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Sample records for human erythroleukemia hel

  1. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    International Nuclear Information System (INIS)

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness; Cook-Moreau, Jeanne; Beneytout, Jean-Louis; Liagre, Bertrand

    2013-01-01

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression

  2. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    Energy Technology Data Exchange (ETDEWEB)

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Cook-Moreau, Jeanne [Université de Limoges, FR 3503 GEIST, UMR CNRS 7276 “Contrôle de la réponse immune B et lymphoproliférations”, Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Beneytout, Jean-Louis [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France)

    2013-04-15

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression.

  3. Increased cyclooxygenase-2 and thromboxane synthase expression is implicated in diosgenin-induced megakaryocytic differentiation in human erythroleukemia cells.

    Science.gov (United States)

    Cailleteau, C; Liagre, B; Battu, S; Jayat-Vignoles, C; Beneytout, J L

    2008-09-01

    Differentiation induction as a therapeutic strategy has, so far, the greatest impact in hematopoietic malignancies, most notably leukemia. Diosgenin is a very interesting natural product because, depending on the specific dose used, its biological effect is very different in HEL (human erythroleukemia) cells. For example, at 10 microM, diosgenin induced megakaryocytic differentiation, in contrast to 40 microM diosgenin, which induced apoptosis in HEL cells previously demonstrated using sedimentation field-flow fractionation (SdFFF). The goal of this work focused on the correlation between cyclooxygenase-2 (COX-2) and thromboxane synthase (TxS) and megakaryocytic differentiation induced by diosgenin in HEL cells. Furthermore, the technique of SdFFF, having been validated in our models, was used in this new study as an analytical tool that provided us with more or less enriched differentiated cell fractions that could then be used for further analyses of enzyme protein expression and activity for the first time. In our study, we showed the implication of COX-2 and TxS in diosgenin-induced megakaryocytic differentiation in HEL cells. Furthermore, we showed that the analytical technique of SdFFF may be used as a tool to confirm our results as a function of the degree of cell differentiation.

  4. Expression of the transcription factor Evi-1 in human erythroleukemia cell lines and in leukemias.

    Science.gov (United States)

    Fontenay-Roupie, M; Bouscary, D; Melle, J; Viguié, F; Picard, F; Guesnu, M; Dreyfus, F

    1997-02-01

    The Evi-1 proto-oncogene is a zinc finger DNA binding protein. Although activation of the Evi-1 gene has been associated with chromosomal rearrangements of the 3q25-q28 region, ectopic expression of Evi-1 could also be observed in acute myelogenous leukemias and myelodysplastic syndromes without cytogenetic abnormalities of the 3q26 locus. In this study, human erythroleukemic cell lines were screened for the expression of Evi-1 mRNA by northern blotting. Evi-1 was expressed in all the erythroid cell lines, whether undifferentiated (K 562, HEL, LAMA 84) or exhibiting spontaneous terminal erythroid differentiation (KU 812, JK-1). Evi-1 mRNA levels were constant or elevated in hemoglobin-synthesizing KU 812 or K 562 cells in response to erythropoietin or hemin treatment, respectively. In human acute myeloblastic leukemias (AML), 11/30 expressed Evi-1 by RT-PCR. Among these cases, 4/6 erythroleukemias without abnormalities of the 3q25-q28 region were found positive. The presence of acidophilic erythroblasts (15-47% of bone marrow cells) accounted for the existence of a terminal erythroid differentiation in all Evi-1-positive AML M6, whereas one negative case was poorly differentiated and referred to as AML M6 variant. These results suggest that Evi-1 mRNA expression can coexist with erythroid differentiation.

  5. Kefir induces apoptosis and inhibits cell proliferation in human acute erythroleukemia.

    Science.gov (United States)

    Jalali, Fatemeh; Sharifi, Mohammadreza; Salehi, Rasoul

    2016-01-01

    Acute erythroleukemia is an uncommon subtype of acute myeloid leukemia which has been considered to be a subtype of AML with a worse prognosis. Intensive chemotherapy is the first line of treatment. In recent years, the effect of kefir on some malignancies has been experimented. Kefir is a kind of beverage, which obtained by incubation of kefir grains with raw milk. Kefir grains are a symbiotic complex of different kinds of yeasts and bacteria, especially lactic acid bacteria which gather in a mostly carbohydrate matrix, named kefiran. We investigated the effect of kefir on acute erythroleukemia cell line (KG-1) and peripheral blood mononuclear cells (PBMCs). The cell line and PBMCs were treated with different doses of kefir and milk and incubated for three different times. We used Polymixin B to block the lipopolysaccharide and NaOH (1 mol/l) to neutralize the acidic media. Viability was detected by MTT assay. Apoptosis and necrosis were assessed by annexin-propidium iodide staining. Our results showed that kefir induced apoptosis and necrosis in KG-1 cell line. It was revealed that kefir decreased proliferation in erythroleukemia cell line. We did not observe a remarkable effect of kefir on PBMCs. Our study suggested that kefir may have potential to be an effective treatment for erythroleukemia.

  6. Cloning of the cDNA for human 12-lipoxygenase

    International Nuclear Information System (INIS)

    Izumi, T.; Hoshiko, S.; Radmark, O.; Samuelsson, B.

    1990-01-01

    A full-length cDNA clone encoding 12-lipoxygenase was isolated from a human platelet cDNA library by using a cDNA for human reticulocyte 15-lipoxygenase as probe for the initial screening. The cDNA had an open reading frame encoding 662 amino acid residues with a calculated molecular weight of 75,590. Three independent clones revealed minor heterogeneities in their DNA sequences. Thus, in three positions of the deduced amino acid sequence, there is a choice between two different amino acids. The deduced sequence from the clone plT3 showed 65% identity with human reticulocyte 15-lipoxygenase and 42% identity with human leukocyte 5-lipoxygenase. The 12-lipoxygenase cDNA recognized a 3.0-kilobase mRNA species in platelets and human erythroleukemia cells (HEL cells). Phorbol 12-tetradecanoyl 13-acetate induced megakaryocytic differentiation of HEL cells and 12-lipoxygenase activity and increased mRNA for 12-lipoxygenase. The identity of the cloned 12-lipoxygenase was assured by expression in a mammalian cell line (COS cells). Human platelet 12-lipoxygenase has been difficult to purify to homogeneity. The cloning of this cDNA will increase the possibilities to elucidate the structure and function of this enzyme

  7. S1 nuclease analysis of α-globin gene expression in preleukemic patients with acquired hemoglobin H disease after transfer to mouse erythroleukemia cells

    International Nuclear Information System (INIS)

    Helder, J.; Deisseroth, A.

    1987-01-01

    The loss of α-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of α-globin gene expression (hemoglobin H disease) in these patients is linked with the α-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human α-globin genes. After transfer to mouse erythroleukemia cells, the expression of human α-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human α-globin genes transferred to mouse erythroleukemia cells from normal donors. These data showed that factor(s) in the mouse erythroleukemia cell can genetically complement the α-globin gene defect in these preleukemia patients with acquired hemoglobin H disease and suggest that altered expression of a gene in trans to the α-globin gene may be responsible for the acquisition of hemoglobin H disease in these patients

  8. Case Report: Congenital Erythroleukemia in a Premature Infant with Dysmorphic Features.

    Science.gov (United States)

    Helin, Heidi; van der Walt, Jon; Holder, Muriel; George, Simi

    2016-01-01

    We present a case of pure erythroleukemia, diagnosed at autopsy, in a dysmorphic premature infant who died of multiorgan failure within 24 hours of birth. Dysmorphic features included facial and limb abnormalities with long philtrum, microagnathia, downturned mouth, short neck as well as abnormal and missing nails, missing distal phalanx from the second toe, and overlapping toes. Internal findings included gross hepatomegaly and patchy hemorrhages in the liver, splenomegaly, and cardiomegaly; and subdural, intracerebral, and intraventricular hemorrhages. Histology revealed infiltration of bone marrow, kidney, heart, liver, adrenal, lung, spleen, pancreas, thyroid, testis, thymus, and placenta by pure erythroleukemia. Only 6 cases of congenital erythroleukemia have been previously reported with autopsy findings similar to those of this case. The dysmorphic features, although not fitting any specific syndrome, make this case unique. Congenital erythroleukemia and possible syndromes suggested by the dysmorphic features are discussed.

  9. Hydroxychloroquine susceptibility determination of Coxiella burnetii in human embryonic lung (HEL) fibroblast cells.

    Science.gov (United States)

    Angelakis, Emmanouil; Khalil, Jacques Bou; Le Bideau, Marion; Perreal, Celine; La Scola, Bernard; Raoult, Didier

    2017-07-01

    Coxiella burnetii, the causative agent of Q fever, survives and replicates in the acidic environment of monocytes/macrophages; hydroxychloroquine, through alkalinisation of the acidic vacuoles, is critical for the management of Q fever. In this study, a collection of C. burnetii strains isolated from human samples was tested to evaluate the in vitro minimum inhibitory concentrations (MICs) of doxycycline and hydroxychloroquine. Serial two-fold dilutions of doxycycline (0.25-8 mg/L) and hydroxychloroquine (0.25-4 mg/L) were added to C. burnetii-infected human embryonic lung (HEL) fibroblast cells after 48 h of incubation, in duplicate. DNA was detected by C. burnetii-specific semi-quantitative PCR with primers and probes designed for amplification of the IS1111 and IS30A spacers. A total of 29 C. burnetii isolates obtained from 29 patients were tested. Doxycycline MICs ranged from 0.25 mg/L to 0.5 mg/L and hydroxychloroquine MICs from 0.25 mg/L to >4 mg/L. Four C. burnetii stains had hydroxychloroquine MICs ≤ 1 mg/L. The concentration of hydroxychloroquine was associated with a significant decrease in C. burnetii DNA copies in HEL cells based on linear regression analysis (P= 0.01). Recommended serum concentrations of hydroxychloroquine significantly reduced the growth of C. burnetii. Moreover, some C. burnetii strains presented hydroxychloroquine MICs below the recommended serum concentrations, indicating that, for these cases, hydroxychloroquine treatment alone may even be effective. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  10. DNA binding and unwinding by Hel308 helicase requires dual functions of a winged helix domain.

    Science.gov (United States)

    Northall, Sarah J; Buckley, Ryan; Jones, Nathan; Penedo, J Carlos; Soultanas, Panos; Bolt, Edward L

    2017-09-01

    Hel308 helicases promote genome stability linked to DNA replication in archaea, and have homologues in metazoans. In the crystal structure of archaeal Hel308 bound to a tailed DNA duplex, core helicase domains encircle single-stranded DNA (ssDNA) in a "ratchet" for directional translocation. A winged helix domain (WHD) is also present, but its function is mysterious. We investigated the WHD in full-length Hel308, identifying that mutations in a solvent exposed α-helix resulted in reduced DNA binding and unwinding activities. When isolated from the rest of Hel308, the WHD protein alone bound to duplex DNA but not ssDNA, and DNA binding by WHD protein was abolished by the same mutations as were analyzed in full-length Hel308. Isolated WHD from a human Hel308 homologue (HelQ) also bound to duplex DNA. By disrupting the interface between the Hel308 WHD and a RecA-like domain, a topology typical of Ski2 helicases, we show that this is crucial for ATPase and helicase activities. The data suggest a model in which the WHD promotes activity of Hel308 directly, through binding to duplex DNA that is distinct from ssDNA binding by core helicase, and indirectly through interaction with the RecA-like domain. We propose how the WHD may contribute to ssDNA translocation, resulting in DNA helicase activity or in removal of other DNA bound proteins by "reeling" ssDNA. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. PU.1 silencing leads to terminal differentiation of erythroleukemia cells

    International Nuclear Information System (INIS)

    Atar, Orna; Levi, Ben-Zion

    2005-01-01

    The transcription factor PU.1 plays a central role in development and differentiation of hematopoietic cells. Evidence from PU.1 knockout mice indicates a pivotal role for PU.1 in myeloid lineage and B-lymphocyte development. In addition, PU.1 is a key player in the development of Friend erythroleukemia disease, which is characterized by proliferation and differentiation arrest of proerythrocytes. To study the role of PU.1 in erythroleukemia, we have used murine erythroleukemia cells, isolated from Friend virus-infected mice. Expression of PU.1 small interfering RNA in these cells led to significant inhibition of PU.1 levels. This was accompanied by inhibition of proliferation and restoration in the ability of the proerythroblastic cells to produce hemoglobin, i.e., reversion of the leukemic phenotype. The data suggest that overexpression of PU.1 gene is the immediate cause for maintaining the leukemic phenotype of the disease by retaining the self-renewal capacity of transformed erythroblastic cells and by blocking the terminal differentiation program towards erythrocytes

  12. RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans

    Science.gov (United States)

    Seo, Mihwa; Seo, Keunhee; Hwang, Wooseon; Koo, Hee Jung; Hahm, Jeong-Hoon; Yang, Jae-Seong; Han, Seong Kyu; Hwang, Daehee; Kim, Sanguk; Jang, Sung Key; Lee, Yoontae; Nam, Hong Gil; Lee, Seung-Jae V.

    2015-01-01

    The homeostatic maintenance of the genomic DNA is crucial for regulating aging processes. However, the role of RNA homeostasis in aging processes remains unknown. RNA helicases are a large family of enzymes that regulate the biogenesis and homeostasis of RNA. However, the functional significance of RNA helicases in aging has not been explored. Here, we report that a large fraction of RNA helicases regulate the lifespan of Caenorhabditis elegans. In particular, we show that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by specifically activating the DAF-16/forkhead box O (FOXO) transcription factor signaling pathway. We find that HEL-1 is required for the longevity conferred by reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is sufficient for extending lifespan. We further show that the expression of HEL-1 in the intestine and neurons contributes to longevity. HEL-1 enhances the induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL-1 appears to promote longevity in response to decreased IIS as a transcription coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a similar mechanism for longevity regulation via an RNA helicase-dependent regulation of FOXO signaling may operate in mammals, including humans. PMID:26195740

  13. Erythroid differentiation and commitment in rat erythroleukemia cells with hypertonic culture conditions.

    OpenAIRE

    Yamaguchi, Y; Kluge, N; Ostertag, W; Furusawa, M

    1981-01-01

    Cell cultures of 7,12-dimethylbenz[a]anthracene-induced rat erythroleukemia can be stimulated to synthesize hemoglobin when cultured in hypertonic media. During hypertonic treatment the intracellular osmotic conditions immediately readjust to those of the extracellular medium. None of the Friend virus-induced mouse erythroleukemia cell lines was inducible for differentiation with the same hypertonic culture conditions used for rat cells. Earliest commitment to erythroid terminal differentiati...

  14. The HelCat basic plasma science device

    Science.gov (United States)

    Gilmore, M.; Lynn, A. G.; Desjardins, T. R.; Zhang, Y.; Watts, C.; Hsu, S. C.; Betts, S.; Kelly, R.; Schamiloglu, E.

    2015-01-01

    The Helicon-Cathode(HelCat) device is a medium-size linear experiment suitable for a wide range of basic plasma science experiments in areas such as electrostatic turbulence and transport, magnetic relaxation, and high power microwave (HPM)-plasma interactions. The HelCat device is based on dual plasma sources located at opposite ends of the 4 m long vacuum chamber - an RF helicon source at one end and a thermionic cathode at the other. Thirteen coils provide an axial magnetic field B >= 0.220 T that can be configured individually to give various magnetic configurations (e.g. solenoid, mirror, cusp). Additional plasma sources, such as a compact coaxial plasma gun, are also utilized in some experiments, and can be located either along the chamber for perpendicular (to the background magnetic field) plasma injection, or at one of the ends for parallel injection. Using the multiple plasma sources, a wide range of plasma parameters can be obtained. Here, the HelCat device is described in detail and some examples of results from previous and ongoing experiments are given. Additionally, examples of planned experiments and device modifications are also discussed.

  15. Random small interfering RNA library screen identifies siRNAs that induce human erythroleukemia cell differentiation.

    Science.gov (United States)

    Fan, Cuiqing; Xiong, Yuan; Zhu, Ning; Lu, Yabin; Zhang, Jiewen; Wang, Song; Liang, Zicai; Shen, Yan; Chen, Meihong

    2011-03-01

    Cancers are characterized by poor differentiation. Differentiation therapy is a strategy to alleviate malignant phenotypes by inducing cancer cell differentiation. Here we carried out a combinatorial high-throughput screen with a random siRNA library on human erythroleukemia K-562 cell differentiation. Two siRNAs screened from the library were validated to be able to induce erythroid differentiation to varying degrees, determined by CD235 and globin up-regulation, GATA-2 down-regulation, and cell growth inhibition. The screen we performed here is the first trial of screening cancer differentiation-inducing agents from a random siRNA library, demonstrating that a random siRNA library can be considered as a new resource in efforts to seek new therapeutic agents for cancers. As a random siRNA library has a broad coverage for the entire genome, including known/unknown genes and protein coding/non-coding sequences, screening using a random siRNA library can be expected to greatly augment the repertoire of therapeutic siRNAs for cancers.

  16. The Hel Peninsula – Smart Grid Pilot Project

    Directory of Open Access Journals (Sweden)

    Sławomir Noske

    2014-12-01

    Full Text Available The paper presents the scope and results of engineering, and the scope of Smart Grid deployment in the Hel Peninsula. The following functionalities will be described: Fault Detection, Isolation & Recovery – FDIR function, Integrated Volt/Var Control (IVVC function, advanced supervision of LV grid, including distributed energy resources. The paper contains implementation results and research findings, as well as preliminary cost-benefit analysis of the project. Moreover, since Smart Metering and Smart Grid projects are being deployed in the same region – the Hel Peninisula – the benefit achieved by merging the two projects will be explained.

  17. Erythroleukemia shares biological features and outcome with myelodysplastic syndromes with excess blasts: a rationale for its inclusion into future classifications of myelodysplastic syndromes.

    Science.gov (United States)

    Calvo, Xavier; Arenillas, Leonor; Luño, Elisa; Senent, Leonor; Arnan, Montserrat; Ramos, Fernando; Ardanaz, María Teresa; Pedro, Carme; Tormo, Mar; Montoro, Julia; Díez-Campelo, María; Arrizabalaga, Beatriz; Xicoy, Blanca; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Benet; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

    2016-12-01

    Erythroleukemia was considered an acute myeloid leukemia in the 2008 World Health Organization (WHO) classification and is defined by the presence of ≥50% bone marrow erythroblasts, having <20% bone marrow blasts from total nucleated cells but ≥20% bone marrow myeloblasts from nonerythroid cells. Erythroleukemia shares clinicopathologic features with myelodysplastic syndromes, especially with erythroid-predominant myelodysplastic syndromes (≥50% bone marrow erythroblasts). The upcoming WHO revision proposes to eliminate the nonerythroid blast cell count rule and to move erythroleukemia patients into the appropriate myelodysplastic syndrome category on the basis of the absolute blast cell count. We conducted a retrospective study of patients with de novo erythroleukemia and compared their clinico-biological features and outcome with those of de novo myelodysplastic syndromes, focusing on erythroid-predominant myelodysplastic syndromes. Median overall survival of 405 erythroid-predominant myelodysplastic syndromes without excess blasts was significantly longer than that observed in 57 erythroid-predominant refractory anemias with excess blasts-1 and in 59 erythroleukemias, but no significant difference was observed between erythroid-predominant refractory anemias with excess blasts-1 and erythroleukemias. In this subset of patients with ≥50% bone marrow erythroblasts and excess blasts, the presence of a high-risk karyotype defined by the International Prognostic Scoring System or by the Revised International Prognostic Scoring System was the main prognostic factor. In the same way, the survival of 459 refractory anemias with excess blasts-2, independently of having ≥20% bone marrow blasts from nonerythroid cells or not, was almost identical to the observed in 59 erythroleukemias. Interestingly, 11 low-blast count erythroleukemias with 5 to <10% bone marrow blasts from total nucleated cells showed similar survival than the rest of erythroleukemias. Our data

  18. Model for visualizing high energy laser (HEL) damage

    Science.gov (United States)

    Erten, Gail

    2017-11-01

    This paper describes and presents results from a model created in MATLAB® to calculate and display the time dependent temperature profile on a target aimpoint as it is being engaged by a high energy laser (HEL) beam. The model uses public domain information namely physics equations of heat conduction and phase changes and material properties such as thermal conductivity/diffusivity, latent heat, specific heat, melting and evaporation points as well as user input material type and thickness. The user also provides time varying characteristics of the HEL beam on the aimpoint, including beam size and intensity distribution (in Watts per centimeter square). The model calculates the temperature distribution at and around the aimpoint and also shows the phase changes of the aimpoint with the material first melting and then evaporating. User programmable features (selecting materials and thickness, erosion rates for melting) make the model highly versatile. The objective is to bridge the divide between remaining faithful to theoretical formulations such as the partial differential equations of heat conduction and at the same time serving practical concerns of the model user who needs to rapidly evaluate HEL thermal effects. One possible use of the tool is to assess lethality values of different aimpoints without costly (as well as often dangerous and destructive) experiments.

  19. BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

    International Nuclear Information System (INIS)

    Goupille, Olivier; Penglong, Tipparat; Lefèvre, Carine; Granger, Marine; Kadri, Zahra; Fucharoen, Suthat; Maouche-Chrétien, Leila; Leboulch, Philippe; Chrétien, Stany

    2012-01-01

    Highlights: ► UT7 erythroleukemia cells are known to be refractory to differentiate. ► Brief JQ1 treatment initiates the first steps of erythroid differentiation program. ► Engaged UT7 cells then maturate in the presence of erythropoietin. ► Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

  20. BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

    Energy Technology Data Exchange (ETDEWEB)

    Goupille, Olivier [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Penglong, Tipparat [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Lefevre, Carine; Granger, Marine; Kadri, Zahra [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Fucharoen, Suthat [Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Maouche-Chretien, Leila [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Leboulch, Philippe [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Genetics Division, Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Chretien, Stany, E-mail: stany.chretien@cea.fr [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer UT7 erythroleukemia cells are known to be refractory to differentiate. Black-Right-Pointing-Pointer Brief JQ1 treatment initiates the first steps of erythroid differentiation program. Black-Right-Pointing-Pointer Engaged UT7 cells then maturate in the presence of erythropoietin. Black-Right-Pointing-Pointer Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

  1. Experimental research on HEL and failure properties of alumina under impact loading

    Directory of Open Access Journals (Sweden)

    Xiao-wei Feng

    2016-06-01

    Full Text Available A series of plate impact experiments on alumina was conducted using a light gas gun in order to further investigate Hugoniot elastic limit (HEL and failure properties of alumina under shock compression. The velocity interferometer system for any reflector (VISAR was used to record the rear-free surface velocity histories of the alumina samples. According to the experimental results, the HELs of tested alumina samples with different thicknesses were measured, and the decay phenomenon of elastic wave in shocked alumina was studied. A phenomenological expression between HEL and thickness of sample was presented, and the causes of the decay phenomenon were discussed. The propagation of failure wave in shocked alumina was probed. The velocity and delayed time of failure wave propagation were obtained. The physical mechanism of the generation and propagation of failure was further discussed.

  2. Pure Erythroleukemia (Variant Acute Myeloid Leukemia-vAML-M6) with Deletion of Chromosome 20, Mainly Presenting as Late Erythroblasts, a Unique Case Report with Review of Literature.

    Science.gov (United States)

    Rasool, Javid; Geelani, Sajad; Khursheed; Yasir; Lone, Mohd Suhail; Shaban, Mohd

    2014-03-01

    Acute erythroleukemia is characterized by a predominant immature erythroid population and accounts for approximately 2-5 % of all cases of acute leukemia. Two subtypes are recognized based on the presence or absence of a significant myeloid component: erythroleukemia and pure erythroid leukemia. Erythroleukemia is predominantly a disease of adults, while pure erythroid leukemia can be seen in any age including children. Here is a case of pure erythroleukemia presenting mainly as late erythroblasts which was diagnosed on bone marrow examination, cytochemistry and was confirmed on immunophenotyping. Possibly this is the only case so for demonstrating deletion of long arm of chromosome 20 in pure erythroleukemia.

  3. A Taq 1 polymorphism for the human platelet glycoprotein IIIa gene (GP3A)

    Energy Technology Data Exchange (ETDEWEB)

    Burk, C; Ingram, C; Weiner, M; Rappaport, E F; Schwartz, E; Poncz, M [Univ. of Pennsylvania School of Medicine, Philadelphia (USA)

    1988-07-25

    A cDNA clone containing a 4.0 kb GPIIIa insert was isolated from a human erythroleukemia (HEL) cell cDNA library. A 2.3 kb Eco RI fragment, representing the 5{prime} portion of this insert, was used as a probe for these Southern blot experiments. Taq I (T/CGA) identifies invariant bands of 5.0, 3.5, 1.3, 1.1, and 0.8 kb and a simple polymorphism with a band(s) at 8.0 kb or 4.8 and 3.2 kb. The frequency of the gene was studied in 17 persons (11 Caucasians, 3 Asians, and 3 blacks). The GPIIIa gene has been localized to the region 17q21{r arrow}22 by somatic cell hybrid and in situ hybridization studies. Mendelian inheritance was demonstrated in one family. The father is homozygous for the 8.0 kb band, and the mother is heterozygous for the 8.0/4.8 and 3.2 kb bands.

  4. t anti tb anti b hadroproduction with massive bottom quarks with PowHel

    International Nuclear Information System (INIS)

    Bevilacqua, G.; Garzelli, M.V.; Kardos, A.

    2017-09-01

    The associated production of top-antitop-bottom-antibottom quarks is a relevant irreducible background for Higgs boson analyses in the top-antitop-Higgs production channel, with Higgs decaying into a bottom-antibottom quark pair. We implement this process in the PowHel event generator, considering the bottom quarks as massive in all steps of the computation which involves hard-scattering matrix-elements in the 4-flavour number scheme combined with 4-flavour Parton Distribution Functions. Predictions with NLO QCD+Parton Shower accuracy, as obtained by PowHel+PYTHIA, are compared to those which resulted from a previous PowHel implementation with hard-scattering matrix-elements in the 5-flavour number scheme, considering as a baseline the example of a realistic analysis of top-antitop hadroproduction with additional b-jet activity, performed by the CMS collaboration at the Large Hadron Collider.

  5. Ptpmt1 induced by HIF-2α regulates the proliferation and glucose metabolism in erythroleukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Qin-Qin [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining, 810001 (China); Qinghai Provincial People' s Hospital, Xining (China); Xiao, Feng-Jun; Sun, Hui-Yan [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850 (China); Shi, Xue-Feng [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining, 810001 (China); Qinghai Provincial People' s Hospital, Xining (China); Wang, Hua; Yang, Yue-Feng; Li, Yu-Xiang [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850 (China); Wang, Li-Sheng, E-mail: wangls@bmi.ac.cn [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, 100850 (China); Ge, Ri-Li, E-mail: geriligao@hotmail.com [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining, 810001 (China)

    2016-03-18

    Hypoxia provokes metabolism misbalance, mitochondrial dysfunction and oxidative stress in both human and animal cells. However, the mechanisms which hypoxia causes mitochondrial dysfunction and energy metabolism misbalance still remain unclear. In this study, we presented evidence that mitochondrial phosphatase Ptpmt1 is a hypoxia response molecule that regulates cell proliferation, survival and glucose metabolism in human erythroleukemia TF-1 cells. Exposure to hypoxia or DFO treatment results in upregulation of HIF1-α, HIF-2α and Ptpmt1. Only inhibition of HIF-2α by shRNA transduction reduces Ptpmt1 expression in TF-1 cells under hypoxia. Ptpmt1 inhibitor suppresses the growth and induces apoptosis of TF-1 cells. Furthermore, we demonstrated that Ptpmt1 inhibition reduces the Glut1 and Glut3 expression and decreases the glucose consumption in TF-1 cells. In additional, Ptpmt1 knockdown also results in the mitochondrial dysfunction determined by JC1 staining. These results delineate a key role for HIF-2α-induced Ptpmt1 upregulation in proliferation, survival and glucose metabolism of erythroleukemia cells. It is indicated that Ptpmt1 plays important roles in hypoxia-induced cell metabolism and mitochondrial dysfunction. - Highlights: • Hypoxia induces upregulation of HIF-1α, HIF-2α and Ptpmt1; HIF-2a induces Ptpmt1 upregulation in TF-1 cells. • PTPMT-1 inhibition reduces growth and induces apoptosis of TF-1 cells. • PTPMT1 inhibition downregulates Glut-1, Glut-3 expression and reduces glucose consumption.

  6. Irradiation-induced erythroleukemia and myelogenous leukemia in the beagle dog: hematology and ultrastructure

    International Nuclear Information System (INIS)

    Seed, T.M.; Tolle, D.V.; Fritz, T.E.; Devine, R.L.; Poole, C.M.; Norris, W.P.

    1977-01-01

    A high incidence of leukemia in adult beagle dogs was induced by continuous whole-body exposure to low doses of 60 Co gamma irradiation. At 5, 10, and 17 R per 22-hr exposure day, 20 animals of 53 died of either myelogenous leukemia (15 of 20) or erythroleukemia (5 of 20); the latter occurred only at 5 R/day. Consistent preclinical changes occurred in the peripheral blood, including a partial recovery from an initial severe leukopenia, a prolonged accommodation-to-irradiation phase, and marked oscillations in platelet values in the preleukemic period. In the terminal condition the dogs were severely anemic, thrombocytopenic, and commonly leukopenic. Peripheral blood buffy-coat preparations contained circulating ''blast'' cells and juvenile forms. Abnormal erythrocyte and platelet morphology was consistently present. The bone marrow was altered most severely; other organs showed variable degrees of leukemic infiltration and proliferation and loss of normal tissue architecture. The marrow was hyperplastic with little or no fat remaining. Differential marrow cell counts showed increased numbers of immature cell forms. Myeloid:erythroid (M:E) ratios ranged from 2.6:1 to 61.5:1 in the granulocytic leukemias, and 0.2:1 to 1:1 in the erythroleukemias. Juvenile leukemic cells (both circulating and tissue forms) displayed a number of distinctive cytologic features, including asynchronous patterns of nuclear-cytoplasmic maturation, increased incidence of nuclear clefts, coalescence of cytoplasmic granules, and bizarre arrangements of endoplasmic reticulum. These experimentally induced canine leukemias have many hematologic and cytologic features in common with both spontaneous and radiation-induced leukemias of man. Thus, they may provide a useful model for the study of human leukemia

  7. Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line

    DEFF Research Database (Denmark)

    Saito, M; Helin, K; Valentine, M B

    1995-01-01

    , we isolated genomic clones encompassing the human E2F1 gene. We then used fluorescence in situ hybridization to localize E2F1 to human chromosome 20q11, telomeric to the p107 locus, a gene whose product is related to the retinoblastoma gene product (pRb). This finding contrasts with the 1p36 and 6q22...

  8. Radiation-induced erythroleukemia in the beagle dog

    International Nuclear Information System (INIS)

    Tolle, D.V.; Fritz, T.E.; Norris, W.P.

    1977-01-01

    Eleven cases of myeloproliferative disease occurred in a group of 24 beagle dogs placed in a 60 Co γ-ray field at about 13 months of age and irradiated at an exposure rate of 5 R/22-hour day for duration of life. Of these 11 dogs, 5 were diagnosed as having erythroleukemia. The bone marrow showed marked erythroblastic hyperplasia, with maturation arrest of the erythroid elements, and increased numbers of myeloblasts and promyelocytes. The terminal peripheral blood was characterized by marked anemia and thrombocytopenia, with circulating erythrocytic precursors and abnormal erythrocyte morphology. Splenomegaly and hepatomegaly occurred in 4 of the 5 animals. In the spleens and livers of all 5, there was extensive leukemic infiltration and proliferation. The extent of leukemic involvement in other tissues and organs varied in individual dogs

  9. Peko helü kujutamisest ja kirätämisest / Kauksi Ülle

    Index Scriptorium Estoniae

    Kauksi Ülle, pseud., 1962-

    2005-01-01

    Näitus "Peko helü" Hobusepea galeriis. Oma loomingut eksponeerivad Obinitsa grupeeringu kunstnikud Evar Riitsaar, Albert Gulk, Toomas Kuusing, Mati Kuusing, Eero Ijavoinen, Erki Jürise. Peko kummardamisest

  10. Mycobacterium smegmatis HelY Is an RNA-Activated ATPase/dATPase and 3'-to-5' Helicase That Unwinds 3'-Tailed RNA Duplexes and RNA:DNA Hybrids.

    Science.gov (United States)

    Uson, Maria Loressa; Ordonez, Heather; Shuman, Stewart

    2015-10-01

    Mycobacteria have a large and distinctive ensemble of DNA helicases that function in DNA replication, repair, and recombination. Little is known about the roster of RNA helicases in mycobacteria or their roles in RNA transactions. The 912-amino-acid Mycobacterium smegmatis HelY (MSMEG_3885) protein is a bacterial homolog of the Mtr4 and Ski2 helicases that regulate RNA 3' processing and turnover by the eukaryal exosome. Here we characterize HelY as an RNA-stimulated ATPase/dATPase and an ATP/dATP-dependent 3'-to-5' helicase. HelY requires a 3' single-strand RNA tail (a loading RNA strand) to displace the complementary strand of a tailed RNA:RNA or RNA:DNA duplex. The findings that HelY ATPase is unresponsive to a DNA polynucleotide cofactor and that HelY is unable to unwind a 3'-tailed duplex in which the loading strand is DNA distinguish HelY from other mycobacterial nucleoside triphosphatases/helicases characterized previously. The biochemical properties of HelY, which resemble those of Mtr4/Ski2, hint at a role for HelY in mycobacterial RNA catabolism. RNA helicases play crucial roles in transcription, RNA processing, and translation by virtue of their ability to alter RNA secondary structure or remodel RNA-protein interactions. In eukarya, the RNA helicases Mtr4 and Ski2 regulate RNA 3' resection by the exosome. Mycobacterium smegmatis HelY, a bacterial homolog of Mtr4/Ski2, is characterized here as a unidirectional helicase, powered by RNA-dependent ATP/dATP hydrolysis, that tracks 3' to 5' along a loading RNA strand to displace the complementary strand of a tailed RNA:RNA or RNA:DNA duplex. The biochemical properties of HelY suggest a role in bacterial RNA transactions. HelY homologs are present in pathogenic mycobacteria (e.g., M. tuberculosis and M. leprae) and are widely prevalent in Actinobacteria and Cyanobacteria but occur sporadically elsewhere in the bacterial domain. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Effects of trichostatins on differentiation of murine erythroleukemia cells

    International Nuclear Information System (INIS)

    Yoshida, M.; Nomura, S.; Beppu, T.

    1987-01-01

    The fungistatic antibiotics trichostatins (TS) A and C were isolated from culture broth of Streptomyces platensis No. 145 and were found to be potent inducers of differentiation in murine erythroleukemia (Friend and RV133) cells at concentrations of 1.5 X 10(-8) M for TSA and 5 X 10(-7) M for TSC. Differentiation induced by TS was cooperatively enhanced by UV irradiation but not by treatment with dimethyl sulfoxide. This enhanced activity was completely inhibited by adding cycloheximide to the culture medium 2 h after exposure to TS, suggesting that TS are dimethyl sulfoxide-type inducers of erythroid differentiation. No inhibitory effect of TS was observed on macromolecular synthesis in cultured cells

  12. P2X7 receptor activation induces cell death and microparticle release in murine erythroleukemia cells.

    NARCIS (Netherlands)

    Constantinescu, P.; Wang, B.; Kovacevic, K.; Jalilian, I.; Bosman, G.J.C.G.M.; Wiley, J.S.; Sluyter, R.

    2010-01-01

    Extracellular ATP induces cation fluxes in and impairs the growth of murine erythroleukemia (MEL) cells in a manner characteristic of the purinergic P2X7 receptor, however the presence of P2X7 in these cells is unknown. This study investigated whether MEL cells express functional P2X7. RT-PCR,

  13. Two Ellagic Acids Isolated from Roots of Sanguisorba officinalis L. Promote Hematopoietic Progenitor Cell Proliferation and Megakaryocyte Differentiation

    Directory of Open Access Journals (Sweden)

    Xiaoping Gao

    2014-04-01

    Full Text Available Using a bioassay-directed chromatographic separation, two ellagic acids were obtained from the ethyl acetate extract of the roots of Sanguisorba officinalis L. On the basis of chemical and spectroscopic methods, the two ellagic acids were identified as 3,3',4-tri-O-methylellagic acid-4'-O-β-d-xyloside and 3,3',4-tri-O-methylellagic acid. Stimulation of cell proliferation was assayed in hematopoietic progenitor cells using the Cell Counting kit-8 method. The megakaryocyte differentiation was determined in human erythroleukemia (HEL cells using Giemsa staining and flow cytometry analysis. The ellagic acids significantly stimulated the proliferation of Baf3/Mpl cells. Morphology analysis and megakaryocyte specific-marker CD41 staining confirmed that the ellagic acids induced megakaryocyte differentiation in HEL cells. This is the first time that 3,3',4-tri-O-methylellagic acid or 3,3',4-tri-O-methylellagic acid-4'-O-β-d-xyloside are reported to induce megakaryopoiesis, suggesting a class of small molecules which differ from others non-peptidyl, and appears to have potential for clinical development as a therapeutic agent for patients with blood platelet disorders.

  14. Proteomic analysis of erythroid differentiation induced by hexamethylene bisacetamide in murine erythroleukemia cells

    Czech Academy of Sciences Publication Activity Database

    Petrák, J.; Myslivcová, D.; Man, Petr; Čmejlová, J.; Čmejla, R.; Vyoral, D.

    2007-01-01

    Roč. 35, - (2007), s. 193-202 ISSN 0301-472X R&D Projects: GA MŠk LC545 Grant - others:CZ(CZ) 023736; GA ČR(CZ) GA303/04/0003; GA MŠk(CZ) LC06044 Institutional research plan: CEZ:AV0Z50200510 Source of funding: V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje Keywords : murine erythroleukemia cells * erythroid differentiation * hexamethylene bisacetamide Subject RIV: EE - Microbiology, Virology Impact factor: 3.147, year: 2007

  15. The autoinhibitory CARD2-Hel2i Interface of RIG-I governs RNA selection.

    Science.gov (United States)

    Ramanathan, Anand; Devarkar, Swapnil C; Jiang, Fuguo; Miller, Matthew T; Khan, Abdul G; Marcotrigiano, Joseph; Patel, Smita S

    2016-01-29

    RIG-I (Retinoic Acid Inducible Gene-I) is a cytosolic innate immune receptor that detects atypical features in viral RNAs as foreign to initiate a Type I interferon signaling response. RIG-I is present in an autoinhibited state in the cytoplasm and activated by blunt-ended double-stranded (ds)RNAs carrying a 5' triphosphate (ppp) moiety. These features found in many pathogenic RNAs are absent in cellular RNAs due to post-transcriptional modifications of RNA ends. Although RIG-I is structurally well characterized, the mechanistic basis for RIG-I's remarkable ability to discriminate between cellular and pathogenic RNAs is not completely understood. We show that RIG-I's selectivity for blunt-ended 5'-ppp dsRNAs is ≈3000 times higher than non-blunt ended dsRNAs commonly found in cellular RNAs. Discrimination occurs at multiple stages and signaling RNAs have high affinity and ATPase turnover rate and thus a high katpase/Kd. We show that RIG-I uses its autoinhibitory CARD2-Hel2i (second CARD-helicase insertion domain) interface as a barrier to select against non-blunt ended dsRNAs. Accordingly, deletion of CARDs or point mutations in the CARD2-Hel2i interface decreases the selectivity from ≈3000 to 150 and 750, respectively. We propose that the CARD2-Hel2i interface is a 'gate' that prevents cellular RNAs from generating productive complexes that can signal. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Rapid desensitization of adrenaline- and neuropeptide Y-stimulated Ca2+ mobilization in HEL-cells

    NARCIS (Netherlands)

    Michel, M. C.

    1994-01-01

    1. Desensitization of Gs-coupled receptors, the beta 2-adrenoceptor for example, involves rapid and slower components but little is known regarding the existence of rapid desensitization of Gi-coupled receptors and its possible mechanisms. In HEL-cells stimulation of alpha 2A-adrenoceptors by

  17. Differential stability of host mRNAs in Friend erythroleukemia cells infected with herpes simplex virus type 1

    International Nuclear Information System (INIS)

    Mayman, B.A.; Nishioka, Y.

    1985-01-01

    The consequences of herpes simplex virus type 1 infection on cellular macromolecules were investigated in Friend erythroleukemia cells. The patterns of protein synthesis, examined by polyacrylamide gel electrophoresis, demonstrated that by 4 h postinfection the synthesis of many host proteins, with the exception of histones, was inhibited. Examination of the steady-state level of histone H3 mRNA by molecular hybridization of total RNA to a cloned mouse histone H3 complementary DNA probe demonstrated that the ratio of histone H3 mRNA to total RNA remained unchanged for the first 4 h postinfection. In contrast, the steady-state levels of globin and actin mRNAs decreased progressively at early intervals postinfection. Studies on RNA synthesis in isolated nuclei demonstrated that the transcription of the histone H3 gene was inhibited to approximately the same extent as that of actin gene. It was concluded that the stabilization of preexisting histone H3 mRNA was responsible for the persistence of H3 mRNA and histone protein synthesis in herpes simplex virus type 1-infected Friend erythroleukemia cells. The possible mechanisms influencing the differential stability of host mRNAs during the course of productive infection with herpes simplex virus type 1 are discussed

  18. Retroviral-mediated transfer and expression of human β-globin genes in cultured murine and human erythroid cells

    International Nuclear Information System (INIS)

    Weber-Benarous, A.; Cone, R.D.; London, I.M.; Mulligan, R.C.

    1988-01-01

    The authors cloned human β-globin DNA sequences from a genomic library prepared from DNA isolated from the human leukemia cell line K562 and have used the retroviral vector pZip-NeoSV(X)1 to introduce a 3.0-kilobase segment encompassing the globin gene into mouse erythroleukemia cells. Whereas the endogenous K562 β-globin gene is repressed in K562 cells, when introduced into mouse erythroleukemia cells by retroviral-mediated gene transfer, the β-globin gene from K562 cells was transcribed and induced 5-20-fold after treatment of the cells with dimethyl sulfoxide. The transcripts were correctly initiated, and expression and regulation of the K562 gene were identical to the expression of a normal human β-globin gene transferred into mouse erythroleukemia cells in the same way. They have also introduced the normal human β-globin gene into K562 cells using the same retrovirus vector. SP6 analysis of the RNA isolated from the transduced cells showed that the normal β-globin gene was transcribed at a moderately high level, before or after treatment with hemin. Based on these data, they suggest that the lack of expression of the endogenous β-globin gene in K562 cells does not result from an alteration in the gene itself and may not result from a lack of factor(s) necessary for β-lobin gene transcription. Retroviral-mediated transfer of the human β-globin gene may, however, uniquely influence expression of the gene K562 cells

  19. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F)+ HEL Leukemia Cells

    International Nuclear Information System (INIS)

    Weber, Axel; Borghouts, Corina; Brendel, Christian; Moriggl, Richard; Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd

    2015-01-01

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl + K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5

  20. Selectivity in Ketenimine Cycloadditions. Photoelectron Hel Spectra of Ketenimines

    Science.gov (United States)

    Bernardi, Fernando; Bottoni, Andrea; Ballaglia, Arturo; Distefano, Giuseppe; Dondoni, Alessandro

    1980-05-01

    The first few bands in the photoelectron (Hel) spectra of ketenimines R1R2C-C=NR3(R1,R2=H, CH3, C5H6, CH2=CH; R3=alkyl or aryl group) are assigned to the corresponding molecular orbitals. The assignment is based on SCF-MO calculations made at three different levels (CNDO/2, ab-initio STO-3C and 4-31G) coupled with perturbational molecular orbital analyses. The π-orbitals of the unsaturated substituents are found to interact with one of the two perpendicular π-electron systems of the>C=C=N- residue, the critical factor being the position of attack of the substituent. The relevance of these results on the site selectivity observed in cycloaddition reactions of these species is discussed.

  1. Hel igen efter amputation - og vejen dertil

    DEFF Research Database (Denmark)

    Østergaard, Elisabeth Bomholt

    Hel igen efter amputation – og vejen dertil Elisabeth Bomholt Østergaard, PT, Master i sundhedsantropologi, Dip.pæd. Baggrund Sundhedsprofessionelle bør udvikle større opmærksomhed på og forståelse for, hvilke måder mennesker oplever ’inkorporation’ af diverse proteser, som fx pacemaker, benprotese.......000 og 300.000 mennesker type 2- diabetes og forekomsten er kraftigt stigende og forekommer i stadig yngre aldersgrupper (Dansk Sygeplejeråd 2006) med amputation som mulig konsekvens. Formål Opnå indsigt i hvad der kan medvirke til, at mennesker kan føle sig hele igen efter en benamputation, føle sig...... kropsbevidsthed/at mærke kroppen – at få fokus væk fra kroppen igen, så kroppen atter kan blive fraværende, så der frigives plads til at kunne rette opmærksomheden andre steder hen: meget tidligt at oplyse om muligheden for og helst opfordre til at få besøg af en person, der selv har oplevet amputation på egen...

  2. Mitu elu on ühel majal? = How many lives does a building have? / Alari Allik

    Index Scriptorium Estoniae

    Allik, Alari

    2012-01-01

    Puidu korduskasutusest Jaapanis. Jaapani pühamute arhitektuurist, mis nõuab pidevat ümbertegemist. Säilinud arusaamast, et ehitusprojektide puhul on oluline mõelda läbi kõik etapid, kuna ühel hoonel võib olla mitu elu. Moodsatest majadest. Uuele elule ärganud tööstushoonetest Tallinnas. Tallinna Linnahallist, mis on läbi raskuste leidmas endale uusi funktsioone

  3. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl{sup +} K562 and Jak2(V617F){sup +} HEL Leukemia Cells

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Axel [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany); Borghouts, Corina [Ganymed Pharmaceuticals AG, Mainz 55131 (Germany); Brendel, Christian [Boston Children’s Hospital, Division of Hematology/Oncology, Boston, MA 02115 (United States); Moriggl, Richard [Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Vienna 1090 (Austria); Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd, E-mail: Groner@em.uni-frankfurt.de [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany)

    2015-03-19

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl{sup +} K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells

  4. Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia.

    Science.gov (United States)

    Gong, Feirong; Chen, Dan; Teng, Xin; Ge, Junhua; Ning, Xianfeng; Shen, Ya-Ling; Li, Jian; Wang, Shanfeng

    2017-08-07

    Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and N-(tert-butoxycarbonyl)-l-phenylalanine end-capped mPEG-PCL (mPEG-PCL-Phe(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG-PCL-Phe(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG-PCL-Phe(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG-PCL micelles. Biodistribution results in Sprague-Dawley rats also showed higher uptake and slower elimination of curcumin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG-PCL-Phe(Boc) micelles, as compared with mPEG-PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumin-loaded mPEG-PCL-Phe(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG-PCL-Phe(Boc) micellar system is promising in overcoming the key challenge of curcumin's to promote its applications in cancer therapy.

  5. Hvor meget hel halm udgør tilstrækkeligt beskæftigelses- og rodemateriale til svin

    DEFF Research Database (Denmark)

    Pedersen, Lene Juul; Herskin, Mette S; Forkman, Bjørn

    tildeling af stigende mængder hel halm fra 10 til 1000 g/gris/dag; samt 2) heraf at udrede hvor meget hel halm der kræves for at tilgodese slagtesvins behov for beskæftigelses- og rodemateriale. Undersøgelsen fokuserede på de involverede halmmængders indflydelse på forekomsten af unormal adfærd. I......I nærværende rapport fra DCA – Nationalt Center for Fødevarer og Jordbrug, Aarhus Universitet, der er udarbejdet på anmodning fra Justitsministeriet, gennemgås resultater fra et forskningsprojekt, hvis formål var at1) beskrive et kurveforløb for forekomst af unormal adfærd hos slagtesvin ved...... undersøgelsen indgik dog også følgende sekundære variable: forekomst af skader på hale, daglig tilvækst, mængde af tilbageværende rent halm, stiklima samt mål for grisenes mavesundhed. Forskningsprojektet er udført i samarbejde mellem Aarhus Universitet, Københavns Universitet og Videncenter for Svineproduktion...

  6. Induction of erythroid differentiation in human erythroleukemia cells by depletion of malic enzyme 2.

    Directory of Open Access Journals (Sweden)

    Jian-Guo Ren

    2010-09-01

    Full Text Available Malic enzyme 2 (ME2 is a mitochondrial enzyme that catalyzes the conversion of malate to pyruvate and CO2 and uses NAD as a cofactor. Higher expression of this enzyme correlates with the degree of cell de-differentiation. We found that ME2 is expressed in K562 erythroleukemia cells, in which a number of agents have been found to induce differentiation either along the erythroid or the myeloid lineage. We found that knockdown of ME2 led to diminished proliferation of tumor cells and increased apoptosis in vitro. These findings were accompanied by differentiation of K562 cells along the erythroid lineage, as confirmed by staining for glycophorin A and hemoglobin production. ME2 knockdown also totally abolished growth of K562 cells in nude mice. Increased ROS levels, likely reflecting increased mitochondrial production, and a decreased NADPH/NADP+ ratio were noted but use of a free radical scavenger to decrease inhibition of ROS levels did not reverse the differentiation or apoptotic phenotype, suggesting that ROS production is not causally involved in the resultant phenotype. As might be expected, depletion of ME2 induced an increase in the NAD+/NADH ratio and ATP levels fell significantly. Inhibition of the malate-aspartate shuttle was insufficient to induce K562 differentiation. We also examined several intracellular signaling pathways and expression of transcription factors and intermediate filament proteins whose expression is known to be modulated during erythroid differentiation in K562 cells. We found that silencing of ME2 leads to phospho-ERK1/2 inhibition, phospho-AKT activation, increased GATA-1 expression and diminished vimentin expression. Metabolomic analysis, conducted to gain insight into intermediary metabolic pathways that ME2 knockdown might affect, showed that ME2 depletion resulted in high orotate levels, suggesting potential impairment of pyrimidine metabolism. Collectively our data point to ME2 as a potentially novel

  7. Oxidative Stress Measures of Lipid and DNA Damage in Human Tears.

    Science.gov (United States)

    Haworth, Kristina M; Chandler, Heather L

    2017-05-01

    We evaluate feasibility and repeatability of measures for lipid peroxidation and DNA oxidation in human tears, as well as relationships between outcome variables, and compared our findings to previously reported methods of evaluation for ocular sun exposure. A total of 50 volunteers were seen for 2 visits 14 ± 2 days apart. Tear samples were collected from the inferior tear meniscus using a glass microcapillary tube. Oxidative stress biomarkers were quantified using enzyme-linked immunosorbent assay (ELISA): lipid peroxidation by measurement of hexanoyl-lysine (HEL) expression; DNA oxidation by measurement of 8-oxo-2'-deoxyguinosone (8OHdG) expression. Descriptive statistics were generated. Repeatability estimates were made using Bland-Altman plots with mean differences and 95% limits of agreement were calculated. Linear regression was conducted to evaluate relationships between measures. Mean (±SD) values for tear HEL and 8OHdG expression were 17368.02 (±9878.42) nmol/L and 66.13 (±19.99) ng/mL, respectively. Repeatability was found to be acceptable for both HEL and 8OHdG expression. Univariate linear regression supported tear 8OHdG expression and spring season of collection to be predictors of higher tear HEL expression; tear HEL expression was confirmed as a predictor of higher tear 8OHdG expression. We demonstrate feasibility and repeatability of estimating previously unreported tear 8OHdG expression. Seasonal temperature variation and other factors may influence tear lipid peroxidation. Support is demonstrated to suggest lipid damage and DNA damage occur concurrently on the human ocular surface.

  8. Hadroproduction of t-anti-t pair with two isolated photons with PowHel

    Science.gov (United States)

    Kardos, A.; Trócsányi, Z.

    2015-08-01

    We simulate the hadroproduction of a t t bar pair in association with two isolated hard photons at 13 TeV LHC using the PowHel package. We use the generated events, stored according to the Les-Houches event format, to make predictions for differential distributions formally at the next-to-leading order (NLO) accuracy. We present predictions at the hadron level employing the cone-type isolation of the photons used by experiments. We also compare the kinematic distributions to the same distributions obtained in the t t bar H final state when the Higgs-boson decays into a photon pair, to which the process discussed here is an irreducible background.

  9. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients.

    Science.gov (United States)

    Pardanani, A; Lasho, T; Smith, G; Burns, C J; Fantino, E; Tefferi, A

    2009-08-01

    Somatic mutations in Janus kinase 2 (JAK2), including JAK2V617F, result in dysregulated JAK-signal transducer and activator transcription (STAT) signaling, which is implicated in myeloproliferative neoplasm (MPN) pathogenesis. CYT387 is an ATP-competitive small molecule that potently inhibits JAK1/JAK2 kinases (IC(50)=11 and 18 nM, respectively), with significantly less activity against other kinases, including JAK3 (IC(50)=155 nM). CYT387 inhibits growth of Ba/F3-JAK2V617F and human erythroleukemia (HEL) cells (IC(50) approximately 1500 nM) or Ba/F3-MPLW515L cells (IC(50)=200 nM), but has considerably less activity against BCR-ABL harboring K562 cells (IC=58 000 nM). Cell lines harboring mutated JAK2 alleles (CHRF-288-11 or Ba/F3-TEL-JAK2) were inhibited more potently than the corresponding pair harboring mutated JAK3 alleles (CMK or Ba/F3-TEL-JAK3), and STAT-5 phosphorylation was inhibited in HEL cells with an IC(50)=400 nM. Furthermore, CYT387 selectively suppressed the in vitro growth of erythroid colonies harboring JAK2V617F from polycythemia vera (PV) patients, an effect that was attenuated by exogenous erythropoietin. Overall, our data indicate that the JAK1/JAK2 selective inhibitor CYT387 has potential for efficacious treatment of MPN harboring mutated JAK2 and MPL alleles.

  10. Enzymatic characterization of a human acyltransferase activity.

    Directory of Open Access Journals (Sweden)

    Akihiko Ozawa

    Full Text Available Non-histone protein acylation is increasingly recognized as an important posttranslational modification, but little is known as to the biochemical properties of protein serine acylating enzymes.We here report that we have identified a metal-stimulated serine octanoyltransferase activity in microsomes from human erythroleukemic (HEL cells. The HEL acylating enzyme was linear with respect to time and protein, exhibited a neutral pH optimum (stimulated by cobalt and zinc, and inhibited by chelating reagents. Hydroxylamine treatment removed most, but not all, of the attached radioactivity. A salt extract of microsomal membranes contained the major portion of enzyme activity, indicating that this acyltransferase is not an integral membrane protein. Sucrose density fractionation showed that the acyltransferase activity is concentrated in the endoplasmic reticulum. In competition experiments, the acyltransferase was well inhibited by activated forms of fatty acids containing at least eight to fourteen carbons, but not by acetyl CoA. The zinc-stimulated HEL acyltransferase did not octanoylate proenkephalin, proopiomelanocortin, His-tagged proghrelin, or proghrelin lacking the amino-terminal His-tag stub of Gly-Ala-Met. The peptides des-acyl ghrelin and ACTH were also not acylated; however, des-acyl ghrelin containing the N-terminal tripeptide Gly-Ala-Met was acylated. Mutagenesis studies indicated a requirement for serine five residues from the amino terminus, reminiscent of myristoyl transferase, but not of ghrelin acylation. However, recombinant myristoyl transferase could not recapitulate the hydroxylamine sensitivity, zinc-stimulation, nor EDTA inhibition obtained with HEL acyltransferase, properties preserved in the HEL cell enzyme purified through four sequential chromatographic steps.In conclusion, our data demonstrate the presence of a zinc-stimulated acyltransferase activity concentrated in the endoplasmic reticulum in HEL cells which is likely

  11. Understanding developmental language disorder - the Helsinki longitudinal SLI study (HelSLI): a study protocol.

    Science.gov (United States)

    Laasonen, Marja; Smolander, Sini; Lahti-Nuuttila, Pekka; Leminen, Miika; Lajunen, Hanna-Reetta; Heinonen, Kati; Pesonen, Anu-Katriina; Bailey, Todd M; Pothos, Emmanuel M; Kujala, Teija; Leppänen, Paavo H T; Bartlett, Christopher W; Geneid, Ahmed; Lauronen, Leena; Service, Elisabet; Kunnari, Sari; Arkkila, Eva

    2018-05-21

    Developmental language disorder (DLD, also called specific language impairment, SLI) is a common developmental disorder comprising the largest disability group in pre-school-aged children. Approximately 7% of the population is expected to have developmental language difficulties. However, the specific etiological factors leading to DLD are not yet known and even the typical linguistic features appear to vary by language. We present here a project that investigates DLD at multiple levels of analysis and aims to make the reliable prediction and early identification of the difficulties possible. Following the multiple deficit model of developmental disorders, we investigate the DLD phenomenon at the etiological, neural, cognitive, behavioral, and psychosocial levels, in a longitudinal study of preschool children. In January 2013, we launched the Helsinki Longitudinal SLI study (HelSLI) at the Helsinki University Hospital ( http://tiny.cc/HelSLI ). We will study 227 children aged 3-6 years with suspected DLD and their 160 typically developing peers. Five subprojects will determine how the child's psychological characteristics and environment correlate with DLD and how the child's well-being relates to DLD, the characteristics of DLD in monolingual versus bilingual children, nonlinguistic cognitive correlates of DLD, electrophysiological underpinnings of DLD, and the role of genetic risk factors. Methods include saliva samples, EEG, computerized cognitive tasks, neuropsychological and speech and language assessments, video-observations, and questionnaires. The project aims to increase our understanding of the multiple interactive risk and protective factors that affect the developing heterogeneous cognitive and behavioral profile of DLD, including factors affecting literacy development. This accumulated knowledge will form a heuristic basis for the development of new interventions targeting linguistic and non-linguistic aspects of DLD.

  12. Dimethyl sulfoxide-inducible cytoplasmic factor involved in erythroid differentiation in mouse erythroleukemia (Friend) cells

    International Nuclear Information System (INIS)

    Watanabe, T.; Oishi, M.

    1987-01-01

    A previous report described an intracellular factor (differentiation-inducing factor I, or DIF-I) that seem to play a role in erythroid differentiation in mouse erythroleukemia (MEL) cells. The authors have detected another erythroid-inducing factor in cell-free extracts from dimethyl sulfoxide- or hexamethylenebis(acetamide)-treated MEL cells, which acts synergistically with DIF-I. The partially purified factor (termed DIF-II) triggered erythroid differentiation when introduced into undifferentiated MEL cells that had been potentiated by the induction of DIF-I. The activity in the extracts appeared in an inducible manner after addition of dimethyl sulfoxide or hexamethylenebis(acetamide), reached a maximum at 6 hr, and then rapidly decreased. The induction was inhibited by phorbol 12-myristate 13-acetate and also by cycloheximide. No induction was observed in a mutant MEL cell line defective in erythroid differentiation. These characteristics are consistent with the supposition that DIF-II is one of the putative dimethyl sulfoxide-inducible factors detected in previously reported cell-fusion and cytoplast-fusion experiments. The role of DIF-II in MEL-cell differentiation and in vitro differentiation in general is discussed

  13. A Study of the Failure Wave Phenomenon in Glasses at Peak Stresses Exceeding the HEL

    International Nuclear Information System (INIS)

    Kanel, G. I.; Razorenov, S. V.; Savinykh, A. S.; Rajendran, A.; Chen Zhen

    2006-01-01

    Shock-wave experiments with two glasses of different hardness have been carried out at shock stress levels above the Hugoniot elastic limit. A comparison between the measured free surface velocity histories from two plate impact experiments performed at approximately the same shock stress level (one with a single thick target plate, and the other with several adjacent target plates of total thickness equal to that of the thick target plate) revealed: 1) at shock loading the failure wave is not formed at stress levels above the HEL, indicating suppression of the fracture process by plasticity, 2) at gradual compression the failure wave process occurs as the stress increases above the failure threshold up to the stress at which plastic deformation begins

  14. Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells.

