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  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. The Relationship between Undergraduate Attendance and Performance Revisited: Alignment of Student and Instructor Goals

    ERIC Educational Resources Information Center

    Westerman, James W.; Perez-Batres, Luis A.; Coffey, Betty S.; Pouder, Richard W.

    2011-01-01

    We revisit the relationship between attendance and performance in the undergraduate university setting and apply agency theory in the instructor-student context. Building on agency theory propositions in the educational setting advanced by Smith, Zsidisin, and Adams (2005), we propose that the student and instructor must align goals to promote the…

  16. 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.

  17. 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…

  18. 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,"…

  19. 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…

  20. 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)

  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. 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

  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. PMID:15545105

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Miscarriage Among Flight Attendants

    PubMed Central

    Grajewski, Barbara; Whelan, Elizabeth A.; Lawson, Christina C.; Hein, Misty J.; Waters, Martha A.; Anderson, Jeri L.; MacDonald, Leslie A.; Mertens, Christopher J.; Tseng, Chih-Yu; Cassinelli, Rick T.; Luo, Lian

    2015-01-01

    Background Cosmic radiation and circadian disruption are potential reproductive hazards for flight attendants. Methods Flight attendants from 3 US airlines in 3 cities were interviewed for pregnancy histories and lifestyle, medical, and occupational covariates. We assessed cosmic radiation and circadian disruption from company records of 2 million individual flights. Using Cox regression models, we compared respondents (1) by levels of flight exposures and (2) to teachers from the same cities, to evaluate whether these exposures were associated with miscarriage. Results Of 2654 women interviewed (2273 flight attendants and 381 teachers), 958 pregnancies among 764 women met study criteria. A hypothetical pregnant flight attendant with median firsttrimester exposures flew 130 hours in 53 flight segments, crossed 34 time zones, and flew 15 hours during her home-base sleep hours (10 pm–8 am), incurring 0.13 mGy absorbed dose (0.36 mSv effective dose) of cosmic radiation. About 2% of flight attendant pregnancies were likely exposed to a solar particle event, but doses varied widely. Analyses suggested that cosmic radiation exposure of 0.1 mGy or more may be associated with increased risk of miscarriage in weeks 9–13 (odds ratio = 1.7 [95% confidence interval = 0.95–3.2]). Risk of a first-trimester miscarriage with 15 hours or more of flying during home-base sleep hours was increased (1.5 [1.1–2.2]), as was risk with high physical job demands (2.5 [1.5–4.2]). Miscarriage risk was not increased among flight attendants compared with teachers. Conclusions Miscarriage was associated with flight attendant work during sleep hours and high physical job demands and may be associated with cosmic radiation exposure. PMID:25563432

  10. 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

  11. 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…

  12. 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.

  13. Student Attendance Accounting Manual.

    ERIC Educational Resources Information Center

    Freitas, Joseph M.

    In response to state legislation authorizing procedures for changes in academic calendars and measurement of student workload in California community colleges, this manual from the Chancellor's Office provides guidelines for student attendance accounting. Chapter 1 explains general items such as the academic calendar, admissions policies, student…

  14. School Counselors Improving Attendance

    ERIC Educational Resources Information Center

    Edwards, LaWanda

    2013-01-01

    This study examined the outcomes of interventions used to address attendance issues at a middle school located in the Southern United States. School-wide interventions were implemented to address absenteeism of all students and individual interventions were implemented to address absenteeism with targeted students. An explanation of each…

  15. 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.

  16. 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

  17. "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…

  18. 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.

  19. 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)

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Increasing Reservation Attendance: Ganado's Approach.

    ERIC Educational Resources Information Center

    Foster, Carl; And Others

    Based on recommendations of a District Attendance Task Force, in 1980 the Ganado School District (a Navajo Reservation District) formulated an Attendance Improvement Plan which decreased the primary school's absentee rate 37% over previous years and which dramatically increased Friday attendance. The primary school targeted "high risk" chronic…

  9. 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)

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. Attendance Policies, Student Attendance, and Instructor Verbal Aggressiveness

    ERIC Educational Resources Information Center

    Snyder, Jason; Forbus, Robert; Cistulli, Mark

    2012-01-01

    The authors utilized an experimental design across six sections of a managerial communications course (N = 173) to test the impact of instructor verbal aggressiveness and class attendance policies on student class attendance. The experimental group received a policy based on the principle of social proof (R. B. Cialdini, 2001), which indicated…

  1. 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.

  2. 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

  3. Student Attendance Accounting Manual, 1996.

    ERIC Educational Resources Information Center

    California Community Colleges, Sacramento. Office of the Chancellor.

    This report documents student attendance in California's community colleges. It begins by outlining the requirements for academic calendars as they relate to student attendance. It then defines who is admissible to community colleges in California and classifies all of the possible enrollment statuses one may take. The first chapter defines which…

  4. Compulsory Attendance vs. Home Instruction.

    ERIC Educational Resources Information Center

    McGee, Jerry C.

    Most states require compulsory attendance of students through age 16. Challenges to the compulsory attendance laws often derive from disputes between parents and school officials over home instruction. This paper reviews prominent court cases that address legal issues pertaining to home schooling. The landmark case of "Pierce v. Society of…

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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...

  10. 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.

  11. Religious Attendance as Reproductive Support

    PubMed Central

    Weeden, Jason; Cohen, Adam B.; Kenrick, Douglas T.

    2009-01-01

    We argue that a central function of religious attendance in the contemporary U.S. is to support a high-fertility, monogamous mating strategy. Although religious attendance is correlated with many demographic, personality, moral, and behavioral variables, we propose that sexual and family variables are at the core of many of these relationships. Numerous researchers have assumed that religious socialization causes people to feel moral reactions and engage in behaviors promoted by religious groups. On our view, mating preferences are centrally involved in individual differences in attraction to religious groups. In a sample of 21,131 individuals who participated in the U.S. General Social Survey, sexual behaviors were the relatively strongest predictors of religious attendance, even after controlling for age and gender. Effects of age and gender on religious attendance were weaker, and substantially reduced when controlling for sexual and family patterns. A sample of 902 college students provided more detailed information on religious, moral, and sexual variables. Results suggest that 1) moral views about sexual behavior are more strongly linked to religious attendance than other moral issues, and 2) mating strategy is more powerful than standard personality variables in predicting religious attendance. These findings suggest that reproductive strategies are at the heart of variations in religious attendance. PMID:21874105

  12. 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…

  13. 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)

  14. 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…

  15. 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

  16. 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

  17. 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

  18. 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…

  19. 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)

  20. 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)

  1. 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…

  2. 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

  3. 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…

  4. 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

  5. Using Attendance Worksheets to Improve Student Attendance, Participation, and Learning

    NASA Astrophysics Data System (ADS)

    Rhoads, Edward

    2013-06-01

    As science instructors we are faced with two main barriers with respect to student learning. The first is motivating our students to attend class and the second is to make them active participants in the learning process once we have gotten them to class. As we head further into the internet age this problem only gets exacerbated as students have replaced newspapers with cell phones which can surf the web, check their emails, and play games. Quizzes can motivated the students to attend class but do not necessarily motivate them to pay attention. Active learning techniques work but we as instructors have been bombarded by the active learning message to the point that we either do it already or refuse to. I present another option which in my classroom has doubled the rate at which students learn my material. By using attendance worksheets instead of end of class quizzes I hold students accountable for not just their attendance but for when they show up and when they leave the class. In addition it makes the students an active participant in the class even without using active learning techniques as they are writing notes and answering the questions you have posed while the class is in progress. Therefore using attendance worksheets is an effective tool to use in order to guide student learning.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. This Is About Attendance Counselling.

    ERIC Educational Resources Information Center

    Prokos, George

    The days of the formidable truant officer who chased after hooky-playing delinquents and led them back to school by the ear are gone. Today's "attendance counselors" see their function as protecting a child's right to a meaningful education. Although their goal is still to get absent students back to classes, their approach is now a more…

  13. Student Satisfaction with Attending Systems.

    ERIC Educational Resources Information Center

    McConnell, Thomas A.; And Others

    1993-01-01

    A survey of 252 dental students in three schools measured student satisfaction with (1) the patient care system in the dental school clinic; and (2) the responsibilities of the attending faculty, who manage 10-student teams. Results indicated general satisfaction but point to some problems in individual situations. (MSE)

  14. Birthday Effects and Preschool Attendance

    ERIC Educational Resources Information Center

    Huang, Francis L.; Invernizzi, Marcia A.

    2013-01-01

    Young-for-grade students have been shown to receive lower grades and have a higher likelihood of retention compared to their oldest peers upon kindergarten entry. Our study of 1474 economically disadvantaged first-time kindergarteners investigates if preschool attendance may ameliorate some of the risks potentially associated with being…

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. [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.

  20. 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

  1. 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

  2. Traditional birth attendants in Malawi.

    PubMed

    Smit, J J

    1994-06-01

    Traditional Birth Attendants (TBAs) and traditional healers form an important link in the chain of health personnel providing primary health care in Malawi. In spite of the establishment of hospitals and health centres, it is to these traditional healers and TBAs that the majority of people turn in times of sickness and child-birth. Approximately 60 per cent of all deliveries in Malawi occur in the villages. It is therefore important that due regard be paid to the activities of these traditional practitioners in order to ensure the achievement of the goal--"Health for all by the year 2000". The training of TBAs is seen as part of the Maternal and Child Health Services in the country. The Ministry of Health is responsible for the training and control of Traditional Birth Attendants and in 1976 opened a register in order to list all those trained. In early 1978 a training course for selected TBAs was conducted at the Kamuzu Central Hospital, Lilongwe and from 1982 the training programme evolved into a national training programme for TBAs. By February 1987, a total of 841 Traditional birth Attendants had been trained and the programme is still continuing.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. An Examination of Attendance in Louisiana Schools.

    ERIC Educational Resources Information Center

    Crone, Linda J.; And Others

    Research results appear inconclusive as to the relationship of student attendance to student achievement, although most practitioners cite increased student attendance as an extremely desirable school outcome. The purpose of the examination of student attendance in the Louisiana public schools was twofold: (1) to determine the relationship of…

  10. 14 CFR 125.269 - Flight attendants.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Flight attendants. 125.269 Section 125.269....269 Flight attendants. (a) Each certificate holder shall provide at least the following flight... passengers—one flight attendant. (2) For airplanes having more than 50 but less than 101...

  11. 14 CFR 121.391 - Flight attendants.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Flight attendants. 121.391 Section 121.391..., FLAG, AND SUPPLEMENTAL OPERATIONS Airman and Crewmember Requirements § 121.391 Flight attendants. Link... least the following flight attendants on each passenger-carrying airplane used: (1) For airplanes...

  12. 14 CFR 125.269 - Flight attendants.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Flight attendants. 125.269 Section 125.269....269 Flight attendants. (a) Each certificate holder shall provide at least the following flight... passengers—one flight attendant. (2) For airplanes having more than 50 but less than 101...

  13. 14 CFR 125.269 - Flight attendants.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Flight attendants. 125.269 Section 125.269....269 Flight attendants. (a) Each certificate holder shall provide at least the following flight... passengers—one flight attendant. (2) For airplanes having more than 50 but less than 101...

  14. 14 CFR 121.391 - Flight attendants.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Flight attendants. 121.391 Section 121.391..., FLAG, AND SUPPLEMENTAL OPERATIONS Airman and Crewmember Requirements § 121.391 Flight attendants. (a... following flight attendants on board each passenger-carrying airplane when passengers are on board: (1)...

  15. 14 CFR 121.391 - Flight attendants.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Flight attendants. 121.391 Section 121.391..., FLAG, AND SUPPLEMENTAL OPERATIONS Airman and Crewmember Requirements § 121.391 Flight attendants. (a... following flight attendants on board each passenger-carrying airplane when passengers are on board: (1)...

  16. 14 CFR 121.391 - Flight attendants.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Flight attendants. 121.391 Section 121.391..., FLAG, AND SUPPLEMENTAL OPERATIONS Airman and Crewmember Requirements § 121.391 Flight attendants. (a... following flight attendants on board each passenger-carrying airplane when passengers are on board: (1)...

  17. 14 CFR 125.269 - Flight attendants.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Flight attendants. 125.269 Section 125.269....269 Flight attendants. (a) Each certificate holder shall provide at least the following flight... passengers—one flight attendant. (2) For airplanes having more than 50 but less than 101...

  18. 14 CFR 121.391 - Flight attendants.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Flight attendants. 121.391 Section 121.391..., FLAG, AND SUPPLEMENTAL OPERATIONS Airman and Crewmember Requirements § 121.391 Flight attendants. (a) Each certificate holder shall provide at least the following flight attendants on each...

