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Sample records for human nontransformed rpe-1

  1. Parabens enable suspension growth of MCF-10A immortalized, non-transformed human breast epithelial cells.

    PubMed

    Khanna, Sugandha; Darbre, Philippa D

    2013-05-01

    Parabens (alkyl esters of p-hydroxybenzoic acid) are used extensively as preservatives in consumer products, and intact esters have been measured in several human tissues. Concerns of a potential link between parabens and breast cancer have been raised, but mechanistic studies have centred on their oestrogenic activity and little attention has been paid to any carcinogenic properties. In the present study, we report that parabens can induce anchorage-independent growth of MCF-10A immortalized but non-transformed human breast epithelial cells, a property closely related to transformation and a predictor of tumour growth in vivo. In semi-solid methocel suspension culture, MCF-10A cells produced very few colonies and only of a small size but the addition of 5 × 10(-4) M methylparaben, 10(-5) M n-propylparaben or 10(-5) M n-butylparaben resulted in a greater number of colonies per dish (P < 0.05 in each case) and an increased average colony size (P < 0.001 in each case). Dose-responses showed that concentrations as low as 10(-6) M methylparaben, 10(-7) M n-propylparaben and 10(-7) M n-butylparaben could increase colony numbers (P = 0.016, P = 0.010, P = 0.008, respectively): comparison with a recent measurement of paraben concentrations in human breast tissue samples from 40 mastectomies (Barr et al., 2012) showed that 22/40 of the patients had at least one of the parabens at the site of the primary tumour at or above these concentrations. To our knowledge, this is the first study to report that parabens can induce a transformed phenotype in human breast epithelial cells in vitro, and further investigation is now justified into a potential link between parabens and breast carcinogenesis.

  2. Evaluation of tellurium toxicity in transformed and non-transformed human colon cells.

    PubMed

    Vij, Puneet; Hardej, Diane

    2012-11-01

    Diphenyl ditelluride (DPDT) and tellurium tetrachloride (TeCl(4)) were evaluated for toxicity in transformed (HT-29, Caco-2) and non-transformed colon cells (CCD-18Co). Significant decreases in viability were observed with DPDT exposure in HT-29 (62.5-1000 μM), Caco-2 (31.25-1000 μM) and CCD-18Co cells (500-1000 μM) and with TeCl(4) in HT-29 (31.25-1000 μM), Caco-2 (31.25-1000 μM) and CCD-18Co cells (500-1000 μM). Light microscopy confirmed viability analysis. Significant increases in caspase 3/7 and 9 activity were observed with DPDT in HT-29 (500-1000 μM) and CCD-18Co cells (1000 μM) indicating apoptosis. No significant increases in caspases were seen with TeCl(4) indicating necrosis. Apoptosis or necrosis was confirmed with fluorescent staining (FITC-Annexin, Hoechst 33342 and Ethidium Homodimer). Significant decreases in GSH/GSSG ratio were observed with DPDT in HT-29 (62.5-1000 μM), and CCD-18Co cells (1000 μM) and with TeCl(4) in HT-29 (62.5-1000 μM) and CCD-18Co cells (250-1000 μM). We concluded that cells treated with DPDT resulted in apoptosis and TeCl(4) treatment in necrosis. GSH/GSSG ratio shifts indicate oxidative mechanisms are involved.

  3. Activation of the Innate Immune Response against DENV in Normal Non-Transformed Human Fibroblasts

    PubMed Central

    Bustos-Arriaga, José; García-Machorro, Jazmín; León-Juárez, Moisés; García-Cordero, Julio; Santos-Argumedo, Leopoldo; Flores-Romo, Leopoldo; Méndez-Cruz, A. René; Juárez-Delgado, Francisco J.; Cedillo-Barrón, Leticia

    2011-01-01

    Background When mosquitoes infected with DENV are feeding, the proboscis must traverse the epidermis several times (“probing”) before reaching a blood vessel in the dermis. During this process, the salivary glands release the virus, which is likely to interact first with cells of the various epidermal and dermal layers, cells which could be physiologically relevant to DENV infection and replication in humans. However, important questions are whether more abundant non-hematopoietic cells such as fibroblasts become infected, and whether they play any role in antiviral innate immunity in the very early stages of infection, or even if they might be used by DENV as primary replication cells. Methodology/Principal Findings Fibroblasts freshly released from healthy skin and infected 12 hours after their isolation show a positive signal for DENV. In addition, when primary skin fibroblast cultures were established and subsequently infected, we showed DENV-2 antigen-positive intracellular signal at 24 hours and 48 hours post-infection. Moreover, the fibroblasts showed productive infection in a conventional plaque assay. The skin fibroblasts infected with DENV-2 underwent potent signaling through both TLR3 and RIG- 1, but not Mda5, triggering up-regulation of IFNβ, TNFα, defensin 5 (HB5) and β defensin 2 (HβD2). In addition, DENV infected fibroblasts showed increased nuclear translocation of interferon (IFN) regulatory factor 3 (IRF3), but not interferon regulatory factor 7 (IRF7), when compared with mock-infected fibroblasts. Conclusions/Significance In this work, we demonstrated the high susceptibility to DENV infection by primary fibroblasts from normal human skin, both in situ and in vitro. Our results suggest that these cells may contribute to the pro-inflammatory and anti-viral microenvironment in the early stages of interaction with DENV-2. Furthermore, the data suggest that fibroblast may also be used as a primary site of DENV replication and provide viral

  4. Exposure to cyclic volatile methylsiloxanes (cVMS) causes anchorage-independent growth and reduction of BRCA1 in non-transformed human breast epithelial cells.

    PubMed

    Farasani, Abdullah; Darbre, Philippa D

    2017-04-01

    Dermal absorption of components of personal care products (PCPs) may contribute to breast cancer development. Cyclic volatile methylsiloxanes (cVMS) are used widely in the formulation of PCPs, and their presence has been recently detected in human blood. The objectives of this study were to investigate any genotoxic effects after short- (1 week) or longer-term (30 weeks) exposure to hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) or decamethylcyclopentasiloxane (D5) in MCF-10 A and MCF-10F immortalized non-transformed human breast epithelial cells. Genotoxic effects were assessed by an ability of cells to grow in suspension culture, from DNA damage measured by comet assays, and from a reduction in levels of DNA repair proteins measured by RT-PCR and western immunoblotting. Dose-dependent anchorage-independent growth in methocel culture was observed after exposure to D3 (10(-)(13)  M-10(-5)  M) and D4/D5 (10(-)(9)  M-10(-5)  M). DNA damage was measured by the comet assay after 1-h exposure to D3 (10(-)(6)  M-10(-5)  M) and D4 (10(-5)  M). BRCA1 mRNA and BRCA1 protein levels were reduced after 30-week exposure to 10(-5)  M D4 and D5 in both cell lines. Reduced levels of mRNAs for other DNA repair proteins (BRCA2, ATM, ATR, CHK1 and CHK2) were also observed after exposure to 10(-5)  M D5 in both cell lines, and some reductions after exposure to D3 and D4. If cVMS can not only enable anchorage-independent growth of non-transformed breast epithelial cells and damage DNA, but also compromise DNA repair systems, then there is the potential for them to impact on breast carcinogenesis. Further risk assessment now requires information concerning the extent to which cVMS may be present in human breast tissues. Copyright © 2016 John Wiley & Sons, Ltd.

  5. PEG-3, a nontransforming cancer progression gene, is a positive regulator of cancer aggressiveness and angiogenesis.

    PubMed

    Su, Z Z; Goldstein, N I; Jiang, H; Wang, M N; Duigou, G J; Young, C S; Fisher, P B

    1999-12-21

    Cancer is a progressive disease culminating in acquisition of metastatic potential by a subset of evolving tumor cells. Generation of an adequate blood supply in tumors by production of new blood vessels, angiogenesis, is a defining element in this process. Although extensively investigated, the precise molecular events underlying tumor development, cancer progression, and angiogenesis remain unclear. Subtraction hybridization identified a genetic element, progression elevated gene-3 (PEG-3), whose expression directly correlates with cancer progression and acquisition of oncogenic potential by transformed rodent cells. We presently demonstrate that forced expression of PEG-3 in tumorigenic rodent cells, and in human cancer cells, increases their oncogenic potential in nude mice as reflected by a shorter tumor latency time and the production of larger tumors with increased vascularization. Moreover, inhibiting endogenous PEG-3 expression in progressed rodent cancer cells by stable expression of an antisense expression vector extinguishes the progressed cancer phenotype. Cancer aggressiveness of PEG-3 expressing rodent cells correlates directly with increased RNA transcription, elevated mRNA levels, and augmented secretion of vascular endothelial growth factor (VEGF). Furthermore, transient ectopic expression of PEG-3 transcriptionally activates VEGF in transformed rodent and human cancer cells. Taken together these data demonstrate that PEG-3 is a positive regulator of cancer aggressiveness, a process regulated by augmented VEGF production. These studies also support an association between expression of a single nontransforming cancer progression-inducing gene, PEG-3, and the processes of cancer aggressiveness and angiogenesis. In these contexts, PEG-3 may represent an important target molecule for developing cancer therapeutics and inhibitors of angiogenesis.

  6. Discovery of a novel proteasome inhibitor selective for cancer cells over non-transformed cells.

    PubMed

    Kazi, Aslamuzzaman; Lawrence, Harshani; Guida, Wayne C; McLaughlin, Mark L; Springett, Gregory M; Berndt, Norbert; Yip, Richard M L; Sebti, Saïd M

    2009-06-15

    Numerous proteins controlling cell cycle progression, apoptosis and angiogenesis are degraded by the ubiquitin/proteasome system, which has become the subject for intense investigations for cancer therapeutics. Therefore, we used in silico and experimental approaches to screen compounds from the NCI chemical libraries for inhibitors against the chymotrypsin-like (CT-L) activity of the proteasome and discovered PI-083. Molecular docking indicates that PI-083 interacts with the Thr21, Gly47 and Ala49 residues of the beta5 subunit and Asp114 of the beta6 subunit of the proteasome. PI-083 inhibits CT-L activity and cell proliferation and induces apoptosis selectively in cancer cells (ovarian T80-Hras, pancreatic C7-Kras and breast MCF-7) as compared to their normal/immortalized counterparts (T80, C7 and MCF-10A, respectively). In contrast, Bortezomib, the only proteasome inhibitor approved by the Food and Drug Administration (FDA), did not exhibit this selectivity for cancer over non-transformed cells. In addition, in all cancer cells tested, including Multiple Myeloma (MM), breast, pancreatic, ovarian, lung, prostate cancer cell lines as well as fresh MM cells from patients, PI-083 required less time than Bortezomib to induce its antitumor effects. Furthermore, in nude mouse xenografts in vivo, PI-083, but not Bortezomib, suppressed the growth of human breast and lung tumors. Finally, following in vivo treatment of mice, PI-083 inhibited tumor, but not hepatic liver CT-L activity, whereas Bortezomib inhibited both tumor and liver CT-L activities. These results suggest that PI-083 is more selective for cancer cells and may have broader antitumor activity and therefore warrants further advanced preclinical studies.