    Science.gov (United States)

    Kaczmarek, Monika Z; Holland, Ryan J; Lavanier, Stephen A; Troxler, Jami A; Fesenkova, Valentyna I; Hanson, Charlotte A; Cmarik, Joan L; Saavedra, Joseph E; Keefer, Larry K; Ruscetti, Sandra K

    2014-03-01

    The nitric oxide (NO) prodrug JS-K, a promising anti-cancer agent, consists of a diazeniumdiolate group necessary for the release of NO as well as an arylating ring. In this study, we research the mechanism by which JS-K kills a murine erythroleukemia cell line and determine the roles of NO and arylation in the process. Our studies indicate that JS-K inhibits the PI 3-kinase/Akt and MAP kinase pathways. This correlates with the activation of the tumor suppressor FoxO3a and increased expression of various caspases, leading to apoptosis. The arylating capability of JS-K appears to be sufficient for inducing these biological effects. Overall, these data suggest that JS-K kills tumor cells by arylating and inactivating signaling molecules that block the activation of a tumor suppressor. Published by Elsevier Ltd.

  15. Specific binding of 125I-rErythropoietin to Friend polycythemia virus-transformed erythroleukemia cells purified by centrifugal elutriation

    International Nuclear Information System (INIS)

    Correa, P.N.; Bard, V.; Axelrad, A.A.

    1990-01-01

    We have used countercurrent centrifugal elutriation (CCE) to determine the distribution of cells with respect to cell volume and buoyant density for an erythroleukemia cell line (JG6) transformed by the polycythemia strain of Friend virus (FV-P), and to determine the effect of inducing the cells to differentiate with dimethylsulfoxide (DMSO) on this distribution. CCE made it possible to obtain suspensions of modal JG6 populations virtually free of dead cells and uniform with respect to volume and buoyant density. These modal populations were assayed for specific binding of erythropoietin (Epo). Between 500 and 550 Epo receptors per cell were detected. These belonged to a single class having a dissociation constant of 0.36 nM. DMSO induction of differentiation of the JG6 cells had no effect on the number of Epo receptors expressed

  16. Co-ordinate expression of activin A and its type I receptor mRNAs during phorbol ester-induced differentiation of human K562 erythroleukemia cells.

    Science.gov (United States)

    Hildén, K; Tuuri, T; Erämaa, M; Ritvos, O

    1999-07-20

    Activins were originally isolated based on their ability to stimulate follicle-stimulating hormone secretion but later they have been shown to regulate a number of different cellular functions such as nerve cell survival, mesoderm induction during early embryogenesis as well as hematopoiesis. We studied the regulation of activin A, a homodimer of betaA-subunits, mRNA and protein in K562 erythroleukemia cells, which are known to be induced toward the erythroid lineage in response to activin or TGF-beta or toward the megakaryocytic lineage by the phorbol ester protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA). Here we show by Northern blot analysis as well as by Western and ligand blotting that TPA strongly promotes activin betaA-subunit mRNA and activin A protein expression in K562 cells in time- and concentration dependent manner. In contrast, neither activin A nor TGF-beta induced betaA-subunit mRNA expression during erythroid differentiation in K562 cells. Interestingly, whereas activin type II receptors are not regulated during K562 cell differentiation (Hilden et al. (1994) Blood 83, 2163-2170), we now show that the activin type I and IB receptor mRNAs are clearly induced by TPA but not by activin or TGF-beta. We also show that the inducing effect of TPA on expression of activin betaA-subunit mRNA is potentiated by the protein kinase A activator 8-bromo-cAMP. We conclude that activin A and its type I receptors appear to be co-ordinately up-regulated during megakaryocytic differentiation of K562 cells.

  17. Variation of radiation sensitivity of Friend Erythroleukemia cells cultured in the presence of the differentiation inducer DMSO

    International Nuclear Information System (INIS)

    Einspenner, M.; Boulton, J.E.; Borsa, J.

    1984-01-01

    Differentiation of Friend erythroleukemia cells (FELC) was induced with 1.5% dimethyl sulfoxide (DMSO) in the culture medium. Cell growth, erythroid differentiation, and radiosensitivity of the proliferative capacity of the cells were measured and compared to a noninduced control culture of identical age. Induced cells first appeared on Day 2 after DMSO addition, and increased to a maximum of 80 to 90% of the cell population on Day 5, whereas in the control culture, induction was less than 2% of the cells. Radiosensitivity of the cells in the induced culture relative to that of cells in the control culture, showed an age-dependent variation. On days 1 and 2 after DMSO addition, the cells in the induced culture were less radiosensitive than those in the control culture. At later times, this relationship was reversed, and between days 3 and 5 the clonable cells in the induced culture were less radiosensitive than those in the control culture. These results suggest that the metabolic events associated with commitment of FELC to differentiate affect their ability to cope with the radiation-induced lesions underlying the loss of division capacity

  18. GeoMag and HelMod webmodels version for magnetosphere and heliosphere transport of cosmic rays

    CERN Document Server

    Bobik, P; Consolandi, C; Della Torre, S; Gervasi, M; Grandi, D; Kudela, K; La Vacca, G; Pensotti, S; Putis, M; Rancoita, P G; Rozza, D; Tacconi, M

    2013-01-01

    We implemented a website to deal with main effects on Cosmic Ray access to the Earth, i.e. the Solar Modulation and the Geomagnetic Field effect. In helmod.org the end user can easily access a web interface to results catalog of the HelMod Monte Carlo Code. This Model uses a Monte Carlo Approach to solves the Parker Transport Equation, obtaining a modulated proton flux for a period (monthly average) between January 1990 and december 2007. geomagsphere.org is instead based on GeoMag Backtracing Code, that solves the Lorentz equation with a Runge-Kutta method of 6th order, and, reversing charge sign and velocity, reconstruct particle trajectories in the Earth Magnetosphere back in time. We use last models of internal (IGRF-11) and external (Tsyganenko 1996 -T96- and 2005 -T05-) field components valid up to 2015. Particles are backtraced to the outer (magnetopause) or inner boundary to separate Primary (allowed trajectory) from Secondary (forbidden) Cosmic Rays. This code has been used both for reproducing known...

  19. Changes in Cerebrospinal Fluid Biomarkers in Human Herpesvirus-6-Associated Acute Encephalopathy/Febrile Seizures

    Directory of Open Access Journals (Sweden)

    Naoyuki Tanuma

    2014-01-01

    Full Text Available To determine the involvement of oxidative stress in the pathogenesis of acute encephalopathy associated with human herpesvirus-6 (HHV-6 infection, we measured the levels of oxidative stress markers 8-hydroxy-2′-deoxyguanosine (8-OHdG and hexanoyl-lysine adduct (HEL, tau protein, and cytokines in cerebrospinal fluid (CSF obtained from patients with HHV-6-associated acute encephalopathy (HHV-6 encephalopathy (n=16 and complex febrile seizures associated with HHV-6 (HHV-6 complex FS (n=10. We also examined changes in CSF-8OHdG and CSF-HEL levels in patients with HHV-6 encephalopathy before and after treatment with edaravone, a free radical scavenger. CSF-8-OHdG levels in HHV-6 encephalopathy and HHV-6 complex FS were significantly higher than in control subjects. In contrast, CSF-HEL levels showed no significant difference between groups. The levels of total tau protein in HHV-6 encephalopathy were significantly higher than in control subjects. In six patients with HHV-6 infection (5 encephalopathy and 1 febrile seizure, the CSF-8-OHdG levels of five patients decreased after edaravone treatment. Our results suggest that oxidative DNA damage is involved in acute encephalopathy associated with HHV-6 infection.

  20. Generation and analyses of human synthetic antibody libraries and their application for protein microarrays

    DEFF Research Database (Denmark)

    Säll, Anna; Walle, Maria; Wingren, Christer

    2016-01-01

    in a high-throughput manner. To address this we designed and constructed two human synthetic antibody fragment (scFv) libraries denoted HelL-11 and HelL-13. By the use of phage display technology, in total 466 unique scFv antibodies specific for 114 different antigens were generated. The specificities......Antibody-based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments...... for diagnostics and therapeutics. In addition, this work provides a great example on how a synthetic approach can be used to optimize library designs. By having precise control of the diversity introduced into the antigen-binding sites, synthetic libraries offer increased understanding of how different diversity...

  1. The action of hyperthermia on gene expression in Friend erythroleukemia cells by dimethyl sulfoxide or X-rays

    International Nuclear Information System (INIS)

    Raaphorst, G.P.; Azzam, E.I.; Einspenner, M.; Ewing, D.; Borsa, J.

    1982-02-01

    The effect of heat on gene control and on cell killing by X-rays or dimethyl sulfoxide (DMSO) was studied in cultured Friend erythroleukemia cells (FELC). FELC are very sensitive to heat and X-rays in terms of survival, as measured by the colony-forming assay. Heat inactivation kinetics are similar for FELC and Chinese hamster cells. Thermal enhancement of cell inactivation by irradiation was observed at 42.0 and 45.0deg C, and increased as a function of heating time. The simultaneous application of heat and X-rays had a greater effect in terms of cell inactivation. Dimethyl sulfoxide could induce FELC to synthesize hemoglobin, and hyperthermia could inhibit this response. Likewise, hyperthermia could affect induction of heme synthesis by irradiation. Heating before irradiation enhanced production of heme synthesis, whereas heating after irradiation inhibited induction of heme synthesis. The effects of hyperthermia on the survival and gene induction endpoints were compared. Thus, heat can affect both cell survival and gene induction by irradiation or DMSO. The two endpoints of gene induction and survival (proliferative capacity) responded differently, both quantitatively and qualitatively, to heat and X-rays, implying that different cellular targets are affected for each of these endpoints

  2. Adsorption and transport of charged vs. neutral hydrophobic molecules at the membrane of murine erythroleukemia (MEL) cells.

    Science.gov (United States)

    Zeng, Jia; Eckenrode, Heather M; Dai, Hai-Lung; Wilhelm, Michael J

    2015-03-01

    The adsorption and transport of hydrophobic molecules at the membrane surface of pre- and post-DMSO induced differentiated murine erythroleukemia (MEL) cells were examined by time- and wavelength-resolved second harmonic light scattering. Two medium (MEL cell, neutral BCP does not. It is suggested that an electrostatic interaction between the opposite charges of the cation and the MEL cell surface is the primary driving force for adsorption. Comparisons of adsorption density and free energy, measured at different pH and cell morphology, indicate that the interaction is predominantly through sialic acid carboxyl groups. MG cation adsorption densities have been determined as (0.6±0.3)×10(6) μm(-2) on the surface of undifferentiated MEL cells, and (1.8±0.5)×10(7) μm(-2) on differentiated MEL cells, while the deduced adsorption free energies are effectively identical (ca. -10.9±0.1 and -10.8±0.1 kcal mol(-1), respectively). The measured MG densities indicate that the total number of surface carboxyl groups is largely conserved following differentiation, and therefore the density of carboxylic groups is much larger on the differentiated cell surface than the undifferentiated one. Finally, in contrast to synthetic liposomes and bacterial membranes, surface adsorbed MG cations are unable to traverse the MEL cell membrane. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Human cytomegalovirus renders cells non-permissive for replication of herpes simplex viruses

    International Nuclear Information System (INIS)

    Cockley, K.D.

    1988-01-01

    The herpes simplex virus (HSV) genome during production infection in vitro may be subject to negative regulation which results in modification of the cascade of expression of herpes virus macromolecular synthesis leading to establishment of HSV latency. In the present study, human embryonic lung (HEL) cells infected with human cytomegalovirus (HCMV) restricted the replication of HSV type-1 (HSV-1). A delay in HSV replication of 15 hr as well as a consistent, almost 1000-fold inhibition of HSV replication in HCMV-infected cell cultures harvested 24 to 72 hr after superinfection were observed compared with controls infected with HSV alone. HSV type-2 (HSV-2) replication was similarly inhibited in HCMV-infected HEL cells. Prior ultraviolet-irradiation (UV) of HCMV removed the block to HSV replication, demonstrating the requirement for an active HCMV genome. HCMV deoxyribonucleic acid (DNA) negative temperature-sensitive (ts) mutants inhibited HSV replications as efficiently as wild-type (wt) HCMV at the non-permissive temperature. Evidence for penetration and replication of superinfecting HSV into HCMV-infected cells was provided by blot hybridization of HSV DNA synthesized in HSV-superinfected cell cultures and by cesium chloride density gradient analysis of [ 3 H]-labeled HSV-1-superinfected cells

  4. Efficacy of vorinostat in a murine model of polycythemia vera

    Science.gov (United States)

    Akada, Hajime; Akada, Saeko; Gajra, Ajeet; Bair, Alicia; Graziano, Stephen; Hutchison, Robert E.

    2012-01-01

    The discovery of the JAK2V617F mutation in most patients with Ph-negative myeloproliferative neoplasms has led to the development of JAK2 kinase inhibitors. However, JAK2 inhibitor therapy has shown limited efficacy and dose-limiting hematopoietic toxicities in clinical trials. In the present study, we describe the effects of vorinostat, a small-molecule inhibitor of histone deacetylase, against cells expressing JAK2V617F and in an animal model of polycythemia vera (PV). We found that vorinostat markedly inhibited proliferation and induced apoptosis in cells expressing JAK2V617F. In addition, vorinostat significantly inhibited JAK2V617F-expressing mouse and human PV hematopoietic progenitors. Biochemical analyses revealed significant inhibition of phosphorylation of JAK2, Stat5, Stat3, Akt, and Erk1/2 in vorinostat-treated, JAK2V617F-expressing human erythroleukemia (HEL) cells. Expression of JAK2V617F and several other genes, including GATA1, KLF1, FOG1, SCL, C/EPBα, PU.1, and NF-E2, was significantly down-regulated, whereas the expression of SOCS1 and SOCS3 was up-regulated by vorinostat treatment. More importantly, we observed that vorinostat treatment normalized the peripheral blood counts and markedly reduced splenomegaly in Jak2V617F knock-in mice compared with placebo treatment. Vorinostat treatment also decreased the mutant allele burden in mice. Our results suggest that vorinostat may have therapeutic potential for the treatment of PV and other JAK2V617F-associated myeloproliferative neoplasms. PMID:22408262

  5. The potential role of ribosomal protein S5 on cell cycle arrest and initiation of murine erythroleukemia cell differentiation.

    Science.gov (United States)

    Matragkou, Christina N; Papachristou, Eleni T; Tezias, Sotirios S; Tsiftsoglou, Asterios S; Choli-Papadopoulou, Theodora; Vizirianakis, Ioannis S

    2008-07-01

    Evidence now exists to indicate that some ribosomal proteins besides being structural components of the ribosomal subunits are involved in the regulation of cell differentiation and apoptosis. As we have shown earlier, initiation of erythroid differentiation of murine erythroleukemia (MEL) cells is associated with transcriptional inactivation of genes encoding ribosomal RNAs and ribosomal proteins S5 (RPS5) and L35a. In this study, we extended these observations and investigated whether transfection of MEL cells with RPS5 cDNA affects the onset of initiation of erythroid maturation and their entrance in cell cycle arrest. Stably transfected MEL cloned cells (MEL-C14 and MEL-C56) were established and assessed for their capacity to produce RPS5 RNA transcript and its translated product. The impact of RPS5 cDNA transfection on the RPS5 gene expression patterns and the accumulation of RPS5 protein in inducible transfected MEL cells were correlated with their ability to: (a) initiate differentiation, (b) enter cell cycle arrest at G(1)/G(0) phase, and (c) modulate the level of cyclin-dependent kinases CDK2, CDK4, and CDK6. The data presented indicate that deregulation of RPS5 gene expression (constitutive expression) affects RPS5 protein level and delays both the onset of initiation of erythroid maturation and entrance in cell cycle arrest in inducer-treated MEL cells. 2008 Wiley-Liss, Inc.

  6. Mpl traffics to the cell surface through conventional and unconventional routes.

    Science.gov (United States)

    Cleyrat, Cédric; Darehshouri, Anza; Steinkamp, Mara P; Vilaine, Mathias; Boassa, Daniela; Ellisman, Mark H; Hermouet, Sylvie; Wilson, Bridget S

    2014-09-01

    Myeloproliferative neoplasms (MPNs) are often characterized by JAK2 or calreticulin (CALR) mutations, indicating aberrant trafficking in pathogenesis. This study focuses on Mpl trafficking and Jak2 association using two model systems: human erythroleukemia cells (HEL; JAK2V617F) and K562 myeloid leukemia cells (JAK2WT). Consistent with a putative chaperone role for Jak2, Mpl and Jak2 associate on both intracellular and plasma membranes (shown by proximity ligation assay) and siRNA-mediated knockdown of Jak2 led to Mpl trapping in the endoplasmic reticulum (ER). Even in Jak2 sufficient cells, Mpl accumulates in punctate structures that partially colocalize with ER-tracker, the ER exit site marker (ERES) Sec31a, the autophagy marker LC3 and LAMP1. Mpl was fused to miniSOG, a genetically encoded tag for correlated light and electron microscopy. Results suggest that a fraction of Mpl is taken up into autophagic structures from the ER and routed to autolyososomes. Surface biotinylation shows that both immature and mature Mpl reach the cell surface; in K562 cells Mpl is also released in exosomes. Both forms rapidly internalize upon ligand addition, while recovery is primarily attributed to immature Mpl. Mpl appears to reach the plasma membrane via both conventional ER-Golgi and autolysosome secretory pathways, as well as recycling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Asynchronous DNA replication within the human β-globin gene locus

    International Nuclear Information System (INIS)

    Epner, E.; Forrester, W.C.; Groudine, M.

    1988-01-01

    The timing of DNA replication of the human β-globin gene locus has been studied by blot hybridization of newly synthesized BrdUrd-substituted DNA from cells in different stages of the S phase. Using probes that span >120 kilobases across the human β-globin gene locus, the authors show that the majority of this domain replicates in early S phase in the human erythroleukemia cell line K562 and in middle-to-late S phase in the lymphoid cell line Manca. However, in K562 cells three small regions display a strikingly different replication pattern than adjacent sequences. These islands, located in the inter-γ-globin gene region and approximately 20 kilobases 5' to the ε-globin gene and 20 kilobases 3' to the β-globin gene, replicate later and throughout S phase. A similar area is also present in the α-globin gene region in K562 cells. They suggest that these regions may represent sites of termination of replication forks

  8. Herpes simplex virus types 1 and 2 induce shutoff of host protein synthesis by different mechanisms in Friend erythroleukemia cells

    International Nuclear Information System (INIS)

    Hill, T.M.; Sinden, R.R.; Sadler, J.R.

    1983-01-01

    Herpes simplex virus type 1 (HSV-1) and HSV-2 disrupt host protein synthesis after viral infection. We have treated both viral types with agents which prevent transcription of the viral genome and used these treated viruses to infect induced Friend erythroleukemia cells. By measuring the changes in globin synthesis after infection, we have determined whether expression of the viral genome precedes the shutoff of host protein synthesis or whether the inhibitor molecule enters the cells as part of the virion. HSV-2-induced shutoff of host protein synthesis was insensitive to the effects of shortwave (254-nm) UV light and actinomycin D. Both of the treatments inhibited HSV-1-induced host protein shutoff. Likewise, treatment of HSV-1 with the cross-linking agent 4,5',8-trimethylpsoralen and longwave (360-nm) UV light prevented HSV-1 from inhibiting cellular protein synthesis. Treatment of HSV-2 with 4,5',8-trimethylpsoralen did not affect the ability of the virus to interfere with host protein synthesis, except at the highest doses of longwave UV light. It was determined that the highest longwave UV dosage damaged the HSV-2 virion as well as cross-linking the viral DNA. The results suggest that HSV-2 uses a virion-associated component to inhibit host protein synthesis and that HSV-1 requires the expression of the viral genome to cause cellular protein synthesis shutoff

  9. Effects of intracellular chelatable iron and oxidative stress on transcription of classical cellular glutathione peroxidase gene in murine erythroleukemia cells

    International Nuclear Information System (INIS)

    Fuchs, O.

    1997-01-01

    The effect of intracellular chelatable iron levels and of oxidative stress on nuclear classical cellular glutathione peroxidase (GSHPx-1) RNA nascent chain elongation (run-on transcription) and on the stability of cytoplasmic GSHPx-1 mRNA was investigated in murine erythroleukemia (MEL) cells. The amount in the intracellular low molecular mass iron pool was changed by incubation of MEL cells transformed by Friend virus with iron donors or iron chelators. Transcription in vitro in isolated nuclei from treated cells showed that the treatment with chelators (desferrioxamine (DFO), pyridoxal isonicotinoyl hydrazone) decrease the rate of nuclear GSHPx-1 RNA nascent chain elongation in both un-induced and with 5 mmol hexamethylenebisacetamide to erythroid differentiation induced MEL cells. Iron donors (diferric transferrin,, Fe-PIH or their combination) and t-butyl hydroperoxide (t-BuOOH) had the opposite effect on GSHPx-1 gene transcription in run-on experiments. On the other hand, 50 μmol DFO or 2.5 μmol t-BuOOH did not change the stability of cytoplasmic GSHPx-1 mRNA in both un-induced and induced MEL cells treated with 5 μmol actinomycin D and with or without these agents for 9 h. These findings indicate that iron and oxidative stress play their role at the transcriptional level of GSHPx-1 gene expression. (author)

  10. Arginase induction by sodium phenylbutyrate in mouse tissues and human cell lines.

    Science.gov (United States)

    Kern, R M; Yang, Z; Kim, P S; Grody, W W; Iyer, R K; Cederbaum, S D

    2007-01-01

    Hyperargininemia is a urea cycle disorder caused by mutations in the gene for arginase I (AI) resulting in elevated blood arginine and ammonia levels. Sodium phenylacetate and a precursor, sodium phenylbutyrate (NaPB) have been used to lower ammonia, conjugating glutamine to produce phenylacetylglutamine which is excreted in urine. The elevated arginine levels induce the second arginase (AII) in patient kidney and kidney tissue culture. It has been shown that NaPB increases expression of some target genes and we tested its effect on arginase induction. Eight 9-week old male mice fed on chow containing 7.5 g NaPB/kg rodent chow and drank water with 10 g NaPB/L, and four control mice had a normal diet. After one week all mice were sacrificed. The arginase specific activities for control and NaPB mice, respectively, were 38.2 and 59.4 U/mg in liver, 0.33 and 0.42 U/mg in kidney, and 0.29 and 1.19 U/mg in brain. Immunoprecipitation of arginase in each tissue with AI and AII antibodies showed the activity induced by NaPB is mostly AI. AII may also be induced in kidney. AI accounts for the fourfold increased activity in brain. In some cell lines, NaPB increased arginase activity up to fivefold depending on dose (1-5 mM) and exposure time (2-5 days); control and NaPB activities, respectively, are: erythroleukemia, HEL, 0.06 and 0.31 U/mg, and K562, 0.46 and 1.74 U/mg; embryonic kidney, HEK293, 1.98 and 3.58 U/mg; breast adenocarcinoma, MDA-MB-468, 1.11 and 4.06 U/mg; and prostate adenocarcinoma, PC-3, 0.55 and 3.20 U/mg. In MDA-MB-468 and HEK most, but not all, of the induced activity is AI. These studies suggest that NaPB may induce AI when used to treat urea cycle disorders. It is relatively less useful in AI deficiency, although it could have some effect in those patients with missense mutations.

  11. HelMod in the Works: From Direct Observations to the Local Interstellar Spectrum of Cosmic-Ray Electrons

    Science.gov (United States)

    Boschini, M. J.; Della Torre, S.; Gervasi, M.; Grandi, D.; Jóhannesson, G.; La Vacca, G.; Masi, N.; Moskalenko, I. V.; Pensotti, S.; Porter, T. A.; Quadrani, L.; Rancoita, P. G.; Rozza, D.; Tacconi, M.

    2018-02-01

    The local interstellar spectrum (LIS) of cosmic-ray (CR) electrons for the energy range 1 MeV to 1 TeV is derived using the most recent experimental results combined with the state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. Two propagation packages, GALPROP and HELMOD, are combined to provide a single framework that is run to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. An iterative maximum-likelihood method is developed that uses GALPROP-predicted LIS as input to HELMOD, which provides the modulated spectra for specific time periods of the selected experiments for model-data comparison. The optimized HelMod parameters are then used to adjust GALPROP parameters to predict a refined LIS with the procedure repeated subject to a convergence criterion. The parameter optimization uses an extensive data set of proton spectra from 1997 to 2015. The proposed CR electron LIS accommodates both the low-energy interstellar spectra measured by Voyager 1 as well as the high-energy observations by PAMELA and AMS-02 that are made deep in the heliosphere; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The interstellar and heliospheric propagation parameters derived in this study agree well with our earlier results for CR protons, helium nuclei, and anti-protons propagation and LIS obtained in the same framework.

  12. Molecular analysis of the human β-globin locus activation region

    International Nuclear Information System (INIS)

    Forrester, W.C.; Novak, U.; Gelinas, R.; Groudine, M.

    1989-01-01

    Recently, DNA sequences containing four erythroid-specific DNase I hypersensitive sites within 20 kilobases 5' of the human ε-globin gene have been identified as an important cis-acting regulatory element, the locus activation region (LAR). Subfragments of the LAR, containing either all or only the two 5' or two 3' hypersensitive sites were linked to the human β-globin gene and analyzed for their effect on globin gene expression in stably transformed mouse erythroleukemia (MEL) cells. Constructs containing all four of the hypersensitive sites increase β-gobin mRNA levels 8- to 13-fold, while constructs with only the 5' or 3' sites increase globin expression to a lesser extent. No effect was seen when the constructs were assayed in 3T3 fibroblasts. All of the LAR derivatives form hypersensitive sites at the corresponding sequence position in MEL cells prior to and after induction of MEL cell differentiation. However, in 3T3 fibroblasts only the hypersensitive site corresponding to the previously described erythroid-specific -10.9 site was formed

  13. Human placental Na+, K+-ATPase α subunit: cDNA cloning, tissue expression, DNA polymorphism, and chromosomal localization

    International Nuclear Information System (INIS)

    Chehab, F.F.; Kan, Y.W.; Law, M.L.; Hartz, J.; Kao, F.T.; Blostein, R.

    1987-01-01

    A 2.2-kilobase clone comprising a major portion of the coding sequence of the Na + , K + -ATPase α subunit was cloned from human placenta and its sequence was identical to that encoding the α subunit of human kidney and HeLa cells. Transfer blot analysis of the mRNA products of the Na + , K + -ATPase gene from various human tissues and cell lines revealed only one band (≅ 4.7 kilobases) under low and high stringency washing conditions. The levels of expression in the tissues were intestine > placenta > liver > pancreas, and in the cell lines the levels were human erythroleukemia > butyrate-induced colon > colon > brain > HeLa cells. mRNA was undetectable in reticulocytes, consistent with the authors failure to detect positive clones in a size-selected ( > 2 kilobases) λgt11 reticulocyte cDNA library. DNA analysis revealed by a polymorphic EcoRI band and chromosome localization by flow sorting and in situ hybridization showed that the α subunit is on the short is on the short arm (band p11-p13) of chromosome 1

  14. Generation and analyses of human synthetic antibody libraries and their application for protein microarrays.

    Science.gov (United States)

    Säll, Anna; Walle, Maria; Wingren, Christer; Müller, Susanne; Nyman, Tomas; Vala, Andrea; Ohlin, Mats; Borrebaeck, Carl A K; Persson, Helena

    2016-10-01

    Antibody-based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments in a high-throughput manner. To address this we designed and constructed two human synthetic antibody fragment (scFv) libraries denoted HelL-11 and HelL-13. By the use of phage display technology, in total 466 unique scFv antibodies specific for 114 different antigens were generated. The specificities of these antibodies were analyzed in a variety of immunochemical assays and a subset was further evaluated for functionality in protein microarray applications. This high-throughput approach demonstrates the ability to rapidly generate a wealth of reagents not only for proteome research, but potentially also for diagnostics and therapeutics. In addition, this work provides a great example on how a synthetic approach can be used to optimize library designs. By having precise control of the diversity introduced into the antigen-binding sites, synthetic libraries offer increased understanding of how different diversity contributes to antibody binding reactivity and stability, thereby providing the key to future library optimization. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Expression of human gamma-globin genes in human erythroleukemia (K562) cells.

    Science.gov (United States)

    Donovan-Peluso, M; Acuto, S; Swanson, M; Dobkin, C; Bank, A

    1987-12-15

    K562 cells express embryonic (epsilon) and fetal (gamma) globins and hemoglobins but not adult (beta) globin. To define the cis acting regulatory elements involved in the discrimination between gamma and beta genes, we have constructed chimeric genes composed of portions of gamma and beta and evaluated their expression in stable K562 transfectants. A gamma beta fusion gene containing gamma 5' sequences to the EcoRI site in exon 3 and beta sequences 3' is expressed at 10-40% that of the endogenous gamma level. In 50% of the lines, this fusion gene appropriately increases its expression in response to hemin, an inducer of endogenous globin gene expression in K562 cells. In contrast, a beta gamma fusion gene, containing beta sequences 5' to the EcoRI site in exon 3 and gamma sequences 3', is neither expressed nor correctly initiated. A beta gene containing gamma-intervening sequence (IVS) 2 accumulates an mRNA transcript when analyzed with a 3' beta probe. However, no correctly initiated beta mRNA is observed. A gamma gene with beta-IVS 2 is only inducible in one of six expressing clones. All the results are consistent with the presence of stage-specific trans acting factors in K562 cells that stimulate expression of gamma genes and suggest a significant role for gamma-IVS 2 in gamma gene expression.

  16. Regulated expression of genes inserted at the human chromosomal β-globin locus by homologous recombination

    International Nuclear Information System (INIS)

    Nandi, A.K.; Roginski, R.S.; Gregg, R.G.; Smithies, O.; Skoultchi, A.I.

    1988-01-01

    The authors have examined the effect of the site of integration on the expression of cloned genes introduced into cultured erythroid cells. Smithies et al. reported the targeted integration of DNA into the human β-globin locus on chromosome 11 in a mouse erythroleukemia-human cell hybrid. These hybrid cells can undergo erythroid differentiation leading to greatly increased mouse and human β-globin synthesis. By transfection of these hybrid cells with a plasmid carrying a modified human β-globin gene and a foreign gene composed of the coding sequence of the bacterial neomycin-resistance gene linked to simian virus 40 transcription signals (SVneo), cells were obtained in which the two genes are integrated at the β-globin locus on human chromosome 11 or at random sites. When they examined the response of the integrated genes to cell differentation, they found that the genes inserted at the β-globin locus were induced during differentiation, whereas randomly positioned copies were not induced. Even the foreign SVneo gene was inducible when it had been integrated at the β-globin locus. The results show that genes introduced at the β-globin locus acquire some of the regulatory properties of globin genes during erythroid differentiation

  17. Human placental Na/sup +/, K/sup +/-ATPase. cap alpha. subunit: cDNA cloning, tissue expression, DNA polymorphism, and chromosomal localization

    Energy Technology Data Exchange (ETDEWEB)

    Chehab, F.F.; Kan, Y.W.; Law, M.L.; Hartz, J.; Kao, F.T.; Blostein, R.

    1987-11-01

    A 2.2-kilobase clone comprising a major portion of the coding sequence of the Na/sup +/, K/sup +/-ATPase ..cap alpha.. subunit was cloned from human placenta and its sequence was identical to that encoding the ..cap alpha.. subunit of human kidney and HeLa cells. Transfer blot analysis of the mRNA products of the Na/sup +/, K/sup +/-ATPase gene from various human tissues and cell lines revealed only one band (approx. = 4.7 kilobases) under low and high stringency washing conditions. The levels of expression in the tissues were intestine > placenta > liver > pancreas, and in the cell lines the levels were human erythroleukemia > butyrate-induced colon > colon > brain > HeLa cells. mRNA was undetectable in reticulocytes, consistent with the authors failure to detect positive clones in a size-selected ( > 2 kilobases) lambdagt11 reticulocyte cDNA library. DNA analysis revealed by a polymorphic EcoRI band and chromosome localization by flow sorting and in situ hybridization showed that the ..cap alpha.. subunit is on the short is on the short arm (band p11-p13) of chromosome 1.

  18. Helicopter Maritime Environment Trainer: Operator Manual (Simulateur D’Entrainement Virtuel Maritime: Manuel de L’Operateur)

    Science.gov (United States)

    2011-06-01

    PROCESS OF DEVELOPING THE STRETCH POTENTIAL OF THIS TECHNOLOGY ". WITH THE ASSISTANCE OF PILOTS, THE HDLS WAS RE-CONFIGURED (HelMET, PILOT/INSTRUCTOR...97 4.3.1.9 HelMET IOS FLYCO Control Panel Area ............................... 100 4.3.1.10 HelMET IOS NFC Control Panel...98 Figure 19 . HelMET IOS Window with NFC Control Panel

  19. Human β-globin locus control region: Analysis of the 5' DNase I hypersensitive site HS 2 in transgenic mice

    International Nuclear Information System (INIS)

    Caterina, J.J.; Ryan, T.M.; Pawlik, K.M.; Townes, T.M.; Brinster, R.L.; Behringer, R.R.; Palmiter, R.D.

    1991-01-01

    The human β-globin locus control region (LCR) is essential for high-level expression of human var-epsilon-, γ-, and β-globin genes. Developmentally stable DNase I hypersensitive sites (designated HS) mark sequences within this region that are important for LCR activity. A 1.9-kilobase (kb) fragment containing the 5' HS 2 site enhances human β-globin gene expression 100-fold in transgenic mice and also confers position-independent expression. To further define important sequences within this region, deletion mutations of the 1.9-kb fragment were introduced upstream of the human β-globin gene, and the constructs were tested for activity in transgenic mice. Although enhancer activity was gradually lost with deletion of both 5' and 3' sequences, a 373-base-pair (BP) fragment retained the ability to confer relative position-independent expression. Three prominent DNase I footprints were observed in this region with extracts from the human erythroleukemia cell line K-562, one of which contained duplicated binding sites for transcription factor AP-1 (activator protein 1). When the 1.9-kb fragment containing an 19-bp deletion of the AP-1 binding sites was tested in transgenic mice, enhancer activity decreased 20-fold but position-independent expression was retained

  20. From the valley floor to the peaks: Stratigraphy and landscape evolution of the Alpine Lateglacial in the Kitzbühel Alps (Tyrol, Austria)

    Science.gov (United States)

    Dippenaar, Elijah; Reitner, Jürgen

    2017-04-01

    Our understanding of Alpine landscape evolution and more specifically, chronology of glacier activity during the Alpine Lateglacial (ALG; c. 19 - 11.7 ka) i.e. the timespan between the Würmian Pleniglacial (= Alpine Last Glacial Maximum; AlpLGM) and the beginning of the Holocene, is based on the evidence of only few areas in the Alps. In order to get a better understanding of glaciation and palaeoclimate during this phase, N-S and E-W transects are needed. The Kitzbühel Alps, which are currently not glaciated, span an area of 1700km2 and have peaks that reach c. 2400m a.s.l. They lie at the center of the Eastern Alps on the northern rim, which is more humid than the relatively dry central parts. A modern geological investigation of the ALG record is missing in the Kitzbühel Alps. In order to overcome this gap of knowledge and to gain a more complete understanding of the ALG landscape development, a pioneering study has been performed in the area of Langer Grund Valley, a tributary valley of the Kelchsau Valley. This was done through detailed field mapping, thereby describing the shape and sediment composition of Quaternary morphological features, such as moraines, landslides and rock glacier deposits. Sedimentary evidence of one short glacial advance and two glacial stadials were identified. In chronological order they were named the: Frommbach advance, the Arnbach (glacier) halt and the Küharn halt. Where possible, palaeoglaciers were constructed using ArcGIS. With the palaeoglaciers, equlibrium line altitudes (ELA) were calculated and compared to ELA values of known glacial stadials in an attempt to correlate the relative local stratigraphy to the Lateglacial stratigraphy. Four methods to calculate ELAs were used; Maximum Elevation of Lateral Moraines (MELM), Toe to Headwall Altitude Ratio (THAR), Area x Altitude (AA) and Accumulation Area Ratio (AAR). Furthermore, the glacial sedimentary sequence of the study area was compared to that of the Gschnitz Valley

  1. Identification of pyrogallol as an antiproliferative compound present in extracts from the medicinal plant Emblica officinalis: effects on in vitro cell growth of human tumor cell lines.

    Science.gov (United States)

    Khan, Mahmud Tareq Hassan; Lampronti, Ilaria; Martello, Dino; Bianchi, Nicoletta; Jabbar, Shaila; Choudhuri, Mohammad Shahabuddin Kabir; Datta, Bidduyt Kanti; Gambari, Roberto

    2002-07-01

    In this study we compared the in vitro antiproliferative activity of extracts from medicinal plants toward human tumor cell lines, including human erythromyeloid K562, B-lymphoid Raji, T-lymphoid Jurkat, erythroleukemic HEL cell lines. Extracts from Emblica officinalis were the most active in inhibiting in vitro cell proliferation, after comparison to those from Terminalia arjuna, Aphanamixis polystachya, Oroxylum indicum, Cuscuta reflexa, Aegle marmelos, Saraca asoka, Rumex maritimus, Lagerstroemia speciosa, Red Sandalwood. Emblica officinalis extracts have been studied previously, due to their hepatoprotective, antioxidant, antifungal, antimicrobial and anti-inflammatory medicinal activities. Gas chromatography/mass spectrometry analyses allowed to identify pyrogallol as the common compound present both in unfractionated and n-butanol fraction of Emblica officinalis extracts. Antiproliferative effects of pyrogallol were therefore determined on human tumor cell lines thus identifying pyrogallol as an active component of Emblica officinalis extracts.

  2. Data in support of transcriptional regulation and function of Fas-antisense long noncoding RNA during human erythropoiesis

    Directory of Open Access Journals (Sweden)

    Olga Villamizar

    2016-06-01

    Full Text Available This paper describes data related to a research article titled, “Fas-antisense long noncoding RNA is differentially expressed during maturation of human erythrocytes and confers resistance to Fas-mediated cell death” [1]. Long noncoding RNAs (lncRNAs are increasingly appreciated for their capacity to regulate many steps of gene expression. While recent studies suggest that many lncRNAs are functional, the scope of their actions throughout human biology is largely undefined including human red blood cell development (erythropoiesis. Here we include expression data for 82 lncRNAs during early, intermediate and late stages of human erythropoiesis using a commercial qPCR Array. From these data, we identified lncRNA Fas-antisense 1 (Fas-AS1 or Saf described in the research article. Also included are 5′ untranslated sequences (UTR for lncRNA Saf with transcription factor target sequences identified. Quantitative RT-PCR data demonstrate relative levels of critical erythroid transcription factors, GATA-1 and KLF1, in K562 human erythroleukemia cells and maturing erythroblasts derived from human CD34+ cells. End point and quantitative RT-PCR data for cDNA prepared using random hexamers versus oligo(dT18 revealed that lncRNA Saf is not effectively polyadenylated. Finally, we include flow cytometry histograms demonstrating Fas levels on maturing erythroblasts derived from human CD34+ cells transduced using mock conditions or with lentivirus particles encoding for Saf.

  3. Phosphorylation of ribosomal protein S6 kinase 1 at Thr421/Ser424 and dephosphorylation at Thr389 regulates SP600125-induced polyploidization of megakaryocytic cell lines.

    Science.gov (United States)

    Li, Chang-Ling; Yang, Jin-Gang; Lin, Di; Zhao, Yong-Shan; Liu, Shuo; Xing, Si-Ning; Zhao, Song; Chen, Cong-Qin; Jiang, Zhi-Ming; Pu, Fei-Fei; Cao, Jian-Ping; Ma, Dong-Chu

    2014-01-01

    Megakaryocytes (MKs) are one of the few cell types that become polyploid; however, the mechanisms by which these cells are designated to become polyploid are not fully understood. In this investigation, we successfully established two relatively synchronous polyploid cell models by inducing Dami and CMK cells with SP600125. We found that SP600125 induced the polyploidization of Dami and CMK cells, concomitant with the phosphorylation of ribosomal protein S6 kinase 1 (S6K1) at Thr421/Ser424 and dephosphorylation at Thr389. The polyploidization was partially blocked by H-89, a cAMP-dependent protein kinase (PKA) inhibitor, through direct binding to S6K1, leading to dephosphorylation at Thr421/Ser424 and phosphorylation at Thr389, independent of PKA. Overexpression of a rapamycin-resistant mutant of S6K1 further enhanced the inhibitory effect of LY294002 on the SP600125-induced polyploidization of Dami and CMK cells. SP600125 also induced the polyploidization of Meg-01 cells, which are derived from a patient with chronic myelogenous leukemia, without causing a significant change in S6K1 phosphorylation. Additionally, SP600125 induced the polyploidization of HEL cells, which are derived from a patient with erythroleukemia, and phosphorylation at Thr389 of S6K1 was detected. However, the polyploidization of both Meg-01 cells and HEL cells as a result of SP600125 treatment was lower than that of SP600125-induced Dami and CMK cells, and it was not blocked by H-89 despite the increased phosphorylation of S6K1 at Thr389 in both cell lines in response to H-89. Given that the Dami and CMK cell lines were derived from patients with acute megakaryocytic leukemia (AMKL) and expressed high levels of platelet-specific antigens, our data suggested that SP600125-induced polyploidization is cell-type specific, that these cell lines were more differentiated, and that phosphorylation at Thr421/Ser424 and dephosphorylation at Thr389 of S6K1 may play an important role in the SP600125

  4. Phosphorylation of ribosomal protein S6 kinase 1 at Thr421/Ser424 and dephosphorylation at Thr389 regulates SP600125-induced polyploidization of megakaryocytic cell lines.

    Directory of Open Access Journals (Sweden)

    Chang-Ling Li

    Full Text Available Megakaryocytes (MKs are one of the few cell types that become polyploid; however, the mechanisms by which these cells are designated to become polyploid are not fully understood. In this investigation, we successfully established two relatively synchronous polyploid cell models by inducing Dami and CMK cells with SP600125. We found that SP600125 induced the polyploidization of Dami and CMK cells, concomitant with the phosphorylation of ribosomal protein S6 kinase 1 (S6K1 at Thr421/Ser424 and dephosphorylation at Thr389. The polyploidization was partially blocked by H-89, a cAMP-dependent protein kinase (PKA inhibitor, through direct binding to S6K1, leading to dephosphorylation at Thr421/Ser424 and phosphorylation at Thr389, independent of PKA. Overexpression of a rapamycin-resistant mutant of S6K1 further enhanced the inhibitory effect of LY294002 on the SP600125-induced polyploidization of Dami and CMK cells. SP600125 also induced the polyploidization of Meg-01 cells, which are derived from a patient with chronic myelogenous leukemia, without causing a significant change in S6K1 phosphorylation. Additionally, SP600125 induced the polyploidization of HEL cells, which are derived from a patient with erythroleukemia, and phosphorylation at Thr389 of S6K1 was detected. However, the polyploidization of both Meg-01 cells and HEL cells as a result of SP600125 treatment was lower than that of SP600125-induced Dami and CMK cells, and it was not blocked by H-89 despite the increased phosphorylation of S6K1 at Thr389 in both cell lines in response to H-89. Given that the Dami and CMK cell lines were derived from patients with acute megakaryocytic leukemia (AMKL and expressed high levels of platelet-specific antigens, our data suggested that SP600125-induced polyploidization is cell-type specific, that these cell lines were more differentiated, and that phosphorylation at Thr421/Ser424 and dephosphorylation at Thr389 of S6K1 may play an important role in

  5. Indirect presentation in the thymus limits naive and regulatory T-cell differentiation by promoting deletion of self-reactive thymocytes.

    Science.gov (United States)

    Yap, Jin Yan; Wirasinha, Rushika C; Chan, Anna; Howard, Debbie R; Goodnow, Christopher C; Daley, Stephen R

    2018-02-07

    Acquisition of T-cell central tolerance involves distinct pathways of self-antigen presentation to thymocytes. One pathway termed indirect presentation requires a self-antigen transfer step from thymic epithelial cells (TECs) to bone marrow-derived cells before the self-antigen is presented to thymocytes. The role of indirect presentation in central tolerance is context-dependent, potentially due to variation in self-antigen expression, processing and presentation in the thymus. Here, we report experiments in mice in which TECs expressed a membrane-bound transgenic self-antigen, hen egg lysozyme (HEL), from either the insulin (insHEL) or thyroglobulin (thyroHEL) promoter. Intrathymic HEL expression was less abundant and more confined to the medulla in insHEL mice compared with thyroHEL mice. When indirect presentation was impaired by generating mice lacking MHC class II expression in bone marrow-derived antigen-presenting cells, insHEL-mediated thymocyte deletion was abolished, whereas thyroHEL-mediated deletion occurred at a later stage of thymocyte development and Foxp3 + regulatory T-cell differentiation increased. Indirect presentation increased the strength of T-cell receptor signalling that both self-antigens induced in thymocytes, as assessed by Helios expression. Hence, indirect presentation limits the differentiation of naive and regulatory T cells by promoting deletion of self-reactive thymocytes. © 2018 John Wiley & Sons Ltd.

  6. Major histocompatibility complex-unrestricted cytolytic activity of human T cells: analysis of precursor frequency and effector phenotype

    International Nuclear Information System (INIS)

    Patel, S.S.; Thiele, D.L.; Lipsky, P.E.

    1987-01-01

    The frequency and phenotype of human T cells that mediate major histocompatibility complex (MHC)-unrestricted cytolysis were analyzed. T cell clones were generated by culturing adherent cell-depleted peripheral blood mononuclear cells at a density of 0.3 cell/well with phytohemagglutinin, recombinant interleukin 2 (rIL-2), and irradiated autologous peripheral blood mononuclear cells and/or Epstein-Barr virus-transformed lymphoblastoid cell lines. All of the 198 clones generated by this method were T cells (CD2 + , CD3 + , CD4 + or CD2 + , CD3 + , CD8 + ) that possessed potent lytic activity against K562, an erythroleukemia line sensitive to lysis by human natural killer cells, and Cur, a renal carcinoma cell line resistant to human natural killer activity. Cytolysis, measured by 51 Cr release, was MHC-unrestricted, since the clones were able to lyse MHC class I or class II negative targets, as well as MHC class I and class II negative targets. Although the clones produced tissue necrosis factor/lymphotoxin-like molecules, lysis of Cur of K562 was not mediated by a soluble factor secreted by the clones. These data indicate that the capacity for MHC-unrestricted tumoricidal activity and expression of NKH1 and CD11b, but not CD 16, are properties common to all or nearly all human peripheral blood-derived T cell clones regardless of CD4 or CD8 phenotype

  7. Factors mediating lipofection potency of a series of cationic phosphonolipids in human cell lines.

    Science.gov (United States)

    Koumbi, Daphne; Clement, Jean-Claude; Sideratou, Zili; Yaouanc, Jean-Jacques; Loukopoulos, Dimitris; Kollia, Panagoula

    2006-08-01

    A series of cationic liposomes known as cationic phosphonolipids (CPs) were evaluated as vehicles for in vitro gene transfer in K562 erythroleukemia cells and 5637 epithelial carcinoma cells. For each CP and target cell type examined, detailed analyses were performed to determine optimal transfection conditions (lipid/ DNA (+/-) charge ratio, amount of complexed episomal DNA, liposomal and lipoplex size, complexation medium and duration of complex-cell exposure time). Lipofection conditions were determined to be both cell- and lipid-type specific. Complexation medium critically affected transfection competence. The initial size of the liposome was not always predictive of lipofection potency. The lipid chemical composition had a strong impact upon lipofection efficiency; DOPE inclusion in the liposome formulations was found to affect the levels of transgene expression in a cell-dependent way. Notably, effective transgene expression was characterized by prominent plasmid nuclear incorporation. Human A gamma- and epsilon-globin transgene nuclear incorporation and expression in 5637 cells post GLB.391-mediated lipofection lends credence to its use as a vehicle of therapeutic transgene delivery.

  8. The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Zulema Romero

    Full Text Available Lentiviral vectors designed for the treatment of the hemoglobinopathies require the inclusion of regulatory and strong enhancer elements to achieve sufficient expression of the β-globin transgene. Despite the inclusion of these elements, the efficacy of these vectors may be limited by transgene silencing due to the genomic environment surrounding the integration site. Barrier insulators can be used to give more consistent expression and resist silencing even with lower vector copies. Here, the barrier activity of an insulator element from the human ankyrin-1 gene was analyzed in a lentiviral vector carrying an antisickling human β-globin gene. Inclusion of a single copy of the Ankyrin insulator did not affect viral titer, and improved the consistency of expression from the vector in murine erythroleukemia cells. The presence of the Ankyrin insulator element did not change transgene expression in human hematopoietic cells in short-term erythroid culture or in vivo in primary murine transplants. However, analysis in secondary recipients showed that the lentiviral vector with the Ankyrin element preserved transgene expression, whereas expression from the vector lacking the Ankyrin insulator decreased in secondary recipients. These studies demonstrate that the Ankyrin insulator may improve long-term β-globin expression in hematopoietic stem cells for gene therapy of hemoglobinopathies.

  9. A conserved helicase processivity factor is needed for conjugation and replication of an integrative and conjugative element.

    Directory of Open Access Journals (Sweden)

    Jacob Thomas

    Full Text Available Integrative and conjugative elements (ICEs are agents of horizontal gene transfer and have major roles in evolution and acquisition of new traits, including antibiotic resistances. ICEs are found integrated in a host chromosome and can excise and transfer to recipient bacteria via conjugation. Conjugation involves nicking of the ICE origin of transfer (oriT by the ICE-encoded relaxase and transfer of the nicked single strand of ICE DNA. For ICEBs1 of Bacillus subtilis, nicking of oriT by the ICEBs1 relaxase NicK also initiates rolling circle replication. This autonomous replication of ICEBs1 is critical for stability of the excised element in growing cells. We found a conserved and previously uncharacterized ICE gene that is required for conjugation and replication of ICEBs1. Our results indicate that this gene, helP (formerly ydcP, encodes a helicase processivity factor that enables the host-encoded helicase PcrA to unwind the double-stranded ICEBs1 DNA. HelP was required for both conjugation and replication of ICEBs1, and HelP and NicK were the only ICEBs1 proteins needed for replication from ICEBs1 oriT. Using chromatin immunoprecipitation, we measured association of HelP, NicK, PcrA, and the host-encoded single-strand DNA binding protein Ssb with ICEBs1. We found that NicK was required for association of HelP and PcrA with ICEBs1 DNA. HelP was required for association of PcrA and Ssb with ICEBs1 regions distal, but not proximal, to oriT, indicating that PcrA needs HelP to progress beyond nicked oriT and unwind ICEBs1. In vitro, HelP directly stimulated the helicase activity of the PcrA homologue UvrD. Our findings demonstrate that HelP is a helicase processivity factor needed for efficient unwinding of ICEBs1 for conjugation and replication. Homologues of HelP and PcrA-type helicases are encoded on many known and putative ICEs. We propose that these factors are essential for ICE conjugation, replication, and genetic stability.

  10. Human platelet glycoprotein IX: An adhesive prototype of leucine-rich glycoproteins with flank-center-flank structures

    International Nuclear Information System (INIS)

    Hickey, M.J.; Williams, S.A.; Roth, G.J.

    1989-01-01

    The glycoprotein (GP) Ib-IX complex on the surface of human platelets functions as the von Willebrand factor receptor and mediates von Willebrand factor-dependent platelet adhesion to blood vessels. GPIX is a relatively small (M r , 17,000) protein that may provide for membrane insertion and orientation of the larger component of the complex. GPIb (M r , 165,000). Using antibody screening, the authors cloned a cDNA encoding GPIX from a human erythroleukemia cell cDNA library constructed in phage λgt11. Lacking a 5' untranslated region and start codon, the cDNA sequence includes 604 nucleotides, beginning with 495 bases at the 5' end coding for 165 amino acids, followed by a stop codon and 106 noncoding bases at the 3' end. By Northern blot analysis, the GPIX cDNA hybridizes with a single 1.0-kilobase species of platelet poly(A) + RNA. Translation of the cDNA sequence gives a predicted protein sequence beginning with a truncated putative signal sequence of 5 amino acids followed by a sequence of 17 amino acids matching that determined directly by Edman degradation of intact GPIX. GPIX contains a leucine-rich glycoprotein (LRG) sequence of 24 amino acids similar to conserved LRG sequences in GPIb and other proteins from humans, Drosophila, and yeast. The role of the flank-LRG center-flank structure in the evolution and function of the LRG proteins remains to be defined

  11. Cell Fusion as a Cause of Prostate Cancer Metastasis

    Science.gov (United States)

    2008-01-01

    Microbiol 10, 335-45 (1985). 86. Young, N. S. & Brown, K. E. Parvovirus B19 . N Engl J Med 350, 586-97 (2004). 87. Sitar, G. G. et al. Possible evolution of...human parvovirus B19 infection into erythroleukemia. Haematologica 84, 957-959 (1999). 88. Vihinen-Ranta, M., Suikkanen, S. & Parrish, C. R. Pathways...inactivate the tumorigenic potential of a cancerous cell, thereby making this cell harmless. g | The reactivation hypothesis is suggested by the reports

  12. Global gene expression changes in human embryonic lung fibroblasts induced by organic extracts from respirable air particles

    Directory of Open Access Journals (Sweden)

    Líbalová Helena

    2012-01-01

    Full Text Available Abstract Background Recently, we used cell-free assays to demonstrate the toxic effects of complex mixtures of organic extracts from urban air particles (PM2.5 collected in four localities of the Czech Republic (Ostrava-Bartovice, Ostrava-Poruba, Karvina and Trebon which differed in the extent and sources of air pollution. To obtain further insight into the biological mechanisms of action of the extractable organic matter (EOM from ambient air particles, human embryonic lung fibroblasts (HEL12469 were treated with the same four EOMs to assess changes in the genome-wide expression profiles compared to DMSO treated controls. Method For this purpose, HEL cells were incubated with subtoxic EOM concentrations of 10, 30, and 60 μg EOM/ml for 24 hours and global gene expression changes were analyzed using human whole genome microarrays (Illumina. The expression of selected genes was verified by quantitative real-time PCR. Results Dose-dependent increases in the number of significantly deregulated transcripts as well as dose-response relationships in the levels of individual transcripts were observed. The transcriptomic data did not differ substantially between the localities, suggesting that the air pollution originating mainly from various sources may have similar biological effects. This was further confirmed by the analysis of deregulated pathways and by identification of the most contributing gene modulations. The number of significantly deregulated KEGG pathways, as identified by Goeman's global test, varied, depending on the locality, between 12 to 29. The Metabolism of xenobiotics by cytochrome P450 exhibited the strongest upregulation in all 4 localities and CYP1B1 had a major contribution to the upregulation of this pathway. Other important deregulated pathways in all 4 localities were ABC transporters (involved in the translocation of exogenous and endogenous metabolites across membranes and DNA repair, the Wnt and TGF-β signaling pathways

  13. FAME in mineral oil products, especially HEL; FAME in Mineraloelprodukten insbesondere HEL

    Energy Technology Data Exchange (ETDEWEB)

    Schmiedel, H.P.

    2001-03-01

    Politicians want to support the use of renewable raw materials for heating of buildings as a means to improve the environment, assist farmers and to secure jobs. Because of their similarity with mineral oil products preference is given to the use of fatty acid methyl esters (FAME). The European Commission has mandated the European Commission for Standardization CEN to define a specification for FAME as a heating fuel. If a standard is to be developed, test methods and critical values have to be determined, that allow a good prediction of the field performance of the products under consideration. For this a determination of the relationship between field performance and laboratory test results is required. So far only a limited amount of data for the use of FAME as a heating fuel is available, because in the past fatty acid methyl esters have mostly been marketed as diesel fuel. As some requirements for heating fuels are similar to those of diesel fuel, the experiences obtained with this are useful. This literature survey summarizes the currently available results. It can be seen that so far especially for oxidative and thermal stability no satisfactory test methods exist. FAME preferably should be stored in the dark excluding air. Presence of water can result in hydrolysis and microbes could cause problems. Manufacturers of heating equipment have found malfunction by corrosion. (orig.) [German] Aus umwelt-, landwirtschafts- und arbeitsmarktpolitischen Gruenden soll der Einsatz nachwachsender Rohstoffe zur Gebaeudebeheizung gefoerdert werden. Bevorzugt ist dabei wegen ihrer Aehnlichkeit mit Mineraloelprodukten an den Einsatz von Fettsaeuremethylestern (FAME) gedacht. Die Europaeische Kommission hat das europaeische Komitee fuer Normung CEN beauftragt, eine Norm fuer den Einsatz von FAME als Heizoel zu entwickeln. Fuer die Erstellung einer Norm muessen Testmethoden und Grenzwerte bestimmt werden, die eine gute Voraussage der Nutzungseigenschaften der jeweiligen Produkte gewaehrleisten, was die Ermittlung der Zusammenhaenge zwischen Praxisverhalten und Laborergebnissen voraussetzt. Fuer FAME liegen bisher nur wenige Ergebnisse fuer den Einsatz als Heizoel vor, weil Fettsaeuremethylester in der Vergangenheit ueberwiegend als Dieselkraftstoff eingesetzt worden sind. Da jedoch die Anforderungen an Heizoel in vieler Beziehung denen an Dieselkraftstoff aehneln, koennen auch die Erfahrungen mit diesem herangezogen werden. Die vorliegende Literaturstudie fasst die bisher vorliegenden Ergebnisse zusammen. Es zeigt sich, dass insbesondere auf dem Gebiet der Oxidations- und thermischen Stabilitaet noch keine zufrieden stellenden Testmoeglichkeiten bestehen. Die Lagerung sollte moeglichst unter Luftabschluss und im Dunklen erfolgen. Gegenwart von Wasser kann durch Hydrolyse und mikrobiellen Befall zu Problemen fuehren. Hersteller von Heizungsanlagen haben Betriebsstoerungen durch Korrosion festgestellt. (orig.)

  14. Dicty_cDB: Contig-U03567-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available A... 32 0.001 4 ( EL490927 ) CHUS5969.b1_A06.ab1 CHU(LMS) puzzle sunflower Hel... 56 0.001 1 ( EL489897 ) CH...US5018.b1_C07.ab1 CHU(LMS) puzzle sunflower Hel... 56 0.001 1 ( EL488260 ) CHUS34...85.b1_I07.ab1 CHU(LMS) puzzle sunflower Hel... 56 0.001 1 ( EE654588 ) CHES4477.b1_I16.ab1 CHE(LMS) serpenti

  15. Dicty_cDB: Contig-U04257-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ne ... 48 0.40 1 ( EL483220 ) CHUM5135.b1_N11.ab1 CHU(LMS) puzzle sunflower Hel... 48 0.40 1 ( EL479670 ) CH...UM1646.b1_L03.ab1 CHU(LMS) puzzle sunflower Hel... 48 0.40 1 ( EL474614 ) CHUL2558.b1_K16.ab1 CHU(LMS) puz...zle sunflower Hel... 48 0.40 1 ( EL474613 ) CHUL2557.b1_I16.ab1 CHU(LMS) puzzle sun

  16. Critical Directed Energy Test and Evaluation Infrastructure Shortfalls: Results of the Directed Energy Test and Evaluation Capability Tri-Service Study Update

    Science.gov (United States)

    2009-06-01

    Sensor H11 HPM Chamber Test Capability—Explosive Equivalent Substitute H12 HEL Irradiance & Temperature H13 HEL Near/In-Beam Path Quality H14 HPM Sensor...such things as artillery shells or UAVs and may impact the earth. Possible targets include missiles in flight or a relatively close command, control...capability is a synergy of four high priority shortfalls identified by the T-SS Update. H13 —HEL near/in-beam path quality H13 is the need for a

  17. Stranded Zostera marina L. vs wrack fauna community interactions on a Baltic sandy beach (Hel, Poland: a short-term pilot study. Part I. Driftline effects of fragmented detritivory, leaching and decay rates

    Directory of Open Access Journals (Sweden)

    Marcin F. Jêdrzejczak

    2002-06-01

    Full Text Available The effects of the beach community structure of macro- and meiofauna on the process of beach wrack decay were investigated by means of a simple field colonisation experiment in a temperate, fine quartz sediment, sandy beach at the end of the Hel Peninsula in Poland. 1260 replicate litterbags of three mesh sizes (12 mm, 0.5 mm, 48 µm containing fresh wrack were used to assess the role of faunal and non-faunal components in the breakdown of stranded Zostera marina. Wrack breakdown was determined during a three-year field study. This paper presents the first part of the results of this field experiment, which refer to the effects of fragmentation detritivory, leaching and decay rates. Material was lost from the bags at a rapid rate, with only 22-32% of the original dry mass remaining after 27 days in the field. This degradation was not directly related to the faunal succession of the eelgrass tissue, which proceeded in two distinct phases throughout the study period. Exclusion of macrofauna from the wrack by the use of finer-mesh litterbags (< 1 mm had no appreciable effect on the rate of dry matter loss. Microbial decay, and abiotic leaching and fragmentation are probably the major causes of seagrass weight loss from the litterbags.