  19. 14 CFR 125.269 - Flight attendants.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Flight attendants. 125.269 Section 125.269....269 Flight attendants. (a) Each certificate holder shall provide at least the following flight... passengers—one flight attendant. (2) For airplanes having more than 50 but less than 101...

  20. Flight Attendants. Aviation Careers Series. Revised.

    ERIC Educational Resources Information Center

    Zaharevitz, Walter

    This booklet, one in a series on aviation careers, outlines the career opportunities of airline flight attendants. General information about airline hiring policies for flight attendants are discussed, and the following information about the flight attendant job classification is provided: nature of the work, working conditions, where the jobs…

  1. 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...

  2. 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

  3. 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.

  4. 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)

  5. 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...

  6. 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...

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Evaluation of Flight Attendant Technical Knowledge

    NASA Technical Reports Server (NTRS)

    Dunbar, Melisa G.; Chute, Rebecca D.; Rosekind, Mark (Technical Monitor)

    1997-01-01

    Accident and incident reports have indicated that flight attendants have numerous opportunities to provide the flight-deck crew with operational information that may prevent or lessen the severity of a potential problem. Additionally, as carrier fleets transition from three person to two person flight-deck crews, the reliance upon the cabin crew for the transfer of this information may increase further. Recent research indicates that flight attendants do not feel confident in their ability to describe mechanical parts or malfunctions of the aircraft, and the lack of flight attendant technical training has been referenced in a number of recent reports. Chute and Wiener describe five factors which may produce communication barriers between cockpit and cabin crews: the historical background of aviation, the physical separation of the two crews, psychosocial issues, regulatory factors, and organizational factors. By examining these areas of division we can identify possible bridges and address the implications of deficient cockpit/cabin communication on flight safety. Flight attendant operational knowledge may provide some mitigation of these barriers. The present study explored both flight attendant technical knowledge and flight attendant and pilot expectations of flight attendant technical knowledge. To assess the technical knowledge of cabin crewmembers, 177 current flight attendants from two U.S. carriers voluntarily completed a 13-item technical quiz. To investigate expectations of flight attendant technical knowledge, 181 pilots and a second sample of 96 flight attendants, from the same two airlines, completed surveys designed to capture each group's expectations of operational knowledge required of flight attendants. Analyses revealed several discrepancies between the present level of flight attendant operational knowledge and pilots' and flight attendants' expected and desired levels of technical knowledge. Implications for training will be discussed.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 42 CFR 35.22 - Attendants.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Attendants. 35.22 Section 35.22 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT Transfer of Patients § 35.22 Attendants. Patients shall be transferred by such...

  11. 33 CFR 401.46 - Attending lines.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Attending lines. 401.46 Section... TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.46 Attending lines. (a) Lines of... vessel is passing through a lock. (b) While a vessel is within a lock chamber and lines are hand held...

  12. 33 CFR 401.46 - Attending lines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Attending lines. 401.46 Section... TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.46 Attending lines. (a) Lines of... vessel is passing through a lock. (b) While a vessel is within a lock chamber and lines are hand held...

  13. 38 CFR 3.667 - School attendance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false School attendance. 3.667..., Compensation, and Dependency and Indemnity Compensation Adjustments and Resumptions § 3.667 School attendance. (a) General. (1) Pension or compensation may be paid from a child's 18th birthday based upon...

  14. 38 CFR 3.667 - School attendance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false School attendance. 3.667..., Compensation, and Dependency and Indemnity Compensation Adjustments and Resumptions § 3.667 School attendance. (a) General. (1) Pension or compensation may be paid from a child's 18th birthday based upon...

  15. 38 CFR 3.667 - School attendance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false School attendance. 3.667..., Compensation, and Dependency and Indemnity Compensation Adjustments and Resumptions § 3.667 School attendance. (a) General. (1) Pension or compensation may be paid from a child's 18th birthday based upon...

  16. Compulsory Attendance: An Analysis of Litigation

    ERIC Educational Resources Information Center

    Leddon, Leo Levy, Jr.

    2010-01-01

    The purpose of this research was to examine court cases dealing with compulsory attendance laws, also known as compulsory education laws, for the purpose of establishing the issues, outcomes, and trends in compulsory attendance litigation. In this manner, school officials could be provided guidance on dealing with issues surrounding the attendance…

  17. Community College Attendance and Socioeconomic Plans

    ERIC Educational Resources Information Center

    Park, Sueuk; Pascarella, Ernest T.

    2010-01-01

    Using data from the National Education Longitudinal Study, 1988 (NELS: 88), this paper documents differences in the socioeconomic plans of students in two-year and four-year colleges. We found attendance at a two-year college led to a modest but statistically significant disadvantage in socioeconomic plans. However, the impact of attending a…

  18. 42 CFR 35.22 - Attendants.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Attendants. 35.22 Section 35.22 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND... nursing attendants shall be qualified to care for persons suffering from the type of disease or...

  19. The Development of Rhythmic Attending in Auditory Sequences: Attunement, Referent Period, Focal Attending.

    ERIC Educational Resources Information Center

    Drake, Carolyn; Jones, Mari Riess; Baruch, Clarisse

    2000-01-01

    Extends dynamic attending theory to developmental questions concerning tempo and time hierarchies. Compares performance of 4- to 10-year-olds, and adults on dynamic attending activities. Suggests that growth trends could be expressed in terms of listeners' engagement of slower attending oscillators with age and musical experience, accompanied by…

  20. Attending Behavior of Children Near a Child Who is Reinforced for Attending

    ERIC Educational Resources Information Center

    Okovita, Hymie Wolf; Bucher, Bradley

    1976-01-01

    The present study investigated effects of a token program for one child on the attending behavior of other children sitting near him. Results show the rewarded child's attending increased in the reinforcement conditions and the unrewarded children's attending increased when they were sitting on either side of the rewarded child. (Author)

  1. 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

  2. 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).

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. The Influence of Religious Attendance on Smoking

    PubMed Central

    Brown, Qiana L.; Linton, Sabriya L.; Harrell, Paul T.; Mancha, Brent Edward; Alexandre, Pierre K.; Chen, Kuan-Fu; Eaton, William W.

    2014-01-01

    Generalized linear models were used to assess the relationship between religious attendance and lifetime smoking status among middle-aged adults (n = 666) sampled from waves three (1993 to 1996) and four (2004 to 2005) of the Baltimore Epidemiologic Catchment Area (ECA) study. Religious attendance once per week or greater as compared to never was inversely associated with smoking status. Future research should explore potential mediating factors of the association between religious attendance and smoking among middle-aged adults in order to gain a greater understanding of the mechanisms underlying this relationship. Funding: NIMH grant DA026652; NIDA grant T32DA007292. PMID:24827865

  16. 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

  17. 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

  18. 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

  19. Improving attendance in weight-control programs.

    PubMed

    Mullen, P D; Culjat, D

    1980-01-01

    This field study evaluated the use of a food dairy as a screening device for admission to a behaviorally oriented weight-reduction program for its effectiveness in improving attendance. All study participants were required (1) to attend an orientation meeting where the program was described and questions were solicited and (2) to pay a $25, nonrefundable fee. During the orientation experimental-group attendees were told that a 2-week food dairy was a requirement for admission to the series. It was expected the experimental requirement would decrease the number of less motivated enrollees, thereby reducing early termination and improving attendance. Keeping the record was in itself expected to modify eating behavior. This would have the effect of adding 2 weeks to the program and, therefore, weight loss at the end of the program was expected to be greater. In general, the hypotheses were confirmed. A smaller proportion of those who had the food-dairy requirement enrolled. a significantly larger proportion of experimental-group women enrollees attended at least three-quarters of the sessions. The attendance records of control-group and experimental-group men were not significantly different. Mean weight loss at the end of the program was greater for those enrolled under the experimental condition. Achievement of a weight loss of at least 8 pounds was found to be positively related to attendance.

  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. Epidemiology of frequent attenders: a 3-year historic cohort study comparing attendance, morbidity and prescriptions of one-year and persistent frequent attenders

    PubMed Central

    Smits, Frans ThM; Brouwer, Henk J; ter Riet, Gerben; van Weert, Henk CP

    2009-01-01

    Background General Practitioners spend a disproportionate amount of time on frequent attenders. So far, trials on the effect of interventions on frequent attenders have shown negative results. However, these trials were conducted in short-term frequent attenders. It would be more reasonable to target intervention at persistent frequent attenders. Typical characteristics of persistent frequent attenders, as opposed to 1-year frequent attenders and non-frequent attenders, may generate hypotheses regarding modifiable factors on which new randomized trials may be designed. Methods We used the data of all 28,860 adult patients from 5 primary healthcare centers. Frequent attenders were patients whose attendance rate ranked in the (age and sex adjusted) top 10 percent during 1 year (1-year frequent attenders) or 3 years (persistent frequent attenders). All other patients on the register over the 3-year period were referred to as non-frequent attenders. The lists of medical problems coded by the GP using the International Classification of Primary Care (ICPC) were used to assess morbidity. First, we determined which proportion of 1-year frequent attenders was still a frequent attender during the next two consecutive years and calculated the GPs' workload for these patients. Second, we compared morbidity and number of prescriptions for non-frequent attenders, 1-year frequent attenders and persistent frequent attenders. Results Of all 1-year frequent attenders, 15.4% became a persistent frequent attender equal to 1.6% of all patients. The 1-year frequent attenders (3,045; 10.6%) were responsible for 39% of the face-to-face consultations; the 470 patients who would become persistent frequent attenders (1.6%) were responsible for 8% of all consultations in 2003. Persistent frequent attenders presented more social problems, more psychiatric problems and medically unexplained physical symptoms, but also more chronic somatic diseases (especially diabetes). They received more

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. Religious Affiliation, Religious Service Attendance, and Mortality.

    PubMed

    Kim, Jibum; Smith, Tom W; Kang, Jeong-han

    2015-12-01

    Very few studies have examined the effects of both religious affiliation and religiosity on mortality at the same time, and studies employing multiple dimensions of religiosity other than religious attendance are rare. Using the newly created General Social Survey-National Death Index data, our report contributes to the religion and mortality literature by examining religious affiliation and religiosity at the same time. Compared to Mainline Protestants, Catholics, Jews, and other religious groups have lower risk of death, but Black Protestants, Evangelical Protestants, and even those with no religious affiliation are not different from Mainline Protestants. While our study is consistent with previous findings that religious attendance leads to a reduction in mortality, we did not find other religious measures, such as strength of religious affiliation, frequency of praying, belief in an afterlife, and belief in God to be associated with mortality. We also find interaction effects between religious affiliation and attendance. The lowest mortality of Jews and other religious groups is more apparent for those with lower religious attendance. Thus, our result may emphasize the need for other research to focus on the effects of religious group and religious attendance on mortality at the same time. PMID:24939004

  17. Religious Affiliation, Religious Service Attendance, and Mortality.

    PubMed

    Kim, Jibum; Smith, Tom W; Kang, Jeong-han

    2015-12-01

    Very few studies have examined the effects of both religious affiliation and religiosity on mortality at the same time, and studies employing multiple dimensions of religiosity other than religious attendance are rare. Using the newly created General Social Survey-National Death Index data, our report contributes to the religion and mortality literature by examining religious affiliation and religiosity at the same time. Compared to Mainline Protestants, Catholics, Jews, and other religious groups have lower risk of death, but Black Protestants, Evangelical Protestants, and even those with no religious affiliation are not different from Mainline Protestants. While our study is consistent with previous findings that religious attendance leads to a reduction in mortality, we did not find other religious measures, such as strength of religious affiliation, frequency of praying, belief in an afterlife, and belief in God to be associated with mortality. We also find interaction effects between religious affiliation and attendance. The lowest mortality of Jews and other religious groups is more apparent for those with lower religious attendance. Thus, our result may emphasize the need for other research to focus on the effects of religious group and religious attendance on mortality at the same time.

  18. 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.

  19. [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.

  20. 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.