  7. cdc25 is a nuclear protein expressed constitutively throughout the cell cycle in nontransformed mammalian cells

    PubMed Central

    1992-01-01

    A family of proteins homologous to the cdc25 gene product of the fission yeast bear specific protein tyrosine phosphatase activity involved in the activation of the p34cdc2-cyclin B kinase. Using affinity-purified antibodies raised against a synthetic peptide corresponding to the catalytic site of the cdc25 phosphatase, we show that cdc25 protein is constitutively expressed throughout the cell cycle of nontransformed mammalian fibroblasts and does not undergo major changes in protein level. By indirect immunofluorescence, cdc25 protein is found essentially localized in the nucleus throughout interphase and during early prophase. Just before the complete nuclear envelope breakdown at the prophase-prometaphase boundary, cdc25 proteins are redistributed throughout the cytoplasm. During metaphase and anaphase, cdc25 staining remains distributed throughout the cell and excludes the condensed chromosomes. The nuclear locale reappears during telophase. In light of the recent data describing the cytoplasmic localization of cyclin B protein (Pines, J., and T. Hunter. 1991. J. Cell Biol. 115:1-17), the data presented here suggest that separation in two distinct cellular compartments of the cdc25 phosphatase and its substrate p34cdc2-cyclin B may be of importance in the regulation of the cdc2 kinase activity. PMID:1500423

  8. Transformed and nontransformed cells differ in stability and cell cycle regulation of a binding activity to the murine thymidine kinase promoter.

    PubMed Central

    Bradley, D W; Dou, Q P; Fridovich-Keil, J L; Pardee, A B

    1990-01-01

    A DNA binding activity to an upstream region of the murine thymidine kinase gene is regulated differently in a transformed and nontransformed cell line pair. Differences in regulation were observed (i) after serum levels were reduced, (ii) when serum levels were returned to initial high levels, and (iii) while protein synthesis was inhibited. After reduction of serum levels, the binding activity was unstable in nontransformed BALB/c 3T3 clone A31 cells but was significantly more stable in benzo[a]pyrene-transformed BALB/c 3T3 cells. After serum concentration was returned to high levels, the kinetic pattern of the binding activity differed between nontransformed and transformed cells. While protein synthesis was inhibited, the binding activity was unstable in nontransformed cells and stable in transformed cells. Partial inhibition of protein synthesis--a more stringent condition to test instability--prevented the induction of the binding activity in nontransformed cells. Previously, the labile protein hypothesis set forth the criterion that a protein regulating the onset of DNA synthesis should be unstable in nontransformed cells and stable in transformed cells. The DNA binding activity described here satisfies this criterion. Images PMID:2251273

  9. Targeted siRNA Screens Identify ER-to-Mitochondrial Calcium Exchange in Autophagy and Mitophagy Responses in RPE1 Cells.

    PubMed

    MacVicar, Thomas D B; Mannack, Lilith V J C; Lees, Robert M; Lane, Jon D

    2015-06-11

    Autophagy is an important stress response pathway responsible for the removal and recycling of damaged or redundant cytosolic constituents. Mitochondrial damage triggers selective mitochondrial autophagy (mitophagy), mediated by a variety of response factors including the Pink1/Parkin system. Using human retinal pigment epithelial cells stably expressing autophagy and mitophagy reporters, we have conducted parallel screens of regulators of endoplasmic reticulum (ER) and mitochondrial morphology and function contributing to starvation-induced autophagy and damage-induced mitophagy. These screens identified the ER chaperone and Ca2+ flux modulator, sigma non-opioid intracellular receptor 1 (SIGMAR1), as a regulator of autophagosome expansion during starvation. Screens also identified phosphatidyl ethanolamine methyl transferase (PEMT) and the IP3-receptors (IP3Rs) as mediators of Parkin-induced mitophagy. Further experiments suggested that IP3R-mediated transfer of Ca2+ from the ER lumen to the mitochondrial matrix via the mitochondrial Ca2+ uniporter (MCU) primes mitochondria for mitophagy. Importantly, recruitment of Parkin to damaged mitochondria did not require IP3R-mediated ER-to-mitochondrial Ca2+ transfer, but mitochondrial clustering downstream of Parkin recruitment was impaired, suggesting involvement of regulators of mitochondrial dynamics and/or transport. Our data suggest that Ca2+ flux between ER and mitochondria at presumed ER/mitochondrial contact sites is needed both for starvation-induced autophagy and for Parkin-mediated mitophagy, further highlighting the importance of inter-organellar communication for effective cellular homeostasis.

  10. Targeted siRNA Screens Identify ER-to-Mitochondrial Calcium Exchange in Autophagy and Mitophagy Responses in RPE1 Cells

    PubMed Central

    MacVicar, Thomas D. B.; Mannack, Lilith V. J. C.; Lees, Robert M.; Lane, Jon D.

    2015-01-01

    Autophagy is an important stress response pathway responsible for the removal and recycling of damaged or redundant cytosolic constituents. Mitochondrial damage triggers selective mitochondrial autophagy (mitophagy), mediated by a variety of response factors including the Pink1/Parkin system. Using human retinal pigment epithelial cells stably expressing autophagy and mitophagy reporters, we have conducted parallel screens of regulators of endoplasmic reticulum (ER) and mitochondrial morphology and function contributing to starvation-induced autophagy and damage-induced mitophagy. These screens identified the ER chaperone and Ca2+ flux modulator, sigma non-opioid intracellular receptor 1 (SIGMAR1), as a regulator of autophagosome expansion during starvation. Screens also identified phosphatidyl ethanolamine methyl transferase (PEMT) and the IP3-receptors (IP3Rs) as mediators of Parkin-induced mitophagy. Further experiments suggested that IP3R-mediated transfer of Ca2+ from the ER lumen to the mitochondrial matrix via the mitochondrial Ca2+ uniporter (MCU) primes mitochondria for mitophagy. Importantly, recruitment of Parkin to damaged mitochondria did not require IP3R-mediated ER-to-mitochondrial Ca2+ transfer, but mitochondrial clustering downstream of Parkin recruitment was impaired, suggesting involvement of regulators of mitochondrial dynamics and/or transport. Our data suggest that Ca2+ flux between ER and mitochondria at presumed ER/mitochondrial contact sites is needed both for starvation-induced autophagy and for Parkin-mediated mitophagy, further highlighting the importance of inter-organellar communication for effective cellular homeostasis. PMID:26110381

  11. USEPA Environmental Quality Index (EQI) - Air, Water, Land, Built, and Sociodemographic Domains Non-Transformed Variables Dataset as Input for the USEPA EQI, by County for the United States

    EPA Pesticide Factsheets

    The US Environmental Protection Agency's (EPA) National Health and Environmental Effects Research Laboratory (NHEERL) in the Environmental Public Health Division (EPHD) is currently engaged in research aimed at developing a measure that estimates overall environmental quality at the county level for the United States. This work is being conducted as an effort to learn more about how various environmental factors simultaneously contribute to health disparities in low-income and minority populations, and to better estimate the total environmental and social context to which humans are exposed. This dataset contains the finalized non-transformed variables chosen to represent the Air, Water, Land, Built, and Sociodemographic Domains of the total environment. This does not represent the final variables for the EQI. The Transformed dataset was used to create the EQI. This dataset is for information purposes only for those who want to see the original non-transformed variables. Six criteria air pollutants and 81 hazardous air pollutants are included in this dataset. Data sources are the EPA's Air Quality system (http://www.epa.gov/ttn/airs/airsaqs/) and the National-scale Air Toxics Assessment (http://www.epa.gov/nata/). Variables are average pollutant concentrations or emissions for 2000-2005 at the county level for all counties in the United States. Data on water impairment, waste permits, beach closures, domestic water source, deposition for 9 pollutants, drought st

  12. Polymethoxyflavone Apigenin-Trimethylether Suppresses LPS-Induced Inflammatory Response in Nontransformed Porcine Intestinal Cell Line IPEC-J2.

    PubMed

    Farkas, Orsolya; Palócz, Orsolya; Pászti-Gere, Erzsébet; Gálfi, Péter

    2015-01-01

    The in vitro anti-inflammatory effect of apigenin and its trimethylated analogue (apigenin-trimethylether) has been investigated in order to evaluate whether these flavonoids could attenuate LPS-induced inflammation in IPEC-J2 non-transformed intestinal epithelial cells. Levels of IL-6, IL-8, TNF-α, and COX-2 mRNA were measured as a marker of inflammatory response. The extracellular H2O2 level in IPEC-J2 cells was also monitored by Amplex Red assay. Our data revealed that both compounds had significant lowering effect on the inflammatory response. Apigenin (at 25 μM) significantly decreased gene expression of IL-6 in LPS-treated cells, while apigenin-trimethylether in the same concentration did not influence IL-6 mRNA level. Both apigenin and apigenin-trimethylether reduced IL-8 gene expression significantly. TNF-α mRNA level was decreased by apigenin-trimethylether, which was not influenced by apigenin. Treatment with both flavonoids caused significant reduction in the mRNA level of COX-2, but the anti-inflammatory effect of the methylated analogue was more effective than the unmethylated one. Furthermore, both flavonoids reduced significantly the level of extracellular H2O2 compared to the control cells. In conclusion, the methylated apigenin analogue could avoid LPS-induced intestinal inflammation and it could be applied in the future as an effective anti-inflammatory compound.

  13. Polymethoxyflavone Apigenin-Trimethylether Suppresses LPS-Induced Inflammatory Response in Nontransformed Porcine Intestinal Cell Line IPEC-J2

    PubMed Central

    Farkas, Orsolya; Palócz, Orsolya; Pászti-Gere, Erzsébet; Gálfi, Péter

    2015-01-01

    The in vitro anti-inflammatory effect of apigenin and its trimethylated analogue (apigenin-trimethylether) has been investigated in order to evaluate whether these flavonoids could attenuate LPS-induced inflammation in IPEC-J2 non-transformed intestinal epithelial cells. Levels of IL-6, IL-8, TNF-α, and COX-2 mRNA were measured as a marker of inflammatory response. The extracellular H2O2 level in IPEC-J2 cells was also monitored by Amplex Red assay. Our data revealed that both compounds had significant lowering effect on the inflammatory response. Apigenin (at 25 μM) significantly decreased gene expression of IL-6 in LPS-treated cells, while apigenin-trimethylether in the same concentration did not influence IL-6 mRNA level. Both apigenin and apigenin-trimethylether reduced IL-8 gene expression significantly. TNF-α mRNA level was decreased by apigenin-trimethylether, which was not influenced by apigenin. Treatment with both flavonoids caused significant reduction in the mRNA level of COX-2, but the anti-inflammatory effect of the methylated analogue was more effective than the unmethylated one. Furthermore, both flavonoids reduced significantly the level of extracellular H2O2 compared to the control cells. In conclusion, the methylated apigenin analogue could avoid LPS-induced intestinal inflammation and it could be applied in the future as an effective anti-inflammatory compound. PMID:26180592

  14. Involvement of a non-hormone-binding 90-kilodalton protein in the nontransformed 8S form of the rabbit uterus progesterone receptor

    SciTech Connect

    Renoir, J.M.; Buchou, T.; Baulieu, E.E.