  18. Understanding Small-Scale Processes Controlling the Bioavailability of Organic Contaminants to Deposit-Feeding Benthos

    DEFF Research Database (Denmark)

    Forbes, T. L.

    1999-01-01

    Proceedings of the NATO Advanced Research Workshop on Biogeochemical Cycling in Marine Sediments held at Hel, Poland, August 1997.......Proceedings of the NATO Advanced Research Workshop on Biogeochemical Cycling in Marine Sediments held at Hel, Poland, August 1997....

  19. Impact of beacon wavelength on phase-compensation performance

    Science.gov (United States)

    Enterline, Allison A.; Spencer, Mark F.; Burrell, Derek J.; Brennan, Terry J.

    2017-09-01

    This study evaluates the effects of beacon-wavelength mismatch on phase-compensation performance. In general, beacon-wavelength mismatch occurs at the system level because the beacon-illuminator laser (BIL) and high-energy laser (HEL) are often at different wavelengths. Such is the case, for example, when using an aperture sharing element to isolate the beam-control sensor suite from the blinding nature of the HEL. With that said, this study uses the WavePlex Toolbox in MATLAB® to model ideal spherical wave propagation through various atmospheric-turbulence conditions. To quantify phase-compensation performance, we also model a nominal adaptive-optics (AO) system. We achieve correction from a Shack-Hartmann wavefront sensor and continuous-face-sheet deformable mirror using a least-squares phase reconstruction algorithm in the Fried geometry and a leaky integrator control law. To this end, we plot the power in the bucket metric as a function of BIL-HEL wavelength difference. Our initial results show that positive BIL-HEL wavelength differences achieve better phase compensation performance compared to negative BIL-HEL wavelength differences (i.e., red BILs outperform blue BILs). This outcome is consistent with past results.

  20. Environmental Aspects of Domestic Cat Care and Management: Implications for Cat Welfare

    OpenAIRE

    Stella, Judith L.; Croney, Candace C.

    2016-01-01

    Domestic cats (Felis silvestris catus) are the most commonly kept companion animals in the US with large populations of owned (86 million), free-roaming (70 million), research (13,000), and shelter (2-3 million) cats. Vast numbers of cats are maintained in homes and other facilities each year and are reliant on humans for all of their care. Understanding cat behavior and providing the highest quality environments possible, including positive human-cat interactions, based on research could hel...

  1. High Energy Laser Joint Technology Office: a mission overview

    Science.gov (United States)

    Seeley, Don D.; Slater, John M.

    2004-10-01

    The High Energy Laser Joint Technology Office (HEL-JTO) was established in 2000 for the purpose of developing and executing a comprehensive investment strategy for HEL science and technology that would underpin weapons development. The JTO is currently sponsoring 80 programs across industry, academia, and government agencies with a budget of approximately $60 million. The competitively awarded programs are chosen to advance the current state of the art in HEL technology and fill technology gaps, thus providing a broad capability that can be harvested in acquisition programs by the military services.

  2. Complete genome of Phenylobacterium zucineum – a novel facultative intracellular bacterium isolated from human erythroleukemia cell line K562

    Directory of Open Access Journals (Sweden)

    Sun Jie

    2008-08-01

    Full Text Available Abstract Background Phenylobacterium zucineum is a recently identified facultative intracellular species isolated from the human leukemia cell line K562. Unlike the known intracellular pathogens, P. zucineum maintains a stable association with its host cell without affecting the growth and morphology of the latter. Results Here, we report the whole genome sequence of the type strain HLK1T. The genome consists of a circular chromosome (3,996,255 bp and a circular plasmid (382,976 bp. It encodes 3,861 putative proteins, 42 tRNAs, and a 16S-23S-5S rRNA operon. Comparative genomic analysis revealed that it is phylogenetically closest to Caulobacter crescentus, a model species for cell cycle research. Notably, P. zucineum has a gene that is strikingly similar, both structurally and functionally, to the cell cycle master regulator CtrA of C. crescentus, and most of the genes directly regulated by CtrA in the latter have orthologs in the former. Conclusion This work presents the first complete bacterial genome in the genus Phenylobacterium. Comparative genomic analysis indicated that the CtrA regulon is well conserved between C. crescentus and P. zucineum.

  3. Hel igen efter amputation

    DEFF Research Database (Denmark)

    Østergaard, Elisabeth Bomholt

    2007-01-01

    aldersgrupper (Dansk Sygeplejeråd 2006) med amputation som mulig konsekvens. Formål Opnå indsigt i • hvad der kan medvirke til, at mennesker kan føle sig hele igen efter en benamputation, føle sig reintegreret i samfundet og opnå et tilfreds-stillende hverdagsliv • kropsforandringers indflydelse på identiteten...... frigives plads til at kunne rette opmærksomheden andre steder hen; meget tidligt at oplyse om muligheden for og helst opfordre til at få besøg af en person, der selv har oplevet amputation på egen krop; tilrettelægge tilbud til grupper, så der skabes mulighed for at møde andre i ’samme’ situation; tage...

  4. Global gene expression changes in human embryonic lung fibroblasts induced by organic extracts from respirable air particles

    Czech Academy of Sciences Publication Activity Database

    Líbalová, Helena; Uhlířová, Kateřina; Kléma, J.; Machala, M.; Šrám, Radim; Ciganek, M.; Topinka, Jan

    2012-01-01

    Roč. 9, č. 1 (2012), s. 1-16 ISSN 1743-8977 R&D Projects: GA MŠk 2B08005; GA ČR GAP503/11/0142 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : air pollution * complex mixtures * HEL cells Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 9.178, year: 2012

  5. A novel core 1 O-linked glycan-specific binding lectin from the fruiting body of Hericium erinaceus.

    Science.gov (United States)

    Kim, Seonghun

    2018-02-01

    Mucin-type O-glycans are involved in biological functions on the cell surface as well as the glycoproteins and can also be used as specific carbohydrate biomarkers of many diseases. In this study, I purified a novel core 1 O-linked glycan specific lectin, Hericium erinaceus lecin (HeL), from the fruiting body of the mushroom Hericium erinaceus, which is known as the natural source for a sialic acid-binding lectin. Upon optimization of the purification conditions, a sequence of ion exchange, affinity, ion exchange, and size-exclusion chromatography resulted in the highest yield and best quality of lectin without protease activity. The resulting purified HeL is an apparent hexameric protein with a subunit molecular weight of 15kDa, and a pI of 4.3. In hemagglutination inhibition assay, the purified lectin was only inhibited by glycoproteins containing mucin-type O-glycans and reacted weakly with Galβ(1,3)GalNAc. Glycan array analyses showed that HeL specifically interacts with core 1 O-linked glycans as well as extended O-glycan structures containing sialylation or fucosylation. The glycan binding specificity of HeL is comparable to that of peanut agglutinin for detection of a broader range of extended core 1 O-glycan structures. Taken together, these results provide an efficient and optimized procedure for the purification of HeL from the fruiting body of the mushroom Hericium erinaceus. Moreover, HeL represents a powerful tool for analyzing core 1 and extended core 1 O- glycan structures in diagnosis assays. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Failure above and Below the Elastic Limit in AD995

    Science.gov (United States)

    Bourne, N. K.; Millett, J. C. F.; Chen, M. W.; Dandekar, D. P.; McCauley, J. W.

    2007-12-01

    There is an ongoing interest in identifying inexpensive armour materials for use in the protection of personnel and vehicles. The response of AD995 under shock loading is one of the materials most extensively investigated. Over recent years, workers have reported failure occurring in various polycrystalline ceramics behind the shock front. This phenomenon has been investigated using embedded stress sensors and a recovery technique that has allowed observation of the microstructure above and below the Hugoniot Elastic Limit (HEL) and these results are brought together here to explain the observed behaviour. The failure front velocity is found to change with the applied stress, in particular it slows as the HEL is exceeded. The microstructure shows the response below the HEL is dominated by intergranular failure whilst above it, the grains exhibit plasticity (including twinning). The HEL is thus shown to be characteristic of alumina viewed as a composite with randomly oriented alumina grains.

  7. Temperature dependence on shock response of stainless steel

    International Nuclear Information System (INIS)

    Gu Zhuowei; Jin Xiaogang

    1998-01-01

    Free surface velocity measurements were reported for HR-2(Cr-Ni-Mn-N) stainless steel, initially heated to 300K∼1000K and shock-compressed to about 8GPa. The corresponding spall strength σ f and Hugoniot elastic limit σ HEL were determined from the wave profiles. It is demonstrated that σ f and σ HEL decrease linearly with increasing temperature T in the range from 300K to 806K, i.e., σ f =5.63-4.32x10 -3 T and σ HEL =2.08-1.54x10 -3 T, and in the range of 806K∼980K, σ HEL increases from 0.84GPa at 806K to 0.93GPa at 980K, σ f has a negligible increase to 2.15GPa from 2.14GPa. Primary TEM test on recovery samples identified the existence of intermatallic compound Ni 3 Ti in the sample of 980K

  8. Prostaglandins with antiproliferative activity induce the synthesis of a heat shock protein in human cells

    International Nuclear Information System (INIS)

    Santoro, M.G.; Garaci, E.; Amici, C.

    1989-01-01

    Prostaglandins (PGs)A 1 and J 2 were found to potently suppress the proliferation of human K562 erythroleukemia cells and to induce the synthesis of a 74-kDa protein (p74) that was identified as a heat shock protein related to the major 70-kDa heat shock protein group. p74 synthesis was stimulated at doses of PGA 1 and PGJ 2 that inhibited cell replication, and its accumulation ceased upon removal of the PG-induced proliferation block. PGs that did not affect K562 cell replication did not induce p74 synthesis. p74 was found to be localized mainly in the cytoplasm of PG-treated cells, but moderate amounts were found also in dense areas of the nucleus after PGJ 2 treatment. p74 was not necessarily associated with cytotoxicity or with inhibition of cell protein synthesis. The results described support the hypothesis that synthesis of the 70-kDa heat shock proteins is associated with changes in cell proliferation. The observation that PGs can induce the synthesis of heat shock proteins expands our understanding of the mechanism of action of these compounds whose regulatory role is well known in many physiological phenomena, including the control of fever production

  9. Evaluation of effects of various drugs on platelet functions using phorbol 12-myristate 13-acetate-induced megakaryocytic human erythroid leukemia cells

    Directory of Open Access Journals (Sweden)

    Tada T

    2016-09-01

    Full Text Available Tomoki Tada,1 Kensaku Aki,2 Wataru Oboshi,1,3 Kazuyoshi Kawazoe,4 Toshiyuki Yasui,5 Eiji Hosoi2 1Subdivision of Biomedical Laboratory Sciences, Graduate School of Health Sciences, Tokushima University, 2Department of Cells and Immunity Analytics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 3Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Kagawa, 4Department of Clinical Pharmacy Practice Pedagogy, Institute of Biomedical Sciences, 5Department of Reproductive and Menopausal Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan Background: The hyperfunction and activation of platelets have been strongly implicated in the development and recurrence of arterial occlusive disease, and various antiplatelet drugs are used to treat and prevent such diseases. New antiplatelet drugs and many other drugs have been developed, but some drugs may have adverse effects on platelet functions. Objective: The aim of this study was to establish an evaluation method for evaluating the effect and adverse effect of various drugs on platelet functions. Materials and methods: Human erythroid leukemia (HEL cells were used after megakaryocytic differentiation with phorbol 12-myristate 13-acetate as an alternative to platelets. Drugs were evaluated by changes in intracellular Ca2+ concentration ([Ca2+]i mobilization in Fura2-loaded phorbol 12-myristate 13-acetate-induced HEL cells. Aspirin and cilostazol were selected as antiplatelet drugs and ibuprofen and sodium valproate as other drugs. Results: There was a positive correlation between [Ca2+]i and platelet aggregation induced by thrombin. Aspirin (5.6–560 µM and cilostazol (5–10 µM significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. On the other hand, ibuprofen (8–200 µM and sodium valproate (50–1,000 µg/mL also significantly inhibited

  10. Dicty_cDB: Contig-U09821-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available .. 46 1e-10 16 ( EL488883 ) CHUS4088.b1_O14.ab1 CHU(LMS) puzzle sunflower Hel... ...70 2e-07 1 ( EL488719 ) CHUS3939.b1_F01.ab1 CHU(LMS) puzzle sunflower Hel... 70 2e-07 1 ( AJ437721 ) Heliant

  11. Dicty_cDB: Contig-U12055-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 941236 ) CHPX9058.b1_C10.ab1 CHP(XYZ) plains sunflower Hel... 34 9.3 2 ( EL485942 ) CHUM7676.b1_H24.ab1 CHU(LMS) puzzle... sunflower Hel... 34 9.4 2 ( EL481883 ) CHUM3888.b1_O11.ab1 CHU(LMS) puzzle

  12. Summary Report: NMSBA CY 2016 - AEgis Technologies Group Inc. #12458.

    Energy Technology Data Exchange (ETDEWEB)

    Bellum, John Curtis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Field, Ella Suzanne [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-12-01

    AEgis requires large area partial mirror optics consisting of partially reflecting optical coatings on large dimension substrates for high energy laser (HEL) applications. The partial mirrors should transmit nearly the same small fraction of HEL radiation incident from a wide range of angles of incidence (AOIs), and the laser-induced damage threshold (LIDT) of the coatings should be high enough for them to be able to withstand direct exposure to near infrared CW HEL radiation at multi-kilowatt/cm2 power levels. The transmitted fraction of incident HEL radiation should reach an array of detectors at power levels high enough for reliable detection but low enough to not damage the detectors. The reflected fraction of incident HEL radiation should scatter into a divergent pattern so as to be eye safe at a distance of ~ 200 m from the mirror in the case of 100 kilowatt incident laser power. The detector array together with the partial mirror optic and possible additional optics that provide divergent scattering of reflected HEL radiation constitute what AEgis refers to as a target board. The target board use environment may vary from benign, indoor laboratory conditions to harsh, outdoor conditions in tests on the ground as well as in air. Under this NMSBA project, Sandia agreed to apply its extensive expertise and capability in the design and production of high LIDT coatings on large dimension optics for high power pulsed laser radiation to advise and assist AEgis in the design and development of high LIDT coatings for the partial mirror optic. Sandia and AEgis met several times to discuss the partial mirror and target board requirements, and Sandia was guided in its work by these discussions as well as by the partial mirror and target board requirement summaries of Tables 1 and 2, respectively, that were provided by AEgis.

  13. Association of manganese superoxide dismutase Ala16Val polymorphism in the incidence of acute myocardial infarction in the Egyptians

    Directory of Open Access Journals (Sweden)

    Lobna M. Abdelrauf

    2017-12-01

    Full Text Available Background: Oxidative stress has been implicated in various diseases including atherosclerosis; the most common pathologic process underlying acute myocardial infarction (AMI. The manganese superoxide dismutase (MnSOD antioxidant enzyme affords the major defense against reactive oxygen species (ROS within the mitochondria. MnSOD Alanine16Valine (A16V single nucleotide polymorphism (SNP has been shown to decrease MnSOD detoxification activity. Aim: A case-control study was conducted to investigate the association between MnSOD A16V polymorphism and the incidence of AMI in the Egyptians, investigate the contribution of oxidative stress represented by hexanoyl lysine adduct (HEL, an oxidative stress biomarker, in the pathogenesis of AMI and finally correlate the MnSOD genotypes with HEL serum levels. Methods: A total of 200 Egyptian subjects were recruited for the study; 100 AMI patients and 100 control subjects. Genotypes of the MnSOD A16V polymorphism were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. Serum HEL was measured by ELISA. Results: A significant difference in the distribution of the MnSOD A16V genotypes was observed; VV genotype was significantly higher in AMI than controls (p ≤ 0.0001. Also, studying the allele frequencies revealed that Val allele was significantly higher in AMI than controls (p ≤ 0.0001. Serum analysis showed higher levels of HEL in AMI patients (p = 0.0142. Furthermore, HEL levels were found to be significantly higher in VV genotype in AMI (p = 0.0273. Conclusions: Our study suggests that MnSOD A16V polymorphism is associated with increased risk of developing AMI in the Egyptians. Moreover, the VV genotype is associated with higher HEL levels.

  14. Dicty_cDB: Contig-U07986-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 4932.b2_H10.ab1 CHU(LMS) puzzle sunflower Hel... 58 5e-04 1 ( EL474789 ) CHUL2734.b1_K11.ab1 CHU(LMS) puzz...le sunflower Hel... 58 5e-04 1 ( EL360649 ) CCEM5342.b1_L16.ab1 CCE(LMS) endive Cic

  15. Dicty_cDB: Contig-U14161-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available us clone CH230-90F19, *** SEQUENCI... 46 0.001 2 ( EL489562 ) CHUS4712.b2_P01.ab1 CHU(LMS) puzzle sunflower ...Hel... 56 0.001 1 ( EL484146 ) CHUM5998.b1_K12.ab1 CHU(LMS) puzzle sunflower Hel... 56 0.001 1 ( AC116979 )

  16. NF-Y recruits both transcription activator and repressor to modulate tissue- and developmental stage-specific expression of human γ-globin gene.

    Directory of Open Access Journals (Sweden)

    Xingguo Zhu

    Full Text Available The human embryonic, fetal and adult β-like globin genes provide a paradigm for tissue- and developmental stage-specific gene regulation. The fetal γ-globin gene is expressed in fetal erythroid cells but is repressed in adult erythroid cells. The molecular mechanism underlying this transcriptional switch during erythroid development is not completely understood. Here, we used a combination of in vitro and in vivo assays to dissect the molecular assemblies of the active and the repressed proximal γ-globin promoter complexes in K562 human erythroleukemia cell line and primary human fetal and adult erythroid cells. We found that the proximal γ-globin promoter complex is assembled by a developmentally regulated, general transcription activator NF-Y bound strongly at the tandem CCAAT motifs near the TATA box. NF-Y recruits to neighboring DNA motifs the developmentally regulated, erythroid transcription activator GATA-2 and general repressor BCL11A, which in turn recruit erythroid repressor GATA-1 and general repressor COUP-TFII to form respectively the NF-Y/GATA-2 transcription activator hub and the BCL11A/COUP-TFII/GATA-1 transcription repressor hub. Both the activator and the repressor hubs are present in both the active and the repressed γ-globin promoter complexes in fetal and adult erythroid cells. Through changes in their levels and respective interactions with the co-activators and co-repressors during erythroid development, the activator and the repressor hubs modulate erythroid- and developmental stage-specific transcription of γ-globin gene.

  17. FY1995 development of a novel rapid immunoassay technology; 1995 nendo shinkina kosoku men'eki sokutei gijutsu no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    By utilizing the phenomenon that the antigen induces association of VH and VL, which are the antigen-recognizing fragments of antibody, develop a novel rapid immunoassay technology which will eliminate the defects of conventional immunoassays, such as long measuring time and requirement of expensive large automated apparatus. In addition, develop a methodology to make Fvs with low VH-VL affinity but that associate tightly in the presence of antigen. Using a model anti-hen egg lysozyme antibody HyHEL-10 Fv and BlAcore, we have clarified the kinetic basis of the Fv stabilization by HEL. By labeling HyHEL-10 VH, VL with succinimide esters of fluorescein and tetramethylrhodamin, respectively, at their N-termini, we could successfully detect VH-VL association by the increment of fluorescence resonance energy transfer. As a result, 1 {mu} g/ml of antigen could be detected homogeneously in less than 5 minutes. Some VH-VL association measurement systems were made by utilizing M13 phage display of VH fragments of HyHEL-10, anti-nitrophenacetyl, anti-digoxin antibodies. (NEDO)

  18. Antibody-independent control of gamma-herpesvirus latency via B cell induction of anti-viral T cell responses.

    Directory of Open Access Journals (Sweden)

    Kelly B McClellan

    2006-06-01

    Full Text Available B cells can use antibody-dependent mechanisms to control latent viral infections. It is unknown whether this represents the sole function of B cells during chronic viral infection. We report here that hen egg lysozyme (HEL-specific B cells can contribute to the control of murine gamma-herpesvirus 68 (gammaHV68 latency without producing anti-viral antibody. HEL-specific B cells normalized defects in T cell numbers and proliferation observed in B cell-/- mice during the early phase of gammaHV68 latency. HEL-specific B cells also reversed defects in CD8 and CD4 T cell cytokine production observed in B cell-/- mice, generating CD8 and CD4 T cells necessary for control of latency. Furthermore, HEL-specific B cells were able to present virally encoded antigen to CD8 T cells. Therefore, B cells have antibody independent functions, including antigen presentation, that are important for control of gamma-herpesvirus latency. Exploitation of this property of B cells may allow enhanced vaccine responses to chronic virus infection.

  19. A demonstration of remote survey and characterization of a buried waste site using the SRIP [Soldier Robot Interface Project] testbed

    International Nuclear Information System (INIS)

    Burks, B.L.; Richardson, B.S.; Armstrong, G.A.; Hamel, W.R.; Jansen, J.F.; Killough, S.M.; Thompson, D.H.; Emery, M.S.

    1990-01-01

    During FY 1990, the Oak Ridge National Laboratory (ORNL) supported the Department of Energy (DOE) Environmental Restoration and Waste Management (ER ampersand WM) Office of Technology Development through several projects including the development of a semiautonomous survey of a buried waste site using a remotely operated all-terrain robotic testbed borrowed from the US Army. The testbed was developed for the US Army's Human Engineering Laboratory (HEL) for the US Army's Soldier Robot Interface Project (SRIP). Initial development of the SRIP testbed was performed by a team including ORNL, HEL, Tooele Army Depot, and Odetics, Inc., as an experimental testbed for a variety of human factors issues related to military applications of robotics. The SRIP testbed was made available to the DOE and ORNL for the further development required for a remote landfill survey. The robot was modified extensively, equipped with environmental sensors, and used to demonstrate an automated remote survey of Solid Waste Storage Area No. 3 (SWSA 3) at ORNL on Tuesday, September 18, 1990. Burial trenches in this area containing contaminated materials were covered with soil nearly twenty years ago. This paper describes the SRIP testbed and work performed in FY 1990 to demonstrate a semiautonomous landfill survey at ORNL. 5 refs

  20. Thermomechanical Assessment of the Collector for the Hollow Electron Lens

    CERN Document Server

    Anderson, George Bowers

    2017-01-01

    The hollow electron lens (HEL) is a system proposed for the High Luminosity upgrade of the Large Hadron Collider LHC (HL-LHC) [1]. Being considered for installation at LHC point 4, the HEL improves halo control and collimation of proton beams in the collider [2]. This is achieved by creating a hollow tube of electrons using an electron gun. This axisymmetric electron cloud travels around the proton beam for a few meters, overlapping with the proton beam halo, until the electron cloud is dissipated in a collector, which is the focus of this project. A 3D image of the HEL system is found in Figure 1 and a further technical description of such electron lenses is available in [3].

  1. Globale paradys of plaaslike hel?

    African Journals Online (AJOL)

    Tienie

    Duiwelskloof (André Brink), Lituma en los Andes ... “Hallowed Ground” – Violent Femmes. 1. ..... bewus van ander magte wat in die area aktief is, in die besonder .... “revolting sex, deceit and the sly torture of children” (8), asook “defile-.

  2. Rapport fra hovedudvalget

    DEFF Research Database (Denmark)

    Danmarks Miljøundersøgelser (bidragyder): Bichel-udvalget

    Bicheludvalget, Udvalget til vurdering af de samlede konsekvenser af en hel eller delvis afvikling af pesticidanvendelsen. Rapporten er Bicheludvalgets endelige rapport til Miljø- og Energiministeren og bygger på 5 faglige baggrundsrapporter.......Bicheludvalget, Udvalget til vurdering af de samlede konsekvenser af en hel eller delvis afvikling af pesticidanvendelsen. Rapporten er Bicheludvalgets endelige rapport til Miljø- og Energiministeren og bygger på 5 faglige baggrundsrapporter....

  3. Novel E3 ubiquitin ligases that regulate histone protein levels in the budding yeast Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar Singh

    Full Text Available Core histone proteins are essential for packaging the genomic DNA into chromatin in all eukaryotes. Since multiple genes encode these histone proteins, there is potential for generating more histones than what is required for chromatin assembly. The positively charged histones have a very high affinity for negatively charged molecules such as DNA, and any excess of histone proteins results in deleterious effects on genomic stability and cell viability. Hence, histone levels are known to be tightly regulated via transcriptional, posttranscriptional and posttranslational mechanisms. We have previously elucidated the posttranslational regulation of histone protein levels by the ubiquitin-proteasome pathway involving the E2 ubiquitin conjugating enzymes Ubc4/5 and the HECT (Homologous to E6-AP C-Terminus domain containing E3 ligase Tom1 in the budding yeast. Here we report the identification of four additional E3 ligases containing the RING (Really Interesting New Gene finger domains that are involved in the ubiquitylation and subsequent degradation of excess histones in yeast. These E3 ligases are Pep5, Snt2 as well as two previously uncharacterized Open Reading Frames (ORFs YKR017C and YDR266C that we have named Hel1 and Hel2 (for Histone E3 Ligases respectively. Mutants lacking these E3 ligases are sensitive to histone overexpression as they fail to degrade excess histones and accumulate high levels of endogenous histones on histone chaperones. Co-immunoprecipitation assays showed that these E3 ligases interact with the major E2 enzyme Ubc4 that is involved in the degradation related ubiquitylation of histones. Using mutagenesis we further demonstrate that the RING domains of Hel1, Hel2 and Snt2 are required for histone regulation. Lastly, mutants corresponding to Hel1, Hel2 and Pep5 are sensitive to replication inhibitors. Overall, our results highlight the importance of posttranslational histone regulatory mechanisms that employ multiple E3

  4. Distance Support In-Service Engineering for the High Energy Laser

    Science.gov (United States)

    2015-03-01

    FEL only) o Isoplanatic angle (if available) o Fried coherence length o Object distance o Dwell time o Laser spot size While many of the items...system and the HEL system. Acquisition Sensor Laser Subsystem Beam Shaping Sensor Suile . Range Finder -. Coarse Tracker . Fine Tracker Optical...distribution is unlimited DISTANCE SUPPORT IN-SERVICE ENGINEERING FOR THE HIGH ENERGY LASER by Team Raising HEL from a Distance Cohort 311-133O March

  5. A new alternative transcript encodes a 60 kDa truncated form of integrin beta 3.

    Science.gov (United States)

    Djaffar, I; Chen, Y P; Creminon, C; Maclouf, J; Cieutat, A M; Gayet, O; Rosa, J P

    1994-05-15

    A cDNA for integrin beta 3 isolated from a human erythroleukaemia (HEL) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta 3c, results from the use of a cryptic AG donor splice site in intron 8 of the beta 3 gene, and is different from a previously described alternative beta 3 mRNA. The predicted open reading frame of beta 3C stops at a TAG stop codon 69 bp downstream from position 1281. It starts with the signal peptide and the 404 N-terminal extracellular residues of beta 3, encompassing the ligand binding sites, followed by 23 C-terminal intron-derived residues, corresponding to a truncated form of beta 3 lacking the cysteine-rich, transmembrane and cytoplasmic domains. Expression of beta 3C mRNA was demonstrated in human platelets, megakaryocytes, endothelial cells and HEL cells by reverse transcriptase/PCR. The beta 3C transcript was also demonstrated in the mouse, suggesting its conservation through evolution. Finally, a 60 kDa polypeptide corresponding to the beta 3C alternative transcript was demonstrated in platelets by Western blotting using a polyclonal antibody raised against a synthetic peptide designed from the beta 3C intronic sequence. Taken together, these results suggest a biological role for beta 3C, the first alternative transcript showing an altered extracellular domain of a beta integrin.

  6. Chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch

    International Nuclear Information System (INIS)

    Melis, M.; Demopulos, G.; Najfeld, V.; Zhang, J.W.; Brice, M.; Papayannopoulou, T.; Stamatoyannopoulos, G.

    1987-01-01

    Hybrids formed by fusing mouse erythroleukemia (MEL) cells with human fetal erythroid cells produce human fetal globin, but they switch to adult globin production as culture time advances. To obtain information on the chromosomal assignment of the elements that control γ-to-β switching, the authors analyzed the chromosomal composition of hybrids producing exclusively or predominantly human fetal globin and hybrids producing only adult human globin. No human chromosome was consistently present in hybrids expressing fetal globin and consistently absent in hybrids expressing adult globin. Subcloning experiments demonstrated identical chromosomal compositions in subclones displaying the fetal globin program and those that had switched to expression of the adult globin program. These data indicate that retention of only one human chromosome -- i.e., chromosome 11 -- is sufficient for expression of human fetal globin and the subsequent γ-to-β switch. The results suggest that the γ-to-β switch is controlled either cis to the β-globin locus of by a trans-acting mechanism, the genes of which reside on human chromosome 11

  7. Statistical analysis of Japanese Thorotrast-administered autopsy cases--1980

    Energy Technology Data Exchange (ETDEWEB)

    Mori, T. (National Inst. of Radiological Sciences, Anagawa, Japan); Kato, Y.; Aoki, N.; Hatakeyama, S.

    1983-01-01

    In 193 cases autopsied between 1945 and 1980, all persons who had been intravascularly injected with Thorotrast in life, the authors found 131 malignant hepatic tumors, 20 liver cirrhoses, 6 myeloid leukemias, 4 erythroleukemias, 5 aplastic anemias, 4 lung cancers, 1 mesothelioma and 1 osteosarcoma. The causes of death in the Thorotrast-administered autopsy group (193 cases) were compared with those of a non-Thorotrast-administered autopsy group (95,000 cases) of the same sex and age at death as recorded in the Annals of Japanese Pathological Autopsy cases from 1958 to 1978. This comparison revealed that the frequencies of malignant hepatic tumors, liver cirrhosis, erythroleukemia, and aplastic anemia were significantly higher in the Thorotrast-administered group than in the non-Thorotrast-administered group.

  8. High-performance polymeric photovoltaic cells with a gold chloride-treated polyacrylonitrile hole extraction interlayer

    Science.gov (United States)

    Jeong, Ji-Ho; Noh, Yong-Jin; Kim, Seok-Soon; Kwon, Sung-Nam; Na, Seok-In

    2018-03-01

    We introduce a high efficiency polymeric photovoltaic cell (PPV) to be obtained by polyacrylonitrile (PAN) hole extraction layer (HEL) modification with gold chloride (AuCl3). The role of PAN HELs with AuCl3 and their effects on solar cell performances were studied with ultraviolet photoemission spectroscopy, atomic force microscopy, internal resistances in PPVs, and current-voltage power curves. The resultant PPVs with AuCl3-treated PAN HELs showed improved cell efficiency compared to PSCs with no interlayer and PAN without AuCl3. Furthermore, with AuCl3-treated PAN, we finally achieved a high efficiency of 6.91%, and a desirable PPV-stability in poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b‧]dithiophe-ne-2,6-diyl][3-fluoro-2-[(2-thylhexyl)carbonyl]-thieno[3,4-b]thiophenediyl

  9. Refractive index of r-cut sapphire under shock pressure range 5 to 65 GPa

    International Nuclear Information System (INIS)

    Cao, Xiuxia; Li, Jiabo; Li, Jun; Li, Xuhai; Xu, Liang; Wang, Yuan; Zhu, Wenjun; Meng, Chuanmin; Zhou, Xianming

    2014-01-01

    High-pressure refractive index of optical window materials not only can provide information on electronic polarizability and band-gap structure, but also is important for velocity correction in particle-velocity measurement with laser interferometers. In this work, the refractive index of r-cut sapphire window at 1550 nm wavelength was measured under shock pressures of 5–65 GPa. The refractive index (n) decreases linearly with increasing shock density (ρ) for shock stress above the Hugoniot elastic limit (HEL): n = 2.0485 (± 0.0197) − 0.0729 (± 0.0043)ρ, while n remains nearly a constant for elastic shocks. This behavior is attributed to the transition from elastic (below HEL) to heterogeneous plastic deformation (above HEL). Based on the obtained refractive index-density relationship, polarizability of the shocked sapphire was also obtained

  10. Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models.

    Science.gov (United States)

    Portwood, Scott; Lal, Deepika; Hsu, Yung-Chun; Vargas, Rodrigo; Johnson, Megan K; Wetzler, Meir; Hart, Charles P; Wang, Eunice S

    2013-12-01

    Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm. Recent evidence has shown the bone marrow microenvironment in patients with AML to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth. We assessed the effects of hypoxia and TH-302 on human AML cells, primary samples, and systemic xenograft models. We observed that human AML cells and primary AML colonies cultured under chronic hypoxia (1% O2, 72 hours) exhibited reduced sensitivity to cytarabine-induced apoptosis as compared with normoxic controls. TH-302 treatment resulted in dose- and hypoxia-dependent apoptosis and cell death in diverse AML cells. TH-302 preferentially decreased proliferation, reduced HIF-1α expression, induced cell-cycle arrest, and enhanced double-stranded DNA breaks in hypoxic AML cells. Hypoxia-induced reactive oxygen species by AML cells were also diminished. In systemic human AML xenografts (HEL, HL60), TH-302 [50 mg/kg intraperitoneally (i.p.) 5 times per week] inhibited disease progression and prolonged overall survival. TH-302 treatment reduced the number of hypoxic cells within leukemic bone marrows and was not associated with hematologic toxicities in nonleukemic or leukemic mice. Later initiation of TH-302 treatment in advanced AML disease was as effective as earlier TH-302 treatment in xenograft models. Our results establish the preclinical activity of TH-302 in AML and provide the rationale for further clinical studies of this and other hypoxia-activated agents for leukemia therapy. ©2013 AACR.

  11. Descomposición de helófitos en un humedal semiárido hipertrófico

    Directory of Open Access Journals (Sweden)

    Ribeiro Orge, Maria Dolores

    2004-06-01

    (descomposición a 7 meses y no perforadas (descomposición a 14 meses con objeto de evaluar la descomposición total debida a invertebrados, microorganismos y procesos estrictamente químicos, y la debida sólo a la quimio-microbiología. A pesar del carácter hipertrófico del humedal, que debía favorecer la descomposición de las plantas, observamos un proceso en que la descomposición fue lenta en ambas especies, lo cual dio como resultado que un año y medio más tarde todavía quedara sin descomponer más de la mitad de su biomasa seca. No hubo diferencias estadísticamente significativas en las tasas diarias de descomposición de materia total entre especies o experimentos, siendo dichas tasas bajas: 0,0022 ± 0,001 día–1 y 0,0029 ± 0,002 día–1 en la descomposición total de Cladium y Phragmites, y 0,0019 ± 0,001 día–1 y 0,0016 ± 0,001 día–1 en su descomposición químico-microbiológica, lo cual indica que la intervención de los invertebrados en el proceso de descomposición, globalmente considerada, fue despreciable. Para ambos helófitos hubo una fase inicial de lavado en la que ocurrieron las tasas más elevadas (P Phragmites australis liberó más fósforo inorgánico (P C. mariscos, pero la liberación de nitrógeno inorgánico al medio fue similar en ambas especies. Las tasas de liberación de nutrientes fueron unas diez veces superiores a las de pérdida de biomasa vegetal en los dos macrófitos. No se encontró correlación significativa alguna entre las tasas de descomposición y las variables ambientales. Nuestros resultados indican una lenta descomposición de la hojarasca en la zona del estudio, lo que sin duda contribuye a la eutrofización del agua y a que exista una sedimentación orgánica muy elevada en el humedal.

  12. KOULUIKÄISEN LAPSEN PELON HELPOTTAMINEN LEI-KIN KEINOIN SAIRAALASSA : Kuvaileva kirjallisuuskatsaus

    OpenAIRE

    Hietanen, Sara

    2017-01-01

    Hietanen, Sara. Kuvaileva kirjallisuuskatsaus kouluikäisen lapsen pelon helpottamisesta leikin keinoin sairaalassa. Kirjallisuuskatsaus. 27 sivua, 2 liitettä. Hel-sinki, kevät 2017. Diakonia-ammattikorkeakoulu, Hoitotyön koulutusohjelma, sai-raanhoitaja (AMK). Opinnäytetyön tarkoituksena oli kuvata leikin keinoja, joiden avulla voidaan hel-pottaa lasten pelkoja ja ahdistusta sairaalassa. Tavoitteena oli kartoittaa muualla maailmalla käytettäviä leikkiin liittyviä työmuotoja ja -menetelmiä...

  13. Comparison of cDNA-derived protein sequences of the human fibronectin and vitronectin receptor α-subunits and platelet glycoprotein IIb

    International Nuclear Information System (INIS)

    Fitzgerald, L.A.; Poncz, M.; Steiner, B.; Rall, S.C. Jr.; Bennett, J.S.; Phillips, D.R.

    1987-01-01

    The fibronectin receptor (FnR), the vitronectin receptor (VnR), and the platelet membrane glycoprotein (GP) IIb-IIIa complex are members of a family of cell adhesion receptors, which consist of noncovalently associated α- and β-subunits. The present study was designed to compare the cDNA-derived protein sequences of the α-subunits of human FnR, VnR, and platelet GP IIb. cDNA clones for the α-subunit of the FnR (FnR/sub α/) were obtained from a human umbilical vein endothelial (HUVE) cell library by using an oligonucleotide probe designed from a peptide sequence of platelet GP IIb. cDNA clones for platelet GP IIb were isolated from a cDNA expression library of human erythroleukemia cells by using antibodies. cDNA clones of the VnR α-subunit (VnR/sub α/) were obtained from the HUVE cell library by using an oligonucleotide probe from the partial cDNA sequence for the VnR/sub α/. Translation of these sequences showed that the FNR/sub α/, the VnR/sub α/, and GP IIb are composed of disulfide-linked large (858-871 amino acids) and small (137-158 amino acids) chains that are posttranslationally processed from a single mRNA. A single hydrophobic segment located near the carboxyl terminus of each small chain appears to be a transmembrane domain. The large chains appear to be entirely extracellular, and each contains four repeated putative Ca 2+ -binding domains of about 30 amino acids that have sequence similarities to other Ca 2+ -binding proteins. The identity among the protein sequences of the three receptor α-subunits ranges from 36.1% to 44.5%, with the Ca 2+ -binding domains having the greatest homology. These proteins apparently evolved by a process of gene duplication

  14. Dicty_cDB: Contig-U12691-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available le sunflower Hel... 44 8.5 1 ( EL473924 ) CHUL1852.b1_H08.ab1 CHU(LMS) puzzle sunfl...ower Hel... 44 8.5 1 ( EL473578 ) CHUL1499.b1_F16.ab1 CHU(LMS) puzzle sunflower H..... 44 8.5 1 ( CG928985 ) MBEKA23TRB mth2 Medicago truncatula genomic clone... 44 8.5 1 ( EL476161 ) CHUL4104.b1_O18.ab1 CHU(LMS) puzz

  15. Improved beam jitter control methods for high energy laser systems

    OpenAIRE

    Frist, Duane C.

    2009-01-01

    Approved for public release, distribution unlimited The objective of this research was to develop beam jitter control methods for a High Energy Laser (HEL) testbed. The first step was to characterize the new HEL testbed at NPS. This included determination of natural frequencies and component models which were used to create a Matlab/Simulink model of the testbed. Adaptive filters using Filtered-X Least Mean Squares (FX-LMS) and Filtered-X Recursive Least Square (FX-RLS) were then implement...

  16. Study of cancer-specific chimeric promoters induced by irradiation

    International Nuclear Information System (INIS)

    Xiong Jie; Zhou Yunfeng; Sun Wenjie; Wang Weifeng; Liao Zhengkai; Zhou Fuxiang; Xie Conghua

    2010-01-01

    Objective: To combine the radio-inducible CArG element with cancer-specific human telomerase reverse transcriptase (hTERT) gene promoter, and to construct the novel chimeric promoters. Methods: The synthetic hTERT promoters containing different number of radio-inducible CArG elements were constructed, and the activities of the promoters in the cancer cells (HeLa, A549, and MHCC97 cells) and nomal cells (hEL cells) were detected by using luciferase-reporter assays after the treatment of irradiation (a single or fractionated irradiation dose). Results: Synthetic promoter containing 6 repeated CArG units was better in radio-inducibility than any other promoters containing different number of CArG units, and nearly maximum levels obtained at 4-6 Gy. The very low activities of the chimeric promoters could be detected in normal hEL cells. A similar level of reporter gene expression was observed after 3 fractionated doses of 2 Gy compared with a single dose of 6 Gy in cancer cells. Conclusions: The cancer-specific chimeric promoter containing 6 CArG elements showes the best radio-response, and the chimeric promoter system has the potential in cancer gene therapy. (authors)

  17. Expression and function of β-adrenergic receptors in human hematopoietic cell lines

    International Nuclear Information System (INIS)

    Maeki, T.; Andersson, L.C.; Kontula, K.K.

    1992-01-01

    We investigated the expression and functional characteristics of β-adrenoceptors in a panel of 10 phenotypically different human hematopoietic cell lines. A binding assay with [ 125 I]iodocyanopindolol as the ligand revealed that cell lines of myelomonocytic or histiocytic derivation (HL-60, ML-2, RC-2A, U-937) expressed high numbers of β-adrenoceptors. An intermediate density of receptors was found in a non-T, non-B cell leukemia line (Nall-1), whereas T-cell (JM, CCRF-CEM), B-cell (Raji) or erythroleukemic cell lines (K-562, HEL) displayed minimala or undetectable binding of the radioligand. Isoprenaline-stimulated cAMP production by the cells correlated to their extent of β-adrenoceptor expression. Southern blot hybridization analysis of genomic DNA from the cell lines with a 32 P-labelled β 2 -adrenoceptor cDNA probe revealed no evidence for major rearrangement or amplification of the receptor gene. Incubation with isoprenaline in vitro suppressed the proliferation of the receptor-rich RC-2A cells but did not affect the growth rate of the receptor-deficient K-562 cells. Treatment with propranolol slightly enhanced the proliferation of the RC-2A cells but did not markedly alter the growth rate of two other cell lines, regardless of their β-adrenoceptor status. These findings indicate a regulatory influence by the sympathoadrenergic system on selected cells of the myelomonocytic lineage. (au)

  18. Bioprocess development for extracellular production of recombinant human interleukin-3 (hIL-3) in Pichia pastoris.

    Science.gov (United States)

    Dagar, Vikas Kumar; Adivitiya; Devi, Nirmala; Khasa, Yogender Pal

    2016-10-01

    Human interleukin-3 (hIL-3) is a therapeutically important cytokine involved in the maturation and differentiation of various cells of the immune system. The codon-optimized hIL-3 gene was cloned in fusion with the N-terminus α-mating factor signal peptide of Saccharomyces cerevisiae under an inducible alcohol oxidase 1 (AOX1) and constitutive glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter. A Zeocin concentration up to 2000 mg/L was used to select hyper-producers. The shake flask cultivation studies in the Pichia pastoris GS115 host resulted a maximum recombinant hIL-3 expression level of 145 mg/L in the extracellular medium under the control of AOX1 promoter. The batch fermentation strategy allowed us to attain a fairly pure glycosylated hIL-3 protein in the culture supernatant at a final concentration of 475 mg/L with a high volumetric productivity of 4.39 mg/L/h. The volumetric product concentration achieved at bioreactor level was 3.28 folds greater than the shake flask results. The 6x His-tagged protein was purified using Ni-NTA affinity chromatography and confirmed further by western blot analysis using anti-6x His tag antibody. The glycosylation of recombinant hIL-3 protein was confirmed in a PNGase F deglycosylation reaction where it showed a molecular weight band pattern similar to E. coli produced non-glycosylated hIL-3 protein. The structural properties of recombinant hIL-3 protein were confirmed by CD and fluorescence spectroscopy where protein showed 40 % α-helix, 12 % β-sheets with an emission maxima at 343 nm. MALDI-TOF-TOF analysis was used to establish the protein identity. The biological activity of purified protein was confirmed by the human erythroleukemia TF-1 cell proliferation assay.

  19. Experiment list: SRX277329 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available me=Murine erythroleukemia (MEL) cells || cell line=non-induced C88 MEL cells || chip antibody=CDK9 C20 antibody (Santa Cruz Biotechno...logy, C20, sc-484) http://dbarchive.biosciencedbc.jp/kyu

  20. On the characterisation of the dynamic compressive behaviour of silicon carbides subjected to isentropic compression experiments

    Directory of Open Access Journals (Sweden)

    Zinszner Jean-Luc

    2015-01-01

    Full Text Available Ceramic materials are commonly used as protective materials particularly due to their very high hardness and compressive strength. However, the microstructure of a ceramic has a great influence on its compressive strength and on its ballistic efficiency. To study the influence of microstructural parameters on the dynamic compressive behaviour of silicon carbides, isentropic compression experiments have been performed on two silicon carbide grades using a high pulsed power generator called GEPI. Contrary to plate impact experiments, the use of the GEPI device and of the lagrangian analysis allows determining the whole loading path. The two SiC grades studied present different Hugoniot elastic limit (HEL due to their different microstructures. For these materials, the experimental technique allowed evaluating the evolution of the equivalent stress during the dynamic compression. It has been observed that these two grades present a work hardening more or less pronounced after the HEL. The densification of the material seems to have more influence on the HEL than the grain size.

  1. A Portrait of Ribosomal DNA Contacts with Hi-C Reveals 5S and 45S rDNA Anchoring Points in the Folded Human Genome.

    Science.gov (United States)

    Yu, Shoukai; Lemos, Bernardo

    2016-12-31

    Ribosomal RNAs (rRNAs) account for >60% of all RNAs in eukaryotic cells and are encoded in the ribosomal DNA (rDNA) arrays. The rRNAs are produced from two sets of loci: the 5S rDNA array resides exclusively on human chromosome 1, whereas the 45S rDNA array resides on the short arm of five human acrocentric chromosomes. The 45S rDNA gives origin to the nucleolus, the nuclear organelle that is the site of ribosome biogenesis. Intriguingly, 5S and 45S rDNA arrays exhibit correlated copy number variation in lymphoblastoid cells (LCLs). Here we examined the genomic architecture and repeat content of the 5S and 45S rDNA arrays in multiple human genome assemblies (including PacBio MHAP assembly) and ascertained contacts between the rDNA arrays and the rest of the genome using Hi-C datasets from two human cell lines (erythroleukemia K562 and lymphoblastoid cells). Our analyses revealed that 5S and 45S arrays each have thousands of contacts in the folded genome, with rDNA-associated regions and genes dispersed across all chromosomes. The rDNA contact map displayed conserved and disparate features between two cell lines, and pointed to specific chromosomes, genomic regions, and genes with evidence of spatial proximity to the rDNA arrays; the data also showed a lack of direct physical interaction between the 5S and 45S rDNA arrays. Finally, the analysis identified an intriguing organization in the 5S array with Alu and 5S elements adjacent to one another and organized in opposite orientation along the array. Portraits of genome folding centered on the ribosomal DNA array could help understand the emergence of concerted variation, the control of 5S and 45S expression, as well as provide insights into an organelle that contributes to the spatial localization of human chromosomes during interphase. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. Dicty_cDB: Contig-U16043-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available phase... 70 5e-30 3 ( EL484923 ) CHUM6717.b1_J23.ab1 CHU(LMS) puzzle sunflower Hel... 74 5e-30 5 ( CN550770 ...ild sunflowe... 66 2e-23 3 ( EL478038 ) CHUL6624.b1_O23.ab1 CHU(LMS) puzzle sunflower Hel... 66 2e-23 3 ( FG...6.f Dekkera bruxellensis Random Genomic Lib... 105 3e-18 1 ( EL475989 ) CHUL3945.b1_B03.ab1 CHU(LMS) puzzle

  3. Shock compression of diamond crystal

    OpenAIRE

    Kondo, Ken-ichi; Ahrens, Thomas J.

    1983-01-01

    Two shock wave experiments employing inclined mirrors have been carried out to determine the Hugoniot elastic limit (HEL), final shock state at 191 and 217 GPa, and the post-shock state of diamond crystal, which is shock-compressed along the intermediate direction between the and crystallographic axes. The HEL wave has a velocity of 19.9 ± 0.3 mm/µsec and an amplitude of 63 ± 28 GPa. An alternate interpretation of the inclined wedge mirror streak record suggests a ramp precursor wave and th...

  4. A new alternative transcript encodes a 60 kDa truncated form of integrin beta 3.

    OpenAIRE

    Djaffar, I; Chen, Y P; Creminon, C; Maclouf, J; Cieutat, A M; Gayet, O; Rosa, J P

    1994-01-01

    A cDNA for integrin beta 3 isolated from a human erythroleukaemia (HEL) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta 3c, results from the use of a cryptic AG donor splice site in intron 8 of the beta 3 gene, and is different from a previously described alternative beta 3 mRNA. The predicted open reading frame of beta 3C stops at a TAG stop codon 69 bp downstream from position 1281. It starts with the signal peptide and the 404 N-terminal extracellular residu...

  5. Interaction of an immunodominant epitope with Ia molecules in T-cell activation

    DEFF Research Database (Denmark)

    Adorini, L; Sette, A; Buus, S

    1988-01-01

    The amino acid sequence corresponding to residues 107-116 of hen egg-white lysozyme (HEL) has been identified as containing an immunodominant T-cell epitope recognized in association with the I-Ed molecule. The immunodominance of this epitope in HEL-primed H-2d mice was demonstrated by analysis o......-120)-peptide was found to be immunogenic in H-2d mice. Thus, a single semiconservative substitution drastically reduces binding capacity and abolishes immunogenicity, suggesting that a strict correlation exists between binding of a peptide to Ia molecules and its immunogenicity....

  6. Hollow Electron Beam Collimation For HL-LHC - Effect On The Beam Core

    CERN Document Server

    Fitterer, M; Valishev, A; Bruce, R; Papadopoulou, S; Papotti, G; Pellegrini, D; Redaelli, S; Valuch, D; Wagner, J F

    2017-01-01

    Collimation with hollow electron beams or lenses (HEL) is currently one of the most promising concepts for active halo control in HL-LHC. In previous studies it has been shown that the halo can be efficiently removed with a hollow electron lens. Equally important as an efficient removal of the halo, is also to demonstrate that the core stays unperturbed. In this paper, we present a summary of the experiment at the LHC and simulations in view of the effect of the HEL on the beam core in case of a pulsed operation.

  7. New-technology MWD and LWD Systems designed for ultra-deepwater drilling

    Energy Technology Data Exchange (ETDEWEB)

    Radzinski, P.; Mack, S.; Cheatham, C. [Computalog Drilling Services, Houston, TX (United States); Brady, K. [Precision Drilling, Houston, TX (United States)

    2003-06-01

    This paper discusses the development of two completely new measurement-while-drilling systems. The first system is the Hostile Environment Logging (HEL) MWD system that comprises directional and gamma ray tools, with options for downhole pressure, vibration and temperature sensors. The second system is the Precision LWD system that all components of the HEL MWD system, but adds resistivity, neutron, and density tools to the tool string. Combining the two systems provides a triple combo logging suite of gamma ray, resistivity, and neutron/density sensors. The primary focus of this paper is the Precision LWD triple combo. (orig.)

  8. The impact of socioeconomic status and multimorbidity on mortality: a population-based cohort study.

    Science.gov (United States)

    Lund Jensen, Nikoline; Pedersen, Henrik Søndergaard; Vestergaard, Mogens; Mercer, Stewart W; Glümer, Charlotte; Prior, Anders

    2017-01-01

    Multimorbidity (MM) is more prevalent among people of lower socioeconomic status (SES), and both MM and SES are associated with higher mortality rates. However, little is known about the relationship between SES, MM, and mortality. This study investigates the association between educational level and mortality, and to what extent MM modifies this association. We followed 239,547 individuals invited to participate in the Danish National Health Survey 2010 (mean follow-up time: 3.8 years). MM was assessed by using information on drug prescriptions and diagnoses for 39 long-term conditions. Data on educational level were provided by Statistics Denmark. Date of death was obtained from the Civil Registration System. Information on lifestyle factors and quality of life was collected from the survey. The main outcomes were overall and premature mortality (death before the age of 75). Of a total of 12,480 deaths, 6,607 (9.5%) were of people with low educational level (LEL) and 1,272 (2.3%) were of people with high educational level (HEL). The mortality rate was higher among people with LEL compared with HEL in groups of people with 0-1 disease (hazard ratio: 2.26, 95% confidence interval: 2.00-2.55) and ≥4 diseases (hazard ratio: 1.14, 95% confidence interval: 1.04-1.24), respectively (adjusted model). The absolute number of deaths was six times higher among people with LEL than those with HEL in those with ≥4 diseases. The 1-year cumulative mortality proportions for overall death in those with ≥4 diseases was 5.59% for people with HEL versus 7.27% for people with LEL, and 1-year cumulative mortality proportions for premature death was 2.93% for people with HEL versus 4.04% for people with LEL. Adjusting for potential mediating factors such as lifestyle and quality of life eliminated the statistical association between educational level and mortality in people with MM. Our study suggests that LEL is associated with higher overall and premature mortality and that the

  9. Coevolution of a Persistent Plant Virus and Its Pepper Hosts.

    Science.gov (United States)

    Safari, Maliheh; Roossinck, Marilyn J

    2018-05-30

    There are many nonpathogenic viruses that are maintained in a persistent lifestyle in plants. Plant persistent viruses are widespread, replicating in their hosts for many generations. So far, Endornaviridae is the only family of plant persistent viruses with a single-stranded RNA genome, containing one large open reading frame. Bell pepper endornavirus (BPEV), Hot pepper endornavirus, Capsicum frutescens endornavirus 1 (CFEV 1) have been identified from peppers. Peppers are native to Central and South America and, as domesticated plants, human selection accelerated their evolution. We investigated the evolution of these endornaviruses in different peppers including Capsicum annuum, C. chacoense, C.chinense, C. frutescens, C.bacccutum, and C. pubescens using two fragments from the viral helicase (Hel) and RNA dependent RNA polymerase (RdRp) domains. In addition, using single nucleotide polymorphisms, we analyzed the pepper host populations and phylogenies. The endornaviruses phylogeny was correlated with its Capsicum species host. In this study, BPEV was limited to C. annuum species, and the RdRp and Hel phylogenies identified two clades that correlated with the host pungency. No C. annuum infected with CFEV 1 was found in this study, but the CFEV 1 RdRp fragment was recovered from C. chinense, C. frutescens, C. bacccutum, and C. pubescens. Hence, during pepper speciation, the ancestor of CFEV 1 may have evolved as a new endornavirus, BPEV, in C. annuum peppers.

  10. Basal cell adhesion molecule/lutheran protein. The receptor critical for sickle cell adhesion to laminin.

    Science.gov (United States)

    Udani, M; Zen, Q; Cottman, M; Leonard, N; Jefferson, S; Daymont, C; Truskey, G; Telen, M J

    1998-01-01

    Sickle red cells bind significant amounts of soluble laminin, whereas normal red cells do not. Solid phase assays demonstrate that B-CAM/LU binds laminin on intact sickle red cells and that red cell B-CAM/LU binds immobilized laminin, whereas another putative laminin binding protein, CD44, does not. Ligand blots also identify B-CAM/LU as the only erythrocyte membrane protein(s) that binds laminin. Finally, transfection of murine erythroleukemia cells with human B-CAM cDNA induces binding of both soluble and immobilized laminin. Thus, B-CAM/LU appears to be the major laminin-binding protein of sickle red cells. Previously reported overexpression of B-CAM/LU by epithelial cancer cells suggests that this protein may also serve as a laminin receptor in malignant tumors. PMID:9616226

  11. Assessment of Dengue virus helicase and methyltransferase as targets for fragment-based drug discovery.

    Science.gov (United States)

    Coutard, Bruno; Decroly, Etienne; Li, Changqing; Sharff, Andrew; Lescar, Julien; Bricogne, Gérard; Barral, Karine

    2014-06-01

    Seasonal and pandemic flaviviruses continue to be leading global health concerns. With the view to help drug discovery against Dengue virus (DENV), a fragment-based experimental approach was applied to identify small molecule ligands targeting two main components of the flavivirus replication complex: the NS3 helicase (Hel) and the NS5 mRNA methyltransferase (MTase) domains. A library of 500 drug-like fragments was first screened by thermal-shift assay (TSA) leading to the identification of 36 and 32 fragment hits binding Hel and MTase from DENV, respectively. In a second stage, we set up a fragment-based X-ray crystallographic screening (FBS-X) in order to provide both validated fragment hits and structural binding information. No fragment hit was confirmed for DENV Hel. In contrast, a total of seven fragments were identified as DENV MTase binders and structures of MTase-fragment hit complexes were solved at resolution at least 2.0Å or better. All fragment hits identified contain either a five- or six-membered aromatic ring or both, and three novel binding sites were located on the MTase. To further characterize the fragment hits identified by TSA and FBS-X, we performed enzymatic assays to assess their inhibition effect on the N7- and 2'-O-MTase enzymatic activities: five of these fragment hits inhibit at least one of the two activities with IC50 ranging from 180μM to 9mM. This work validates the FBS-X strategy for identifying new anti-flaviviral hits targeting MTase, while Hel might not be an amenable target for fragment-based drug discovery (FBDD). This approach proved to be a fast and efficient screening method for FBDD target validation and discovery of starting hits for the development of higher affinity molecules that bind to novel allosteric sites. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. l-Amino acid oxidase isolated from Calloselasma rhodostoma snake venom induces cytotoxicity and apoptosis in JAK2V617F-positive cell lines

    Directory of Open Access Journals (Sweden)

    Cristiane Tavares

    2016-06-01

    Full Text Available ABSTRACT BACKGROUND: Myeloproliferative neoplasms are Philadelphia chromosome-negative diseases characterized by hyperproliferation of mature myeloid cells, associated or not with the Janus kinase 2 tyrosine kinase mutation, JAK2V617F. As there is no curative therapy, researchers have been investigating new drugs to treat myeloproliferative neoplasms, including l-amino acid oxidase from Calloselasma rhodostoma snake venom (CR-LAAO, which is a toxin capable of eliciting apoptosis in several tumor cell lines. OBJECTIVE: To evaluate the effects of l-amino acid oxidase from C. rhodostoma snake venom in the apoptotic machinery of JAK2-mutated cell lines. METHODS: The HEL 92.1.7 and SET-2 cell lines were cultured with l-amino acid oxidase and catalase for 12 h at 37 °C in 5% carbon dioxide. The cell viability was assessed by the multi-table tournament method, the level of apoptosis was measured by flow cytometry, and the expression of cysteine-dependent aspartate-specific proteases and cleaved Poly(ADP-ribose polymerase were analyzed by Western blotting. RESULTS: l-Amino acid oxidase from C. rhodostoma snake venom was cytotoxic to HEL 92.1.7 and SET-2 cells (50% inhibitory concentration = 0.15 µg/mL and 1.5 µg/mL, respectively and induced apoptosis in a concentration-dependent manner. Cell treatment with catalase mitigated the l-amino acid oxidase toxicity, indicating that hydrogen peroxide is a key component of its cytotoxic effect.The activated caspases 3 and 8 expression and cleaved PARP in HEL 92.1.7 and SET-2 cells confirmed the apoptosis activation by CR-LAAO. CONCLUSIONS: l-Amino acid oxidase from C. rhodostoma snake venom is a potential antineoplastic agent against HEL 92.1.7 and SET-2 JAK2V617F-positive cells as it activates the extrinsic apoptosis pathway.

