12. Three-dimensional viscoelastic time-domain finite-difference seismic modelling using the staggered Adams-Bashforth time integrator

    NASA Astrophysics Data System (ADS)

    Bohlen, Thomas; Wittkamp, Florian

    2016-03-01

    We analyse the performance of a higher order accurate staggered viscoelastic time-domain finite-difference method, in which the staggered Adams-Bashforth (ABS) third-order and fourth-order accurate time integrators are used for temporal discretization. ABS is a multistep method that uses previously calculated wavefields to increase the order of accuracy in time. The analysis shows that the numerical dispersion is much lower than that of the widely used second-order leapfrog method. Numerical dissipation is introduced by the ABS method which is significantly smaller for fourth-order than third-order accuracy. In 1-D and 3-D simulation experiments, we verify the convincing improvements of simulation accuracy of the fourth-order ABS method. In a realistic elastic 3-D scenario, the computing time reduces by a factor of approximately 2.4, whereas the memory requirements increase by approximately a factor of 2.2. The ABS method thus provides an alternative strategy to increase the simulation accuracy in time by investing computer memory instead of computing time.

  13. Example evaluation of a permit application for a proposed hazardous-waste landfill in eastern Adams County, Colorado

    USGS Publications Warehouse

    Banta, E.R.

    1986-01-01

    A project was undertaken by the U.S. Geological Survey in cooperation with the U. S. Environmental Protection Agency to demonstrate methods by which RCRA (Resources Conservation and Recovery Act of 1976) Part B permit applications might be evaluated. The purpose of the project was to prepare a report that would supplement a series of case studies to be made available to permit writers in the U.S. Environmental Protection Agency. Four sites in the United States were chosen for their potential applicability to geologically similar sites. The Adams County, Colorado, site was chosen to be representative of sites in the Upper Cretaceous Pierre Shale. The intent of this report is to provide an example of how available earth-science information might be used in evaluating an application and not to evaluate the acceptability of the site. Because this study is an evaluation of a permit application, the data used are limited to the data supplied in the application and in published reports. Of the five criteria required by the U.S. Environmental Protection Agency to be addressed in the permit application considered in the case study, the application was evaluated to be inadequate in addressing three criteria: (1) Site characterization, (2) ability to monitor the location, and (3) flow paths and 100-foot time of travel. Details of the inadequacies and a description of the information needed to eliminate the inadequacies are included in the report. (USGS)

  14. 'Nothing is so soon forgot as pain': Reading Agony in Adam Smith's The Theory of Moral Sentiments.

    PubMed

    Franson, Craig

    2014-01-01

    Giving a rigorous philosophical explanation to the imagination's role in sympathy, Adam Smith's The Theory of Moral Sentiments became a central text in Romantic aesthetics. It not only justified the age's vogue for making suffering an object of artistic pleasure, it treated suffering's affectivity as the very foundation of society. Depicting agony as a spectacle to be read by others, Smith transformed morality into rhetoric, making human subjects into readers of a sentimentalised, textual world. Yet Smith's work restricted the bonds of sympathy, too, following established distinctions between mind and body that helped him to exclude physical pain from sympathetic response. This essay looks to Smith's context in the overlapping philosophical and medical discourses of the Scottish Enlightenment, exploring his moral theory's resonance with the nerve theories of Robert Whytt and William Cullen, then the leading figures in Scotland's rising medical community. Deepening our understanding of Smith's probable sources, it reframes Smith's intellectual and ideological legacy, foregrounding some of the ambivalent cultural and political implications of Smith's troubling censure of physical pain.

  15. The Moral Dignity of Inductive Method and the Reconciliation of Science and Faith in Adam Sedgwick's Discourse

    NASA Astrophysics Data System (ADS)

    Bellon, Richard

    2012-07-01

    Science's inductive method required patient, humble and self-controlled behavior; Christian revelation demanded the same virtues. The discoveries of science and the truths of scripture would always harmonize as long as both men of science and men of faith conducted themselves in scrupulous accordance with their duty. So ran a central argument in A Discourse on the studies of the university (1833; 5th ed, 1850) by Adam Sedgwick (1785-1873), the longtime professor of geology at the University of Cambridge. This sanctification of the inductive method provided the foundation for a theistic science which (in theory) did not subordinate scientific theory to religious doctrine. This vision provided the foundation for Sedgwick's lifelong crusade against all forms of evolutionary theory. Evolution's impiety, he insisted, resulted from (and exacerbated) a failure to behave inductively. The fact that Sedgwick (in principle if not always in practice) elevated norms of behavior above systems of belief had an important and paradoxical consequence. Even though his personal hatred of evolution never cooled, his Discourse nonetheless provided a dominant model for younger theists to reconcile faith with Charles Darwin's evolutionary theory.

  16. Correlates of benzodiazepine use among a sample of arrestees surveyed through the Arrestee Drug Abuse Monitoring (ADAM) Program.

    PubMed

    Yacoubian, George S

    2003-01-01

    While marijuana and cocaine are the two most prevalent drugs used among arrestee populations, benzodiazepine use has surpassed that of opiates in several jurisdictions across the United States. Despite this proliferation, few scholarly works have focused on benzodiazepine use among individuals under criminal justice supervision. In the present study, chi-square statistics and logistic regression are utilized to identify significant associations between recent benzodiazepine use (as measured by urinalysis), demographic characteristics, and alcohol and other drug (AOD) use among a sample of 862 adult Philadelphia arrestees interviewed in 1997 through the Arrestee Drug Abuse Monitoring (ADAM) Program. Compared to nonusers, benzodiazepine-positive respondents were more likely to be White, to have used alcohol and barbiturates in the three days preceding the interview, and to have tested positive by urinalysis for marijuana, cocaine, opiates, and phencyclidine (PCP). Moreover, logistic regression identified that if an arrestee reported three-day barbiturate use, the odds ratio (OR) of recent benzodiazepine use was more than nine times higher than an arrestee who reported no three-day barbiturate use. Implications for drug surveillance are assessed in light of the current findings.

  17. The Relationship of Dynamical Heterogeneity to the Adam-Gibbs and Random First-Order Transition Theories of Glass Formation

    NASA Astrophysics Data System (ADS)

    Starr, Francis; Douglas, Jack; Sastry, Srikanth

    2013-03-01

    We examine measures of dynamical heterogeneity for a bead-spring polymer melt and test how these scales compare with the scales hypothesized by the Adam and Gibbs (AG) and random first-order transition (RFOT) theories. We show that the time scale of the high-mobility clusters and strings is associated with a diffusive time scale, while the low-mobility particles' time scale relates to a structural relaxation time. The difference of the characteristic times naturally explains the decoupling of diffusion and structural relaxation time scales. We examine the appropriateness of identifying the size scales of mobile particle clusters or strings with the size of cooperatively rearranging regions (CRR) in the AG and RFOT theories. We find that the string size appears to be the most consistent measure of CRR for both the AG and RFOT models. Identifying strings or clusters with the``mosaic'' length of the RFOT model relaxes the conventional assumption that the``entropic droplet'' are compact. We also confirm the validity of the entropy formulation of the AG theory, constraining the exponent values of the RFOT theory. This constraint, together with the analysis of size scales, enables us to estimate the characteristic exponents of RFOT.

  18. High-throughput Protease Activity Cytometry Reveals Dose-dependent Heterogeneity in PMA-mediated ADAM17 Activation†

    PubMed Central

    Wu, Lidan; Claas, Allison M.; Sarkar, Aniruddh; Lauffenburger, Douglas A.; Han, Jongyoon

    2015-01-01

    As key components of autocrine signaling, pericellular proteases, A Disintegrin and Metalloproteinases (ADAMs) in particular, are known to impact the microenvironment of individual cells and have significant implications in various pathological situations including cancer, inflammatory and vascular diseases.1-3 There is great incentive to develop a high-throughput platform for single-cell measurement of pericellular protease activity, as it is essential for studying the heterogeneity of protease response and the corresponding cell behavioral consequences. In this work, we developed a microfluidic platform to simultaneously monitor protease activity of many single cells in a time-dependent manner. This platform isolates individual microwells rapidly on demand and thus allows single-cell activity measurement of both cell-surface and secreted proteases by confining individual cells with diffusive FRET-based substrates. With this platform, we observed dose-dependent heterogeneous protease activation of HepG2 cells treated with phorbol 12-myristate 13-acetate (PMA). To study the temporal behavior of PMA-induced protease response, we monitored the pericellular protease activity of the same single cells during three different time periods and revealed the diversity in the dynamic patterns of single-cell protease activity profile upon PMA stimulation. The unique temporal information of single-cell protease response can help unveil the complicated functional role of pericellular proteases. PMID:25832727

  19. Hydrogeology and analysis of ground-water withdrawal from the Catahoula aquifer system in the Natchez area, Adams County, Mississippi

    USGS Publications Warehouse

    Strom, E.W.; Burt, D.E.; Oakley, W.T.

    1995-01-01

    The city of Natchez, located in Adams County, Mississippi, relies on ground water for public supply and industrial needs. Most public supply and industrial wells are developed in Catahoula Formation sands of Miocene age. In 1991, an investigation began to describe the hydrogeology, analyze the effects of ground-water withdrawal from currently pumped wells, and project the possible effects of increased ground-water withdrawals on water levels in the Catahoula aquifer system within the Natchez area. The study area covers about 80 square miles in Adams County, southwestern Mississippi. The study area contains several aquifers; however, the most important aquifers in terms of water supply are the Mississippi River alluvial aquifer and the Catahoula aquifer system. In the Natchez area, the Catahoula aquifer system consists of three main sand intervals that form the upper, middle, and lower Catahoula aquifers. Ground-water withdrawal from the Catahoula aquifer system in the study area currently (March 1995) is from 24 wells screened in the three aquifers. The current daily rate of withdrawal is about 9.2 million gallons of water per day. Analysis of the effect of ground-water withdrawal from these wells was made using the Theis nonequilibrium equation and applying the principle of superposition. The calculated drawdown surfaces under current conditions indicate cones of depression surrounding the principal wells. In the upper Catahoula sand, most of the drawdown is concentrated about 1 mile east of the downtown Natchez area, where a maximum drawdown of 95x11 feet was calculated. Most of the drawdown in the middle Catahoula sand occurred in the same general vicinity as in the upper sand, with a maximum calculated drawdown of about 113 feet. Drawdown in the lower Catahoula sand was concentrated about 4x11 miles northeast of downtown Natchez, with a maximum calculated drawdown of about 31 feet. Drawdown-surface maps were made using calculations based on current pumping

  20. Molecular structure, configurational entropy and viscosity of silicate melts: link through the Adam and Gibbs theory of viscous flow

    NASA Astrophysics Data System (ADS)

    Le Losq, Charles; Neuville, Daniel R.

    2016-04-01

    The rheological and thermodynamic properties of silicate melts played a crucial role in the formation and the evolution of the Earth. For instance, they influenced the evolution of a plausible primordial magma ocean, and, as a result, the differentiation of the Earth mantle and crust. Further, they control the dynamic of volcanic eruptions. Because of that, modelling the viscosity or the heat capacity of silicate melts is crucial in order to model the physical processes they are involved in. The Adam and Gibbs theory of viscous flow offers a thermodynamic framework that assumes that the viscosity η (Pa s) at a temperature T (K) of a melt can be expressed as: log(η) = A + ----Be--- e T Sconf(T) (1) with Ae a pre-exponential constant related to the viscosity at infinite temperature, Be (J mol‑1) a constant proportional to the potential energy barrier opposed to the cooperative rearrangement of the liquid structure and Sconf(T) (J mol‑1 K‑1) the melt configurational entropy. With expressing Sconf(T) as the sum of the residual entropy of the glass and of the variation in melt configurational heat capacity, it is possible to link existing thermodynamic and viscosity data for melts with various chemical composition, e.g., SiO2, NaAlSi3O8 or CaAl2Si2O8. Further, it also is possible to describe the viscosity variation induced by mixing Ca and Mg or Na and K in silicate melts, under the assumption that such mixing produces an ideal excess entropy of mixing. An interesting point in the Adam and Gibbs framework is that it assumes that viscous flow occurs through the cooperative re-arrangement of molecular sub-regions in the melt. From high temperature 29Si NMR and Raman spectroscopy data, it actually is known that viscous flow occurs because of the cooperative exchange of oxygen atoms between tetrahedral SiO2 units, allowing their motions. Therefore, it is tempting to link such structural knowledge to heat capacity and viscosity data through the use of equation 1. In

  1. Rock property measurements guide interpretation of electromagnetic, magnetic and gravity models at Mts. Adams, Baker, Rainier and St. Helens (Invited)

    NASA Astrophysics Data System (ADS)

    Finn, C.; Bedrosian, P. A.; Horton, R.; Polster, S.

    2010-12-01

    Mt. Adams north of the summit. Alteration at Mt. Baker is restricted to thinner (<300 m) zones beneath Sherman Crater and the Dorr Fumerole Fields. The presence of water not only helps form clay minerals that weaken the edifice but also can reduce the pore pressures, increasing the potential for slope failure. In addition, water with entrained melting ice acts as a lubricant to transform debris avalanches into lahars. The EM data identified water-saturated rocks from the surface to the detection limit (100 - 200 m) in discreet zones at Mt. Rainier and Mt Adams and over the entire summit region at Mt. Baker. At Mt. St. Helens, perched aquifers are identified in the 1980 avalanche deposits as well as in older, thick breccia or avalanche deposits. The modeled distribution of alteration and pore fluids helps identify likely sources for future alteration-related debris flows and clearly shows that debris flow hazard studies on altered volcanoes are greatly enhanced by magnetic, EM and gravity data.