  1. Does Attendance Matter? An Examination of Student Attitudes, Participation, Performance and Attendance

    ERIC Educational Resources Information Center

    Massingham, Peter; Herrington, Tony

    2006-01-01

    Non attendance of lectures and tutorials appears to be a growing trend. The literature suggests many possible reasons including students' changing lifestyle, attitudes, teaching and technology. This paper looks at the reasons for non attendance of students in the Faculty of Commerce at the University of Wollongong and identifies relationships…

  2. An Analysis of Florida's School Districts' Attendance Policies and their Relationship to High School Attendance Rates

    ERIC Educational Resources Information Center

    Reardon, Ryan Turner

    2008-01-01

    The purpose of this non-experimental correlational study was to determine the relationship between the type of attendance policies in the high schools of the 67 Florida school districts, the size of the school district (number of high school students), the socioeconomic status SES) of the school district, and the average daily attendance rate of…

  3. A Guide for the Personal Care Attendant: Independent Living with Attendant Care.

    ERIC Educational Resources Information Center

    Board, Mary Ann; And Others

    The first of three booklets on attendant care of severely disabled persons is addressed to the personal care attendants (PCAs). An introductory section reviews the basic concepts of independent living, noting the role of PCAs in promoting independence. Discussions of congenital and acquired disability are followed by information on equipment and…

  4. 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.

  5. 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

  6. 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…

  7. 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…

  8. 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...

  9. 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...

  10. 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...

  11. 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.

  12. Social Capital, Place of Residence, and College Attendance.

    ERIC Educational Resources Information Center

    Smith, Mark H.; And Others

    1995-01-01

    Analysis of High School and Beyond data reveals that suburban students were most likely and rural students were least likely to attend college. Parental expectation of college attendance was the most powerful predictor of subsequent college attendance across residence categories. College attendance of rural students was also predicted by community…

  13. Crackdown on Attendance--The Word Is Out.

    ERIC Educational Resources Information Center

    DuFour, Richard

    1983-01-01

    Procedures successful for one school in establishing good attendance include phone calls on all unexplained absences, discipline for unexcused absences, incentives for good attendance, charting attendance patterns, and staff coordination for monitoring attendance. Increased state aid, a more positive school climate, and greater student achievement…

  14. 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

  15. 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.

  16. Service Station Attendant. Performance Objectives. Basic Course.

    ERIC Educational Resources Information Center

    Davis, John

    Several intermediate performance objectives and corresponding criterion measures are listed for each of 24 terminal objectives for a basic secondary level service station attendant course. The materials were developed for a two-semester course (2 and 3 hours daily). The specialized classroom and shop experiences are designed to enable the student…

  17. Medical specialist attendance in nursing homes.

    PubMed

    Balzer, Katrin; Butz, Stefanie; Bentzel, Jenny; Boulkhemair, Dalila; Lühmann, Dagmar

    2013-01-01

    The care in nursing homes was examined based on scientific studies. The analysis focuses on dementia and type II diabetes. There is evidence for deficits in the supply of medical specialist attendance to nursing home residents with these diseases in Germany. Compared with corresponding guidelines the medical care for nursing home residents may be too low or inadequate.

  18. Assessing Reasons for School Non-Attendance

    ERIC Educational Resources Information Center

    Havik, Trude; Bru, Edvin; Ertesvåg, Sigrun K.

    2015-01-01

    The aim of the present study is to assess reasons for school non-attendance including somatic symptoms, subjective health complaints, truancy, and school refusal and to investigate the relationship of these with gender, grade, and self-reported special educational needs. The study is based on a self-reported questionnaire distributed to students…

  19. Medical specialist attendance in nursing homes

    PubMed Central

    Balzer, Katrin; Butz, Stefanie; Bentzel, Jenny; Boulkhemair, Dalila; Lühmann, Dagmar

    2013-01-01

    The care in nursing homes was examined based on scientific studies. The analysis focuses on dementia and type II diabetes. There is evidence for deficits in the supply of medical specialist attendance to nursing home residents with these diseases in Germany. Compared with corresponding guidelines the medical care for nursing home residents may be too low or inadequate. PMID:23755088

  20. Adolescent Marijuana Use and School Attendance

    ERIC Educational Resources Information Center

    Roebuck, M. Christopher; French, Michael T.; Dennis, Michael L.

    2004-01-01

    This paper explores the relationship between adolescent marijuana use and school attendance. Data were pooled from the 1997 and 1998 National Household Surveys on Drug Abuse to form a sample of 15 168 adolescents, aged 12-18 years, who had not yet complete high school. The analysis determined the role of marijuana use in adolescent school dropout…

  1. International Determinants of Private School Attendance

    ERIC Educational Resources Information Center

    Rutkowski, Leslie; Rutkowski, David; Plucker, Jonathan

    2012-01-01

    The current study uses Programme for International Student Assessment (PISA) 2006 data to investigate international determinants of private school attendance. In particular, we seek to understand whether student achievement and home background factors such as socioeconomic status (SES) or motivational and goal-oriented factors are more predictive…

  2. The Effects of Attending a Diverse College

    ERIC Educational Resources Information Center

    Hinrichs, Peter

    2011-01-01

    The question of whether there are benefits to be obtained from having a diverse student body is a key issue in the debate over affirmative action. This paper estimates the effects of college racial diversity on post-college earnings, civic behavior, and satisfaction with the college attended. I use the Beginning Postsecondary Students survey,…

  3. School Climate, Academic Performance, Attendance, and Dropout.

    ERIC Educational Resources Information Center

    Gottfredson, Gary D.; Gottfredson, Denise C.

    Correlates of the teacher scales from the Effective School Battery (ESB) were examined in the Charleston County School District (CCSD) in South Carolina. Focus was on determining the relations between the ESB teacher scales and student academic achievement, progress through the grades, attendance, and dropout. This study was conducted as part of a…

  4. 9 CFR 91.24 - Attendants.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Attendants. 91.24 Section 91.24 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS INSPECTION AND HANDLING...

  5. 9 CFR 91.24 - Attendants.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Attendants. 91.24 Section 91.24 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS INSPECTION AND HANDLING...

  6. 9 CFR 91.24 - Attendants.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Attendants. 91.24 Section 91.24 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS INSPECTION AND HANDLING OF LIVESTOCK FOR EXPORTATION Inspection of Vessels...

  7. 9 CFR 91.24 - Attendants.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Attendants. 91.24 Section 91.24 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS INSPECTION AND HANDLING...

  8. 9 CFR 91.24 - Attendants.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Attendants. 91.24 Section 91.24 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS INSPECTION AND HANDLING...

  9. Attendance and Truancy Programs. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2007-01-01

    According to the 2000 census, high school dropouts had a 52% employment rate, compared to 71% for high school graduates and 83% for college graduates. According to NCSE, the national dropout rate is 30% of which 80% had been chronically absent from school ("School attendance tracking: Challenges and effective practices"), which puts the high…

  10. Encouraging Faculty Attendance at Professional Development Events

    ERIC Educational Resources Information Center

    Burdick, Dakin; Doherty, Tim; Schoenfeld, Naomi

    2015-01-01

    For faculty development events to have the greatest impact on campus practice, faculty developers need to attract and include as many faculty members as possible at their events. This article describes the testing of a checklist regarding faculty attendance at professional development events through a survey of 238 faculty members at small…

  11. Hidden Transcripts of Flight Attendant Resistance.

    ERIC Educational Resources Information Center

    Murphy, Alexandra G.

    1998-01-01

    Analyzes (using flight attendants) hidden transcripts--interactions, stories, myths, and rituals in which employees participate beyond direct observation--to provide an avenue to identify resistance and change in the organizing process. Challenges the outdated ideal of transmissional meaning, questions organizational power by including the…

  12. 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…

  13. 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).

  14. 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…

  15. 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…

  16. 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…

  17. 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.…

  18. 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…

  19. 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…

  20. 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,…

  1. 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)

  2. 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)

  3. 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…

  4. 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)

  5. 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)

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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"…

  11. 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.…

  12. 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)

  13. 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…

  14. 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…

  15. 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…

  16. 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)…

  17. 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.

  18. "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…

  19. 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

  20. 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.

  1. 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…

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. Quantitative analyses of observing and attending.

    PubMed

    Shahan, Timothy A; Podlesnik, Christopher A

    2008-06-01

    We review recent experiments examining whether simple models of the allocation and persistence of operant behavior are applicable to attending. In one series of experiments, observing responses of pigeons were used as an analog of attending. Maintenance of observing is often attributed to the conditioned reinforcing effects of a food-correlated stimulus (i.e., S+), so these experiments also may inform our understanding of conditioned reinforcement. Rates and allocations of observing were governed by rates of food or S+ delivery in a manner consistent with the matching law. Resistance to change of observing was well described by behavioral momentum theory only when rates of primary reinforcement in the context were considered. Rate and value of S+ deliveries did not affect resistance to change. Thus, persistence of attending to stimuli appears to be governed by primary reinforcement rates in the training context rather than conditioned reinforcing effects of the stimuli. An additional implication of these findings is that conditioned "reinforcers" may affect response rates through some mechanism other than response-strengthening. In a second series of experiments, we examined the applicability of the matching law to the allocation of attending to the elements of compound stimuli in a divided-attention task. The generalized matching law described performance well, and sensitivity to relative reinforcement varied with sample duration. The bias and sensitivity terms of the generalized matching law may provide measures of stimulus-driven and goal-driven control of divided attention. Further application of theories of operant behavior to performance on attention tasks may provide insights into what is referred to variously as endogenous, top-down, or goal-directed control of attention.

  12. Household Income and Preschool Attendance in China

    ERIC Educational Resources Information Center

    Gong, Xin; Xu, Di; Han, Wen-Jui

    2015-01-01

    This article draws upon the literature showing the benefits of high-quality preschools on child well-being to explore the role of household income on preschool attendance for a cohort of 3-to 6-year-olds in China using data from the China Health and Nutrition Survey, 1991-2006. Analyses are conducted separately for rural (N = 1,791) and urban…

  13. 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

  14. 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

  15. A Linear Programming Model for Assigning Students to Attendance Centers.

    ERIC Educational Resources Information Center

    Ontjes, Robert L.

    A linear programing model and procedures for optimal assignment of students to attendance centers are presented. An example of the use of linear programing for the assignment of students to attendance centers in a particular school district is given. (CK)

  16. 14 CFR 135.107 - Flight attendant crewmember requirement.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Flight attendant crewmember requirement... Flight Operations § 135.107 Flight attendant crewmember requirement. No certificate holder may operate an... is a flight attendant crewmember on board the aircraft....

  17. 14 CFR 135.107 - Flight attendant crewmember requirement.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Flight attendant crewmember requirement... Flight Operations § 135.107 Flight attendant crewmember requirement. No certificate holder may operate an... is a flight attendant crewmember on board the aircraft....

  18. 14 CFR 135.107 - Flight attendant crewmember requirement.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Flight attendant crewmember requirement... Flight Operations § 135.107 Flight attendant crewmember requirement. No certificate holder may operate an... is a flight attendant crewmember on board the aircraft....

  19. 38 CFR 21.374 - Authorization for travel of attendants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Authorization for travel... 38 U.S.C. Chapter 31 Interregional and Intraregional Travel of Veterans § 21.374 Authorization for travel of attendants. (a) Travel for attendants. The services of an attendant to accompany a...

  20. 38 CFR 21.374 - Authorization for travel of attendants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Authorization for travel... 38 U.S.C. Chapter 31 Interregional and Intraregional Travel of Veterans § 21.374 Authorization for travel of attendants. (a) Travel for attendants. The services of an attendant to accompany a...

  1. Class Attendance and Exam Performance: A Randomized Experiment

    ERIC Educational Resources Information Center

    Chen, Jennjou; Lin, Tsui-Fang

    2008-01-01

    The determination of college students' academic performance is an important issue in higher education. Whether students' attendance at lectures affects students' exam performance has received considerable attention. The authors conduct a randomized experiment to study the average attendance effect for students who choose to attend lectures, which…

  2. 14 CFR 135.107 - Flight attendant crewmember requirement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Flight attendant crewmember requirement... Flight Operations § 135.107 Flight attendant crewmember requirement. No certificate holder may operate an... is a flight attendant crewmember on board the aircraft....