  13. Introducing Undergraduate Students to Real-Time PCR

    Science.gov (United States)

    Hancock, Dale; Funnell, Alister; Jack, Briony; Johnston, Jill

    2010-01-01

    An experiment is conducted, which in four 3 h laboratory sessions, introduces third year undergraduate Biochemistry students to the technique of real-time PCR in a biological context. The model used is a murine erythroleukemia cell line (MEL cells). These continuously cycling, immature red blood cells, arrested at an early stage in erythropoiesis,…

  14. Narva-Jõesuu semmib Hispaania veekeskuste ehitajaga / Tanel Mazur

    Index Scriptorium Estoniae

    Mazur, Tanel, 1971-

    2006-01-01

    Narva-Jõesuu linnavalitsus plaanib ühel linna omanduses olevatest kruntidest alustada aktiivset veekeskuse arendust, partneriks ligi 40-aastase kogemusega Hispaania firma "Action Park Multiforma Grupo S.L."

  15. Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing.

    Science.gov (United States)

    Valdés-Alemán, Javier; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Godoy-Lozano, Elizabeth; Velázquez-Ramírez, Daniel; Valdovinos-Torres, Humberto; Gómez-Barreto, Rosa E; Martinez-Barnetche, Jesús

    2014-01-01

    High-throughput sequencing of the antibody repertoire is enabling a thorough analysis of B cell diversity and clonal selection, which may improve the novel antibody discovery process. Theoretically, an adequate bioinformatic analysis could allow identification of candidate antigen-specific antibodies, requiring their recombinant production for experimental validation of their specificity. Gene synthesis is commonly used for the generation of recombinant antibodies identified in silico. Novel strategies that bypass gene synthesis could offer more accessible antibody identification and validation alternatives. We developed a hybridization-based recovery strategy that targets the complementarity-determining region 3 (CDRH3) for the enrichment of cDNA of candidate antigen-specific antibody sequences. Ten clonal groups of interest were identified through bioinformatic analysis of the heavy chain antibody repertoire of mice immunized with hen egg white lysozyme (HEL). cDNA from eight of the targeted clonal groups was recovered efficiently, leading to the generation of recombinant antibodies. One representative heavy chain sequence from each clonal group recovered was paired with previously reported anti-HEL light chains to generate full antibodies, later tested for HEL-binding capacity. The recovery process proposed represents a simple and scalable molecular strategy that could enhance antibody identification and specificity assessment, enabling a more cost-efficient generation of recombinant antibodies.

  16. A High-Purity Alumina for Use in Studies of Shock Loaded Samples

    Science.gov (United States)

    Lacina, David; Neel, Christopher

    2017-06-01

    We report the results of plate impact experiments on a potential new ``standard'' material, Coorstek Plasmapure-UC (99.9% purity) polycrystalline alumina, for use in non-conduction, impact environment, shock loading studies. This work was motivated by a desire to find a 99.9% purity alumina to replace the now unavailable Coors Vistal (99.9%) alumina, as it was hoped the Hugoniot elastic limit (HEL) of the new standard would match the 9-11 GPa value of Vistal. Shock response data, including the HEL, Hugoniot particle velocities, Hugoniot shock velocities, stress vs volume, and release wave speeds, was obtained up to 14 GPa. This data will be compared with Hugoniot curve data for other high purity alumina to contrast differences in the shock response, and is intended to be useful in impedance matching calculations. We will show that the HEL of Plasmapure-UC alumina is 5.5 GPa and speculate on causes for this lower than expected value. We will also explore why the elastic-plastic response for Plasmapure-UC alumina differs from what has been observed from other high purity alumina. The final result of this work is to recommend a well-characterized, lower purity alumina (Coorstek AD-995) as a potential new ``standard'' material.

  17. Gender Role Orientation with Health Literacy and Self-Efficacy for Healthy Eating among Japanese Workers in Early Adulthood.

    Science.gov (United States)

    Hosokawa, Chizuru; Ishikawa, Hirono; Okada, Masafumi; Kato, Mio; Okuhara, Tsuyoshi; Kiuchi, Takahiro

    2016-01-01

    Gender role, independent of biological sex, affects health. However, research on healthy eating that considers the importance of gender norms is scarce. People who are androgynous and have high masculinity and femininity are reported to have better health practices than other people. The present study aimed to examine the differences in health literacy (HL) and self-efficacy for healthy eating by gender role in Japanese men and women. Participants were 629 men and women aged 25-34 years, recruited via a Japanese Internet research company database. Participants were categorized into four gender role groups using the Japanese Gender Role Index. HL and self-efficacy for healthy eating were assessed using the healthy eating literacy (HEL) scale and the healthy eating and weight self-efficacy (HEWSE) scale. Analysis of variance with Bonferroni-adjusted post hoc tests and hierarchical multiple regression were used to test the research hypotheses. We found that the Androgynous group had significantly higher HEL and HEWSE scores than the Feminine and Undifferentiated groups. The Masculine group scored significantly higher on both measures than the Undifferentiated group. Being Androgynous (HEL: β = 0.34, p gender role orientation and individual HL and self-efficacy for healthy eating. These findings may be relevant for promoting healthy eating from the perspective of gender norms.

  18. Mehhiklane troonil: kas Bill Gatesi ajastu sai tõesti otsa? / Heiki Suurkask

    Index Scriptorium Estoniae

    Suurkask, Heiki, 1972-

    2010-01-01

    Ajakirja Forbes koostatud maailma rikkaimate inimeste edetabelist, mille tipus on Mehhiko telekomi monopoli suuromanik Carlos Slim Helú, seniselt liidripositsioonilt on teisele kohale langenud Microsofti rajaja Bill Gates

  19. Chemistry and Selective Tumor Cell Growth Inhibitory Activity of Polyketides from the South China Sea Sponge Plakortis sp.

    Science.gov (United States)

    Li, Jiao; Li, Cui; Riccio, Raffaele; Lauro, Gianluigi; Bifulco, Giuseppe; Li, Tie-Jun; Tang, Hua; Zhuang, Chun-Lin; Ma, Hao; Sun, Peng; Zhang, Wen

    2017-05-03

    Simplextone E ( 1 ), a new metabolite of polyketide origin, was isolated with eight known analogues ( 2 - 9 ) from the South China Sea sponge Plakortis sp. The relative configuration of the new compound was elucidated by a detailed analysis of the spectroscopic data and quantum mechanical calculation of NMR chemical shifts, aided by the newly reported DP4+ approach. Its absolute configuration was determined by the TDDFT/ECD calculation. Simplextone E ( 1 ) is proven to be one of the isomers of simplextone D. The absolute configuration at C-8 in alkyl chain of plakortone Q ( 2 ) was also assigned based on the NMR calculation. In the preliminary in vitro bioassay, compounds 6 and 7 showed a selective growth inhibitory activity against HCT-116 human colon cancer cells with IC 50 values of 8.3 ± 2.4 and 8.4 ± 2.3 μM, corresponding to that of the positive control, adriamycin (IC 50 4.1 μM). The two compounds also showed selective activities towards MCF-7 human breast cancer and K562 human erythroleukemia cells while compound 3 only displayed weak activity against K562 cells.

  20. Hispaania kuningapaar külastab Eestit! / Koidu Raudvere

    Index Scriptorium Estoniae

    Raudvere, Koidu

    2009-01-01

    Portreeartikkel Hispaania kuningast Juan Carlosest ja kuninganna Sofiast. Ühel juuresolevatest fotodest president Toomas Hendrik Ilves ja proua Evelin Ilves riigivisiidil Hispaanias. Vabariigi President riigivisiidil Hispaaniasse 8.-11.07.2007

  1. Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets

    Science.gov (United States)

    Möhle, Robert; Green, David; Moore, Malcolm A. S.; Nachman, Ralph L.; Rafii, Shahin

    1997-01-01

    We have shown that coculture of bone marrow microvascular endothelial cells with hematopoietic progenitor cells results in proliferation and differentiation of megakaryocytes. In these long-term cultures, bone marrow microvascular endothelial cell monolayers maintain their cellular integrity in the absence of exogenous endothelial growth factors. Because this interaction may involve paracrine secretion of cytokines, we evaluated megakaryocytic cells for secretion of vascular endothelial growth factor (VEGF). Megakaryocytes (CD41a+) were generated by ex vivo expansion of hematopoietic progenitor cells with kit-ligand and thrombopoietin for 10 days and further purified with immunomagnetic microbeads. Using reverse transcription–PCR, we showed that megakaryocytic cell lines (Dami, HEL) and purified megakaryocytes expressed mRNA of the three VEGF isoforms (121, 165, and 189 amino acids). Large quantities of VEGF (>1 ng/106 cells/3 days) were detected in the supernatant of Dami cells, ex vivo-generated megakaryocytes, and CD41a+ cells isolated from bone marrow. The constitutive secretion of VEGF by CD41a+ cells was stimulated by growth factors of the megakaryocytic lineage (interleukin 3, thrombopoietin). Western blotting of heparin–Sepharose-enriched supernatant mainly detected the isoform VEGF165. In addition, immunohistochemistry showed intracytoplasmic VEGF in polyploid megakaryocytes. Thrombin stimulation of megakaryocytes and platelets resulted in rapid release of VEGF within 30 min. We conclude that human megakaryocytes produce and secrete VEGF in an inducible manner. Within the bone marrow microenvironment, VEGF secreted by megakaryocytes may contribute to the proliferation of endothelial cells. VEGF delivered to sites of vascular injury by activated platelets may initiate angiogenesis. PMID:9012841

  2. Kinesteesia : Ühel teatrikriitikute kokkusaamisel juhtunust / Anneli Saro

    Index Scriptorium Estoniae

    Saro, Anneli, 1968-

    2003-01-01

    Mais 2002 Stockholmis toimunud Rahvusvahelise Teatrikriitikute Assotsiatsiooni organiseeritud noorte kriitikute seminarist : E. Nekroshiuse lavastusest "Hamlet", I. Bergmani lavastusest Ibseni järgi "Kummitused" ja Mats Eki tantsulavastusest "Andromache"J. Racine'i järgi

  3. Epidemiological study on gastrointestinal tract hel- minthosis of ...

    African Journals Online (AJOL)

    zone practice a crop - livestock mixed farming and keep combination of live- ... of animals (Goat and sheep), sex of animals (male and female), age of animals .... Mean worm burden of Haemonchus contortus was significantly high in older ..... high and mid land portion of the study site where sheep were forced to graze.

  4. August Kingu reisikaaslane Richard Vilmansen / Rein Saukas

    Index Scriptorium Estoniae

    Saukas, Rein, 1947-

    2008-01-01

    Bibl. lk. 212. Ette kantud 25. oktoobril 2007 Akadeemilise Rahvaluule Seltsi kogumiskonverentsil "Võõrsil ja kodus". R. Vilmansen osales ühel rahvaluule kogumismatkal - koos August Kinguga Vaivara kihelkonnas 1913. a. kevadsuvel

  5. The Simulation of Off-Axis Laser Propagation Using Heleeos

    National Research Council Canada - National Science Library

    Belton, Scott L

    2006-01-01

    .... The scatter from these aerosols and molecules can redirect some of the HEL's concentrated energy towards unintended targets such as the eyes of pilots, friendly fighters on the surface, or innocent bystanders...

  6. Eesti lülitumine modernsusesse : "Noor-Eesti" roll poliitilise ja sotsiaalse mõtte mitmekesistamisel / Toivo Raun ; tõlkinud Anne Lange

    Index Scriptorium Estoniae

    Raun, Toivo, 1943-

    2009-01-01

    Eestis juhatas modernse poliitika sisse 1905. a. revolutsioon. Revolutsiooniga ühel aastal ilmus "Noor-Eesti" esimene album. Rühmituse juhtivate teoreetikute seisukohti rahvusküsimuse, välispoliitika jt. küsimustes

  7. High-Energy Laser Weapon Integration with Ground Vehicles

    National Research Council Canada - National Science Library

    Hafften, Michael; Stratton, Robert

    2004-01-01

    .... The architecture of an electric, solid-state HEL weapon system would likely be based upon a hybrid electric vehicle that provides a common electrical power source for the propulsion and weapon subsystems...

  8. VizieR Online Data Catalog: Local interstellar spectra of cosmic-ray species (Boschini+, 2017)

    Science.gov (United States)

    Boschini, M. J.; Torre, S. D.; Gervasi, M.; Grandi, D.; Johannesson, G.; Kachelriess, M.; La Vacca, G.; Masi, N.; Moskalenko, I. V.; Orlando, E.; Ostapchenko, S. S.; Pensotti, S.; Porter, T. A.; Quadrani, L.; Rancoita, P. G.; Rozza, D.; Tacconi, M.

    2017-11-01

    Local interstellar spectra (LIS) for protons, helium, and antiprotons are built using the most recent experimental results combined with state-of-the-art models for propagation in the Galaxy and heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of cosmic-ray (CR) species at different modulation levels and at both polarities of the solar magnetic field. To do so in a self-consistent way, an iterative procedure was developed, where the GALPROP LIS output is fed into HelMod, providing modulated spectra for specific time periods of selected experiments to compare with the data; the HelMod parameter optimization is performed at this stage and looped back to adjust the LIS using the new GALPROP run. The parameters were tuned with the maximum likelihood procedure using an extensive data set of proton spectra from 1997 to 2015. The proposed LIS accommodate both the low-energy interstellar CR spectra measured by Voyager 1 and the high-energy observations by BESS, Pamela, AMS-01, and AMS-02 made from the balloons and near-Earth payloads; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The found solution is in a good agreement with proton, helium, and antiproton data by AMS-02, BESS, and PAMELA in the whole energy range. (3 data files).

  9. Solution of Heliospheric Propagation: Unveiling the Local Interstellar Spectra of Cosmic-ray Species

    Energy Technology Data Exchange (ETDEWEB)

    Boschini, M. J.; Torre, S. Della; Gervasi, M.; Grandi, D.; Vacca, G. La; Pensotti, S.; Rancoita, P. G.; Rozza, D.; Tacconi, M. [INFN, Milano-Bicocca, Milano (Italy); Jóhannesson, G. [Science Institute, University of Iceland, Dunhaga 3, IS-107 Reykjavik (Iceland); Kachelriess, M. [Institutt for fysikk, NTNU, NO-7491 Trondheim (Norway); Masi, N.; Quadrani, L. [INFN, Bologna (Italy); Moskalenko, I. V.; Orlando, E.; Porter, T. A. [Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA 94305 (United States); Ostapchenko, S. S. [Frankfurt Institute of Advanced Studies, Frankfurt (Germany)

    2017-05-10

    Local interstellar spectra (LIS) for protons, helium, and antiprotons are built using the most recent experimental results combined with state-of-the-art models for propagation in the Galaxy and heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of cosmic-ray (CR) species at different modulation levels and at both polarities of the solar magnetic field. To do so in a self-consistent way, an iterative procedure was developed, where the GALPROP LIS output is fed into HelMod, providing modulated spectra for specific time periods of selected experiments to compare with the data; the HelMod parameter optimization is performed at this stage and looped back to adjust the LIS using the new GALPROP run. The parameters were tuned with the maximum likelihood procedure using an extensive data set of proton spectra from 1997 to 2015. The proposed LIS accommodate both the low-energy interstellar CR spectra measured by Voyager 1 and the high-energy observations by BESS, Pamela, AMS-01, and AMS-02 made from the balloons and near-Earth payloads; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The found solution is in a good agreement with proton, helium, and antiproton data by AMS-02, BESS, and PAMELA in the whole energy range.

  10. Antioxidant and Antiproliferative Activities of Leaf Extracts from Plukenetia volubilis Linneo (Euphorbiaceae

    Directory of Open Access Journals (Sweden)

    Ana Karina Lima Nascimento

    2013-01-01

    Full Text Available Plukenetia volubilis Linneo, or Sacha inca, is an oleaginous plant from the Euphorbiaceae family. The aim of this work was to perform a chemical and biological analysis of different leaf extracts from P. volubilis such as aqueous extract (AEL, methanol (MEL, ethanol (EEL, chloroform (CEL, and hexane (HEL. Thin layer chromatography analysis revealed the presence of phenolic compounds, steroids, and/or terpenoídes. Furthermore, the antioxidant activities were analyzed by in vitro assays and their effects on cell lineages by in vivo assays. The Total Antioxidant Capacity (TCA was expressed as equivalent ascorbic acid (EEA/g and it was observed that the extracts showed values ranging from 59.31 to 97.76 EAA/g. Furthermore, the DPPH assay values ranged from 62.8% to 88.3%. The cell viability assay showed that the extracts were able to reduce viability from cancer cells such as HeLa and A549 cells. The extracts MEL and HEL (250 µg/mL were able to reduce the proliferation of HeLa cells up to 54.3% and 48.5%, respectively. The flow cytometer results showed that these extracts induce cell death via the apoptosis pathway. On the other hand, the extracts HEL and AEL were able to induce cell proliferation of normal fibroblast 3T3 cells.

  11. Further investigation of surface velocity measurements for material characterization in laser shockwave experiments

    Science.gov (United States)

    Smith, James A.; Lacy, Jeffrey M.; Scott, Clark L.; Benefiel, Bradley C.; Lévesque, Daniel; Monchalin, Jean-Pierre; Lord, Martin

    2018-04-01

    As part of the U.S. High Performance Research Reactor program, a laser shock test system is being developed by the Idaho National Laboratory (INL) to characterize interface strength in innovative plate fuel for research reactors around the world. The INL has been working with National Research Council Canada (NRC) on this project for the last five years. One of the concerns is the difficulty of calibrating and standardizing the laser shock technique. A recent analytical study and testing support the use of the Hugoniot Elastic Limit (HEL) in materials as a robust and simple benchmark to compare stresses generated by different laser shock systems. Using a non-contact laser velocimeter based on a solid Fabry-Perot etalon, the systems at NRC and INL show that the back-surface velocity reached at the HEL is consistent, and independent of the laser power used. In this work, the laser velocimeter of the NRC system is tested against a fast rotating wheel to verify accuracy and determine best operating conditions. A round robin test between the two laser shock systems on plates of different aluminum alloys is presented that shows the consistent characterization of the aluminum alloys based on the HEL velocities as well as determines the bias between the systems. The effects of setup parameters on other characteristics of the back-surface velocity trace and corresponding stress wave are also discussed.

  12. Mercury in marine fish, mammals, seabirds, and human hair in the coastal zone of the southern Baltic.

    Science.gov (United States)

    Bełdowska, Magdalena; Falkowska, Lucyna

    Mercury (Hg), aside from having high toxicity, is characterized by its ability to biomagnify in the marine trophic chain. This is an important problem especially in estuaries, or in the coastal zone, particularly near the mouths of large rivers. This study was conducted in the years 2001-2011, in the coastal zone of the Baltic Sea near to the mouth of the River Vistula, which is the second biggest river discharging into the Baltic. Mercury concentration was measured in the tissues and organs of cod, flounder, herring, seals (living in the wild and in captivity), great black-backed gulls, and African penguins from Gdańsk Zoo, and also in human hair. Penguins and seals at the seal sanctuary in Hel were fed only herring. In marine birds and mammals and in the pelagic herring, the highest Hg concentration was observed in the kidney and in the liver, while in cod and flounder (located on a higher trophic level) the muscles were the most contaminated with mercury. In gray seals living in the seal sanctuary, Hg concentration in all analyzed tissues and organs except the kidneys was lower in comparison with seals living in the wild. The comparatively small share of fish in the diet of local Polish people and their preference towards the consumption of herring contributed to low concentration of Hg in their hair. The protective mechanisms related to detoxification and elimination of mercury were shown to be more effective in the seals than in the penguins, despite the former consuming around 10 times more food per day.

  13. Kasvuvisioon 2018 - Eesti riigi järgmine juhtimisülesanne / Priit Põldoja

    Index Scriptorium Estoniae

    Põldoja, Priit, 1969-

    2010-01-01

    Ettevõtja hinnagul peab Eesti riigil olema aktiivne ettekujutus, kuidas positiivselt eristuda ja kuhu edasi liikuda. Arengufondi initsiatiiv Eesti kasvuvisiooni loomisel peaks leidma ühel või teisel viisil tee Eesti otsustajate tegevuskavva

  14. Heitlikud üheksakümnendad / Pekka Erelt

    Index Scriptorium Estoniae

    Erelt, Pekka, 1965-

    2008-01-01

    Ülevaade sündmustest Eestis 1990ndatel aastatel. Ühel juuresolevatest fotodest president Lennart Meri, proua Helle Meri, USA kaitseminister William Perry ja Eesti suursaadik USAs Toomas Hendrik Ilves 1995. a. novembris

  15. Genetic differentiation among geographically isolated populations of Criollo cattle and their divergence from other Bos taurus breeds.

    Science.gov (United States)

    Russell, N D; Rios, J; Erosa, G; Remmenga, M D; Hawkins, D E

    2000-09-01

    The microsatellites HEL5, HEL9, INRA063, and BM2113 were used to analyze genetic similarities and differences of geographically isolated Criollo cattle herds in Mexico. Criollo cattle from five counties within the state of Chihuahua and one county from the state of Tamaulipas (n = 60) were sampled. The five counties in Chihuahua included Cerocahui (n = 14), Chinipas (n = 10), Guachochi (n = 15), Morelos (n = 30), and Temoris (n = 9). Samples of DNA were amplified by PCR and separated on a 7% polyacrylamide gel. Microsatellite size was established by comparison to M13mp18 DNA ladder and a documented set of four bovine controls. Allele frequencies and genotypic deviations from Hardy-Weinberg equilibrium were tested using the GENEPOP program. Eleven alleles were generated at HEL5 for the populations sampled (149 to 169 bp). Allele frequencies were greatest for the 163-bp allele in Criollo cattle from Cerocahui, Chinipas, Moralos, and Tamaulipas (0.23 to 0.5). Cattle from Guachochi had an allele frequency of 0.38 for the 151-bp allele, and cattle from Temoris had an allele frequency of 0.25 for the 149- and 167-bp alleles, with no 163-bp allele. Amplification with HEL9 produced 12 alleles (145, 149 to 169 bp) and showed common high-frequency alleles at 149, 157, and 159 bp for animals from all regions. The Chinipas population showed a moderate allele frequency at 145 bp; no other regions contained this allele. For INRA063 there were five alleles with 182 and 184 bp in low frequency. For BM2113 there were 10 alleles in the Criollo cattle (125 to 143 bp), with an equal distribution of frequencies for all alleles. In two regions, Guachochi and Morelos, genotypic frequencies deviated from Hardy-Weinberg equilibrium. Cattle from the Temoris region were genetically most distant from Criollo cattle of the other five regions.

  16. Ar-Xe Laser: The Path to a Robust, All-Electric Shipboard Directed Energy Weapon

    National Research Council Canada - National Science Library

    Apruzese, J. P; Sethian, J. D; Giuliani, J. L; Wolford, M. F

    2008-01-01

    .... However, no HELs have been deployed to date. Until recently, there was no laser that had credible prospects of meeting the Navy's requirements for safety, power, size, beam quality, electrical drive, and atmospheric propagation...

  17. Dicty_cDB: Contig-U16068-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Primary rat hepatocyte toxicity modeling. 46 1e-13 5 ( EL485357 ) CHUM7113.b1_A04.ab1 CHU(LMS) puzzle...T(LMS) Jerusalem artichoke ... 54 8e-08 3 ( EL484942 ) CHUM6734.b1_K04.ab1 CHU(LMS) puzzle sunflower Hel... ... MUSR Musa acuminata cDNA 5', mRNA seque... 44 3e-07 4 ( EL513970 ) CHUY742.b1_L18.ab1 CHU(XYZ) puzzle sunfl...Y525.b1_J11.ab1 CHU(XYZ) puzzle sunflower Heli... 54 5e-06 2 ( DY934089 ) CHPX124...ld sunflowe... 54 5e-06 2 ( EL476432 ) CHUL4354.b1_D09.ab1 CHU(LMS) puzzle sunflower Hel... 54 5e-06 2 ( DY9

  18. Dicty_cDB: Contig-U14068-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available A(XYZ) common wild sunflowe... 52 3e-06 2 ( EL475764 ) CHUL3727.b1_M20.ab1 CHU(LMS) puzzle sunflower Hel... ...44 2e-05 3 ( EL484083 ) CHUM594.b1_C06.ab1 CHU(LMS) puzzle sunflower Heli... 44 3e-05 3 ( EH295921 ) UAHYP_0...) serpentine sunflower... 44 5e-04 2 ( EL482465 ) CHUM4440.b1_O06.ab1 CHU(LMS) puzzle sunflower Hel... 44 5e...16607_g1 Cowpea IT97K-461-4 Mixed Tis... 38 5e-04 2 ( EL489951 ) CHUS5070.b1_K19.ab1 CHU(LMS) puzzle... hirsutum cDNA clon... 34 0.002 3 ( EL480989 ) CHUM2981.b1_J02.ab1 CHU(LMS) puzzle

  19. Alumina strength degradation in the elastic regime

    International Nuclear Information System (INIS)

    Furnish, Michael D.; Chhabildas, Lalit C.

    1998-01-01

    Measurements of Kanel et al. [1991] have suggested that deviatoric stresses in glasses shocked to nearly the Hugoniot Elastic Limit (HEL) relax over a time span of microseconds after initial loading. 'Failure' (damage) waves have been inferred on the basis of these measurements using time-resolved manganin normal and transverse stress gauges. Additional experiments on glass by other researchers, using time-resolved gauges, high-speed photography and spall strength determinations have also lead to the same conclusions. In the present study we have conducted transmitted-wave experiments on high-quality Coors AD995 alumina shocked to roughly 5 and 7 GPa (just below or at the HEL). The material is subsequently reshocked to just above its elastic limit. Results of these experiments do show some evidence of strength degradation in the elastic regime

  20. Thyroid Hormone Receptor Mutations in Cancer and Resistance to Thyroid Hormone: Perspective and Prognosis

    Directory of Open Access Journals (Sweden)

    Meghan D. Rosen

    2011-01-01

    Full Text Available Thyroid hormone, operating through its receptors, plays crucial roles in the control of normal human physiology and development; deviations from the norm can give rise to disease. Clinical endocrinologists often must confront and correct the consequences of inappropriately high or low thyroid hormone synthesis. Although more rare, disruptions in thyroid hormone endocrinology due to aberrations in the receptor also have severe medical consequences. This review will focus on the afflictions that are caused by, or are closely associated with, mutated thyroid hormone receptors. These include Resistance to Thyroid Hormone Syndrome, erythroleukemia, hepatocellular carcinoma, renal clear cell carcinoma, and thyroid cancer. We will describe current views on the molecular bases of these diseases, and what distinguishes the neoplastic from the non-neoplastic. We will also touch on studies that implicate alterations in receptor expression, and thyroid hormone levels, in certain oncogenic processes.

  1. 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate promotes megakaryocytic differentiation of myeloid leukaemia cells and primary human CD34⁺ haematopoietic stem cells.

    Science.gov (United States)

    Limb, Jin-Kyung; Song, Doona; Jeon, Mijeong; Han, So-Yeop; Han, Gyoonhee; Jhon, Gil-Ja; Bae, Yun Soo; Kim, Jaesang

    2015-04-01

    In this study we showed that 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient differentiation of megakaryocytes. Specifically, (R)-TEMOSPho induces cell cycle arrest, cell size increase and polyploidization from K562 and HEL cells, which are used extensively to model megakaryocytic differentiation. In addition, megakaryocyte-specific cell surface markers showed a dramatic increase in expression in response to (R)-TEMOSPho treatment. Importantly, we demonstrated that such megakaryocytic differentiation can also be induced from primary human CD34(+) haematopoietic stem cells. Activation of the PI3K-AKT pathway and, to a lesser extent, the MEK-ERK pathway appears to be required for this process, as blocking with specific inhibitors interferes with the differentiation of K562 cells. A subset of (R)-TEMOSPho-treated K562 cells undergoes spontaneous apoptosis and produces platelets that are apparently functional, as they bind to fibrinogen, express P-selectin and aggregate in response to SFLLRN and AYPGFK, the activating peptides for the PAR1 and PAR4 receptors, respectively. Taken together, these results indicate that (R)-TEMOSPho will be useful for dissecting the molecular mechanisms of megakaryocytic differentiation, and that this class of compounds represents potential therapeutic reagents for thrombocytopenia. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Disease: H01641 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ratoconjunctivitis sicca) is multifactorial disease of the tears, lids, and ocular surface which can result ...omian glands. Artificial tears of various kinds are recommended if the symptoms are mild. Lid hygiene is hel

  3. Natural single amino acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells.

    Science.gov (United States)

    Ruiz, Federico M; Scholz, Barbara A; Buzamet, Eliza; Kopitz, Jürgen; André, Sabine; Menéndez, Margarita; Romero, Antonio; Solís, Dolores; Gabius, Hans-Joachim

    2014-03-01

    Natural amino acid substitution by single-site nucleotide polymorphism can become a valuable tool for structure-activity correlations, especially if evidence for association to disease parameters exists. Focusing on the F19Y change in human galectin-8, connected clinically to rheumatoid arthritis, we here initiate the study of consequences of a single-site substitution in the carbohydrate recognition domain of this family of cellular effectors. We apply a strategically combined set of structural and cell biological techniques for comparing properties of the wild-type and variant proteins. The overall hydrodynamic behavior of the full-length protein and of the separate N-domain is not noticeably altered, but displacements in the F0 β-strand of the β-sandwich fold in the N-domain are induced, as evidenced by protein crystallography. Analysis of thermal stability by circular dichroism spectroscopy revealed perceptible differences for the full-length proteins, pointing to an impact of the substitution beyond the N-domain. In addition, small differences in thermodynamic parameters of carbohydrate binding are detected. On the level of two types of tumor cells, characteristics of binding appeared rather similar. In further comparison of the influence on proliferation, the variant proved to be more active as growth regulator in the six tested lines of neuroblastoma, erythroleukemia and colon adenocarcinoma. The seemingly subtle structural change identified here thus has functional implications in vitro, encouraging further analysis in autoimmune regulation and, in a broad context, in work with other natural single-site variants, using the documented combined strategy. The atomic coordinates and structure factors (codes 4BMB, 4BME) have been deposited in the Protein Data Bank. © 2014 FEBS.

  4. Identification of sequences in herpes simplex virus type 1 ICP22 that influence RNA polymerase II modification and viral late gene expression.

    Science.gov (United States)

    Bastian, Thomas W; Rice, Stephen A

    2009-01-01

    Previous studies have shown that the herpes simplex virus type 1 (HSV-1) immediate-early protein ICP22 alters the phosphorylation of the host cell RNA polymerase II (Pol II) during viral infection. In this study, we have engineered several ICP22 plasmid and virus mutants in order to map the ICP22 sequences that are involved in this function. We identify a region in the C-terminal half of ICP22 (residues 240 to 340) that is critical for Pol II modification and further show that the N-terminal half of the protein (residues 1 to 239) is not required. However, immunofluorescence analysis indicates that the N-terminal half of ICP22 is needed for its localization to nuclear body structures. These results demonstrate that ICP22's effects on Pol II do not require that it accumulate in nuclear bodies. As ICP22 is known to enhance viral late gene expression during infection of certain cultured cells, including human embryonic lung (HEL) cells, we used our engineered viral mutants to map this function of ICP22. It was found that mutations in both the N- and C-terminal halves of ICP22 result in similar defects in viral late gene expression and growth in HEL cells, despite having distinctly different effects on Pol II. Thus, our results genetically uncouple ICP22's effects on Pol II from its effects on viral late gene expression. This suggests that these two functions of ICP22 may be due to distinct activities of the protein.

  5. Led Zeppelin reklaamib Narvat / Anti Ronk

    Index Scriptorium Estoniae

    Ronk, Anti

    2007-01-01

    Ilmus Narva-teemaline kahest CD-st koosnev album, kus ühel plaadil on 60 minutit videot linna vaatamisväärsuste ja informatsiooniga, teisel - briti rockansambli Led Zeppelini teosed Narva sümfooniaorkestri ja rockansambli Led R esituses

  6. PA1317(L13): A linac BPM Calibration Program

    International Nuclear Information System (INIS)

    McCrory, E.

    1993-01-01

    The purpose of this program is to determine the centers of the high-energy linac (HEL) BPMs using beam information, and to compare this information with the existing surveying information. It measures directly and quantitatively the amount of quad steering in each of the HEL quads. It is hoped that this program is all that is needed to make this measurement This procedure is based on the observation of the beam position in a BPM downstream of a quad while changing the magnetic field in that quad. If the beam is centered in the quad, then this change will have no effect on the trajectory of the beam. However, if the beam is off center at the quad, changing the field will steer the beam. This measurement therefore can be used to measure the position of the beam in the quad under examination

  7. "Õhtuti süütasid nad kassi haual küünla..." : [luuletused] / Tomi Kontio ; soome keelest tõlkinud Jan Kaus

    Index Scriptorium Estoniae

    Kontio, Tomi

    2007-01-01

    Sisu: "Õhtuti süütasid nad kassi haual küünla..." ; "Meri on plekkis, terasest neiu seisab..." ; "Lumi puude okstel, kirmetis aknal, jää..." ; Kontula kaar ; Vastavalt tahtele ; Ühel kaardil ; Esimene lumi ; Dimensioonid ; Pieta

  8. Piezo-electric automatic vehicle classification system : Oregon Department of Transportation with Castle Rock Consultants for a SHRP Long Term Pavement Performance Site.

    Science.gov (United States)

    1990-05-01

    Oregon has twelve sites that are part of the Strategic Highway Research Program (SHRP), Long Term Pavement Performance (LTPP) studies. Part of the data gathering on these sites involves vehicle weight and classification. This pilot project was to hel...

  9. Saksa ekspert : ökomaksust pensioni rahastamine oleks suur rumalus / Kai Schlegelmilch ; interv. Toivo Tänavsuu

    Index Scriptorium Estoniae

    Schlegelmilch, Kai

    2005-01-01

    Saksa keskkonnaministeeriumi ekspert vastab küsimustele, mis puudutavad ökomaksureformi elluviimist Saksamaal. Tema sõnul oleks Eesti puhul olnud kõige mõistlikum ühel ja samal ajal tõsta energiamakse ning alandada tulumaksumäära. Diagramm: Keskkonnamaksud 2002

  10. Dicty_cDB: Contig-U08228-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ianthus annuus isolate Mexico-M... 42 0.011 FJ373728_1( FJ373728 |pid:none) Helia...23_1( FJ373723 |pid:none) Helianthus annuus cultivar Mandan ... 42 0.011 FJ373709_1( FJ373709 |pid:none) Hel

  11. AQMEII3 evaluation of regional NA/EU simulations and analysis of scale, boundary conditions and emissions error-dependence

    Science.gov (United States)

    Through the comparison of several regional-scale chemistry transport modelling systems that simulate meteorology and air quality over the European and American continents, this study aims at i) apportioning the error to the responsible processes using time-scale analysis, ii) hel...

  12. "Süüdi, sest oled tšetšeen!" / Aadu Hiietamm

    Index Scriptorium Estoniae

    Hiietamm, Aadu, 1954-

    2001-01-01

    Organisatsioon Arstid Inimõiguste Eest küsitles möödunud aastal umbes 1200 Tšetšeenia tsiviilelanikku. Küsitletutest tervelt 46% olid vähemalt ühel korral näinud, kuidas Vene sõdurid tsiviilisikuid tapsid

  13. Antimicrobial, antioxidant and cytotoxic activities of propolis from Melipona orbignyi (Hymenoptera, Apidae).

    Science.gov (United States)

    Campos, Jaqueline Ferreira; dos Santos, Uilson Pereira; Macorini, Luis Fernando Benitez; de Melo, Adriana Mary Mestriner Felipe; Balestieri, José Benedito Perrella; Paredes-Gamero, Edgar Julian; Cardoso, Claudia Andrea Lima; de Picoli Souza, Kely; dos Santos, Edson Lucas

    2014-03-01

    Propolis from stingless bees is well known for its biologic properties; however, few studies have demonstrated these effects. Therefore, this study aimed to investigate the chemical composition and antimicrobial, antioxidant and cytotoxic activities of propolis from the stingless bee Melipona orbignyi, found in Mato Grosso do Sul, Brazil. The chemical composition of the ethanol extract of propolis (EEP) indicated the presence of aromatic acids, phenolic compounds, alcohols, terpenes and sugars. The EEP was active against the bacterium Staphylococcus aureus and the fungus Candida albicans. The EEP showed antioxidant activity by scavenging free radicals and inhibiting hemolysis and lipid peroxidation in human erythrocytes incubated with an oxidizing agent. Additionally, EEP promoted cytotoxic activity and primarily necrotic death in K562 erythroleukemia cells. Taken together, these results indicate that propolis from M. orbignyi has therapeutic potential for the treatment and/or prevention of diseases related to microorganism activity, oxidative stress and tumor cell proliferation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Synthesis, Cytotoxicity and Molecular Docking Study of Complexes Containing Thiazole Moiety

    Directory of Open Access Journals (Sweden)

    Mohammed Shafeeulla

    2017-07-01

    Full Text Available The ligand 5-methyl-2-phenyl-4-[(E-1,3-thiazol-2-yldiazenyl]-2,4-dihydro-3H-pyrazol-3-one (Dy has been synthesized by diazo coupling reactions of 5-methyl-2-phenyl- 2,4-dihydro-3H-pyrazol-3-one with 2-aminothiazole and ferric hydrogen sulfate (FHS, as a catalyst, under solvent-free conditions. A series of complexes of the ligand with Co(II, Ni(II, Cu(II, and Zn(II ions are synthesized and structurally characterized by 1H NMR, FTIR, and UV–Visible spectral techniques. The cytotoxic activity of the complexes and the uncoordinated ligand against human breast cancer (MCF-7 and chronic myelogenous leukemia cell line (human erythroleukemia (K-562 cell lines exhibits good viability in the range of 50.16–55.16% at a concentration of >100-110 µg/mL as compared to the inhibition in the untreated cells. Further, the metal complexes and ligand were screened against antibacterial strains of S. typhi, S. aureus, and E. coli. Both the cytotoxicity and antioxidant studies are correlated with computational docking analysis and powder XRD studies reviles that all complexes are in crystalline nature.

  15. Radiobiology effects of radiation-induced horseradish peroxidase/indole-3-acetic suicide gene expression in lung cancer cells

    International Nuclear Information System (INIS)

    Xiong Jie; Zhou Yunfeng; Wang Weifeng; Sun Wenjie; Liao Zhengkai; Zhou Fuxiang; Xie Conghua

    2010-01-01

    Objective: To detect specific cell killing effect of radiation combined with horseradish peroxidase (HRP)/indole-3-acetic (IAA) suicide gene therapy controlled by a novel radio-inducible and cancer-specific chimeric gene promoter in lung cancer. Methods: We constructed a plasmid expressing HRP enzyme under the control of chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 CArG elements, a plasmid expressing HRP enzyme under the control of hTERT promoter carrying single CArG element, and two control plasmids, which named pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControlluc, respectively. After radiation, the proliferation inhibition and apoptosis induction effect of each type of plasmid in lung cancer cells (A549, SPC-A1) and normal lung cells (hEL) was detected by cell counting and Annexin V-FITC staining. The change of radiosensitivity of lung cancer cells with plasmid system was also detected by clonogenic assays. Results: After a single dose radiation of 6 Gy,the average proliferation inhibition rates of pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControlluc systems were 72.92% ,40.60% , 51.00% and 25.19% (F= 67.31, P< 0.01) in A549 cells, 64.63%, 30.02%, 48.23% and 23.16% (F=64.94, P< 0.01) in SPC-A1 cells, and 20.81%, 18.05%, 44.20% and 18.32% (F=52.19, P<0.01) in normal hEL cells, respectively. The average early apoptosis rates of these four plasmid systems were 36.63%, 22.30%, 24.33% and 12.53% (F =50.99, P <0.01) in A549 cells, 33.73%, 17.37%, 22.43% and 11.20% (F = 20. 76, P < 0.01) in SPC-A1 cells, and 13.53 %, 12.5%, 21.93% and 12.16% (F = 15.08, P < 0.01) in normal hEL cells,respectively. The sensitizing enhancement ratios of the four plasmid systems were 3.45, 2.29, 3.05 and 1.21 in A549 cells, while 2.68, 2.15, 3.05 and 1.21 in SPC-A1 cells, respectively. Conclusions: The new suicide gene system controlled by chimeric promoter may provide a novel therapeutic modality for lung cancer. (authors)

  16. [SP600125-induced polyploidization of megakaryocytic leukemia cell lines by ribosomal protein S6 kinase 1 depends on the degree of cell differentiation].

    Science.gov (United States)

    Wang, Lili; Yang, Jingang; Li, Changling; Xing, Sining; Yu, Ying; Liu, Shuo; Zhao, Song; Ma, Dongchu

    2016-10-01

    Objective To investigate regulatory role of ribosomal protein S6 kinase 1 (S6K1) in the polyploidization of different megakaryocytic leukemia cell lines at the different differentiation stages. Methods Megakaryocytic leukemia cell lines (Dami, Meg-01 and HEL cells) were induced towards polyploidization by SP600125, a c-Jun N-terminal kinase (JNK) inhibitor. The SP600125-inducing process was blocked by H-89, a cAMP-dependent protein kinase (PKA) inhibitor. The phenotype (CD41a, CD42a and CD42b) and DNA ploidy were detected by flow cytometry. The expression and phosphorylation of S6K1 and related proteins were detected by Western blotting. Results SP600125 induced polyploidization and increased the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1) in Dami, Meg-01 and HEL cells. However, the effect of SP600125 on polyploidization of the three cell lines was different, with the strongest effect on Dami cells and the weakest on Meg-01 cells. Moreover, SP600125 increased the phosphorylation of S6K1 Thr421/Ser424 and decreased the phosphorylation of Thr389 in Dami cells. However, it only increased the phosphorylation of Thr389 in HEL cells and had no effect on the phosphorylation of S6K1 in Meg-01 cells. Interestingly, H-89 only partially blocked the polyploidization of Dami cells, although it decreased the phosphorylation of 4E-BP1 in all SP600125-induced three cell lines. Noticeably, H-89 decreased the phosphorylation of S6K1 Thr421/Ser424 and increased the phosphorylation of Thr389 in Dami cells. However, H-89 had no effect on the phosphorylation of Thr421/Ser424, although it increased the phosphorylation of Thr389 in Meg-01 and HEL cells. Phenotypic analysis showed that the three cell lines were at different levels of differentiation in megakaryocytic lineage, with the highest differentiation in Dami and the lowest in Meg-01 cells. Conclusion SP600125-induced polyploidization of megakaryocytic leukemia cell lines is dependent on the effect

  17. Influence of different metal ions on the ultrastructure, biochemical properties, and protein localization of the K562 cell nuclear matrix.

    Science.gov (United States)

    Neri, L M; Bortul, R; Zweyer, M; Tabellini, G; Borgatti, P; Marchisio, M; Bareggi, R; Capitani, S; Martelli, A M

    1999-06-01

    The higher order of chromatin organization is thought to be determined by the nuclear matrix, a mainly proteinaceous structure that would act as a nucleoskeleton. The matrix is obtained from isolated nuclei by a series of extraction steps involving the use of high salt and nonspecific nucleases, which remove chromatin and other loosely bound components. It is currently under debate whether these structures, isolated in vitro by unphysiological extraction buffers, correspond to a nucleoskeleton existing in vivo. In most cell types investigated, the nuclear matrix does not spontaneously resist these extractions steps; rather, it must be stabilized before the application of extracting agents. In this study nuclei, isolated from K562 human erythroleukemia cells, were stabilized by incubation with different metal ions (Ca2+, Cu2+, Zn2+, Cd2+), and the matrix was obtained by extraction with 2 M NaCl. By means of ultrastructural analysis of the resulting structures, we determined that, except for Ca2+, all the other metals induced a stabilization of the matrix, which retained the inner fibrogranular network and residual nucleoli. The biochemical composition, analyzed by two-dimensional gel electrophoresis separation, exhibited a distinct matrix polypeptide pattern, characteristic of each type of stabilizing ion employed. We also investigated to what extent metal ions could maintain in the final structures the original distribution of three inner matrix components, i.e. NuMA, topoisomerase IIalpha, and RNP. Confocal microscopy analysis showed that only NuMa, and, to a lesser extent, topoisomerase IIalpha, were unaffected by stabilization with divalent ions. On the contrary, the fluorescent RNP patterns detected in the resulting matrices were always disarranged, irrespective of the stabilization procedure. These results indicate that several metal ions are powerful stabilizing agents of the nuclear matrix prepared from K562 erythroleukemia cells and also strengthen the

  18. Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene

    International Nuclear Information System (INIS)

    Hoatlin, M.E.; Kozak, S.L.; Kabat, D.; Lilly, F.; Chakraborti, A.; Kozak, C.A.

    1990-01-01

    The leukemogenic membrane glycoprotein (gp55) encoded by Friend spleen focus-forming virus appears to bind to erythropoietin receptors (EpoR) to stimulate erythroblastosis. To directly compare the effects of gp55 with erythropoietin (Epo), the authors produced retrovirions that encode either gp55, Epo, or EpoR. After infection with EpoR virus, interleukin 3-dependent DA-3 cells bound 125 I-labeled Epo and grew without interleukin 3 in the presence of Epo. These latter cells, but not parental DA-3 cells, became factor-independent after superinfection either with Epo virus or with Friend spleen focus-forming virus. In addition, Epo virus caused a disease in mice that mimicked Friend erythroleukemia. Although Fv-2 r homozygotes are susceptible to all other retroviral diseases, they are resistant to both Epo viral and Friend viral erythroleukemia. These results indicate that both gp55 and Epo stimulate EpoR and that the Fv-2 gene encodes a protein that controls response to these ligands. However, the Fv-2 protein is not EpoR because the corresponding genes map to opposite ends of mouse chromosome 9. These results have important implications for understanding signal transduction by EpoR and the role of host genetic variation in controlling susceptibility to an oncogenic protein

  19. Zagadki Klemensa Pale / Vladimir Lesment

    Index Scriptorium Estoniae

    Lesment, Vladimir, 1931-

    2004-01-01

    Ehitusmeister ja kujur Clemens Pale'st (16. saj.) ja tema loodust Tallinnas. Osales Oleviste kiriku Maarja kabeli ehitamises ja raius osa Hans Pawelsi kenotaafi reljeefe. Kõrge mütsi ja habemega mehe figuuri kabeli konsoolil ja ühel reljeefidest peetakse tema autoportreedeks

  20. Nissi Maarja kiriku kooriruumi kahe vitraažakna restaureerimine / H. Beyermann, Illar Kannelmäe, Dolores Hoffmann

    Index Scriptorium Estoniae

    Beyermann, H.

    2005-01-01

    4 ill.; aknad valmistas Riia meister H. Beyermann, ühel aknal on kujutatud evangelist Johannest, teisel apostel Peetrust; töid teostasid Dolores Hoffmanni juhendamisel OÜ Domini Canes meistrid B. Morejev, S. Ganin ja A. Bruk, kaitseklaaside projekti tegi Illar Kannelmäe

  1. Eestlane saab tööd ka Mustal Mandril / Reelika Võsang

    Index Scriptorium Estoniae

    Võsang, Reelika

    2005-01-01

    Heategevusorganisatsiooni Humana People to People projektidega on võimalik liituda igaühel, kes ei karda väljakutseid, pingelist koolitust ja tööd ning soovib teisi aidata. Samas räägib vabatahtliku elust Aafrikas Jana Teppih. Lisa: Fakte aidsist

  2. Ärimehed tahavad riigi raamatupidamise üle võtta / Andrus Karnau

    Index Scriptorium Estoniae

    Karnau, Andrus

    2009-01-01

    Kuuest ettevõttest koosnev kontsortsium (Helmes, Ernst & Young, Oracle, Pricewaterhouse Coopers, Raidla Leijins & Norcous ja SAP Estonia) tahab Eesti riigi senisest palju tõhusamalt toimima panna, luues hiigelfirma, mis oleks ühel ajal riigi raamatupidaja, personalijuht, IT-korraldaja ja vajaliku kauba ostja

  3. Бизнесмены хотят взять на себя госбухгалтерию / Андрус Карнау

    Index Scriptorium Estoniae

    Карнау, Андрус

    2009-01-01

    Kuuest ettevõttest koosnev kontsortsium (Helmes, Ernst & Young, Oracle, Pricewaterhouse Coopers, Raidla Leijins & Norcous ja SAP Estonia) tahab Eesti riigi senisest palju tõhusamalt toimima panna, luues hiigelfirma, mis oleks ühel ajal riigi raamatupidaja, personalijuht, IT-korraldaja ja vajaliku kauba ostja

  4. Seltskond / Annika Haas

    Index Scriptorium Estoniae

    Haas, Annika

    2008-01-01

    Eesti Kunstimuuseumi Kunstisõprade Seltsi eestvõttel tähistati 4. novembril 2008 Kumule Euroopa aasta muuseumi tiitli andmist. Ühel juuresolevatest fotodest president Toomas Hendrik Ilves koos Kumu kunstimuuseumi direktrissi Sirje Helme ja Eesti Kunstimuuseumi Kunstisõprade Seltsi juhatuse esimehe Enn Kunilaga

  5. Wastewater Treatment Anaerobic Digester Foaming Prevention and Control Methods - Literature Review and Survey - Full-Scale Studies (WERF Report INFR1SG10)

    Science.gov (United States)

    This project addresses the issue of anaerobic digester (AD) foaming in different water resource recovery facilities (WRRFs). This two-volume report is a compilation of an AD foaming literature review, a plant survey, and findings from full-scale studies. The literature review hel...

  6. Skoone bastion tekitas aukartust juba oma olemasoluga / Oliver Õunmaa

    Index Scriptorium Estoniae

    Õunmaa, Oliver

    2011-01-01

    Arhitektuuriajaloolane Rein Zobel Skoone bastioni minevikust ja peagi teatriks muunduva endise muldkindlustuse kasutusviisidest läbi aegade. 1948. a. avati ühel bastioni osal Nõukogude armeele kuuluv Madruste Klubi lõbustuspark ja puidust Suveteatri hoone, mis põles 10. juunil 1997. a. maha

  7. Helsingi loomaaia jääskulptuuridest valiti parimad

    Index Scriptorium Estoniae

    2004-01-01

    Soomes Korgeasaaris lõppes jääskulptuurivõistlus. Võitjad. Esikohatöö autorid olid Steve Lester Ameerikast ja Ljudmila Lester Venemaalt. Eestist osalesid ühel võistlusel Lembit Palm ja Jaak Soans ning teisel võistlusel Tiiu Kirsipuu ja Aime Kuulbusch

  8. Thermodynamic properties of CO2 absorption in hydroxyl ammonium ionic liquids at pressures of (100-1600) kPa

    International Nuclear Information System (INIS)

    Kurnia, K.A.; Harris, F.; Wilfred, C.D.; Abdul Mutalib, M.I.; Murugesan, T.

    2009-01-01

    Solubility of CO 2 in six hydroxyl ammonium ionic liquids 2-hydroxyethanaminium acetate [hea], bis(2-hydroxyethyl)ammonium acetate [bheaa], 2-hydroxy-N-(2-hydroxyethyl)-N-methylethanaminium acetate [hhemea], 2-hydroxyethanaminium lactate [hel], bis(2-hydroxyethyl)ammonium lactate [bheal], 2-hydroxy-N-(2-hydroxyethyl)-N-methylethanaminium lactate [hhemel] at temperatures (298.15, 313.15, and 328.16) K and pressures ranging from (100 to 1600) kPa was determined. From the experimental solubility data, the Henry's constant of CO 2 for each hydroxyl ammonium ionic liquids was estimated and reported as a function of temperature. Furthermore, enthalpy and entropy of absorption were obtained from estimated Henry's constant. The results showed that the solubility increase with increasing pressure and decrease with increasing temperature and the solubility of CO 2 in these six hydroxyl ammonium ionic liquids was in sequence: [hea] > [bheaa] > [hel] > [bheal] > [hhemel] > [hhemea].

  9. Shock compression of a recrystallized anorthositic rock from Apollo 15

    Science.gov (United States)

    Ahrens, T. J.; Gibbons, R. V.; O'Keefe, J. D.

    1973-01-01

    Hugoniot measurements on 15,418, a recrystallized and brecciated gabbroic anorthosite, yield a value of the Hugoniot elastic limit (HEL) varying from 45 to 70 kbar as the final shock pressure is varied from 70 to 280 kbar. Above the HEL and to 150 kbar, the pressure-density Hugoniot is closely described by a hydrostatic equation of state constructed from ultrasonic data for single-crystal plagioclase and pyroxene. Above 150 kbar, the Hugoniot states indicate that a series of one or more shock-induced phase changes are occurring in the plagioclase and pyroxene. From Hugoniot data for both the single-crystal minerals and the Frederick diabase, we infer that the shock-induced high-pressure phases in 15,418 probably consists of a 3.71 g/cu cm density, high-pressure structure for plagioclase and a 4.70 g/cu cm perovskite-type structure for pyroxene.

  10. Variability in dynamic properties of tantalum : spall, attenuation and load/unload.

    Energy Technology Data Exchange (ETDEWEB)

    Furnish, Michael David; Reinhart, William Dodd; Trott, Wayne Merle; Vogler, Tracy John; Chhabildas, Lalit Chandra

    2005-07-01

    A suite of impact experiments was conducted to assess spatial and shot-to-shot variability in dynamic properties of tantalum. Samples had a uniform refined {approx}20 micron grain structure with a strong axisymmetric [111] crystallographic texture. Two experiments performed with sapphire windows (stresses of approximately 7 and 12 GPa) clearly showed elastic-plastic loading and slightly hysteretic unloading behavior. An HEL amplitude of 2.8 GPa (corresponding to Y 1.5 GPa) was observed. Free-surface spall experiments showed clear wave attenuation and spallation phenomena. Here, loading stresses were {approx} 12.5 GPa and various ratios of impactor to target thicknesses were used. Spatial and shot-to-shot variability of the spall strength was {+-} 20%, and of the HEL, {+-} 10%. Experiments conducted with smaller diameter flyer plates clearly showed edge effects in the line and point VISAR records, indicating lateral release speeds of roughly 5 km/s.

  11. Expression of Lipid Peroxidation Markers in the Tear Film and Ocular Surface of Patients with Non-Sjogren Syndrome: Potential Biomarkers for Dry Eye Disease.

    Science.gov (United States)

    Choi, Won; Lian, Cui; Ying, Li; Kim, Ga Eon; You, In Cheon; Park, Soo Hyun; Yoon, Kyung Chul

    2016-09-01

    To investigate the expression of lipid peroxidation markers in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease. The concentrations of hexanoyl-lysine (HEL), 4-hydroxy-2-nonenal (HNE), and malondialdehyde (MDA) were measured with enzyme-linked immunosorbent assays in tears obtained from 44 patients with non-Sjogren syndrome dry eye and 33 control subjects. The correlations between the marker levels and the tear film and ocular surface parameters, including tear film break-up time (BUT), Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, corneal sensitivity, conjunctival goblet cell density, and symptom score, were analyzed. The expression of the lipid peroxidation markers HEL, 4-HNE, and MDA in the conjunctiva was evaluated using immunohistochemistry. The concentrations of HEL, 4-HNE, and MDA were 279.84 ± 69.98 nmol/L, 0.02 ± 0.01 μg/mL, and 3.80 ± 1.05 pmol/mg in control subjects and 283.21 ± 89.67 nmol/L (p = 0.97), 0.20 ± 0.03 μg/mL (p dry eye patients. 4-HNE and MDA levels significantly correlated with BUT, Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, conjunctival goblet cell density, and symptom score (p dry eye patients. The expression of late lipid peroxidation markers, 4-HNE and MDA, increases in the tear film and ocular surface of patients with dry eye. The levels correlate with various tear film and ocular surface parameters and may reflect the severity of dry eye disease.

  12. Heart rate and leukocytes after air and ground transportation in artificially ventilated neonates: a prospective observational study.

    Science.gov (United States)

    Grosek, Stefan; Mlakar, Gorazd; Vidmar, Ivan; Ihan, Alojz; Primozic, Janez

    2009-01-01

    To evaluate the effect of interhospital air and ground transportation of artificially ventilated neonates on heart rate and peripheral blood leukocyte counts. Prospective, observational study. Level III multidisciplinary Neonatal and Pediatric Intensive Care Unit. Fifty-eight near-term artificially ventilated transported neonates between May 2006 and April 2007. Day-helicopter, day- and night-ground transportation. Heart rate at retrieval, on admission to the ICU and 1 h later, and peripheral blood leukocyte counts on admission and 1 d later were compared. Fifteen neonates were transported by helicopter during the daytime (D-HEL), 20 by daytime ground and 23 by nighttime ground transportation (D-GROUND, N-GROUND). No differences in delivery mode, birth weight, gestational age, gender, primary diagnoses for transportation, response time and duration of transportation were found between the groups. Similarly, no differences in pH, pCO(2), blood pressure and skin temperature at retrieval and on admission to the ICU were found between the three groups. The mean heart rate at retrieval did not differ significantly, while on arrival in the ICU and 1 h later the D-GROUND group of patients showed a significantly higher mean heart rate compared to the D-HEL and N-GROUND groups. Moreover, leukocyte counts on arrival in the ICU showed significantly higher leukocyte counts in the D-GROUND group of patients compared to the D-HEL group of patients. These results demonstrate that there is an association between daytime ground transportation and higher heart rate and peripheral blood leukocytes.

  13. Shock Wave Response of Iron-based In Situ Metallic Glass Matrix Composites.

    Science.gov (United States)

    Khanolkar, Gauri R; Rauls, Michael B; Kelly, James P; Graeve, Olivia A; Hodge, Andrea M; Eliasson, Veronica

    2016-03-02

    The response of amorphous steels to shock wave compression has been explored for the first time. Further, the effect of partial devitrification on the shock response of bulk metallic glasses is examined by conducting experiments on two iron-based in situ metallic glass matrix composites, containing varying amounts of crystalline precipitates, both with initial composition Fe49.7Cr17.7Mn1.9Mo7.4W1.6B15.2C3.8Si2.4. The samples, designated SAM2X5-600 and SAM2X5-630, are X-ray amorphous and partially crystalline, respectively, due to differences in sintering parameters during sample preparation. Shock response is determined by making velocity measurements using interferometry techniques at the rear free surface of the samples, which have been subjected to impact from a high-velocity projectile launched from a powder gun. Experiments have yielded results indicating a Hugoniot Elastic Limit (HEL) to be 8.58 ± 0.53 GPa for SAM2X5-600 and 11.76 ± 1.26 GPa for SAM2X5-630. The latter HEL result is higher than elastic limits for any BMG reported in the literature thus far. SAM2X5-600 catastrophically loses post-yield strength whereas SAM2X5-630, while showing some strain-softening, retains strength beyond the HEL. The presence of crystallinity within the amorphous matrix is thus seen to significantly aid in strengthening the material as well as preserving material strength beyond yielding.

  14. Strength properties and structure of a submicrocrystalline Al-Mg-Mn alloy under shock compression

    Science.gov (United States)

    Petrova, A. N.; Brodova, I. G.; Razorenov, S. V.

    2017-06-01

    The results of studying the strength of a submicrocrystalline aluminum A5083 alloy (chemical composition was 4.4Mg-0.6Mn-0.11Si-0.23Fe-0.03Cr-0.02Cu-0.06Ti wt % and Al base) under shockwave compression are presented. The submicrocrystalline structure of the alloy was produced in the process of dynamic channel-angular pressing at a strain rate of 104 s-1. The average size of crystallites in the alloy was 180-460 nm. Hugoniot elastic limit σHEL, dynamic yield stress σy, and the spall strength σSP of the submicrocrystalline alloy were determined based on the free-surface velocity profiles of samples during shock compression. It has been established that upon shock compression, the σHEL and σy of the submicrocrystalline alloy are higher than those of the coarse-grained alloy and σsp does not depend on the grain size. The maximum value of σHEL reached for the submicrocrystalline alloy is 0.66 GPa, which is greater than that in the coarse-crystalline alloy by 78%. The dynamic yield stress is σy = 0.31 GPa, which is higher than that of the coarse-crystalline alloy by 63%. The spall strength is σsp = 1.49 GPa. The evolution of the submicrocrystalline structure of the alloy during shock compression was studied. It has been established that a mixed nonequilibrium grain-subgrain structure with a fragment size of about 400 nm is retained after shock compression, and the dislocation density and the hardness of the alloy are increased.