  2. Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams-Oliver Syndrome with Variable Cardiac Anomalies

    PubMed Central

    Southgate, Laura; Sukalo, Maja; Karountzos, Anastasios S.V.; Taylor, Edward J.; Collinson, Claire S.; Ruddy, Deborah; Snape, Katie M.; Dallapiccola, Bruno; Joss, Shelagh; Brancati, Francesco; Digilio, M. Cristina; Graul-Neumann, Luitgard M.; Salviati, Leonardo; Coerdt, Wiltrud; Jacquemin, Emmanuel; Wuyts, Wim; Zenker, Martin

    2015-01-01

    Background Adams-Oliver syndrome (AOS) is a rare disorder characterized by congenital limb defects and scalp cutis aplasia. In a proportion of cases, notable cardiac involvement is also apparent. Despite recent advances in the understanding of the genetic basis of AOS, for the majority of affected subjects the underlying molecular defect remains unresolved. This study aimed to identify novel genetic determinants of AOS. Methods and Results Whole-exome sequencing was performed for 12 probands, each with a clinical diagnosis of AOS. Analyses led to the identification of novel heterozygous truncating NOTCH1 mutations (c.1649dupA and c.6049_6050delTC) in two kindreds in which AOS was segregating as an autosomal dominant trait. Screening a cohort of 52 unrelated AOS subjects, we detected 8 additional unique NOTCH1 mutations, including three de novo amino-acid substitutions, all within the ligand-binding domain. Congenital heart anomalies were noted in 47% (8/17) of NOTCH1-positive probands and affected family members. In leucocyte-derived RNA from subjects harboring NOTCH1 extracellular domain mutations, we observed significant reduction of NOTCH1 expression, suggesting instability and degradation of mutant mRNA transcripts by the cellular machinery. Transient transfection of mutagenized NOTCH1 missense constructs also revealed significant reduction in gene expression. Mutant NOTCH1 expression was associated with down-regulation of the Notch target genes HEY1 and HES1, indicating that NOTCH1-related AOS arises through dysregulation of the Notch signaling pathway. Conclusions These findings highlight a key role for NOTCH1 across a range of developmental anomalies that include cardiac defects, and implicate NOTCH1 haploinsufficiency as a likely molecular mechanism for this group of disorders. PMID:25963545

  3. Elevated plasma-soluble CD16 levels in porcine reproductive and respiratory syndrome virus-infected pigs: correlation with ADAM17-mediated shedding.

    PubMed

    Gu, Weihong; Guo, Longjun; Li, Ren; Niu, Junwei; Luo, Xiaolei; Zhang, Jian; Xu, Yunfei; Tian, Zhijun; Feng, Li; Wang, Yue

    2016-03-01

    Soluble CD16 (sCD16) is closely correlated with chronic diseases in humans. Here, plasma sCD16 levels in pigs were increased by infection with porcine reproductive and respiratory syndrome virus (PRRSV) but not with porcine epidemic diarrhea virus, porcine circovirus type 2 and pseudorabies virus. Of interest, PRRSV attached to blood neutrophils and reduced surface CD16 expression on neutrophils. In vitro data confirmed that PRRSV caused CD16 shedding in neutrophils. Further analyses revealed that ADAM17 was involved in porcine CD16 shedding. Thus, our findings suggest that increase in sCD16 levels may be an indicator of PRRSV infection. PMID:26653711

  4. The relationship of dynamical heterogeneity to the Adam-Gibbs and random first-order transition theories of glass formation.

    PubMed

    Starr, Francis W; Douglas, Jack F; Sastry, Srikanth

    2013-03-28

    We carefully examine common measures of dynamical heterogeneity for a model polymer melt and test how these scales compare with those hypothesized by the Adam and Gibbs (AG) and random first-order transition (RFOT) theories of relaxation in glass-forming liquids. To this end, we first analyze clusters of highly mobile particles, the string-like collective motion of these mobile particles, and clusters of relative low mobility. We show that the time scale of the high-mobility clusters and strings is associated with a diffusive time scale, while the low-mobility particles' time scale relates to a structural relaxation time. The difference of the characteristic times for the high- and low-mobility particles naturally explains the well-known decoupling of diffusion and structural relaxation time scales. Despite the inherent difference of dynamics between high- and low-mobility particles, we find a high degree of similarity in the geometrical structure of these particle clusters. In particular, we show that the fractal dimensions of these clusters are consistent with those of swollen branched polymers or branched polymers with screened excluded-volume interactions, corresponding to lattice animals and percolation clusters, respectively. In contrast, the fractal dimension of the strings crosses over from that of self-avoiding walks for small strings, to simple random walks for longer, more strongly interacting, strings, corresponding to flexible polymers with screened excluded-volume interactions. We examine the appropriateness of identifying the size scales of either mobile particle clusters or strings with the size of cooperatively rearranging regions (CRR) in the AG and RFOT theories. We find that the string size appears to be the most consistent measure of CRR for both the AG and RFOT models. Identifying strings or clusters with the "mosaic" length of the RFOT model relaxes the conventional assumption that the "entropic droplets" are compact. We also confirm the

  5. The relationship of dynamical heterogeneity to the Adam-Gibbs and random first-order transition theories of glass formation

    PubMed Central

    Starr, Francis W.; Douglas, Jack F.; Sastry, Srikanth

    2013-01-01

    We carefully examine common measures of dynamical heterogeneity for a model polymer melt and test how these scales compare with those hypothesized by the Adam and Gibbs (AG) and random first-order transition (RFOT) theories of relaxation in glass-forming liquids. To this end, we first analyze clusters of highly mobile particles, the string-like collective motion of these mobile particles, and clusters of relative low mobility. We show that the time scale of the high-mobility clusters and strings is associated with a diffusive time scale, while the low-mobility particles' time scale relates to a structural relaxation time. The difference of the characteristic times for the high- and low-mobility particles naturally explains the well-known decoupling of diffusion and structural relaxation time scales. Despite the inherent difference of dynamics between high- and low-mobility particles, we find a high degree of similarity in the geometrical structure of these particle clusters. In particular, we show that the fractal dimensions of these clusters are consistent with those of swollen branched polymers or branched polymers with screened excluded-volume interactions, corresponding to lattice animals and percolation clusters, respectively. In contrast, the fractal dimension of the strings crosses over from that of self-avoiding walks for small strings, to simple random walks for longer, more strongly interacting, strings, corresponding to flexible polymers with screened excluded-volume interactions. We examine the appropriateness of identifying the size scales of either mobile particle clusters or strings with the size of cooperatively rearranging regions (CRR) in the AG and RFOT theories. We find that the string size appears to be the most consistent measure of CRR for both the AG and RFOT models. Identifying strings or clusters with the “mosaic” length of the RFOT model relaxes the conventional assumption that the “entropic droplets” are compact. We also confirm

  6. The relationship of dynamical heterogeneity to the Adam-Gibbs and random first-order transition theories of glass formation

    NASA Astrophysics Data System (ADS)

    Starr, Francis W.; Douglas, Jack F.; Sastry, Srikanth

    2013-03-01

    We carefully examine common measures of dynamical heterogeneity for a model polymer melt and test how these scales compare with those hypothesized by the Adam and Gibbs (AG) and random first-order transition (RFOT) theories of relaxation in glass-forming liquids. To this end, we first analyze clusters of highly mobile particles, the string-like collective motion of these mobile particles, and clusters of relative low mobility. We show that the time scale of the high-mobility clusters and strings is associated with a diffusive time scale, while the low-mobility particles' time scale relates to a structural relaxation time. The difference of the characteristic times for the high- and low-mobility particles naturally explains the well-known decoupling of diffusion and structural relaxation time scales. Despite the inherent difference of dynamics between high- and low-mobility particles, we find a high degree of similarity in the geometrical structure of these particle clusters. In particular, we show that the fractal dimensions of these clusters are consistent with those of swollen branched polymers or branched polymers with screened excluded-volume interactions, corresponding to lattice animals and percolation clusters, respectively. In contrast, the fractal dimension of the strings crosses over from that of self-avoiding walks for small strings, to simple random walks for longer, more strongly interacting, strings, corresponding to flexible polymers with screened excluded-volume interactions. We examine the appropriateness of identifying the size scales of either mobile particle clusters or strings with the size of cooperatively rearranging regions (CRR) in the AG and RFOT theories. We find that the string size appears to be the most consistent measure of CRR for both the AG and RFOT models. Identifying strings or clusters with the "mosaic" length of the RFOT model relaxes the conventional assumption that the "entropic droplets" are compact. We also confirm the

  7. The relationship of dynamical heterogeneity to the Adam-Gibbs and random first-order transition theories of glass formation.

    PubMed

    Starr, Francis W; Douglas, Jack F; Sastry, Srikanth

    2013-03-28

    We carefully examine common measures of dynamical heterogeneity for a model polymer melt and test how these scales compare with those hypothesized by the Adam and Gibbs (AG) and random first-order transition (RFOT) theories of relaxation in glass-forming liquids. To this end, we first analyze clusters of highly mobile particles, the string-like collective motion of these mobile particles, and clusters of relative low mobility. We show that the time scale of the high-mobility clusters and strings is associated with a diffusive time scale, while the low-mobility particles' time scale relates to a structural relaxation time. The difference of the characteristic times for the high- and low-mobility particles naturally explains the well-known decoupling of diffusion and structural relaxation time scales. Despite the inherent difference of dynamics between high- and low-mobility particles, we find a high degree of similarity in the geometrical structure of these particle clusters. In particular, we show that the fractal dimensions of these clusters are consistent with those of swollen branched polymers or branched polymers with screened excluded-volume interactions, corresponding to lattice animals and percolation clusters, respectively. In contrast, the fractal dimension of the strings crosses over from that of self-avoiding walks for small strings, to simple random walks for longer, more strongly interacting, strings, corresponding to flexible polymers with screened excluded-volume interactions. We examine the appropriateness of identifying the size scales of either mobile particle clusters or strings with the size of cooperatively rearranging regions (CRR) in the AG and RFOT theories. We find that the string size appears to be the most consistent measure of CRR for both the AG and RFOT models. Identifying strings or clusters with the "mosaic" length of the RFOT model relaxes the conventional assumption that the "entropic droplets" are compact. We also confirm the

  8. ADAM17 and EGFR regulate IL-6 receptor and amphiregulin mRNA expression and release in cigarette smoke-exposed primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD).

    PubMed

    Stolarczyk, Marta; Amatngalim, Gimano D; Yu, Xiao; Veltman, Mieke; Hiemstra, Pieter S; Scholte, Bob J

    2016-08-01

    Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, and epidermal growth factor receptor (EGFR) has been suggested to contribute to chronic obstructive pulmonary disease (COPD) development and progression. The aim of this study was to investigate the role of these proteins in activation of primary bronchial epithelial cells differentiated at the air-liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing cells from COPD patients with non-COPD CS exposure of ALI-PBEC enhanced ADAM17-mediated shedding of the IL-6 receptor (IL6R) and the EGFR agonist amphiregulin (AREG) toward the basolateral compartment, which was more pronounced in cells from COPD patients than in non-COPD controls. CS transiently increased IL6R and AREG mRNA in ALI-PBEC to a similar extent in cultures from both groups, suggesting that posttranslational events determine differential shedding between COPD and non-COPD cultures. We show for the first time by in situ proximity ligation (PLA) that CS strongly enhances interactions of phosphorylated ADAM17 with AREG and IL-6R in an intracellular compartment, suggesting that CS-induced intracellular trafficking events precede shedding to the extracellular compartment. Both EGFR and ADAM17 activity contribute to CS-induced IL-6R and AREG protein shedding and to mRNA expression, as demonstrated using selective inhibitors (AG1478 and TMI-2). Our data are consistent with an autocrine-positive feedback mechanism in which CS triggers shedding of EGFR agonists evoking EGFR activation, in ADAM17-dependent manner, and subsequently transduce paracrine signaling toward myeloid cells and connective tissue. Reducing ADAM17 and EGFR activity could therefore be a therapeutic approach for the tissue remodeling and inflammation observed in COPD. PMID:27561911

  9. Differential Expression of ADAM23, CDKN2A (P16), MMP14 and VIM Associated with Giant Cell Tumor of Bone

    PubMed Central

    Conceição, André Luis Giacometti; Babeto, Erica; Candido, Natalia Maria; Franco, Fernanda Craveiro; de Campos Zuccari, Débora Aparecida Pires; Bonilha, Jane Lopes; Cordeiro, José Antônio; Calmon, Marilia Freitas; Rahal, Paula

    2015-01-01

    Though benign, giant cell tumor of bone (GCTB) can become aggressive and can exhibit a high mitotic rate, necrosis and rarely vascular invasion and metastasis. GCTB has unique histologic characteristics, a high rate of multinucleated cells, a variable and unpredictable growth potential and uncertain biological behavior. In this study, we sought to identify genes differentially expressed in GCTB, thus building a molecular profile of this tumor. We performed quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry and analyses of methylation to identify genes that are putatively associated with GCTB. The expression of the ADAM23 and CDKN2A genes was decreased in GCTB samples compared to normal bone tissue, measured by qPCR. Additionally, a high hypermethylation frequency of the promoter regions of ADAM23 and CDKN2A in GCTB was observed. The expression of the MAP2K3, MMP14, TIMP2 and VIM genes was significantly higher in GCTB than in normal bone tissue, a fact that was confirmed by qPCR and immunohistochemistry. The set of genes identified here furthers our understanding of the molecular basis of GCTB. PMID:26078788

  10. Change over time in brain serotonin transporter binding in major depression: effects of therapy measured with [(123) I]-ADAM SPECT.

    PubMed

    Amsterdam, Jay D; Newberg, Andrew B; Newman, Cory F; Shults, Justine; Wintering, Nancy; Soeller, Irene

    2013-10-01

    Several studies have reported low brain serotonin transporter (SERT) binding in individuals with major depression. We hypothesized that the SERT standardized uptake ratio (SUR) values using [(123) I]-ADAM single photon emission computed tomography would increase in depressed subjects who responded to cognitive behavior therapy (CBT) compared to CBT nonresponders. [(123) I]-ADAM scans were acquired before and after 12 weeks of CBT from 20 depressed subjects and on two occasions 12 weeks apart from 10 nondepressed, healthy volunteers. The primary outcome measure was change over time in SUR values in the midbrain, medial temporal lobe, and basal ganglia regions. Depressed subjects demonstrated low pretreatment mean SUR values that significantly increased over time in the midbrain (P = .011), right medial temporal lobe (P = .008), and left medial temporal lobe (P = .000) regions. Treatment responders showed a significant increase over time in SUR values in left medial temporal lobe (P = .029) and right medial temporal lobe (P = .007) regions. Partial and nonresponder subjects also showed a significant increase over time in SUR values in the left medial temporal region (P = .040) (vs. healthy volunteers), but to a lesser degree. The findings suggest that low pretreatment SERT binding may increase over time in some depressed individuals who experience symptom improvement.

  11. Airborne Magnetic and Electromagnetic Data map Rock Alteration and Water Content at Mount Adams, Mount Baker and Mount Rainier, Washington: Implications for Lahar Hazards and Hydrothermal Systems

    NASA Astrophysics Data System (ADS)

    Finn, C. A.; Deszcz-Pan, M.; Horton, R.; Breit, G.; John, D.