    1986-10-21

    Nontransformed 8S progesterone receptor (8S-PR) was purified by hormone-specific affinity chromatography from rabbit uterine low-salt cytosol containing 20 mM molybdate. In the eluate obtained with radioactive progestin, sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE) showed the presence of several bands, including three that corresponded to approx.90, approx.120, and approx.85-kDa proteins. None of these three proteins was found in the eluate of the affinity column when the molybdate-containing cytosol was chromatographed in the presence of nonradioactive progesterone (mock purification). Subsequent purification of the affinity eluate by DEAE-Sephacel chromatography gave a single radioactive receptor peak at 0.15 M KCl with a sedimentation coefficient of 8.5 S. Silver staining after SDS-PAGE revealed that this purified 8S-PR fraction contained mainly the 120-, 90-, and 85-kDa proteins. (/sup 3/H)R5020-labeled 8S-PR purified by DEAE-Sephacel column chromatography was UV irradiated, and after SDS-PAGE the 120- and 85-kDa proteins were revealed, but the 90-kDa protein was not. Further evidence for the presence of the 90-kDa non-hormone-binding protein in the purified molybdate-stabilized nontransformed 8S-PR structure was demonstrated. In the course of this work, it was verified that 0.3 M KCl added in cytosol in the absence of molybdate dissociated the 8S-PR complex, and purified 120- and 85-kDa progestin binding proteins were obtained by hormone-specific affinity chromatography of the salt-treated cytosol. In summer, the results demonstrated that, as for the nontransformed avian 8S-PR the nontransformed 8S form of the rabbit uterus PR includes a non-hormone-binding 90-kDa protein.

  15. Lithospheric Structure, Stress, and Magmatism at the Rainbow Non-Transform Offset on the Mid-Atlantic Ridge

    NASA Astrophysics Data System (ADS)

    Paulatto, M.; Canales, J. P.; Dunn, R. A.

    2014-12-01

    New oceanic lithosphere is formed at slow-spreading mid-ocean ridges by a combination of eruption and intrusion of magma and by tectonic exhumation and alteration of lower crustal and mantle rocks. We look at the relationship between these two processes and how their relative contributions vary at non-transform ridge-segment offsets (NTOs). Models of mantle upwelling predict magmatic input and heat flux to be relatively low at NTOs, yet many host high-temperature hydrothermal systems, which are difficult to explain without the presence of a crustal magmatic source. We analyzed newly acquired swath bathymetry, gravity and magnetic data from the MARINER experiment together with archived data from the Rainbow NTO (36º10' N) on the Mid-Atlantic Ridge. This NTO is currently experiencing both mantle exhumation and magmatic input as evidenced by the active Rainbow high-temperature hydrothermal field. We calculate mantle Bouguer gravity anomalies and crustal magnetization to constrain the lithospheric structure and tectonic evolution of the NTO during the past ~2 Myr. The swath bathymetry data are used to map faults, extrusive volcanic terrain and tectonized blocks and show that the style of crustal accretion varies along the adjacent ridge segments. Spatial changes in the style of extensional faulting are indicative of variations in the mechanical properties and the state of stress of the lithosphere. We suggest that the availability of magma to drive hydrothermal activity at Rainbow and other similar settings is controlled not only by the thermal regime and the structure of the lithosphere but also by the effect of local stress conditions on magma migration. Models of magma migration and dyking show that changes in the direction of minimum compressive stress affect the propagation of magmatic intrusions. We argue that stress rotation can explain the formation of crustal magma chambers at NTOs despite a reduced magmatic flux. These constraints help determine the role of

  16. A preliminary study of apoptosis induction in glioma cells via alteration of the Bax/Bcl-2-p53 axis by transformed and non-transformed root extracts of Leonurus sibiricus L.

    PubMed

    Sitarek, Przemysław; Skała, Ewa; Toma, Monika; Wielanek, Marzena; Szemraj, Janusz; Nieborowska-Skorska, Malgorzata; Kolasa, Maciej; Skorski, Tomasz; Wysokińska, Halina; Śliwiński, Tomasz

    2016-07-01

    Leonurus sibiricus L. is a traditional medicinal plant which occurs in southern Siberia, China, Korea, Japan, and Vietnam. The plant shows several pharmacological effects, but the most interesting is its anti-cancer activity. The aim of our study was to examine the induction of apoptosis in malignant glioma cells, the most aggressive primary brain tumors of the central nervous system, following treatment with transformed root (TR) or non-transformed root (NR) L. sibiricus extracts. Both the NR and TR extracts were found to have cytotoxic activity in the glioma primary cells. The human glioblastoma cell lines obtained from patients were confirmed to be tumorogenic by the following three markers: D10S1709, D10S1172, and D22S283. HPLC and MS analysis revealed the presence of polyphenolic compounds (chlorogenic acid, ferulic acid, caffeic acid, p-coumaric acid, ellagic acid, and verbascoside) in both sets of root extracts. In summary, our findings demonstrate that treatment of the glioma cells with NR and TR extracts resulted (a) in significant cell growth inhibition, (b) S- and G2/M-phase cell cycle arrest, and (c) apoptosis in a dose-dependent fashion by changing Bax/Bcl-2 ratio (about 4-fold increase) and p53 (5-fold increase) activation. These findings indicate that NR and TR extracts exhibit anti-cancer activity through the regulation of genes involved in apoptosis. This is the first report to demonstrate the cytotoxic effect of polyphenolic extracts from L. sibiricus roots against glioma cells, but further studies are required to understand the complete mechanism of its apoptosic activity.

  17. Helicobacter pylori CagA Suppresses Apoptosis through Activation of AKT in a Nontransformed Epithelial Cell Model of Glandular Acini Formation

    PubMed Central

    Vallejo-Flores, Gabriela; Torres, Javier; Sandoval-Montes, Claudia; Arévalo-Romero, Haruki; Meza, Isaura; Camorlinga-Ponce, Margarita; Torres-Morales, Julián; Chávez-Rueda, Adriana Karina; Legorreta-Haquet, María Victoria; Fuentes-Pananá, Ezequiel M.

    2015-01-01

    H. pylori infection is the most important environmental risk to develop gastric cancer, mainly through its virulence factor CagA. In vitro models of CagA function have demonstrated a phosphoprotein activity targeting multiple cellular signaling pathways, while cagA transgenic mice develop carcinomas of the gastrointestinal tract, supporting oncogenic functions. However, it is still not completely clear how CagA alters cellular processes associated with carcinogenic events. In this study, we evaluated the capacity of H. pylori CagA positive and negative strains to alter nontransformed MCF-10A glandular acini formation. We found that CagA positive strains inhibited lumen formation arguing for an evasion of apoptosis activity of central acini cells. In agreement, CagA positive strains induced a cell survival activity that correlated with phosphorylation of AKT and of proapoptotic proteins BIM and BAD. Anoikis is a specific type of apoptosis characterized by AKT and BIM activation and it is the mechanism responsible for lumen formation of MCF-10A acini in vitro and mammary glands in vivo. Anoikis resistance is also a common mechanism of invading tumor cells. Our data support that CagA positive strains signaling function targets the AKT and BIM signaling pathway and this could contribute to its oncogenic activity through anoikis evasion. PMID:26557697

  18. Validation of Reference Genes for Quantitative Real-Time PCR in Bovine PBMCs Transformed and Non-transformed by Theileria annulata

    PubMed Central

    Zhao, Hongxi; Liu, Junlong; Li, Youquan; Yang, Congshan; Zhao, Shuaiyang; Liu, Juan; Liu, Aihong; Liu, Guangyuan; Yin, Hong; Guan, Guiquan; Luo, Jianxun

    2016-01-01

    Theileria annulata is a tick-borne intracellular protozoan parasite that causes tropical theileriosis, a fatal bovine lymphoproliferative disease. The parasite predominantly invades bovine B lymphocytes and macrophages and induces host cell transformation by a mechanism that is not fully comprehended. Analysis of signaling pathways by quantitative real-time PCR (qPCR) could be a highly efficient means to understand this transformation mechanism. However, accurate analysis of qPCR data relies on selection of appropriate reference genes for normalization, yet few papers on T. annulata contain evidence of reference gene validation. We therefore used the geNorm and NormFinder programs to evaluate the stability of 5 candidate reference genes; 18S rRNA, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ACTB (β-actin), PRKG1 (protein kinase cGMP-dependent, type I) and TATA box binding protein (TBP). The results showed that 18S rRNA was the reference gene most stably expressed in bovine PBMCs transformed and non-transformed with T. annulata, followed by GAPDH and TBP. While 18S rRNA and GAPDH were the best combination, these 2 genes were chosen as references to study signaling pathways involved in the transformation mechanism of T. annulata. PMID:26951977

  19. Epidermal growth factor receptor transactivation is implicated in IL-6-induced proliferation and ERK1/2 activation in non-transformed prostate epithelial cells.

    PubMed

    Poncet, Nadège; Guillaume, Johann; Mouchiroud, Guy

    2011-03-01

    Epidermal growth factor receptor (EGF-R) is a receptor tyrosine kinase that can be activated by molecules other than its cognate ligands. This form of crosstalk called transactivation is frequently observed in both physiological and pathological cellular responses, yet it involves various mechanisms. Using the RWPE-1 cell line as a model of non-transformed prostate epithelial progenitor cells, we observed that interleukin-6 (IL-6) is able to promote cell proliferation and ERK1/2 activation provided that EGF-R kinase activity is not impaired. Treatment with GM6001, a general matrix metalloprotease inhibitor, indicated that IL-6 activates EGF-R through cleavage and release of membrane-anchored EGF-R ligands. Several inhibitors were used to test implication of "a disintegrin and metalloprotease" ADAM10 and ADAM17. GW280264X that targets both ADAM10 and ADAM17 blocked IL-6-induced proliferation and ERK1/2 phosphorylation with same potency as GM6001. However, ADAM10 inhibitor GI254023X and ADAM17 inhibitor TAPI-2 were less efficient in inhibiting response of RWPE-1 cells to IL-6, indicating possible cooperation of ADAM17 with ADAM10 or other metalloproteases. Accordingly, our findings suggest that IL-6 stimulates shedding of EGF-R ligands and transactivation of EGF-R in normal prostate epithelial cells, which may be an important mechanism to promote cell proliferation in inflammatory prostate.