  15. A hybrid Eulerian–Lagrangian numerical scheme for solving prognostic equations in fluid dynamics

    Directory of Open Access Journals (Sweden)

    E. Kaas

    2013-11-01

    Full Text Available A new hybrid Eulerian–Lagrangian numerical scheme (HEL for solving prognostic equations in fluid dynamics is proposed. The basic idea is to use an Eulerian as well as a fully Lagrangian representation of all prognostic variables. The time step in Lagrangian space is obtained as a translation of irregularly spaced Lagrangian parcels along downstream trajectories. Tendencies due to other physical processes than advection are calculated in Eulerian space, interpolated, and added to the Lagrangian parcel values. A directionally biased mixing amongst neighboring Lagrangian parcels is introduced. The rate of mixing is proportional to the local deformation rate of the flow. The time stepping in Eulerian representation is achieved in two steps: first a mass-conserving Eulerian or semi-Lagrangian scheme is used to obtain a provisional forecast. This forecast is then nudged towards target values defined from the irregularly spaced Lagrangian parcel values. The nudging procedure is defined in such a way that mass conservation and shape preservation is ensured in Eulerian space. The HEL scheme has been designed to be accurate, multi-tracer efficient, mass conserving, and shape preserving. In Lagrangian space only physically based mixing takes place; i.e., the problem of artificial numerical mixing is avoided. This property is desirable in atmospheric chemical transport models since spurious numerical mixing can impact chemical concentrations severely. The properties of HEL are here verified in two-dimensional tests. These include deformational passive transport on the sphere, and simulations with a semi-implicit shallow water model including topography.

  16. 78 FR 25939 - Submission for OMB Review; Comment Request

    Science.gov (United States)

    2013-05-03

    ...) is predominate, or designate land on which HEL is predominated to be set aside, diverted, devoted to... erosion. Description of Respondents: Individuals or households; Business or other for-profit; Not-for-profit institutions; Federal Government; State, Local or Tribal Government. Number of Respondents: 259...

  17. Dicty_cDB: Contig-U11964-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available .. 42 0.87 4 ( EK022497 ) 1092955341513 Global-Ocean-Sampling_GS-31-01-01-1... 48 1.1 1 ( EL474594 ) CHUL2538.b1_C12.ab1 CHU(LMS) puz...zle sunflower Hel... 48 1.1 1 ( BJ370153 ) Dictyostelium

  18. Kui Kerry saab USA presidendiks, siis... / Anvar Samost

    Index Scriptorium Estoniae

    Samost, Anvar, 1971-

    2004-01-01

    Autor võrdleb USA presidendi George W. Bushi ja presidendikandidaat John Kerry välispoliitilisi seisukohti ning leiab, et peaaegu kõigis välispoliitika küsimustes on nad ühel meelel ja mõnes küsimuses on Kerry vaated pigem radikaalsemad

  19. Trigon Farming ostis Kaiu LT / Margus Mikomägi

    Index Scriptorium Estoniae

    Mikomägi, Margus, 1956-

    2006-01-01

    Raplamaalt suuruselt neljas põllumajandusühistu Kaiu LT müüdi üldkoosoleku otsusega ühel häälel firmale Trigon Farming. Kaiu LT nõukogu esimees on viimased kolm aastat olnud Riigikogu liige Tiit Tammsaar. Lisa: Trigon Tarming investeerib põllumajandusse

  20. Konstruktionen af en fælles europæisk skriftlighed

    DEFF Research Database (Denmark)

    Holm, Lars

    2007-01-01

    Europarådets "Common European Framework of References for Langauges: Learning, teaching, assessment" (1996,2001) fremstår som en hel central publikation for mange landes uddannelsespolitiske praksis i relation til evaluering af sprog og sprogundervisning. I denne artikel afdækkes det teoretiske o...

  1. Talibani üllatusrünnak president Karzai tapmiseks läks luhta / Heiki Suurkask

    Index Scriptorium Estoniae

    Suurkask, Heiki, 1972-

    2008-01-01

    Talibani võitlejad ründasid Kabulis sõjaväeparaadi, millega tähistati kommunistliku režiimi kukutamist. Kui 20 aastat tagasi olid hilisemad Talibani võitlejad ja praegune president Hamid Karzai ühel poolel, siis alates 2001. aastast on Karzai islamistidega konfliktis

  2. Inessa Josing Flash Artis

    Index Scriptorium Estoniae

    1999-01-01

    'Flash Art'i' 1998. a. nov.-dets. numbris Rosa Martínezi artiklis suvisest Manifesta II näitusest Luxembourg'is on positiivselt mainitud ka Inessa Josingut. Illustratsiooniks toodud seitsmest fotost ühel on I. Josingu aknakujundus 'What Must I Do to be Saved?'

  3. Transportan 10 improves the anticancer activity of cisplatin.

    Science.gov (United States)

    Izabela, Rusiecka; Jarosław, Ruczyński; Magdalena, Alenowicz; Piotr, Rekowski; Ivan, Kocić

    2016-05-01

    The aim of this paper was to examine whether cell-penetrating peptides (CPPs) such as transportan 10 (TP10) or protein transduction domain (PTD4) may improve the anticancer activity of cisplatin (cPt). The complexes of TP10 or PTD4 with cPt were used in the experiments. They were carried out on two non-cancer (HEK293 (human embryonic kidney) and HEL299 (human embryo lung)) and two cancer (HeLa (human cervical cancer) and OS143B (human osteosarcoma 143B)) cell lines. Both complexes were tested (MTT assay) with respect to their anticancer or cytotoxic actions. TAMRA (fluorescent dye)-stained preparations were visualized in a fluorescence microscope. The long-term effect of TP10 + cPt and its components on non-cancer and cancer cell lines was observed in inverted phase contrast microscopy. In the MTT test (cell viability assay), the complex of TP10 + cPt produced a more potent effect on the cancer cell lines (HeLa, OS143B) in comparison to that observed after separate treatment with TP10 or cPt. At the same time, the action of the complex and its components was rather small on non-cancer cell lines. On the other hand, a complex of another CPP with cPt, i.e., PTD4 + cPt, was without a significant effect on the cancer cell line (OS143B). The images of the fluorescent microscopy showed TAMRA-TP10 or TAMRA-TP10 + cPt in the interior of the HeLa cells. In the case of TAMRA-PTD4 or TAMRA-PTD4 + cPt, only the first compound was found inside the cancer cell line. In contrast, none of the tested compounds gained access to the interior of the non-cancer cells (HEK293, HEL299). Long-term incubation with the TP10 + cPt (estimated by inverted phase contrast microscopy) lead to an enhanced action of the complex on cell viability (decrease in the number of cells and change in their morphology) as compared with that produced by each single agent. With regard to the tested CPPs, only TP10 improved the anticancer activity of cisplatin if both compounds were used in the form of a

  4. Karakteriga kodu / Karen Jagodin ; kommenteerinud Enn Rajasaar

    Index Scriptorium Estoniae

    Jagodin, Karen, 1982-

    2009-01-01

    2008. aastal valminud 2-korruseline eramu Mähel. Arhitekt Enn Rajasaar. Sisearhitekt Aet Seire. Välisviimistluses on kombineeritud tumedat tellist ja heledat krohvi. Sisekujundust läbivad värvid punane ja must. Osa mööbliesemeid (raamatukapid, söögitoa laud) valmisid sisearhitekti erilahendusena

  5. Effect of Batch-to-Batch Variability on the Phase Transition of Precipitated Erbium-Doped Alumina Particles

    Science.gov (United States)

    2017-11-01

    and Education through an interagency agreement between the US Department of Energy and ARL. The authors would also like to thank Dr Robert Pavlacka...calcination temperature required to transform the powder to the desired phase, which for HEL applications is α-alumina due to its high mechanical

  6. Baltics to cash in on reality-based TV craze / Jaclyn M. Sindrich

    Index Scriptorium Estoniae

    Sindrich, Jaclyn M.

    2000-01-01

    TV 3 teeb ühel Läänemere laiul meelelahutuslikku dokumentaalsarja "Robinson" suletud keskkonnas viibivate tavaliste inimeste omavaheliste suhete ning hakkamasaamisoskuse näitamiseks, Kanal 2 jälgib tõsielusarjas "112" Nõmme komando päästjate-tuletõrjujate ja parameedikute tööd

  7. The influence of microstructure on the shock and spall behaviour of the magnesium alloy, Elektron 675

    International Nuclear Information System (INIS)

    Hazell, P.J.; Appleby-Thomas, G.J.; Wielewski, E.; Stennett, C.; Siviour, C.

    2012-01-01

    Alloying elements such as aluminium, zinc and rare earth metals allow precipitation hardening of magnesium (Mg). The low densities of such strengthened Mg alloys have led to their adoption as aerospace materials and (more recently) they are being considered as armour materials. Consequently, understanding their response to high strain-rate loading is becoming increasingly important. Here, the plate-impact technique was employed to measure stress evolution in an armour-grade wrought Mg alloy (Elektron 675) under one-dimensional shock loading. The effects of sample orientation and heat treatment were examined. The spall behaviour was interrogated using a heterodyne velocimeter system, with an estimate made of the material’s spall strength and Hugoniot elastic limit (HEL) for both aged and unaged materials. In particular, it is shown that the HEL and spall strength values are higher along the extrusion direction. It is thought that this is caused by striations of relatively small grains that run along the extrusion direction.

  8. v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII

    DEFF Research Database (Denmark)

    Disela, C; Glineur, C; Bugge, T

    1991-01-01

    The v-erbA oncoprotein represents a retrovirus-transduced oncogenic version of the thyroid hormone (T3/T4) receptor c-erbA (type alpha). It contributes to virus-induced erythroleukemia by efficiently arresting differentiation of red cell progenitors and by suppressing transcription of erythrocyte...... of this CAII reporter construct could only be suppressed by very high amounts of v-erbA. Our results suggest that overexpression of v-erbA is required for its function as an oncoprotein....

  9. Acute erythroblastic leukemia presenting as acute undifferentiated leukemia: a report of two cases with ultrastructural features.

    Science.gov (United States)

    Reiffers, J; Bernard, P; Larrue, J; Dachary, D; David, B; Boisseau, M; Broustet, A

    1985-01-01

    This report describes two elderly patients with acute leukemia in which blast cells were undifferentiated with conventional light microscopy (L.M.) and cytochemistry. Blast cells were identified as belonging to the erythroblastic line by their ultrastructural features: glycogen deposits, lipidic vacuoles, cytoplasmic ferritin molecules and rhopheocytotic invagination. Moreover, blast cells were surrounding a central macrophage. Thus, these two patients had acute erythroblastic leukemia which differs from erythroleukemia (M6 of FAB classification) in which blast cells present myeloblastic characteristics.

  10. Dlk1 in normal and abnormal hematopoiesis

    DEFF Research Database (Denmark)

    Sakajiri, S; O'kelly, J; Yin, D

    2005-01-01

    normals. Also, Dlk1 mRNA was elevated in mononuclear, low density bone marrow cells from 11/38 MDS patients, 5/11 AML M6 and 2/4 AML M7 samples. Furthermore, 5/6 erythroleukemia and 2/2 megakaryocytic leukemia cell lines highly expressed Dlk1 mRNA. Levels of Dlk1 mRNA markedly increased during...... (particularly M6, M7), and it appears to be associated with normal development of megakaryocytes and B cells....

  11. Characterization of the env gene and long terminal repeat of molecularly cloned Friend mink cell focus-inducing virus DNA.

    OpenAIRE

    Adachi, A; Sakai, K; Kitamura, N; Nakanishi, S; Niwa, O; Matsuyama, M; Ishimoto, A

    1984-01-01

    The highly oncogenic erythroleukemia-inducing Friend mink cell focus-inducing (MCF) virus was molecularly cloned in phage lambda gtWES.lambda B, and the DNA sequences of the env gene and the long terminal repeat were determined. The nucleotide sequences of Friend MCF virus and Friend spleen focus-forming virus were quite homologous, supporting the hypothesis that Friend spleen focus-forming virus might be generated via Friend MCF virus from an ecotropic Friend virus mainly by some deletions. ...

  12. Photoperiod and growing degree days effect on dry matter partitioning in Jerusalem artichoke

    Science.gov (United States)

    The effect of photoperiod and growing degree days (GDD) on dry matter and dry partitioning in Jerusalem artichoke was investigated during 2008-09 and 2009-10. Three Jerusalem artichoke genotypes (CN-52867, JA-89 and HEL-65) were planted in 15 day-intervals between with thirteen different dates (Sep...

  13. Dicty_cDB: Contig-U15319-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ltivar Ohio43 histone aceytl-transfera... 48 3e-12 5 ( EL478722 ) CHUL7255.b1_N14.ab1 CHU(LMS) puzzle sunflo...wer Hel... 72 3e-12 2 ( EL480423 ) CHUM2410.b1_D03.ab1 CHU(LMS) puzzle sunflower

  14. Nancay "blind" 21 cm line survey of the Canes Venatici group region

    NARCIS (Netherlands)

    Kraan-Korteweg, RC; van Driel, W; Briggs, F; Binggeli, B; Mostefaoui, TI

    A radio spectroscopic driftscan survey in the 21 cm line with the Nancay decimetric radio telescope of 0.08 steradians of sky in the direction of the constellation Canes Venatici covering a heliocentric velocity range of -350 hel <2350 kms(-1) produced 53 spectral features, which was further

  15. Predicting weight status stability and change from fifth grade to eighth grade: the significant role of adolescents' social-emotional well-being.

    Science.gov (United States)

    Chang, Yiting; Gable, Sara

    2013-04-01

    The primary objective of this study was to predict weight status stability and change across the transition to adolescence using parent reports of child and household routines and teacher and child self-reports of social-emotional development. Data were from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K), a nationally representative sample of children who entered kindergarten during 1998-1999 and were followed through eighth grade. At fifth grade, parents reported on child and household routines and the study child and his/her primary classroom teacher reported on the child's social-emotional functioning. At fifth and eighth grade, children were directly weighed and measured at school. Nine mutually-exclusive weight trajectory groups were created to capture stability or change in weight status from fifth to eighth grade: (1) stable obese (ObeSta); (2) obese to overweight (ObePos1); (3) obese to healthy (ObePos2); (4) stable overweight (OverSta); (5) overweight to healthy (OverPos); (6) overweight to obese (OverNeg); (7) stable healthy (HelSta); (8) healthy to overweight (HelNeg1); and (9) healthy to obese (HelNeg2). Except for breakfast consumption at home, school-provided lunches, nighttime sleep duration, household and child routines did not predict stability or change in weight status. Instead, weight status trajectory across the transition to adolescence was significantly predicted by measures of social-emotional functioning at fifth grade. Assessing children's social-emotional well-being in addition to their lifestyle routines during the transition to adolescence is a noteworthy direction for adolescent obesity prevention and intervention. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  16. 108aastase Liviko tooted koguvad tunnustust nii kodus kui välismaal / Tiit Reinart

    Index Scriptorium Estoniae

    Reinart, Tiit, 1964-

    2006-01-01

    Tänavu tunnustati AS-i Liviko tooteid Vana Tallinna Liköör, Üx Vodka ja Vana Tallinn Cream ühel mainekamal rahvusvahelisel konkursil International Wine & Spirit Competition (IWSC), ühtlasi tegeleb ettevõte jätkuvalt tootearenduse ja kvaliteetveinide importimisega. Vt. samas: Maksumärgita alkohol on illegaalne

  17. INVASION OF ROUND GOBY NEOGOBIUS MELANOSTOMUS (PALLAS, 1814 – ECO-THREAT OR ENVIROMENTAL ENRICHMENT?

    Directory of Open Access Journals (Sweden)

    Katarzyna Stepanowska

    2014-10-01

    Full Text Available Round goby Neogobius melanostomus (Pallas, 1814 is a fish species of Ponto-Caspian basin origin. However, since the second part of the 80’s of the last century has observed spreading of this species in European waters, including in Polish waters. In the last two decades, from 1990 when it was first caught of round goby near the fishing port in Hel, takes a massive and rapid spread of this fish throughout the Gulf of Gdańsk, Vistula Lagoon, along the southern Baltic coastal zone and the Pomeranian Bay and also the River Odra estuary. In 2009, first round goby in commercial catches conducted in Lake Dąbie was recorded. In this situation the question is that invasion can be a eco-threat or even enrichment of the environment to the human being?

  18. SATB1 regulates SPARC expression in K562 cell line through binding to a specific sequence in the third intron

    International Nuclear Information System (INIS)

    Li, K.; Cai, R.; Dai, B.B.; Zhang, X.Q.; Wang, H.J.; Ge, S.F.; Xu, W.R.; Lu, J.

    2007-01-01

    Special AT-rich binding protein 1 (SATB1), a cell type-specific nuclear matrix attachment region (MAR) DNA-binding protein, tethers to a specific DNA sequence and regulates gene expression through chromatin remodeling and HDAC (histone deacetylase complex) recruitment. In this study, a SATB1 eukaryotic expression plasmid was transfected into the human erythroleukemia K562 cell line and individual clones that stably over-expressed the SATB1 protein were isolated. Microarray analysis revealed that hundreds of genes were either up- or down-regulated in the SATB1 over-expressing K562 cell lines. One of these was the extra-cellular matrix glycoprotein, SPARC (human secreted protein acidic and rich in cysteine). siRNA knock-down of SATB1 also reduced SPARC expression, which was consistent with elevated SPARC levels in the SATB1 over-expressing cell line. Bioinformatics software Mat-inspector showed that a 17 bp DNA sequence in the third intron of SPARC possessed a high potential for SATB1 binding; a finding confirmed by Chromatin immunoprecipitation (ChIP) with anti-SATB1 antibody. Our results show for the first time that forced-expression of SATB1 in K562 cells triggers SPARC up-regulation by binding to a 17 bp DNA sequence in the third intron

  19. Sequences responsible for the distinctive hemolytic potentials of Friend and Moloney murine leukemia viruses are dispersed but confined to the psi-gag-PR region.

    OpenAIRE

    Richardson, J; Corbin, A; Pozo, F; Orsoni, S; Sitbon, M

    1993-01-01

    Friend and Moloney murine leukemia viruses (F- and M-MuLV) induce distinct diseases in hematopoietic tissues following inoculation of newborn mice of susceptible strains. F-MuLV induces erythroleukemia preceded by severe early hemolytic anemia; M-MuLV induces thymomas and only very mild hemolysis. The major viral determinant of severe early hemolytic anemia residues in the env gene, but sequences located outside this gene can modulate this effect. By means of genetic chimeras of F- and M-MuLV...

  20. Zippo Marx

    Directory of Open Access Journals (Sweden)

    Robin Aaron Bright

    2017-09-01

    Full Text Available Goddesses, like Norse Hel, signify love for women, and between women, because `woman`s seed` is the `seed` of Eve represented by Jesus, who was tortured to death by the Romans as a `dissident` Jewish rabbi nailed to a cross of wood on the hill of Calvary outside the city of Jerusalem in occupied Palestine and left there until he died. Jesus` Resurrection and Ascension to heaven thereafter prefigured that of `woman`s seed`, which is why his mother, the Virgin Mary, approaches to the role of goddess in Christianity, because women who`re loved appear to be worshipped as goddesses by those who don`t love women. So God specifically punishes Eve and Adam for accepting that they`ll be `as gods`, because Eve is Adam`s `goddess`, who he`s to love in order to be redeemed through `woman`s seed`, and the birth of human brainpower to liberate the species from host womb slavery in parasitism, which wants ephemerality for humans in order to keep them as slaves without labor saving technologies conferring freedom.

  1. (HEL MRI) 3D Meta Optics for High Energy Lasers

    Science.gov (United States)

    2016-09-13

    optical communication link using orbital angular momentum multiplexing ." Optics express 24, no. 9 (2016): 9794-9805. 3. Li, Yuan, Wenzhe Li, J. Miller, and...Magnusson, R.; Binun, P.; McCormick, K., "Wavelength Selection and Polarization Multiplexing of Blue Laser Diodes," in Photonics Technology Letters, IEEE...spatial multiplexing can take advantage of a non-Gaussian beam profile. If the components are to be used as out-couplers in bulk lasers , the optics

  2. Measurement and Modeling of High Energy Laser (HEL)-Droplet Interactions

    Science.gov (United States)

    2016-05-11

    water, phytoplankton is the primary particulate that determines optical properties, at lengths of 1 to 200 μm [4]. Chlorophyll and related pigments ...previously. In this series of tests, the final drop sizes show more separation , as the distilled water displays a larger decay rate towards the end of...video and beam profiles, and also for the image analysis from video frames. A separate laboratory computer contained the software necessary to run

  3. A novel heavy domain antibody library with functionally optimized complementarity determining regions.

    Directory of Open Access Journals (Sweden)

    Ole Aalund Mandrup

    Full Text Available Today a number of synthetic antibody libraries of different formats have been created and used for the selection of a large number of recombinant antibodies. One of the determining factors for successful isolation of recombinant antibodies from libraries lies in the quality of the libraries i.e. the number of correctly folded, functional antibodies contained in the library. Here, we describe the construction of a novel, high quality, synthetic single domain antibody library dubbed Predator. The library is based on the HEL4 domain antibody with the addition of recently reported mutations concerning the amino acid composition at positions critical for the folding characteristics and aggregation propensities of domain antibodies. As a unique feature, the CDR3 of the library was designed to mimic the natural human immune response by designating amino acids known to be prevalent in functional antibodies to the diversity in CDR3. CDR randomizations were performed using trinucleotide synthesis to avoid the presence of stop codons. Furthermore a novel cycle free elongation method was used for the conversion of the synthesized single stranded DNA containing the randomized CDRs into double stranded DNA of the library. In addition a modular approach has been adopted for the scaffold in which each CDR region is flanked by unique restrictions sites, allowing easy affinity maturation of selected clones by CDR shuffling. To validate the quality of the library, one round phage display selections were performed on purified antigens and highly complex antigen mixtures such as cultured eukaryotic cells resulting in several specific binders. The further characterization of some of the selected clones, however, indicates a reduction in thermodynamic stability caused by the inclusion the additional mutations to the HEL4 scaffold.

  4. 7 CFR 610.14 - Use of USLE, RUSLE, and WEQ.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Use of USLE, RUSLE, and WEQ. 610.14 Section 610.14..., DEPARTMENT OF AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.14 Use of USLE, RUSLE, and WEQ. (a) All Highly Erodible Land (HEL) determinations are based on the...

  5. lammerooie op suur winterveld; (b) Naspeen

    African Journals Online (AJOL)

    Utilization of monensin in protein-energy licks by lactating ewes on sour winter veld; (b) Postweaning. High (HEL) and low. (LEL) energy protein licks, with and without monensin, were fed to Oohne Merino ewes before and after weaning on Oohne sourveld during the winter. Creep feed and growth rations with and without ...

  6. Reduced endogenous urinary total antioxidant power and its relation of plasma antioxidant activity of superoxide dismutase in individuals with autism spectrum disorder.

    Science.gov (United States)

    Yui, Kunio; Tanuma, Nasoyuki; Yamada, Hiroshi; Kawasaki, Yohei

    2017-08-01

    Individuals with autism spectrum disorders (ASD) have impaired detoxification capacity. Investigating the neurobiological bases of impaired antioxidant capacity is thus a research priority in the pathophysiology of ASD. We measured the urinary levels of hexanoyl-lysine (HEL) which is a new oxidative stress biomarker, total antioxidant power (TAP) and DNA methylation biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG), and the plasma levels of superoxide dismutase (SOD), which is a major antioxidant enzyme. We examined whether the urinary levels of these enzymes and biomarkers may be related to symptoms of social impairment in 20 individuals with ASD (meanage,11.1±5.2years) and 12 age- and gender-matched healthy controls (meanage,14.3±6.2years). Symptoms of social impairment were assessed using the Social Responsiveness Scale (SRS). The dietary TAP of the fruit juice, chocolate, cookies, biscuits, jam and marmalade were significantly higher in the ASD group than in the control group, although the intake of nutrients was not significantly different between the groups. The urinary TAP levels were significantly lower in the ASD group than in the control group. There were no significantly differences in urinary HEL and 8-OHdG levels between the ASD and control groups. The SRS scores were significantly higher in the ASD group than in the control group. Stepwise regression analysis revealed that urinary TAP levels and plasma SOD levels can differences in the biomarkers and the SRS scores between the ASD group and the control group. The endogenous antioxidant capacity may be deficient without altered urinary HEL and 8-OHdG levels in individuals with ASD. The plasma SOD levels may be related to reduced endogenous antioxidant capacity. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  7. JAK2 V617F-dependent upregulation of PU.1 expression in the peripheral blood of myeloproliferative neoplasm patients.

    Directory of Open Access Journals (Sweden)

    Tamotsu Irino

    Full Text Available Myeloproliferative neoplasms (MPN are multiple disease entities characterized by clonal expansion of one or more of the myeloid lineages (i.e. granulocytic, erythroid, megakaryocytic and mast cell. JAK2 mutations, such as the common V617F substitution and the less common exon 12 mutations, are frequently detected in such tumor cells and have been incorporated into the diagnostic criteria published by the World Health Organization since 2008. However, the mechanism by which these mutations contribute to MPN development is poorly understood. We examined gene expression profiles of MPN patients focusing on genes in the JAK-STAT signaling pathway using low-density real-time PCR arrays. We identified the following 2 upregulated genes in MPN patients: a known target of the JAK-STAT axis, SOCS3, and a potentially novel target, SPI1, encoding PU.1. Induction of PU.1 expression by JAK2 V617F in JAK2-wildtype K562 cells and its downregulation by JAK2 siRNA transfection in JAK2 V617F-positive HEL cells supported this possibility. We also found that the ABL1 kinase inhibitor imatinib was very effective in suppressing PU.1 expression in BCR-ABL1-positive K562 cells but not in HEL cells. This suggests that PU.1 expression is regulated by both JAK2 and ABL1. The contribution of the two kinases in driving PU.1 expression was dominant for JAK2 and ABL1 in HEL and K562 cells, respectively. Therefore, PU.1 may be a common transcription factor upregulated in MPN. PU.1 is a transcription factor required for myeloid differentiation and is implicated in erythroid leukemia. Therefore, expression of PU.1 downstream of activated JAK2 may explain why JAK2 mutations are frequently observed in MPN patients.

  8. Shock-induced mechanical response and spall fracture behavior of an extra-low interstitial grade Ti–6Al–4V alloy

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Yu; Wang, Fuchi [School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081 (China); National Key Laboratory of Science and Technology on Materials Under Shock and Impact, Beijing Institute of Technology, Beijing 100081 (China); Tan, Chengwen, E-mail: tanchengwen@126.com [School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081 (China); National Key Laboratory of Science and Technology on Materials Under Shock and Impact, Beijing Institute of Technology, Beijing 100081 (China); Wang, Shuyou [State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing 100081 (China); Yu, Xiaodong [School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081 (China); National Key Laboratory of Science and Technology on Materials Under Shock and Impact, Beijing Institute of Technology, Beijing 100081 (China); Jiang, Jianwei [State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing 100081 (China); Ma, Honglei [China Astronaut Research and Training Center, Beijing 100094 (China); Cai, Hongnian [School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081 (China); National Key Laboratory of Science and Technology on Materials Under Shock and Impact, Beijing Institute of Technology, Beijing 100081 (China)

    2013-08-20

    The mechanical response and spall fracture behavior of an extra-low interstitial (ELI) grade Ti–6Al–4V alloy are systemically investigated during one-dimensional shock loading. The effects of oxygen content on the shock response and dynamic failure characteristic of Ti–6Al–4V are also shown through the comparison of the obtained results with those for commercial Ti–6Al–4V. The measured Hugoniot elastic limit (HEL) of Ti–6Al–4V ELI is lower than that of commercial Ti–6Al–4V. While the fitted shock parameters and the measured Hugoniot in the stress-particle velocity space of Ti–6Al–4V ELI are found to be almost identical to those of commercial Ti–6Al–4V. These results indicate that the oxygen content can significantly affect the HEL of Ti–6Al–4V, but has little or no influence on the shock response of this alloy beyond the HEL. The postshock Ti–6Al–4V ELI does not display shock-induced strengthening during quasistatic and dynamic compression tests. Transmission electron microscopy (TEM) analyses reveal that the lack of high density dislocations or dislocation cells limits the shock-induced strengthening effect, although dislocation multiplication and tangles lead to increased yield strength and strain hardening rate of the reloaded material. Finally, Ti–6Al–4V ELI is demonstrated to spall in a ductile manner, and has similar spall strengths to those of commercial Ti–6Al–4V under different shock loading conditions. The oxygen content exerts no effect on the spall fracture manner of Ti–6Al–4V, although reducing the oxygen content enables this alloy to endure more micro-damages.

  9. Shock-induced mechanical response and spall fracture behavior of an extra-low interstitial grade Ti–6Al–4V alloy

    International Nuclear Information System (INIS)

    Ren, Yu; Wang, Fuchi; Tan, Chengwen; Wang, Shuyou; Yu, Xiaodong; Jiang, Jianwei; Ma, Honglei; Cai, Hongnian

    2013-01-01

    The mechanical response and spall fracture behavior of an extra-low interstitial (ELI) grade Ti–6Al–4V alloy are systemically investigated during one-dimensional shock loading. The effects of oxygen content on the shock response and dynamic failure characteristic of Ti–6Al–4V are also shown through the comparison of the obtained results with those for commercial Ti–6Al–4V. The measured Hugoniot elastic limit (HEL) of Ti–6Al–4V ELI is lower than that of commercial Ti–6Al–4V. While the fitted shock parameters and the measured Hugoniot in the stress-particle velocity space of Ti–6Al–4V ELI are found to be almost identical to those of commercial Ti–6Al–4V. These results indicate that the oxygen content can significantly affect the HEL of Ti–6Al–4V, but has little or no influence on the shock response of this alloy beyond the HEL. The postshock Ti–6Al–4V ELI does not display shock-induced strengthening during quasistatic and dynamic compression tests. Transmission electron microscopy (TEM) analyses reveal that the lack of high density dislocations or dislocation cells limits the shock-induced strengthening effect, although dislocation multiplication and tangles lead to increased yield strength and strain hardening rate of the reloaded material. Finally, Ti–6Al–4V ELI is demonstrated to spall in a ductile manner, and has similar spall strengths to those of commercial Ti–6Al–4V under different shock loading conditions. The oxygen content exerts no effect on the spall fracture manner of Ti–6Al–4V, although reducing the oxygen content enables this alloy to endure more micro-damages

  10. Light illumination intensity dependence of photovoltaic parameter in polymer solar cells with ammonium heptamolybdate as hole extraction layer.

    Science.gov (United States)

    Liu, Zhiyong; Niu, Shengli; Wang, Ning

    2018-01-01

    A low-temperature, solution-processed molybdenum oxide (MoO X ) layer and a facile method for polymer solar cells (PSCs) is developed. The PSCs based on a MoO X layer as the hole extraction layer (HEL) is a significant advance for achieving higher photovoltaic performance, especially under weaker light illumination intensity. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) measurements show that the (NH 4 ) 6 Mo 7 O 24 molecule decomposes and forms the molybdenum oxide (MoO X ) molecule when undergoing thermal annealing treatment. In this study, PSCs with the MoO X layer as the HEL exhibited better photovoltaic performance, especially under weak light illumination intensity (from 100 to 10mWcm -2 ) compared to poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS)-based PSCs. Analysis of the current density-voltage (J-V) characteristics at various light intensities provides information on the different recombination mechanisms in the PSCs with a MoO X and PEDOT:PSS layer as the HEL. That the slopes of the open-circuit voltage (V OC ) versus light illumination intensity plots are close to 1 unity (kT/q) reveals that bimolecular recombination is the dominant and weaker monomolecular recombination mechanism in open-circuit conditions. That the slopes of the short-circuit current density (J SC ) versus light illumination intensity plots are close to 1 reveals that the effective charge carrier transport and collection mechanism of the MoO X /indium tin oxide (ITO) anode is the weaker bimolecular recombination in short-circuit conditions. Our results indicate that MoO X is an alternative candidate for high-performance PSCs, especially under weak light illumination intensity. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Occupational Asthma after Withdrawal from the Occupational Allergen Exposure

    Czech Academy of Sciences Publication Activity Database

    Klusáčková, P.; Pelclová, D.; Lebedová, J.; Marečková, H.; Brabec, Marek

    2006-01-01

    Roč. 44, č. 4 (2006), s. 629-638 ISSN 0019-8366 Source of funding: V - iné verejné zdroje Keywords : occupational asthma * allergen exposure withdrawal Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.911, year: 2006 http://www.jniosh.go.jp/en/indu_hel/pdf/indhealth_44_4_629.pdf

  12. Venemaa ei kavatse Abhaasia iseseisvust tunnustada / Gwynne Dyer ; tõlk. Indrek Veiserik

    Index Scriptorium Estoniae

    Dyer, Gwynne

    2008-01-01

    Autori sõnul on Moskvat sügavalt häirinud viis, kuidas NATO ja EL tükeldavad Serbiat ilma ÜRO loata. Kui Venemaa tunnustaks ühel päeval Abhaasia iseseisvust, eirates Gruusia ja ÜRO Julgeolekunõukogu heakskiitu, tähendaks see, et Venemaa on lõplikult kaotanud usu rahvusvahelisse õigusesse

  13. DIE SAGD - SY ONTSTAAN EN ONTWIKKELING

    African Journals Online (AJOL)

    31 Okt 1977 ... stelling van 'n higiene afdeling het in 'n belang- rike behoefte voorsien. Die pligte van die SAGO het dus op hierdie stadium die ondersoek van soldate, die sanita- sie van kampe, die verpleging van pasiente in militere hospitale en die opleiding van lede be- hels. 'n Hoogtepunt was die opening van die.

  14. Using a Mixed Methods Research Design in a Study Investigating the "Heads of e-Learning" Perspective towards Technology Enhanced Learning

    Science.gov (United States)

    Almpanis, Timos

    2016-01-01

    This paper outlines the research design, methodology and methods employed in research conducted in the context of Higher Education Institutions (HEIs) and focuses on the Heads of e-Learning (HeLs) perspective about Technology Enhanced Learning (TEL) by campus-based UK institutions. This paper aims to expand on the research design and the research…

  15. Optomechanical performance of 3D-printed mirrors with embedded cooling channels and substructures

    Science.gov (United States)

    Mici, Joni; Rothenberg, Bradley; Brisson, Erik; Wicks, Sunny; Stubbs, David M.

    2015-09-01

    Advances in 3D printing technology allow for the manufacture of topologically complex parts not otherwise feasible through conventional manufacturing methods. Maturing metal and ceramic 3D printing technologies are becoming more adept at printing complex shapes, enabling topologically intricate mirror substrates. One application area that can benefit from additive manufacturing is reflective optics used in high energy laser (HEL) systems that require materials with a low coefficient of thermal expansion (CTE), high specific stiffness, and (most importantly) high thermal conductivity to effectively dissipate heat from the optical surface. Currently, the limits of conventional manufacturing dictate the topology of HEL optics to be monolithic structures that rely on passive cooling mechanisms and high reflectivity coatings to withstand laser damage. 3D printing enables the manufacture of embedded cooling channels in metallic mirror substrates to allow for (1) active cooling and (2) tunable structures. This paper describes the engineering and analysis of an actively cooled composite optical structure to demonstrate the potential of 3D printing on the improvement of optomechanical systems.

  16. Cross activity of orthologous WRKY transcription factors in wheat and Arabidopsis

    NARCIS (Netherlands)

    Poietti, S.; Bertini, L.; Ent, S. van der; Leon Reyes, H.A.; Pieterse, C.M.J.; Tucci, M.; Caporale, C.; Caruso, C.

    2011-01-01

    WRKY proteins are transcription factors involved in many plant processes including plant responses to pathogens. Here, the cross activity of TaWRKY78 from the monocot wheat and AtWRKY20 from the dicot Arabidopsis on the cognate promoters of the orthologous PR4-type genes wPR4e and AtHEL of wheat and

  17. Arhitektuurivõistlus "Europan 7"

    Index Scriptorium Estoniae

    2004-01-01

    Rahvusvahelisel Euroopa riikide noorte arhitektide ideevõistlusel "Europan 7" osalesid Eestist Tallinn ja Pärnu kumbki ühel võistlusalal. Pärnu võistlusalale laekus 47 ja Tallinna võistlusalale (Lasnamäe Paevälja asum) 12 tööd. Tallinna võistlusalal parim - Andres Fernandes Atela, Mathieu Andrieu' ja Iman Moshedi töö

  18. Benutting van monensin in proteien-energielekke deur lammerooie ...

    African Journals Online (AJOL)

    17 Jun 1983 ... Utilization of monensin in protein-energy licks by lactating ewes on sour winter veld; (a) Preweaning. The influence of monensin, at a level of 0,36 mg/kg body mass, to ewes in high and low energy licks (HEL and LEL) and in creep feed for lambs was investigated during the 1979 to 1981 winter seasons.

  19. Two cases of acute leukemia developed after therapeutic radiation for malignant tumors

    International Nuclear Information System (INIS)

    Takahashi, Naoki; Matsuo, Kakaru; Yamaguchi, Hiroshi; Tsuno, Sumio; Toyoda, Shigeki

    1978-01-01

    Report was made as to two cases of acute leukemia developed after therapeutic radiation for malignant tumors. Both cases were exposed to atomic-bomb at the places 4 and 3 km far from the center of explosion, and they did not suffer from injuries and acute symptoms due to radiation. Case 1. -A 78 year old man had a mass in a right hypogastric region in April of 1975. In March of 1976, he received laparotomy and was diagnosed as malignant schwannoma. He received radiation therapy with 4,600 R and MFC therapy. In February of 1977, a clinical diagnosis of erythroleukemia was made according to the findings by bone marrow puncture, and he died in March. Postmortem examination revealed that main lesions were malignant schwannoma, its metastases, and leukemia. Case 2. -A 51 year old woman had a finger-tip sized tumor in the left breast in November of 1965, and had a radical operation on the basis of a diagnosis of comedo sarcoma. After that she received 60 Co irradiation with 18,800 R, and she was admitted in December of 1971, because she was suspected of having leukemia. She died in January of 1972. Postmortem examination revealed acute myelocytic leukemia. It is suspected that the onset of erythroleukemia within one year after irradiation would be influenced by MFC therapy in addition to radiotherapy. It was thought that leukemia in Case 2 was influenced by radiotherapy rather than atomic-bomb radioactivity. (Serizawa, K.)

  20. Dicty_cDB: Contig-U15926-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available d CBBG Lottia gigantea 12,15,18h embr... 44 3e-10 3 ( EL474352 ) CHUL2291.b1_F22.ab1 CHU(LMS) puzzle sunflow...58 2e-06 2 ( EL476412 ) CHUL4336.b1_P03.ab1 CHU(LMS) puzzle sunflower Hel... 48 2e-06 2 ( CX707230 ) gmrtDrN

  1. Assessment of Optical Turbulence Profiles Derived From Probabilistic Climatology

    Science.gov (United States)

    2007-03-01

    654.3.1 Transformed Data Results . . . . . . . . . . . . 664.3.2 Untransformed Data Results . . . . . . . . . . . 704.4 Application of ...the needed repower to destroy surface based enemy targets.Courtesy of Boeing Corporation. http://www.boeing.com/news/ fea-ture/aa2004/backgrounders...medium is cornerstone to successful employ-ment of these HELs. 1.3 Introduction to Optical Turbulence Lethal application of directed energy repower

  2. ge&rniA:.

    African Journals Online (AJOL)

    Test

    de hel" vertaal, hulle in die Kanttekeninge sê: ,,O f het graf, en ook. ,,Dat is: het graf, en ,,A nders: het graf ' '). .... Die Afrikaanse vertaling wat, virsover ek sien, orals net die een ver taling ..doderyk gee, verdien hier seker ..... Kan u goedertierenheid vertel word in die graf, u trou in die plek van vertering? Kan u wondermag in ...

  3. Mitu tundi strateegiat ühel lehel! / Martine Vanremoortele ; intervjueerinud Helen Unt

    Index Scriptorium Estoniae

    Vanremoortele, Martine

    2014-01-01

    Intervjuu kommunikatsiooni- ja turundustaustaga belglanna Martine Vanremoortelega visual harvesting-meetodist, mille abil salvestatakse grupi või esineja loodav sisu piltides või joonisel, eesmärgiks parandada inimestevahelist koostööd ja kaasata kõik osalejad mõtteprotsessi

  4. Increasing the Kill Effectiveness of High Energy Laser (HEL) Combat System

    Science.gov (United States)

    2015-03-01

    Quantity (estimated) Corvette Mowj 1 Hamzeh 1 Bayandor 2 Kaman 9 Sina 3 Thondor 10 Tir 12 Peykaap 20 Bavar 25 Torpedo and Zolfaghar 8...Kosar Nasr Harpoon (C-802) UAVs/UCAVs Mohajer Ababil Ra’ad 85 Yassir Kanar Fotros Small Boats Kaman/ SINA Thondor C-14 "China Kajami IPS-16 (FAC/FIAC...59 Table 17. Small Boat Data (after Open Som ce Intelligence Project 2011, 32, 34-36, 40) Small Boat AoA #1 #2 #3 #5 #6 IPS-16 Name Kaman/ SINA

  5. Berliini biennal : teater ühel tänaval : biennaalikunst / Rael Artel

    Index Scriptorium Estoniae

    Artel, Rael, 1980-

    2006-01-01

    IV Berliini kaasaegse kunsti biennaal "Of Mice and Men / Hiirtest ja inimestest" Berliinis Auguststrasse ümbruses kuni 28. V. Kuraatorid Maurizio Cattelan, Massimiliano Gioni ja Ali Subotnick. Väljapanekust, toimumiskohast

  6. Indicadores de tercera generación para cuantificar la sustentabilidad urbana: ¿Avances o estancamiento?

    Directory of Open Access Journals (Sweden)

    Silvia León A

    2013-09-01

    Full Text Available Las intrincadas relaciones que caracterizan el metabolismo de las zonas urbanas precisan ser visualizadas mediante fórmulas simplificadas, capaces de respaldar la toma de decisiones en favor de la sustentabilidad urbana. En el marco teórico ordenador de la Coevolución (Norgaard, 1984, y el cálculo del Análisis de Flujo de Materiales (AFM y de la Huella Ecológica Local (HEL para la Región Metropolitana de Santiago (Chile y la ciudad-región de Bogotá (Colombia, se muestra dicha dupla (AFM y HEL como indicadores de tercera generación - vinculantes, locales, sinérgicos y transversales- que incorporan simultáneamente diversas variables con amplias categorías y dimensiones, además de un alto grado de aporte (el 80% a la cuantificación de la sustentabilidad urbana. El posicionamiento de lo local, por medio de la huella ecológica local, también prevalece en el mejoramiento de los indicadores relativos a la sustentabilidad de una urbe específica, por encima de la estandarización de las metodologías basadas en comparaciones o rankings internacionales.

  7. Analyzing panel acoustic contributions toward the sound field inside the passenger compartment of a full-size automobile.

    Science.gov (United States)

    Wu, Sean F; Moondra, Manmohan; Beniwal, Ravi

    2015-04-01

    The Helmholtz equation least squares (HELS)-based nearfield acoustical holography (NAH) is utilized to analyze panel acoustic contributions toward the acoustic field inside the interior region of an automobile. Specifically, the acoustic power flows from individual panels are reconstructed, and relative contributions to sound pressure level and spectrum at any point of interest are calculated. Results demonstrate that by correlating the acoustic power flows from individual panels to the field acoustic pressure, one can correctly locate the panel allowing the most acoustic energy transmission into the vehicle interior. The panel on which the surface acoustic pressure amplitude is the highest should not be used as indicative of the panel responsible for the sound field in the vehicle passenger compartment. Another significant advantage of this HELS-based NAH is that measurements of the input data only need to be taken once by using a conformal array of microphones in the near field, and ranking of panel acoustic contributions to any field point can be readily performed. The transfer functions between individual panels of any vibrating structure to the acoustic pressure anywhere in space are calculated not measured, thus significantly reducing the time and effort involved in panel acoustic contributions analyses.

  8. From deep water to deep rock: MWD/LWD technology advancing

    Energy Technology Data Exchange (ETDEWEB)

    Jaremko, D.

    2004-01-01

    Measurement-while-drilling (MWD) and logging-while-drilling (LWD) tools that help operators learn about the geological formations they drill while drilling them, are discussed. New MWD and LWD systems are quickly being developed for both offshore and onshore applications, even though both services are relatively expensive. For the offshore market a new seismic-while-drilling LWD tool has just been introduced by Schlumberger. The seismicVision tool acquires and transmits traditional borehole seismic data without interrupting drilling operations. Similarly, Baker-Atlas also introduced a new LWD system for onshore applications that uses advanced downhole sensing technology in a shorter, lighter, reliable instrument package to carry out well logging with accuracy and precision at up to twice the speed of conventional technology. Precision Drilling Inc. also has a new MWD system out, called HEL (hostile environment logging) which is designed to address shortcomings of currently available deepwater MWD systems. The HEL MWD is rated to operate at downhole pressures of up to 30,000 psi and temperatures of up to 180 degrees C. The entire system, including telemetry tools, environmental severity measurement sensors, and other sophisticated measuring tools are housed in one drill collar. photos.

  9. Evolution of elastic precursor and plastic shock wave in copper via molecular dynamics simulations

    International Nuclear Information System (INIS)

    Perriot, Romain; Zhakhovsky, Vasily V; Oleynik, Ivan I; Inogamov, Nail A

    2014-01-01

    Large-scale molecular dynamics (MD) simulations are performed to investigate shock propagation in single crystal copper. It is shown that the P-V plastic Hugoniot is unique regardless of the sample's orientation, its microstructure, or its length. However, the P-V pathway to the final state is not, and depends on many factors. Specifically, it is shown that the pressure in the elastic precursor (the Hugoniot elastic limit (HEL)) decreases as the shock wave propagates in a micron-sized sample. The attenuation of the HEL in sufficiently-long samples is the main source of disagreement between previous MD simulations and experiment: while single crystal experiments showed that the plastic shock speed is orientation-independent, the simulated plastic shock speed was observed to be orientation-dependent in relatively short single-crystal samples. Such orientation dependence gradually disappears for relatively long, micrometer-sized, samples for all three low-index crystallographic directions (100), (110), and (111), and the plastic shock velocities for all three directions approach the one measured in experiment. The MD simulations also demonstrate the existence of subsonic plastic shock waves generated by relatively weak supporting pressures.

  10. A rotorcraft flight/propulsion control integration study

    Science.gov (United States)

    Ruttledge, D. G. C.

    1986-01-01

    An eclectic approach was taken to a study of the integration of digital flight and propulsion controls for helicopters. The basis of the evaluation was the current Gen Hel simulation of the UH-60A Black Hawk helicopter with a model of the GE T700 engine. A list of flight maneuver segments to be used in evaluating the effectiveness of such an integrated control system was composed, based on past experience and an extensive survey of the U.S. Army Air-to-Air Combat Test data. A number of possible features of an integrated system were examined and screened. Those that survived the screening were combined into a design that replaced the T700 fuel control and part of the control system in the UH-60A Gen Hel simulation. This design included portions of an existing pragmatic adaptive fuel control designed by the Chandler-Evans Company and an linear quadratic regulator (LQR) based N(p) governor designed by the GE company, combined with changes in the basic Sikorsky Aircraft designed control system. The integrated system exhibited improved total performance in many areas of the flight envelope.

  11. Shock wave response of ammonium perchlorate single crystals to 6 GPa

    International Nuclear Information System (INIS)

    Yuan, G.; Feng, R.; Gupta, Y. M.; Zimmerman, K.

    2000-01-01

    Plane shock wave experiments were carried out on ammonium perchlorate single crystals compressed along [210] and [001] orientations to peak stresses ranging from 1.2 to 6.2 GPa. Quartz gauge and velocity interferometer techniques were used to measure the elastic and plastic shock wave velocities, and stress and particle velocity histories in the shocked samples. The measured Hugoniot elastic limit (HEL) was 0.48±0.09 GPa. Above the HEL and up to about 6 GPa, the data show a clear two-wave structure, indicating an elastic-plastic response. Time-dependent elastic precursor decay and plastic wave ramping are discernable and orientation dependent in the low stress data. However, the orientation dependence of the peak state response is small. Hence, data for both orientations were summarized into a single isotropic, elastic-plastic-stress relaxation model. Reasonable agreement was obtained between the numerical simulations using this model and the measured wave profiles. At a shock stress of about 6 GPa and for the time duration and crystal orientations examined, we did not observe any features that may be identified as a sustained chemical reaction or a phase transformation. (c) 2000 American Institute of Physics

  12. Hannes Schwarzbauer (1950 - 2012)

    CERN Multimedia

    2012-01-01

    Hannes came to CERN in October 1973 to take up a post with the Computer Operations Group in DD Division, leaving Stuttgart where he had been working up until then.   He quickly settled into the task of computer operations, becoming a very valued member of the team, demonstrating excellent skills in both technical knowledge and human relations. The latter was helped by his excellent command of both English and French, despite having had very little training in this particular domain. He was much appreciated by his colleagues for his calmness and approachability, and was popularly known as “Schwarzy”, a name which followed him throughout his entire CERN career. Following the outsourcing of the computer operations service in 1991, he moved to the User Support Group, where he had already assisted with the Help Desk. He continued developing his computing skills such that he provided PC 2nd level support, successfully deflecting many user queries away from the PC Group. He hel...

  13. Control of heme synthesis during Friend cell differentiation: role of iron and transferrin

    International Nuclear Information System (INIS)

    Laskey, J.D.; Ponka, P.; Schulman, H.M.

    1986-01-01

    In many types of cells the synthesis of σ-aminolevulinic acid (ALA) limits the rate of heme formation. However, results from this laboratory with reticulocytes suggest that the rate of iron uptake from 125 I-transferrin (Tf), rather than ALA synthase activity, limits the rate of heme synthesis in erythroid cells. To determine whether changes occur in iron metabolism and the control of heme synthesis during erythroid cell development Friend erythroleukemia cells induced to erythroid differentiation by dimethylsulfoxide (DMSO) were studied. While added ALA stimulated heme synthesis in uninduced Friend cells (suggesting ALA synthase is limiting) it did not do so in induced cells. Therefore the possibility was investigated that, in induced cells, iron uptake from Tf limits and controls heme synthesis. Several aspects of iron metabolism were investigated using the synthetic iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH). Both induced and uninduced Friend cells take up and utilize Fe for heme synthesis directly from Fe-SIH without the involvement of transferrin and transferrin receptors and to a much greater extent than from saturating levels or 59 Fe-Tf (20 μM). Furthermore, in induced Friend cells 100 μM Fe-SIH stimulated 2- 14 C-glycine incorporation into heme up to 3.6-fold as compared to the incorporation observed with saturating concentrations of Fe-Tf. These results indicate that some step(s) in the pathway of iron from extracellular Tf to protoporphyrin, rather than the activity of ALA synthase, limits and controls the overall rate of heme and possibly hemoglobin synthesis in differentiating Friend erythroleukemia cells

  14. Specific receptors for phorbol diesters on freshly isolated human myeloid and lymphoid leukemia cells: comparable binding characteristics despite different cellular responses.

    Science.gov (United States)

    Goodwin, B J; Moore, J O; Weinberg, J B

    1984-02-01

    Freshly isolated human leukemia cells have been shown in the past to display varying in vitro responses to phorbol diesters, depending on their cell type. Specific receptors for the phorbol diesters have been demonstrated on numerous different cells. This study was designed to characterize the receptors for phorbol diesters on leukemia cells freshly isolated from patients with different kinds of leukemia and to determine if differences in binding characteristics for tritium-labeled phorbol 12,13-dibutyrate (3H-PDBu) accounted for the different cellular responses elicited in vitro by phorbol diesters. Cells from 26 patients with different kinds of leukemia were studied. PDBu or phorbol 12-myristate 13-acetate (PMA) caused cells from patients with acute myeloblastic leukemia (AML), acute promyelocytic (APML), acute myelomonocytic (AMML), acute monocytic (AMoL), acute erythroleukemia (AEL), chronic myelocytic leukemia (CML) in blast crisis (myeloid), acute undifferentiated leukemia (AUL), and hairy cell leukemia (HCL) (n = 15) to adhere to plastic and spread. However, they caused no adherence or spreading and only slight aggregation of cells from patients with acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or CML-blast crisis (lymphoid) (n = 11). All leukemia cells studied, irrespective of cellular type, displayed specific receptors for 3H-PDBu. The time courses for binding by all leukemia types were similar, with peak binding at 5-10 min at 37 degrees C and 120 min at 4 degrees C. The binding affinities were similar for patients with ALL (96 +/- 32 nM, n = 4), CLL (126 +/- 32 nM, n = 6), and acute nonlymphoid leukemia (73 +/- 14 nM, n = 11). Likewise, the numbers of specific binding sites/cell were comparable for the patients with ALL (6.2 +/- 1.3 X 10(5) sites/cell, n = 4), CLL (5.0 +/- 2.0 X 10(5) sites/cell, n = 6), and acute nonlymphoid leukemia (4.4 +/- 1.9 X 10(5) sites/cell, n = 11). Thus, the differing responses to phorbol diesters of

  15. Stress, Predictability, and Oral Fentanyl Self-Administration in Female and Male Rats

    Science.gov (United States)

    1995-03-09

    naloxone. When dissolved in water, fentanyl hydrochloride (Hel) is less bitter-tasting than morphine and it is readily self- administered by rats...and for assessment of the biochemical effects of the stressor. Drugs Fentanyl- hydrochloride (HCI) (NIDA, Baltimore, MD), in a concentration of 50...responses despite lower opioid SA, treatment for men might focus on pharmacologic replacement therapies, such as methadone maintenance programs. The

  16. Feasibility of High Energy Lasers for Interdiction Activities

    Science.gov (United States)

    2017-12-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS FEASIBILITY OF HIGH ENERGY LASERS FOR INTERDICTION ACTIVITIES by Carlos Abel Javier Romero... ENERGY LASERS FOR INTERDICTION ACTIVITIES 5. FUNDING NUMBERS 6. AUTHOR(S) Carlos Abel Javier Romero Chero 7. PERFORMING ORGANIZATION NAME(S) AND...the people or cargo. High Energy Laser (HEL) weapons are an effective way to deliver energy precisely from a relative long range. This thesis studies

  17. Spatial and spectral studies of solar phenomena. Final report, September 1970--August 1971

    International Nuclear Information System (INIS)

    Harvey, K.L.; Kulander, J.L.; Martin, S.F.; Ramsey, H.E.

    1971-09-01

    Work proceeded simultaneously in four different areas of solar research. These were: assembly and testing of the components of a multiple-slit H alpha spectrograph, simultaneous observations of the wings of the H alpha line with a newly modified filter, analysis of H alpha high resolution observations in conjunction with magnetic field observations obtained at Kitt Peak, and theoretical analysis of the D3 line Hel

  18. Sammenhæng mellem fodring og gødningskonsistens hos malkekøer

    DEFF Research Database (Denmark)

    Bligaard, H B; Petersen, M B; Trinderup, M

    Der er mange bud på sammenhæng mellem fodringen og gødningskonsistensen base-ret på praktiske erfaringer. Blandt andet tyder erfaringerne på, at mere græs og et højt proteinindhold kan give en mere tynd gødning, hvorimod fodring med majs- og helsædsensilage kan give en mere fast gødning. Formålet...

  19. A Descoberta da Morte e Mundo Homérico

    Directory of Open Access Journals (Sweden)

    Linneu Camargo Schutzer

    1956-11-01

    Full Text Available A insistência com que os historiadores da filosofia apresentam o mundo grego a partir do naturalismo jônio, com breves referências ao pensamento helênico anterior, leva-nos algumas vêzes a aceitar a ordem natural como a primeira sugestão para um pensamento racional, nela procurando a própria origem da noção de devir.

  20. Implications and Constraints of Fiscal Laws in Contingency Contracting

    Science.gov (United States)

    2013-08-30

    located near the town of Umm Quasar, near the Iraq-Kuwait border . The camp hosted soldiers from multiple branches of the U.S. military and Coalition...MOM -----~~-~-~----­ ThP~~31! VlceCh~JCS (hel ol Sial! hrrrf Ch8l of /lb.-..1 ()pr.ltJarK ctlel ol Sbll. ,. fon:e Calmlndari. M:mB Colli ’ I I

  1. CD4+ virtual memory: Antigen-inexperienced T cells reside in the naïve, regulatory, and memory T cell compartments at similar frequencies, implications for autoimmunity.

    Science.gov (United States)

    Marusina, Alina I; Ono, Yoko; Merleev, Alexander A; Shimoda, Michiko; Ogawa, Hiromi; Wang, Elizabeth A; Kondo, Kayo; Olney, Laura; Luxardi, Guillaume; Miyamura, Yoshinori; Yilma, Tilahun D; Villalobos, Itzel Bustos; Bergstrom, Jennifer W; Kronenberg, Daniel G; Soulika, Athena M; Adamopoulos, Iannis E; Maverakis, Emanual

    2017-02-01

    It is widely accepted that central and effector memory CD4 + T cells originate from naïve T cells after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true the diversity of T cell receptor (TCR) sequences within the naïve T cell compartment should be far greater than that of the memory T cell compartment, which is not supported by TCR sequencing data. Here we demonstrate that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing the same TCR sequence as their younger counterparts. CD4 + T cell repertoire analysis of highly purified T cell populations from naive animals revealed that the HEL-specific clones displayed effector and central "memory" cell surface phenotypes even prior to having encountered their cognate antigen. Furthermore, HEL-inexperienced CD4 + T cells were found to reside within the naïve, regulatory, central memory, and effector memory T cell populations at similar frequencies and the majority of the CD4 + T cells within the regulatory and memory populations were unexpanded. These findings support a new paradigm for CD4 + T cell maturation in which a specific clone can undergo a differentiation process to exhibit a "memory" or regulatory phenotype without having undergone a clonal expansion event. It also demonstrates that a foreign-specific T cell is just as likely to reside within the regulatory T cell compartment as it would the naïve compartment, arguing against the specificity of the regulatory T cell compartment being skewed towards self-reactive T cell clones. Finally, we demonstrate that the same set of foreign and autoreactive CD4 + T cell clones are repetitively generated throughout adulthood. The latter observation argues against T cell-depleting strategies or autologous stem cell transplantation as therapies for autoimmunity-as the immune system has the ability to regenerate pathogenic clones. Published by

  2. Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

    Science.gov (United States)

    2016-05-13

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  3. Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in Mice.

    Science.gov (United States)

    Tang, Chih-Hang Anthony; Chang, Shiun; Hashimoto, Ayumi; Chen, Yi-Ju; Kang, Chang Won; Mato, Anthony R; Del Valle, Juan R; Gabrilovich, Dmitry I; Hu, Chih-Chi Andrew

    2018-06-01

    Chronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B-cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells that developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL. The MD4/Eμ-TCL1 mice had reduced survival, increased myeloid-derived suppressor cells (MDSC), and decreased numbers of T cells. We tested whether sIgM could contribute to the accumulation of MDSCs by crossing μS -/- mice, which could not produce sIgM, with Eμ-TCL1 mice. The μS -/- /Eμ-TCL1 mice survived longer than Eμ-TCL1 mice and developed decreased numbers of MDSCs which were less able to suppress proliferation of T cells. We targeted the synthesis of sIgM by deleting the function of XBP-1s and showed that targeting XBP-1s genetically or pharmacologically could lead to decreased sIgM, accompanied by decreased numbers and reduced functions of MDSCs in MD4/Eμ-TCL1 mice. Additionally, MDSCs from μS -/- mice grafted with Lewis lung carcinoma were inefficient suppressors of T cells, resulting in slower tumor growth. These results demonstrate that sIgM produced by B cells can upregulate the functions of MDSCs in tumor-bearing mice to aggravate cancer progression. In a mouse model of CLL, production of secretory IgM led to more MDSCs, fewer T cells, and shorter survival times for the mice. Thus, secretory IgM may aggravate the progression of this cancer. Cancer Immunol Res; 6(6); 696-710. ©2018 AACR . ©2018 American Association for Cancer Research.