    2007-12-01

    High resolution helicopter-borne magnetic and electromagnetic (EM) data flown over the rugged, ice-covered, highly magnetic and mostly resistive volcanoes of Mount Rainier, Mount Adams and Mount Baker, along with rock property measurements, reveal the distribution of alteration, water and hydrothermal fluids that are essential to evaluating volcanic landslide hazards and understanding hydrothermal systems. Hydrothermally altered rocks, particularly if water saturated, can weaken stratovolcanoes, thereby increasing the potential for catastrophic sector collapses that can lead to far-traveled, destructive debris flows. Intense hydrothermal alteration significantly reduces the magnetization and resistivity of volcanic rock resulting in clear recognition of altered rock by helicopter magnetic and EM measurements. Magnetic and EM data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses of hydrothermally altered rock west of the modern summit of Mount Rainier in the Sunset Amphitheater region, in the central core of Mount Adams north of the summit, and in much of the central cone of Mount Baker. We identify the Sunset Amphitheater region and steep cliffs at the western edge of the central altered zone at Mount Adams as likely sources for future debris flows. In addition, the EM data identified water-saturated rocks in the upper 100-200 m of the three volcanoes. The water-saturated zone could extend deeper, but is beyond the detection limits of the EM data. Water in hydrothermal fluids reacts with the volcanic rock to produce clay minerals. The formation of clay minerals and presence of free water reduces the effective stress, thereby increasing the potential for slope failure, and acts, with entrained melting ice, as a lubricant to transform debris avalanches into lahars. Therefore, knowing the distribution of water is also important for hazard assessments. Finally, modeling requires extremely low

  12. Association of a disintegrin and metalloprotease 33 (ADAM33) gene polymorphisms with the risk of COPD: an updated meta-analysis of 2,644 cases and 4,804 controls.

    PubMed

    Zhou, Deng-Chuan; Zhou, Cheng-Fan; Toloo, Sam; Shen, Tong; Tong, Shi-Lu; Zhu, Qi-Xing

    2015-02-01

    A series of observational studies have been made to investigate the association of the ADAM33 gene polymorphisms with the risk of COPD, but their results were conflicting. Therefore, we performed an updated meta-analysis to quantitatively summarize the associations of ADAM33 gene polymorphisms with the risk of COPD. Thirteen case-control studies referring to nine SNPs were identified: V4 (rs2787094), T+1 (rs2280089), T2 (rs2280090), T1 (rs2280091), S2 (rs528557), S1 (rs3918396), Q-1 (rs612709), F+1 (rs511898) and ST+5 (rs597980). A dominant model (AA+Aa vs. aa), recessive model (AA vs. Aa+aa), additive model (AA vs. aa) and allelic model (A vs. a) were used to evaluate the association of ADAM33 polymorphism with the risk of COPD. The results indicated that significant associations were found for ADAM33 T1, T2, S1, Q-1, F+1 and ST+5 polymorphisms associated with the risk of COPD in different populations. However, no significant associations were found for V4, T+1 and S2 polymorphisms with the risk of COPD in all genetic models, even in the subgroup analysis by ethnicity. This meta-analysis provided evidence that the ADAM33 T1, T2, S1, Q-1, F+1 and ST+5 six locus polymorphisms association with the risk of COPD. Furthermore, T2, Q-1 and ST+5 indicated an association with the risk of COPD in the European populations, whereas T1, T2, S1, F+1 and Q-1 indicated an association with the risk of COPD in the Asian populations. PMID:25280544

  13. Essential-oil variability of Juniperus deltoides R.P.Adams along the east Adriatic coast - how many chemotypes are there?

    PubMed

    Rajčević, Nemanja; Janaćković, Peđa; Dodoš, Tanja; Tešević, Vele; Marin, Petar D

    2015-01-01

    The composition of the essential oils isolated from twigs of ten Juniperus deltoides R.P. Adams populations from the east Adriatic coast was determined by GC-FID and GC/MS analyses. Altogether, 169 compounds were identified, representing 95.6-98.4% of the total oil composition. The oils were dominated by monoterpenes (average content of 61.6%), which are characteristic oil components of species of the Juniperus section. Two monoterpenes, α-pinene and limonene, were the dominant constituents, comprising on average 46.78% of the essential oils. Statistical methods were deployed to determine the diversity of the terpene classes and the common terpenes between the investigated populations. These statistical analyses revealed the existence of three chemotypes within all populations, i.e., a α-pinene, limonene, and limonene/α-pinene type.

  14. Synthesis, Anti-HIV Activity, and Metabolic Stability of New Alkenyldiarylmethane (ADAM) HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

    PubMed Central

    Deng, Bo-Liang; Hartman, Tracy L.; Buckheit, Robert W.; Pannecouque, Christophe; De Clercq, Erik; Fanwick, Phillip E.; Cushman, Mark

    2008-01-01

    Non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) are part of the combination therapy currently used to treat HIV infection. Based on analogy with known HIV-1 NNRT inhibitors, eighteen novel alkenyldiarylmethanes (ADAMs) containing 5-chloro-2-methoxyphenyl, 3-cyanophenyl or 3-fluoro-5-trifluoromethylphenyl groups were synthesized and evaluated as HIV inhibitors. Their stabilities in rat plasma have also been investigated. Although introducing 5-chloro-2-methoxyphenyl, or 3-fluoro-5-trifluoromethylphenyl groups into alkenyldiarylmethanes does not maintain the antiviral potency, the structural modification of alkenyldiarylmethanes with a 3-cyanophenyl substituent can be made without a large decrease in activity. The oxazolidinonyl group was introduced into the alkenyldiarylmethane framework and found to confer enhanced metabolic stability in rat plasma. PMID:16162014

  15. The up-right/down-left advantage occurs for both participant- and computer-paced conditions: an empirical observation on Adam, Boon, Paas, and Umiltà (1998).

    PubMed

    Proctor, R W; Cho, Y S

    2001-04-01

    When up and down stimuli are mapped to left and right keypresses or "left" and "right" vocalizations in a 2-choice reaction task, performance is often better with the up-right/down-left mapping than with the opposite mapping. J. J. Adam, B. Boon, F. G. W. C. Paas, and C. Umiltà (1998) presented evidence that the up-right/down-left advantage is obtained when trials are participant paced but not when they are computer paced. In all, 3 experiments are reported that show no difference in magnitude of the up-right/down-left advantage between computer-paced and participant-paced conditions. The advantage was eliminated, however, in Experiment 3 when a response deadline was imposed. Response speed, rather than participant or computer pacing of trials, is crucial.

  16. Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study.

    PubMed

    Shih, Jui-Hu; Ma, Kuo-Hsing; Chen, Chien-Fu F; Cheng, Cheng-Yi; Pao, Li-Heng; Weng, Shao-Ju; Huang, Yuahn-Sieh; Shiue, Chyng-Yann; Yeh, Ming-Kung; Li, I-Hsun

    2016-01-01

    The misuse of 3,4-methylenedioxymethamphetamine (MDMA) has drawn a growing concern worldwide for its psychophysiological impacts on humans. MDMA abusers are often accompanied by long-term serotonergic neurotoxicity, which is associated with reduced density of cerebral serotonin transporters (SERT) and depressive disorders. Resveratrol (RSV) is a natural polyphenolic phytoalexin that has been known for its antidepressant and neuroprotective effects. However, biological targets of RSV as well as its neuroprotective effects against MDMA remained largely unknown. In this study, we examined binding potency of RSV and MDMA to SERT using small-animal positron emission tomography (PET) with the SERT radioligand, N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) and investigated the protection of RSV against the acute and long-term adverse effects of MDMA. We found that RSV exhibit binding potentials to SERT in vivo in a dose-dependent manner with variation among brain regions. When the MDMA-treated rats (10mg/kg, s.c.) were co-injected with RSV (20mg/kg, i.p.) twice daily for 4 consecutive days, MDMA-induced acute elevation in plasma corticosterone was significantly reduced. Further, 4-[(18)F]-ADAM PET imaging revealed that RSV protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus 2 weeks following the co-treatment. The PET data were comparable to the observation from the forced swim test that RSV sufficiently ameliorated the depressive-like behaviors of the MDMA-treated rats. Together, these findings suggest that RSV is a potential antidepressant and may confer protection against neurobiological and behavioral changes induced by MDMA. PMID:26612383

  17. Implication of TNF-alpha convertase (TACE/ADAM17) in inducible nitric oxide synthase expression and inflammation in an experimental model of colitis.

    PubMed

    Colón, A L; Menchén, L A; Hurtado, O; De Cristóbal, J; Lizasoain, I; Leza, J C; Lorenzo, P; Moro, M A

    2001-12-21

    Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine which is shed in its soluble form by a disintegrin and metalloproteinase (ADAM) called TNF-alpha convertase (TACE; ADAM17). TNF-alpha plays a role in inflammatory bowel disease (IBD) and is involved in the expression of inducible nitric oxide synthase (iNOS) which has also been implicated in IBD. The study was designed to investigate whether colitis induced by trinitrobenzene sulphonic acid (TNBS) in rats produces an increase in TACE activity and/or expression and whether its pharmacological inhibition reduces TNF-alpha levels, iNOS expression and colonic damage in this model. TNBS (30 mg in 0.4 ml of 50% ethanol) was instilled into the colon of female Wistar rats. Saline or TACE inhibitor BB1101 (10 mg/kg/day) was administered intraperitoneally 5 days after TNBS instillation. On day 10, colons were removed and assessed for pathological score, myeloperoxidase (MPO), NO synthase (NOS), TACE enzymatic activity and protein levels, colonic TNF-alpha and NOx- levels. Instillation of TNBS caused an increase in TACE activity and expression and the release of TNF-alpha. TNBS also resulted in iNOS expression and colonic damage. BB1101 blocked TNBS-induced increase in TACE activity, TNF-alpha release and iNOS expression. Concomitantly, BB1101 ameliorated TNBS-induced colonic damage and inflammation. TNBS causes TNF-alpha release by an increase in TACE activity and expression and this results in the expression of iNOS and subsequent inflammation, suggesting that TACE inhibition may prove useful as a therapeutic means in IBD. PMID:11884025

  18. Ground-water resources of the South Platte River Basin in western Adams and southwestern Weld Counties, Colorado

    USGS Publications Warehouse

    Smith, Rex O.; Schneider, P.A.; Petri, Lester R.

    1964-01-01

    The area described in this report consists of about 970 square miles in western Adams and southwestern Weld Counties in northeastern Colorado. It includes that part of the South Platte River valley between Denver and Kuner, Colo., all of Beebe Draw, and the lower part of the valley of Box Elder Creek. The stream-valley lowlands are separated by rolling uplands. The climate is semiarid, the normal annual precipitation being about 13 inches; thus, irrigation is essential for stable agricultural development. The area contains about 220,000 acres of irrigated land in the stream valleys. Most of the remaining 400,000 acres of land is used for dry farming or grazing because it lacks irrigation water. Most of the lowlands were brought under irrigation with surface water during the early 1900's, and now nearly all the surface water in the area is appropriated for irrigation within and downstream from the area. Because the natural flow of the streams is sometimes less than the demand for water, ground water is used to supplement the surface-water supply. Wells, drilled chiefly since 1930, supply the supplemental water and in some places are the sole supply for irrigation use. Rocks exposed in the area are of sedimentary origin and range in age from Lato Cretaceous to Recent. Those that are consolidated, called 'bedrock' in this report, consist of the Fox Hills sandstone and the Laramie and Arapahoe formations, all of Late Cretaceous age, and the Denver formation and Dawson arkose of Late Cretaceous and Tertiary age. The surface of the bedrock was shaped by ancestral streams, the valleys of which are reflected by the present surface topography. Dune sand, slope wash, and thin upland deposits of Quaternary age mantle the bedrock in the divide areas, and stream deposits ranging in thickness from 0 to about 125 feet partly fill the ancestral valleys. The valley-fill deposits consist of beds and lenses of clay, silt, sand, gravel, cobbles, and boulders. Abundant supplies of

  19. Discriminating assimilants and decoupling deep- vs. shallow-level crystal records at Mount Adams using 238U- 230Th disequilibria and Os isotopes

    NASA Astrophysics Data System (ADS)

    Jicha, Brian R.; Johnson, Clark M.; Hildreth, Wes; Beard, Brian L.; Hart, Garret L.; Shirey, Steven B.; Singer, Brad S.

    2009-01-01

    A suite of 23 basaltic to dacitic lavas erupted over the last 350 kyr from the Mount Adams volcanic field has been analyzed for U-Th isotope compositions to evaluate the roles of mantle versus crustal components during magma genesis. All of the lavas have ( 230Th/ 238U) > 1 and span a large range in ( 230Th/ 232Th) ratios, and most basalts have higher ( 230Th/ 232Th) ratios than andesites and dacites. Several of the lavas contain antecrysts (crystals of pre-existing material), yet internal U-Th mineral isochrons from six of seven lavas are indistinguishable from their eruption ages. This indicates a relatively brief period of time between crystal growth and eruption for most of the phenocrysts (olivine, clinopyroxene, plagioclase, magnetite) prior to eruption. One isochron gave a crystallization age that is ~ 20-25 ka older than its corresponding eruptive age, and is interpreted to reflect mixing of older and juvenile crystals or a protracted period of magma storage in the crust. Much of the eruptive volume since 350 ka consists of lavas that have small to moderate 230Th excesses (2-16%), which are likely inherited from melting of a garnet-bearing intraplate ("OIB-like") mantle source. Following melt generation and subsequent migration through the upper mantle, most Mt. Adams magmas interacted with young, mafic lower crust, as indicated by 187Os/ 188Os ratios that are substantially more radiogenic than the mantle or those expected via mixing of subducted material and the mantle wedge. Moreover, Os-Th isotope variations suggest that unusually large 230Th excesses (25-48%) and high 187Os/ 188Os ratios in some peripheral lavas reflect assimilation of small degree partial melts of pre-Quaternary basement that had residual garnet or Al-rich clinopyroxene. Despite the isotopic evidence for lower crustal assimilation, these processes are not generally recorded in the erupted phenocrysts, indicating that the crystal record of the deep-level 'cryptic' processes has been

  20. Discriminating assimilants and decoupling deep- vs. shallow-level crystal records at Mount Adams using 238U-230Th disequilibria and Os isotopes

    USGS Publications Warehouse

    Jicha, B.R.; Johnson, C.M.; Hildreth, W.; Beard, B.L.; Hart, G.L.; Shirey, S.B.; Singer, B.S.