  20. Helicobacter pylori CagA and IL-1β Promote the Epithelial-to-Mesenchymal Transition in a Nontransformed Epithelial Cell Model

    PubMed Central

    Arévalo-Romero, Haruki; Meza, Isaura; Vallejo-Flores, Gabriela

    2016-01-01

    Gastric cancer is the third cause of cancer death worldwide and infection by Helicobacter pylori (H. pylori) is considered the most important risk factor, mainly by the activity of its virulence factor CagA. H. pylori/CagA-induced chronic inflammation triggers a series of gastric lesions of increased severity, starting with gastritis and ending with cancer. IL-1β has been associated with tumor development and invasiveness in different types of cancer, including gastric cancer. Currently, it is not clear if there is an association between CagA and IL-1β at a cellular level. In this study, we analyzed the effects of IL-1β and CagA on MCF-10A nontransformed cells. We found evidence that both CagA and IL-1β trigger the initiation of the epithelial-to-mesenchymal transition characterized by β-catenin nuclear translocation, increased expression of Snail1 and ZEB1, downregulation of CDH1, and morphological changes during MCF-10A acini formation. However, only CagA induced MMP9 activity and cell invasion. Our data support that IL-1β and CagA target the β-catenin pathway, with CagA leading to acquisition of a stage related to aggressive tumors. PMID:27525003

  1. The non-transform discontinuity on the Central Indian Ridge at 11°S: The transtensional basin formation and hydrothermal activity

    NASA Astrophysics Data System (ADS)

    Pak, S. J.; Kim, H. S.; Son, J.; Kim, J.; Moon, J. W.; Son, S. K.

    2014-12-01

    The bathymetric and magnetic survey, hydrocasting and seabed sampling have been carried out in the middle portion of the Central Indian Ridge (MCIR) between 7°S and 17°S. The MCIR constitutes six first-order segments and seven second-order segments with four non-transform discontinuities (NTDs) and twelve ocean core complexes (OCCs). These segments are characterized by asymmetric accretion that corresponds to about 70% of the surveyed MCIR segment. One of the outstanding NTD in the area is a basin like NTD3-1 at 11°S (50km in length) which strike at 035°, approximately 45° oblique in a clockwise direction to the orientation of two adjoining second-order segments. The hydrothermal activity is recognized at the tips of NTD3-1. No abyssal hills paralleling to basin-shape NTD3-1 are observed. Anomalous depth of the basin, lack of positive magnetic anomaly across the basin and rare seismic activities in the basin floor suggests that extensional tectonism with a sparse volcanism is the dominant process occurring along the NTD3-1. Based on the previous researches that the counterclockwise rotation of ridge is predominant in the area, the region of NTD3-1 largely accommodates shear strain by left-lateral sense motion and consequently forms a transtensional basin, i.e., a pull-apart basin. The strong and frequent hydrothermal plume signals, and highly tectonized rocks in both tips of the NTD3-1 are reflective of the dilation zones or tensional fractures accompanied by the pull-apart basin formation. It is the first identification of a pull-apart basin associated with hydrothermal activity in the Central Indian Ridge.

  2. Analysis of microearthquakes at the non-transform offset of the Mid-Atlantic Ridge hosting the Rainbow hydrothermal system (36°14'N)

    NASA Astrophysics Data System (ADS)

    Horning, G.; Canales, J. P.; Sohn, R. A.; Dunn, R. A.

    2015-12-01

    The Rainbow hydrothermal field is an active, ultramafic-hosted system located on the Mid-Atlantic Ridge (MAR) at 36° 14'N. It is located at a non-transform discontinuity (NTD) of the MAR at the AMAR-AMAR minor segment intersection [German et al., 1996]. Rainbow, in contrast to other ultramafic-hosted systems such as Lost City, is a high-temperature site with fluids up to 365 °C [Douville et al., 2002]. A magmatic heat source must be present to account for the long-lived, high-temperature, heat flux of 1-5 GW [Thurnherr and Richards, 2001], but the nearest, known neovolcanic activity is 15-20 km away on the AMAR segment [German and Parson, 1998]. In 2013, a long-term, ocean bottom seismometer (OBS) microearthquake network of 13 instruments was deployed as part of the MARINER geophysical experiment [Dunn et al., 2013]. Over 40,000 events were detected and located within ~16 km of the active hydrothermal field during the ~200 day deployment. We present hypocenters estimated using P- and S-wave arrival times and a crustal velocity model derived from the active-source tomography component of the MARINER experiment. Moment/magnitude estimates from spectral methods indicate that the majority of events have local magnitudes (ML) of 0-1, with the largest events approaching ML ~2. First arrival polarity data demonstrate that many of the events have non-double couple source mechanisms, and we explore the use of P/S-wave amplitude ratios to constrain these focal mechanisms. The detection of predominantly non-double events indicates processes other than simple fault slip (e.g., serpentinization) are contributing to the observed seismicity and deformation. We use the spatial distribution, magnitudes, rate, and source mechanisms of the seismic events to constrain the coupled processes of hydrothermal circulation and deformation at the Rainbow massif.

  3. Progastrin overexpression imparts tumorigenic/metastatic potential to embryonic epithelial cells: phenotypic differences between transformed and non-transformed stem cells

    PubMed Central

    Sarkar, Shubhashish; Kantara, Carla; Ortiz, Ixiu; Swiercz, Rafal; Kuo, Joyce; Davey, Robert; Escobar, Kenneth; Ullrich, Robert; Singh, Pomila

    2012-01-01

    -cells, unlike non-transformed stem-cells, co-express stem-cell-markers DCLK1 and CD44 with CS-ANXA2. PMID:22532325

  4. 1,25-Dihydroxyvitamin D induces the glutamate transporter SLC1A1 and alters glutamate handling in non-transformed mammary cells

    PubMed Central

    Beaudin, Sarah; Welsh, JoEllen

    2016-01-01

    Genomic profiling of immortalized human mammary epithelial (hTERT-HME1) cells identified several metabolic genes, including the membrane glutamate transporter, SLC1A1, as 1,25-dihydroxyvitamin D3 (1,25D) regulated. In these studies we have surveyed the effects of 1,25D on known glutamate transporters and evaluated its impact on cellular glutamate handling. We confirm that expression of SLC1A1 and all of its known transcript variants are significantly upregulated in hTERT-HME1 cells following 1,25D treatment. Expression of the full-length cognate protein, EAAT3 is correspondingly increased in 1,25D treated hTERT-HME1 cells. Under the same conditions, the expression of two other glutamate transporters - SLC1A6 (EAAT4) and SLC1A2 (EAAT2 or GLT-1) - is enhanced by 1,25D while that of SLC1A3 (EAAT1 or GLAST) and SLC7A11 (xCT) is decreased. Glutamate is not essential for growth of hTERT-HME1 cells, and supplemental glutamate (up to 0.5 mM) does not abrogate the growth inhibitory effects of 1,25D. These data suggest that extracellular glutamate is not a major contributor to cellular energy metabolism in hTERT-HME1 cells under basal conditions and that the growth inhibitory effects of 1,25D are not secondary to its effects on glutamate handling. Instead, the effects of 1,25D on glutamate transporters translated to a decrease in cellular glutamate concentration and an increase in media glutamate concentration, suggesting that one or more of these transporters functions to export glutamate in response to 1,25D exposure. The reduced cellular glutamate concentration may also reflect its incorporation into the cellular glutathione (GSH) pool, which is increased upon 1,25D treatment. In support of this concept, the expression of GCLC (which codes for the rate-limiting enzyme in GSH synthesis) and genes which generate reducing equivalents in the form of NADPH (ie, G6PD, PGD, IDH2) are elevated in 1,25D treated cells. Taken together, these data identify 1,25D as a physiological

  5. Genetic alterations by human papillomaviruses in oncogenesis.

    PubMed

    Lazo, P A; Gallego, M I; Ballester, S; Feduchi, E

    1992-03-30

    The integration sites in the cellular genome of human papillomavirus are located in chromosomal regions always associated with oncogenes or other known tumor phenotypes. Two regions, 8q24 and 12q13, are common to several cases of cervical carcinoma and can have integrated more than one type of papillomavirus DNA. These two chromosomal regions contain several genes implicated in oncogenesis. These observations strongly imply that viral integration sites of DNA tumor viruses can be used as the access point to chromosomal regions where genes implicated in the tumor phenotype are located, a situation similar to that of non-transforming retroviruses.

  6. Replication of Human Noroviruses in Stem Cell-Derived Human Enteroids

    PubMed Central

    Ettayebi, Khalil; Crawford, Sue E.; Murakami, Kosuke; Broughman, James R.; Karandikar, Umesh; Tenge, Victoria R.; Neill, Frederick H.; Blutt, Sarah E.; Zeng, Xi-Lei; Qu, Lin; Kou, Baijun; Opekun, Antone R.; Burrin, Douglas; Graham, David Y.; Ramani, Sasirekha; Atmar, Robert L.

    2016-01-01

    The major barrier to research and development of effective interventions for human noroviruses (HuNoVs) has been the lack of a robust and reproducible in vitro cultivation system. HuNoVs are the leading cause of gastroenteritis worldwide. We report successful cultivation of multiple HuNoV strains in enterocytes in stem cell-derived, nontransformed human intestinal enteroid monolayer cultures. Bile, a critical factor of the intestinal milieu, is required for strain-dependent HuNoV replication. Lack of appropriate histoblood group antigen expression in intestinal cells restricts virus replication, and infectivity is abrogated by inactivation (e.g., irradiation, heating) and serum neutralization. This culture system recapitulates the human intestinal epithelium, permits human host-pathogen studies of previously noncultivatable pathogens, and allows the assessment of methods to prevent and treat HuNoV infections. PMID:27562956

  7. Impaired OMA1-dependent cleavage of OPA1 and reduced DRP1 fission activity combine to prevent mitophagy in cells that are dependent on oxidative phosphorylation

    PubMed Central

    MacVicar, Thomas D. B.; Lane, Jon D.