  4. Tarkus, juurikad ja moos tulevad oma kooli aiast / Juhani Püttsepp

    Index Scriptorium Estoniae

    Püttsepp, Juhani, 1964-

    2007-01-01

    Bioloog Juhani Püttseppa ja tema sõbra Ingmar Muusikuse rännakutest mööda Eesti külasid ja alevikke, et enam teada saada kohalikest maakoolidest, külaraamatukogudest, lasteaedadest ja aidata neid püsima jääda. Need on ühel päeval ainsad kohad, mis aitavad meil ära tunda iseend, oma juuri ja seda, millist elu on aastatuhendeid elanud meie esivanemad

  5. TSUNAMI INFORMATION SOURCES PART 3

    Directory of Open Access Journals (Sweden)

    Robert L. Wiegel

    2009-01-01

    Full Text Available This is Part 3 of Tsunami Information Sources published by Robert L. Wiegel, as Technical Report UCB/HEL 2006-3 of the Hydraulic Engineering Laboratory of the Department of Civil & Environmental Engineering of the University of California at Berkeley. Part 3 is published in "SCIENCE OF TSUNAMI HAZARDS" -with the author's permission -so that it can receive wider distribution and use by the Tsunami Scientific Community.

  6. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, Des

    2009-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  7. Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia

    Science.gov (United States)

    Capretto, Lorenzo; Mazzitelli, Stefania; Brognara, Eleonora; Lampronti, Ilaria; Carugo, Dario; Hill, Martyn; Zhang, Xunli; Gambari, Roberto; Nastruzzi, Claudio

    2012-01-01

    This report shows that the DNA-binding drug, mithramycin, can be efficiently encapsulated in polymeric micelles (PM-MTH), based on Pluronic® block copolymers, by a new microfluidic approach. The effect of different production parameters has been investigated for their effect on PM-MTH characteristics. The compared analysis of PM-MTH produced by microfluidic and conventional bulk mixing procedures revealed that microfluidics provides a useful platform for the production of PM-MTH with improved controllability, reproducibility, smaller size, and polydispersity. Finally, an investigation of the effects of PM-MTH, produced by microfluidic and conventional bulk mixing procedures, on the erythroid differentiation of both human erythroleukemia and human erythroid precursor cells is reported. It is demonstrated that PM-MTH exhibited a slightly lower toxicity and more pronounced differentiative activity when compared to the free drug. In addition, PM-MTH were able to upregulate preferentially γ-globin messenger ribonucleic acid production and to increase fetal hemoglobin (HbF) accumulation, the percentage of HbF-containing cells, and their HbF content without stimulating α-globin gene expression, which is responsible for the clinical symptoms of β-thalassemia. These results represent an important first step toward a potential clinical application, since an increase in HbF could alleviate the symptoms underlying β-thalassemia and sickle cell anemia. In conclusion, this report suggests that PM-MTH produced by microfluidic approach warrants further evaluation as a potential therapeutic protocol for β-thalassemia. PMID:22287841

  8. Performance of irrigated green corn cultivars in different plant populations at sowing

    Directory of Open Access Journals (Sweden)

    José C. Soares Neto

    Full Text Available ABSTRACT This study aimed to evaluate the yield of green corn hybrids grown under irrigation in different plant populations at sowing. The assay was carried out in the experimental area located in the city of Arapiraca, Alagoas State, Brazil, from November 2015 to January 2016. A randomized complete block design (RCBD was used, in a 2 x 5 factorial scheme with four replicates. A double- and a single-cross hybrid (AG 1051 and BM 3061, which are suitable for green corn production, were cultivated in five spacings between plants at sowing (15.0, 17.5, 20.0, 22.5 and 25.0 cm. The characteristics photosynthetic rate (PR, ear length with rusk (HEL and without husk (UEL, husked ear weight (HEW, unhusked ear weight (UEW, percentage of marketable ears (%ME and weight of husk (HW were evaluated. The double- and single-cross hybrids AG 1051 and BM 3061 showed green ears with commercial standard. The cultivar BM 3061 showed the best results for most of the characteristics related to the performance of green corn (PR, HEL, UEL, UEW, HEW, %ME. The spacing of 17.5 cm between plants at sowing was the most indicated for irrigated green corn cultivation.

  9. Dynamics of Turbulence Suppression in a Helicon Plasma

    Science.gov (United States)

    Hayes, Tiffany; Gilmore, Mark

    2012-10-01

    Experiments are currently being conducted in the the Helicon-Cathode Device (HelCat) at the University of New Mexico. The goal is to the study in detail the transition from a turbulent to a non-turbulent state in the presence of flow shear. HelCat has intrinsic fluctuations that have been identified as drift-waves. Using simple electrode biasing, it has been found that these fluctuations can be completely suppressed. In some extreme cases, a different instability, possibly the Kelvin-Helmholtz instability, can be excited. Detailed studies are underway in order to understand the characteristics of each mode, and to elucidate the underlying physics that cause the change between an unstable plasma, and an instability-free plasma. Dynamics being observed include changes in flow profiles, both azimuthal and parallel, as well as changes in potential and temperature gradients. Further understanding is being sought using several computer codes developed at EPFL: a linear stability solver (LSS,footnotetextP. Ricci and B.N. Rogers (2009). Phys Plasmas 16, 062303. a one-dimensional PIC code/sheath solver, ODISEE,footnotetextJ. Loizu, P. Ricci, and C. Theiler (2011). Phys Rev E 83, 016406 and a global, 3D Braginski code, GBS.footnotetextRicci, Rogers (2009) A basic overview of results will be presented.

  10. Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 2. The bone marrow distribution in leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Fujimori, K [Kyoto Univ. (Japan). Faculty of Medicine

    1976-04-01

    Distribution of the leukemic marrow was investigated in 42 cases by bone marrow scintigraphy using sup(99m)Tc sulfur colloid in association with clinical findings and ferrokinetics studies in order to clarify hematopoietic function in leukemia. 17 of chronic myelogenous leukemia, 3 of lymphatic leukemia, 2 of monocytic leukemia, 7 of atypical leukemia and one of erythroleukemia. 12 acute myelogenous leukemia were classified into 3 types A, B and C. Type A showed the distribution similar to those obtained with normal controls. Ferrokinetics studies, however, indicated complete absence of erythropoiesis. Type B showed complete lack of sup(99m)Tc activity in usual marrow sites, although ferrokinetics data showed normal erythropoeitic function. Type C showed abnormal concentration of sup(99m)Tc sulfur colloid in the tibiae. 17 chronic myelogenous leukemia showed reduced sup(99m)Tc activity in usual marrow sites and remarkable expanded marrow extending into distal femurs, proximal and distal tibiae and bones of feet. 2 acute lymphotic leukemia patients showed complete absence of sup(99m)Tc activity. The one chronic type showed almost normal distribution. Monocytic leukemia showed decreased marrow distribution in the sternum and vertebrae. Of 6 atypical leukemias one showed almost normal distribution. The others, including a case with hypoplastic luekemia, demonstrated marrow extension similar to that observed in chronic myelogenous leukemia or monocytic leukemia. Erythroleukemia showed increased concentrations of sup(99m)Tc activity in the usual marrow sites and marked marrow expansion throughout all long bones. These results suggest that there is a discrepancy between bone marrow distribution and hematopoietic function in the cases of acute myelogenous leukemia.

  11. Studies on the distribution of hematopoietic bone marrow by bone marrow scintigraphy, 2

    International Nuclear Information System (INIS)

    Fujimori, Katsuhiko

    1976-01-01

    Distribution of the leukemic marrow was investigated in 42 cases by bone marrow scintigraphy using sup(99m)Tc sulfur colloid in association with clinical findings and ferrokinetics studies in order to clarify hematopoietic function in leukemia. 17 of chronic myelogenous leukemia, 3 of lymphatic leukemia, 2 of monocytic leukemia, 7 of atypical leukemia and one of erythroleukemia. 12 acute myelogenous leukemia were classified into 3 types A, B and C. Type A showed the distribution similar to those obtained with normal controls. Ferrokinetics studies, however, indicated complete absence of erythropoiesis. Type B showed complete lack of sup(99m)Tc activity in usual marrow sites, although ferrokinetics data showed normal erythropoeitic function. Type C showed abnormal concentration of sup(99m)Tc sulfur colloid in the tibiae. 17 chronic myelogenous leukemia showed reduced sup(99m)Tc activity in usual marrow sites and remarkable expanded marrow extending into distal femurs, proximal and distal tibiae and bones of feet. 2 acute lymphotic leukemia patients showed complete absence of sup(99m)Tc activity. The one chronic type showed almost normal distribution. Monocytic leukemia showed decreased marrow distribution in the sternum and vertebrae. Of 6 atypical leukemias one showed almost normal distribution. The others, including a case with hypoplastic luekemia, demonstrated marrow extension similar to that observed in chronic myelogenous leukemia or monocytic leukemia. Erythroleukemia showed increased concentrations of sup(99m)Tc activity in the usual marrow sites and marked marrow expansion throughout all long bones. These results suggest that there is a discrepancy between bone marrow distribution and hematopoietic function in the cases of acute myelogenous leukemia. (J.P.N.)

  12. Case Report HeLs malnourished o admit him to the nutrition unit ...

    African Journals Online (AJOL)

    and vocal resonance on the left side, anterior and posterior, with reduced breath ... hint that she may have been the source of the child's HIV infection, before, during or ... child's HIV status? Has either of them been on anti-retroviral therapy?

  13. The HEL Counter-Air Program (HELCAP) Combined Arms Counter-Air Simulation Facility

    Science.gov (United States)

    1992-12-01

    helicopters are en route, ADTOC detects an enemy rotary-wing aircraft on an intercept heading ( frack 211). ADTOC notifies A VTOC that there are no...subsystems (engine, transmission, fuel, hydraulics , electrical, and auxiliary power unit-APU), and the last switch is a checklist switch. Three additional

  14. The UN’s moral responsibility in the ‘spill-over’ of genocide from Rwanda to the Democratic Republic of the Congo

    OpenAIRE

    Kovras, I.

    2011-01-01

    In recent years there has been growing interest in how societies and states should address past wrongdoing. Despite attention to issues of responsibility and moral reparation, however, institutional (moral) responsibility remains relatively unstudied. To this end, the article critically evaluates the UN’s moral responsibility in the world’s deadliest conflict since World War II, namely the conflict in the Democratic Republic of Congo (DRC). It argues that the UN Security Council should be hel...

  15. Firemní nadace v kontextu společenské odpovědnosti firem

    OpenAIRE

    Bjačková, Jana

    2006-01-01

    The thesis deals with Corporate Social Responsibility with an emphasis on corporate foundations. The first, theoretical part of the thesis defines Corporate Social Responsibility, discusses its history and also describes the implementation of the concept in the Czech Republic. The second part of the thesis deals with the legal definition of foundations and the history of foundations in general. A relatively new category of foundations are corporate foundations, which are analysed with the hel...

  16. Eesti Vabariigiga ühevanused memmed kirjutavad presidendile / Rein Sikk

    Index Scriptorium Estoniae

    Sikk, Rein

    2007-01-01

    Neli memme, kes on sündinud 1918. a. veebruaris, Eesti Vabariigiga ühel ajal, kirjutavad ajakirjaniku vahendusel presidendile. Vt. samas: Alide Sepp: ehk saate päästa meie hooldekodu; Meeta Hütt: kaege perra, et elu oles rahulik; Milli Rump: andke pidustuste raha hoopis vaeslastele; Helmi Kõrnas: mõelge alati hästi. Sõna saavad Alide Sepp ja Helmi Kõrnas Pärnust, Meeta Hütt Võrust ja Milli Rump Väike-Maarjast

  17. A cost of long-term memory in Drosophila

    OpenAIRE

    Mery, Frederic; Kawecki, Tadeusz J.

    2005-01-01

    Two distinct forms of consolidated associative memory are known in Drosophila: long-term memory and so-called anesthesia-resistant memory. Long-term memory is more stable, but unlike anesthesia-resistant memory, its formation requires protein synthesis. We show that flies induced to form long-term memory become more susceptible to extreme stress (such as desiccation). In contrast, induction of anesthesia-resistant memory had no detectable effect on desiccation resistance. This finding may hel...

  18. Work–Life Balance: History, Costs, and Budgeting for Balance

    OpenAIRE

    Raja, Siva; Stein, Sharon L.

    2014-01-01

    The concept and difficulties of work–life balance are not unique to surgeons, but professional responsibilities make maintaining a work–life balance difficult. Consequences of being exclusively career focused include burn out, physical, and mental ailments. In addition, physician burn out may hinder optimal patient care and incur significant costs on health care in general. Assessing current uses of time, allocating goals catered to an individual surgeon, and continual self-assessment may hel...

  19. Double Taxation, Tax Credits and the Information Exchange Puzzle

    OpenAIRE

    Wolfgang Eggert

    2003-01-01

    This paper analyzes the choice of taxes and international information exchange by governments in a capital tax competition model. We explain situations where countries can choose tax rates on tax savings income and exchange information about the domestic savings of foreigners, implying that the decentralized equilibrium is efficient. However, we also identify situations with adverse welfare properties in which information exchange is compatible with zero taxes on capital income. The model hel...

  20. The Issues of Effectiveness of Advertisement Communication Process: A Case Study of Lithuania Consumers

    OpenAIRE

    Laimona Sliburyte

    2007-01-01

    The goal of this study was to disclose the core of the advertising research based on the psychological aspects by acquainting with the nature of advertising research and revealing the importance of psychological aspects of advertising during the advertising research. The growing interest in consumer response to advertisement served as an encouragement to make the analysis of psychological aspects of the advertising research, because the information obtained during the advertising research hel...

  1. Knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among urban high-risk groups: findings of a cross-sectional study in Dhaka, Bangladesh

    OpenAIRE

    Wahed, Tasnuva; Kaukab, Sheikh Shah Tanvir; Saha, Nirod Chandra; Khan, Iqbal Ansary; Khanam, Farhana; Chowdhury, Fahima; Saha, Amit; Khan, Ashraful Islam; Siddik, Ashraf Uddin; Cravioto, Alejandro; Qadri, Firdausi; Uddin, Jasim

    2013-01-01

    Background In endemic countries such as Bangladesh, consequences of cholera place an enormous financial and social burden on patients and their families. Cholera vaccines not only provide health benefits to susceptible populations but also have effects on the earning capabilities and financial stability of the family. Community-based research and evaluations are necessary to understand perceptions about and practices of the community relating to cholera and oral cholera vaccines. This may hel...

  2. Characterization and evaluation of boron carbide for plate-impact conditions

    International Nuclear Information System (INIS)

    Holmquist, T. J.; Johnson, G. R.

    2006-01-01

    This article addresses the response of boron carbide (B 4 C) to high-velocity impact. The authors previously characterized this material in 1999, using the Johnson-Holmquist [AIP Conf. Proc. 309, 981 (1994)] (JH-2) model. Since then, there have been additional experimental data presented in the literature that better describe the hydrostatic pressure (including a phase change). In addition, a series of plate-impact experiments (one-dimensional, uniaxial strain) that used configurations that produced either a shock, a shock release, or a shock reshock was performed. These experiments provide material behavior regarding the damage, failed strength, and hydrostat for which previously there has been little or no data. Constitutive model constants were obtained for the Johnson-Holmquist-Beissel [J. Appl. Phys. 94, 1639 (2003)] model using some of these plate-impact experiments. Computations of all the experiments were performed and analyzed to better understand the material response. The analysis provided the following findings: (1) The material fails and loses strength when the Hugoniot elastic limit (HEL) is exceeded. (2) The material has significant strength after failure and gradually increases as the pressure increases. (3) The shear modulus does not degrade when the material fails (as has been postulated), but rather increases. (4) When the material is reloaded from an initial shocked (failed) state, the loading appears to be elastic, indicating the material is not on the yield surface after failure. To provide more insight into the behavior of B 4 C, the strength versus pressure response was compared to that of silicon carbide (SiC). The strength of SiC increases as the pressure increases beyond the HEL, probably due to pressure hardening or strain hardening. It appears that B 4 C does not experience any hardening effects and fails at the HEL. Although the HEL for B 4 C is higher than that of SiC, the hardening ability of SiC produces a similar maximum strength

  3. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  4. Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

  5. Human niche, human behaviour, human nature.

    Science.gov (United States)

    Fuentes, Agustin

    2017-10-06

    The concept of a 'human nature' or 'human natures' retains a central role in theorizing about the human experience. In Homo sapiens it is clear that we have a suite of capacities generated via our evolutionary past, and present, and a flexible capacity to create and sustain particular kinds of cultures and to be shaped by them. Regardless of whether we label these capacities 'human natures' or not, humans occupy a distinctive niche and an evolutionary approach to examining it is critical. At present we are faced with a few different narratives as to exactly what such an evolutionary approach entails. There is a need for a robust and dynamic theoretical toolkit in order to develop a richer, and more nuanced, understanding of the cognitively sophisticated genus Homo and the diverse sorts of niches humans constructed and occupied across the Pleistocene, Holocene, and into the Anthropocene. Here I review current evolutionary approaches to 'human nature', arguing that we benefit from re-framing our investigations via the concept of the human niche and in the context of the extended evolutionary synthesis (EES). While not a replacement of standard evolutionary approaches, this is an expansion and enhancement of our toolkit. I offer brief examples from human evolution in support of these assertions.

  6. Multiple post-transcriptional regulatory mechanisms in ferritin gene expression

    International Nuclear Information System (INIS)

    Mattia, E.; Den Blaauwen, J.; Van Renswoude, J.; Ashwell, G.

    1989-01-01

    The authors have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. They show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemin-induced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant. They conclude that iron-induced ferritin biosynthesis is governed by multiple post-transcriptional regulatory mechanisms. They propose that exposure of cells to iron leads to stabilization of ferritin mRNAs, in addition to activation and translation of stored H-and L-subunit mRNAs

  7. Functional interrelationship between TFII-I and E2F transcription factors at specific cell cycle gene loci.

    Science.gov (United States)

    Shen, Yong; Nar, Rukiye; Fan, Alex X; Aryan, Mahmoud; Hossain, Mir A; Gurumurthy, Aishwarya; Wassel, Paul C; Tang, Ming; Lu, Jianrong; Strouboulis, John; Bungert, Jörg

    2018-01-01

    Transcription factor TFII-I is a multifunctional protein implicated in the regulation of cell cycle and stress-response genes. Previous studies have shown that a subset of TFII-I associated genomic sites contained DNA-binding motifs for E2F family transcription factors. We analyzed the co-association of TFII-I and E2Fs in more detail using bioinformatics, chromatin immunoprecipitation, and co-immunoprecipitation experiments. The data show that TFII-I interacts with E2F transcription factors. Furthermore, TFII-I, E2F4, and E2F6 interact with DNA-regulatory elements of several genes implicated in the regulation of the cell cycle, including DNMT1, HDAC1, CDKN1C, and CDC27. Inhibition of TFII-I expression led to a decrease in gene expression and in the association of E2F4 and E2F6 with these gene loci in human erythroleukemia K562 cells. Finally, TFII-I deficiency reduced the proliferation of K562 cells and increased the sensitivity toward doxorubicin toxicity. The results uncover novel interactions between TFII-I and E2Fs and suggest that TFII-I mediates E2F function at specific cell cycle genes. © 2017 Wiley Periodicals, Inc.

  8. Mesua beccariana (Clusiaceae, A Source of Potential Anti-cancer Lead Compounds in Drug Discovery

    Directory of Open Access Journals (Sweden)

    Soek Sin Teh

    2012-09-01

    Full Text Available An investigation on biologically active secondary metabolites from the stem bark of Mesua beccariana was carried out. A new cyclodione, mesuadione (1, along with several known constituents which are beccamarin (2, 2,5-dihydroxy-1,3,4-trimethoxy anthraquinone (3, 4-methoxy-1,3,5-trihydroxyanthraquinone (4, betulinic acid (5 and stigmasterol (6 were obtained from this ongoing research. Structures of these compounds were elucidated by extensive spectroscopic methods, including 1D and 2D-NMR, GC-MS, IR and UV techniques. Preliminary tests of the in vitro cytotoxic activities of all the isolated metabolites against a panel of human cancer cell lines Raji (lymphoma, SNU-1 (gastric carcinoma, K562 (erythroleukemia cells, LS-174T (colorectal adenocarcinoma, HeLa (cervical cells, SK-MEL-28 (malignant melanoma cells, NCI-H23 (lung adenocarcinoma, IMR-32 (neuroblastoma and Hep-G2 (hepatocellular liver carcinoma were carried out using an MTT assay. Mesuadione (1, beccamarin (2, betulinic acid (5 and stigmasterol (6 displayed strong inhibition of Raji cell proliferation, while the proliferation rate of SK-MEL-28 and HeLa were strongly inhibited by stigmasterol (6 and beccamarin (2, indicating these secondary metabolites could be anti-cancer lead compounds in drug discovery.

  9. INTERVIEW WITH MS. TEIA GAVRILESCU, PRESIDENT OF VIITORPLUS ASSOCIATION

    OpenAIRE

    Cătălin Luca

    2012-01-01

    The interview presents the social economy activities carried out by the Atelierul de pânză* and Recicleta** projects, two initiatives implemented by ViitorPlus Association. Issues such as heavy traffic and pollution or the low level of waste management are what determined the creation of the two projects which focus on sustainable development, as well as on the professional integration of people with disabilities. Ms. Teia Gavrilescu believes that social economy activities in Romania are hel...

  10. Smoothing dynamic positron emission tomography time courses using functional principal components

    OpenAIRE

    Jiang, Ci-Ren; Aston, John A. D.; Wang, Jane-Ling

    2009-01-01

    A functional smoothing approach to the analysis of PET time course data is presented. By borrowing information across space and accounting for this pooling through the use of a non-parametric covariate adjustment, it is possible to smooth the PET time course data thus reducing the noise. A new model for functional data analysis, the Multiplicative Nonparametric Random Effects Model, is introduced to more accurately account for the variation in the data. A locally adaptive bandwidth choice hel...

  11. Effectiveness of CRM in HAAGA-HELIA

    OpenAIRE

    Hirvonen, Hanna-Reetta; Ify, Kingsley John

    2011-01-01

    This was a project organized and supervised by HAAGA-HELIA University of Applied Sciences to enhance the international students’ employment rate through work pair model (an international student and Finnish student working together), and the project was done by two students from different majors. The thesis task was to revive, create and strengthen the use of customer relationship management (CRM) in HAAGA-HELIA. The main aim of the project was to examine the effectiveness of CRM in HAAGA-HEL...

  12. Simulation of a Diode Pumped Alkali Laser; a Three Level Numerical Approach

    Science.gov (United States)

    2010-03-01

    APPROACH THESIS Presented to the Faculty Department of Engineering Physics Graduate School of Engineering and Management Air Force Institute of...1 26.24 * 10-9 H*Lewis Hz*L; A32@85D = 0; A32@87D = 0; III. Parameters Printed by Mathematica for Students 65 III. Parameters A. Enviromental ...Institute of Technology Graduate School of Engineering and Management (AFIT/EN) 2950 Hobson Way WPAFB OH 45433-7765 AFIT/GAP/ENP/10-M06 HEL-JTO 901

  13. Effects of Naloxone on Stress and Performance

    Science.gov (United States)

    1987-11-10

    sixth honey sveep boaGt bu::::hel chalk cloci-: pri lll:e juicy unfold motor duke con !’ide scorn foWld route cliff socf:et moou locket syrup four...duchecs jostle coerce vcni~on vigil impetus resound tonic hyciene elude duplex diverse vital z.ellith poem gristle shre\\ld cough crct1.rny eagle...l:eener closed do cile profess IDllrine tutor gopher ethics chemist entice instep lyrical cured flourish scope mildew porter sleigh initial clique

  14. Poema: Constantino Cavafi [Parte I

    Directory of Open Access Journals (Sweden)

    Fernando Arbelaéz

    1967-11-01

    Full Text Available En 1863 nació en Alejandría Constantino Cavafi y en la misma ciudad muerta - la moderna Alejandría- murió en 1933. La vida de este singular poeta helénico, alternó entre su trabajo de poeta y su cotidiano oficio en el tráfico bursátil del puerto, haciendo homenaje a su tradición, como que era descendiente de una familia de comerciantes venida de Constantinopla.

  15. Preemia maitseb paremini targa laitusest ja lolli kiitusest / Ilona Martson

    Index Scriptorium Estoniae

    Martson, Ilona, 1970-

    2000-01-01

    Lisa: Kirjanduspreemiad 2000. Proosa: Jaan Kaplinski, romaan "Silm" (Looming, 1999, 1-3). Mari Saat, romaan "Sinikõrguste tuultes..." (Looming, 1999, 10-11). Luulepreemia jäi välja andmata. Lastekirjandus: Ellen Niit, "Ühel viivul vikervalgel". Esseistika: Mihkel Mutt, artiklitekogu "Muti tabloid". Näitekirjandus:¡ Jaan Undusk, "Goodbye, Vienna (Gertrud)" (Vikerkaar, 1999, 8/9). Tõlked: Paul-Eerik Rummo, T. S. Elioti "Ahermaa ja teisi luuletusi" eestindus; venekeelse "Eesti luule antoloogia" tegijad Elviira Mihhailova ja Svetlan Semenenko

  16. Henri Fayol’un Yönetim Düşüncesi Üzerine Notlar(Notes on Managerial Thought of Henry Fayol)

    OpenAIRE

    Ramazan ŞENGÜL

    2007-01-01

    Henri Fayol, developed a managerial approach which is a perfect guide for both private and public sectors through focusing systematically upon managerial process. A major advantage of Fayol in creating a general managerial doctrine was his pratician side. His managerial thought which was developed in the early 20th century lasted up to our times. The distinguished characteristic of Fayol’s thought was studying the administrative reality through separating it into its functions, in that it hel...

  17. Markkinointisuunnitelma Carean Helmi -kahvilalle

    OpenAIRE

    Pöyhönen, Terhi

    2013-01-01

    Tämän opinnäytetyön tarkoituksena oli tuottaa Helmi Cafelle markkinointisuunnitelma, jota se voi hyödyntää markkinoinnissaan. Tavoitteena oli tuoda esiin seikkoja, joiden avulla Helmi Cafe saa kasvatettua tunnettuuttaan ja tuotua toimintaideologiaansa ihmisten tietoisuuteen. Työn tavoitteena oli myös kehittää kahvilalle keinoja markkinoida palvelujaan tehokkaammin. Työ toteutettiin kirjoituspöytätyyppisenä tutkimuksena, jossa tutustuttiin markkinoinnin teorioihin ja sovellettiin niitä Hel...

  18. Dietary lactoferrin alleviates age-related lacrimal gland dysfunction in mice.

    Directory of Open Access Journals (Sweden)

    Motoko Kawashima

    Full Text Available BACKGROUND: Decrease in lacrimal gland secretory function is related to age-induced dry eye disease. Lactoferrin, the main glycoprotein component of tears, has multiple functions, including anti-inflammatory effects and the promotion of cell growth. We investigated how oral administration of lactoferrin affects age-related lacrimal dysfunction. METHODS AND FINDINGS: Twelve-month-old male C57BL/6Cr Slc mice were randomly divided into a control fed group and an oral lactoferrin treatment group. Tear function was measured at a 6-month time-point. After euthanasia, the lacrimal glands were subjected to histological examination with 8-hydroxy-2'-deoxyguanosine (8-OHdG antibodies, and serum concentrations of 8-OHdG and hexanoyl-lysine adduct (HEL were evaluated. Additionally, monocyte chemotactic protein-1(MCP-1 and tumor necrosis factor-α (TNF-α gene expression levels were determined by real-time PCR. The volume of tear secretion was significantly larger in the treated group than in the control. Lactoferrin administration reduced inflammatory cell infiltration and the MCP-1 and TNF-α expression levels. Serum concentrations of 8-OHdG and HEL in the lactoferrin group were lower than those in the control group and were associated with attenuated 8-OHdG immunostaining of the lacrimal glands. CONCLUSION: Oral lactoferrin administration preserves lacrimal gland function in aged mice by attenuating oxidative damage and suppressing subsequent gland inflammation.

  19. Prevalence of Zoonotic Intestinal Helminths of Canids in Mog­han Plain, Northwestern Iran

    Directory of Open Access Journals (Sweden)

    M Zare-Bidaki

    2010-06-01

    Full Text Available Background: The present study was aimed to elucidate the status of intestinal hel­minth infec­tions in canids of Moghan Plain, northwestern Iran.Methods: Eighty-five intestine samples from dead or shot wild canids, 59 fecal samples from sheepdogs and 5 from red foxes were collected from 2006 to 2008 and examined in Parasitology department of Pasteur Institute of Iran.Results: Generally, adult worms, larvae, and eggs of 13 species of various parasitic hel­minths were recovered. Necropsy examinations showed that 96.47% animals harbored at least one helminth species. The prevalence of different species in necropsy were Mesoces­toides sp. 84.7%, Rictolaria spp. 55.3%, Macranthorhynchus hirudinaceus 45.9%, Toxocara canis 43.5%, Toxas­caris spp. 35.3%, Joyeuxiella sp. 34.1%; hook­worms; 22.4%, Taenia spp. 11.8%, Alaria spp. 2.4% and Dipylidium caninum 1.2%. Be­sides, eggs belonging to 10 species of parasitic helminths were identified in 46 fecal sam­ples and generally, 30.9% of samples harbored eggs of at least one helminth species.Conclusion: The high prevalence of various helminth infections among canids in Mog­han plain and contamination of environment by helminths eggs may increase the risk of infection for native peo­ple.

  20. Using rule-based machine learning for candidate disease gene prioritization and sample classification of cancer gene expression data.

    Science.gov (United States)

    Glaab, Enrico; Bacardit, Jaume; Garibaldi, Jonathan M; Krasnogor, Natalio

    2012-01-01

    Microarray data analysis has been shown to provide an effective tool for studying cancer and genetic diseases. Although classical machine learning techniques have successfully been applied to find informative genes and to predict class labels for new samples, common restrictions of microarray analysis such as small sample sizes, a large attribute space and high noise levels still limit its scientific and clinical applications. Increasing the interpretability of prediction models while retaining a high accuracy would help to exploit the information content in microarray data more effectively. For this purpose, we evaluate our rule-based evolutionary machine learning systems, BioHEL and GAssist, on three public microarray cancer datasets, obtaining simple rule-based models for sample classification. A comparison with other benchmark microarray sample classifiers based on three diverse feature selection algorithms suggests that these evolutionary learning techniques can compete with state-of-the-art methods like support vector machines. The obtained models reach accuracies above 90% in two-level external cross-validation, with the added value of facilitating interpretation by using only combinations of simple if-then-else rules. As a further benefit, a literature mining analysis reveals that prioritizations of informative genes extracted from BioHEL's classification rule sets can outperform gene rankings obtained from a conventional ensemble feature selection in terms of the pointwise mutual information between relevant disease terms and the standardized names of top-ranked genes.

  1. The light cycle controls the hatching rhythm in Bombyx mori via negative feedback loop of the circadian oscillator.

    Science.gov (United States)

    Tao, Hui; Li, Xue; Qiu, Jian-Feng; Liu, Heng-Jiang; Zhang, Da-Yan; Chu, Feng; Sima, Yanghu; Xu, Shi-Qing

    2017-10-01

    Hatching behavior is a key target in silkworm (Bombyx mori) rearing, especially for the control of Lepidoptera pests. According to previous research, hatching rhythms appear to be controlled by a clock mechanism that restricts or "gates" hatching to a particular time. However, the underlying mechanism remains elusive. Under 12-h light:12-h dark photoperiod (LD) conditions, the transcriptional levels of the chitinase5 (Cht5) and hatching enzyme-like (Hel) genes, as well as the enzymatic activities of their gene products, oscillated in time with ambient light cycles, as did the transcriptional levels of the cryptochrome 1, cryptochrome 2, period (per), and timeless genes, which are key components of the negative feedback loop of the circadian rhythm. These changes were related to the expression profile of the ecdysteroid receptor gene and the hatching behavior of B. mori eggs. However, under continuous light or dark conditions, the hatching behavior, the expression levels of Cht5 and Hel, as well as the enzymatic activities of their gene products, were not synchronized unlike under LD conditions. In addition, immunohistochemistry experiments showed that light promoted the translocation of PER from the cytoplasm to the nucleus. In conclusion, LD cycles regulate the hatching rhythm of B. mori via negative feedback loop of the circadian oscillator. © 2017 Wiley Periodicals, Inc.

  2. RY Geminorum: an Algol binary with moderate circumstellar emission

    International Nuclear Information System (INIS)

    Hall, D.S.; Eaton, J.A.; Wilson, J.W.; Stuhlinger, T.

    1982-01-01

    RY Gem was observed extensively on the UBV system at two observatories over a period of 13 years. One new time of minimum, JD (Hel.) 2,444,215.490+-0.001 is derived, and a revised ephemeris for epochs since 1950: JD (Hel.)=2,439,732.6328+9sup(d).300567n is presented. Analyses carried out for both the Russell model and the Roche model give consistent values for the geometrical elements of the system: rsub(h)=r 1 =0.093+-0.001, rsub(c)=r 2 =0.2285+-0.0008, i=83 deg.5+-0 deg.2. For any reasonable value of the mass of the hotter component, the system consists of an early A-type star only slightly (Osup(m).5) above the main sequence and a cooler component having the surface temperature and gravity of a K1,3-K4,5 star. The most likely absolute dimensions of the components are M 1 =2.0+-03Msub(sun), R 1 =2.3+-0.1Rsub(sun) and M 2 =0.31+-0.06Msub(sun), R 2 =5.6+-0.2Rsub(sun). The effects of ring emission, which were removed from the observations before they were analyzed, seem to be typical of circumstellar emission in many other long-period Algol systems. (author)

  3. A parametric study of laser spot size and coverage on the laser shock peening induced residual stress in thin aluminium samples

    Directory of Open Access Journals (Sweden)

    M. Sticchi

    2015-07-01

    Full Text Available Laser Shock Peening is a fatigue enhancement treatment using laser energy to induce compressive Residual Stresses (RS in the outer layers of metallic components. This work describes the variations of introduced RS-field with peen size and coverage for thin metal samples treated with under-water-LSP. The specimens under investigation were of aluminium alloy AA2024-T351, AA2139-T3, AA7050-T76 and AA7075-T6, with thickness 1.9 mm. The RS were measured by using Hole Drilling with Electronic Speckle Pattern Interferometry and X-ray Diffraction. Of particular interest are the effects of the above mentioned parameters on the zero-depth value, which gives indication of the amount of RS through the thickness, and on the value of the surface compressive stresses, which indicates the magnitude of induced stresses. A 2D-axisymmetrical Finite Element model was created for a preliminary estimation of the stress field trend. From experimental results, correlated with numerical and analytical analysis, the following conclusions can be drawn: increasing the spot size the zero-depth value increases with no significant change of the maximum compressive stress; the increase of coverage leads to significant increase of the compressive stress; thin samples of Al-alloy with low Hugoniot Elastic Limit (HEL reveal deeper compression field than alloy with higher HEL value.

  4. Bussijuhtide streigi ärahoidmiseks on täna jäänud viimane võimalus / Ingvar Bärenklau, Hindrek Riikoja, Eno-Gerrit Link

    Index Scriptorium Estoniae

    Bärenklau, Ingvar, 1967-

    2007-01-01

    Ilmunud ka: Postimees : na russkom jazõke, 11. dets. 2007, lk. 6. Postimees : na russkom jazõke lüh. Transpordi ametiühingu ja autoettevõtete liidu delegatsioonid annavad hinnangu riikliku lepitaja ettepanekule palgatüli lahendamiseks, mis on viimane võimalus üldstreigi ärahoidmiseks. Lisa: Võimaliku streigi ajakava; Kuidas elab Tartu streigipäevadel?; Streigid ja streigiähvardused. Vt. samas intervjuud bussijuht Leo Sillastega: 6000-kroonist kuupalka peetakse kodus valejutuks; Pärnu bussijuhid on streigi osas ühel meelel

  5. Microstructural Effects on the Spall Properties of ECAE-Processed AZ31B Magnesium Alloy

    Science.gov (United States)

    2016-10-01

    stresses using 51 mm and 105 mm bore gas guns . The Hugoniot Elastic Limit (HEL) was measured to be approximately 181 ± 3 MPa. The spall strengths...MD 21218, USA b Institute of Shock Physics, Imperial College London, London SW7 2AZ, UK c U.S. Army Research Laboratory, Aberdeen Proving Ground, MD...21005, USA d Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA A R T I C L E I N F O Article history: Received

  6. Dicty_cDB: Contig-U15509-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available UM1404.b1_G16.ab1 CHU(LMS) puzzle sunflower Hel... 46 3.5 1 ( EL468759 ) CHTS7396.b1_H01.ab1 CHT(LMS) Jerusa...69.b1_I21.ab1 CHU(XYZ) puzzle sunflower Heli... 46 3.5 1 ( EL512621 ) CHTY392.b1_O01.ab1 CHT(XYZ) Jerusalem ... CHWX417.b1_A09.ab1 CHW(XYZ) silverleaf sunflower ... 46 3.5 1 ( EL513701 ) CHUY4

  7. Experimental investigation of coaxial-gun-formed plasmas injected into a background transverse magnetic field or plasma

    OpenAIRE

    Zhang, Yue; Fisher, Dustin M.; Gilmore, Mark; Hsu, Scott C.; Lynn, Alan G.

    2017-01-01

    Injection of coaxial-gun-formed magnetized plasmas into a background transverse vacuum magnetic field or into a background magnetized plasma has been studied in the helicon-cathode (HelCat) linear plasma device at the University of New Mexico [M. Gilmore et al., J. Plasma Phys.81, 345810104 (2015)]. Magnetized plasma jet launched into a background transverse magnetic field shows emergent kink stabilization of the jet due to the formation of a sheared flow in the jet above the kink-stabilizati...

  8. SACRED ARCHITECTURE ORIENTATION ACROSS THE MEDITERRANEAN: A COMPARATIVE STATISTICAL ANALYSIS

    OpenAIRE

    García, A. César González; Belmonte, Juan Antonio

    2014-01-01

    The idea of temporality and how this concept is introduced in the ritual domain could be investigated in past cultures through measurements of the orientation of cultic build-ings, provided that such orientations are linked with particular astronomical events. Hel-lenic societies, among those of the Mediterranean Iron Age, had a need to regulate time through a calendar. The orientation of Hellenic temples in present day Greece and the South of Italy have recently been shown to be somewhat dis...

  9. Dual Functions of the C5a Receptor as a Connector for the K562 Erythroblast-Like Cell-THP-1 Macrophage-Like Cell Island and as a Sensor for the Differentiation of the K562 Erythroblast-Like Cell during Haemin-Induced Erythropoiesis

    Directory of Open Access Journals (Sweden)

    Hiroshi Nishiura

    2012-01-01

    Full Text Available The transcriptional nuclear factor binding to the Y box of human leukocyte antigen genes (NF-Y for the C5a receptor (C5aR gene is active in erythroblasts. However, the roles of the C5aR in erythropoiesis are unclear. We have previously demonstrated that apoptotic cell-derived ribosomal protein S19 (RP S19 oligomers exhibit extraribosomal functions in promoting monocyte chemotaxis and proapoptosis via the C5aR without receptor internalisation. In contrast to the extraribosomal functions of the RP S19, a proapoptotic signal in pro-EBs, which is caused by mutations in the RP S19 gene, is associated with the inherited erythroblastopenia, Diamond-Blackfan anaemia. In this study, we detected C5aR expression and RP S19 oligomer generation in human erythroleukemia K562 cells during haemin-induced erythropoiesis. Under monocell culture conditions, the differentiation into K562 erythrocyte-like cells was enhanced following the overexpression of Wild-type RP S19. Conversely, the differentiation was repressed following the overexpression of mutant RP S19. An RP S19 oligomer inhibitor and a C5aR inhibitor blocked the association of the K562 basophilic EB-like cells and the THP-1 macrophage-like cells under coculture conditions. When bound to RP S19 oligomers, the C5aR may exhibit dual functions as a connector for the EB-macrophage island and as a sensor for EB differentiation in the bone marrow.

  10. Movement coordination in applied human-human and human-robot interaction

    DEFF Research Database (Denmark)

    Schubö, Anna; Vesper, Cordula; Wiesbeck, Mathey

    2007-01-01

    and describing human-human interaction in terms of goal-oriented movement coordination is considered an important and necessary step for designing and describing human-robot interaction. In the present scenario, trajectories of hand and finger movements were recorded while two human participants performed......The present paper describes a scenario for examining mechanisms of movement coordination in humans and robots. It is assumed that coordination can best be achieved when behavioral rules that shape movement execution in humans are also considered for human-robot interaction. Investigating...... coordination were affected. Implications for human-robot interaction are discussed....

  11. Characterization of HelD, an interacting partner of RNA polymerase from Bacillus subtilis

    Czech Academy of Sciences Publication Activity Database

    Wiedermannova, J.; Sudzinova, Z.; Koval, T.; Rabatinova, A.; Sanderova, H.; Ramaniuk, O.; Rittich, S.; Dohnálek, Jan; Fu, Z.; Halada, P.; Lewis, P.; Krasny, L.

    2014-01-01

    Roč. 42, č. 8 (2014), s. 5155-5163 ISSN 0305-1048 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA ČR GAP302/11/0855 Institutional support: RVO:86652036 Keywords : RICHIA-COLI * BACTERIAL HOMOLOG * DELTA-SUBUNIT Subject RIV: CE - Biochemistry Impact factor: 9.112, year: 2014

  12. Design and synthesis of novel C14-urea-tetrandrine derivatives with potent anti-cancer activity.

    Science.gov (United States)

    Lan, Junjie; Huang, Lan; Lou, Huayong; Chen, Chao; Liu, Tangjingjun; Hu, Shengcao; Yao, Yao; Song, Junrong; Luo, Jun; Liu, Yazhou; Xia, Bin; Xia, Lei; Zeng, Xueyi; Ben-David, Yaacov; Pan, Weidong

    2018-01-01

    Tetrandrine is a dibenzyltetrahydroisoquinoline alkaloid, isolated from traditional Chinese medicinal plant Stephania tetrandra, with anti-tumor activity. Our previous study identified several derivatives of tetrandrine showing better activities than parental compound against human hepatocellular carcinoma cells. To increase diversity and cytotoxic activities of the original compound, a series of novel 14-urea-tetrandrine derivatives were synthesized through structural modification of tetrandrine. These derivaties demonstrated a moderate to strong anti-proliferative activities against human cell lines HEL and K562 (Leukemia), prostate (PC3), breast (MDA-MB-231) and melanoma (WM9). Compound 4g showed strongest cytotoxic effect against PC3 cells with IC 50 value of 0.64 μM, which was 12-fold, 31-fold and 26-fold lower than the parental tetrandrine, 5-fluorouracil and cisplatin, respectively. Preliminary structure-activity relationship study indicated that urea subsititution was the key pharmacophore for the enhancement of their antitumor activities. Induction of apoprosis by 4g was associated with the activation of pro-apoptotic protein BAX and inhibition of antiapoptosis proteins survivin as well as Bcl-2. Moreover, activation of caspases led to increase cleavage of PARP, which further accelerates apoptotic cell death. These results reveal that the compound 4g may be used as a potential anticancer drug candidate. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Human Face as human single identity

    OpenAIRE

    Warnars, Spits

    2014-01-01

    Human face as a physical human recognition can be used as a unique identity for computer to recognize human by transforming human face with face algorithm as simple text number which can be primary key for human. Human face as single identity for human will be done by making a huge and large world centre human face database, where the human face around the world will be recorded from time to time and from generation to generation. Architecture database will be divided become human face image ...

  14. Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia

    Directory of Open Access Journals (Sweden)

    Capretto L

    2012-01-01

    Full Text Available Lorenzo Capretto1, Stefania Mazzitelli2, Eleonora Brognara2, Ilaria Lampronti2, Dario Carugo1, Martyn Hill1, Xunli Zhang1, Roberto Gambari2, Claudio Nastruzzi31Engineering Sciences, University of Southampton, Southampton, UK; 2Department of Biochemistry and Molecular Biology, 3Department of Pharmaceutical Sciences, University of Ferrara, Ferrara, ItalyAbstract: This report shows that the DNA-binding drug, mithramycin, can be efficiently encapsulated in polymeric micelles (PM-MTH, based on Pluronic® block copolymers, by a new microfluidic approach. The effect of different production parameters has been investigated for their effect on PM-MTH characteristics. The compared analysis of PM-MTH produced by microfluidic and conventional bulk mixing procedures revealed that microfluidics provides a useful platform for the production of PM-MTH with improved controllability, reproducibility, smaller size, and polydispersity. Finally, an investigation of the effects of PM-MTH, produced by microfluidic and conventional bulk mixing procedures, on the erythroid differentiation of both human erythroleukemia and human erythroid precursor cells is reported. It is demonstrated that PM-MTH exhibited a slightly lower toxicity and more pronounced differentiative activity when compared to the free drug. In addition, PM-MTH were able to upregulate preferentially γ-globin messenger ribonucleic acid production and to increase fetal hemoglobin (HbF accumulation, the percentage of HbF-containing cells, and their HbF content without stimulating α-globin gene expression, which is responsible for the clinical symptoms of ß-thalassemia. These results represent an important first step toward a potential clinical application, since an increase in HbF could alleviate the symptoms underlying ß-thalassemia and sickle cell anemia. In conclusion, this report suggests that PM-MTH produced by microfluidic approach warrants further evaluation as a potential therapeutic protocol

  15. Proposal for Research on High-Brightness Cathodes for High-Power Free-Electron Lasers (FEL)

    Science.gov (United States)

    2013-05-09

    many failed double tips. Quad-tip emitters: If the KOH etching of the silicon mold is terminated prior to completion of the pyramid, then a small...process with 4" quartz tube furnace (Fig. 2.10). Optical microscope picture (left) and Raman spectrum (right). 5/9/2013 Vanderbilt University JTO...ONR/HEL/MRI Final Report 11 300-nm thick Si02 on silicon wafer. The Raman spectrum in Figure 2.11 clearly shows a 2700-cm" 1 peak and a 1590-cmŕ

  16. Impact of Brexit on the United Kingdom’s Housing Market

    OpenAIRE

    Syromiatnikova, Sofia

    2017-01-01

    This thesis aims to analyse the changes in the real estate market in the United Kingdom and trace and identify the factors that would trigger a price change. The dissertation investigates the possible change in the value of housing caused by Brexit, which is a specific group of investment assets and a major component of household wealth for the UK. Understanding the nature and degree of change in housing prices will make market participants aware of the size of their risk exposure and can hel...

  17. AIR MEETS SPACE: SHAPING THE FUTURE OF COMMERCIAL SPACE TRAFFIC: I. STUDY INTRODUCTION AND INITIAL RESULTS

    OpenAIRE

    Tüllmann, Ralph; Arbinger, Christian; Baskcomb, Stuart; Berdermann, Jens; Fiedler, Hauke; Klock, Erich; Schildknecht, Thomas

    2016-01-01

    There are high expectations for a globally growing market of commercial space travel which is likely to turn in the next 10 to 20 years into a multi-billion Euro business. Those growth expectations are also backed up by OneWeb’s order of about 700 small satellites which are likely to be brought into LEO via air launches and by a continuously growing LEO launch rate showing an increase of about 60% in the last decade. Advances in electric propulsion and spacecraft design (CubeSats) hel...

  18. Dicty_cDB: Contig-U05265-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 9439 ) Sequence 1140 from Patent WO2006024892. 34 0.61 3 ( EL484723 ) CHUM6535.b1_M01.ab1 CHU(LMS) puzzle su... CCFS1822.b1_K24.ab1 CCF(STU) sunflower Helianthus... 42 0.71 2 ( EL476128 ) CHUL4073.b1_A12.ab1 CHU(LMS) puzzle....6 1 ( EL479088 ) CHUL7595.b1_F04.ab1 CHU(LMS) puzzle sunflower Hel... 44 5.6 1 ( EL149373 ) EB3RODY01A41QO

  19. Combating gender stereotypes in the education system: success stories

    OpenAIRE

    Alvarez, Teresa

    2015-01-01

    GEC 2015. Conferência realizada em Helsínquia, de 9-10 october 2014. Conferência de Abertura do Painel 2 – Combating gender stereotypes in the education system: success stories, da Conferência promovida pelo Conselho da Europa sobre “Combating gender stereotypes in and through education”. Apresentam-se alguns desafios decorrentes do combate ao sexismo na escola e propõem-se algumas linhas de ação, ao nível individual, coletivo, organizacional e institucional. info:eu-repo/semantics/pub...

  20. KR’PTA. Samtidspoesin och Derrida : Spår och ärrbildningar hos Johannes Heldén, Ingrid Storholmen och Anna Hallberg

    OpenAIRE

    Schmidt, Lisa

    2006-01-01

    Lisa Schmidt, KR’PTA. Samtidspoesin och Derrida. Spår och ärrbildningar hos Johannes Hel­dén, Ingrid Storholmen och Anna Hallberg. (CR’PT. Contemporary Poetry and Derrida: Traces and Scarring in the Poetry of Johannes Heldén, Ingrid Storholmen and Anna Hallberg.) Through the analyses of three contemporary Nordic poets whose work challenges the boun­daries of literature and even the laws of grammar, I draw attention to the term linguistic materialism. I also sketch an historical line between t...

  1. Human Technology and Human Affects

    DEFF Research Database (Denmark)

    Fausing, Bent

    2009-01-01

    Human Technology and Human Affects  This year Samsung introduced a mobile phone with "Soul". It was made with a human touch and included itself a magical touch. Which function does technology and affects get in everyday aesthetics like this, its images and interactions included this presentation...... will ask and try to answer. The mobile phone and its devices are depicted as being able to make a unique human presence, interaction, and affect. The medium, the technology is a necessary helper to get towards this very special and lost humanity. Without the technology, no special humanity - soul....... The paper will investigate how technology, humanity, affects, and synaesthesia are presented and combined with examples from everyday aesthetics, e.g. early computer tv-commercial, net-commercial for mobile phones. Technology and affects point, is the conclusion, towards a forgotten pre-human and not he...

  2. APRIL facilitates viral-induced erythroleukemia but is dispensable for T cell immunity and lymphomagenesis

    NARCIS (Netherlands)

    Hardenberg, Gijs; Fernandez, Leticia; Hendriks, Jenny; Chebli, Karim; Jacquet, Chantal; Sitbon, Marc; Hahne, Michel; Medema, Jan Paul

    2008-01-01

    The TNF family member, a proliferation-inducing ligand (APRIL), has been suggested to act as a costimulatory molecule in T cell responses. However, studies addressing this role in vivo are largely lacking. Here, we evaluated the effects of APRIL on physiological T cell responses in vivo. Although

  3. The golden triangle of human dignity: human security, human development and human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2004-01-01

    The success or failure of processes of democratization cannot be detached from processes of development related to the aspirations of people at the grassroots. Human rights, in a more theoretical terminology, require human development in order to enhance human security.

  4. Adjuvant effects of therapeutic glycolipids administered to a cohort of NKT cell-diverse pigs.

    Science.gov (United States)

    Artiaga, Bianca L; Whitener, Robert L; Staples, Charles R; Driver, John P

    2014-11-15

    CD1d-restricted natural killer T (NKT) cells are a unique lymphocyte population that makes important contributions to host defense against numerous microbial pathogens. The powerful immunomodulatory effects of these cells can be exploited in mice by cognate antigens for multiple therapeutic purposes, including for protection from infectious diseases and as adjuvants to improve vaccines against microbial organisms. These applications have potential to treat and prevent infectious diseases in livestock species that express NKT cells, including pigs. In this study, immune tissues from commercial swine of mixed genetic background were compared for NKT cell frequency, cytokine secretion and subset ratios. Pigs were also injected with the model antigen hen-egg lysozyme (HEL) in conjunction with one of three glycosphingolipids, alpha-galactosylceramide (αGC), OCH and C-glycoside that selectively activate NKT cells, to assess the adjuvant potential of each. There was significant variation between individual pigs for all NKT cell parameters measured. The NKT cell agonists elicited HEL-specific immune responses of different quality, but only αGC increased the systemic concentration of NKT cells. Peripheral blood NKT cell frequency measured prior to treatment was a poor predictor of how individual animals responded to NKT cell therapy. However, our results show that although NKT cells vary considerably between pigs, there exists considerable potential to harness these cells to protect swine from infectious diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Using rule-based machine learning for candidate disease gene prioritization and sample classification of cancer gene expression data.

    Directory of Open Access Journals (Sweden)

    Enrico Glaab

    Full Text Available Microarray data analysis has been shown to provide an effective tool for studying cancer and genetic diseases. Although classical machine learning techniques have successfully been applied to find informative genes and to predict class labels for new samples, common restrictions of microarray analysis such as small sample sizes, a large attribute space and high noise levels still limit its scientific and clinical applications. Increasing the interpretability of prediction models while retaining a high accuracy would help to exploit the information content in microarray data more effectively. For this purpose, we evaluate our rule-based evolutionary machine learning systems, BioHEL and GAssist, on three public microarray cancer datasets, obtaining simple rule-based models for sample classification. A comparison with other benchmark microarray sample classifiers based on three diverse feature selection algorithms suggests that these evolutionary learning techniques can compete with state-of-the-art methods like support vector machines. The obtained models reach accuracies above 90% in two-level external cross-validation, with the added value of facilitating interpretation by using only combinations of simple if-then-else rules. As a further benefit, a literature mining analysis reveals that prioritizations of informative genes extracted from BioHEL's classification rule sets can outperform gene rankings obtained from a conventional ensemble feature selection in terms of the pointwise mutual information between relevant disease terms and the standardized names of top-ranked genes.

  6. Human Rights/Human Needs.

    Science.gov (United States)

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  7. Leukemic blast cell colony formation in semisolid culture with erythropoietin: a case report of acute poorly differentiated erythroid leukemia.

    Science.gov (United States)

    Tomonaga, M; Jinnai, I; Tagawa, M; Amenomori, T; Nishino, K; Yao, E; Nonaka, H; Kuriyama, K; Yoshida, Y; Matsuo, T

    1987-02-01

    The bone marrow of a patient with acute undifferentiated leukemia developed unique colonies after a 14-day culture in erythropoietin (EPO)-containing methylcellulose. The colonies consisted of 20 to 200 nonhemoglobinized large blast cells. Cytogenetic analysis of single colonies revealed hypotetraploid karyotypes with several marker chromosomes that were identical to those found in directly sampled bone marrow. The concurrently formed erythroid bursts showed only normal karyotypes. No leukemic colony formation was observed in other culture systems with either colony-stimulating activity (CSA) or phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). The leukemic colonies exhibited a complete EPO-dose dependency similar to that of the patient's normal BFU-E. Although cytochemical and immunologic marker studies of the bone marrow cells failed to clarify the cell lineage of the leukemic cells with extraordinarily large cell size, ultrastructural study revealed erythroid differentiation such as siderosome formation in the cytoplasm and ferritin particles in the rhophecytosis invaginations. These findings indicate that the patient had poorly differentiated erythroid leukemia and that some of the clonogenic cells might respond to EPO in vitro. Corresponding to this biological feature, the leukemic cells were markedly decreased in number in response to repeated RBC transfusions, and partial remission was obtained. These observations suggest that erythroid leukemia distinct from erythroleukemia (M6) with a myeloblastic component, can develop as a minor entity of human acute leukemia.

  8. Characterization of the structure of the erythropoietin receptor by ligand blotting

    International Nuclear Information System (INIS)

    Atkins, H.L.; Broudy, V.C.; Papayannopoulou, T.

    1991-01-01

    Erythropoietin (Epo) regulates the growth and differentiation of erythroid cells by binding to a specific receptor. We characterized the native Epo receptor on erythroleukemia cell lines by ligand blotting. Solubilized cell membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred onto nitrocellulose, and probed with 125I-Epo. Specificity was demonstrated by inhibition of 125I-Epo binding by unlabeled excess Epo but not other peptide growth factors and by the cellular distribution of the Epo binding protein. A single membrane protein of 61 Kd ± 4 Kd was sufficient to bind 125I Epo in both human (OCIM2, K562) and murine (GM979, Rauscher, DA-1) cell lines. This finding is consistent with the predicted size of the Epo receptor from the murine cDNA clone. However, chemical crosslinking of 125I-Epo to its receptor has identified two Epo binding proteins of 105 Kd and 85 Kd. This difference may occur because the receptor is size fractionated before Epo binding in the ligand blot, but after Epo binding in crosslinking studies. Ligand blotting demonstrates that the native Epo receptor is composed of a single 61-Kd Epo binding protein, and suggests the presence of additional proteins of 20 to 25 Kd that associate with the receptor after Epo binding

  9. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-06-27

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  10. Inference of coastal submergence from the study of beach rock off Visakhapatnam

    Digital Repository Service at National Institute of Oceanography (India)

    Rajamanickam, G.V.; Rao, K.M.; Rao, T.C.S.

    . and the respective weight percentages were used tocalculat~the size parameters following Folk (I974). The composition of the cementing material w.as examined by directly staining with alizarin red-S on a weB poJished and Hel etched rock surface and by X... Bacteria and on the action of denitrifying bacteria in tropical and temperate seas, pap. Totuga Lab Carnegie Inst., Wash Publ., p. 182. Emery, K.O. and Cox, D.C., (I 956) Beach rock in the Jawaliah Islands, Pacific Science, V. 10, pp', 383. Folk, R.L, (1974...

  11. La circunstancia social en el arte

    Directory of Open Access Journals (Sweden)

    Luis Vidales

    1968-01-01

    Full Text Available Los árabes fueron aprovechados discípulos de los persas, como suele ocurrir a los conquistadores de pueblos, en circunstancias de que la Persia sasánida, que se extendía del Eufrates al Himalaya, era uno de los focos mayores de la expansión del haber cultural griego en el mundo. Ya por entonces, textos enteros de medicina, astronomía y metafísica helénicos entraron a engrosar el Avesta o libro sagrado de los persas (el Zend- Avesta, hoy conocido.

  12. Ужель та самая "Русалка" / Наталья Веденеева

    Index Scriptorium Estoniae

    Веденеева, Наталья

    2009-01-01

    Aleksandr Puškin esitas näidendi "Näkineid" tervikuna ühel kirjandusõhtul 1836. a., kuid pärast tema surma avaldati see lõpetamata kujul. Kirjandusõhtul viibinud Dmitri Pavlovitš Zujev taastas mälu järgi näidendi lõpu ning avaldas selle 1876 a. ajakirjas Russki arhiv ("Русский архив"). Puškinistide arvamused teksti autorsuse kohta lahknesid. Küsimuse teksti ehtsuse kohta tõstatas taas tema järglane ja nimekaim Dmitri Zujev

  13. Análisis comparativo experimental de algunos morteros de restauración

    OpenAIRE

    Riera Juan, Santiago; Gonçalves Soares, Miguel Angelo

    2010-01-01

    En el presente documento se estudia el mortero de cal, material de construcción fundamental desde la época Helénica (ss. II y I a.C.) hasta la introducción y la utilización masiva del cemento portland desde finales del s. XVIII, que relega a un minúsculo segundo plano la milenaria tradición constructiva con mortero de cal. Concretamente se estudian algunos morteros de cal pre-dosificados que ofrece el mercado actual, destinados a obras de restauración. Se expone un estudio objetiv...

  14. Elastic-plastic waves in UV 0.2 Uranium alloy

    International Nuclear Information System (INIS)

    Bernier, H.; Lalle, P.

    1984-09-01

    Release waves coming from the back face of an uranium alloy projectile in a symmetric collision are used to estimate some dynamic characteristics of this material. In the pressure range experimentally covered (<=29GPa) the velocity of the elastic precursor is about 3,45 km/s, and the Hugoniot elastic limit (HEL) is 1,15GPa. The pressure decrease behind the 20GPa (29GPa) shock wave begins with a quasi-elastic wave which velocity is 3,9 km/s (4,2 km/s), and pressure jump of 3GPa (3,7GPa)

  15. Infrastrukturel Accountability

    DEFF Research Database (Denmark)

    Ubbesen, Morten Bonde

    Hvordan redegør man troværdigt for noget så diffust som en hel nations udledning af drivhusgasser? Det undersøger denne afhandling i et etnografisk studie af hvordan Danmarks drivhusgasregnskab udarbejdes, rapporteres og kontrolleres. Studiet trækker på begreber og forståelser fra 'Science & Tech...... & Technology Studies', og bidrager med begrebet 'infrastrukturel accountability' til nye måder at forstå og tænke om det arbejde, hvormed højt specialiserede praksisser dokumenterer og redegør for kvaliteten af deres arbejde....