    2009-01-01

    A suite of 23 basaltic to dacitic lavas erupted over the last 350??kyr from the Mount Adams volcanic field has been analyzed for U-Th isotope compositions to evaluate the roles of mantle versus crustal components during magma genesis. All of the lavas have (230Th/238U) > 1 and span a large range in (230Th/232Th) ratios, and most basalts have higher (230Th/232Th) ratios than andesites and dacites. Several of the lavas contain antecrysts (crystals of pre-existing material), yet internal U-Th mineral isochrons from six of seven lavas are indistinguishable from their eruption ages. This indicates a relatively brief period of time between crystal growth and eruption for most of the phenocrysts (olivine, clinopyroxene, plagioclase, magnetite) prior to eruption. One isochron gave a crystallization age that is ~ 20-25??ka older than its corresponding eruptive age, and is interpreted to reflect mixing of older and juvenile crystals or a protracted period of magma storage in the crust. Much of the eruptive volume since 350??ka consists of lavas that have small to moderate 230Th excesses (2-16%), which are likely inherited from melting of a garnet-bearing intraplate ("OIB-like") mantle source. Following melt generation and subsequent migration through the upper mantle, most Mt. Adams magmas interacted with young, mafic lower crust, as indicated by 187Os/188Os ratios that are substantially more radiogenic than the mantle or those expected via mixing of subducted material and the mantle wedge. Moreover, Os-Th isotope variations suggest that unusually large 230Th excesses (25-48%) and high 187Os/188Os ratios in some peripheral lavas reflect assimilation of small degree partial melts of pre-Quaternary basement that had residual garnet or Al-rich clinopyroxene. Despite the isotopic evidence for lower crustal assimilation, these processes are not generally recorded in the erupted phenocrysts, indicating that the crystal record of the deep-level 'cryptic' processes has been

  1. DigitSeis: A New Digitization Software and its Application to the Harvard-Adam Dziewoński Observatory Collection

    NASA Astrophysics Data System (ADS)

    Bogiatzis, P.; Altoé, I. L.; Karamitrou, A.; Ishii, M.; Ishii, H.

    2015-12-01

    DigitSeis is a new open-source, interactive digitization software written in MATLAB that converts digital, raster images of analog seismograms to readily usable, discretized time series using image processing algorithms. DigitSeis automatically identifies and corrects for various geometrical distortions of seismogram images that are acquired through the original recording, storage, and scanning procedures. With human supervision, the software further identifies and classifies important features such as time marks and notes, corrects time-mark offsets from the main trace, and digitizes the combined trace with an analysis to obtain as accurate timing as possible. Although a large effort has been made to minimize the human input, DigitSeis provides interactive tools for challenging situations such as trace crossings and stains in the paper. The effectiveness of the software is demonstrated with the digitization of seismograms that are over half a century old from the Harvard-Adam Dziewoński observatory that is still in operation as a part of the Global Seismographic Network (station code HRV and network code IU). The spectral analysis of the digitized time series shows no spurious features that may be related to the occurrence of minute and hour marks. They also display signals associated with significant earthquakes, and a comparison of the spectrograms with modern recordings reveals similarities in the background noise.

  2. Recessive mutations in DOCK6, encoding the guanidine nucleotide exchange factor DOCK6, lead to abnormal actin cytoskeleton organization and Adams-Oliver syndrome.

    PubMed

    Shaheen, Ranad; Faqeih, Eissa; Sunker, Asma; Morsy, Heba; Al-Sheddi, Tarfa; Shamseldin, Hanan E; Adly, Nouran; Hashem, Mais; Alkuraya, Fowzan S

    2011-08-12

    Adams-Oliver syndrome (AOS) is defined by the combination of aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLD). It is usually inherited as an autosomal-dominant trait, but autosomal-recessive inheritance has also been documented. In an individual with autosomal-recessive AOS, we combined autozygome analysis with exome sequencing to identify a homozygous truncating mutation in dedicator of cytokinesis 6 gene (DOCK6) which encodes an atypical guanidine exchange factor (GEF) known to activate two members of the Rho GTPase family: Cdc42 and Rac1. Another homozygous truncating mutation was identified upon targeted sequencing of DOCK6 in an unrelated individual with AOS. Consistent with the established role of Cdc42 and Rac1 in the organization of the actin cytoskeleton, we demonstrate a cellular phenotype typical of a defective actin cytoskeleton in patient cells. These findings, combined with a Dock6 expression profile that is consistent with an AOS phenotype as well as the very recent demonstration of dominant mutations of ARHGAP31 in AOS, establish Cdc42 and Rac1 as key molecules in the pathogenesis of AOS and suggest that other regulators of these Rho GTPase proteins might be good candidates in the quest to define the genetic spectrum of this genetically heterogeneous condition.

  3. Phase change alloy viscosities down to Tg using Adam-Gibbs-equation fittings to excess entropy data: A fragile-to-strong transition

    NASA Astrophysics Data System (ADS)

    Wei, Shuai; Lucas, Pierre; Angell, C. Austen

    2015-07-01

    A striking anomaly in the viscosity of Te85Ge15 alloys noted by Greer and coworkers from the work of Neumann et al. is reminiscent of the equally striking comparison of liquid tellurium and water anomalies documented long ago by Kanno et al. In view of the power laws that are used to fit the data on water, we analyze the data on Te85Ge15 using the Speedy-Angell power-law form, and find a good account with a singularity Ts only 25 K below the eutectic temperature. However, the heat capacity data in this case are not diverging, but instead exhibit a sharp maximum like that observed in fast cooling in the Molinero-Moore model of water. Applying the Adam-Gibbs viscosity equation to these calorimetric data, we find that there must be a fragile-to-strong liquid transition at the heat capacity peak temperature, and then predict the "strong" liquid course of the viscosity down to Tg at 406 K (403.6 K at 20 K min-1 in this study). Since crystallization can be avoided by moderately fast cooling in this case, we can check the validity of the extrapolation by making a direct measurement of fragility at Tg, using differential scanning calorimetric techniques, and then comparing with the value from the extrapolated viscosity at Tg. The agreement is encouraging, and prompts discussion of relations between water and phase change alloy anomalies.

  4. Recessive Mutations in DOCK6, Encoding the Guanidine Nucleotide Exchange Factor DOCK6, Lead to Abnormal Actin Cytoskeleton Organization and Adams-Oliver Syndrome

    PubMed Central

    Shaheen, Ranad; Faqeih, Eissa; Sunker, Asma; Morsy, Heba; Al-Sheddi, Tarfa; Shamseldin, Hanan E.; Adly, Nouran; Hashem, Mais; Alkuraya., Fowzan S.

    2011-01-01

    Adams-Oliver syndrome (AOS) is defined by the combination of aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLD). It is usually inherited as an autosomal-dominant trait, but autosomal-recessive inheritance has also been documented. In an individual with autosomal-recessive AOS, we combined autozygome analysis with exome sequencing to identify a homozygous truncating mutation in dedicator of cytokinesis 6 gene (DOCK6) which encodes an atypical guanidine exchange factor (GEF) known to activate two members of the Rho GTPase family: Cdc42 and Rac1. Another homozygous truncating mutation was identified upon targeted sequencing of DOCK6 in an unrelated individual with AOS. Consistent with the established role of Cdc42 and Rac1 in the organization of the actin cytoskeleton, we demonstrate a cellular phenotype typical of a defective actin cytoskeleton in patient cells. These findings, combined with a Dock6 expression profile that is consistent with an AOS phenotype as well as the very recent demonstration of dominant mutations of ARHGAP31 in AOS, establish Cdc42 and Rac1 as key molecules in the pathogenesis of AOS and suggest that other regulators of these Rho GTPase proteins might be good candidates in the quest to define the genetic spectrum of this genetically heterogeneous condition. PMID:21820096

  5. Serotonin transporter binding of [123I]ADAM in bulimic women, their healthy twin sisters, and healthy women: a SPET study

    PubMed Central

    Koskela, Anu K; Keski-Rahkonen, Anna; Sihvola, Elina; Kauppinen, Tomi; Kaprio, Jaakko; Ahonen, Aapo; Rissanen, Aila

    2007-01-01

    Background Bulimia Nervosa (BN) is believed to be caused by an interaction of genetic and environmental factors. Previous studies support the existence of a bulimia-related endophenotype as well as disturbances in serotonin (5-HT) transmission. We studied serotonin transporter (SERT) binding in BN, and to investigate the possibility of a SERT-related endophenotype for BN, did this in a sample of female twins. We hypothesized clearly reduced SERT binding in BN women as opposed to healthy women, and intermediate SERT binding in unaffected co-twins. Methods We studied 13 female twins with BN (9 with purging and 4 with non-purging BN) and 25 healthy women, including 6 healthy twin sisters of BN patients and 19 women from 10 healthy twin pairs. [123I]ADAM, a selective SERT radioligand for single photon emission tomography (SPET) imaging, was used to assess SERT availability in the midbrain and the thalamus. Results No differences in SERT binding were evident when comparing the BN women, their unaffected co-twins and the healthy controls (p = 0.14). The healthy sisters of the BN patients and the healthy control women had similar SERT binding in both brain regions. In a post hoc subgroup analysis, the purging bulimics had higher SERT binding than the healthy women in the midbrain (p = 0.03), but not in the thalamus. Conclusion Our finding of increased SERT binding in the midbrain in the purging BN women raises the possibility that this subgroup of bulimics might differ in serotonergic function from the non-purging ones. The similarity of the unaffected co-twins and the healthy controls doesn't support our initial assumption of a SERT-related endophenotype for BN. Due to the small sample size, our results need to be interpreted with caution and verified in a larger sample. PMID:17511889

  6. Phase change alloy viscosities down to T{sub g} using Adam-Gibbs-equation fittings to excess entropy data: A fragile-to-strong transition

    SciTech Connect

    Wei, Shuai; Lucas, Pierre; Angell, C. Austen

    2015-07-21

    A striking anomaly in the viscosity of Te{sub 85}Ge{sub 15} alloys noted by Greer and coworkers from the work of Neumann et al. is reminiscent of the equally striking comparison of liquid tellurium and water anomalies documented long ago by Kanno et al. In view of the power laws that are used to fit the data on water, we analyze the data on Te{sub 85}Ge{sub 15} using the Speedy-Angell power-law form, and find a good account with a singularity T{sub s} only 25 K below the eutectic temperature. However, the heat capacity data in this case are not diverging, but instead exhibit a sharp maximum like that observed in fast cooling in the Molinero-Moore model of water. Applying the Adam-Gibbs viscosity equation to these calorimetric data, we find that there must be a fragile-to-strong liquid transition at the heat capacity peak temperature, and then predict the 'strong' liquid course of the viscosity down to T{sub g} at 406 K (403.6 K at 20 K min{sup −1} in this study). Since crystallization can be avoided by moderately fast cooling in this case, we can check the validity of the extrapolation by making a direct measurement of fragility at T{sub g}, using differential scanning calorimetric techniques, and then comparing with the value from the extrapolated viscosity at T{sub g}. The agreement is encouraging, and prompts discussion of relations between water and phase change alloy anomalies.

  7. FOREWORD: Foreword from Peter Adams Foreword from Peter Adams

    NASA Astrophysics Data System (ADS)

    Adams, Peter D.

    2009-11-01

    As part of this twentieth anniversary special issue I was asked to write a few words about Richard Palmer, the one permanent fixture on the journal over its twenty year history. Richard and I go back a (very) long way! He began his career at IOP Publishing in Bristol in 1971 while my publishing career with the American Physical Society began a little earlier, located at Brookhaven National Laboratory on Long Island NY. Since then, and for nearly forty years we have met often, if irregularly, at many locations throughout the world. As members of two very strong physics organizations we were clearly in competition with each other to seek out and publish the best physics research. At the same time we frequently exchanged experiences and policy ideas for dealing with serious violations of scientific ethical standards and how academic society-run journals can best serve the general scientific community. Overall my relationship with Richard has been a most rewarding one and I shall miss his opinions and sage advice. Richard: Compatriot; competitor; collaborator; I salute you!

  8. Homozygous loss of ADAM3A revealed by genome-wide analysis of pediatric high-grade glioma and diffuse intrinsic pontine gliomas

    PubMed Central

    Barrow, Jennifer; Adamowicz-Brice, Martyna; Cartmill, Maria; MacArthur, Donald; Lowe, James; Robson, Keith; Brundler, Marie-Anne; Walker, David A.; Coyle, Beth; Grundy, Richard

    2011-01-01

    Overall, pediatric high-grade glioma (pHGG) has a poor prognosis, in part due to the lack of understanding of the underlying biology. High-resolution 244 K oligo array comparative genomic hybridization (CGH) was used to analyze DNA from 38 formalin-fixed paraffin-embedded predominantly pretreatment pHGG samples, including 13 diffuse intrinsic pontine gliomas (DIPGs). The patterns of gains and losses were distinct from those seen in HGG arising in adults. In particular, we found 1q gain in up to 27% of our cohort compared with 9% reported in adults. A total of 13% had a balanced genetic profile with no large-scale copy number alterations. Homozygous loss at 8p12 was seen in 6 of 38 (16%) cases of pHGG. This novel deletion, which includes the ADAM3A gene, was confirmed by quantitative real-time PCR (qPCR). Loss of CDKN2A/CDKN2B in 4 of 38 (10%) samples by oligo array CGH was confirmed by fluorescent in situ hybridization on tissue microarrays and was restricted to supratentorial tumors. Only ∼50% of supratentorial tumors were positive for CDKN2B expression by immunohistochemistry (IHC), while ∼75% of infratentorial tumors were positive for CDKN2B expression (P = 0.03). Amplification of the 4q11–13 region was detected in 8% of cases and included PDGFRA and KIT, and subsequent qPCR analysis was consistent with the amplification of PDGFRA. MYCN amplification was seen in 5% of samples being significantly associated with anaplastic astrocytomas (P= 0.03). Overall, DIPG shared similar spectrum of changes to supratentorial HGG with some notable differences, including high-frequency loss of 17p and 14q and lack of CDKN2A/CDKN2B deletion. Informative genetic data providing insight into the underlying biology and potential therapeutic possibilities can be generated from archival tissue and typically small biopsies from DIPG. Our findings highlight the importance of obtaining pretreatment samples. PMID:21138945

  9. Identification of an ADAM17 cleavage region in human CD16 (FcγRIII) and the engineering of a non-cleavable version of the receptor in NK cells.

    PubMed

    Jing, Yawu; Ni, Zhenya; Wu, Jianming; Higgins, LeeAnn; Markowski, Todd W; Kaufman, Dan S; Walcheck, Bruce

    2015-01-01

    CD16a and CD16b are IgG Fc receptors expressed by human natural killer (NK) cells and neutrophils, respectively. Both CD16 isoforms undergo a rapid down-regulation in expression by ADAM17-mediated proteolytic cleavage upon cell activation by various stimuli. We examined soluble CD16 released from activated NK cells and neutrophils by mass spectrometric analysis, and identified three separate cleavage sites in close proximity at P1/P1' positions alanine195/valine196, valine196/serine197, and threonine198/isoleucine199, revealing a membrane proximal cleavage region in CD16. Substitution of the serine at position 197 in the middle of the cleavage region for a proline (S197P) effectively blocked CD16a and CD16b cleavage in cell-based assays. We also show that CD16a/S197P was resistant to cleavage when expressed in the human NK cell line NK92 and primary NK cells derived from genetically-engineered human induced pluripotent stem cells. CD16a is a potent activating receptor and despite blocking CD16a shedding, the S197P mutation did not disrupt IgG binding by the receptor or its activation of NK92 cells by antibody-treated tumor cells. Our findings provide further characterization of CD16 cleavage by ADAM17 and they demonstrate that a non-cleavable version of CD16a can be expressed in engineered NK cells.