    2014-01-01

    ABSTRACT Mitochondrial dynamics play crucial roles in mitophagy-based mitochondrial quality control, but how these pathways are regulated to meet cellular energy demands remains obscure. Using non-transformed human RPE1 cells, we report that upregulation of mitochondrial oxidative phosphorylation alters mitochondrial dynamics to inhibit Parkin-mediated mitophagy. Despite the basal mitophagy rates remaining stable upon the switch to dependence on oxidative phosphorylation, mitochondria resist fragmentation when RPE1 cells are treated with the protonophore carbonyl cyanide m-chlorophenyl hydrazone. Mechanistically, we show that this is because cleavage of the inner membrane fusion factor L-OPA1 is prevented due to the failure to activate the inner membrane protease OMA1 in mitochondria that have a collapsed membrane potential. In parallel, mitochondria that use oxidative phosphorylation are protected from damage-induced fission through the impaired recruitment and activation of mitochondrial DRP1. Using OMA1-deficient MEF cells, we show that the preservation of a stable pool of L-OPA1 at the inner mitochondrial membrane is sufficient to delay mitophagy, even in the presence of Parkin. The capacity of cells that are dependent on oxidative phosphorylation to maintain substantial mitochondrial content in the face of acute damage has important implications for mitochondrial quality control in vivo. PMID:24634514

  8. In non-transformed cells Bak activates upon loss of anti-apoptotic Bcl-XL and Mcl-1 but in the absence of active BH3-only proteins

    PubMed Central

    Senft, D; Weber, A; Saathoff, F; Berking, C; Heppt, M V; Kammerbauer, C; Rothenfusser, S; Kellner, S; Kurgyis, Z; Besch, R; Häcker, G

    2015-01-01

    Mitochondrial apoptosis is controlled by proteins of the B-cell lymphoma 2 (Bcl-2) family. Pro-apoptotic members of this family, known as BH3-only proteins, initiate activation of the effectors Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), which is counteracted by anti-apoptotic family members. How the interactions of Bcl-2 proteins regulate cell death is still not entirely clear. Here, we show that in the absence of extrinsic apoptotic stimuli Bak activates without detectable contribution from BH3-only proteins, and cell survival depends on anti-apoptotic Bcl-2 molecules. All anti-apoptotic Bcl-2 proteins were targeted via RNA interference alone or in combinations of two in primary human fibroblasts. Simultaneous targeting of B-cell lymphoma-extra large and myeloid cell leukemia sequence 1 led to apoptosis in several cell types. Apoptosis depended on Bak whereas Bax was dispensable. Activator BH3-only proteins were not required for apoptosis induction as apoptosis was unaltered in the absence of all BH3-only proteins known to activate Bax or Bak directly, Bcl-2-interacting mediator of cell death, BH3-interacting domain death agonist and p53-upregulated modulator of apoptosis. These findings argue for auto-activation of Bak in the absence of anti-apoptotic Bcl-2 proteins and provide evidence of profound differences in the activation of Bax and Bak. PMID:26610208

  9. Concise review: Human cell engineering: cellular reprogramming and genome editing.

    PubMed

    Mali, Prashant; Cheng, Linzhao

    2012-01-01

    Cell engineering is defined here as the collective ability to both reset and edit the genome of a mammalian cell. Until recently, this had been extremely challenging to achieve as nontransformed human cells are significantly refractory to both these processes. The recent success in reprogramming somatic cells into induced pluripotent stem cells that are self-renewable in culture, coupled with our increasing ability to effect precise and predesigned genomic editing, now readily permits cellular changes at both the genetic and epigenetic levels. These dual capabilities also make possible the generation of genetically matched, disease-free stem cells from patients for regenerative medicine. The objective of this review is to summarize the key enabling developments on these two rapidly evolving research fronts in human cell engineering, highlight unresolved issues, and outline potential future research directions.

  10. Reliable and versatile immortal muscle cell models from healthy and myotonic dystrophy type 1 primary human myoblasts.

    PubMed

    Pantic, Boris; Borgia, Doriana; Giunco, Silvia; Malena, Adriana; Kiyono, Tohru; Salvatori, Sergio; De Rossi, Anita; Giardina, Emiliano; Sangiuolo, Federica; Pegoraro, Elena; Vergani, Lodovica; Botta, Annalisa

    2016-03-01

    Primary human skeletal muscle cells (hSkMCs) are invaluable tools for deciphering the basic molecular mechanisms of muscle-related biological processes and pathological alterations. Nevertheless, their use is quite restricted due to poor availability, short life span and variable purity of the cells during in vitro culture. Here, we evaluate a recently published method of hSkMCs immortalization, relying on ectopic expression of cyclin D1 (CCND1), cyclin-dependent kinase 4 (CDK4) and telomerase (TERT) in myoblasts from healthy donors (n=3) and myotonic dystrophy type 1 (DM1) patients (n=2). The efficacy to maintain the myogenic and non-transformed phenotype, as well as the main pathogenetic hallmarks of DM1, has been assessed. Combined expression of the three genes i) maintained the CD56(NCAM)-positive myoblast population and differentiation potential; ii) preserved the non-transformed phenotype and iii) maintained the CTG repeat length, amount of nuclear foci and aberrant alternative splicing in immortal muscle cells. Moreover, immortal hSkMCs displayed attractive additional features such as structural maturation of sarcomeres, persistence of Pax7-positive cells during differentiation and complete disappearance of nuclear foci following (CAG)7 antisense oligonucleotide (ASO) treatment. Overall, the CCND1, CDK4 and TERT immortalization yields versatile, reliable and extremely useful human muscle cell models to investigate the basic molecular features of human muscle cell biology, to elucidate the molecular pathogenetic mechanisms and to test new therapeutic approaches for DM1 in vitro.

  11. Hepatocyte growth factor/scatter factor effects on epithelia. Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-met receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epithelium.

    PubMed Central

    Nusrat, A; Parkos, C A; Bacarra, A E; Godowski, P J; Delp-Archer, C; Rosen, E M; Madara, J L

    1994-01-01

    Intestinal epithelial cells rest on a fibroblast sheath. Thus, factors produced by these fibroblasts may influence epithelial function in a paracrine fashion. We examined modulation of intestinal epithelial function by one such fibroblast product, scatter factor/hepatocyte growth factor (HGF/SF). This effect was studied in vitro by using model T84 intestinal epithelial cells. When applied to confluent T84 monolayers, HGF/SF attenuates transepithelial resistance to passive ion flow in a dose-dependent manner (maximum fall at 300 ng/ml, 28% control monolayer resistance, P < 0.001, ED50 of 1.2 nM), t1/2 of 20 h. This functional effect of HGF/SF and distribution of its receptor, c-met, are polarized to the basolateral membranes of T84 intestinal epithelial cells. HGF/SF effects on resistance are not attributable to altered transcellular resistance (opening of Cl- and/or basolateral K+ channels), cytotoxicity, or enhanced cell proliferation; they therefore represent specific regulation of paracellular tight junction resistance. Analysis with biochemically purified rodent HGF/SF and Madin-Darby canine kidney cells reveals that effects on paracellular tight junctions also occur in other nontransformed epithelia. Binding of HGF/SF to its receptor in T84 intestinal epithelial cells is accompanied by tyrosine phosphorylation of the receptor. Because loosening of intercellular junctions between cells could facilitate separation, spreading, and migration of epithelial cells during physiologic processes such as wound resealing, we determined the effects of HGF/SF on intestinal epithelial wound resealing using our previously published in vitro model (Nusrat, A., C. Delp, and J. L. Madara. 1992. J. Clin. Invest. 89:1501-1511). HGF/SF markedly enhanced wound closure (> 450% increase in rate, P < 0.001) by influencing the migratory and spreading response in not only cells adjoining the wound but also cells many positions removed from the wound. We thus speculate that HGF/SF may

  12. Identification of Cripto-1 in human milk.

    PubMed

    Bianco, C; Wechselberger, C; Ebert, A; Khan, N I; Sun, Y; Salomon, D S

    2001-03-01

    Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related peptide that plays an important role in normal mammary gland development. CR-1 is expressed in the growing terminal end buds in the virgin mouse mammary gland and its expression increases during pregnancy and lactation. Furthermore, CR-I is involved in the early stages of mouse mammary tumorigenesis and in the pathogenesis of human breast cancer. Since CR-1 is expressed in the mouse mammary gland at high levels during pregnancy and lactation, we have evaluated whether this protein is present in human milk. In the present study we demonstrate that a 28 kDa immunoreactive CR-1 protein is present in 24 human milk samples as assessed by western blot analysis and that by enzyme-linked immunosorbent assay the concentration of CR-1 ranges between 62 and 118 ng/ml. In addition, CR-1 that had been purified from human milk is able to stimulate the phosphorylation of mitogen activated protein kinase in nontransformed NMuMG mouse mammary epithelial cells. These results suggest that CR-1 in human milk may be important in regulating mammary gland development during pregnancy and lactation.

  13. Opposing roles of TGF-β and EGF in the regulation of TRAIL-induced apoptosis in human breast epithelial cells.

    PubMed

    Cano-González, Ana; López-Rivas, Abelardo

    2016-08-01

    Transforming growth factor-beta (TGF-β) induces the epithelial to mesenchymal transition (EMT) in breast epithelial cells and plays an important role in mammary morphogenesis and breast cancer. In non-transformed breast epithelial cells TGF-β antagonizes epidermal growth factor (EGF) action and induces growth inhibition. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to participate in lumen formation during morphogenesis of human breast epithelial cells. Our previous work indicated that sensitivity of human breast epithelial cells to TRAIL can be modulated through the activation of the epidermal growth factor receptor-1 (EGFR). Here, we show that TGF-β opposes EGF-mediated sensitization to TRAIL-induced caspase-8 activation and apoptosis in non-transformed breast epithelial cells. Death-inducing signalling complex (DISC) formation by TRAIL was significantly reduced in cells treated with TGF-β. TGF-β treatment activates cytoprotective autophagy and down-regulates TRAIL-R2 expression at the cell surface by promoting the intracellular accumulation of this receptor. Lastly, we demonstrate that EMT is not involved in the inhibitory effect of TGF-β on apoptosis by TRAIL. Together, the data reveal a fine regulation by EGF and TGF-β of sensitivity of human breast epithelial cells to TRAIL which may be relevant during morphogenesis.

  14. Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology

    PubMed Central

    Saxena, Kapil; Blutt, Sarah E.; Ettayebi, Khalil; Zeng, Xi-Lei; Broughman, James R.; Crawford, Sue E.; Karandikar, Umesh C.; Sastri, Narayan P.; Conner, Margaret E.; Opekun, Antone R.; Graham, David Y.; Qureshi, Waqar; Sherman, Vadim; Foulke-Abel, Jennifer; In, Julie; Kovbasnjuk, Olga; Zachos, Nicholas C.; Donowitz, Mark

    2015-01-01

    ABSTRACT Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of

  15. Neoplastic transformation of human cells

    NASA Technical Reports Server (NTRS)

    Goth-Goldstein, Regine

    1995-01-01

    The goal of this project was to gain a better understanding of the cellular mechanisms of cancer induction by ionizing radiation as a risk assessment for workers subjected to high LET irradiation such as that found in space. The following ions were used for irradiation: Iron, Argon, Neon, and Lanthanum. Two tests were performed: growth in low serum and growth in agar were used as indicators of cell transformation. The specific aims of this project were to: (1) compare the effectiveness of various ions on degree of transformation of a single dose of the same RBE; (2) determine if successive irradiations with the same ion (Ge 600 MeV/u) increases the degree of transformation; (3) test if clones with the greatest degree of transformation produce tumors in nude mice; and (4) construct a cell hybrid of a transformed and control (non-transformed) clone. The cells used for this work are human mammary epithelial cells with an extended lifespan and selected for growth in MEM + 10% serum.