  16. Managing the Human in Human Brands

    Directory of Open Access Journals (Sweden)

    Fournier Susan

    2018-05-01

    Full Text Available The physical and social realities, mental biases and limitations of being human differentiate human brands from others. It is their very humanness that introduces risk while generating the ability for enhanced returns. Four particular human characteristics can create imbalance or inconsistency between the person and the brand: mortality, hubris, unpredictability and social embeddedness. None of these qualities manifest in traditional non-human brands, and all of them present risks requiring active managerial attention. Rather than treating humans as brands and making humans into brands for sale in the commercial marketplace, our framework forces a focus on keeping a balance between the person and the personified object.

  17. NATO Human View Architecture and Human Networks

    Science.gov (United States)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  18. Humanized mouse models: Application to human diseases.

    Science.gov (United States)

    Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

    2018-05-01

    Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

  19. More Human than Human.

    Science.gov (United States)

    Lawrence, David

    2017-07-01

    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  20. "Paratamatus elada ühel ajal" = "Destiny to Live at the Same Time" / Kalle Komissarov

    Index Scriptorium Estoniae

    Komissarov, Kalle, 1976-

    2004-01-01

    Avaliku ja privaatse ruumi seotusest ühiskonnakorraldusega. Inimeste eluviisi muutumisest rõhutatult individualiseerituks, nõudlusest erinevate eluruumide järele ja sellest tulenevatest muutustest elamuehituses. Tallinna näitel poolavalikust ruumist, mis ootab alles mõtestamist

  1. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  2. Considering Bone Marrow Blasts From Nonerythroid Cellularity Improves the Prognostic Evaluation of Myelodysplastic Syndromes.

    Science.gov (United States)

    Arenillas, Leonor; Calvo, Xavier; Luño, Elisa; Senent, Leonor; Alonso, Esther; Ramos, Fernando; Ardanaz, María Teresa; Pedro, Carme; Tormo, Mar; Marco, Víctor; Montoro, Julia; Díez-Campelo, María; Brunet, Salut; Arrizabalaga, Beatriz; Xicoy, Blanca; Andreu, Rafael; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Benet; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

    2016-09-20

    WHO classification of myeloid malignancies is based mainly on the percentage of bone marrow (BM) blasts. This is considered from total nucleated cells (TNCs), unless there is erythroid-hyperplasia (erythroblasts ≥ 50%), calculated from nonerythroid cells (NECs). In these instances, when BM blasts are ≥ 20%, the disorder is classified as erythroleukemia, and when BM blasts are < 20%, as myelodysplastic syndrome (MDS). In the latter, the percentage of blasts is considered from TNCs. We assessed the percentage of BM blasts from TNCs and NECs in 3,692 patients with MDS from the Grupo Español de Síndromes Mielodisplásicos, 465 patients with erythroid hyperplasia (MDS-E) and 3,227 patients without erythroid hyperplasia. We evaluated the relevance of both quantifications on classification and prognostication. By enumerating blasts systematically from NECs, 22% of patients with MDS-E and 12% with MDS from the whole series diagnosed within WHO categories with < 5% BM blasts, were reclassified into higher-risk categories and showed a poorer overall survival than did those who remained in initial categories (P = .006 and P = .001, respectively). Following WHO recommendations, refractory anemia with excess blasts (RAEB)-2 diagnosis is not possible in MDS-E, as patients with 10% to < 20% BM blasts from TNCs fulfill erythroleukemia criteria; however, by considering blasts from NECs, 72 patients were recoded as RAEB-2 and showed an inferior overall survival than did patients with RAEB-1 without erythroid hyperplasia. Recalculating the International Prognostic Scoring System by enumerating blasts from NECs in MDS-E and in the overall MDS population reclassified approximately 9% of lower-risk patients into higher-risk categories, which indicated the survival expected for higher-risk patients. Regardless of the presence of erythroid hyperplasia, calculating the percentage of BM blasts from NECs improves prognostic assessment of MDS. This fact should be considered in future

  3. The Human/Machine Humanities: A Proposal

    Directory of Open Access Journals (Sweden)

    Ollivier Dyens

    2016-03-01

    Full Text Available What does it mean to be human in the 21st century? The pull of engineering on every aspect of our lives, the impact of machines on how we represent ourselves, the influence of computers on our understanding of free-will, individuality and species, and the effect of microorganisms on our behaviour are so great that one cannot discourse on humanity and humanities without considering their entanglement with technology and with the multiple new dimensions of reality that it opens up. The future of humanities should take into account AI, bacteria, software, viruses (both organic and inorganic, hardware, machine language, parasites, big data, monitors, pixels, swarms systems and the Internet. One cannot think of humanity and humanities as distinct from technology anymore.

  4. Characterization of Elements Regulating the Nuclear-to-Cytoplasmic Translocation of ICP0 in Late Herpes Simplex Virus 1 Infection.

    Science.gov (United States)

    Samrat, Subodh Kumar; Ha, Binh L; Zheng, Yi; Gu, Haidong

    2018-01-15

    Infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) is an immediate early protein containing a RING-type E3 ubiquitin ligase. It targets several host factors for proteasomal degradation and subsequently activates viral expression. ICP0 has a nuclear localization sequence and functions in the nucleus early during infection. However, later in infection, ICP0 is found solely in the cytoplasm. The molecular mechanism and biological function of the ICP0 nuclear-to-cytoplasmic translocation are not well understood. In this study, we sought to characterize elements important for this translocation. We found that (i) in human embryonic lung fibroblast (HEL) cells, ICP0 C-terminal residues 741 to 775 were necessary but not sufficient for the nuclear-to-cytoplasmic translocation; (ii) the loss of ICP0 E3 ubiquitin ligase activity, which led to defective viral replication in nonpermissive cells, also caused mutant ICP0 to be retained in the nucleus of HEL cells; (iii) in permissive U2OS cells, however, ICP0 lacking E3 ligase activity was translocated to the cytoplasm at a pace faster than that of wild-type ICP0, suggesting that nuclear retention of ICP0 occurs in an ICP0 E3 ligase-dependent manner; and (iv) the ICP0 C terminus and late viral proteins cooperate in order to overcome nuclear retention and stimulate ICP0 cytoplasmic translocation. Taken together, less ICP0 nuclear retention may contribute to the permissiveness of U2OS cells to HSV-1 in the absence of functional ICP0. IMPORTANCE A distinct characteristic for eukaryotes is the compartmentalization of cell metabolic pathways, which allows greater efficiency and specificity of cellular functions. ICP0 of HSV-1 is a multifunctional viral protein that travels through different compartments as infection progresses. Its main regulatory functions are carried out in the nucleus, but it is translocated to the cytoplasm late during HSV-1 infection. To understand the biological significance of cytoplasmic ICP0 in

  5. Human trafficking in Germany: strengthening victim's human rights

    OpenAIRE

    Follmar-Otto, Petra; Rabe, Heike

    2009-01-01

    The first study - "A human rights approach against human trafficking - International obligations and the status of implementation in Germany" - analyses how the prohibition of human trafficking and the resulting state obligations are anchored in human rights. The more recent specialised international agreements on human trafficking and law-making in the European Union are then presented. The emphasis is on the Council of Europe Convention, which professes to treat human trafficking in a human...

  6. Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

    Science.gov (United States)

    2018-05-24

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  7. Faults in clays their detection and properties

    International Nuclear Information System (INIS)

    Baldi, G.; Carabelli, E.; Chiantore, V.; Colombo, P.F.; Gruszka, A.; Pensieri, R.; Superbo, S.; Gera, F.

    1991-01-01

    The 'Faults in clays project', a cooperative research effort between Ismes and Enea of Italy and BGS and Exeter University of the UK, has been aimed at assessing and improving the resolution capability of some high resolution geophysical techniques for the detection of discontinuities in clay formations. All Ismes activities have been carried out in Italy: they consisted in the search of one or more sites - faulted clay formations - suitable for the execution of geophysical and geotechnical investigations, in the execution of such tests and in additional geological surveys and laboratory (geotechnical and geochemical) testing. The selected sites were two quarries in plio-pleistocenic clay formations in central Italy where faults had been observed. The greatest part of the research work has been carried out in the Orte site where also two 90 m boreholes have been drilled and cored. Geophysical work at Orte consisted of vertical electrical soundings (VESs) and horizontal electrical lines (HELs), four high resolution seismic reflection lines, and in-hole and cross-hole logs. Laboratory activities were geotechnical characterization and permeability tests, and measurements of disequilibrium in the uranium decay series. At Narni, where Exeter University sampled soil gases for geochemical analyses, the geophysical work consisted in a geo-electrical survey (five VESs and two HELs), and in two high resolution reflection seismic lines. Additional investigations included a structural geology survey. The main conclusion of the research is that current geophysical techniques do not have a resolution capacity sufficient to detect the existence and determine the characteristics of faults in deep homogeneous clay formations

  8. Dynamic behaviors of a Zr-based bulk metallic glass under ramp wave and shock wave loading

    Directory of Open Access Journals (Sweden)

    Binqiang Luo

    2015-06-01

    Full Text Available Dynamic behaviors of Zr51Ti5Ni10Cu25Al9 bulk metallic glass were investigated using electric gun and magnetically driven isentropic compression device which provide shock and ramp wave loading respectively. Double-wave structure was observed under shock compression while three-wave structure was observed under ramp compression in 0 ∼ 18GPa. The HEL of Zr51Ti5Ni10Cu25Al9 is 8.97 ± 0.61GPa and IEL is 8.8 ± 0.3GPa, respectively. Strength of Zr51Ti5Ni10Cu25Al9 estimated from HEL is 5.0 ± 0.3GPa while the strength estimated from IEL is 3.6 ± 0.1GPa. Shock wave velocity versus particle velocity curve of Zr51Ti5Ni10Cu25Al9 under shock compression appears to be bilinear and a kink appears at about 18GPa. The Lagrangian sound speed versus particle velocity curve of Zr51Ti5Ni10Cu25Al9 under ramp wave compression exhibits two discontinuances and are divided to three regions: elastic, plastic-I and plastic-II. The first jump-down occurs at elastic-plastic transition and the second appears at about 17GPa. In elastic and plastic-I regions, Lagrangian sound speed increases linearly with particle velocity, respectively. Characteristic response of sound speed in plastic-I region disagree with shock result in the same pressure region(7GPa ∼ 18GPa, but is consistent with shock result at higher pressure(18-110GPa.

  9. Dicty_cDB: Contig-U15443-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available lic Acid Glyc... 42 7e-04 2 ( EL475659 ) CHUL3619.b1_F17.ab1 CHU(LMS) puzzle sunf...Schistosoma japonicum cDNA similar ... 42 0.12 2 ( EL482406 ) CHUM4387.b1_F17.ab1 CHU(LMS) puzzle sunflower ...200.b1_O04.ab1 CHU(LMS) puzzle sunflower Hel... 42 5e-04 3 ( CD414213 ) Gm_ck46258 Soybean induced by Salicy.... 58 2e-04 2 ( EH303465 ) UAHYP_14C_F_G04 UaHyphae_ARS Uromyces appendicula... 46 3e-04 2 ( EL483290 ) CHUM5

  10. Odnim blazhennõm dnjom : [luuletused] / Uku Masing ; lühibiograafia: A. K. [Ain Kaalep

    Index Scriptorium Estoniae

    Masing, Uku, 1909-1985

    1999-01-01

    Sisu: Odnim blazhennõm dnjom ; Veter tshelnok bõl ; Pesn soldat, otstupajushishih pod natiskom netshistoi silõ / tlk. Svetlan Semenenko ; "Tõ groznaja gora..." ; "Ne mozhet ditja bez ottsa naroditsja..." ; K predelam ; Vestnik iz "Magellanovõh oblakov" : katkend ; Postigaja i verja ; V kazhdom strannike - nadezhda / tlk. A. Zorin. Orig.: Ühel kaunil päeval ; Süstik on tuul ; Tontide eest taganejate sõdurite laul ; "Sa oled mägi, mida kardavad me karjad..." ; "Välja südamest visata..." ; Piiridele püüdes ; Saadik Magellani pilvest : katkend ; Mõistu saades ja uskudes ; Iga rändur on lootus

  11. Retrospektiv undersökning av främre korsbandsskada hos fotbollsspelande damer på liganivå i Finland

    OpenAIRE

    Widjeskog, Maria

    2013-01-01

    Främre korsbandsskador är en av de vanligaste allvarliga skadorna bland kvinnliga fotbollsspelare och leder till minst 6 månaders uppehåll från tävlingssammanhang. En hel del studier har gjorts inom området. Den här studien försöker få fram riskfaktorer för skada, i hurudana situationer skadan sker, förebyggande möjligheter samt olikheter i rehabilitering. Studien är retrospektiv och 19 spelare deltog. Deltagarna är damfotbollsspelare som spelat ligafotboll i Finland något år mellan åren ...

  12. Continuación de Cavafi

    Directory of Open Access Journals (Sweden)

    Fernando Arbelaéz

    1967-12-01

    Full Text Available Al continuar presentando en español la versión francesa de los poemas de Costantino Cavafi, hecha por Yorgos Paputsakis, me he dejado llevar por un ejercicio fascinante y por una lección admirable de poesía. Lo que en otras lecturas había sido mero recubrimiento y adorno, se me ha revelado aquí con el peso de una experiencia humana cargada de meditaciones y de preocupación por la existencia. Ni heroicidad ni idealismo encontramos en este mundo helénico resucitado por el poeta; tan solo una realidad estricta y agobiadora.

  13. Nice Teams Finish Last The Secret to Unleashing Your Team's Maximum Potential

    CERN Document Server

    Miller, Brian Cole

    2010-01-01

    Don't rock the boat. Don't make waves. Don't offend anyone. There's a palpable feeling that clouds many team meetings and keeps them from being productive: over-politeness. And while the conflict that naturally exists in most organizations hasn't gone away, it manifests itself in passive-aggression, mediocrity, and a molasses-like inability to get anything done. Nice Teams Finish Last provides the antidote to this all-too-common tendency, giving managers, team leaders and members, and facilitators the practical support they need to battle "the nice trap" and start getting results! The book hel

  14. Delayed Failure in a Shock Loaded Alumina

    International Nuclear Information System (INIS)

    Cooper, G. A.; Millett, J. C. F.; Bourne, N. K.; Dandekar, D. P.

    2006-01-01

    Manganin stress gauges have been used to measure the lateral stress in a shock-loaded alumina. In combination with known longitudinal stresses, these have been used to determine the shear strength of this material, behind the shock front. The two-step nature of the lateral stress traces shows a slow moving front behind the main shock, behind which shear strength undergoes a significant decrease. Results also show that this front decreases markedly in velocity as the HEL is crossed, suggesting that limited plasticity occurs during inelastic deformation. Finally, comparison of measured shear strengths with other aluminas shows a high degree of agreement

  15. The Digital Humanities as a Humanities Project

    Science.gov (United States)

    Svensson, Patrik

    2012-01-01

    This article argues that the digital humanities can be seen as a humanities project in a time of significant change in the academy. The background is a number of scholarly, educational and technical challenges, the multiple epistemic traditions linked to the digital humanities, the potential reach of the field across and outside the humanities,…

  16. Human reliability

    International Nuclear Information System (INIS)

    Embrey, D.E.

    1987-01-01

    Concepts and techniques of human reliability have been developed and are used mostly in probabilistic risk assessment. For this, the major application of human reliability assessment has been to identify the human errors which have a significant effect on the overall safety of the system and to quantify the probability of their occurrence. Some of the major issues within human reliability studies are reviewed and it is shown how these are applied to the assessment of human failures in systems. This is done under the following headings; models of human performance used in human reliability assessment, the nature of human error, classification of errors in man-machine systems, practical aspects, human reliability modelling in complex situations, quantification and examination of human reliability, judgement based approaches, holistic techniques and decision analytic approaches. (UK)

  17. The Humanities, Human Rights, and the Comparative Imagination

    OpenAIRE

    McClennen, Sophia A.

    2007-01-01

    In her paper "The Humanities, Human Rights, and the Comparative Imagination" Sophia A. McClennen argues that understanding the relationship between culture and human rights depends on humanist perspectives attentive to the relationship between storytelling and identity, mass culture and ideology, text and audience, critical thinking and engaged citizenship. After briefly considering how the divide between the humanities and human rights advocates developed and how it might best be overcome, s...

  18. Human-centered Computing: Toward a Human Revolution

    OpenAIRE

    Jaimes, Alejandro; Gatica-Perez, Daniel; Sebe, Nicu; Huang, Thomas S.

    2007-01-01

    Human-centered computing studies the design, development, and deployment of mixed-initiative human-computer systems. HCC is emerging from the convergence of multiple disciplines that are concerned both with understanding human beings and with the design of computational artifacts.

  19. Human engineering

    International Nuclear Information System (INIS)

    Yang, Seong Hwan; Park, Bum; Gang, Yeong Sik; Gal, Won Mo; Baek, Seung Ryeol; Choe, Jeong Hwa; Kim, Dae Sung

    2006-07-01

    This book mentions human engineering, which deals with introduction of human engineering, Man-Machine system like system design, and analysis and evaluation of Man-Machine system, data processing and data input, display, system control of man, human mistake and reliability, human measurement and design of working place, human working, hand tool and manual material handling, condition of working circumstance, working management, working analysis, motion analysis working measurement, and working improvement and design in human engineering.

  20. Simulating human behavior for national security human interactions.

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, Michael Lewis; Hart, Dereck H.; Verzi, Stephen J.; Glickman, Matthew R.; Wolfenbarger, Paul R.; Xavier, Patrick Gordon

    2007-01-01

    This 3-year research and development effort focused on what we believe is a significant technical gap in existing modeling and simulation capabilities: the representation of plausible human cognition and behaviors within a dynamic, simulated environment. Specifically, the intent of the ''Simulating Human Behavior for National Security Human Interactions'' project was to demonstrate initial simulated human modeling capability that realistically represents intra- and inter-group interaction behaviors between simulated humans and human-controlled avatars as they respond to their environment. Significant process was made towards simulating human behaviors through the development of a framework that produces realistic characteristics and movement. The simulated humans were created from models designed to be psychologically plausible by being based on robust psychological research and theory. Progress was also made towards enhancing Sandia National Laboratories existing cognitive models to support culturally plausible behaviors that are important in representing group interactions. These models were implemented in the modular, interoperable, and commercially supported Umbra{reg_sign} simulation framework.

  1. Heme-dependent up-regulation of the α-globin gene expression by transcriptional repressor Bach1 in erythroid cells

    International Nuclear Information System (INIS)

    Tahara, Tsuyoshi; Sun Jiying; Igarashi, Kazuhiko; Taketani, Shigeru

    2004-01-01

    The transcriptional factor Bach1 forms a heterodimer with small Maf family, and functions as a repressor of the Maf recognition element (MARE) in vivo. To investigate the involvement of Bach1 in the heme-dependent regulation of the expression of the α-globin gene, human erythroleukemia K562 cells were cultured with succinylacetone (SA), a heme biosynthetic inhibitor, and the level of α-globin mRNA was examined. A decrease of α-globin mRNA was observed in SA-treated cells, which was restored by the addition of hemin. The heme-dependent expression of α-globin occurred at the transcriptional level since the expression of human α-globin gene promoter-reporter gene containing hypersensitive site-40 (HS-40) was decreased when K562 cells were cultured with SA. Hemin treatment restored the decrease of the promoter activity by SA. The regulation of the HS-40 activity by heme was dependent on the NF-E2/AP-1 (NA) site, which is similar to MARE. The NA site-binding activity of Bach1 in K562 increased upon SA-treatment, and the increase was diminished by the addition of hemin. The transient expression of Bach1 and mutated Bach1 lacking CP motifs suppressed the HS-40 activity, and cancellation of the repressor activity by hemin was observed when wild-type Bach1 was expressed. The expression of NF-E2 strengthened the restoration of the Bach1-effect by hemin. Interestingly, nuclear localization of Bach1 increased when cells were treated with SA, while hemin induced the nuclear export of Bach1. These results indicated that heme plays an important role in the induction of α-globin gene expression through disrupting the interaction of Bach1 and the NA site in HS-40 enhancer in erythroid cells

  2. Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis.

    Science.gov (United States)

    Danz, Henning; Stoyanova, Stefka; Thomet, Olivier A R; Simon, Hans-Uwe; Dannhardt, Gerd; Ulbrich, Holger; Hamburger, Matthias

    2002-10-01

    The indolo[2,1- b]quinazoline alkaloid tryptanthrin has previously been identified as the cyclooxygenase-2 (COX-2) inhibitory principle in the extract ZE550 prepared from the medicinal plant Isatis tinctoria (Brassicaceae). We here investigated the potential inhibitory activity of tryptanthrin and ZE550 on COX-2, COX-1 in cellular and cell-free systems. A certain degree of selectivity towards COX-2 was observed when COX-1-dependent formation of thromboxane B(2) (TxB(2)) in HEL cells and COX-2-dependent formation of 6-ketoprostaglandin F(1alpha) (6-keto-PGF(1alpha)) in Mono Mac 6 and RAW 264.7 cells were compared. Preferential inhibition of COX-2 by two orders of magnitude was found in phorbol myristate acetate (PMA) activated bovine aortic coronary endothelial cells (BAECs). Assays with purified COX isoenzymes from sheep confirmed the high selectivity towards COX-2. The leukotriene B(4) (LTB(4)) release from calcium ionophore-stimulated human granulocytes (neutrophils) was used as a model to determine 5-lipoxygenase (5-LOX) activity. Tryptanthrin and the extract ZE550 inhibited LTB(4) release in a dose dependent manner and with a potency comparable to that of the clinically used 5-LOX inhibitor zileuton.

  3. Human Rights and Human Function

    Directory of Open Access Journals (Sweden)

    Mohsen Javadi

    2006-03-01

    Full Text Available This paper firstly explores some theories of Human Rights justification and then assents to the theory that Human Rights is based on justified moral values. In order to justify moral values, Aristotle’s approach called “Function Argument” is reviewed. Propounding this argument, the writer attempts to show that all analysis of human identity will directly contribute to the man’s view of his rights. Not only Human rights is really determined by human function or human distinguishing characteristic i.e. human identity, but in the world of knowledge the proper method to know human rights is to know human being himself. n cloning violates man’s rights due to two reasons: damage of human identity and violation of the right to be unique. Attempting to clarify the nature of human cloning, this article examines the aspects to be claimed to violate human rights and evaluates the strength of the reasons for this claim. این مقاله پس از بررسی اجمالی برخی از نظریه‌های توجیه حقوق بشر، نظریة ابتنای آن بر ارزش‌های اخلاقی موجّه را می‌پذیرد. دربارة چگونگی توجیه ارزش اخلاقی، رویکرد ارسطو که به «برهان ارگن» موسوم است، مورد بحث و بررسی قرار می‌گیرد. مؤلف با طرح این برهان می‌کوشد نشان دهد ارائه هرگونه تحلیل از هویت انسان در نگرش آدمی به حقوق خود تأثیر مستقیم خواهد گذاشت. حقوق آدمی نه فقط از ناحیة کارویژه یا فصل ممیز وی (هویت انسان تعیّن واقعی می‌گیرد، بلکه در عالم معرفت هم راه درست شناخت حقوق بشر، شناخت خود انسان است.

  4. Habitability and Human Factors Contributions to Human Space Flight

    Science.gov (United States)

    Sumaya, Jennifer Boyer

    2011-01-01

    This slide presentation reviews the work of the Habitability and Human Factors Branch in support of human space flight in two main areas: Applied support to major space programs, and Space research. The field of Human Factors applies knowledge of human characteristics for the design of safer, more effective, and more efficient systems. This work is in several areas of the human space program: (1) Human-System Integration (HSI), (2) Orion Crew Exploration Vehicle, (3) Extravehicular Activity (EVA), (4) Lunar Surface Systems, (5) International Space Station (ISS), and (6) Human Research Program (HRP). After detailing the work done in these areas, the facilities that are available for human factors work are shown.

  5. Human dignity according to international instruments on human rights

    Directory of Open Access Journals (Sweden)

    José Pablo Alzina de Aguilar

    2011-01-01

    Full Text Available According to international instruments on human rights, the dignity of the human person is the foundation of human rights, and both human dignity and human rights are inherent to the human being, universal and inviolable. This understanding of human dignity is not a fruitless truism, but the solid foundation on which to build a world community under the rule of the new ius gentium: the International Law for Humankind. Moreover, it is the clue to answer many questions raised by the new world of globalization and of the exponential growth of international rules.Consequently, there is a need to a common doctrine on a notion of human dignity which will allow the implementation and adjudication of the aforementioned instruments, at the service of the human person and in conformity with the juridical conscience which they reflect. Philosophy of Law concepts which can be traced back to Aristotle provide that notion. According to these concepts, the demanding nature of “human dignity” sustains the notion of “legal personhood”, and both notions pertain to the realm of Law and Right, not of Morale and Values. Thus, human dignity and human rights are and must be, respectively, a basic principle and a necessary part of any Law system, including international law

  6. Human-Robot Teams Informed by Human Performance Moderator Functions

    Science.gov (United States)

    2012-08-29

    performance factors that affect the ability of a human to drive at night, which includes the eyesight of the driver, the fatigue level of the driver...where human factors are factors that affect the performance of an individual. 7 for human interaction. For instance, they explain the various human... affecting trust in human-robot interaction. Human Factors 53(5), 517-527 (2001) 35. Hart, S. G. and Staveland, L. E. Development of NASA-TLX (Task

  7. Modeling Human Leukemia Immunotherapy in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Jinxing Xia

    2016-08-01

    Full Text Available The currently available human tumor xenograft models permit modeling of human cancers in vivo, but in immunocompromised hosts. Here we report a humanized mouse (hu-mouse model made by transplantation of human fetal thymic tissue plus hematopoietic stem cells transduced with a leukemia-associated fusion gene MLL-AF9. In addition to normal human lymphohematopoietic reconstitution as seen in non-leukemic hu-mice, these hu-mice showed spontaneous development of B-cell acute lymphoblastic leukemia (B-ALL, which was transplantable to secondary recipients with an autologous human immune system. Using this model, we show that lymphopenia markedly improves the antitumor efficacy of recipient leukocyte infusion (RLI, a GVHD-free immunotherapy that induces antitumor responses in association with rejection of donor chimerism in mixed allogeneic chimeras. Our data demonstrate the potential of this leukemic hu-mouse model in modeling leukemia immunotherapy, and suggest that RLI may offer a safe treatment option for leukemia patients with severe lymphopenia.

  8. From Human-Computer Interaction to Human-Robot Social Interaction

    OpenAIRE

    Toumi, Tarek; Zidani, Abdelmadjid

    2014-01-01

    Human-Robot Social Interaction became one of active research fields in which researchers from different areas propose solutions and directives leading robots to improve their interactions with humans. In this paper we propose to introduce works in both human robot interaction and human computer interaction and to make a bridge between them, i.e. to integrate emotions and capabilities concepts of the robot in human computer model to become adequate for human robot interaction and discuss chall...

  9. Comparability of Conflict Opportunities in Human-to-Human and Human-to-Agent Online Collaborative Problem Solving

    Science.gov (United States)

    Rosen, Yigal

    2014-01-01

    Students' performance in human-to-human and human-to-agent collaborative problem solving assessment task is investigated in this paper. A secondary data analysis of the research reported by Rosen and Tager (2013) was conducted in order to investigate the comparability of the opportunities for conflict situations in human-to-human and…

  10. Treatment for Relapsed/Refractory AML Based on a High Throughput Drug Sensitivity Assay

    Science.gov (United States)

    2018-04-11

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  11. Human-Robot Interaction and Human Self-Realization

    DEFF Research Database (Denmark)

    Nørskov, Marco

    2014-01-01

    is to test the basis for this type of discrimination when it comes to human-robot interaction. Furthermore, the paper will take Heidegger's warning concerning technology as a vantage point and explore the possibility of human-robot interaction forming a praxis that might help humans to be with robots beyond...

  12. Human nature, human culture: the case of cultural evolution.

    Science.gov (United States)

    Lewens, Tim

    2017-10-06

    In recent years, far from arguing that evolutionary approaches to our own species permit us to describe the fundamental character of human nature, a prominent group of cultural evolutionary theorists has instead argued that the very idea of 'human nature' is one we should reject. It makes no sense, they argue, to speak of human nature in opposition to human culture. The very same sceptical arguments have also led some thinkers-usually from social anthropology-to dismiss the intimately related idea that we can talk of human culture in opposition to human nature. How, then, are we supposed to understand the cultural evolutionary project itself, whose proponents seem to deny the distinction between human nature and human culture, while simultaneously relying on a closely allied distinction between 'genetic' (or sometimes 'organic') evolution and 'cultural' evolution? This paper defends the cultural evolutionary project against the charge that, in refusing to endorse the concept of human nature, it has inadvertently sabotaged itself.

  13. Ancient humans and the origin of modern humans.

    Science.gov (United States)

    Kelso, Janet; Prüfer, Kay

    2014-12-01

    Recent advances in sequencing technologies and molecular methods have facilitated the sequencing of DNA from ancient human remains which has, in turn, provided unprecedented insight into human history. Within the past 4 years the genomes of Neandertals and Denisovans, as well as the genomes of at least two early modern humans, have been sequenced. These sequences showed that there have been several episodes of admixture between modern and archaic groups; including admixture from Neandertals into modern human populations outside of Africa, and admixture from Denisovans into modern human populations in Oceania. Recent results indicate that some of these introgressed regions may have been advantageous for modern humans as they expanded into new regions outside of Africa. Copyright © 2014. Published by Elsevier Ltd.

  14. Long-term changes in migration timing of Song Thrush Turdus philomelos at the southern Baltic coast in response to temperatures on route and at breeding grounds.

    Science.gov (United States)

    Redlisiak, Michał; Remisiewicz, Magdalena; Nowakowski, Jarosław K

    2018-05-26

    Climate warming causes the advancement of spring arrival of many migrant birds breeding in Europe, but the effects on their autumn migration are less known. We aimed to determine any changes in the timing of Song Thrush captured during spring and autumn migrations at the Polish Baltic coast from 1975 to 2014, and if these were related to long-term changes of temperature at their breeding grounds and migration routes. The timing of spring migration at Hel ringing station in 1975-2014 did not show long-term advance, but they had responded to environmental conditions on the year-to-year basis. The warmer the temperatures were in April on their migration route, the earlier were the dates of the median and the end of spring migration at Hel. The beginning of autumn migration at the Mierzeja Wiślana ringing station advanced by 5 days between 1975 and 2014. The warmer the April on route, and the July at the Song Thrushes' breeding grounds, the earlier young birds began autumn migration across the Baltic coast. We suggest this was a combined effect of adults' migration and breeding early during warm springs and young birds getting ready faster for autumn migration during warm summers. The average time span of 90% of the autumn migration was extended by 5 days, probably because of early migration of young birds from first broods and late of those from second broods enabled by warm springs and summers. The response of Song Thrushes' migration timing to temperatures on route and at the breeding grounds indicated high plasticity in the species and suggested it might adapt well to climate changes.

  15. Sobre la morfología y distribución de Rorippa microphylla (Cruciferae y táxones afínes en la Península Ibérica

    Directory of Open Access Journals (Sweden)

    Molina Abril, José A.

    1997-12-01

    Full Text Available A morphological and chorological study of Rorippa microphylla, R. nasturtium-aquaticum and R. x sterilis in the Iberian Península was carried out. The number of areolae per side on the seed coat is confirmed as the best distinguishing character between these taxa. The length of the atiricies in caulinar leaves is also pointed out as a valuable trait. R. microphylla reaches in the center of the Iberian Península the southernmost and only Mediterranean localities of this species in Europe. Both R. microphylla and R. nasturtium-aquaticum form part of two types of communities of flowing waters, one in which decumbent helophytes of shallow waters domínate, and the other dominated by erect helophytes of somewhat deeper waters.Se lleva a cabo una revisión morfológica y corológica de Rorippa microphylla, R. nasturtiumaquaticum y R. x sterilis en la Península Ibérica. El número de fovéolas de la testa seminal se confirma como el mejor carácter diagnóstico de estos táxones; como carácter adicional, se destaca la longitud de las aurículas de las hojas caulinares R. microphylla alcanza en el centro de la Península Ibérica sus localidades más meridionales y las únicas mediterráneas del continente europeo R. microphylla y R. nasturtium-aquaticum forman parte de dos tipos de comunidades de aguas fluentes, una en la que dominan helóntos decumbentes, de aguas someras, y otra dominada por helóntos erectos, de aguas algo más profundas.

  16. Development velocity interferometer system for any reflector for measurement of mechanical properties of materials during high strain - rate compression and decompression process

    International Nuclear Information System (INIS)

    Joshi, K.D.; Rav, Amit S.; Gupta, Satish C.

    2011-02-01

    Velocity interferometer system for any reflector (VISAR) has been developed to study the dynamic mechanical properties of materials subjected to high strain rates. This instrument is essentially a wide angle Michelson interferometer for measuring the Doppler shift of the monochromatic light from a laser (in our case λ 0 = 532 nm) after it gets reflected off the free surface of the moving target. A fiber optical arrangement directs the laser beam to the target and transports the scattered light signal into the interferometer. The interferometer beats the light signals reflected from the target at the two different instant of time separated by the delay (τ) decided by the length of the etalon in one of the leg of the interferometer. The interferometer signal is fed to the photomultiplier tube, the output of which is recorded in a digital storage oscilloscope. The oscilloscope record is then analysed to deduce the velocity history of moving free surface of target which is then used to determine various important mechanical properties during high strain rate compression and decompression. This instrument has been used to determine the Hugoniot elastic limit (σ HEL ), spall strength (σ s ) and dynamic yield strength (Y) of Al2024-T4 and SS304 alloys shocked to peak pressures of 4.4 GPa and 12 GPa, respectively in gas gun experiments. The σ HEL , σ s and Y determined from measured free surface velocity profiles of shocked Al2024-T4 target plate are 0.70 GPa, 1.46 GPa and 0.36 GPa, respectively. These values determined for SS304 target plate are 1.35 GPa, 2.6 GPa and 0.8 GPa, respectively. (author)

  17. Human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2006-01-01

    Human rights reflect a determined effort to protect the dignity of each and every human being against abuse of power. This endeavour is as old as human history. What is relatively new is the international venture for the protection of human dignity through internationally accepted legal standards

  18. Universe, human immortality and future human evaluation

    CERN Document Server

    Bolonkin, Alexander

    2011-01-01

    This book debates the universe, the development of new technologies in the 21st century and the future of the human race. Dr Bolonkin shows that a human soul is only the information in a person's head. He offers a new unique method for re-writing the main brain information in chips without any damage to the human brain. This is the scientific prediction of the non-biological (electronic) civilization and immortality of the human being. Such a prognosis is predicated upon a new law, discovered by the author, for the development of complex systems. According to this law, every self-copying system tends to be more complex than the previous system, provided that all external conditions remain the same. The consequences are disastrous: humanity will be replaced by a new civilization created by intellectual robots (which Dr Bolonkin refers to as "E-humans" and "E-beings"). These creatures, whose intellectual and mechanical abilities will far exceed those of man, will require neither food nor oxygen to sustain their...

  19. Human Modeling for Ground Processing Human Factors Engineering Analysis

    Science.gov (United States)

    Stambolian, Damon B.; Lawrence, Brad A.; Stelges, Katrine S.; Steady, Marie-Jeanne O.; Ridgwell, Lora C.; Mills, Robert E.; Henderson, Gena; Tran, Donald; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over the last few years using human modeling for human factors engineering analysis for design of spacecraft. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the human modeling currently used at Kennedy Space Center (KSC), and to explain the future plans for human modeling for future spacecraft designs

  20. SharePoint 2007 Collaboration For Dummies

    CERN Document Server

    Harvey, Greg

    2009-01-01

    If you're looking for a way to help your teams access what they need to know, work together, and get the job done, SharePoint can do just that. SharePoint 2007 Collaboration For Dummies shows you the easiest way to set up and customize SharePoint, manage your data, interact using SharePoint blogs and wikis, integrate Office programs, and make your office more productive. You'll learn what SharePoint can do and how to make it work for your business, understand the technical terms, and enable your people to collaborate on documents and spreadsheets. You'll even discover how to get SharePoint hel

  1. Handbook of Ballistic and Engineering Data for Ammunition. Volume 1. 20-1-95 to 75-1-310 Included

    Science.gov (United States)

    1950-07-01

    steel uistead of cast iron)witb the PD Fuze M52 as standard for limited procurement. OCM items 16026 and 16122 recommended and approved standardization of...BALLSTIC AND ENGINEERIN DATA II DRAG~E75 COFFCINT MACH NUMBER PLDT -14 44 SHELLI H5-mM .. a; FUZE,CPD, 7PI SEL;HEL, 75-MM M48; UE,TJ 3 fill 1.5 I . 2I...INLUDED IN FIRE AIREA3L Ptl MAN HE[Gff Of BURST + to".~ it t~ 125 I - HIELDI G MUM *LET - 14,K 1."~ 4 41-L H ,T - -1* 𔃻 - 1) 100 3000 4000 000 0 1 1 i

  2. Issues on combining human and non-human intelligence

    Science.gov (United States)

    Statler, Irving C.; Connors, Mary M.

    1991-01-01

    The purpose here is to call attention to some of the issues confronting the designer of a system that combines human and non-human intelligence. We do not know how to design a non-human intelligence in such a way that it will fit naturally into a human organization. The author's concern is that, without adequate understanding and consideration of the behavioral and psychological limitations and requirements of the human member(s) of the system, the introduction of artificial intelligence (AI) subsystems can exacerbate operational problems. We have seen that, when these technologies are not properly applied, an overall degradation of performance at the system level can occur. Only by understanding how human and automated systems work together can we be sure that the problems introduced by automation are not more serious than the problems solved.

  3. Human Dignity – Constitutional Principle of Fundamental Human Rights

    Directory of Open Access Journals (Sweden)

    Lucian Pop

    2011-07-01

    Full Text Available As a constitutional principle of the human rights, the human dignity is a supreme value, a norm and a right, thus that the reconfiguration of protection standards of fundamental human rights is made by cohesion of the legal, social and moral dimensions of human dignity. With this article, the author argues that legal meaning, social meaning and moral meaning of human dignity, are centerpiece of protection of freedom under law.

  4. Human herpesvirus 8 – A novel human pathogen

    Directory of Open Access Journals (Sweden)

    Edelman Daniel C

    2005-09-01

    Full Text Available Abstract In 1994, Chang and Moore reported on the latest of the gammaherpesviruses to infect humans, human herpesvirus 8 (HHV-8 1. This novel herpesvirus has and continues to present challenges to define its scope of involvement in human disease. In this review, aspects of HHV-8 infection are discussed, such as, the human immune response, viral pathogenesis and transmission, viral disease entities, and the virus's epidemiology with an emphasis on HHV-8 diagnostics.

  5. Human Parvoviruses

    Science.gov (United States)

    Söderlund-Venermo, Maria; Young, Neal S.

    2016-01-01

    SUMMARY Parvovirus B19 (B19V) and human bocavirus 1 (HBoV1), members of the large Parvoviridae family, are human pathogens responsible for a variety of diseases. For B19V in particular, host features determine disease manifestations. These viruses are prevalent worldwide and are culturable in vitro, and serological and molecular assays are available but require careful interpretation of results. Additional human parvoviruses, including HBoV2 to -4, human parvovirus 4 (PARV4), and human bufavirus (BuV) are also reviewed. The full spectrum of parvovirus disease in humans has yet to be established. Candidate recombinant B19V vaccines have been developed but may not be commercially feasible. We review relevant features of the molecular and cellular biology of these viruses, and the human immune response that they elicit, which have allowed a deep understanding of pathophysiology. PMID:27806994

  6. "Taking the human out of human rights" human rights or group rights?

    Directory of Open Access Journals (Sweden)

    Bojanić Petar

    2015-01-01

    Full Text Available What interest me are the reasons why “human” or “human rights” could be important or possibly most important in constituting a group (hence the introduction of the complicated word “group” and “group right(s” in the subtitle. If I had to justify the existence of the latest debates on nature, justification and universality of human rights, on their distinction from other normative standards, on the philosophy and (legal foundation of human rights, on “Human Rights without (or with Foundations” (Raz, Tasioulas, Besson, then I would immediately conclude that this “process of grandiose concretization” of a complete fabrication is far from over. Despite the innumerable pacts and international conventions established after World War II, the slew of obligations to which states have agreed in the last few decades, the establishment of rights to secession or humanitarian intervention it is as if the constitution of classification of basic human rights and their universality is far from over. [Projekat Ministarstva nauke Republike Srbije, br. 43007

  7. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    International Nuclear Information System (INIS)

    Ramasharma, K.; Li, C.H.

    1987-01-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and α-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin

  8. Human intrusion

    International Nuclear Information System (INIS)

    Hora, S.; Neill, R.; Williams, R.; Bauser, M.; Channell, J.

    1993-01-01

    This paper focused on the possible approaches to evaluating the impacts of human intrusion on nuclear waste disposal. Several major issues were reviewed. First, it was noted that human intrusion could be addressed either quantitatively through performance assessments or qualitatively through design requirements. Second, it was decided that it was impossible to construct a complete set of possible future human intrusion scenarios. Third, the question of when the effect of possible human intrusion should be considered, before or after site selection was reviewed. Finally, the time frame over which human intrusion should be considered was discussed

  9. Modern Human Engineering

    International Nuclear Information System (INIS)

    Jeong, Byeong Yong; Lee Dong Kyeong

    2005-08-01

    These are the titles of each chapter. They are as in the following; design of human-centerdness, human machine system, information processing process, sense of human, user interface, elements of human body, vital dynamics, measurement of reaction of human body, estimation and management of working environment, mental characteristic of human, human error, group, organization and leadership, safety supervision, process analysis, time studying, work sampling, work factor and methods time measurement, introduction of muscular skeletal disease and program of preventive management.

  10. Modern Human Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Byeong Yong; Lee Dong Kyeong

    2005-08-15

    These are the titles of each chapter. They are as in the following; design of human-centerdness, human machine system, information processing process, sense of human, user interface, elements of human body, vital dynamics, measurement of reaction of human body, estimation and management of working environment, mental characteristic of human, human error, group, organization and leadership, safety supervision, process analysis, time studying, work sampling, work factor and methods time measurement, introduction of muscular skeletal disease and program of preventive management.

  11. Human to human transmission of arthropod-borne pathogens

    NARCIS (Netherlands)

    Martina, B.E.; Barzon, L.; Pijlman, G.P.; Fuente, J. de la; Rizzoli, A.; Wammes, L.J.; Takken, W.; Rij, R.P. van; Papa, A.

    2017-01-01

    Human-to-human (H2H) transmitted arthropod-borne pathogens are a growing burden worldwide, with malaria and dengue being the most common mosquito-borne H2H transmitted diseases. The ability of vectors to get infected by humans during a blood meal to further propel an epidemic depends on complex

  12. Improved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice

    Directory of Open Access Journals (Sweden)

    Susann Rahmig

    2016-10-01

    Full Text Available Human erythro-megakaryopoiesis does not occur in humanized mouse models, preventing the in vivo analysis of human hematopoietic stem cell (HSC differentiation into these lineages in a surrogate host. Here we show that stably engrafted KIT-deficient NOD/SCID Il2rg−/− KitW41/W41 (NSGW41 mice support much improved human erythropoiesis and platelet formation compared with irradiated NSG recipients. Considerable numbers of human erythroblasts and mature thrombocytes are present in the bone marrow and blood, respectively. Morphology, composition, and enucleation capacity of de novo generated human erythroblasts in NSGW41 mice are comparable with those in human bone marrow. Overexpression of human erythropoietin showed no further improvement in human erythrocyte output, but depletion of macrophages led to the appearance of human erythrocytes in the blood. Human erythropoiesis up to normoblasts and platelet formation is fully supported in NSGW41 mice, allowing the analysis of human HSC differentiation into these lineages, the exploration of certain pathophysiologies, and the evaluation of gene therapeutic approaches.

  13. Human to human transmission of arthropod-borne pathogens

    NARCIS (Netherlands)

    Martina, Byron E.; Barzon, Luisa; Pijlman, Gorben P.; Fuente, de la José; Rizzoli, Annapaola; Wammes, Linda J.; Takken, Willem; Rij, van Ronald P.; Papa, Anna

    2017-01-01

    Human-to-human (H2H) transmitted arthropod-borne pathogens are a growing burden worldwide, with malaria and dengue being the most common mosquito-borne H2H transmitted diseases. The ability of vectors to get infected by humans during a blood meal to further propel an epidemic depends on complex

  14. Boundaries of Humanities: Writing Medical Humanities

    Science.gov (United States)

    Bolton, Gillie

    2008-01-01

    Literature and medicine is a discipline within medical humanities, which challenges medicine to reconfigure its scientific model to become interdisciplinary, and be disciplined by arts and humanities as well as science. The psychological, emotional, spiritual and physical are inextricably linked in people, inevitably entailing provisionality,…

  15. The Ubiquity of Humanity and Textuality in Human Experience

    Directory of Open Access Journals (Sweden)

    Daihyun Chung

    2015-11-01

    Full Text Available The so-called “crisis of the humanities” can be understood in terms of an asymmetry between the natural and social sciences on the one hand and the humanities on the other. While the sciences approach topics related to human experience in quantificational or experimental terms, the humanities turn to ancient, canonical, and other texts in the search for truths about human experience. As each approach has its own unique limitations, it is desirable to overcome or remove the asymmetry between them. The present article seeks to do just that by advancing and defending the following two claims: (a that humanity is ubiquitous wherever language is used; and (b that anything that can be experienced by humans is in need of an interpretation. Two arguments are presented in support of these claims. The first argument concerns the nature of questions, which are one of the fundamental marks or manifestations of human language. All questions are ultimately attempts to find meanings or interpretations of what is presented. As such, in questioning phenomena, one seeks to transcend the negative space or oppression of imposed structures; in doing so, one reveals one’s humanity. Second, all phenomena are textual in nature: that which astrophysicists find in distant galaxies or which cognitive neuroscientists find in the structures of the human brain are no less in need of interpretation than the dialogues of Plato or the poems of Homer. Texts are ubiquitous. The implications of these two arguments are identified and discussed in this article. In particular, it is argued that the ubiquity of humanity and textuality points to a view of human nature that is neither individualistic nor collectivist but rather integrational in suggesting that the realization of oneself is inseparable from the realization of others.

  16. Human-machine interactions

    Science.gov (United States)

    Forsythe, J Chris [Sandia Park, NM; Xavier, Patrick G [Albuquerque, NM; Abbott, Robert G [Albuquerque, NM; Brannon, Nathan G [Albuquerque, NM; Bernard, Michael L [Tijeras, NM; Speed, Ann E [Albuquerque, NM

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  17. Human Smuggling

    NARCIS (Netherlands)

    Siegel - Rozenblit, Dina; Zaitch, Damian

    2014-01-01

    Human smuggling is based on a consensus between smuggler, smuggled, and his/her family (which usually guarantees or effectuates payment). However, unauthorized immigrants are violating immigration laws and human smugglers are profiting from enabling illegal immigration. Both human smuggling and its

  18. The effects of human resource flexibility on human resources development

    Directory of Open Access Journals (Sweden)

    SeidMehdi Veise

    2014-08-01

    Full Text Available Human resources are the primary factor for development of competitiveness and innovation and reaching competitive advantage and they try to improve corporate capabilities through various characteristics such as value creation, scarcity and difficulty of imitation. This paper investigates the effect of human resource flexibility and its dimensions on human resource development and its dimensions. The survey was conducted using descriptive-correlation method that intended to describe how human resource flexibility was effective on human resource development. Questionnaire was tool of data collection. The statistical population included one hundred employees of the Electric Company in Ilam province, thus census method was used. Reliability of the questionnaire was measured via Cronbach's alpha equal to 0.96. The findings revealed that flexibility and its dimensions were effective on human resource development and dimensions of it. As a result, human resource flexibility should be considered for development of human resources and employees with the highest flexibility should be selected.

  19. Human Adaptive Mechatronics and Human-System Modelling

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are 'Human Adaptive Mechatronics (HAM' and 'Human-System Modelling (HSM', are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operators' skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory-motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human-mechatronics systems are also mentioned.

  20. Human-specific HERV-K insertion causes genomic variations in the human genome.

    Directory of Open Access Journals (Sweden)

    Wonseok Shin

    Full Text Available Human endogenous retroviruses (HERV sequences account for about 8% of the human genome. Through comparative genomics and literature mining, we identified a total of 29 human-specific HERV-K insertions. We characterized them focusing on their structure and flanking sequence. The results showed that four of the human-specific HERV-K insertions deleted human genomic sequences via non-classical insertion mechanisms. Interestingly, two of the human-specific HERV-K insertion loci contained two HERV-K internals and three LTR elements, a pattern which could be explained by LTR-LTR ectopic recombination or template switching. In addition, we conducted a polymorphic test and observed that twelve out of the 29 elements are polymorphic in the human population. In conclusion, human-specific HERV-K elements have inserted into human genome since the divergence of human and chimpanzee, causing human genomic changes. Thus, we believe that human-specific HERV-K activity has contributed to the genomic divergence between humans and chimpanzees, as well as within the human population.

  1. Human-specific protein isoforms produced by novel splice sites in the human genome after the human-chimpanzee divergence

    Directory of Open Access Journals (Sweden)

    Kim Dong Seon

    2012-11-01

    Full Text Available Abstract Background Evolution of splice sites is a well-known phenomenon that results in transcript diversity during human evolution. Many novel splice sites are derived from repetitive elements and may not contribute to protein products. Here, we analyzed annotated human protein-coding exons and identified human-specific splice sites that arose after the human-chimpanzee divergence. Results We analyzed multiple alignments of the annotated human protein-coding exons and their respective orthologous mammalian genome sequences to identify 85 novel splice sites (50 splice acceptors and 35 donors in the human genome. The novel protein-coding exons, which are expressed either constitutively or alternatively, produce novel protein isoforms by insertion, deletion, or frameshift. We found three cases in which the human-specific isoform conferred novel molecular function in the human cells: the human-specific IMUP protein isoform induces apoptosis of the trophoblast and is implicated in pre-eclampsia; the intronization of a part of SMOX gene exon produces inactive spermine oxidase; the human-specific NUB1 isoform shows reduced interaction with ubiquitin-like proteins, possibly affecting ubiquitin pathways. Conclusions Although the generation of novel protein isoforms does not equate to adaptive evolution, we propose that these cases are useful candidates for a molecular functional study to identify proteomic changes that might bring about novel phenotypes during human evolution.

  2. Securing Humanity - Situating 'Human Security' as Concept and Discourse

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2005-01-01

    markdownabstractAbstract The label ‘human security’ (HS) has attracted much attention since the 1994 Human Development Report, but there are numerous conflicting definitions and agendas and widespread scepticism. The Ogata-Sen Commission report Human Security Now has proposed a unified yet

  3. HUMANISM OF ANTROPOCENTRISM AND ANTROPOCENTRISM WITHOUT HUMANISM

    Directory of Open Access Journals (Sweden)

    N. S. Shilovskaya

    2014-01-01

    Full Text Available Article is devoted to the distinction of humanism and anthropocentrism which is based on the parity of the person and being. Genetic communication of humanism and anthropocentrism and their historical break comes to light.

  4. Human Performance Modeling for Dynamic Human Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald Laurids [Idaho National Laboratory; Joe, Jeffrey Clark [Idaho National Laboratory; Mandelli, Diego [Idaho National Laboratory

    2015-08-01

    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  5. Human Respiratory Syncytial Virus and Human Metapneumovirus

    Directory of Open Access Journals (Sweden)

    Luciana Helena Antoniassi da Silva

    2009-08-01

    Full Text Available The human respiratory syncytial virus (hRSV and the human metapneumovírus (hMPV are main etiological agents of acute respiratory infections (ARI. The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV is the best characterized agent viral of this group, associated with respiratory diseases in lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV, which is structurally similar to the hRSV, in genomic organization, viral structure, antigenicity and clinical symptoms.  The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains hRSV, the bovine (bRSV, as well as the ovine and caprine respiratory syncytial virus and pneumonia virus of mice, the second genus Metapneumovirus, consists of avian metapneumovirus (aMPV and human metapneumovirus (hMPV. In this work, we present a brief narrative review of the literature on important aspects of the biology, epidemiology and clinical manifestations of infections by two respiratory viruses.

  6. Human erythrocytes inhibit complement-mediated solubilization of immune complexes by human serum

    International Nuclear Information System (INIS)

    Dorval, B.L.

    1987-01-01

    The aim of this study was to develop an autologus human system to evaluate the effects of human erythrocytes on solubilization of immune complex precipitates (IC) by human serum. Incubation of IC with fresh human serum or guinea pig serum resulted in solubilization of IC. When packed erythrocytes were added to human serum or guinea pig serum binding of IC to the erythrocyte occurred and IC solubilization was inhibited significantly (p <.025). Sheep erythrocytes did not bind IC or inhibit IC solubilization. To evaluate the role of human erythrocyte complement receptor (CR1) on these findings, human erythrocytes were treated with trypsin or anti-CR1 antibodies. Both treatments abrogated IC binding to human erythrocytes but did not affect the ability of the human erythrocyte to inhibit IC solubilization. Radioimmunoassay was used to measure C3, C4 and C5 activation in human serum after incubation with IC, human erythrocytes, human erythrocytes plus IC, whole blood or in whole blood plus IC

  7. Human-to-human transmission of Brucella - a systematic review.

    Science.gov (United States)

    Tuon, Felipe F; Gondolfo, Regina B; Cerchiari, Natacha

    2017-05-01

    The most common form of transmitting human brucellosis is through contaminated food or direct contact with infected animals. Human-to-human transmission (HHT) has been described as isolated case reports. The aim of this systematic review was to describe all cases of HHT of human brucellosis reported in the medical literature. A literature search was conducted using PubMed, Scopus and Scielo databases using specific search terms published until March 2016. Two investigators independently determined study eligibility. All clinical data were evaluated to construct a table comprising the most important clinical aspects, age, gender, confirmed infection and detection method, transmission method and HHT confirmation and potential source of infection for human transmission. No statistical method was employed in this study. The initial search resulted in 615 publications, but only 35 were included. 45 brucellosis HHT cases were identified. 61% of patients who acquired brucellosis from another human were <1 year old (newborn and breastfeeding). Other cases include sexual transmission, blood transfusion, bone marrow transplantation and aerosol from an infected patient. Most patients (40/45) presented symptoms upon diagnosis. Diagnostic tests included culture, molecular methods and serum testing. Human brucellosis is a disease liable to transmission between humans by placental barrier, lactation, sexual and tissues such as blood and bone marrow. The indication for screening in tissue banks, transplants, blood and pregnancy is not yet established. © 2017 John Wiley & Sons Ltd.

  8. Human Rights Texts: Converting Human Rights Primary Source Documents into Data.

    Science.gov (United States)

    Fariss, Christopher J; Linder, Fridolin J; Jones, Zachary M; Crabtree, Charles D; Biek, Megan A; Ross, Ana-Sophia M; Kaur, Taranamol; Tsai, Michael

    2015-01-01

    We introduce and make publicly available a large corpus of digitized primary source human rights documents which are published annually by monitoring agencies that include Amnesty International, Human Rights Watch, the Lawyers Committee for Human Rights, and the United States Department of State. In addition to the digitized text, we also make available and describe document-term matrices, which are datasets that systematically organize the word counts from each unique document by each unique term within the corpus of human rights documents. To contextualize the importance of this corpus, we describe the development of coding procedures in the human rights community and several existing categorical indicators that have been created by human coding of the human rights documents contained in the corpus. We then discuss how the new human rights corpus and the existing human rights datasets can be used with a variety of statistical analyses and machine learning algorithms to help scholars understand how human rights practices and reporting have evolved over time. We close with a discussion of our plans for dataset maintenance, updating, and availability.

  9. Chromatic blur perception in the presence of luminance contrast.

    Science.gov (United States)

    Jennings, Ben J; Kingdom, Frederick A A

    2017-06-01

    Hel-Or showed that blurring the chromatic but not the luminance layer of an image of a natural scene failed to elicit any impression of blur. Subsequent studies have suggested that this effect is due either to chromatic blur being masked by spatially contiguous luminance edges in the scene (Journal of Vision 13 (2013) 14), or to a relatively compressed transducer function for chromatic blur (Journal of Vision 15 (2015) 6). To test between the two explanations we conducted experiments using as stimuli both images of natural scenes as well as simple edges. First, we found that in color-and-luminance images of natural scenes more chromatic blur was needed to perceptually match a given level of blur in an isoluminant, i.e. colour-only scene. However, when the luminance layer in the scene was rotated relative to the chromatic layer, thus removing the colour-luminance edge correlations, the matched blur levels were near equal. Both results are consistent with Sharman et al.'s explanation. Second, when observers matched the blurs of luminance-only with isoluminant scenes, the matched blurs were equal, against Kingdom et al.'s prediction. Third, we measured the perceived blur in a square-wave as a function of (i) contrast (ii) number of luminance edges and (iii) the relative spatial phase between the colour and luminance edges. We found that the perceived chromatic blur was dependent on both relative phase and the number of luminance edges, or dependent on the luminance contrast if only a single edge is present. We conclude that this Hel-Or effect is largely due to masking of chromatic blur by spatially contiguous luminance edges. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. SARA South Observations and Analysis of the Solar Type, Totally Eclipsing, Over Contact Binary, PY Aquarii

    Science.gov (United States)

    Chamberlain, Heather; Samec, Ronald G.; Caton, Daniel Bruce; Van Hamme, Walter

    2018-01-01

    PY Aqr (GSC 05191-00853) is a solar Type (T ~ 5750K) eclipsing binary. It was observed in July to October, 2017 at Cerro Tololo in remote mode with the 0.6-m SARA South reflector. Two times of minimum light were calculated from our present observations, a primary and a secondary eclipse:HJD Min I = 2457951.7762±0.0006 HJD Min II = 2458019.5295±00.0003. Both weighted as 1.0.In addition, four timings were determined from online data given in IBVS 5600 and five observations at minima were determined from archived All Sky Automated Survey Data:HJD Min I = 2452908.3165, 2452912.33612 HJD Min II = 2452877.5621, 2452913.34465. All weighted as 0.5.ASAS Observations at minima: 2452094.688, 2453478.882, 2453266.576, 2452093.685 and 54729.600. Each weighted as 0.10The following linear and quadratic ephemerides were determined from all available times of minimum light:JD Hel Min I=2452951.7443±0.0008d + 0.402093441±0.000000099 X E {1} JD Hel Min I=2452951.7439±0.0007d + 0.4020912±0.0000007 X E +0.00000000018 ± 0.00000000006 X E2 {2}A BVRI Bessell filtered simultaneous Wilson-Devinney Program (W-D) solution reveals that the system has a mass ratio of ~0.34 and a component temperature difference of only ~40 K. One low luminosity (Tfact ~ 0.94, ~66 degree radius) large cool region of spots was iterated on the primary component in the WD Synthetic Light Curve computations. It appears in the Southern Hemisphere (colatitude 155 degrees). The Roche Lobe fill-out of the binary is ~17%. The inclination is ~86 degrees. An eclipse duration of ~10 minutes was determined for the primary eclipse and the light curve solution. Additional and more detailed information is given in this report.

  11. Genomic-Enabled Prediction in Maize Using Kernel Models with Genotype × Environment Interaction.

    Science.gov (United States)

    Bandeira E Sousa, Massaine; Cuevas, Jaime; de Oliveira Couto, Evellyn Giselly; Pérez-Rodríguez, Paulino; Jarquín, Diego; Fritsche-Neto, Roberto; Burgueño, Juan; Crossa, Jose

    2017-06-07

    Multi-environment trials are routinely conducted in plant breeding to select candidates for the next selection cycle. In this study, we compare the prediction accuracy of four developed genomic-enabled prediction models: (1) single-environment, main genotypic effect model (SM); (2) multi-environment, main genotypic effects model (MM); (3) multi-environment, single variance G×E deviation model (MDs); and (4) multi-environment, environment-specific variance G×E deviation model (MDe). Each of these four models were fitted using two kernel methods: a linear kernel Genomic Best Linear Unbiased Predictor, GBLUP (GB), and a nonlinear kernel Gaussian kernel (GK). The eight model-method combinations were applied to two extensive Brazilian maize data sets (HEL and USP data sets), having different numbers of maize hybrids evaluated in different environments for grain yield (GY), plant height (PH), and ear height (EH). Results show that the MDe and the MDs models fitted with the Gaussian kernel (MDe-GK, and MDs-GK) had the highest prediction accuracy. For GY in the HEL data set, the increase in prediction accuracy of SM-GK over SM-GB ranged from 9 to 32%. For the MM, MDs, and MDe models, the increase in prediction accuracy of GK over GB ranged from 9 to 49%. For GY in the USP data set, the increase in prediction accuracy of SM-GK over SM-GB ranged from 0 to 7%. For the MM, MDs, and MDe models, the increase in prediction accuracy of GK over GB ranged from 34 to 70%. For traits PH and EH, gains in prediction accuracy of models with GK compared to models with GB were smaller than those achieved in GY. Also, these gains in prediction accuracy decreased when a more difficult prediction problem was studied. Copyright © 2017 Bandeira e Sousa et al.