  3. Should We Bother Improving Students' Attendance at Seminars?

    ERIC Educational Resources Information Center

    Gbadamosi, Gbolahan

    2015-01-01

    This study uses action research intervention to improve students' attendance at seminars. Specifically, the study asks the question: will students' attendance improve if they drive their own learning by running their own seminars? Records of lecture and seminar attendance at a module and comparative ones were used. Focus group interviews…

  4. Defining frequent attendance in general practice

    PubMed Central

    Smits, Frans TM; Mohrs, Jacob J; Beem, Ellen E; Bindels, Patrick JE; van Weert, Henk CPM

    2008-01-01

    Background General practitioners (GPs) or researchers sometimes need to identify frequent attenders (FAs) in order to screen them for unidentified problems and to test specific interventions. We wanted to assess different methods for selecting FAs to identify the most feasible and effective one for use in a general (group) practice. Methods In the second Dutch National Survey of General Practice, data were collected on 375 899 persons registered with 104 practices. Frequent attendance is defined as the top 3% and 10% of enlisted patients in each one-year age-sex group measured during the study year. We used these two selections as our reference standard. We also selected the top 3% and 10% FAs (90 and 97 percentile) based on four selection methods of diminishing preciseness. We compared the test characteristics of these four methods. Results Of all enlisted patients, 24 % did not consult the practice during the study year. The mean number of contacts in the top 10% FAs increased in men from 5.8 (age 15–24 years) to 17.5 (age 64–75 years) and in women from 9.7 to 19.8. In the top 3% of FAs, contacts increased in men from 9.2 to 24.5 and in women from 14 to 27.8. The selection of FAs becomes more precise when smaller age classes are used. All selection methods show acceptable results (kappa 0.849 – 0.942) except the three group method. Conclusion To correctly identify frequent attenders in general practice, we recommend dividing patients into at least three age groups per sex. PMID:18412954

  5. 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.

  6. 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

  7. 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

  8. 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).

  9. 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.

  10. 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

  11. 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…

  12. 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

  13. 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

  14. 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

  15. A Comparison of Sexual Minority Youth Who Attend Religiously Affiliated Schools and Their Nonreligious-School-Attending Counterparts

    ERIC Educational Resources Information Center

    Stewart, Brandon T.; Heck, Nicholas C.; Cochran, Bryan N.

    2015-01-01

    Sexual minority youth are an at-risk group for negative health outcomes. The present study compares descriptive characteristics and outness of sexual minority youth who attend religious schools to sexual minorities who do not attend religious schools, and also investigates if attending religiously affiliated schools is associated with levels of…

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. Religious Attendance and Loneliness in Later Life

    PubMed Central

    Rote, Sunshine; Hill, Terrence D.; Ellison, Christopher G.

    2013-01-01

    Purpose of the Study:  Studies show that loneliness is a major risk factor for health issues in later life. Although research suggests that religious involvement can protect against loneliness, explanations for this general pattern are underdeveloped and undertested. In this paper, we propose and test a theoretical model, which suggests that social integration and social support are key mechanisms that link religious attendance and loneliness. Design and Methods:  To formally test our theoretical model, we use data from the National Social Life Health and Aging Project (2005/2006), a large national probability sample of older adults aged 57–85 years. Results:  We find that religious attendance is associated with higher levels of social integration and social support and that social integration and social support are associated with lower levels of loneliness. A series of mediation tests confirm our theoretical model. Implications:  Taken together, our results suggest that involvement in religious institutions may protect against loneliness in later life by integrating older adults into larger and more supportive social networks. Future research should test whether these processes are valid across theoretically relevant subgroups. PMID:22555887

  3. Acute symptomatic hyponatremia in a flight attendant.

    PubMed

    Madero, Magdalena; Monares, Enrique; Domínguez, Aurelio Méndez; Ayus, Juan Carlos

    2015-08-01

    Acute symptomatic hyponatremia after thiazide diuretic initiation is a medical emergency. Here we describe the case of a flight attendant who developed acute hyponatremia during a flight and the potential risk factors for developing this condition. A 57-year-old flight attendant with history of essential hypertension was recently started on a thiazide diuretic. As she did routinely when working, she increased her water intake during a flight from London to Mexico City. She complained of nausea and headache during the flight. Upon arrival, she developed severe disorientation and presented to the hospital emergency room (ER) with a Glasgow scale of 12, hypoxia, and a generalized tonic clonic seizure. Her laboratory results on arrival were consistent with severe hyponatremia (serum Na 116 mEql/L) and severe cerebral edema by CT scan. She was treated with hypertonic saline, with complete resolution of the neurologic symptoms. We describe high water intake and hypoxia related to decreased partial pressure of oxygen in the cabin as the two main risk factors for thiazide-induced acute hyponatremia in this case. PMID:25500297

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Traditional birth attendants in Sierra Leone.

    PubMed

    Sisay, L

    1988-03-01

    Traditional Birth Attendants (TBAs) play a very significant role in the lives of a multitude of people in the traditional settlements and societies. They are people of eminent dignity and personality because their valuable contribution to society is appreciated by all, and they are known as those who keep the secrets of their society. In this article some of the practices of the TBAs are described, including the use of herbs in pregnancy tests, determining whether a delivery will be difficult, and determining labor signs, as well as the traditional method of care for premature babies. No cash payment is made to TBAs for their services, but gifts of rum and kola nuts are offered. PMID:12157965

  10. Lipoid Pneumonia in a Gas Station Attendant

    PubMed Central

    Yampara Guarachi, Gladis Isabel; Barbosa Moreira, Valeria; Santos Ferreira, Angela; Sias, Selma M. De A.; Rodrigues, Cristovão C.; Teixeira, Graça Helena M. do C.

    2014-01-01

    The exogenous lipoid pneumonia, uncommon in adults, is the result of the inhalation and/or aspiration of lipid material into the tracheobronchial tree. This is often confused with bacterial pneumonia and pulmonary tuberculosis due to a nonspecific clinical and radiologic picture. It presents acutely or chronically and may result in pulmonary fibrosis. We describe here a case of lipoid pneumonia in a gas station attendant who siphoned gasoline to fill motorcycles; he was hospitalized due to presenting with a respiratory infection that was hard to resolve. The patient underwent bronchoscopy with bronchoalveolar lavage, which, on cytochemical (oil red O) evaluation, was slightly positive for lipid material in the foamy cytoplasm of alveolar macrophages. Due to his occupational history and radiographic abnormalities suggestive of lipoid pneumonia, a lung biopsy was performed to confirm the diagnosis. The patient was serially treated with segmental lung lavage and showed clinical, functional, and radiological improvement. PMID:25374742

  11. 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.

  12. 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.

  13. 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

  14. 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.

  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 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. [Attendance in the Norwegian Breast Cancer Screening Programme].

    PubMed

    Sebuødegård, Sofie; Sagstad, Silje; Hofvind, Solveig

    2016-09-01

    BACKGROUND A high rate of attendance among women invited to the Norwegian Breast Cancer Screening Programme (NBCSP) is essential to achieve optimal effect, including reduction in breast cancer mortality. This article describes attendance in the programme by county, period and women's age at invitation.MATERIAL AND METHOD All women in the age group 50 - 69 years who are registered in the National Population Register are invited to attend the NBCSP every second year. In the study period 2007 - 2014, 2 142 369 invitations were sent, and 1 600 293 screening examinations were performed for 710 169 women. Use of the data is pursuant to the Cancer Registry Regulations.RESULTS Altogether 84 % of the women invited attended at least once in the study period. The average attendance rate per screening round was 75 %. In Rogaland, Nordland and Sogn og Fjordane counties more than 80 % attended, while in Oslo the figure was 62 %. The highest rate of attendance recorded was for women in the age group 62 - 67 years. The attendance in the prior screening round was of influence for reattendance.INTERPRETATION The mammography screening programme has a high level of acceptance among women in the target group. Possible reasons for the variation in attendance among the county districts should be identified. PMID:27686204

  3. 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

  4. 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.

  5. [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

  6. 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

  7. 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

  8. [Liu Jie attends Henan planned parenthood meeting].

    PubMed

    1981-03-01

    Henan scored excellent results in planned parenthood work last year. The natural population growth rate fell to 9.53/1000, a fall of 3.35/1000 from the 1979 level. The province victoriously fulfilled the population plan assigned by the state. Some 320,000 couples with 1 child have taken out single-child certificates. The provincial CCP Committee recently convened a planned parenthood meeting. Provincial CCP Committee 1st Secretary Liu Jie and Secretaries Dai Suli and Zhang Shude spoke at the meeting. Li Xiuzhen, deputy director of the State Council's planned parenthood leading group and director of its administrative office, also attended and spoke at the meeting. The speakers stressed: Party committees and government at all levels must strengthen leadership over planned parenthood, put this work in an important place on their agenda, resolve to promote this work, and succeed in grasping the 2 items of production together. We must further publicize and implement the Central Committee's open letter, vigorously advocate that each couple should have only 1 child, strictly control the birth of a 2nd child, and take resolute measures to prevent the birth of more than 2. We must put ideological education in the primary position. CCP and CYL members and cadres at all levels must take the lead in practicing planned parenthood.

  9. Profile of Clients Attending a Methadone Clinic

    PubMed Central

    JACOB, Sabrina Anne; MOHAMMED, Fauziah; HASSALI, Mohamed Azmi Ahmad

    2015-01-01

    Background: Client characteristics provide useful information for designing programs that target individuals with risk factors for substance use and for determining client retention. Therefore, this study examined the profiles of clients attending a methadone clinic. Methods: A cross-sectional analysis of clients of a methadone clinic was conducted through a survey to obtain a profile of methadone clients. Results: Of the 51 patients who responded (response rate: 66.2%), the mean (SD) age at which they started substance use was 19.8 (5.1) years. Friends were cited as the most regular source of drugs (82.4%), and heroin was the most commonly used drug (98%). Daily substance use was reported by 72.5% of the respondents; 23.5% admitted to having stolen money to purchase drugs; 92.2% tried quitting substance use on their own and 98% stated that the main reason for registering at the clinic was that they wanted to stop their drug dependence. Approximately 60% of clients were receiving methadone doses of less than 60 mg/day. Conclusion: Heroin is still the most popular drug of abuse and most clients still receive methadone doses below the recommended level, despite evidence of poor patient retention rates associated with these low doses. PMID:25892951

  10. Predictors of skilled attendance at delivery among antenatal clinic attendants in Ghana: a cross-sectional study of population data

    PubMed Central

    Amoakoh-Coleman, Mary; Ansah, Evelyn K; Agyepong, Irene Akua; Grobbee, Diederick E; Kayode, Gbenga A; Klipstein-Grobusch, Kerstin

    2015-01-01

    Objective To identify demographic, maternal and community predictors of skilled attendance at delivery among women who attend antenatal clinic at least once during their pregnancy in Ghana. Design A cross-sectional study using the 2008 Ghana Demographic and Health Survey (DHS) data. We used frequencies for descriptive analysis, χ2 test for associations and logistic regression to identify significant predictors. Predictive models were built with estimation of area under the receiver operating characteristic curves (AUC). Setting Ghana. Participants A total of 2041 women who had a live birth in the 5 years preceding the survey, and attended an antenatal clinic having a skilled provider, at least once, during the pregnancy. Outcome Skilled attendance at delivery. Results Overall, 60.5% (1235/2041) of women in our study sample reported skilled attendance at delivery. Significant positive associations existed between skilled attendance at delivery and the variables such as maternal educational level, wealth status class, ever use of contraception, previous pregnancy complications and health insurance coverage (p<0.001). Significant predictors of skilled attendance were wealth status class, residency, previous delivery complication, health insurance coverage and religion in a model with AUC (95% CI) of 0.85 (0.83 to 0.88). Conclusions Women less likely to have skilled attendance at delivery can be identified during antenatal care by using data on wealth status class, health insurance coverage, residence, history of previous birth complications and religion, and targeted with interventions to improve skilled attendance at delivery. PMID:25991459

  11. 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.

  12. 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.

  13. 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.

  14. 10 CFR 13.23 - Subpoenas for attendance at hearing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Subpoenas for attendance at hearing. 13.23 Section 13.23 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.23 Subpoenas for attendance at... under the control of a party may be served by first class mail. (f) A party or the individual to...

  15. 10 CFR 13.23 - Subpoenas for attendance at hearing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Subpoenas for attendance at hearing. 13.23 Section 13.23 Energy NUCLEAR REGULATORY COMMISSION PROGRAM FRAUD CIVIL REMEDIES § 13.23 Subpoenas for attendance at... under the control of a party may be served by first class mail. (f) A party or the individual to...

  16. 38 CFR 3.504 - Parents; aid and attendance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Parents; aid and... § 3.504 Parents; aid and attendance. The effective date of discontinuance of an increased award because of the parent's need for aid and attendance will be the day of last payment if need for aid...

  17. Net Cost of Attending Postsecondary Education. Indicator of the Month.

    ERIC Educational Resources Information Center

    National Center for Education Statistics (ED), Washington, DC.

    This sheet offers statistics and analysis of national data from the National Postsecondary Student Aid Study (1993) on the net costs of attending institutions of postsecondary education including tuition, fees, and living expenses minus grants, loans and work study compensation. One table shows costs of college attendance and student financial aid…

  18. 19 CFR 201.5 - Attendance fees and mileage.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Attendance fees and mileage. 201.5 Section 201.5 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION GENERAL RULES OF GENERAL APPLICATION Miscellaneous § 201.5 Attendance fees and mileage. (a) Deponents and witnesses. Any person compelled to...