  16. Comparative transforming potential of different human papillomaviruses associated with non-melanoma skin cancer

    SciTech Connect

    Massimi, Paola; Thomas, Miranda; Bouvard, Veronique; Ruberto, Irene; Campo, M. Saveria; Tommasino, Massimo; Banks, Lawrence

    2008-02-20

    It is well established that high-risk human papillomaviruses (HPVs) that infect mucosal epithelia are the causative agents of cervical cancer. In contrast, the association of cutaneo-tropic HPV types with the development of non-melanoma skin cancer (NMSC) is less well defined. In this study, we have analysed the in vitro transforming potential of various cutaneous HPV types. Using oncogene cooperation assays with activated ras, we have shown that diverse cutaneous types, including 12, 14, 15, 24, 36 and 49, have significant transforming potential. Interestingly, most of this activity appears to be encoded by the E6 gene product. In contrast, the common HPV-10 exhibits no significant transforming potential in these assays. This difference may be a reflection of different patterns of cellular localization, with transforming E6s being nuclear and non-transforming being cytoplasmic. These results provide molecular support for a role of these viruses in the development of certain human malignancies.

  17. Human cell toxicogenomic analysis of bromoacetic acid: a regulated drinking water disinfection by-product.

    PubMed

    Muellner, Mark G; Attene-Ramos, Matias S; Hudson, Matthew E; Wagner, Elizabeth D; Plewa, Michael J

    2010-04-01

    The disinfection of drinking water is a major achievement in protecting the public health. However, current disinfection methods also generate disinfection by-products (DBPs). Many DBPs are cytotoxic, genotoxic, teratogenic, and carcinogenic and represent an important class of environmentally hazardous chemicals that may carry long-term human health implications. The objective of this research was to integrate in vitro toxicology with focused toxicogenomic analysis of the regulated DBP, bromoacetic acid (BAA) and to evaluate modulation of gene expression involved in DNA damage/repair and toxic responses, with nontransformed human cells. We generated transcriptome profiles for 168 genes with 30 min and 4 hr exposure times that did not induce acute cytotoxicity. Using qRT-PCR gene arrays, the levels of 25 transcripts were modulated to a statistically significant degree in response to a 30 min treatment with BAA (16 transcripts upregulated and nine downregulated). The largest changes were observed for RAD9A and BRCA1. The majority of the altered transcript profiles are genes involved in DNA repair, especially the repair of double strand DNA breaks, and in cell cycle regulation. With 4 hr of treatment the expression of 28 genes was modulated (12 upregulated and 16 downregulated); the largest fold changes were in HMOX1 and FMO1. This work represents the first nontransformed human cell toxicogenomic study with a regulated drinking water disinfection by-product. These data implicate double strand DNA breaks as a feature of BAA exposure. Future toxicogenomic studies of DBPs will further strengthen our limited knowledge in this growing area of drinking water research.

  18. Radiogenic transformation of human mammary epithelial cells in vitro

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Georgy, K. A.; Tavakoli, A.; Craise, L. M.; Durante, M.

    1996-01-01

    Cancer induction by space radiations is a major concern for manned space exploration. Accurate assessment of radiation risk at low doses requires basic understanding of mechanism(s) of radiation carcinogenesis. For determining the oncogenic effects of ionizing radiation in human epithelial cells, we transformed a mammary epithelial cell line (185B5), which was immortalized by benzo(a)pyrene, with energetic heavy ions and obtained several transformed clones. These transformed cells showed growth properties on Matrigel similar to human mammary tumor cells. To better understand the mechanisms of radiogenic transformation of human cells, we systematically examined the alterations in chromosomes and cancer genes. Among 16 autosomes examined for translocations, by using fluorescence in situ hybridization (FISH) technique, chromosomes 3, 12, 13, 15, 16, and 18 appeared to be normal in transformed cells. Chromosomes 1, 4, 6, 8, and 17 in transformed cells, however, showed patterns different from those in nontransformed cells. Southern blot analyses indicated no detectable alterations in myc, ras, Rb, or p53 genes. Further studies of chromosome 17 by using in situ hybridization with unique sequence p53 gene probe and a centromere probe showed no loss of p53 gene in transformed cells. Experimental results from cell fusion studies indicated that the transforming gene(s) is recessive. The role of genomic instability and tumor suppressor gene(s) in radiogenic transformation of human breast cells remains to be identified.

  19. Oncolytic Activity of Avian Influenza Virus in Human Pancreatic Ductal Adenocarcinoma Cell Lines

    PubMed Central

    Pizzuto, Matteo S.; Silic-Benussi, Micol; Pavone, Silvia; Ciminale, Vincenzo; Capua, Ilaria

    2014-01-01

    ABSTRACT Pancreatic ductal adenocarcinoma (PDA) is the most lethal form of human cancer, with dismal survival rates due to late-stage diagnoses and a lack of efficacious therapies. Building on the observation that avian influenza A viruses (IAVs) have a tropism for the pancreas in vivo, the present study was aimed at testing the efficacy of IAVs as oncolytic agents for killing human PDA cell lines. Receptor characterization confirmed that human PDA cell lines express the alpha-2,3- and the alpha-2,6-linked glycan receptor for avian and human IAVs, respectively. PDA cell lines were sensitive to infection by human and avian IAV isolates, which is consistent with this finding. Growth kinetic experiments showed preferential virus replication in PDA cells over that in a nontransformed pancreatic ductal cell line. Finally, at early time points posttreatment, infection with IAVs caused higher levels of apoptosis in PDA cells than gemcitabine and cisplatin, which are the cornerstone of current therapies for PDA. In the BxPC-3 PDA cell line, apoptosis resulted from the engagement of the intrinsic mitochondrial pathway. Importantly, IAVs did not induce apoptosis in nontransformed pancreatic ductal HPDE6 cells. Using a model based on the growth of a PDA cell line as a xenograft in SCID mice, we also show that a slightly pathogenic avian IAV significantly inhibited tumor growth following intratumoral injection. Taken together, these results are the first to suggest that IAVs may hold promise as future agents of oncolytic virotherapy against pancreatic ductal adenocarcinomas. IMPORTANCE Despite intensive studies aimed at designing new therapeutic approaches, PDA still retains the most dismal prognosis among human cancers. In the present study, we provide the first evidence indicating that avian IAVs of low pathogenicity display a tropism for human PDA cells, resulting in viral RNA replication and a potent induction of apoptosis in vitro and antitumor effects in vivo. These

  20. 27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells

    PubMed Central

    Zhang, Lei; Hou, Yubin; Li, Zhiyuan; Ji, Xinmiao; Wang, Ze; Wang, Huizhen; Tian, Xiaofei; Yu, Fazhi; Yang, Zhenye; Pi, Li; Mitchison, Timothy J; Lu, Qingyou; Zhang, Xin

    2017-01-01

    Purified microtubules have been shown to align along the static magnetic field (SMF) in vitro because of their diamagnetic anisotropy. However, whether mitotic spindle in cells can be aligned by magnetic field has not been experimentally proved. In particular, the biological effects of SMF of above 20 T (Tesla) have never been reported. Here we found that in both CNE-2Z and RPE1 human cells spindle orients in 27 T SMF. The direction of spindle alignment depended on the extent to which chromosomes were aligned to form a planar metaphase plate. Our results show that the magnetic torque acts on both microtubules and chromosomes, and the preferred direction of spindle alignment relative to the field depends more on chromosome alignment than microtubules. In addition, spindle morphology was also perturbed by 27 T SMF. This is the first reported study that investigated the cellular responses to ultra-high magnetic field of above 20 T. Our study not only found that ultra-high magnetic field can change the orientation and morphology of mitotic spindles, but also provided a tool to probe the role of spindle orientation and perturbation in developmental and cancer biology. DOI: http://dx.doi.org/10.7554/eLife.22911.001 PMID:28244368

  1. Low calcium culture condition induces mesenchymal cell-like phenotype in normal human epidermal keratinocytes

    SciTech Connect

    Takagi, Ryo; Yamato, Masayuki; Murakami, Daisuke; Sugiyama, Hiroaki; Okano, Teruo

    2011-08-26

    Highlights: {yields} Normal human epidermal keratinocytes serially cultured under low calcium concentration were cytokeratin and vimentin double positive cells. {yields} The human keratinocytes expressed some epithelial stem/progenitor cell makers, mesenchymal cell markers, and markers of epithelial-mesenchymal transition. {yields} Mesenchymal cell-like phenotype in the keratinocytes was suppressed under high-calcium condition. -- Abstract: Epithelial-mesenchymal transition (EMT) is an important cellular phenomenon in organ developments, cancer invasions, and wound healing, and many types of transformed cell lines are used for investigating for molecular mechanisms of EMT. However, there are few reports for EMT in normal human epithelial cells, which are non-transformed or non-immortalized cells, in vitro. Therefore, normal human epidermal keratinocytes (NHEK) serially cultured in low-calcium concentration medium (LCM) were used for investigating relations between differentiation and proliferation and mesenchymal-like phenotype in the present study, since long-term cultivation of NHEK is achieved in LCM. Interestingly, NHEK serially cultured in LCM consisted essentially of cytokeratin-vimentin double positive cells (98%), although the NHEK exhibited differentiation under high-calcium culture condition with 3T3 feeder layer. The vimentin expression was suppressed under high-calcium condition. These results may indicate the importance of mesenchymal-like phenotype for serially cultivation of NHEK in vitro.

  2. Multiple promoter elements govern expression of the human ornithine decarboxylase gene in colon carcinoma cells.

    PubMed Central

    Moshier, J A; Osborne, D L; Skunca, M; Dosescu, J; Gilbert, J D; Fitzgerald, M C; Polidori, G; Wagner, R L; Friezner Degen, S J; Luk, G D

    1992-01-01

    Overexpression of the ornithine decarboxylase (ODC) gene may be important to the development and maintenance of colonic neoplasms, as well as tumors in general. In this study, we examined the promoter elements governing constitutive expression of the human ODC gene in HCT 116 human colon carcinoma cells and, for comparison, K562 human erythro-leukemia cells. It was determined by functional analysis that the promoter elements responsible reside within the 378 bp immediately upstream from the transcription start site. Within this sequence, there are at least three regions that modulate the efficiency of the ODC promoter cooperatively. Both DNA bandshift and footprint assays demonstrated all three regions to be rich in sites that bind to nuclear proteins isolated from HCT 116 and K562 cells; the protein binding pattern of non-transformed, diploid fibroblasts was found to be much less complex. Several of the protein binding sequences have little or no homology to common regulatory elements. We suggest that the constitutive activity of the ODC gene in HCT 116 colon carcinoma cells, and perhaps transformed cells in general, involves a complex interaction of multiple regulatory sequences and their associated nuclear proteins. Finally, the saturation of the promoter in these transformed cell lines suggests that high levels of protein binding in the ODC promoter may contribute to elevated constitutive expression of this gene. Images PMID:1598217

  3. Induction by inorganic metal salts of sister chromatid exchanges and chromosome aberrations in human and Syrian hamster cell strains

    SciTech Connect

    Larramendy, M.L.; Popescu, N.C.; DiPaolo, J.A.