  12. Identifying Stable Reference Genes for qRT-PCR Normalisation in Gene Expression Studies of Narrow-Leafed Lupin (Lupinus angustifolius L..

    Directory of Open Access Journals (Sweden)

    Candy M Taylor

    Full Text Available Quantitative Reverse Transcription PCR (qRT-PCR is currently one of the most popular, high-throughput and sensitive technologies available for quantifying gene expression. Its accurate application depends heavily upon normalisation of gene-of-interest data with reference genes that are uniformly expressed under experimental conditions. The aim of this study was to provide the first validation of reference genes for Lupinus angustifolius (narrow-leafed lupin, a significant grain legume crop using a selection of seven genes previously trialed as reference genes for the model legume, Medicago truncatula. In a preliminary evaluation, the seven candidate reference genes were assessed on the basis of primer specificity for their respective targeted region, PCR amplification efficiency, and ability to discriminate between cDNA and gDNA. Following this assessment, expression of the three most promising candidates [Ubiquitin C (UBC, Helicase (HEL, and Polypyrimidine tract-binding protein (PTB] was evaluated using the NormFinder and RefFinder statistical algorithms in two narrow-leafed lupin lines, both with and without vernalisation treatment, and across seven organ types (cotyledons, stem, leaves, shoot apical meristem, flowers, pods and roots encompassing three developmental stages. UBC was consistently identified as the most stable candidate and has sufficiently uniform expression that it may be used as a sole reference gene under the experimental conditions tested here. However, as organ type and developmental stage were associated with greater variability in relative expression, it is recommended using UBC and HEL as a pair to achieve optimal normalisation. These results highlight the importance of rigorously assessing candidate reference genes for each species across a diverse range of organs and developmental stages. With emerging technologies, such as RNAseq, and the completion of valuable transcriptome data sets, it is possible that other

  13. Genomic-Enabled Prediction in Maize Using Kernel Models with Genotype × Environment Interaction

    Directory of Open Access Journals (Sweden)

    Massaine Bandeira e Sousa

    2017-06-01

    Full Text Available Multi-environment trials are routinely conducted in plant breeding to select candidates for the next selection cycle. In this study, we compare the prediction accuracy of four developed genomic-enabled prediction models: (1 single-environment, main genotypic effect model (SM; (2 multi-environment, main genotypic effects model (MM; (3 multi-environment, single variance G×E deviation model (MDs; and (4 multi-environment, environment-specific variance G×E deviation model (MDe. Each of these four models were fitted using two kernel methods: a linear kernel Genomic Best Linear Unbiased Predictor, GBLUP (GB, and a nonlinear kernel Gaussian kernel (GK. The eight model-method combinations were applied to two extensive Brazilian maize data sets (HEL and USP data sets, having different numbers of maize hybrids evaluated in different environments for grain yield (GY, plant height (PH, and ear height (EH. Results show that the MDe and the MDs models fitted with the Gaussian kernel (MDe-GK, and MDs-GK had the highest prediction accuracy. For GY in the HEL data set, the increase in prediction accuracy of SM-GK over SM-GB ranged from 9 to 32%. For the MM, MDs, and MDe models, the increase in prediction accuracy of GK over GB ranged from 9 to 49%. For GY in the USP data set, the increase in prediction accuracy of SM-GK over SM-GB ranged from 0 to 7%. For the MM, MDs, and MDe models, the increase in prediction accuracy of GK over GB ranged from 34 to 70%. For traits PH and EH, gains in prediction accuracy of models with GK compared to models with GB were smaller than those achieved in GY. Also, these gains in prediction accuracy decreased when a more difficult prediction problem was studied.

  14. Minimizing Human Risk: Human Performance Models in the Space Human Factors and Habitability and Behavioral Health and Performance Elements

    Science.gov (United States)

    Gore, Brian F.

    2016-01-01

    Human space exploration has never been more exciting than it is today. Human presence to outer worlds is becoming a reality as humans are leveraging much of our prior knowledge to the new mission of going to Mars. Exploring the solar system at greater distances from Earth than ever before will possess some unique challenges, which can be overcome thanks to the advances in modeling and simulation technologies. The National Aeronautics and Space Administration (NASA) is at the forefront of exploring our solar system. NASA's Human Research Program (HRP) focuses on discovering the best methods and technologies that support safe and productive human space travel in the extreme and harsh space environment. HRP uses various methods and approaches to answer questions about the impact of long duration missions on the human in space including: gravity's impact on the human body, isolation and confinement on the human, hostile environments impact on the human, space radiation, and how the distance is likely to impact the human. Predictive models are included in the HRP research portfolio as these models provide valuable insights into human-system operations. This paper will provide an overview of NASA's HRP and will present a number of projects that have used modeling and simulation to provide insights into human-system issues (e.g. automation, habitat design, schedules) in anticipation of space exploration.

  15. Rootsi põllumajandusminister Ann-Christin Nykvist : Oleme ühel meelel / Ann-Christin Nykvist ; interv. Annika Poldre

    Index Scriptorium Estoniae

    Nykvist, Ann-Christin

    2004-01-01

    Eestis külaskäigul viibinud Rootsi põllumajandus-, toidu- ja tarbimisminister tutvustab oma tööd, Rootsi põllumajanduspoliitikat, räägib Rootsi toidukaupade eelistamisest, EL-i laienemise mõjust Rootsi põllumajandusele, Rootsi ja Eesti koostööst põllumajanduses

  16. Integrated Environmental Modelling: Human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  17. Trafficking in human beings, enslavement, crimes against humanity: unravelling the concepts

    NARCIS (Netherlands)

    van der Wilt, H.

    2014-01-01

    This article explores the conceptual relationship between trafficking in human beings, enslavement and crimes against humanity. The analysis of case law of the International Criminal Tribunal for the Former Yugoslavia and the European Court on Human Rights reveals that, while trafficking in human

  18. Rejecting medical humanism: medical humanities and the metaphysics of medicine.

    Science.gov (United States)

    Bishop, Jeffrey P

    2008-03-01

    The call for a narrative medicine has been touted as the cure-all for an increasingly mechanical medicine. It has been claimed that the humanities might create more empathic, reflective, professional and trustworthy doctors. In other words, we can once again humanise medicine through the addition of humanities. In this essay, I explore how the humanities, particularly narrative medicine, appeals to the metaphysical commitments of the medical institution in order to find its justification, and in so doing, perpetuates a dualism of humanity that would have humanism as the counterpoint to the biopsychosociologisms of our day.

  19. Stendhal lecteur d’Helvétius et des Idéologues sur les avatars de l’amitié

    OpenAIRE

    Bassou, Muriel

    2015-01-01

    En janvier 1812, au moment de la conception du « beylisme », Henri Beyle, qui n’est pas encore Stendhal, fait le point sur le « Character of Mr Mys[elf] » en ces termes : Ses pensées sont neuves parce qu’il a refait à neuf beaucoup d’idées générales qui servent de mesure, comme : gloire, grandeur, bonheur, etc.Les autres mesurent ce qu’ils aperçoivent dans la nature avec une aune qui a quarante-deux pouces. Celle qu’il s’est faite au moyen d’Hel[vétius], de Tra[cy] et de l’expérience, est de ...

  20. From the Other Shore: Alice Rühle-Gerstel and Otto Rühle. The Experience of Left-Wing Political Exile in Mexico, 1935-1943

    Directory of Open Access Journals (Sweden)

    Lizette Jacinto

    2014-07-01

    Full Text Available This work seeks to critically analyze the intellectual conditions that the Rühle couple faced during their 1935-1943 political exile in Mexico, after fleeing German National Socialism. Both of them were renowned thinkers both in the academic and political fields, and both before and after World War I, specially during the so-called Weimar Republic. The paper highlights the personality of Alice Rühel-Gerstel, born in Prague to a Jewish family, for she would become a feminist and writer renowned in her time, but forgotten after Nazi censorship. This subject, as yet unpublished in Mexico, feeds on deep archive research carried out in Germany, the Netherlands, and Mexico.

  1. Hadroproduction of t anti-t pair in association with an isolated photon at NLO accuracy matched with parton shower

    Science.gov (United States)

    Kardos, Adam; Trócsányi, Zoltán

    2015-05-01

    We simulate the hadroproduction of a -pair in association with a hard photon at LHC using the PowHel package. These events are almost fully inclusive with respect to the photon, allowing for any physically relevant isolation of the photon. We use the generated events, stored according to the Les-Houches event format, to make predictions for differential distributions formally at the next-to-leading order (NLO) accuracy and we compare these to existing predictions accurate at NLO using the smooth isolation prescription of Frixione. Our fixed-order predictions include the direct-photon contribution only. We also make predictions for distributions after full parton shower and hadronization using the standard experimental cone-isolation of the photon.

  2. Emergent kink stability of a magnetized plasma jet injected into a transverse background magnetic field

    Science.gov (United States)

    Zhang, Yue; Gilmore, Mark; Hsu, Scott C.; Fisher, Dustin M.; Lynn, Alan G.

    2017-11-01

    We report experimental results on the injection of a magnetized plasma jet into a transverse background magnetic field in the HelCat linear plasma device at the University of New Mexico [M. Gilmore et al., J. Plasma Phys. 81(1), 345810104 (2015)]. After the plasma jet leaves the plasma-gun muzzle, a tension force arising from an increasing curvature of the background magnetic field induces in the jet a sheared axial-flow gradient above the theoretical kink-stabilization threshold. We observe that this emergent sheared axial flow stabilizes the n = 1 kink mode in the jet, whereas a kink instability is observed in the jet when there is no background magnetic field present.

  3. Atypical presentations of eosinophilic fasciitis

    Directory of Open Access Journals (Sweden)

    Tulin Ergun

    2016-01-01

    Full Text Available Eosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia.

  4. Konkursi "Parim puitehitis 2007" võitjad

    Index Scriptorium Estoniae

    2007-01-01

    Parim puitehitis 2007 - eramu Kiili vallas (arhitekt ja tellija Karmo Tõra, projekteerijad K. Tõra, Andres Sokk, Tõnu Peipmam). Äramärgitud - eramu Mähel (arhitekt Raul Vaiksoo, projekteerija Raul Vaiksoo Arhitektuuribüroo), Eesti Kunstiakadeemia üliõpilaste ehitised Pedaspeal (juhendajad Andres Alver ja Jaan Tiidemann, üliõpilased Anu Arm, 2006 ja Ivan Sergejev, 2007). Liimpuidu kasutamise eriauhind - AS Palmako tootmishoone Kavastus Tartumaal (projekteerija AS Resand, Villu Leppik ja Alar Just, arhitektuuriprojekt: Tartu Arhitektuuribüroo, Roman Smushkin). Voodrilaua kasutamise eriauhind - Tammeõue kortermajad Viimsis (arhitekt: Agabus, Endjärv, Truverk Arhitektid, Mattias Agabus, Eero Endjärv, Illimat Truverk, Priit Pent, projekteerimine: Pikoprojekt OÜ, ehitaja: AS NCC Ehitus). Žürii koosseis

  5. Na pjatom konkurse derevjannoi arhitekturõ pobedili individualnõje zhilõje doma / Märt Riistop

    Index Scriptorium Estoniae

    Riistop, Märt

    2008-01-01

    Konkursist "Eesti parim puitehitis 2007", premeeritud töödest. Parim puitehitis 2007 - eramu Kiili vallas (arhitekt ja tellija Karmo Tõra, projekteerijad K. Tõra, Andres Sokk, Tõnu Peipmam). Äramärgitud - eramu Mähel (arhitekt Raul Vaiksoo, projekteerija Raul Vaiksoo Arhitektuuribüroo), Eesti Kunstiakadeemia üliõpilaste ehitised Pedaspeal (juhendajad Andres Alver ja Jaan Tiidemann, üliõpilased Anu Arm, 2006 ja Ivan Sergejev, 2007). Liimpuidu kasutamise eriauhind - AS Palmako tootmishoone Tartumaal Kavastus (projekteerija AS Resand, Villu Leppik ja Alar Just, arhitektuuriprojekt: Tartu Arhitektuuribüroo, Roman Smushkin). Voodrilaua kasutamise eriauhind - Tammeõue kortermajad Viimsis (arhitekt: Agabus, Endjärv, Truverk Arhitektid, projekteerimine: Pikoprojekt OÜ, ehitaja: AS NCC Ehitus). Žürii koosseis

  6. The failure of aluminium nitride under shock

    International Nuclear Information System (INIS)

    Pickup, I.M.; Bourne, N.K.

    2002-01-01

    The shear strength of aluminium nitride has been measured over a range of impact stresses by measuring lateral stresses in plate impact experiments. The range of impact stress spanned several key shock thresholds for the material, pre and post Hugoniot elastic limit and up to values where the hexagonal to cubic phase transition starts. The shear strength measurements indicate significant inelastic damage at stress levels in excess of the HEL, but a significant recovery of strength at the highest impact stress was observed. This stress equates to the phase transition stress. The shear strength behaviour is compared to that of silicon carbide, which does not exhibit a phase change at these impact velocities

  7. Human Milk Glycoproteins Protect Infants Against Human Pathogens

    Science.gov (United States)

    Liu, Bo

    2013-01-01

    Abstract Breastfeeding protects the neonate against pathogen infection. Major mechanisms of protection include human milk glycoconjugates functioning as soluble receptor mimetics that inhibit pathogen binding to the mucosal cell surface, prebiotic stimulation of gut colonization by favorable microbiota, immunomodulation, and as a substrate for bacterial fermentation products in the gut. Human milk proteins are predominantly glycosylated, and some biological functions of these human milk glycoproteins (HMGPs) have been reported. HMGPs range in size from 14 kDa to 2,000 kDa and include mucins, secretory immunoglobulin A, bile salt-stimulated lipase, lactoferrin, butyrophilin, lactadherin, leptin, and adiponectin. This review summarizes known biological roles of HMGPs that may contribute to the ability of human milk to protect neonates from disease. PMID:23697737

  8. Development and function of human innate immune cells in a humanized mouse model.

    Science.gov (United States)

    Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A

    2014-04-01

    Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

  9. Human Factors Interface with Systems Engineering for NASA Human Spaceflights

    Science.gov (United States)

    Wong, Douglas T.

    2009-01-01

    This paper summarizes the past and present successes of the Habitability and Human Factors Branch (HHFB) at NASA Johnson Space Center s Space Life Sciences Directorate (SLSD) in including the Human-As-A-System (HAAS) model in many NASA programs and what steps to be taken to integrate the Human-Centered Design Philosophy (HCDP) into NASA s Systems Engineering (SE) process. The HAAS model stresses systems are ultimately designed for the humans; the humans should therefore be considered as a system within the systems. Therefore, the model places strong emphasis on human factors engineering. Since 1987, the HHFB has been engaging with many major NASA programs with much success. The HHFB helped create the NASA Standard 3000 (a human factors engineering practice guide) and the Human Systems Integration Requirements document. These efforts resulted in the HAAS model being included in many NASA programs. As an example, the HAAS model has been successfully introduced into the programmatic and systems engineering structures of the International Space Station Program (ISSP). Success in the ISSP caused other NASA programs to recognize the importance of the HAAS concept. Also due to this success, the HHFB helped update NASA s Systems Engineering Handbook in December 2007 to include HAAS as a recommended practice. Nonetheless, the HAAS model has yet to become an integral part of the NASA SE process. Besides continuing in integrating HAAS into current and future NASA programs, the HHFB will investigate incorporating the Human-Centered Design Philosophy (HCDP) into the NASA SE Handbook. The HCDP goes further than the HAAS model by emphasizing a holistic and iterative human-centered systems design concept.

  10. Human Thermal Model Evaluation Using the JSC Human Thermal Database

    Science.gov (United States)

    Bue, Grant; Makinen, Janice; Cognata, Thomas

    2012-01-01

    Human thermal modeling has considerable long term utility to human space flight. Such models provide a tool to predict crew survivability in support of vehicle design and to evaluate crew response in untested space environments. It is to the benefit of any such model not only to collect relevant experimental data to correlate it against, but also to maintain an experimental standard or benchmark for future development in a readily and rapidly searchable and software accessible format. The Human thermal database project is intended to do just so; to collect relevant data from literature and experimentation and to store the data in a database structure for immediate and future use as a benchmark to judge human thermal models against, in identifying model strengths and weakness, to support model development and improve correlation, and to statistically quantify a model s predictive quality. The human thermal database developed at the Johnson Space Center (JSC) is intended to evaluate a set of widely used human thermal models. This set includes the Wissler human thermal model, a model that has been widely used to predict the human thermoregulatory response to a variety of cold and hot environments. These models are statistically compared to the current database, which contains experiments of human subjects primarily in air from a literature survey ranging between 1953 and 2004 and from a suited experiment recently performed by the authors, for a quantitative study of relative strength and predictive quality of the models.

  11. Human milk donation is an alternative to human milk bank.

    Science.gov (United States)

    Hsu, Ho-Torng; Fong, Tze-Vun; Hassan, Nurulhuda Mat; Wong, Hoi-Ling; Rai, Jasminder Kaur; Khalid, Zorina

    2012-04-01

    Human milk bank is a source of human milk supply in many neonatal intensive care units. However, there are some hospitals without this facility because of financial or religious impediments, such as the Muslim community. We introduced human milk donation as an alternative to human milk banking based on Islamic principles. The suitable donor is a healthy rooming-in mother whose expressed breastmilk is in excess of her baby's demand. The milk is used after 72 hours of freezing at -20°C. The donor must fulfill the criteria for selection of donors and be nonreactive to human immunodeficiency virus and syphilis. Once the recipient's family and the donor state their desire for the human milk donation, a meeting with both parties is made. Unpasteurized frozen-thawed donor's milk will be provided to the recipient after written consents are obtained from both parties. This study was carried out in the Duchess of Kent Hospital (Sandakan, Sabah, Malaysia) between January 2009 and December 2010. A total of 48 babies received donated breastmilk. Forty-two infants were from the special care nursery, and the remaining six were from the pediatric ward. Eighty-eight percent of the donors and 77% of the recipients were Muslims. Sixty percent of the infants who received donated human milk were premature. Two infants died because of the underlying nature of their disease. Human milk donation is an option for hospitals without a human milk bank or in the Muslim community.

  12. Human algorithmic stability and human Rademacher complexity

    NARCIS (Netherlands)

    Vahdat, Mehrnoosh; Oneto, L.; Ghio, A; Anguita, D.; Funk, M.; Rauterberg, G.W.M.

    2015-01-01

    In Machine Learning (ML), the learning process of an algo- rithm given a set of evidences is studied via complexity measures. The way towards using ML complexity measures in the Human Learning (HL) domain has been paved by a previous study, which introduced Human Rademacher Complexity (HRC): in this

  13. I Reach Faster When I See You Look: Gaze Effects in Human-Human and Human-Robot Face-to-Face Cooperation.

    Science.gov (United States)

    Boucher, Jean-David; Pattacini, Ugo; Lelong, Amelie; Bailly, Gerrard; Elisei, Frederic; Fagel, Sascha; Dominey, Peter Ford; Ventre-Dominey, Jocelyne

    2012-01-01

    Human-human interaction in natural environments relies on a variety of perceptual cues. Humanoid robots are becoming increasingly refined in their sensorimotor capabilities, and thus should now be able to manipulate and exploit these social cues in cooperation with their human partners. Previous studies have demonstrated that people follow human and robot gaze, and that it can help them to cope with spatially ambiguous language. Our goal is to extend these findings into the domain of action, to determine how human and robot gaze can influence the speed and accuracy of human action. We report on results from a human-human cooperation experiment demonstrating that an agent's vision of her/his partner's gaze can significantly improve that agent's performance in a cooperative task. We then implement a heuristic capability to generate such gaze cues by a humanoid robot that engages in the same cooperative interaction. The subsequent human-robot experiments demonstrate that a human agent can indeed exploit the predictive gaze of their robot partner in a cooperative task. This allows us to render the humanoid robot more human-like in its ability to communicate with humans. The long term objectives of the work are thus to identify social cooperation cues, and to validate their pertinence through implementation in a cooperative robot. The current research provides the robot with the capability to produce appropriate speech and gaze cues in the context of human-robot cooperation tasks. Gaze is manipulated in three conditions: Full gaze (coordinated eye and head), eyes hidden with sunglasses, and head fixed. We demonstrate the pertinence of these cues in terms of statistical measures of action times for humans in the context of a cooperative task, as gaze significantly facilitates cooperation as measured by human response times.

  14. Modelling Engagement in Multi-Party Conversations : Data-Driven Approaches to Understanding Human-Human Communication Patterns for Use in Human-Robot Interactions

    OpenAIRE

    Oertel, Catharine

    2016-01-01

    The aim of this thesis is to study human-human interaction in order to provide virtual agents and robots with the capability to engage into multi-party-conversations in a human-like-manner. The focus lies with the modelling of conversational dynamics and the appropriate realization of multi-modal feedback behaviour. For such an undertaking, it is important to understand how human-human communication unfolds in varying contexts and constellations over time. To this end, multi-modal human-human...

  15. Human dignity and human rights in bioethics: the Kantian approach.

    Science.gov (United States)

    Rothhaar, Markus

    2010-08-01

    The concept of human dignity plays an important role in the public discussion about ethical questions concerning modern medicine and biology. At the same time, there is a widespread skepticism about the possibility to determine the content and the claims of human dignity. The article goes back to Kantian Moral Philosophy, in order to show that human dignity has in fact a determinable content not as a norm in itself, but as the principle and ground of human rights and any deontological norms in biomedical ethics. When it comes to defining the scope of human dignity, i.e., the question which entities are protected by human dignity, Kant clearly can be found on the "pro life"-side of the controversy. This, however, is the result of some specific implications of Kant's transcendental approach that may be put into question.

  16. Nõukogude anneksioon ja riigi järjepidevus : Eesti, Läti ja Leedu staatus rahvusvahelises õiguses 1940. a.-1991. a. ja pärast 1991. a : uurimus pingest normatiivsuse ja võimu vahel rahvusvahelises õiguses / Lauri Mälksoo ; tõlkinud Alar Hels

    Index Scriptorium Estoniae

    Mälksoo, Lauri, 1975-

    2005-01-01

    Tõlgitud väljaandest: Mälksoo, Lauri. Illegal Annexation and State Continuity : the case of the Incorporation of the Baltic States by the USSR. A Study of the Tension between Normativity and Power in International Law. - Leiden ; Boston : Brill, 2003. - 373 lk. - Bibl. lk. 341- 370 ja joonealustes märkustes. - (Monographs on International Law and Human Rights / Erik Castrén Institute of International Law and Human Rights ; 5). ISBN 90-411-2177-3

  17. Managing human performance

    International Nuclear Information System (INIS)

    Bishop, J.; LaRhette, R.

    1988-01-01

    Evaluating human error or human performance problems and correcting the root causes can help preclude recurrence. The Institute of Nuclear Power Operations (INPO), working with several members and participant utilities in an extended pilot program, has developed a nonpunitive program designed to identify, evaluate, and correct situations that cause human performance errors. The program is called the Human Performance Evaluation System (HPES). Its primary goal is to improve human reliability in overall nuclear plant operations by reducing human error through correction of the conditions that cause the errors. Workers at participating nuclear utilities are encouraged to report their errors and a specially trained plant coordinator investigates and recommends actions to correct the root causes of these errors

  18. Theories about evolutionary origins of human hepatitis B virus in primates and humans

    Directory of Open Access Journals (Sweden)

    Breno Frederico de Carvalho Dominguez Souza

    2014-09-01

    Conclusion: Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the ‘90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate hosts because of the proximity between the phylogeny of Old and New World non-human primate and their human hepatitis B virus variants. The importance of further research, related to the subject in South American wild fauna, is paramount and highly relevant for understanding the origin of human hepatitis B virus.

  19. HUMAN BEINGS TRAFFICKING IN THE EUROPEAN COURT OF HUMAN RIGHTS CASE-LAW

    OpenAIRE

    Laura-Cristiana SPĂTARU-NEGURĂ

    2017-01-01

    After last year’s analysis regarding the European Union’s commitment to fight against the human beings trafficking, we have considered to further explore the human beings trafficking approach in the European Court of Human Rights case-law, the most developped regional jurisdiction on human rights. Surprisingly, the European Convention for the Protection of Human Rights and Fundamental Freedoms does not make an express reference to the human beings trafficking. However, we have to bear in mind...

  20. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

    OpenAIRE

    Jiae Kim; Jiae Kim; Kristina K. Peachman; Kristina K. Peachman; Ousman Jobe; Ousman Jobe; Elaine B. Morrison; Atef Allam; Atef Allam; Linda Jagodzinski; Sofia A. Casares; Mangala Rao

    2017-01-01

    Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several...

  1. A Human-Robot Co-Manipulation Approach Based on Human Sensorimotor Information.

    Science.gov (United States)

    Peternel, Luka; Tsagarakis, Nikos; Ajoudani, Arash

    2017-07-01

    This paper aims to improve the interaction and coordination between the human and the robot in cooperative execution of complex, powerful, and dynamic tasks. We propose a novel approach that integrates online information about the human motor function and manipulability properties into the hybrid controller of the assistive robot. Through this human-in-the-loop framework, the robot can adapt to the human motor behavior and provide the appropriate assistive response in different phases of the cooperative task. We experimentally evaluate the proposed approach in two human-robot co-manipulation tasks that require specific complementary behavior from the two agents. Results suggest that the proposed technique, which relies on a minimum degree of task-level pre-programming, can achieve an enhanced physical human-robot interaction performance and deliver appropriate level of assistance to the human operator.

  2. Economics of human trafficking.

    Science.gov (United States)

    Wheaton, Elizabeth M; Schauer, Edward J; Galli, Thomas V

    2010-01-01

    Because freedom of choice and economic gain are at the heart of productivity, human trafficking impedes national and international economic growth. Within the next 10 years, crime experts expect human trafficking to surpass drug and arms trafficking in its incidence, cost to human well-being, and profitability to criminals (Schauer and Wheaton, 2006: 164-165). The loss of agency from human trafficking as well as from modern slavery is the result of human vulnerability (Bales, 2000: 15). As people become vulnerable to exploitation and businesses continually seek the lowest-cost labour sources, trafficking human beings generates profit and a market for human trafficking is created. This paper presents an economic model of human trafficking that encompasses all known economic factors that affect human trafficking both across and within national borders. We envision human trafficking as a monopolistically competitive industry in which traffickers act as intermediaries between vulnerable individuals and employers by supplying differentiated products to employers. In the human trafficking market, the consumers are employers of trafficked labour and the products are human beings. Using a rational-choice framework of human trafficking we explain the social situations that shape relocation and working decisions of vulnerable populations leading to human trafficking, the impetus for being a trafficker, and the decisions by employers of trafficked individuals. The goal of this paper is to provide a common ground upon which policymakers and researchers can collaborate to decrease the incidence of trafficking in humans.

  3. Human Milk Banking.

    Science.gov (United States)

    Haiden, Nadja; Ziegler, Ekhard E

    2016-01-01

    Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula. © 2017 S. Karger AG, Basel.

  4. Chapter 8. Ionisation radiation and human organism. Radioactivity of human tissues

    International Nuclear Information System (INIS)

    Toelgyessy, J.; Harangozo, M.

    2000-01-01

    This is a chapter of textbook of radioecology for university students. In this chapter authors deal with ionisation radiation and human organism as well as with radioactivity of human tissues. Chapter consists of next parts: (1) Radiation stress of human organism; (2) Radioactivity of human tissues and the factors influencing radioactive contamination; (3) Possibilities of decreasing of radiation stress

  5. Foucault and Human Rights: Seeking the Renewal of Human Rights Education

    Science.gov (United States)

    Zembylas, Michalinos

    2016-01-01

    This article takes up Foucault's politics of human rights and suggests that it may constitute a point of departure for the renewal of HRE, not only because it rejects the moral superiority of humanism--the grounding for the dominant liberal framework of international human rights--but also because it makes visible the complexities of human rights…

  6. How Health Humanities Will Save the Life of the Humanities.

    Science.gov (United States)

    Klugman, Craig M

    2017-12-01

    In the last decade, the humanities have been shrinking in number of students, percent of faculty, and in number of degrees awarded. Humanities students also earn lower salaries than their STEM-prepared peers. At the same time, the health humanities have been in ascendance over the last fifteen years. The number of majors, minors and certificates has increased 266% in that time frame, attracting large numbers of students and preparing future patients, lay caregivers, and health care providers to interact with a complicated and dehumanized medical system. In 1982, British philosopher and educator Stephen Toulmin declared that medicine saved philosophy from irrelevance and possibly extinction. I propose that the health humanities can serve a similar function to stave off the decline of the broader humanities. The health humanities can (1) model an applied approach for the broader humanities to attract student interest; (2) develop students' capacity for critical reading, writing and reflection about health and medicine in society, practice, and their own lives and (3) inoculate all students against the influence of medicine, whether through preparing pre-health students to navigate the hidden medical curriculum or preparing future patients to navigate the health care system.

  7. Theories about evolutionary origins of human hepatitis B virus in primates and humans.

    Science.gov (United States)

    Souza, Breno Frederico de Carvalho Dominguez; Drexler, Jan Felix; Lima, Renato Santos de; Rosário, Mila de Oliveira Hughes Veiga do; Netto, Eduardo Martins

    2014-01-01

    The human hepatitis B virus causes acute and chronic hepatitis and is considered one of the most serious human health issues by the World Health Organization, causing thousands of deaths per year. There are similar viruses belonging to the Hepadnaviridae family that infect non-human primates and other mammals as well as some birds. The majority of non-human primate virus isolates were phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial. However, there is a possibility that human hepatitis B virus originated in primates. Knowing whether these viruses might be common to humans and primates is crucial in order to reduce the risk to humans. To review the existing knowledge about the evolutionary origins of viruses of the Hepadnaviridae family in primates. This review was done by reading several articles that provide information about the Hepadnaviridae virus family in non-human primates and humans and the possible origins and evolution of these viruses. The evolutionary origin of viruses of the Hepadnaviridae family in primates has been dated back to several thousand years; however, recent analyses of genomic fossils of avihepadnaviruses integrated into the genomes of several avian species have suggested a much older origin of this genus. Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the '90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate

  8. Instinct(ive) play behaviour in human and non-human players

    DEFF Research Database (Denmark)

    Wirman, Hanna; Jørgensen, Ida Kathrine Hammeleff

    ), the part of instinctual also remains a mystery. In Wirman’s recent studies (e.g. Wirman 2015), however, we can recognise a human tendency to see ‘instinctive’ in animal behaviour while ‘play’ substitutes it in categorising human actions. This poses intriguing questions for multispecies game and play...... studies: Why is it commonsensical to label an animal’s touch screen interaction as ‘instinctive’? While we consider a human ‘playing’ a game? How much do we actually know about the instinctive aspects of human and non-human animal play behaviour? What is the specific importance and role of instincts...... in human play? What kind of definition of ‘instinctual’ is meaningful for the study of games and play? Finally, how to design for instinctual or for non-instinctual play? While many such questions remain out of the reach of a humanist or a design researcher, this paper aims to focus on one single aspect...

  9. Rethinking medical humanities.

    Science.gov (United States)

    Chiapperino, Luca; Boniolo, Giovanni

    2014-12-01

    This paper questions different conceptions of Medical Humanities in order to provide a clearer understanding of what they are and why they matter. Building upon former attempts, we defend a conception of Medical Humanities as a humanistic problem-based approach to medicine aiming at influencing its nature and practice. In particular, we discuss three main conceptual issues regarding the overall nature of this discipline: (i) a problem-driven approach to Medical Humanities; (ii) the need for an integration of Medical Humanities into medicine; (iii) the methodological requirements that could render Medical Humanities an effective framework for medical decision-making.

  10. Distinctively human motivation and another view on human evolution

    OpenAIRE

    Prudkov, Pavel N.

    2006-01-01

    Human evolution is a multidisciplinary problem, one of its aspects is the origin and development of distinctively human psychological features. Cognitive properties (language, symbolic thinking) are considered as such features and numerous authors hypothesize its evolution. We suggest that the most important human characteristic is connected with motivation rather than cognition; this is the ability to construct and maintain long-term goal-directed processes having no biological basis. Once...

  11. Humans mimicking animals: A cortical hierarchy for human vocal communication sounds

    Science.gov (United States)

    Talkington, William J.; Rapuano, Kristina M.; Hitt, Laura; Frum, Chris A.; Lewis, James W.

    2012-01-01

    Numerous species possess cortical regions that are most sensitive to vocalizations produced by their own kind (conspecifics). In humans, the superior temporal sulci (STS) putatively represent homologous voice-sensitive areas of cortex. However, STS regions have recently been reported to represent auditory experience or “expertise” in general rather than showing exclusive sensitivity to human vocalizations per se. Using functional magnetic resonance imaging and a unique non-stereotypical category of complex human non-verbal vocalizations – human-mimicked versions of animal vocalizations – we found a cortical hierarchy in humans optimized for processing meaningful conspecific utterances. This left-lateralized hierarchy originated near primary auditory cortices and progressed into traditional speech-sensitive areas. These results suggest that the cortical regions supporting vocalization perception are initially organized by sensitivity to the human vocal tract in stages prior to the STS. Additionally, these findings have implications for the developmental time course of conspecific vocalization processing in humans as well as its evolutionary origins. PMID:22674283

  12. Propagating Humanized BLT Mice for the Study of Human Immunology and Immunotherapy.

    Science.gov (United States)

    Smith, Drake J; Lin, Levina J; Moon, Heesung; Pham, Alexander T; Wang, Xi; Liu, Siyuan; Ji, Sunjong; Rezek, Valerie; Shimizu, Saki; Ruiz, Marlene; Lam, Jennifer; Janzen, Deanna M; Memarzadeh, Sanaz; Kohn, Donald B; Zack, Jerome A; Kitchen, Scott G; An, Dong Sung; Yang, Lili

    2016-12-15

    The humanized bone marrow-liver-thymus (BLT) mouse model harbors a nearly complete human immune system, therefore providing a powerful tool to study human immunology and immunotherapy. However, its application is greatly limited by the restricted supply of human CD34 + hematopoietic stem cells and fetal thymus tissues that are needed to generate these mice. The restriction is especially significant for the study of human immune systems with special genetic traits, such as certain human leukocyte antigen (HLA) haplotypes or monogene deficiencies. To circumvent this critical limitation, we have developed a method to quickly propagate established BLT mice. Through secondary transfer of bone marrow cells and human thymus implants from BLT mice into NSG (NOD/SCID/IL-2Rγ -/- ) recipient mice, we were able to expand one primary BLT mouse into a colony of 4-5 proBLT (propagated BLT) mice in 6-8 weeks. These proBLT mice reconstituted human immune cells, including T cells, at levels comparable to those of their primary BLT donor mouse. They also faithfully inherited the human immune cell genetic traits from their donor BLT mouse, such as the HLA-A2 haplotype that is of special interest for studying HLA-A2-restricted human T cell immunotherapies. Moreover, an EGFP reporter gene engineered into the human immune system was stably passed from BLT to proBLT mice, making proBLT mice suitable for studying human immune cell gene therapy. This method provides an opportunity to overcome a critical hurdle to utilizing the BLT humanized mouse model and enables its more widespread use as a valuable preclinical research tool.

  13. Comprehensive evaluation of leukocyte lineage derived from human hematopoietic cells in humanized mice.

    Science.gov (United States)

    Takahashi, Masayuki; Tsujimura, Noriyuki; Otsuka, Kensuke; Yoshino, Tomoko; Mori, Tetsushi; Matsunaga, Tadashi; Nakasono, Satoshi

    2012-04-01

    Recently, humanized animals whereby a part of the animal is biologically engineered using human genes or cells have been utilized to overcome interspecific differences. Herein, we analyzed the detail of the differentiation states of various human leukocyte subpopulations in humanized mouse and evaluated comprehensively the similarity of the leukocyte lineage between humanized mice and humans. Humanized mice were established by transplanting human CD34(+) cord blood cells into irradiated severely immunodeficient NOD/Shi-scid/IL2Rγ(null) (NOG) mice, and the phenotypes of human cells contained in bone marrow, thymus, spleen and peripheral blood from the mice were analyzed at monthly intervals until 4 months after cell transplantation. The analysis revealed that transplanted human hematopoietic stem cells via the caudal vein homed and engrafted themselves successfully at the mouse bone marrow. Subsequently, the differentiated leukocytes migrated to the various tissues. Almost all of the leukocytes within the thymus were human cells. Furthermore, analysis of the differentiation states of human leukocytes in various tissues and organs indicated that it is highly likely that the human-like leukocyte lineage can be developed in mice. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. The contributions of human factors on human error in Malaysia aviation maintenance industries

    Science.gov (United States)

    Padil, H.; Said, M. N.; Azizan, A.

    2018-05-01

    Aviation maintenance is a multitasking activity in which individuals perform varied tasks under constant pressure to meet deadlines as well as challenging work conditions. These situational characteristics combined with human factors can lead to various types of human related errors. The primary objective of this research is to develop a structural relationship model that incorporates human factors, organizational factors, and their impact on human errors in aviation maintenance. Towards that end, a questionnaire was developed which was administered to Malaysian aviation maintenance professionals. Structural Equation Modelling (SEM) approach was used in this study utilizing AMOS software. Results showed that there were a significant relationship of human factors on human errors and were tested in the model. Human factors had a partial effect on organizational factors while organizational factors had a direct and positive impact on human errors. It was also revealed that organizational factors contributed to human errors when coupled with human factors construct. This study has contributed to the advancement of knowledge on human factors effecting safety and has provided guidelines for improving human factors performance relating to aviation maintenance activities and could be used as a reference for improving safety performance in the Malaysian aviation maintenance companies.

  15. The idea of human prehistory: the natural sciences, the human sciences, and the problem of human origins in Victorian Britain.

    Science.gov (United States)

    Goodrum, Matthew R

    2012-01-01

    The idea of human prehistory was a provocative and profoundly influential new notion that took shape gradually during the nineteenth century. While archaeology played an important role in providing the evidence for this idea many other sciences such as geology, paleontology, ethnology, and physical anthropology all made critical contributions to discussions about human prehistory. Many works have explored the history of prehistoric archaeology but this paper examines the conceptual content of the idea of "human prehistory" as it developed in the British scientific community. Both the natural and the human sciences contributed to what was in fact a complex collection of individual elements that together constituted the prevailing idea of human prehistory, although there were other competing conceptions of human prehistory endorsed by various scientists and critics of the new view of early human history.

  16. Human versus Non-Human Face Processing: Evidence from Williams Syndrome

    Science.gov (United States)

    Santos, Andreia; Rosset, Delphine; Deruelle, Christine

    2009-01-01

    Increased motivation towards social stimuli in Williams syndrome (WS) led us to hypothesize that a face's human status would have greater impact than face's orientation on WS' face processing abilities. Twenty-nine individuals with WS were asked to categorize facial emotion expressions in real, human cartoon and non-human cartoon faces presented…

  17. The search for novel anticancer agents: a differentiation-based assay and analysis of a folklore product.

    Science.gov (United States)

    Dinnen, R D; Ebisuzaki, K

    1997-01-01

    One alternative approach to the current use of cytotoxic anticancer drugs involves the use of differentiation-inducing agents. However, a wider application of this strategy would require the development of assays to search for new differentiation-inducing agents. In this report we describe an in vitro assay using the murine erythroleukemia (clone 3-1) cells. Tests for the efficacy of this assay for the analysis of antineoplastic activity in natural products led to studies on pau d'arco, a South American folklore product used in the treatment of cancer. Purification of the activity in aqueous extracts by solvent partition and thin layer chromatography (TLC) indicated the presence of two activities, one of which was identified as lapachol. The activity in the pau d'arco extracts and of lapachol was inhibited by vitamin K1. As a vitamin K antagonist, lapachol might target such vitamin K-dependent reactions as the activation of a ligand for the Axl receptor tyrosine kinase.

  18. Appendix: a solution hybridization assay to detect radioactive globin messenger RNA nucleotide sequences

    Energy Technology Data Exchange (ETDEWEB)

    Ross, J

    1976-09-15

    In view of the sensitivity and specificity of the solution hybridization assay for unlabeled globin mRNA a similar technique has been devised to detect radioactive globin mRNA sequences with unlabeled globin cDNA. Several properties of the hybridization reaction are presented since RNA kinetic experiments reported recently depend on the validity of this assay. Data on hybridization analysis of (/sup 3/H)RNA from mouse fetal liver or erythroleukemia cell cytoplasm are presented. These data indicate that the excess cDNA solution assay for radioactive globin mRNA detection is specific for globin mRNA sequences. It can be performed rapidly and is highly reproducible from experiment. It is at least 500-fold less sensitive than the assay for unlabeled globin mRNA, due to the RNAase backgrounds of 0.05 to 0.15 %. However, this limitation has not affected kinetic experiments with non-dividing fetal liver erythroid cells, which synthesize relatively large quantities of globin mRNA.

  19. Cytotoxicity and Glycan-Binding Properties of an 18 kDa Lectin Isolated from the Marine Sponge Halichondria okadai

    Directory of Open Access Journals (Sweden)

    Yasuhiro Ozeki

    2012-04-01

    Full Text Available A divalent cation-independent lectin—HOL-18, with cytotoxic activity against leukemia cells, was purified from a demosponge, Halichondria okadai. HOL-18 is a 72 kDa tetrameric lectin that consists of four non-covalently bonded 18 kDa subunits. Hemagglutination activity of the lectin was strongly inhibited by chitotriose (GlcNAcβ1-4GlcNAcβ1-4GlcNAc, fetuin and mucins from porcine stomach and bovine submaxillary gland. Lectin activity was stable at pH 4–12 and temperatures lower than 60 °C. Frontal affinity chromatography with 16 types of pyridylaminated oligosaccharides indicated that the lectin had an affinity for N-linked complex-type and sphingolipid-type oligosaccharides with N-acetylated hexosamines and neuramic acid at the non-reducing termini. The lectin killed Jurkat leukemia T cells and K562 erythroleukemia cells in a dose- and carbohydrate-dependent manner.

  20. Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children's Oncology Group.

    Science.gov (United States)

    Barnard, Dorothy R; Alonzo, Todd A; Gerbing, Robert B; Lange, Beverly; Woods, William G

    2007-07-01

    Myelodysplastic syndromes (MDS), acute erythroleukemia (FAB M6), and acute megakaryocytic leukemia (FAB M7) have overlapping features. Children without Down syndrome or acute promyelocytic leukemia who were newly diagnosed with primary myelodysplastic syndrome or acute myeloid leukemia (AML) M6 or M7 were compared to children with de novo AML M0-M5. All children were entered on the Children's Cancer Group therapeutic research study CCG 2891. The presentation and outcomes of the 132 children diagnosed with MDS (60 children), AML FAB M6 (19 children), or AML FAB M7 (53 children) were similar. Children with AML FAB M7 were diagnosed at a significantly younger age (P = 0.001). Children with MDS, M6, or M7 had significantly lower white blood cell (WBC) counts (P = 0.001), lower peripheral blast counts (P M6 and AML M7 resemble MDS in presentation, poor induction success rates, and outcomes.

  1. Preleukemic state in atomic bomb survivors

    International Nuclear Information System (INIS)

    Mikami, Motoko

    1980-01-01

    Hematology data before onset of leukemia were available for 55 of the 1462 acute leukemia cases (as of the end of June 1976) collected by RERF. Among these, 8 showed preleukemic state and 2 were polycythemia. In content, preleukemic state comprised anemia, leukopenia and morphological abnormalities of RBC, platelets and WBC. Leukemia cases presenting preleukemic state were, by type, mostly erythroleukemia and monocytic leukemia. Preleukemic state was not necessarily frequent among cases of leukemia in A-bomb survivors exposed to high dose. The prevalence of the 5 items, prescribed as preleukemic state, i.e., anemia (female =50%), and relative monocytosis (>=10%), could not be said to be high in the survivors exposed to high dose. Anemia in males and leukopenia in males and females were increased significantly with age. Leukemia prevalence was significantly high especially in those cases that had presented leukopenia, relative neutropenia or relative lymphocytosis among the 5 items prescribed as preleukemic state. (author)

  2. Two cases of acute leukemia in heavily exposed a-bomb survivors following radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Mikami, Motoko; Kuramoto, Atsushi; Kamada, Nanao; Ohkita, Takeshi; Sawada, Hisao.

    1980-03-01

    Two cases of acute leukemia in heavily exposed atomic bomb survivors following postoperative 60 Co radiotherapy for breast cancer are presented. Case 1, a female who received an estimated dose of 364 rad from the A-bomb at the age of 22, was diagnosed as having left breast cancer 17 years later. At the age of 48, about 8 years after undergoing postoperative 60 Co radiotherapy, she developed acute monocytic leukemia. Case 2, a female who received an estimated dose of 594 rad from the A-bomb at the age of 37, was diagnosed as having right breast cancer 22 years later. At the age of 63, 4 years after postoperative 60 Co radiotherapy, she was found to have acute erythroleukemia. Both cases had been exposed to the A-bomb in Hiroshima and to therapeutic radiation after developing breast cancer presumably induced by A-bomb exposure. Thus it is proposed that acute leukemia was induced by exposure to large doses of radiation from two sources. (author)

  3. Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics

    Directory of Open Access Journals (Sweden)

    Nigel G. Kooreman

    2017-08-01

    Full Text Available There is growing interest in using embryonic stem cell (ESC and induced pluripotent stem cell (iPSC derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an “allogenized” mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.

  4. The 'Disadapted' Animal: Niko Tinbergen on Human Nature and the Human Predicament.

    Science.gov (United States)

    Vicedo, Marga

    2018-06-01

    This paper explores ethologist Niko Tinbergen's path from animal to human studies in the 1960s and 1970s and his views about human nature. It argues, first, that the confluence of several factors explains why Tinbergen decided to cross the animal/human divide in the mid 1960s: his concern about what he called "the human predicament," his relations with British child psychiatrist John Bowlby, the success of ethological explanations of human behavior, and his professional and personal situation. It also argues that Tinbergen transferred his general adaptationist view of animal behavior to the realm of human biology; here, his concern about disadaptation led him to a view of human behavior that was strongly determined by the species' evolutionary past, a position that I call evolutionary determinism. These ideas can be seen in the work he carried out with his wife, Elisabeth Tinbergen, on autism. The paper concludes that Tinbergen's vision of human nature constitutes another version of what anthropologist Clifford Geertz called in 1966 the "stratigraphic" conception of the human: a view of human nature as a composite of levels in which a universal ancestral biological core is superimposed by psychological and cultural layers that represent accidental variation at best and pathological deviation at worst.

  5. ECONOMICS OF HUMAN RESOURCES

    Directory of Open Access Journals (Sweden)

    IOANA - JULIETA JOSAN

    2011-04-01

    Full Text Available The purpose of this paper is to analyze human resources in terms of quantitative and qualitative side with special focus on the human capital accumulation influence. The paper examines the human resources trough human capital accumulation in terms of modern theory of human resources, educational capital, health, unemployment and migration. The findings presented in this work are based on theoretical economy publications and data collected from research materials. Sources of information include: documents from organizations - the EUROSTAT, INSSE - studies from publications, books, periodicals, and the Internet. The paper describes and analyzes human resources characteristics, human resource capacities, social and economic benefits of human capital accumulation based on economy, and the government plans and policies on health, education and labor market.

  6. Human Resource Management and Human Resource Development: Evolution and Contributions

    Science.gov (United States)

    Richman, Nicole

    2015-01-01

    Research agrees that a high performance organization (HPO) cannot exist without an elevated value placed on human resource management (HRM) and human resource development (HRD). However, a complementary pairing of HRM and HRD has not always existed. The evolution of HRD from its roots in human knowledge transference to HRM and present day HRD…

  7. Reconstruction of living bilayer human skin equivalent utilizing human fibrin as a scaffold.

    Science.gov (United States)

    Mazlyzam, A L; Aminuddin, B S; Fuzina, N H; Norhayati, M M; Fauziah, O; Isa, M R; Saim, L; Ruszymah, B H I

    2007-05-01

    Our aim of this study was to develop a new methodology for constructing a bilayer human skin equivalent to create a more clinical compliance skin graft composite for the treatment of various skin defects. We utilized human plasma derived fibrin as the scaffold for the development of a living bilayer human skin equivalent: fibrin-fibroblast and fibrin-keratinocyte (B-FF/FK SE). Skin cells from six consented patients were culture-expanded to passage 1. For B-FF/FK SE formation, human fibroblasts were embedded in human fibrin matrix and subsequently another layer of human keratinocytes in human fibrin matrix was stacked on top. The B-FF/FK SE was then transplanted to athymic mice model for 4 weeks to evaluate its regeneration and clinical performance. The in vivo B-FF/FK SE has similar properties as native human skin by histological analysis and expression of basal Keratin 14 gene in the epidermal layer and Collagen type I gene in the dermal layer. Electron microscopy analysis of in vivo B-FF/FK SE showed well-formed and continuous epidermal-dermal junction. We have successfully developed a technique to engineer living bilayer human skin equivalent using human fibrin matrix. The utilization of culture-expanded human skin cells and fibrin matrix from human blood will allow a fully autologous human skin equivalent construction.

  8. Skin and the non-human human

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2013-01-01

    The article puts forward an aesthetic and psychoanalytic analysis of Titian's painting, The Flaying of Marsyas, arguing that the painting is a reflection on the human subject as a being constituted by skin and by a core of non-humanity. The analysis is partly an answer to Melanie Hart's (2007) ar...... of the 'Muselmann', and Anton Ehrenzweig's psychoanalytic theory of artistic creation. Whereas Hart is focusing on form and colour, I also turn my attention towards the texture of the painting....

  9. Human expunction

    Science.gov (United States)

    Klee, Robert

    2017-10-01

    Thomas Nagel in `The Absurd' (Nagel 1971) mentions the future expunction of the human species as a `metaphor' for our ability to see our lives from the outside, which he claims is one source of our sense of life's absurdity. I argue that the future expunction (not to be confused with extinction) of everything human - indeed of everything biological in a terran sense - is not a mere metaphor but a physical certainty under the laws of nature. The causal processes by which human expunction will take place are presented in some empirical detail, so that philosophers cannot dismiss it as merely speculative. I also argue that appeals to anthropic principles or to forms of mystical cosmology are of no plausible avail in the face of human expunction under the laws of physics.

  10. Pushing Human Frontiers

    Science.gov (United States)

    Zubrin, Robert

    2005-01-01

    With human colonization of Mars, I think you will see a higher standard of civilization, just as America set a higher standard of civilization which then promulgated back into Europe. I think that if you want to maximize human potential, you need a higher standard of civilization, and that becomes an example that benefits everyone. Without an open frontier, closed world ideologies, such as the Malthus Theory, tend to come to the forefront. It is that there are limited resources; therefore, we are all in deadly competition with each other for the limited pot. The result is tyrannical and potentially genocidal regimes, and we've already seen this in the twentieth century. There s no truth in the Malthus Theory, because human beings are the creators of their resources. With every mouth comes a pair of hands and a brain. But if it seems to be true, you have a vector in this direction, and it is extremely unfortunate. It is only in a universe of infinite resources that all humans can be brothers and sisters. The fundamental question which affects humanity s sense of itself is whether the world is changeable or fixed. Are we the makers of our world or just its inhabitants? Some people have a view that they re living at the end of history within a world that s already defined, and there is no fundamental purpose to human life because there is nothing humans can do that matters. On the other hand, if humans understand their own role as the creators of their world, that s a much more healthy point of view. It raises the dignity of humans. Indeed, if we do establish a new branch of human civilization on Mars that grows in time and potency to the point where it cannot really settle Mars, but transforms Mars, and brings life to Mars, we will prove to everyone and for all time the precious and positive nature of the human species and every member of it.

  11. Impact of Human like Cues on Human Trust in Machines: Brain Imaging and Modeling Studies for Human-Machine Interactions

    Science.gov (United States)

    2018-01-05

    opponent had some human-likeness. In particular, the research shows that activity in the left parietal region correlating with a human players future ...human-likeness. In particular, our research shows that activity in the left parietal region correlating with a human player’s future behavior can be...this work. - Emotional Conversational Agent: The 4th Korean Flagship AI Project, from December 2016 to December 2020, about US$14,000,000 (Principal

  12. "This Ever More Amorphous Thing called Digital Humanities": Whither the Humanities Project?

    Science.gov (United States)

    Deegan, Marilyn

    2014-01-01

    In 2012, Digital Humanities became one of the most talked-about topics in the humanities and was suggested as a movement that could possibly help halt the decline in the traditional humanities. A flurry of books appeared, and "AHHE" produced two special issues, "Digital humanities," "digital futures" and "The…

  13. Bursty human dynamics

    CERN Document Server

    Karsai, Márton; Kaski, Kimmo

    2018-01-01

    This book provides a comprehensive overview on emergent bursty patterns in the dynamics of human behaviour. It presents common and alternative understanding of the investigated phenomena, and points out open questions worthy of further investigations. The book is structured as follows. In the introduction the authors discuss the motivation of the field, describe bursty phenomena in case of human behaviour, and relate it to other disciplines. The second chapter addresses the measures commonly used to characterise heterogeneous signals, bursty human dynamics, temporal paths, and correlated behaviour. These definitions are first introduced to set the basis for the discussion of the third chapter about the observations of bursty human patterns in the dynamics of individuals, dyadic interactions, and collective behaviour. The subsequent fourth chapter discusses the models of bursty human dynamics. Various mechanisms have been proposed about the source of the heterogeneities in human dynamics, which leads to the in...

  14. Superintelligence, Humans, and War

    Science.gov (United States)

    2015-04-13

    Recent studies of the human mind debunk the myth that humans only use 10-20 percent of the human mind. A healthy human mind uses up to 90 percent...way. They will eat what is in front of them to satiate their appetite not knowing if there is anymore food for the future. Humans can predict

  15. Managing human performance

    International Nuclear Information System (INIS)

    Strucic, M.; Kavsek, D.

    2004-01-01

    Human performance remains a significant factor for management attention not only from a reactor safety perspective, but also from a financial one. Recent significant events analysis shows that human errors are still dominant causes and contributors to them. An analysis of significant events in nuclear industry occurred through 15-years period revealed that three of four significant events were triggered by human error, although the number of events have dropped by more than a factor of four. A number of human performance breakdowns occurred in the application of errorprevention techniques. These included a lack of pre-job briefs, inadequate turnover of tasks, ineffective use of peer checking, inadequate procedure adherence, and failure to apply a questioning attitude when unexpected changes were encountered in the task. Attempts by the industry to improve human performance have traditionally focused at the worker level. However, human error occurs within the context of the organization, which can either foster or resist human error. The greatest room for improvement lies not only in the continued improvement of front-line worker performance but more so in the identification and elimination of weaknesses in the organizational and managerial domains that contributes to worker performance at the job site. Based on mentioned analysis, other industrial sources and own operating experience, NPP Krsko is paying more attention to improve human performance among own as well as contractor workers. Through series of programs and activities, such as Reactivity Management Program, Safety Culture Program, Self-assessment Program, Corrective Action Program, Plant Performance Monitoring Program, developed in last few years, and through new procedures, written guides and publications, training and management efforts, number of human errors is going to be reduced. Involvement of higher levels of NPP Krsko organization in promotion and use of Human Performance techniques is

  16. Palynological evidence of human activity on the gulf of Gdansk coast during the late holocene

    Directory of Open Access Journals (Sweden)

    Grazyna Miotk-Szpiganowicz

    2010-01-01

    Full Text Available The Gulf of Gdansk is located in the southern part of the Baltic Sea. The shores of the Gulf are dominated by the sandy barriers which have developed in front of the Vistula Lagoon and the Vistula Delta Plain to the south-east and south and in front of the Puck Lagoon in the north-west such as the Hel Peninsula. Cliffs occur on the western coast of the Gulf. Neolithic settlements around the coast of the Gulf of Gdansk are mainly located at the foot of the upland slope and on the Vistula Spit and the Vistula Delta and are closely related to the rise and displacement of the shoreline during the Late Holocene. Pollen analyses of the sediment cores from the Vistula Delta, the Vistula Lagoon and the coast of the Puck Lagoon allow four anthropogenic phases to be distinguished in the area of the Gulf of Gdansk. It has been shown that the first indicators of an early husbandry economy in the vicinity of the Gulf of Gdansk appeared in the Atlantic Period. Pollen grains of plants related to this kind of human activity those of the goosefoot family (Chenopodiaceae, motherwort (Artemisia, sorrel (Rumex are present and the first pollen grains of the plantain (Plantago lanceolata also appear. The second anthropogenic phase of Neolithic settlement is one of the best investigated cultures. This is the Rzucewo Culture. Pollen analyses indicate increasing human activity at the beginning of the Subboreal Period. The preserved traces of fauna show that the seal hunting and fishing economy was preferred. Radiocarbon dating of archaeological artifacts indicates the beginning of the settlement at ca. 2 400 B.C. (ca. 4 400 years B.P. (Król 1997. The altitude of peat and marine mollusks shells and their radiocarbon age shows that during the Early Subboreal Period the water level rose from ca. 2.8 m to 1.1 m below the present-day sea level. The date of the beginning of the seal hunters settlement correlates well with the period when the shores of the Puck Lagoon

  17. Human factors in training

    International Nuclear Information System (INIS)

    Dutton, J.W.; Brown, W.R.

    1981-01-01

    The Human Factors concept is a focused effort directed at those activities which require human involvement. Training is, by its nature, an activity totally dependent on the Human Factor. This paper identifies several concerns significant to training situations and discusses how Human Factor awareness can increase the quality of learning. Psychology in the training arena is applied Human Factors. Training is a method of communication represented by sender, medium, and receiver. Two-thirds of this communications model involves the human element directly

  18. Human Reliability Analysis for Design: Using Reliability Methods for Human Factors Issues

    Energy Technology Data Exchange (ETDEWEB)

    Ronald Laurids Boring

    2010-11-01

    This paper reviews the application of human reliability analysis methods to human factors design issues. An application framework is sketched in which aspects of modeling typically found in human reliability analysis are used in a complementary fashion to the existing human factors phases of design and testing. The paper provides best achievable practices for design, testing, and modeling. Such best achievable practices may be used to evaluate and human system interface in the context of design safety certifications.

  19. Human Reliability Analysis for Design: Using Reliability Methods for Human Factors Issues

    International Nuclear Information System (INIS)

    Boring, Ronald Laurids

    2010-01-01

    This paper reviews the application of human reliability analysis methods to human factors design issues. An application framework is sketched in which aspects of modeling typically found in human reliability analysis are used in a complementary fashion to the existing human factors phases of design and testing. The paper provides best achievable practices for design, testing, and modeling. Such best achievable practices may be used to evaluate and human system interface in the context of design safety certifications.

  20. Human factor reliability program

    International Nuclear Information System (INIS)

    Knoblochova, L.

    2017-01-01

    The human factor's reliability program was at Slovenske elektrarne, a.s. (SE) nuclear power plants. introduced as one of the components Initiatives of Excellent Performance in 2011. The initiative's goal was to increase the reliability of both people and facilities, in response to 3 major areas of improvement - Need for improvement of the results, Troubleshooting support, Supporting the achievement of the company's goals. The human agent's reliability program is in practice included: - Tools to prevent human error; - Managerial observation and coaching; - Human factor analysis; -Quick information about the event with a human agent; -Human reliability timeline and performance indicators; - Basic, periodic and extraordinary training in human factor reliability(authors)