  10. Interplay of metabolism and transport in determining oral drug absorption and gut wall metabolism: a simulation assessment using the "Advanced Dissolution, Absorption, Metabolism (ADAM)" model.

    PubMed

    Darwich, A S; Neuhoff, S; Jamei, M; Rostami-Hodjegan, A

    2010-11-01

    systematic variation of drug characteristics, in accordance with the Biopharmaceutics Classification System (BCS) within one of the most physiological models of oral drug absorption currently available, respectively ADAM. Variables studied included the intrinsic clearance (CLint) and the Michaelis-Menten Constant (Km) for CYP3A4 and P-gp (C(Lint-CYP3A4) and K(m-CYP3A4), CL(int-P-gp) and K(m-P-gp)). The impact of CYP3A4 and P-gp intracellular topography were not investigated since a well-stirred enterocyte is assumed within ADAM. An increased CLint-CYP3A4 resulted in a reduced F(G) whereas an increase in C(Lint-P-gp) resulted in a reduced F(a), but interestingly decreased F(G) too. The reduction in FG was limited to certain conditions and was modest. Non-linear relationships between various parameters determining the permeability (e.g. P(app), C(Lint-P-gp,) and K(m-P-gp)) and gut wall metabolism (e.g. C(Lint-CYP3A4,) K(m-CYP3A4)) resulted in disproportionate changes in F(G) compared to the magnitude of singular effects. The results suggest that P-gp efflux decreases enterocytic drug concentration for drugs given at reasonably high dose which possess adequate passive permeability (high P(app)), by de-saturating CYP3A4 in the gut resulting in a lower F(G). However, these findings were observed only in a very limited area of the parameters space matching very few therapeutic drugs (a group with very high metabolism, high turn-over by efflux transporters and low F(a)). The systematic approach in this study enabled us to recognise the combination of parameters values where the potential interplay between metabolising enzymes and efflux transporters is expected to be highest, using a realistic range of parameter values taken from an intensive literature search.

  11. Success, Succession, and Adam Smith

    ERIC Educational Resources Information Center

    Woodwell, G. M.

    1974-01-01

    Offers a contemporary analysis of the interaction of man and the rest of the biota. Suggests that the dependence of man on nature is, more than the crisis of energy and world economics, the emergent scientific and political issue of the next years. (JR)

  12. Definition of peptide inhibitors from a synthetic peptide library by targeting gelatinase B/matrix metalloproteinase-9 (MMP-9) and TNF-α converting enzyme (TACE/ADAM-17).

    PubMed

    Qiu, Zheng; Yan, Ming; Li, Qian; Liu, Datao; Van den Steen, Philippe E; Wang, Min; Opdenakker, Ghislain; Hu, Jialiang

    2012-08-01

    Gelatinase B/matrix metalloproteinase-9 (MMP-9) is a regulatory and effector metalloproteinase in inflammation. TNF-α is an important proinflammatory cytokine and is released by the action of a Zn(2+)-containing converting enzyme (TACE/ADAM-17). Both metallo-enzymes play important roles during the development of shock syndromes. Combinatorial chemical synthesis and subsequent library deconvolution were previously used to define a peptide inhibitor (Regasepin1) acting, almost to the same degree, on neutrophil collagenase/MMP-8 and MMP-9 in vitro, and protecting mice against lethal endotoxinemia in vivo. We have now extended this approach by incorporating D-form amino acids and residues preferred by TACE. A new peptide library was designed and synthesized, and by deconvolution new peptide inhibitors were defined. These included a TACE-specific inhibitor, an MMP-9- specific inhibitor, and inhibitors for both enzymes.

  13. Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

    PubMed Central

    Yeh, Yi-Wei; Ho, Pei-Shen; Kuo, Shin-Chang; Chen, Chun-Yen; Liang, Chih-Sung; Yen, Che-Hung; Huang, Chang-Chih; Ma, Kuo-Hsing; Shiue, Chyng-Yann; Huang, Wen-Sheng; Shyu, Jia-Fwu; Wan, Fang-Jung; Lu, Ru-Band

    2015-01-01

    Background: Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants. Methods: We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more. Results: Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders. Conclusions: The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD. PMID:25568284

  14. Geographic information system datasets of regolith-thickness data, regolith-thickness contours, raster-based regolith thickness, and aquifer-test and specific-capacity data for the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado

    USGS Publications Warehouse

    Arnold, L. Rick

    2010-01-01

    These datasets were compiled in support of U.S. Geological Survey Scientific-Investigations Report 2010-5082-Hydrogeology and Steady-State Numerical Simulation of Groundwater Flow in the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. The datasets were developed by the U.S. Geological Survey in cooperation with the Lost Creek Ground Water Management District and the Colorado Geological Survey. The four datasets are described as follows and methods used to develop the datasets are further described in Scientific-Investigations Report 2010-5082: (1) ds507_regolith_data: This point dataset contains geologic information concerning regolith (unconsolidated sediment) thickness and top-of-bedrock altitude at selected well and test-hole locations in and near the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. Data were compiled from published reports, consultant reports, and from lithologic logs of wells and test holes on file with the U.S. Geological Survey Colorado Water Science Center and the Colorado Division of Water Resources. (2) ds507_regthick_contours: This dataset consists of contours showing generalized lines of equal regolith thickness overlying bedrock in the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. Regolith thickness was contoured manually on the basis of information provided in the dataset ds507_regolith_data. (3) ds507_regthick_grid: This dataset consists of raster-based generalized thickness of regolith overlying bedrock in the Lost Creek Designated Ground Water Basin, Weld, Adams, and Arapahoe Counties, Colorado. Regolith thickness in this dataset was derived from contours presented in the dataset ds507_regthick_contours. (4) ds507_welltest_data: This point dataset contains estimates of aquifer transmissivity and hydraulic conductivity at selected well locations in the Lost Creek Designated Ground Water Basin, Weld, Adams, and

  15. Quantitative prediction of formulation-specific food effects and their population variability from in vitro data with the physiologically-based ADAM model: a case study using the BCS/BDDCS Class II drug nifedipine.

    PubMed

    Patel, Nikunjkumar; Polak, Sebastian; Jamei, Masoud; Rostami-Hodjegan, Amin; Turner, David B

    2014-06-16

    Quantitative prediction of food effects (FE) upon drug pharmacokinetics, including population variability, in advance of human trials may help with trial design by optimising the number of subjects and sampling times when a clinical study is warranted or by negating the need for conduct of clinical studies. Classification and rule-based systems such as the BCS and BDDCS and statistical QSARs are widely used to anticipate the nature of FE in early drug development. However, their qualitative rather than quantitative nature makes them less appropriate for assessing the magnitude of FE. Moreover, these approaches are based upon drug properties alone and are not appropriate for estimating potential formulation-specific FE on modified or controlled release products. In contrast, physiologically-based mechanistic models can consider the scope and interplay of a range of physiological changes after food intake and, in combination with appropriate in vitro drug- and formulation-specific data, can make quantitative predictions of formulation-specific FE including the inter-individual variability of such effects. Herein the Advanced Dissolution, Absorption and Metabolism (ADAM) model is applied to the prediction of formulation-specific FE for BCS/BDDCS Class II drug and CYP3A4 substrate nifedipine using as far as possible only in vitro data. Predicted plasma concentration profiles of all three studied formulations under fasted and fed states are within 2-fold of clinically observed profiles. The % prediction error (%PE) in fed-to-fasted ratio of Cmax and AUC were less than 5% for all formulations except for the Cmax of Nifedicron (%PE=-29.6%). This successful case study should help to improve confidence in the use of mechanistic physiologically-based models coupled with in vitro data for the anticipation of FE in advance of in vivo studies. However, it is acknowledged that further studies with drugs/formulations exhibiting a wide range of properties are required to further

  16. Carnosic acid suppresses the production of amyloid-β 1-42 and 1-43 by inducing an α-secretase TACE/ADAM17 in U373MG human astrocytoma cells.

    PubMed

    Yoshida, Hidemi; Meng, Pengfei; Matsumiya, Tomoh; Tanji, Kunikazu; Hayakari, Ryo; Xing, Fei; Wang, Liang; Tsuruga, Kazushi; Tanaka, Hiroshi; Mimura, Junsei; Kosaka, Kunio; Itoh, Ken; Takahashi, Ippei; Imaizumi, Tadaatsu

    2014-02-01

    Amyloid beta (Aβ) peptides are key molecules in the pathogenesis of Alzheimer's disease (AD). The sequential cleavage of amyloid precursor protein (APP) by the β- and γ-secretases generates Aβ peptides; however, the alternate cleavage of APP by the α- and γ-secretases decreases Aβ production. We previously reported that carnosic acid (CA), a phenolic diterpene compound found in the labiate herbs rosemary and sage, suppresses Aβ (1-40 and 1-42) production by activating α-secretase in cultured SH-SY5Y human neuroblastoma cells (Neurosci. Res. 2013; 75: 94-102). Here, we investigated the effect of CA on the production of Aβ peptides (1-40, 1-42 and 1-43) in U373MG human astrocytoma cells. The treatment of cells with CA suppressed Aβ40/42/43 release (55-71% decrease at 50μM). CA treatment enhanced the mRNA expressions of an α-secretase TACE (tumor necrosis factor-α-converting enzyme, also called a disintegrin and metalloproteinase-17, ADAM17); however, the β-secretase BACE1 (β-site APP-cleaving enzyme-1) was not increased by CA. Knockdown of TACE by siRNA reduced soluble-APPα release enhanced by CA and partially recovered the CA-suppressed Aβ40/42/43 release. These results suggest that CA reduces Aβ production, at least partially, by activating TACE in human astroglial cells. The use of CA may have a potential in the prevention of Aβ-mediated diseases. PMID:24295810

  17. Adaptation of the South-West Wing of Collegium Chemicum of Adam Mickiewicz University in Poznań for Storage Facilities/ Adaptacja Południowo-Zachodniego Skrzydła Budynku Collegium Chemicum Uam W Poznaniu Na Cele Magazynowe

    NASA Astrophysics Data System (ADS)

    Ścigałło, Jacek

    2015-06-01

    The article refers to the problems of adaptation of Collegium Chemicum facilities belonging to Adam Mickiewicz Uniwersity in Poznań to its storage needs. The subject building is situated in Grunwaldzka Street in Poznań. In the introduction part, the building and its structural solutions are described. The results of the materials research and the measurements of the used reinforcement have been presented. The structure diagnostic analyses were performed basing on measurements and research. The analysis allowed the determination of the limit loads. The results of the performed analysis of the current state turned out to be unsatisfactory, not only in terms of the planned storage load but also in terms of the current load state, as was shown by the construction analysis. W pracy przedstawiono problemy związane z adaptacją budynku dydaktycznego Collegium Chemicum przy ul. Grunwaldzkiej w Poznaniu na cele magazynowe Biblioteki Głównej UAM. Na wstępie opisano badany budynek oraz scharakteryzowano zastosowane w nim rozwiązania konstrukcyjne. Przedstawiono wyniki wykonanych badań materiałowych oraz pomiarów inwentaryzacyjnych zastosowanego zbrojenia. Na podstawie wykonanych pomiarów i badań przeprowadzono analizę diagnostyczną konstrukcji, która pozwoliła na wyznaczenie dopuszczalnych wartości obciążeń powierzchni stropowych. Wyniki wykonanej analizy konstrukcji w stanie istniejącym okazały się dalece niezadowalające nie tylko z punktu widzenia planowanych, znacznych obciążeń magazynowych. Analiza wykazała bowiem, że konstrukcja jest już znacznie przeciążona w aktualnym stanie jej obciążenia

  18. Adam Walsh Reauthorization Act of 2012

    THOMAS, 112th Congress

    Rep. Sensenbrenner, F. James, Jr. [R-WI-5

    2012-01-19

    08/02/2012 Received in the Senate and Read twice and referred to the Committee on the Judiciary. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  19. Economic Heritage: Adam Smith vs. Karl Marx

    ERIC Educational Resources Information Center

    Manton, Edgar J.; English, Donald E.

    2008-01-01

    The problem of this study was to determine the number of first semester college freshmen who could correctly identify the individuals who are generally considered the "fathers" of communism and capitalism. A questionnaire was administered to 241 freshmen students enrolled in English 101, College Reading and Writing, at Texas A&M…

  20. Karl Marx vs. Adam Smith Revisited

    ERIC Educational Resources Information Center

    Manton, Edgar J.; English, Donald E.; Flanagan, Jennifer; Dubey, Anvit

    2013-01-01

    The purpose of this study was to determine whether the ability of freshman college students to identify the founding fathers of free enterprise and of communism has improved. This study is a follow-up to four previous studies. A questionnaire was developed and distributed to College of Business and College of Education & Human Services…

  1. ADAM-M Data and Information

    Atmospheric Science Data Center

    2013-05-30

    ... Information Creating a Unified Airborne Database for Assessment and Validation of Global Models of Atmospheric ...  (3)  To generate a standardized in-situ observational database with best possible matching temporal and spatial scales to model ...

  2. Adam Smith in the Mathematics Classroom

    ERIC Educational Resources Information Center

    Lipsey, Sally I.

    1975-01-01

    The author describes a series of current economic ideas and situations which can be used in the mathematics classroom to illustrate the use of signed numbers, the coordinate system, univariate and multivariate functions, linear programing, and variation. (SD)

  3. Genetics Home Reference: Adams-Oliver syndrome

    MedlinePlus

    ... scalp, and skull AOS aplasia cutis congenita with terminal transverse limb defects congenital scalp defects with distal ... of clinical phenotypes in aplasia cutis congenita and terminal transverse limb defects. Am J Med Genet A. ...

  4. Adams, John Couch (1819-92)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Born in Laneast, Cornwall, England, he became fellow and mathematical tutor at Cambridge. He developed a procedure for numerical integration of differential equations and, inspired by MARY SOMERVILLE, he deduced mathematically the existence and location of the planet Neptune from its perturbations on the planet Uranus. Neptune was discovered by JOHANN GALLE in Berlin, in September 1846, using URB...

  5. Adam Walsh Reauthorization Act of 2016

    THOMAS, 113th Congress

    Rep. Sensenbrenner, F. James, Jr. [R-WI-5

    2016-09-22

    10/11/2016 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  6. Adam's Escape: Children and the Discordant Nature of Colonial Conversions

    ERIC Educational Resources Information Center

    Vallgarda, Karen A. A.

    2011-01-01

    The article traces the fundamental incoherency that structured the Danish Missionary Society's work at a boarding school for low-caste "heathen" children in South India in the 1860s and 1870s. Through elaborate disciplinary methods, the missionaries set out to Christianize and civilize the Indian children's morality, social behaviour and bodily…

  7. Revisiting Adam's Rib: Student Performance, Gender Stereotyping, and Trial Simulations

    ERIC Educational Resources Information Center

    Zeigler, Sara L.; Moran, Sheena M.