    1981-01-01

    Sister chromatid exchange (SCE) and chromosome aberration induction were determined for several inorganic metal salts. Arsenic, nickel, and beryllium salts at concentrations effective in causing transformation of Syrian hamster cells (HEC) induced SCE and chromosome aberrations of HEC and human lymphocytes, whereas sodium tungstate, a non-transforming chemical, neither induced SCE nor chromosome aberrations. Normal human and hamster cells exhibited equal sensitivity to SCE induction; nontoxic concentrations of sodium arsenite, beryllium sulfate, and nickel sulfate caused an increase of 8-10 SCE/cell over control values. Sodium arsenite, a trivalent arsenic, and sodium arsenate, a pentavalent arsenic, produced increases in SCE but the former was effective at lower concentrations. Both arsenic salts were less efficient in inducing SCE in human whole blood than in purified lymphocyte cultures. Sodium arsenite, sodium arsenate, nickel sulfate, and beryllium sulfate also caused damage consisting primarily of chromatid type of aberrations. In HEC, with doses most effective in SCE induction , all four metals produced aberrations in 16-21% of cells. In human lymphocytes, 34 and 30% of the cells had chromosome damage after sodium arsenite and sodium arsenate, respectively, whereas beryllium sulfate or nickel sulfate caused damage in about 10% of the cells. The induction of SCE and chromosomal aberrations by metals reemphasizes the sensitivity of cytological assays and their importance for detecting genetic damage caused by carcinogens.

  4. Differences in snRNP localization between transformed and nontransformed cells.

    PubMed Central

    Spector, D L; Lark, G; Huang, S

    1992-01-01

    We have examined the localization of snRNPs in a variety of mammalian cells and have observed differences in the organization of these factors in transformed cells, immortal cells, and cells of defined passage number. Cells of defined passage number exhibit a speckled staining pattern after immunolabeling with anti-Sm, anti-B'', or anti-m3G antibodies. Furthermore, 2-3% of the cells, in a given population, exhibit labeling of 1 or 2 round coiled bodies in addition to the speckled-labeling pattern. However, transformed cells exhibited 1-4 intensely stained coiled bodies, in 81-99% of the cells, in addition to the speckled-labeling pattern. Immortal cells exhibited 1-4 intensely stained smaller coiled bodies in 4-40% of the cells, in addition to the speckled-labeling pattern. When immortal cells (REF-52) that had been transformed by adenovirus (REF-52Ad5.4) were examined, these cells exhibited an increase in the percentage of cells containing 1 or 2 intensely stained coiled bodies, in addition to the speckled labeling, from 24 to 99%. On the basis of this study, we conclude that the organization of snRNPs within the mammalian cell nucleus is a reflection of the physiology of the cell that may change upon transformation or immortalization. Images PMID:1535243

  5. Mechanisms of Radiation Toxicity in Transformed and Non-Transformed Cells

    PubMed Central

    Panganiban, Ronald-Allan M.; Snow, Andrew L.; Day, Regina M.

    2013-01-01

    Radiation damage to biological systems is determined by the type of radiation, the total dosage of exposure, the dose rate, and the region of the body exposed. Three modes of cell death—necrosis, apoptosis, and autophagy—as well as accelerated senescence have been demonstrated to occur in vitro and in vivo in response to radiation in cancer cells as well as in normal cells. The basis for cellular selection for each mode depends on various factors including the specific cell type involved, the dose of radiation absorbed by the cell, and whether it is proliferating and/or transformed. Here we review the signaling mechanisms activated by radiation for the induction of toxicity in transformed and normal cells. Understanding the molecular mechanisms of radiation toxicity is critical for the development of radiation countermeasures as well as for the improvement of clinical radiation in cancer treatment. PMID:23912235

  6. Germ-line variant of human NTH1 DNA glycosylase induces genomic instability and cellular transformation.

    PubMed

    Galick, Heather A; Kathe, Scott; Liu, Minmin; Robey-Bond, Susan; Kidane, Dawit; Wallace, Susan S; Sweasy, Joann B

    2013-08-27

    Base excision repair (BER) removes at least 20,000 DNA lesions per human cell per day and is critical for the maintenance of genomic stability. We hypothesize that aberrant BER, resulting from mutations in BER genes, can lead to genomic instability and cancer. The first step in BER is catalyzed by DNA N-glycosylases. One of these, n(th) endonuclease III-like (NTH1), removes oxidized pyrimidines from DNA, including thymine glycol. The rs3087468 single nucleotide polymorphism of the NTH1 gene is a G-to-T base substitution that results in the NTH1 D239Y variant protein that occurs in ∼6.2% of the global population and is found in Europeans, Asians, and sub-Saharan Africans. In this study, we functionally characterize the effect of the D239Y variant expressed in immortal but nontransformed human and mouse mammary epithelial cells. We demonstrate that expression of the D239Y variant in cells also expressing wild-type NTH1 leads to genomic instability and cellular transformation as assessed by anchorage-independent growth, focus formation, invasion, and chromosomal aberrations. We also show that cells expressing the D239Y variant are sensitive to ionizing radiation and hydrogen peroxide and accumulate double strand breaks after treatment with these agents. The DNA damage response is also activated in D239Y-expressing cells. In combination, our data suggest that individuals possessing the D239Y variant are at risk for genomic instability and cancer.

  7. Comparative human cell toxicogenomic analysis of monohaloacetic acid drinking water disinfection byproducts.

    PubMed

    Attene-Ramos, Matias S; Wagner, Elizabeth D; Plewa, Michael J

    2010-10-01

    The monohaloacetic acids (monoHAAs), iodoacetic, bromoacetic and chloroacetic acids are toxic disinfection byproducts. In vitro toxicological end points were integrated with DNA damage and repair pathway-focused toxicogenomic analyses to evaluate monoHAA-induced alterations of gene expression in normal nontransformed human cells. When compared to concurrent control transcriptome profiles, metabolic pathways involved in the cellular responses to toxic agents were identified and provided insight into the biological mechanisms of toxicity. Using the Database for Annotation, Visualization and Integrated Discovery to analyze the gene array data, the majority of the altered transcriptome profiles were associated with genes responding to DNA damage or those regulating cell cycle or apoptosis. The major pathways involved with altered gene expression were ATM, MAPK, p53, BRCA1, BRCA2, and ATR. These latter pathways highlight the involvement of DNA repair, especially the repair of double strand DNA breaks. All of the resolved pathways are involved in human cell stress response to DNA damage and regulate different stages in cell cycle progression or apoptosis.

  8. Selective advantage of trisomic human cells cultured in non-standard conditions

    PubMed Central

    Rutledge, Samuel D.; Douglas, Temple A.; Nicholson, Joshua M.; Vila-Casadesús, Maria; Kantzler, Courtney L.; Wangsa, Darawalee; Barroso-Vilares, Monika; Kale, Shiv D.; Logarinho, Elsa; Cimini, Daniela

    2016-01-01

    An abnormal chromosome number, a condition known as aneuploidy, is a ubiquitous feature of cancer cells. A number of studies have shown that aneuploidy impairs cellular fitness. However, there is also evidence that aneuploidy can arise in response to specific challenges and can confer a selective advantage under certain environmental stresses. Cancer cells are likely exposed to a number of challenging conditions arising within the tumor microenvironment. To investigate whether aneuploidy may confer a selective advantage to cancer cells, we employed a controlled experimental system. We used the diploid, colorectal cancer cell line DLD1 and two DLD1-derived cell lines carrying single-chromosome aneuploidies to assess a number of cancer cell properties. Such properties, which included rates of proliferation and apoptosis, anchorage-independent growth, and invasiveness, were assessed both under standard culture conditions and under conditions of stress (i.e., serum starvation, drug treatment, hypoxia). Similar experiments were performed in diploid vs. aneuploid non-transformed human primary cells. Overall, our data show that aneuploidy can confer selective advantage to human cells cultured under non-standard conditions. These findings indicate that aneuploidy can increase the adaptability of cells, even those, such as cancer cells, that are already characterized by increased proliferative capacity and aggressive tumorigenic phenotypes. PMID:26956415

  9. Sex steroids do not prevent amylin-induced apoptosis in human cells.

    PubMed

    Schwingshackl, A; Blasko, I; Steiner, E; Pozzilli, P; Cavallo, M G; Berger, P; Grubeck-Loebenstein, B

    1998-05-25

    Formation of amylin-containing islet amyloid deposits may contribute to the progressive deterioration of beta cell function in non-insulin-dependent diabetes mellitus. As diabetes mellitus occurs in male, but rarely in female transgenic mice expressing human amylin in their pancreatic beta cells, it is of interest to study the influence of estradiol (E2) and testosterone (T) on amylin-induced cytotoxicity in human cells. The insulinoma cell line CM, thyroid epithelial cells (TEC) in primary culture, and nontransformed fibroblast lines were used. The occurrence of apoptotic cell death was assessed by nuclear labeling with propidium iodide. Amylin was cytotoxic on all cell types tested, but had the most pronounced effect on TEC and the weakest on the CM cell line. Although both E2 and T decreased the proportion of apoptotic cells in cultures kept in the absence of amylin, neither of the two hormones was able to counteract amylin-induced cytotoxicity. beta cell death and hyperglycemia can thus presumably not be prevented by the neutralization of amylin effects by sex steroids.

  10. The Human Ubiquitin Conjugating Enzyme, UBE2E3, Is Required for Proliferation of Retinal Pigment Epithelial Cells

    PubMed Central

    Plafker, Kendra S.; Farjo, Krysten M.; Wiechmann, Allan F.; Plafker, Scott M.