  19. 19 CFR 201.5 - Attendance fees and mileage.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 3 2011-04-01 2011-04-01 false Attendance fees and mileage. 201.5 Section 201.5 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION GENERAL RULES OF GENERAL APPLICATION Miscellaneous § 201.5 Attendance fees and mileage. (a) Deponents and witnesses. Any person compelled to...

  20. Breast cancer risk in flight attendants: an update.

    PubMed

    Salhab, M; Mokbel, K

    2006-01-01

    Although further research is required, epidemiological evidence indicates that breast cancer risk is increased by 40% among flight attendants. Female flight attendants and women who fly frequently should be informed of this potential increase in risk and be encouraged to participate in appropriate breast cancer screening programs. PMID:17269586

  1. 6 CFR 13.23 - Subpoenas for attendance at hearing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 6 Domestic Security 1 2011-01-01 2011-01-01 false Subpoenas for attendance at hearing. 13.23 Section 13.23 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.23 Subpoenas for attendance at hearing. (a) A party wishing to procure...

  2. 6 CFR 13.23 - Subpoenas for attendance at hearing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 6 Domestic Security 1 2012-01-01 2012-01-01 false Subpoenas for attendance at hearing. 13.23 Section 13.23 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.23 Subpoenas for attendance at hearing. (a) A party wishing to procure...

  3. 38 CFR 3.504 - Parents; aid and attendance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Parents; aid and attendance. 3.504 Section 3.504 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... because of the parent's need for aid and attendance will be the day of last payment if need for aid...

  4. 38 CFR 3.504 - Parents; aid and attendance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Parents; aid and attendance. 3.504 Section 3.504 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... because of the parent's need for aid and attendance will be the day of last payment if need for aid...

  5. 38 CFR 3.504 - Parents; aid and attendance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Parents; aid and attendance. 3.504 Section 3.504 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... because of the parent's need for aid and attendance will be the day of last payment if need for aid...

  6. Strategies to Increase Student Attendance at an Elementary School

    ERIC Educational Resources Information Center

    Fitzpatrick-Doria, Geraldine Ann

    2013-01-01

    This action research study addressed the need to increase student attendance at an elementary school. Previously, this school's Average Daily Attendance (ADA) has been 92%. With having nearly 900 students, there are approximately 70 daily absences, 1,400 monthly absences, and 13,000 yearly absences. To address the challenge, the researcher…

  7. Attendance Factors for a Regional Research Organization's Annual Meeting.

    ERIC Educational Resources Information Center

    Boser, Judith A.; And Others

    One of the indicators of the health of an organization is the number of individuals participating in its annual meeting. Factors influencing meeting attendance and the relationships between positive attendance indicators and registration were studied for the Mid-South Educational Research Association, using participant data for 1984 through 1992.…

  8. Class Attendance and Performance in Principles of Economics

    ERIC Educational Resources Information Center

    Cohn, Elchanan; Johnson, Eric

    2006-01-01

    A sample of 347 students, enrolled in principles of economics classes during the period 1997-2001, is used to examine the relation between class attendance and student performance on examinations. Among the questions examined are: Is attendance related to performance, with and without controls for other factors? Do only substantial levels of…

  9. Attendance Feedback in An Academic Setting: Preliminary Results

    ERIC Educational Resources Information Center

    Broucek, Willard G.; Bass, William

    2008-01-01

    In the fall of 2005, the attendance behavior of 118 business students at Northern State University (NSU) was monitored in 4 classes. After 10 weeks of classes Absenteeism Feedback was given to these students. Examination of the data indicated a strong correlation between attendance and subsequent course grade. (Contains 1 table.)

  10. States Mull Obama's Call to Raise Compulsory-Attendance Age

    ERIC Educational Resources Information Center

    Maxwell, Lesli A.

    2012-01-01

    President Barack Obama's call for every state to require school attendance until age 18 may spark a flurry of action in some statehouses, but changing attendance laws will do little by itself to drive down the nation's dropout rates, experts on the issue say. In his State of the Union address last month, President Obama said states should require…

  11. Why September Matters: Improving Student Attendance. Policy Brief

    ERIC Educational Resources Information Center

    Olsen, Linda S.

    2014-01-01

    This brief examines absences in September and students' attendance over the rest of the year. Attendance should be addressed before it becomes problematic. Chronic absenteeism, missing more than 20 days of a school year, is an early indicator of disengagement. High absence rates have negative consequences not only for individual students, but also…

  12. Use Rewards to Boost Student Attendance (And Public Goodwill).

    ERIC Educational Resources Information Center

    VanSciver, James

    1986-01-01

    Describes a low-cost experiment to reinforce good student attendance and abandon the punitive approach of lowering grades and suspending chronic absentees. The Pocomoke High School program (Maryland) rewards students for superior attendance with certificates, press releases, congratulatory letters, positive phone calls to parents, and homeroom…

  13. 47 CFR 74.734 - Attended and unattended operation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... EXPERIMENTAL RADIO, AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Low Power TV, TV Translator, and TV Booster Stations § 74.734 Attended and unattended operation. (a) Low power TV, TV translator, and TV booster stations may be operated without a designated person in attendance if...

  14. 47 CFR 74.734 - Attended and unattended operation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... EXPERIMENTAL RADIO, AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Low Power TV, TV Translator, and TV Booster Stations § 74.734 Attended and unattended operation. (a) Low power TV, TV translator, and TV booster stations may be operated without a designated person in attendance if...

  15. 47 CFR 74.734 - Attended and unattended operation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... EXPERIMENTAL RADIO, AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Low Power TV, TV Translator, and TV Booster Stations § 74.734 Attended and unattended operation. (a) Low power TV, TV translator, and TV booster stations may be operated without a designated person in attendance if...

  16. 47 CFR 74.734 - Attended and unattended operation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... EXPERIMENTAL RADIO, AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Low Power TV, TV Translator, and TV Booster Stations § 74.734 Attended and unattended operation. (a) Low power TV, TV translator, and TV booster stations may be operated without a designated person in attendance if...

  17. Evaluation of the Attendant Care Pilot Project. Final Report.

    ERIC Educational Resources Information Center

    Clark, Anne; Faragher, Jean

    An Attendant Care Pilot Project, administered by the Home Care Service of New South Wales, Australia, and providing attendant care for 24 permanently severely physically disabled adults for 2 years, was evaluated. The patients were medically stable and intellectually capable of managing their own affairs; all had impairments which required…

  18. Point-Counterpoint: Should Attendance Be Required in Collegiate Classrooms?

    ERIC Educational Resources Information Center

    Pinto, Jo Ann M.; Lohrey, Peter

    2016-01-01

    This paper examines two divergent viewpoints about whether or not class attendance should be mandatory in higher education. The authors, both accounting professors at the same institution, delineate their respective viewpoints citing school policy, federal regulations and academic freedom as factors which motivate their attendance policy.

  19. Public Policy Implications of Changing Student Attendance Patterns.

    ERIC Educational Resources Information Center

    Longanecker, David A.; Blanco, Cheryl D.

    2003-01-01

    Examines the challenges that changing student characteristics and attendance patterns pose for policymakers. Describes how federal and state policies can influence attendance patterns (through funding programs, contracting with private entities to provide services, creating incentives for private action, and mandating action through law or…

  20. 16 CFR 1012.4 - Public attendance at agency meetings.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... lack of space, provided that such meetings are open to the news media; (3) Meetings with outside... meetings between Agency employees and outside parties are open to the public, attendance may be limited by space. When feasible, a person or organization desiring to attend such a meeting should give at...

  1. Are unintentional nurse-attended deliveries a patient safety issue?

    PubMed

    Veltman, Larry

    2016-08-01

    Unintentional nurse-attended deliveries occur on most labor and delivery units. Some precipitous deliveries are unavoidable, but others, occurring after admission with the expectation that the woman's designated provider would attend the delivery are, for a variety of reasons, still attended only by nursing staff. This study was undertaken to establish a benchmark for unintentional nurse-attended deliveries. Fifty perinatal units were studied with respect to their statistics regarding unintentional nurse-attended deliveries. Ten of the 50 perinatal units (20%) did not keep statistics on unintentional nurse-attended deliveries. The average percentage of unintentional nurse-attended deliveries in the 40 perinatal units that did keep this statistic was 1.38% (range 0-5.3%). This benchmark should be useful as the safety issues for these types of deliveries are analyzed. Audits regarding timing of examinations during labor, practices regarding notification of providers and other communication practices, provider arrival times, and involved personnel should help perinatal units develop policies, protocols, and strategies to minimize the chances for unintentional nurse-attended deliveries when there should be enough time and appropriate communication to allow the woman's provider to be present at the delivery. PMID:27547875

  2. The Effects of Microtraining for Attending Behaviors in Adult Testing.

    ERIC Educational Resources Information Center

    Taylor, Stephen S.; Jahns, Irwin R.

    It has been the experience of most adult basic education teachers that their students are apprehensive about taking tests. The study evaluates the effects of training adult basic education teachers in behavioral attending skills. Two basic questions were investigated: (1) Would the training of instructors in the use of behavior attending skills…

  3. Implementing Nunavut Education Act: Compulsory School Attendance Policy

    ERIC Educational Resources Information Center

    Kwarteng, E. Fredua

    2006-01-01

    This paper discusses the implementation of Nunavut compulsory school attendance policy as part of the Nunavut Education Act (2002). Using a bottom-up approach to policy implementation in the literature and the author's six years teaching experience in Nunavut, the paper argues that the compulsory school attendance policy may not achieve its…

  4. The Influence of Advertising on Attendance at Park Programs

    ERIC Educational Resources Information Center

    Reyburn, Jerry H.; Knudson, Douglas M.

    1975-01-01

    Investigated were the effects on attendance of four types of pre-program advertising: no advertising, personal invitation, signs, and innovation. All three advertising treatments increased program attendance over no advertising. Each advertising technique has advantages and disadvantages. Signs are impersonal, but effective. Personal invitation is…

  5. Improving Attendance of Kindergarten Students through Behavior Modification Techniques.

    ERIC Educational Resources Information Center

    Schofield, Betty D.

    A behavior modification program was implemented to improve attendance and punctuality patterns of kindergarten students attending a small, rural elementary school. Also incorporated into the intervention were self-esteem and parent involvement components. Motivational strategies used were: a token economy; group-oriented behavior management…

  6. 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.

  7. 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.

  8. 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…

  9. 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

  10. Self-Sampling for Human Papillomavirus Testing among Non-Attenders Increases Attendance to the Norwegian Cervical Cancer Screening Programme.

    PubMed

    Enerly, Espen; Bonde, Jesper; Schee, Kristina; Pedersen, Helle; Lönnberg, Stefan; Nygård, Mari

    2016-01-01

    Increasing attendance to screening offers the best potential for improving the effectiveness of well-established cervical cancer screening programs. Self-sampling at home for human papillomavirus (HPV) testing as an alternative to a clinical sampling can be a useful policy to increase attendance. To determine whether self-sampling improves screening attendance for women who do not regularly attend the Norwegian Cervical Cancer Screening Programme (NCCSP), 800 women aged 25-69 years in the Oslo area who were due to receive a 2nd reminder to attend regular screening were randomly selected and invited to be part of the intervention group. Women in this group received one of two self-sampling devices, Evalyn Brush or Delphi Screener. To attend screening, women in the intervention group had the option of using the self-sampling device (self-sampling subgroup) or visiting their physician for a cervical smear. Self-sampled specimens were split and analyzed for the presence of high-risk (hr) HPV by the CLART® HPV2 test and the digene® Hybrid Capture (HC)2 test. The control group consisted of 2593 women who received a 2nd reminder letter according to the current guidelines of the NCCSP. The attendance rates were 33.4% in the intervention group and 23.2% in the control group, with similar attendance rates for both self-sampling devices. Women in the self-sampling subgroup responded favorably to both self-sampling devices and cited not remembering receiving a call for screening as the most dominant reason for previous non-attendance. Thirty-two of 34 (94.1%) hrHPV-positive women in the self-sampling subgroup attended follow-up. In conclusion, self-sampling increased attendance rates and was feasible and well received. This study lends further support to the proposal that self-sampling may be a valuable alternative for increasing cervical cancer screening coverage in Norway.