    2008-01-01

    The manuscript explores gender stereotyping in performance evaluations in undergraduate mock trial competitions. The central hypothesis is that gendered expectations for attorney and witness behavior in the legal community inform and influence the evaluation of undergraduate performance in relation to communication methods, argumentation…

  8. Schall von Bell, Johann Adam (1592-1666)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Astronomer, born in Cologne, Germany, became a Jesuit and studied astronomy in Rome. He was one of numerous Jesuit missionaries sent to China, and was the first European ever to be a member of the court bureaucracy in Peking, becoming head of the Imperial Board of Astronomy, and adviser to the young emperor Shun-chih (ruled 1644-61). He produced a large six-part cosmological map, accompanied by p...

  9. Geologic map of the Mount Adams Quadrangle, Washington

    SciTech Connect

    Korosec, M.A.

    1987-01-01

    This report is comprised of a 1:100,000 scale geologic map and accompanying text. The text consists of unit descriptions, a table of age dates, a table of major element geochemistry, correlation diagram, and a source of mapping diagram. (ACR)

  10. The Marriage of Alma Mater to Adam Smith.

    ERIC Educational Resources Information Center

    Buescher, John B.

    1987-01-01

    Businesses and universities must be encouraged to act from their traditional positions of strength, based on the longest view and the broadest interests. They must examine carefully their potential sources of conflict as well as opportunities for benefit before engaging in alliances that may become complex and difficult to manage. (MSE)

  11. Mike Fuller Receives 2012 John Adam Fleming Medal: Response

    NASA Astrophysics Data System (ADS)

    Fuller, Mike

    2013-01-01

    Thank you, Chris and Subir, for nominating me for the Fleming Medal and for your very kind comments on my research. In looking back over the medalists since 1962, it is hard to believe that I could be lucky enough to join such distinguished company. Yet, I have been very lucky through life. First, I was lucky to go to Christ's Hospital and Cambridge University. Second, my Aunt Marjorie married a physicist, Johnnie Clegg, who was an excellent teacher and inspiration for me. Third, to be born in England in the mid-1930s was to be a member of a fortunate generation of scientists. Providing one safely negotiated World War II, one joined the academic world at a time of great excitement, of expansion, and support for science.

  12. Spiro K. Antiochos Receives 2013 John Adam Fleming Medal: Response

    NASA Astrophysics Data System (ADS)

    Antiochos, Spiro K.

    2014-01-01

    Thank you, Jim Klimchuk, for this far too generous citation, and thank you very much, my AGU colleagues, for honoring me with the Fleming Medal. When I consider the list of excellent scientists who have been awarded the Fleming Medal, I am humbled that you have included me in their company. I am especially proud that this award is from AGU because only later in my career did I change my science focus and join AGU. This was the best professional decision I have ever made. As a result, I have met many wonderful colleagues. I've always loved doing research, but my colleagues in AGU have made it so much more enjoyable. Also, moving to AGU gave me the opportunity to participate in truly exciting science. My present position is that of senior scientist for space weather at NASA Goddard. It is interesting to note that the field of space weather science did not even exist when I started my career. I was very fortunate to be part of the beginning of a new field and, as a result, to be able to participate in the explosive advances of space weather science over the past 2 decades.

  13. DETECTION OF K-RAS AND P53 MUTATIONS IN SPUTUM SAMPLES OF LUNG CANCER PATIENTS USING LASER CAPTURE MICRODISSECTION MICROSCOPE AND MUTATION ANALYSIS

    EPA Science Inventory

    Detection of K-ras and p53 Mutations in Sputum Samples of Lung Cancer Patients Using Laser Capture Microdissection Microscope and Mutation Analysis

    Phouthone Keohavong a,*, Wei-Min Gao a, Kui-Cheng Zheng a, Hussam Mady b, Qing Lan c, Mona Melhem b, and Judy Mumford d.
    <...

  14. VizieR Online Data Catalog: Emission-line galaxies from HETDEX pilot survey (Adams+, 2011)

    NASA Astrophysics Data System (ADS)

    Adams, J. J.; Blanc, G. A.; Hill, G. J.; Gebhardt, K.; Drory, N.; Hao, L.; Bender, R.; Byun, J.; Ciardullo, R.; Cornell, M. E.; Finkelstein, S. L.; Fry, A.; Gawiser, E.; Gronwall, C.; Hopp, U.; Jeong, D.; Kelz, A.; Kelzenberg, R.; Komatsu, E.; MacQueen, P. J.; Murphy, J.; Odoms, P. S.; Roth, M.; Schneider, D. P.; Tufts, J. R.; Wilkinson, C. P.

    2011-03-01

    We obtained regular fall/winter/spring dark time observations from 2007 September to 2010 February on the McDonald 2.7m Harlan J. Smith telescope with the Visible Integral-field Replicable Unit Spectrograph Prototype (VIRUS-P). (3 data files).

  15. 75 FR 81641 - Odessa Subarea Special Study; Adams, Franklin, Grant, and Lincoln Counties, WA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-28

    ... Ritzville Public Library, 302 West Main, Ritzville, WA 99169. Basin City Branch, Mid-Columbia Library, Basin... Public Library, 405 West Main Street, Coulee City, WA 99115. Ephrata City Library, 45 Alder Street... 5th Avenue, Moses Lake, WA 98837-1797. Odessa Public Library, 21 East 1st Avenue, Odessa, WA...

  16. Grades of Severity and the Validation of an Atopic Dermatitis Assessment Measure (ADAM).

    ERIC Educational Resources Information Center

    Charman, Denise P.; Varigos, George A.

    1999-01-01

    Studied the validity of the Atopic Dermatitis Assessment Measure (D. Charman and others, 1999) with 171 pediatric patients in Australia using partial credit analyses to produce clinically relevant "word pictures" of grades of severity for atopic dermatitis. Discusses implications for measurement in medicine. (SLD)

  17. The Development of a Practical and Reliable Assessment Measure for Atopic Dermatitis (ADAM).

    ERIC Educational Resources Information Center

    Charman, Denise; Varigos, George; Horne, David J. de L.; Oberklaid, Frank

    1999-01-01

    A study was conducted in Australia to develop a reliable, valid, and practical measure of atopic dermatitis. The test development process and validity evaluation with two doctors and 51 patients are discussed. Results suggest that operational definitions of the scales need to be defined more clearly. The measure satisfies assumptions for a partial…

  18. Video-atlas on minimally invasive mitral valve surgery-The David Adams technique.

    PubMed

    Castillo, Javier G; Milla, Federico; Anyanwu, Anelechi C; Adams, David H

    2013-11-01

    Median sternotomy has unquestionably evolved over recent decades. Modern sternotomy involves a 7-8 cm lower midline skin incision, tunneling of the subcutaneous tissues with subsequent creation of myocutaneous flaps, full sternotomy, and standard cardiopulmonary bypass techniques with central cannulation. In experienced centers, modern sternotomy may achieve all the goals of minimally invasive surgery, including excellent cosmesis, excellent postoperative pain control, low rates of bleeding and transfusion (our re-exploration rate for bleeding is <1%), and the ability to perform any reconstructive technique that would be used in a standard sternotomy, with very high repair rates (our most recent series documented a repair rate exceeding 99% in an all-comers population of degenerative disease regardless of complexity).

  19. "Adam Smith Meets Walt Disney": School Image on the World Wide Web

    ERIC Educational Resources Information Center

    Smith, Alison

    2007-01-01

    This article describes a small-scale research project undertaken as part of the coursework in a Doctor of Education programme. The project investigated the organisational images or identities portrayed by ten secondary schools in Auckland, New Zealand on their school websites. The recent proliferation of school websites has provided schools with a…

  20. Neo-classical theory of competition or Adam Smith's hand as mathematized ideology

    NASA Astrophysics Data System (ADS)

    McCauley, Joseph L.

    2001-10-01

    Orthodox economic theory (utility maximization, rational agents, efficient markets in equilibrium) is based on arbitrarily postulated, nonempiric notions. The disagreement between economic reality and a key feature of neo-classical economic theory was criticized empirically by Osborne. I show that the orthodox theory is internally self-inconsistent for the very reason suggested by Osborne: lack of invertibility of demand and supply as functions of price to obtain price as functions of supply and demand. The reason for the noninvertibililty arises from nonintegrable excess demand dynamics, a feature of their theory completely ignored by economists.

  1. An Analysis of the Doctor-Patient Relationship Using "Patch Adams"

    ERIC Educational Resources Information Center

    Pettit, Michelle L.

    2008-01-01

    Navigating the contemporary health care system represents an arduous challenge for consumers. In response to this challenge, health educators should prepare informed and skilled consumers to assume active roles in their health care. Through active participation in health care decisions, consumers can maximize the quality and duration of…

  2. From the Adam Smith Institute to the Zapatistas: An Internet Gateway to all Development Knowledge.

    ERIC Educational Resources Information Center

    Wilks, Alex

    2002-01-01

    Examines the World Bank Internet initiative, the Development Gateway. Describes the importance of the Bank as a knowledge bank and the threats posed by the Internet to its near monopoly of development thinking. Argues that the initiative reveals biases and misunderstandings in the World Bank's approach to knowledge for development. (CAJ)

  3. Video-atlas on minimally invasive mitral valve surgery—The David Adams technique

    PubMed Central

    Castillo, Javier G.; Milla, Federico; Anyanwu, Anelechi C.

    2013-01-01

    Median sternotomy has unquestionably evolved over recent decades. Modern sternotomy involves a 7-8 cm lower midline skin incision, tunneling of the subcutaneous tissues with subsequent creation of myocutaneous flaps, full sternotomy, and standard cardiopulmonary bypass techniques with central cannulation. In experienced centers, modern sternotomy may achieve all the goals of minimally invasive surgery, including excellent cosmesis, excellent postoperative pain control, low rates of bleeding and transfusion (our re-exploration rate for bleeding is <1%), and the ability to perform any reconstructive technique that would be used in a standard sternotomy, with very high repair rates (our most recent series documented a repair rate exceeding 99% in an all-comers population of degenerative disease regardless of complexity). PMID:24349990

  4. 76 FR 45600 - Columbia National Wildlife Refuge, Adams and Grant Counties, WA; Draft Comprehensive Conservation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-29

    ... CCP/ EA describes our proposal and alternatives for managing the Refuge for the next 15 years. DATES... CCP is to provide refuge managers with a 15-year plan for achieving refuge purposes and contributing... interpretation. We will review and update the CCP at least every 15 years in accordance with the...

  5. Orbital Prosthetic Rehabilitation in “ADAM Complex” Multiple Orofacial-Cleft Disruption Syndrome

    PubMed Central

    Barabde, Aparna; Barabde, Shailesh M.; Bhagat, Ashish; Thakare, Amar

    2013-01-01

    To be human is great; to look human is wonderful! It is nature's greatest gift! Mother nature's womb is the safest place on earth for any life, but the calamity strikes and no one knows how Hence, Treasure your exceptions!, since nature seems nowhere accustomed more openly to display, its secret mysteries than in cases where it shows traces of its workings apart from the beaten path. A dismorphological pattern of congenital oro-craniofacial and limb defects which is a rare form of amniotic rupture sequence required persistent coordinated efforts of multiple disciplines and had manifested as bizarre orofacial clefting, cat eye syndrome with an ectopic eye, and aberrant tissue band lesions on limb. The challenge was to meet the child's clamour for functional demands on premature exposure to open world and was overcome through a phased treatment implementation. Anophthalmos resulting from multiple ophthalmic surgeries for aberrant ectopic left eye and cat eye syndrome of right eye required a staged sequential preemptive planning for a successful outcome. Every phase of fabrication of orbital prosthesis comes with an impending challenge. Thus, a well-defined technique eliminating the common errors and creating a natural looking prosthesis, in the face of limitations, is imperative. PMID:23762737

  6. Beyond Adam Smith and Marcus Welby: a data system for prudent purchasers. Part 1.

    PubMed

    MacKay, C K

    1985-01-01

    Are purchasers selling providers the rope with which providers are hanging them? The President of the Lehigh Valley Business Conference on Health Care believes so because he sees the rhetorical traps of "competition" and "quality" stalling movement toward data acquisition and use. He presents a way out via a provider-focused, microcomputer-based data system. Part 1 of a two-part article.

  7. Adam Smith's Pins, Sausage Making and the Funding of College Education

    ERIC Educational Resources Information Center

    Barrett, Ralph V.

    2005-01-01

    Using the language and concepts of economic markets for the purpose of describing and evaluating the function and performance of educational institutions has been a common and growing practice throughout Western industrial societies for many years. The critique of such market analysis also has a long history. Critical assessments of market theory…

  8. Post-KR Delay Intervals and Mental Practice: A Test of Adams' Closed Loop Theory

    ERIC Educational Resources Information Center

    Bole, Ronald

    1976-01-01

    The present study suggests that post-KR delay interval time or activity in the interval has little to do with learning on a self-paced positioning task, not ruling out that on ballistic tasks or more complex nonballistic tasks that a learner could make use of additional time or strategy. (MB)

  9. Epidemiology and risk factors of amniotic band syndrome, or ADAM sequence

    PubMed Central

    Cignini, Pietro; Giorlandino, Claudio; Padula, Francesco; Dugo, Nella; Cafà, Ester Valentina; Spata, Anna

    2012-01-01

    Summary Amniotic band sequence (ABS) is the term applied to a wide range of congenital anomalies, most typically limb and digital amputations and constriction rings, that occur in association with fibrous bands (1). These alterations may be associated or not with cutaneous and visceral abnormalities. This work, which is a literature review, examines several studies that relate to cases of amniotic band syndrome (SBA). In particular, our attention was focused on the causes and pathogenesis of the SBA. These for the most part are still unknown, but from what we observe in different jobs, are due to a mechanism of vascular damage. Therefore in this paper we examine chemical risk factors, like smoking, drug use, maternal hyperglycemia, mechanical risk factors such as the puncture of the amniotic sac after amniocentesis. We also speak of the altitude as a risk factor related to blood pressure, of the increased incidence of disease in primigravid, in women with a low level of education, in which the pregnancy was not planned, and then we talk of a higher incidence in young fathers and of the role of familiarity. PMID:23272276

  10. Higher Education Gains for African Americans Erode Following Dismissal of "Adams," Observers Say.

    ERIC Educational Resources Information Center

    Barnes, Esmeralda

    1993-01-01

    Since a federal appeals court dropped a case 3 years ago, ruling that states, not the federal government, are responsible for ensuring equal educational opportunity, educators feel African-American education has lost ground. The case argued states sanctioned dual systems of education. States' elimination of some programs now threatens…

  11. A Beacon of Light: Tougaloo during the Presidency of Dr. Adam Daniel Beittel (1960-1964)

    ERIC Educational Resources Information Center

    Speed, John Gregory

    2014-01-01

    This study examines leadership efforts that supported the civil rights movements that came from administrators and professors, students and staff at Tougaloo College between 1960 and 1964. A review of literature reveals that little has been written about the college's role in the Civil Rights Movement during this time. Thus, one goal of this study…

  12. Leaf surface chemicals fromNicotiana affecting germination ofPeronospora tabacina (adam) sporangia.

    PubMed

    Kennedy, B S; Nielsen, M T; Severson, R F; Sisson, V A; Stephenson, M K; Jackson, D M

    1992-09-01

    A bioassay was used to evaluate the effects of cuticular leaf components, isolated fromN. tabacum, N. glutinosa (accessions 24 and 24a), and 23other Nicotiana species, on germinationof P. tabacina (blue mold). The leaf surface compounds includedα- andβ-4,8,13,-duvatriene-l,3-diols (DVT-diols), (13-E)-labda-13-ene-8α-,15-diol (labdenediol), (12-Z)-labda-12,14-diene-8α-ol (cis-abienol), (13-R)-labda-8,14-diene-13-ol (manool), 2-hydroxymanool, a mixture of (13-R)-labda-14-ene-8α,13-diol (sclareol), and (13-S)-labda-14-ene-8α,13-diol (episclareol), and various glucose and/or sucrose ester isolates. The above in acetone were applied onto leaf disks of the blue moldsusceptibleN. tabacum cv. TI 1406, which was then inoculated with blue mold sporangia. Estimated IC50 values (inhibitory concentration) were 3.0μg/cm(2) forα-DVT-diol, 2.9μ/cm(2) forβ-DVT-diol, 0.4μg/cm(2) for labdenediol and 4.7μg/cm(2) for the sclareol mixture. Manool, 2-hydroxymanool, andcis-abienol at application rates up to 30μg/cm(2) had little or no effect on sporangium germination. Glucose and/or sucrose ester isolates from the cuticular leaf extracts of 23Nicotiana species and three different fractions fromN. bigelovii were also evaluated for antimicrobial activity at a concentration of 30μg/cm(2). Germination was inhibited by >20% when exposed to sugar esters isolated fromN. acuminata, N. benthamiana, N. attenuata, N. clevelandii, andN. miersii, and accessions 10 and 12 ofN. bigelovii. These results imply that a number of compounds may influence resistance to blue mold in tobacco. PMID:24254279

  13. Accelerators and Superconductivity: A Marriage of Convenience. Second John Adams Memorial Lecture

    NASA Astrophysics Data System (ADS)

    Wilson, Martin

    1987-06-01

    This lecture deals with the relationship between accelerator technology in high-energy-physics laboratories and the development of superconductors. It concentrates on synchrotron magnets, showing how their special requirements have brought about significant advances in the technology, particularly the development of filamentary superconducting composites. Such developments have made large superconducting accelerators an actuality: the Tevatron in routine operation, the Hadron Electron Ring Accelerator (HERA) under construction, and the Superconducting Super Collider (SSC) and Large Hadron Collider (LHC) at the conceptual design stage. Other applications of superconductivity have also been facilitated - for example medical imaging and small accelerators for industrial and medical use.

  14. 77 FR 2992 - Columbia National Wildlife Refuge, Adams and Grant Counties, WA; Final Comprehensive Conservation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-20

    ... process for Columbia NWR. We started this process through a notice in the Federal Register (74 FR 25576; May 28, 2009). We released the draft CCP/EA to the public, announcing and requesting comments in a notice of availability in the Federal Register (76 FR 45600; July 29, 2011). We announce our CCP...

  15. 78 FR 69140 - CSMI, LLC; Request for Action

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-18

    .../reading-rm/adams.html . To begin the search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems with ADAMS, please contact the NRC's Public Document Room...

  16. To extend the legislative authority of the Adams Memorial Foundation to establish a commemorative work in honor of former President John Adams and his legacy, and for other purposes.

    THOMAS, 113th Congress

    Rep. Lynch, Stephen F. [D-MA-8

    2013-12-19

    07/23/2014 Received in the Senate and Read twice and referred to the Committee on Energy and Natural Resources. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  17. A bill to provide for an extension of the legislative authority of the Adams Memorial Foundation to establish a commemorative work in honor of former President John Adams and his legacy.

    THOMAS, 113th Congress

    Sen. Markey, Edward J. [D-MA

    2013-12-19

    07/23/2014 Committee on Energy and Natural Resources Senate Subcommittee on National Parks. Hearings held. With printed Hearing: S.Hrg. 113-493. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  18. The Moral Dignity of Inductive Method and the Reconciliation of Science and Faith in Adam Sedgwick's "Discourse"

    ERIC Educational Resources Information Center

    Bellon, Richard

    2012-01-01

    Science's inductive method required patient, humble and self-controlled behavior; Christian revelation demanded the same virtues. The discoveries of science and the truths of scripture would always harmonize as long as both men of science and men of faith conducted themselves in scrupulous accordance with their duty. So ran a central argument in…

  19. 77 FR 64847 - Union Pacific Railroad Company-Abandonment Exemption-in Adams, Weld and Boulder Counties, Colo.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-23

    ... network for the greater Denver, Colo. area). UP also states that it had retained a common carrier freight... and would pay for it. UP has certified that: (1) No local traffic has moved over the line for at least two years; (2) there is no overhead traffic on the line; (3) no formal complaint filed by a user...

  20. A Century of Writing Early American History: Then and Now Compared; or How Henry Adams Got It Wrong.

    ERIC Educational Resources Information Center

    Wood, Gordon S.

    1995-01-01

    Compares historical writing and historiography of the 19th and 20th centuries. Asserts that early history, written primarily by amateur historians, was simplistic and prone to error. Maintains that present-day histories provide more coverage of ethnic groups and women. (CFR)

  1. Bringing Adam Smith's Pin Factory to Life: Field Trips and Discussions as Forms of Experiential Learning

    ERIC Educational Resources Information Center

    Galizzi, Monica

    2014-01-01

    Educators are often aware of the need to implement a variety of teaching techniques to reach out to students with different learning styles. I describe an attempt to target multimodal learners by bringing classical economic texts and concepts to life through discussions, field visits and role playing exercises. In my Labor Economics class I…

  2. Association of "ADAM10" and "CAMK2A" Polymorphisms with Conduct Disorder: Evidence from Family-Based Studies

    ERIC Educational Resources Information Center

    Jian, Xue-Qiu; Wang, Ke-Sheng; Wu, Tie-Jian; Hillhouse, Joel J.; Mullersman, Jerald E.

    2011-01-01

    Twin and family studies have shown that genetic factors play a role in the development of conduct disorder (CD). The purpose of this study was to identify genetic variants associated with CD using a family-based association study. We used 4,720 single nucleotide polymorphisms (SNPs) from the Illumina Panel and 11,120 SNPs from the Affymetrix 10K…

  3. Hydrogeology and simulation of ground-water flow at the Gettysburg Elevator Plant Superfund Site, Adams County, Pennsylvania

    USGS Publications Warehouse

    Low, Dennis J.; Goode, Daniel J.; Risser, Dennis W.

    2000-01-01

    Ground water in Triassic-age sedimentary fractured-rock aquifers in the area of Gettysburg, Pa., is used as drinking water and for industrial and commercial supply. In 1983, ground water at the Gettysburg Elevator Plant was found by the Pennsylvania Department of Environmental Resources to be contaminated with trichloroethene, 1,1,1-trichloroethane, and other synthetic organic compounds. As part of the U.S. Environmental Protection Agency?s Comprehensive Environmental Response, Compensation, and Liability Act, 1980 process, a Remedial Investigation was completed in July 1991, a method of site remediation was issued in the Record of Decision dated June 1992, and a Final Design Report was completed in May 1997. In cooperation with the U.S. Environmental Protection Agency in the hydrogeologic assessment of the site remediation, the U.S. Geological Survey began a study in 1997 to determine the effects of the onsite and offsite extraction wells on ground-water flow and contaminant migration from the Gettysburg Elevator Plant. This determination is based on hydrologic and geophysical data collected from 1991 to 1998 and on results of numerical model simulations of the local ground-water flow-system. The Gettysburg Elevator Site is underlain by red, green, gray, and black shales of the Heidlersburg Member of the Gettysburg Formation. Correlation of natural-gamma logs indicates the sedimentary rock strike about N. 23 degrees E. and dip about 23 degrees NW. Depth to bedrock onsite commonly is about 6 feet but offsite may be as deep as 40 feet. The ground-water system consists of two zones?a thin, shallow zone composed of soil, clay, and highly weathered bedrock and a thicker, nonweathered or fractured bedrock zone. The shallow zone overlies the bedrock zone and truncates the dipping beds parallel to land surface. Diabase dikes are barriers to ground-water flow in the bedrock zone. The ground-water system is generally confined or semi-confined, even at shallow depths. Depth to water can range from flowing at land surface to more than 71 feet below land surface. Potentiometric maps based on measured water levels at the Gettysburg Elevator Plant indicate ground water flows from west to east, towards Rock Creek. Multiple-well aquifer tests indicate the system is heterogeneous and flow is primarily in dipping beds that contain discrete secondary openings separated by less permeable beds. Water levels in wells open to the pumped bed, as projected along the dipping stratigraphy, are drawn down more than water levels in wells not open to the pumped bed. Ground-water flow was simulated for steady-state conditions prior to pumping and long-term average pumping conditions. The three-dimensional numerical flow model (MODFLOW) was calibrated by use of a parameter estimation program (MODFLOWP). Steady-state conditions were assumed for the calibration period of 1996. An effective areal recharge rate of 7 inches was used in model calibration. The calibrated flow model was used to evaluate the effectiveness of the current onsite and offsite extraction well system. The simulation results generally indicate that the extraction system effectively captures much of the ground-water recharge at the Gettysburg Elevator Plant and, hence, contaminated ground-water migrating from the site. Some of the extraction wells pump at low rates and have very small contributing areas. Results indicate some areal recharge onsite will move to offsite extraction wells.

  4. Pathologic survey on the Manila clam Ruditapes philippinarum (Adams and Reeve 1850) from Haeju off the western coastal Yellow Sea

    NASA Astrophysics Data System (ADS)

    Yang, Hyun-Sung; Park, Kwang-Jae; Choi, Kwang-Sik

    2010-06-01

    Pathologic condition of Manila clam, Ruditapes philippinarum collected from Haeju off the west coast of North Korea in February and March 2007 was investigated in this study. The diagnostics included a protozoan parasite, Perkinsus olseni, the brown ring disease (BRD) caused by bacteria Vibrio tapetis and metazoan parasites Trematod and Cestod. P. olseni infection was examined using histology and Ray’s fluid thioglycollate medium (RFTM) assay along with Choi’s NaOH digestion technique. Trematode and cestode infection was also examined from the histology. A total of 140 clams with 35-45 mm in shell length (2-3 years old) were analyzed. Condition factor (CF), a ratio of the wet tissue weight to the shell dry weight, ranged from 0.445±0.074 (February) to 0.544±0.132 (March). Total body burden of P. olseni (i.e. infection intensity) ranged from 18,644±37,755 (February) to 26,933±80,611 cells/g wet tissue (March) with the prevalence of 76.7-43.3% (March) respectively. Prevalence of trematode and cestode infection in February and March varied 22.5-25.0 and 15.0-22.5% respectively. Infection intensity of V. tapetis ranged 1-2 and the prevalence was 1.4 (February) and 5.7% (March). Prevalence and infection intensity of P. olseni in clams from Haeju was comparatively lower than those of clams reported on the west coast of Korea. BRD and the other metazoan parasite infection were also relatively lower or similar to the condition of the clams reported previously. CF of Haeju clams was also relatively higher than the clams in Gyeonggi Bay and Taean, suggesting that Haeju clams had relatively better pathologic and health condition.

  5. Neoliberalism, Emotional Experience in Education and Adam Smith: Reading "The Theory of Moral Sentiments" Alongside "The Wealth of Nations"

    ERIC Educational Resources Information Center

    Hanley, Christopher

    2015-01-01

    This paper examines some critical accounts of emotional life shaped by neoliberalism. A range of literature concerned with neoliberalism and emotional experience in educational contexts is reviewed. I argue that neoliberal "reforms" in public institutions create an ever-increasing demand for emotional performance. Neoliberals often refer…

  6. Gender Wars at John Adams High School. A Case Study. Teaching Cases in Cross-Cultural Education No. 6.

    ERIC Educational Resources Information Center

    Finley, Paris; Kleinfeld, Judith, Ed.

    This case report describes a series of conflicts centering on gender issues at a large metropolitan high school. The case is accompanied by discussion questions designed to present prospective teachers with complex professional problems, asking them to interpret the situation and decide upon possible solutions. The report was written to develop…

  7. 75 FR 65503 - Odessa Subarea Special Study; Adams, Franklin, Grant, and Lincoln Counties, Washington INT-DES 10-54

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-25

    ... Subarea Special Study. The Washington Department of Ecology (Ecology) is a joint lead with Reclamation in..., Congress has funded Reclamation to investigate this problem. Ecology has partnered with Reclamation by... legislature passed the Columbia River Water Resource Management Act (HB 2860) that directs Ecology...

  8. The influence of emerging administrative scientists: an interview with Dr Maja Djukic. Interview by Jeffrey M. Adams.

    PubMed

    Djukic, Maja

    2014-01-01

    This department highlights emerging nursing leaders and scientists who have demonstrated great promise and findings in advancing innovation and patient care leadership in practice, policy, research, education and theory. This interview profiles Maja Djukic, PhD, RN, assistant professor, New York University College of Nursing. PMID:24316612

  9. Computation and visualization of the MacAdam limits for any lightness, hue angle, and light source

    NASA Astrophysics Data System (ADS)

    Martínez-Verdú, Francisco; Perales, Esther; Chorro, Elisabet; de Fez, Dolores; Viqueira, Valentín; Gilabert, Eduardo

    2007-06-01

    We present a systematic algorithm capable of searching for optimal colors for any lightness L* (between 0 and 100), any illuminant (D65, F2, F7, F11, etc.), and any light source reported by CIE. Color solids are graphed in some color spaces (CIELAB, SVF, DIN99d, and CIECAM02) by horizontal (constant lightness) and transversal (constant hue angle) sections. Color solids plotted in DIN99d and CIECAM02 color spaces look more spherical or homogeneous than the ones plotted in CIELAB and SVF color spaces. Depending on the spectrum of the light source or illuminant, the shape of its color solid and its content (variety of distinguishable colors, with or without color correspondence) change drastically, particularly with sources whose spectrum is discontinuous and/or very peaked, with correlated color temperature lower than 5500 K. This could be used to propose an absolute colorimetric quality index for light sources comparing the volumes of their gamuts, in a uniform color space.