  11. Self-Sampling for Human Papillomavirus Testing among Non-Attenders Increases Attendance to the Norwegian Cervical Cancer Screening Programme

    PubMed Central

    Enerly, Espen; Bonde, Jesper; Schee, Kristina; Pedersen, Helle; Lönnberg, Stefan; Nygård, Mari

    2016-01-01

    Increasing attendance to screening offers the best potential for improving the effectiveness of well-established cervical cancer screening programs. Self-sampling at home for human papillomavirus (HPV) testing as an alternative to a clinical sampling can be a useful policy to increase attendance. To determine whether self-sampling improves screening attendance for women who do not regularly attend the Norwegian Cervical Cancer Screening Programme (NCCSP), 800 women aged 25–69 years in the Oslo area who were due to receive a 2nd reminder to attend regular screening were randomly selected and invited to be part of the intervention group. Women in this group received one of two self-sampling devices, Evalyn Brush or Delphi Screener. To attend screening, women in the intervention group had the option of using the self-sampling device (self-sampling subgroup) or visiting their physician for a cervical smear. Self-sampled specimens were split and analyzed for the presence of high-risk (hr) HPV by the CLART® HPV2 test and the digene® Hybrid Capture (HC)2 test. The control group consisted of 2593 women who received a 2nd reminder letter according to the current guidelines of the NCCSP. The attendance rates were 33.4% in the intervention group and 23.2% in the control group, with similar attendance rates for both self-sampling devices. Women in the self-sampling subgroup responded favorably to both self-sampling devices and cited not remembering receiving a call for screening as the most dominant reason for previous non-attendance. Thirty-two of 34 (94.1%) hrHPV-positive women in the self-sampling subgroup attended follow-up. In conclusion, self-sampling increased attendance rates and was feasible and well received. This study lends further support to the proposal that self-sampling may be a valuable alternative for increasing cervical cancer screening coverage in Norway. PMID:27073929

  12. 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.

  13. 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

  14. 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

  15. Rural/Nonrural Differences in College Attendance Patterns

    PubMed Central

    Byun, Soo-yong; Irvin, Matthew J.; Meece, Judith L.

    2014-01-01

    Using data from the National Education Longitudinal Study of 1988, this study documented college attendance patterns of rural youth in terms of the selectivity of first postsecondary institution of attendance, the timing of transition to postsecondary education, and the continuity of enrollment. The study also examined how these college attendance patterns among rural students differed from those among their non-rural counterparts and which factors explained these rural/nonrural differences. Results showed that rural youth were less likely than their nonrural counterparts to attend a selective institution. In addition, rural youth were more likely to delay entry to postsecondary education, compared to their urban counterparts. Finally, rural students were less likely than their urban counterparts to be continuously enrolled in college. Much of these rural/nonrural disparities in college attendance patterns were explained by rural/nonrural differences in socioeconomic status and high school preparation. Policy implications, limitations of the study, and future research directions are also discussed. PMID:25983357

  16. The use of positive reinforcement in conditioning attending behavior.

    PubMed

    Walker, H M; Buckley, N K

    1968-01-01

    Individual conditioning techniques were applied in a controlled setting to increase attending behavior of an underachieving 9-yr-old male subject. The procedure involved: (1) determining a stable response pattern, (2) introducing a treatment variable to establish a high rate of task-attending behavior, (3) measuring the effect of withdrawal of the treatment variable after attaining criterion performance, and (4) transferring control to the classroom. The interval of attending behavior required for reinforcement was systematically increased from 30 sec to 600 sec as the behavior came under experimental control. Manipulating the reinforcing contingencies measurably changed the proportion of attending behavior and the frequency and duration of non-attending events. Once the behaviors were under experimental control, procedures were established to program generalization and to maintain the behavior outside the experimental setting.

  17. The use of positive reinforcement in conditioning attending behavior1

    PubMed Central

    Walker, Hill M.; Buckley, Nancy K.

    1968-01-01

    Individual conditioning techniques were applied in a controlled setting to increase attending behavior of an underachieving 9-yr-old male subject. The procedure involved: (1) determining a stable response pattern, (2) introducing a treatment variable to establish a high rate of task-attending behavior, (3) measuring the effect of withdrawal of the treatment variable after attaining criterion performance, and (4) transferring control to the classroom. The interval of attending behavior required for reinforcement was systematically increased from 30 sec to 600 sec as the behavior came under experimental control. Manipulating the reinforcing contingencies measurably changed the proportion of attending behavior and the frequency and duration of non-attending events. Once the behaviors were under experimental control, procedures were established to program generalization and to maintain the behavior outside the experimental setting. PMID:16795182

  18. The Dynamics and Correlates of Religious Service Attendance in Adolescence

    PubMed Central

    Hardie, Jessica Halliday; Pearce, Lisa D.; Denton, Melinda Lundquist

    2013-01-01

    This study examines changes in religious service attendance over time for a contemporary cohort of adolescents moving from middle to late adolescence. We use two waves of a nationally representative panel survey of youth from the National Study of Youth and Religion (NSYR) to examine the dynamics of religious involvement during adolescence. We then follow with an analysis of how demographic characteristics, family background, and life course transitions relate to changes in religious service attendance during adolescence. Our findings suggest that, on average, adolescent religious service attendance declines over time, related to major life course transitions such as becoming employed, leaving home, and initiating sexual activity. Parents’ affiliation and attendance, on the other hand, are protective factors against decreasing attendance. PMID:26900186

  19. Computer program for the automated attendance accounting system

    NASA Technical Reports Server (NTRS)

    Poulson, P.; Rasmusson, C.

    1971-01-01

    The automated attendance accounting system (AAAS) was developed under the auspices of the Space Technology Applications Program. The task is basically the adaptation of a small digital computer, coupled with specially developed pushbutton terminals located in school classrooms and offices for the purpose of taking daily attendance, maintaining complete attendance records, and producing partial and summary reports. Especially developed for high schools, the system is intended to relieve both teachers and office personnel from the time-consuming and dreary task of recording and analyzing the myriad classroom attendance data collected throughout the semester. In addition, since many school district budgets are related to student attendance, the increase in accounting accuracy is expected to augment district income. A major component of this system is the real-time AAAS software system, which is described.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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…

  8. Improving School Attendance: Can Participation in Outdoor Learning Influence Attendance for Young People with Social, Emotional and Behavioural Difficulties?

    ERIC Educational Resources Information Center

    Price, Alan

    2015-01-01

    The link between good attendance in school and academic performance has been acknowledged for some time now. However, improving school attendance for young people with social, emotional and behavioural difficulties (SEBD) or pupils at risk of exclusion can be a challenging task for educational leaders. This paper begins with a discussion of…

  9. 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

  10. 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.

  11. How the Non-attending Brain Hears Its Owner's Name.

    PubMed

    Nakane, Toshiki; Miyakoshi, Makoto; Nakai, Toshiharu; Naganawa, Shinji

    2016-10-01

    We used functional magnetic resonance imaging to investigate how attended and non-attended hearing of a subject's own name (SON) captures his or her attention. It has been reported that SON presentation activates the medial prefrontal cortex (mPFC), which is considered to be the key region for self-recognition. However, it remains unclear whether non-attended SON presentation also activates the mPFC. We hypothesized that an attended SON should activate mPFC more than a non-attended SON. To test this hypothesis, we designed an experiment in which we manipulated the task-relevance of SON; in a name-detection task, SON was a target stimulus, whereas in a tone-judgment task, SON was unrelated to the task. In each condition, identical sets of sound stimuli were presented. SON activated mPFC in the name-detection task but not in the tone-judgment task, supporting our hypothesis. In contrast, non-attended SON activated midbrain reticular formation, thalamus, insula, auditory cortex, and precuneus. We interpreted these to be related to low-level, automatic SON detection. Thus, hearing one's own name in a non-attended condition does not primarily engage the mPFC, but recruits a cortico-subcortical auditory attention network; this may account for the oft-observed salience of SON. PMID:26374785

  12. How the Non-attending Brain Hears Its Owner's Name.

    PubMed

    Nakane, Toshiki; Miyakoshi, Makoto; Nakai, Toshiharu; Naganawa, Shinji

    2016-10-01

    We used functional magnetic resonance imaging to investigate how attended and non-attended hearing of a subject's own name (SON) captures his or her attention. It has been reported that SON presentation activates the medial prefrontal cortex (mPFC), which is considered to be the key region for self-recognition. However, it remains unclear whether non-attended SON presentation also activates the mPFC. We hypothesized that an attended SON should activate mPFC more than a non-attended SON. To test this hypothesis, we designed an experiment in which we manipulated the task-relevance of SON; in a name-detection task, SON was a target stimulus, whereas in a tone-judgment task, SON was unrelated to the task. In each condition, identical sets of sound stimuli were presented. SON activated mPFC in the name-detection task but not in the tone-judgment task, supporting our hypothesis. In contrast, non-attended SON activated midbrain reticular formation, thalamus, insula, auditory cortex, and precuneus. We interpreted these to be related to low-level, automatic SON detection. Thus, hearing one's own name in a non-attended condition does not primarily engage the mPFC, but recruits a cortico-subcortical auditory attention network; this may account for the oft-observed salience of SON.

  13. 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

  14. 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

  15. 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.

  16. 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…

  17. 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.

  18. 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."

  19. 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."

  20. Wanting to attend isn’t just wanting to quit: why some disadvantaged smokers regularly attend smoking cessation behavioural therapy while others do not: a qualitative study

    PubMed Central

    2014-01-01

    Background Attendance of a behavioural support programme facilitates smoking cessation. Disadvantaged smokers have been shown to attend less than their more affluent peers. We need to gain in-depth insight into underlying reasons for differing attendance behaviour in disadvantaged smokers, to better address this issue. This study aims to explore the underlying motivations, barriers and social support of smokers exhibiting different patterns of attendance at a free smoking cessation behavioural support programme in a disadvantaged neighbourhood of The Netherlands. Methods In 29 smokers undertaking smoking cessation group therapy or telephone counselling in a disadvantaged neighbourhood, qualitative interviews were completed, coded and analysed. Major themes were motivations, barriers to attend and social support. Motivations and social support were analysed with reference to the self-determination theory. Results Two distinct patterns of attendance emerged: those who missed up to two sessions (“frequent attenders”), and those who missed more than two sessions (“infrequent attenders”). The groups differed in their motivations to attend, barriers to attendance, and in the level of social support they received. In comparison with the infrequent attenders, frequent attenders more often had intrinsic motivation to attend (e.g. enjoyed attending), and named more self-determined extrinsic motivations to attend, such as commitment to attendance and wanting to quit. Most of those mentioning intrinsic motivation did not mention a desire to quit as a motivation for attendance. No organizational barriers to attendance were mentioned by frequent attenders, such as misunderstandings around details of appointments. Frequent attenders experienced more social support within and outside the course. Conclusion Motivation to attend behavioural support, as distinct from motivation to quit smoking, is an important factor in attendance of smoking cessation courses in disadvantaged

  1. 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.

  2. 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’.

  3. 17. Photographer unknown, March 1928 PARK ROAD BOOSTERS ATTEND A ...

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

    17. Photographer unknown, March 1928 PARK ROAD BOOSTERS ATTEND A MEETING IN MARCH OF 1928, WHEN A $5 MILLION GIFT FOR THE LAURA SPELLMAN ROCKEFELLER MEMORIAL WAS ANNOUNCED. - Great Smoky Mountains National Park Roads & Bridges, Gatlinburg, Sevier County, TN

  4. 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.

  5. 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

  6. [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

  7. The validity and reliability of attending evaluations of medicine residents

    PubMed Central

    Kay, Cynthia; Frank, Michael

    2015-01-01

    Objectives: To assess the reliability and validity of faculty evaluations of medicine residents. Methods: We conducted a retrospective study (2004–2012) involving 228 internal medicine residency graduates at the Medical College of Wisconsin who were evaluated by 334 attendings. Measures included evaluations of residents by attendings, based on six competencies and interns and residents’ performance on the American Board of Internal Medicine certification exam and annual in-service training examination. All residents had at least one in-service training examination result and 80% allowed the American Board of Internal Medicine to release their scores. Results: Attending evaluations had good consistency (Cronbach’s α = 0.96). There was poor construct validity with modest inter-rater reliability and evidence that attendings were rating residents on a single factor rather than the six competencies intended to be measured. There was poor predictive validity as attending ratings correlated weakly with performance on the in-service training examination or American Board of Internal Medicine certification exam. Conclusion: We conclude that attending evaluations are poor measures for assessing progress toward competency. It may be time to move beyond evaluations that rely on global, end-of-rotation appraisals. PMID:26770788

  8. Targeting zero non-attendance in healthcare clinics.

    PubMed

    Chan, Ka C; Chan, David B

    2012-01-01

    Non-attendance represents a significant cost to many health systems, resulting in inefficiency, wasted resources, poorer service delivery and lengthened waiting queues. Past studies have considered extensively the reasons for non-attendance and have generally concluded that the use of reminder systems is effective. Despite this, there will always be a certain level of non-attendance arising from unforeseeable and unpreventable circumstances, such as illness or accidents, leading to unfilled appointments. This paper reviews current approaches to the non-attendance problem, and presents a high-level approach to fill last minute appointments arising out of unforeseeable non-attendance. However, no single approach will work for all clinics and implementation of these ideas must occur at a local level. These approaches include use of social networks, such as Twitter and Facebook, as a communication tool in order to notify prospective patients when last-minute appointments become available. In addition, teleconsultation using video-conferencing technologies would be suitable for certain last-minute appointments where travel time would otherwise be inhibiting. Developments of new and innovative technologies and the increasing power of social media, means that zero non-attendance is now an achievable target. We hope that this will lead to more evidence-based evaluations from the implementation of these strategies in various settings at a local level. PMID:23138079

  9. Managing a Bone Healthy Lifestyle After Attending Multifaceted Group Education.

    PubMed

    Jensen, Annesofie Lunde; Lomborg, Kirsten; Langdahl, Bente Lomholt; Wind, Gitte

    2016-09-01

    We examined patients with osteoporosis implementation of recommendations regarding a bone healthy lifestyle after the patients attended multifaceted osteoporosis group education (GE). Our findings suggest that GE can support and influence patients' transfer of preventive actions. Still patients are challenged by concerns related to social roles and physical ability. We investigated if and how patients implemented knowledge from attending multifaceted osteoporosis GE in their daily lives. An interpretive description design using ethnographic field work was applied. In all 14 women and three men diagnosed with osteoporosis who attended multifaceted GE at a Danish hospital participated. Data consisted of field work and individual interviews in the participants' everyday environment after completion of GE. After attending multifaceted GE, participants experienced increased attention to and reflected more on how to implement osteoporosis preventive actions or activities. Participants who felt confident on how to act and experienced a clear need and motivation, or who could make the preventive activity into a social event, demonstrated an increased implementation of the preventive activity. On the contrary, attending GE was in some cases not sufficient to overcome social and physical concerns, or to eliminate uncertainty about recommendations or to make participants identify with the osteoporosis diagnosis, which thus impeded implementation of a bone healthy lifestyle. Attending multifaceted GE can support and influence participants' transfer of preventive actions into daily life. Being aware of how concerns about valued social roles and physical ability interfere with the implementation of medical recommendations obviously needs attention during GE. PMID:27146664

  10. Mobile Attendance Checking System on Android Platform for Kazakhstani University

    NASA Astrophysics Data System (ADS)

    Saparkhojayev, N.; Shakhov, E.; Mailybayev, Y.

    2016-04-01

    In the 21st century-the century of Information Technology, it is difficult to imagine life without any gadgets: phones, tablets, computers, laptops, and so on. Today, smartphones and tablets are becoming popular, and thus their operating systems become popular too. Android is designed for low-power devices that run on battery power at full capacity, using all of its services, such as cameras, lights, GPS navigation, Wi-Fi, etc. In Kazakhstani universities, the process of checking students’ attendance is one of the important issues, because final grade evaluation of students is based on their total number of appearances and their grades during the whole semester. This raises the question of having some tool to control students’ attendance. There are many possible ways of controlling attendance: there are many examples when universities prefer to control attendance by the use of paper sheet, and some universities prefer to use two-stage way of controlling attendance: firstly, teachers and professors use paper sheet for checking students’ attendance and after this, they fill out these information into a system manually. However, this is not an efficient way since there will be spent much of time for calling students names and putting marks like “presence” or “absence” if the class is a lecture class, and in this class at least 5 groups are presented. Furthermore, some students may call his/her friend as “presence” nevertheless to the fact that this student is currently absent. After taking into consideration all these issues and the fact that many gadgets use Android platform, authors of the following research paper decided to create a mobile system that makes easier to check students’ attendance automatically, and this system is implemented in Almaty Management University, Kazakhstan. The system is based on Android platform, and in this paper, details of this system are presented.

  11. Evidence for a fixed capacity limit in attending multiple locations.

    PubMed

    Ester, Edward F; Fukuda, Keisuke; May, Lisa M; Vogel, Edward K; Awh, Edward

    2014-03-01

    A classic question concerns whether humans can attend multiple locations or objects at once. Although it is generally agreed that the answer to this question is "yes," the limits on this ability are subject to extensive debate. According to one view, attentional resources can be flexibly allocated to a variable number of locations, with an inverse relationship between the number of selected locations and the quality of information processing at each location. Alternatively, these resources might be quantized in a "discrete" fashion that enables concurrent access to a small number of locations. Here, we report a series of experiments comparing these alternatives. In each experiment, we cued participants to attend a variable number of spatial locations and asked them to report the orientation of a single, briefly presented target. In all experiments, participants' orientation report errors were well-described by a model that assumes a fixed upper limit in the number of locations that can be attended. Conversely, report errors were poorly described by a flexible-resource model that assumes no fixed limit on the number of locations that can be attended. Critically, we showed that these discrete limits were predicted by cue-evoked neural activity elicited before the onset of the target array, suggesting that performance was limited by selection processes that began prior to subsequent encoding and memory storage. Together, these findings constitute novel evidence supporting the hypothesis that human observers can attend only a small number of discrete locations at an instant.

  12. Out of hours attendance in an army practice.

    PubMed

    Grundy-Wheeler, N J

    1991-05-01

    There is some evidence that rates of out of hours calls in army general practices are higher than the average for the NHS. In an attempt to reduce out of hours demand a programme of preventive and educational initiatives for patients was introduced at an army practice in Hohne, West Germany early in 1985. This included regular child development clinics, well woman clinics, a practice booklet and leaflets about the management of simple illnesses, a library of books and videos for patients and health education videos in the waiting room. The project was complemented by an audit of doctors' prescribing habits followed by drawing up agreed protocols for the treatment of common disorders such as sore throat. Annual attendance rates per registered patient were recorded for 1984-86 to compare use of out of hours services by patients before and after the introduction of the project. Out of hours attendance rates fell by 35% (from 0.17 per annum to 0.11 per annum) overall and by 61% in young children. The total annual attendance rate dropped by 14% (from 5.13 to 4.43) during the same period, but fell by only 1% over the same period at a similar practice in Osnabruck. The decrease was particularly marked for out of hours attendances which the doctor classified as lower urgency: attendances classed as very low urgency decreased by 78% between 1984 and 1986 but those classed as medium urgency decreased by only 2%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1878273

  13. 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

  14. 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

  15. 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

  16. 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.

  17. [The qualification of nursing attendants: transformations in work and life].

    PubMed

    Aguiar Neto, Zenaide; Soares, Cássia Baldini

    2004-01-01

    This study examines the transformations that occurred in the work, life and especially in the way of thinking and acting of nursing attendants after their professional qualification through the Projeto Larga Escala (PLE). Subjects were attendants who qualified as nursing auxiliaries through the PLE, which was conducted by the Regional Health Administration-5 (São Paulo city), from 1990 to 1992. The study used life stories as a strategy to apprehend reality, and work and qualification were used a analytical categories. The analysis allowed us to recognize the possibilities and limitations of the training process that guarantee the attendants with: promotion to a professional category and conquest of some rights; knowledge improvement and care humanization. The qualification process seems to have some power to modify the quality of health care, although it does not seem capable to promote changes in the health care model.

  18. Migrant Home Attendants: Regulation and Practice in 7 Countries

    PubMed Central

    Garms-Homolová, Vjenka; Bentwich, Miriam

    2013-01-01

    We compared regulation and working and living conditions of foreign home attendants in 7 countries (Canada, Germany, Israel, Singapore, Spain, United Kingdom, United States). We conducted a literature search in the PSYCinfo, MEDLINE, and Google Scholar databases for 2002 to 2012. We found substantial between-country differences in the legal status of migrant caregivers and regulations regarding working and living conditions and drew 3 conclusions. Improving regulations will likely improve not only the well-being of foreign home attendants but also the care they provide. Countries in which many foreign home attendants work without specific legal entry programs should rethink their policies. Finally, requiring an employer’s recommendation to obtain permanent residency may constrain foreign workers from registering complaints or leaving suboptimal employment situations. PMID:24134377

  19. Welcome back? Frequent attenders to a pediatric primary care center.

    PubMed

    Klein, Melissa; Vaughn, Lisa M; Baker, Raymond C; Taylor, Trisha

    2011-09-01

    This study examines frequent attenders of a pediatric primary care clinic at a large urban children's hospital--who they are and their reasons for frequent attendance to the clinic. The literature suggests that some visits by frequent attenders may not be medically necessary, and these additional appointments may impair others' access to medical care within the same system. The key to eliminating excessive primary care visits is to determine if it is a problem in the primary care practice (quantify the problem), explore the reasons for the visits (from the patients' perspective), and then provide educational interventions that address the various causes for the extra visits and encourage the use of available resources, either ancillary services in the practice itself or resources and agencies available in the community (e.g. social service, legal aid).

  20. 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

  1. 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

  2. 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).

  3. Flying the smoky skies: secondhand smoke exposure of flight attendants

    PubMed Central

    Repace, J

    2004-01-01

    Objective: To assess the contribution of secondhand smoke (SHS) to aircraft cabin air pollution and flight attendants' SHS exposure relative to the general population. Methods: Published air quality measurements, modelling studies, and dosimetry studies were reviewed, analysed, and generalised. Results: Flight attendants reported suffering greatly from SHS pollution on aircraft. Both government and airline sponsored studies concluded that SHS created an air pollution problem in aircraft cabins, while tobacco industry sponsored studies yielding similar data concluded that ventilation controlled SHS, and that SHS pollution levels were low. Between the time that non-smoking sections were established on US carriers in 1973, and the two hour US smoking ban in 1988, commercial aircraft ventilation rates had declined three times as fast as smoking prevalence. The aircraft cabin provided the least volume and lowest ventilation rate per smoker of any social venue, including stand up bars and smoking lounges, and afforded an abnormal respiratory environment. Personal monitors showed little difference in SHS exposures between flight attendants assigned to smoking sections and those assigned to non-smoking sections of aircraft cabins. Conclusions: In-flight air quality measurements in ~250 aircraft, generalised by models, indicate that when smoking was permitted aloft, 95% of the harmful respirable suspended particle (RSP) air pollution in the smoking sections and 85% of that in the non-smoking sections of aircraft cabins was caused by SHS. Typical levels of SHS-RSP on aircraft violated current (PM2.5) federal air quality standards ~threefold for flight attendants, and exceeded SHS irritation thresholds by 10 to 100 times. From cotinine dosimetry, SHS exposure of typical flight attendants in aircraft cabins is estimated to have been >6-fold that of the average US worker and ~14-fold that of the average person. Thus, ventilation systems massively failed to control SHS air

  4. ATTEND: toward a mindfulness-based bereavement care model.

    PubMed

    Cacciatore, Joanne; Flint, Melissa

    2012-01-01

    Few, if any, mindfulness-based bereavement care models exist. The ATTEND (attunement, trust, touch, egalitarianism, nuance, and death education) model is an interdisciplinary paradigm for providers, including physicians, social workers, therapists, nursing staff and others. Using a case example to enhance the breadth and depth of understanding, this article focuses on attunement as a means to moderate the negative effects of traumatic bereavement, support the framework for posttraumatic growth in the bereaved, improve psychological outcomes for providers, and set the stage for the other aspects of the ATTEND model. PMID:24567995

  5. Saliva alcohol concentrations in accident and emergency attendances

    PubMed Central

    Simpson, T; Murphy, N; Peck, D

    2001-01-01

    Objectives—Although alcohol is known to play a key part in accidents, no UK study has assessed alcohol concentrations in a comprehensive sample of accident and emergency (A&E) attenders. This study set out to do this, and examine the relation between alcohol concentrations and the severity, type and circumstances of presentation, and the sociodemographic characteristics of patients. Methods—A survey was conducted of all new A&E attenders (aged 10 years or over). Two 24 hour periods for each day of the week were covered in 6, 7 or 11 hour sessions over a two month period. Alcohol concentrations were assessed from saliva samples using a disposable device. Data were collected from 638 attenders, of whom 544 provided saliva samples; the remainder refused or were unable to participate. Results—Positive saliva alcohol readings were obtained in 22% of attenders (95%CI 19% to 26%); this increased to 25% if others were included (for example, those who refused to participate but were judged to be intoxicated). Alcohol was associated with 94% of incidents of self harm, 54% of non-specific/multiple complaints, 47% of collapses, 50% of assaults, and 50% of patients admitted to hospital. Higher concentrations of alcohol were found from Friday to Sunday, between midnight and 0900, and in patients aged 41 to 60. Among people with positive alcohol results, those attending with a companion had higher concentrations than those attending alone. There were no significant differences between men and women in alcohol concentrations. Discussion—These findings show that alcohol use is an important factor in A&E attendance, but it should not be assumed that there is a causal relation between alcohol use and injury. Several accident related and sociodemographic variables were predictive of alcohol use before attending. The overall level of prediction was too weak to permit accurate identification of drinkers for screening purposes, but routine alcohol concentration assessments may be

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. School Characteristics that Influence Student Attendance: Experiences of Students in a School Avoidance Program

    ERIC Educational Resources Information Center

    Wilkins, Julia

    2008-01-01

    This study examined the reasons that four high school students who had previously refused to attend school willingly attended an alternative K-12 school for students with special needs. The two research questions that framed this study were (a) why do students who refused to attend their regular schools willingly attend Brookfield Park? and (b) in…

  12. 20 CFR 219.55 - Evidence of school attendance for child age 18.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Evidence of school attendance for child age... school attendance for child age 18. The child will be asked to submit (on a form furnished by the Board... is attending school full-time and is not being paid by an employer to attend school; and (b)...