  10. The influence of emerging administrative scientists: an interview with Dr Maja Djukic. Interview by Jeffrey M. Adams.

    PubMed

    Djukic, Maja

    2014-01-01

    This department highlights emerging nursing leaders and scientists who have demonstrated great promise and findings in advancing innovation and patient care leadership in practice, policy, research, education and theory. This interview profiles Maja Djukic, PhD, RN, assistant professor, New York University College of Nursing.

  11. A cybertaxonomic revision of the micro-landsnail genus Plectostoma Adam (Mollusca, Caenogastropoda, Diplommatinidae), from Peninsular Malaysia, Sumatra and Indochina

    PubMed Central

    Liew, Thor-Seng; Vermeulen, Jaap Jan; Marzuki, Mohammad Effendi bin; Schilthuizen, Menno

    2014-01-01

    Abstract Plectostoma is a micro land snail restricted to limestone outcrops in Southeast Asia. Plectostoma was previously classified as a subgenus of Opisthostoma because of the deviation from regular coiling in many species in both taxa. This paper is the first of a two-part revision of the genus Plectostoma, and includes all non-Borneo species. In the present paper, we examined 214 collection samples of 31 species, and obtained 62 references, 290 pictures, and 155 3D-models of 29 Plectostoma species and 51 COI sequences of 19 species. To work with such a variety of taxonomic data, and then to represent it in an integrated, scaleable and accessible manner, we adopted up-to-date cybertaxonomic tools. All the taxonomic information, such as references, classification, species descriptions, specimen images, genetic data, and distribution data, were tagged and linked with cyber tools and web servers (e.g. Lifedesks, Google Earth, and Barcoding of Life Database). We elevated Plectostoma from subgenus to genus level based on morphological, ecological and genetic evidence. We revised the existing 21 Plectostoma species and described 10 new species, namely, P. dindingensis sp. n., P. mengaburensis sp. n., P. whitteni sp. n., P. kayiani sp. n., P. davisoni sp. n., P. relauensis sp. n., P. kubuensis sp. n., P. tohchinyawi sp. n., P. tenggekensis sp. n., and P. ikanensis sp. n. All the synthesised, semantic-tagged, and linked taxonomic information is made freely and publicly available online. PMID:24715783

  12. What Would Adam Smith Have on His iPod? Uses of Music in Teaching the History of Economic Thought

    ERIC Educational Resources Information Center

    Van Horn, Robert; Van Horn, Monica

    2013-01-01

    In this article, the authors examine two ways that they use music (i.e., popular song lyrics) as an active learning technique in an undergraduate history of economic thought course. First, they use music to help students grasp the ideas of the great thinkers in economics and see their relevance today. Second, because they require students to read…

  13. Mineral Resources of the Hells Canyon Study Area, Wallowa County, Oregon, and Idaho and Adams Counties, Idaho

    USGS Publications Warehouse

    Simmons, George C.; Gualtieri, James L.; Close, Terry J.; Federspiel, Francis E.; Leszcykowski, Andrew M.

    2007-01-01

    Field studies supporting the evaluation of the mineral potential of the Hells Canyon study area were carried out by the U.S. Geological Survey and the U.S. Bureau of Mines in 1974-76 and 1979. The study area includes (1) the Hells Canyon Wilderness; (2) parts of the Snake River, Rapid River, and West Fork Rapid River Wild and Scenic Rivers; (3) lands included in the second Roadless Area Review and Evaluation (RARE II); and (4) part of the Hells Canyon National Recreation Area. The survey is one of a series of studies to appraise the suitability of the area for inclusion in the National Wilderness Preservation System as required by the Wilderness Act of 1964. The spectacular and mineralized area covers nearly 950 mi2 (2,460 km2) in northeast Oregon and west-central Idaho at the junction of the Northern Rocky Mountains and the Columbia Plateau.

  14. 77 FR 21593 - V. C. Summer Nuclear Station, Units 2 and 3 Combined Licenses and Record of Decision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-10

    ...://www.nrc.gov/reading-rm/adams.html . From this site, persons can access the NRC's Agencywide Document... not have access to ADAMS or who encounter problems in accessing the documents located in ADAMS...

  15. 78 FR 35072 - Proposed Revisions to Reliability Assurance Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-11

    ... documents online in the NRC Library at http://www.nrc.gov/reading-rm/adams.html . To begin the search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems...

  16. Title VI and Title IX Compliance by the Office for Civil Rights in State-Operated Special Purpose and Vocational Schools Pursuant to Adams v. Mathews.

    ERIC Educational Resources Information Center

    McClure, Phyllis

    This paper examines the compliance activities of the Office for Civil Rights (OCR) undertaken to eliminate racial and sex discrimination in special purpose schools administered by State departments of education. After reviewing background to non-enforcement of Title VI, and briefly explaining Title IX, the activities of OCR with regard to special…

  17. Large-Scale Simulation of the Effects of Climate Change on Runoff Erosion Following Extreme Wildfire Events Authors: Gould, Adam, Warren, Barber, Wagenbrenner, Robichaud, Wang, Cherkauer

    NASA Astrophysics Data System (ADS)

    Gould, G.; Adam, J. C.; Barber, M. E.; Wagenbrenner, J. W.; Robichaud, P. R.; Wang, L.; Cherkauer, K. A.

    2012-12-01

    Across the western U.S., there is clear concern for increases in wildfire occurrence, severity, and post-fire runoff erosion due to projected climate changes. The aim of this study was to advance our capability to simulate post-fire runoff erosion at scales larger than a single hillslope to examine the relative contribution of sediment being released to larger streams and rivers in response to wildfire. We applied the Variable Capacity Infiltration-Water Erosion Prediction Project (VIC-WEPP), a newly-developed physically-based modeling framework that combines large-scale hydrology with hillslope-scale runoff erosion, over the Salmon River basin (SRB) in central Idaho. We selected the SRB for this study because of recent research that suggested that forest wildfires are likely contributing the majority of coarser sands that settle in downstream navigation channels and in reservoirs, causing adverse impacts to aquatic life, navigation, and flood storage. Using the Normalized Burn Ratio (NBR), burn intensity and severity maps show the regularity of wildfire occurrence in the SRB. These maps compare pre-fire images to next growing season images from the Landsat Thematic Mapper multispectral scanning sensor. Rather than implementing WEPP over all hillslopes within the SRB, we applied a representative hillslope approach. A monofractal scaling method downscales globally available 30 arc second digital elevation model (DEM) data to a 30 m resolution for simulations. This information determined the distribution of slope gradients within each VIC grid cell. This study applied VIC-WEPP over the 1979-2010 period and compared an ensemble of future climate simulations for the period of 2041-2070. For future scenarios, we only considered meteorological impacts on post-fire erosion and did not incorporate changes in future fire occurrence or severity. We ran scenarios for a variety of land cover and soil parameter sets, particularly those that relate to pre and post-fire characteristics, such as vegetative cover, interrill and rill erodibility factors, and saturated hydraulic conductivity. Evaluation of runoff erosion at experimental sites, observed by the U.S. Forest Service, involved using Disturbed WEPP which showed reasonable first post-fire year annual erosion predictions. We evaluated VIC-WEPP by comparing sediment observations downstream of the SRB with simulated yields for both pre and post-fire conditions. Generation of maps showing erosion over the SRB for each of the scenarios show specific areas within the SRB to be high, moderate, or low runoff-induced post-fire erosion regions. Our methodology will enable forest managers in the region to incorporate the impacts of changes in meteorological events on runoff erosion into their strategic management plans.

  18. Effects of agricultural best-management practices on the Brush Run Creek headwaters, Adams County, Pennsylvania, prior to and during nutrient management

    USGS Publications Warehouse

    Langland, M.J.; Fishel, D.K.

    1996-01-01

    The U.S. Geological Survey, in cooperation with the Susquehanna River Basin Commission and the Pennsylvania Department of Environmental Resources, investigated the effects of agricultural best-management practices on surface-water quality as part of the U.S. Environmental Protection Agency's Chesapeake Bay Program. This report characterizes a 0.63-square- mile agricultural watershed underlain by shale, mudstone, and red arkosic sandstone in the Lower Susquehanna River Basin. The water quality of the Brush Run Creek site was studied from October 1985 through September 1991, prior to and during the implementation of nutrient management designed to reduce sediment and nutrient discharges into Conewago Creek, a tributary to the Chesapeake Bay. The original study area was 0.38 square mile and included an area immediately upstream from a manure lagoon. The study area was increased to 0.63 square mile in the fall of 1987 after an extensive tile-drain network was discovered upstream and downstream from the established streamflow gage, and the farm owner made plans to spray irrigate manure to the downstream fields. Land use for about 64 percent of the 0.63 square mile watershed is cropland, 14 percent is pasture, 7 percent is forest, and the remaining 15 percent is yards, buildings, water, or gardens. About 73 percent of the cropland was used to produce corn during the study. The average annual animal population consisted of 57,000 chickens, 1,530 hogs, and 15 sheep during the study. About 59,340 pounds of nitrogen and 13,710 pounds of phosphorus were applied as manure and commercial fertilizer to fields within the subbasin during the 3-year period prior to implementation of nutrient management. During nutrient management, about 14 percent less nitrogen and 57 percent less phosphorus were applied as commercial and manure fertilizer. Precipitation totaled 209 inches, or 13 percent less than the long-term normal, during the 6-year study. Concentrations of total ammonia in precipitation were as high as 2.7 mg/L (milligrams per liter); in dry deposition the concentrations were as high as 5.4 mg/L, probably because of the ammonia that had volatilized from the manure-storage lagoon. Nitrate nitrogen in the upper 4 feet of the soil ranged from 17 to 452 pounds per acre and soluble phosphorus content ranged from 0.29 to 65 pounds per acre. The maximum concentration of total nitrogen was 2,400 mg/L on September 10, 1986, in discharge from the tile drain near the streamflow gage. Median concentrations of total nitrogen and dissolved nitrite plus nitrate in base flow at the water-quality gage were 14 mg/L and 4.4 mg/L, respectively; prior to nutrient management and during nutrient management, median concentrations were 14 mg/L and 6.2 mg/L, respectively. Significant reductions in total phosphorus and suspended-sediment concentrations occurred at the water-quality gage. The maximum concentrations of total phosphorus (160 mg/L) and suspended sediment (3,530 mg/L) were measured at a tile line above the water-quality gage. Concentrations of total nitrogen, dissolved ammonia, and total phosphorus in base flow increased during dry periods when discharges from the tile drain were not diluted. During nutrient management, only base-flow loads of suspended sediment increased. Total streamflow was about 121.8 inches. About 81 percent was storm runoff. Loads of total nitrogen, total phosphorus in stormflow, and suspended sediment increased 14, 44, and 41 percent during nutrient management, respectively. A load of about 787,780 pounds of sediment, 22,418 pounds of nitrogen, and 5,479 pounds of phosphorus was measured during 214 sampled stormflow days that represented 84 percent of the stormflow. About 812,924 pounds of sediment, 38,421 pounds of nitrogen, and 6,377 pounds of phosphorus were discharged during the 6-year study.

  19. Flood-inundation maps for the Hoosic River, North Adams and Williamstown, Massachusetts, from the confluence with the North Branch Hoosic River to the Vermont State line

    USGS Publications Warehouse

    Lombard, Pamela J.; Bent, Gardner C.

    2015-01-01

    The availability of the flood-inundation maps, combined with information regarding current (near real-time) stage from USGS streamgage Hoosic River near Williamstown, and forecasted flood stages from the National Weather Service Advanced Hydrologic Prediction Service will provide emergency management personnel and residents with information that is critical for flood response activities such as evacuations and road closures, and post-flood recovery efforts. The flood-inundation maps are nonregulatory, but provide Federal, State, and local agencies and the public with estimates of the potential extent of flooding during selected peak-flow events.

  20. Ground-water availability in part of the Borough of Carroll Valley, Adams County, Pennsylvania, and the establishment of a drought-monitor well

    USGS Publications Warehouse

    Low, Dennis J.; Conger, Randall W.

    2002-01-01

    Continued population growth in the Borough of Carroll Valley (Borough) coupled with the drought of 2001 have increased the demand for ground water in the Borough. This demand has led Borough officials to undertake an effort to evaluate the capability of the crystalline-bedrock aquifers to meet future, projected growth and to establish a drought-monitor well within and for the use of the Borough. As part of this effort, this report summarizes ground-water data available from selected sections within the Borough and provides geohydrologic information needed to evaluate ground-water availability and recharge sources within part of the Borough. The availability of ground water in the Borough is limited by the physical characteristics of the underlying bedrock, and its upland topographic setting. The crystalline rocks (metabasalt, metarhyolite, greenstone schist) that underlie most of the study area are among the lowest yielding aquifers in the Commonwealth. More than 25 percent of the wells drilled in the metabasalt, the largest bedrock aquifer in the study area, have driller reported yields less than 1.25 gallons per minute. Driller reports indicate also that water-producing zones are shallow and few in number. In general, 50 percent of the water-producing zones reported by drillers are penetrated at depths of 200 feet or less and 90 percent at depths of 370 feet or less. Borehole geophysical data indicate that most of the water-producing zones are at lithologic contacts, but such contacts are penetrated infrequently and commonly do not intersect areas of ground-water recharge. Single-well aquifer tests and slug tests indicate that the bedrock aquifers also do not readily transmit large amounts of water. The median hydraulic conductivity and transmissivity of the bedrock aquifers are 0.01 foot per dayand 2.75 feet squared per day, respectively. The crystalline and siliciclastic (Weverton and Loudoun Formations) bedrock aquifers are moderately to highly resistant to weathering, resulting in topographic highs coupled with steep, narrow valleys. This rugged topography results in extensive surface runoff, which limits infiltration and hence recharge to the shallow and deep ground-water systems. Streams that flow through the study area generally are small and ephemeral. Where perennial, the streams represent areas of ground-water discharge. Thickness of the overlying mantle (regolith or depth to bedrock) varies from 0 to more than 65 feet over short distances. In general, a thick regolith will store and transmit large quantities of water to the underlying bedrock aquifers. In the study area, however, there is no correlation between thick regolith and greater reported yields. Thus, it appears that the hydraulic connection between water-bearing fractures at depth and ground water stored in the regolith is poor, which further limits ground-water availability. Recharge to the bedrock aquifers from the approximately 46 inches of annual precipitation aver-ages about 13 inches per year, or 975 gallons per day per acre. During drought years, however, this recharge rate may average only 9 inches per year [675 gallons per day per acre]. Decreased recharge to the bedrock aquifers results in declining water levels and possibly dry wells, as well as reduced flows to streams and other surface-water bodies. Although the consumptive use of ground water by homeowners is minor (about 14 percent), the pumping of a well will change the natural flow paths of ground water and reduce the amount of water stored (at least temporarily) in the bedrock aquifers.