  13. Compulsory School Attendance and Truancy Laws. Information Memorandum 98-27.

    ERIC Educational Resources Information Center

    Wisconsin State Legislative Council, Madison.

    This information memorandum describes Wisconsin laws relating to compulsory school attendance and truancy. It outlines school-attendance requirements, exceptions, and alternatives; the written attendance policy; key definitions regarding truancy and school-attendance enforcement; and information on the truancy-planning committee and truancy plan.…

  14. Relations between Faculty Use of Online Academic Resources and Student Class Attendance

    ERIC Educational Resources Information Center

    Kinlaw, C. Ryan; Dunlap, Linda L.; D'Angelo, Jeffrey A.

    2012-01-01

    We investigated connections between faculty use of online resources and student class attendance. Of particular interest was whether online submission of course assignments is detrimental to attendance. Students and faculty at a small, liberal arts college completed surveys about student attendance patterns, student reasons for non-attendance,…

  15. Studying Absenteeism in Principles of Macroeconomics: Do Attendance Policies Make a Difference?

    ERIC Educational Resources Information Center

    Self, Sharmistha

    2012-01-01

    The primary objective of this article is to see if and how attendance policy influences class attendance in undergraduate-level principles of macroeconomics classes. The second objective, which is related to the first, is to examine whether the nature of the attendance policy matters in terms of its impact on class attendance behavior. The results…

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Two Polarities of Attention in Social Contexts: From Attending-to-Others to Attending-to-Self

    PubMed Central

    Kuang, Shenbing

    2016-01-01

    Social attention is one special form of attention that involves the allocation of limited processing resources in a social context. Previous studies on social attention often regard how attention is directed toward socially relevant stimuli such as faces and gaze directions of other individuals. In contrast to attending-to-others, a different line of researches has shown that self-related information such as own face and name automatically captures attention and is preferentially processed comparing to other-related information. These contrasting behavioral effects between attending-to-others and attending-to-self prompt me to consider a synthetic viewpoint for understanding social attention. I propose that social attention operates at two polarizing states: In one extreme, individual tends to attend to the self and prioritize self-related information over others', and, in the other extreme, attention is allocated to other individuals to infer their intentions and desires. Attending-to-self and attending-to-others mark the two ends of an otherwise continuum spectrum of social attention. For a given behavioral context, the mechanisms underlying these two polarities will interact and compete with each other in order to determine a saliency map of social attention that guides our behaviors. An imbalanced competition between these two behavioral and cognitive processes will cause cognitive disorders and neurological symptoms such as autism spectrum disorders and Williams syndrome. I have reviewed both behavioral and neural evidence that support the notion of polarized social attention, and have suggested several testable predictions to corroborate this integrative theory for understanding social attention. PMID:26869965

  7. Two Polarities of Attention in Social Contexts: From Attending-to-Others to Attending-to-Self.

    PubMed

    Kuang, Shenbing

    2016-01-01

    Social attention is one special form of attention that involves the allocation of limited processing resources in a social context. Previous studies on social attention often regard how attention is directed toward socially relevant stimuli such as faces and gaze directions of other individuals. In contrast to attending-to-others, a different line of researches has shown that self-related information such as own face and name automatically captures attention and is preferentially processed comparing to other-related information. These contrasting behavioral effects between attending-to-others and attending-to-self prompt me to consider a synthetic viewpoint for understanding social attention. I propose that social attention operates at two polarizing states: In one extreme, individual tends to attend to the self and prioritize self-related information over others', and, in the other extreme, attention is allocated to other individuals to infer their intentions and desires. Attending-to-self and attending-to-others mark the two ends of an otherwise continuum spectrum of social attention. For a given behavioral context, the mechanisms underlying these two polarities will interact and compete with each other in order to determine a saliency map of social attention that guides our behaviors. An imbalanced competition between these two behavioral and cognitive processes will cause cognitive disorders and neurological symptoms such as autism spectrum disorders and Williams syndrome. I have reviewed both behavioral and neural evidence that support the notion of polarized social attention, and have suggested several testable predictions to corroborate this integrative theory for understanding social attention. PMID:26869965

  8. Late Pregnancy Outcomes among Women who Attended and Women who did not Attend First Trimester Antenatal Care Visits in a Suburban Regional Hospital in Cameroon

    PubMed Central

    Njim, Tsi N

    2016-01-01

    Background: Despite relatively high number of women who attend antenatal care (ANC) in Cameroon, there is an ever-increasing maternal mortality ratio, and pregnancy outcomes remain inadequate. A new suggested Optimal ANC Package includes attending ANC in the first trimester. This study assesses the overall ANC coverage, the percentage, and pregnancy outcomes among women who attended and did not attend ANC in the first trimester in the Buea Regional Hospital (BRH) in Cameroon. Methods: A cross-sectional study was carried out among 200 consenting pregnant women presenting for delivery at the BRH. A bivariate analysis was used to compare the frequencies of various pregnancy outcomes within the the two categories of women who attended and who did not attend first trimester ANC. Results: Ninety-six percent of the women attended at least 1 ANC visit with 20.5% of these women attending ANC in the first trimester and 60.2% attending at least 4 visits. Sociodemographic and obstetric factors were not found to be associated with attending ANC in the first trimester. Also, there was no statistically significant association between all the late pregnancy outcomes assessed and attending ANC in the first trimester. Conclusions and Global Health Implications: Trends in most sub-Saharan countries seem to suggest that most women do not attend first trimester ANC. This could have negative consequences on overall perinatal outcome. More user-friendly educational programs for women of childbearing age is required in such regions to address this situation. PMID:27622008

  9. Personal Assistance: Attendant Services, Readers, and Interpreters: Topic Paper I.

    ERIC Educational Resources Information Center

    National Council on the Handicapped, Washington, DC.

    Federal legislation and programs affecting personal assistance services for persons with disabilities are examined. Personal assistance services may be provided for activities of daily living, communication, cognitive tasks, or mobility, depending on the needs of the individual. The population in need of attendant services has increased with…

  10. Geographical Location and Attendance for a Regional Research Association.

    ERIC Educational Resources Information Center

    Kennedy, Robert L.; Boser, Judith A.

    This study evaluated the relationship between site location of and attendance at an organization's annual meeting. It assessed whether participation in the annual meeting increased or decreased in the host state; if participation increases when the meeting is in the home state, whether that participation level is maintained in the following year;…

  11. 16 CFR 1012.4 - Public attendance at agency meetings.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... meetings between Agency employees and outside parties are open to the public, attendance may be limited by... permit members of the public to participate as well. (d) The following Agency meetings are not open to... her designee has determined that proprietary data are to be discussed in such a manner as to...

  12. What Good Is College? The Economics of College Attendance

    ERIC Educational Resources Information Center

    Covaleskie, John F.

    2014-01-01

    Until relatively recently, college was for only the few, and only loosely related to economic success. College graduates have always done economically better, on average, than those who did not graduate from college, but that was mostly because only the well-to-do could afford college. Few attended college in the hope of economic advancement in…

  13. Effective Dropout Prevention and College Attendance Programs for Latino Students.

    ERIC Educational Resources Information Center

    Fashola, Olatokunbo S.; Slavin, Robert E.

    This paper reviews research related to effective secondary school programs aimed at dropout prevention and increasing college enrollment rates for at-risk Latino youth. The review identifies programs that have demonstrated a significant impact on dropout rates, college attendance, school performance, or related outcomes in rigorous evaluations;…

  14. Introverts' and Extraverts' Responses to Nonverbal Attending Behavior

    ERIC Educational Resources Information Center

    Genthner, Robert W.; Moughan, James

    1977-01-01

    The different responses of introverts and extraverts to two types of helper nonverbal attending were examined. Subjects were 26 introverts and 26 extraverts, as defined by Eysenck and Eysenck's questionnaire. Introverts rated the listener higher than did extraverts, independent of his posture. (Author)

  15. A Theory of Attending and Reinforcement in Conditional Discriminations

    ERIC Educational Resources Information Center

    Nevin, John A.; Davison, Michael; Shahan, Timothy A.

    2005-01-01

    A model of conditional discrimination performance (Davison & Nevin, 1999) is combined with the notion that unmeasured attending to the sample and comparison stimuli, in the steady state and during disruption, depends on reinforcement in the same way as predicted for overt free-operant responding by behavioral momentum theory (Nevin & Grace, 2000).…

  16. The Importance of Price in College Attendance: A Pennsylvania Conundrum

    ERIC Educational Resources Information Center

    Change: The Magazine of Higher Learning, 2006

    2006-01-01

    One of the predominant characteristics of higher education in Pennsylvania is the high cost of attendance across the Commonwealth. The average tuition charged by a Pennsylvania community college--the benchmark measure used by "The National Report Card on Higher Education"--in 2004 was $2,514, making Pennsylvania the 14th most expensive state in…

  17. Fifteen Effective Strategies for Improving Student Attendance and Truancy Prevention

    ERIC Educational Resources Information Center

    Smink, Jay; Reimer, Mary S.

    2005-01-01

    Improving student attendance and truancy prevention have always been areas of concern for educators, as well as, community members, and legislators. Students who are not in school cannot learn, and frequently drop out. Truant students often engage in high-risk behaviors that eventually entangle them in the juvenile justice system. Since 1986, the…

  18. The impact of mass school immunization on school attendance.

    PubMed

    Wiggs-Stayner, Kathleen S; Purdy, Teresa R; Go, Gailya N; McLaughlin, Natalie C; Tryzynka, Penny S; Sines, Joyce R; Hlaing, Thein

    2006-08-01

    The purpose of this study was to assess the impact a free, on-site influenza immunization program could have on attendance in Title 1 schools. Four Title 1 elementary schools participated in the study. Students at 2 schools were offered free FluMist immunizations on site, and students at 2 control schools were not. Compliance on receiving FluMist was measured on the percentage of students participating after evaluating for medical exclusions. Documentation on the reason for absences at all 4 schools included self- or parent-reported influenza. Attendance rates for the year also were compared with the previous year for all 4 schools. A comparison was done of total days absent versus total days enrolled between schools receiving FluMist and schools not receiving the vaccine. Despite the fact that FluMist is a new vaccine and is not required for children, 57% of those medically eligible to receive it had parental permission and received the vaccine. The 2 schools receiving FluMist increased their attendance rates from 95.3% and 93.9% to 96.1% and 95.8%. Previously, the comparison schools each had a 94.6% attendance rate; one fell to 94.4% and the other rose very slightly to 94.7%. The differences in self- or parent-reported influenza absences were not significant. However, the difference in days absent between individual vaccinated and nonvaccinated schools was statistically significant. PMID:16856776

  19. 29 CFR 2203.3 - Public attendance at Commission meetings.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Public attendance at Commission meetings. 2203.3 Section 2203.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION... procedures, or (vi) Endanger the life or physical safety of law enforcement personnel; (8)...

  20. Progress of Pupils Attending Resourced Provision for Specific Learning Difficulties

    ERIC Educational Resources Information Center

    Warhurst, Amy; Norgate, Roger

    2012-01-01

    An analysis of the improvement in attainments of 109 students attending specialist-resourced provision for specific learning difficulties (SpLD) attached to mainstream secondary schools was conducted as they progressed through Key Stages 3 and 4. Steady progress was made in terms of reading accuracy, reading comprehension, spelling ability and…