    2008-01-01

    Purpose Cell cycle progression is governed by the coordinated activities of kinases, phosphatases, and the ubiquitin system. The entire complement of ubiquitin pathway components that mediate this process in retinal pigment epithelial (RPE) cells remains to be identified. This study was undertaken to determine whether the human ubiquitin-conjugating enzyme, UBE2E3, is essential for RPE cell proliferation. Methods UBE2E3 expression and localization in telomerase-immortalized, human RPE cells was determined with a UBE2E3-specific antibody. The necessity for UBE2E3 in RPE proliferation was determined using small interfering (si)RNA to target the expression of the enzyme. Cell counts and immunolabeling for the proliferation marker Ki-67 and the cyclin-dependent kinase inhibitor p27Kip1 were performed to assess the consequences of UBE2E3 depletion. A mouse strain harboring a disrupted allele of UbcM2 (the mouse counterpart of UBE2E3) with the coding sequence for β-galactosidase was used to track the developmental expression of the enzyme in murine RPE cells. Results UBE2E3 localized in the nucleus of the immortalized RPE cells. Depletion of the enzyme by siRNA resulted in a cell-cycle exit accompanied by a loss of Ki-67, an increase in p27Kip1, and a doubling in cell area. Rescue experiments confirmed the specificity of the RNA interference. In vivo, UbcM2 was transcriptionally downregulated during RPE development in the mouse. Conclusions UBE2E3 is essential for the proliferation of RPE-1 cells and is downregulated during RPE layer maturation in the developing mouse eye. These findings indicate that UBE2E3 is a major enzyme in modulating the balance between RPE cell proliferation and differentiation. PMID:18614808

  11. Human alpha-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival.

    PubMed

    Fischer, Walter; Gustafsson, Lotta; Mossberg, Ann-Kristin; Gronli, Janne; Mork, Sverre; Bjerkvig, Rolf; Svanborg, Catharina

    2004-03-15

    Malignant brain tumors present a major therapeutic challenge because no selective or efficient treatment is available. Here, we demonstrate that intratumoral administration of human alpha-lactalbumin made lethal to tumor cells (HAMLET) prolongs survival in a human glioblastoma (GBM) xenograft model, by selective induction of tumor cell apoptosis. HAMLET is a protein-lipid complex that is formed from alpha-lactalbumin when the protein changes its tertiary conformation and binds oleic acid as a cofactor. HAMLET induces apoptosis in a wide range of tumor cells in vitro, but the therapeutic effect in vivo has not been examined. In this study, invasively growing human GBM tumors were established in nude rats (Han:rnu/rnu Rowett, n = 20) by transplantation of human GBM biopsy spheroids. After 7 days, HAMLET was administered by intracerebral convection-enhanced delivery for 24 h into the tumor area; and alpha-lactalbumin, the native, folded variant of the same protein, was used as a control. HAMLET reduced the intracranial tumor volume and delayed the onset of pressure symptoms in the tumor-bearing rats. After 8 weeks, all alpha-lactalbumin-treated rats had developed pressure symptoms, but the HAMLET-treated rats remained asymptomatic. Magnetic resonance imaging scans revealed large differences in tumor volume (456 versus 63 mm(3)). HAMLET caused apoptosis in vivo in the tumor but not in adjacent intact brain tissue or in nontransformed human astrocytes, and no toxic side effects were observed. The results identify HAMLET as a new candidate in cancer therapy and suggest that HAMLET should be additionally explored as a novel approach to controlling GBM progression.

  12. Relocalization of cell adhesion molecules during neoplastic transformation of human fibroblasts.

    PubMed

    Belgiovine, Cristina; Chiodi, Ilaria; Mondello, Chiara

    2011-11-01

    Studying neoplastic transformation of telomerase immortalized human fibroblasts (cen3tel), we found that the transition from normal to tumorigenic cells was associated with the loss of growth contact inhibition, the acquisition of an epithelial-like morphology and a change in actin organization, from stress fibers to cortical bundles. We show here that these variations were paralleled by an increase in N-cadherin expression and relocalization of different adhesion molecules, such as N-cadherin, α-catenin, p-120 and β-catenin. These proteins presented a clear membrane localization in tumorigenic cells compared to a more diffuse, cytoplasmic distribution in primary fibroblasts and non-tumorigenic immortalized cells, suggesting that tumorigenic cells could form strong cell-cell contacts and cell contacts did not induce growth inhibition. The epithelial-like appearance of tumorigenic cells did not reflect a mesenchymal-epithelial transition; in fact, cen3tel cells expressed vimentin and did not express cytokeratins at all transformation stages. Moreover, they did not express epithelial proteins such as occluding and claudin-1. In contrast, ZO-1 showed higher levels and a more defined membrane localization in tumorigenic cells compared to non-tumorigenic cells; this confirms its role in adherens junction formation in mesenchymal cells and is in agreement with the strong cell-cell contact formation by neoplastically transformed cells. Finally, we found α-catenin and ZO-1 nuclear localization in non-transformed cells, suggestive of possible additional roles of these proteins besides cell junction formation.

  13. FSH-Receptor Isoforms and FSH-dependent Gene Transcription in Human Monocytes and Osteoclasts

    PubMed Central

    Robinson, Lisa J; Tourkova, Irina; Wang, Yujuan; Sharrow, Allison C; Landau, Michael S; Yaroslavskiy, Beatrice B; Li, Sun; Zaidi, Mone; Blair, Harry C

    2010-01-01

    Cells of the monocyte series respond to follicle stimulating hormone (FSH) by poorly characterized mechanisms. We studied FSH-receptors (FSH-R) and FSH response in nontransformed human monocytes and in osteoclasts differentiated from these cells. Western blot and PCR confirmed FSH-R expression on monocytes or osteoclasts, although at low levels relative to ovarian controls. Monocyte and osteoclast FSH-Rs differed from FSH-R from ovarian cells, reflecting variable splicing in exons 8–10. Monocytes produced no cAMP, the major signal in ovarian cells, in response to FSH. However, monocytes or osteoclasts transcribed TNFα in response to the FSH. No relation of expression of osteoclast FSH-R to the sex of cell donors or to exposure to sex hormones was apparent. Controls for FSH purity and endotoxin contamination were negative. Unamplified cRNA screening in adherent CD14 cells after 2 hours in 25 ng/ml FSH showed increased transcription of RANKL signalling proteins. Transcription of key proteins that stimulate bone turnover, TNFα and TSG-6, increased 2–3 fold after FSH treatment. Smaller but significant changes occurred in transcripts of selected signalling, adhesion, and cytoskeletal proteins. We conclude that monocyte and osteoclast FSH response diverges from that of ovarian cells, reflecting, at least in part, varying FSH-R isoforms. PMID:20171950

  14. CD45 phosphatase is crucial for human and murine acute myeloid leukemia maintenance through its localization in lipid rafts.

    PubMed

    Saint-Paul, Laetitia; Nguyen, Chi-Hung; Buffière, Anne; Pais de Barros, Jean-Paul; Hammann, Arlette; Landras-Guetta, Corinne; Filomenko, Rodolphe; Chrétien, Marie-Lorraine; Johnson, Pauline; Bastie, Jean-Noël; Delva, Laurent; Quéré, Ronan

    2016-10-04

    CD45 is a pan-leukocyte protein with tyrosine phosphatase activity involved in the regulation of signal transduction in hematopoiesis. Exploiting CD45 KO mice and lentiviral shRNA, we prove the crucial role that CD45 plays in acute myeloid leukemia (AML) development and maintenance. We discovered that CD45 does not colocalize with lipid rafts on murine and human non-transformed hematopoietic cells. Using a mouse model, we proved that CD45 positioning within lipid rafts is modified during their oncogenic transformation to AML. CD45 colocalized with lipid rafts on AML cells, which contributes to elevated GM-CSF signal intensity involved in proliferation of leukemic cells. We furthermore proved that the GM-CSF/Lyn/Stat3 pathway that contributes to growth of leukemic cells could be profoundly affected, by using a new plasma membrane disrupting agent, which rapidly delocalized CD45 away from lipid rafts. We provide evidence that this mechanism is also effective on human primary AML samples and xenograft transplantation. In conclusion, this study highlights the emerging evidence of the involvement of lipid rafts in oncogenic development of AML and the targeting of CD45 positioning among lipid rafts as a new strategy in the treatment of AML.

  15. CD45 phosphatase is crucial for human and murine acute myeloid leukemia maintenance through its localization in lipid rafts

    PubMed Central

    Saint-Paul, Laetitia; Nguyen, Chi-Hung; Buffière, Anne; de Barros, Jean-Paul Pais; Hammann, Arlette; Landras-Guetta, Corinne; Filomenko, Rodolphe; Chrétien, Marie-Lorraine; Johnson, Pauline; Bastie, Jean-Noël; Delva, Laurent; Quéré, Ronan

    2016-01-01

    CD45 is a pan-leukocyte protein with tyrosine phosphatase activity involved in the regulation of signal transduction in hematopoiesis. Exploiting CD45 KO mice and lentiviral shRNA, we prove the crucial role that CD45 plays in acute myeloid leukemia (AML) development and maintenance. We discovered that CD45 does not colocalize with lipid rafts on murine and human non-transformed hematopoietic cells. Using a mouse model, we proved that CD45 positioning within lipid rafts is modified during their oncogenic transformation to AML. CD45 colocalized with lipid rafts on AML cells, which contributes to elevated GM-CSF signal intensity involved in proliferation of leukemic cells. We furthermore proved that the GM-CSF/Lyn/Stat3 pathway that contributes to growth of leukemic cells could be profoundly affected, by using a new plasma membrane disrupting agent, which rapidly delocalized CD45 away from lipid rafts. We provide evidence that this mechanism is also effective on human primary AML samples and xenograft transplantation. In conclusion, this study highlights the emerging evidence of the involvement of lipid rafts in oncogenic development of AML and the targeting of CD45 positioning among lipid rafts as a new strategy in the treatment of AML. PMID:27579617

  16. T Cell Receptor-induced Activation and Apoptosis In Cycling Human T Cells Occur throughout the Cell Cycle

    PubMed Central

    Karas, Michael; Zaks, Tal Z.; JL, Liu; LeRoith, Derek

    1999-01-01

    Previous studies have found conflicting associations between susceptibility to activation-induced cell death and the cell cycle in T cells. However, most of the studies used potentially toxic pharmacological agents for cell cycle synchronization. A panel of human melanoma tumor-reactive T cell lines, a CD8+ HER-2/neu-reactive T cell clone, and the leukemic T cell line Jurkat were separated by centrifugal elutriation. Fractions enriched for the G0–G1, S, and G2–M phases of the cell cycle were assayed for T cell receptor-mediated activation as measured by intracellular Ca2+ flux, cytolytic recognition of tumor targets, and induction of Fas ligand mRNA. Susceptibility to apoptosis induced by recombinant Fas ligand and activation-induced cell death were also studied. None of the parameters studied was specific to a certain phase of the cell cycle, leading us to conclude that in nontransformed human T cells, both activation and apoptosis through T cell receptor activation can occur in all phases of the cell cycle. PMID:10588669

  17. Requirement of a dopaminergic neuronal phenotype for toxicity of low concentrations of 1-methyl-4-phenylpyridinium to human cells

    SciTech Connect

    Schildknecht, Stefan; Poeltl, Dominik; Nagel, Daniel M.; Matt, Florian; Scholz, Diana; Lotharius, Julie; Schmieg, Nathalie; Salvo-Vargas, Alberto; Leist, Marcel

    2009-11-15

    LUHMES cells are conditionally-immortalized non-transformed human fetal cells that can be differentiated to acquire a dopaminergic neuron-like phenotype under appropriate growth conditions. After differentiation by GDNF and cyclic adenosine monophosphate, LUHMES were sensitive to 1-methyl-4-phenylpyridinium (MPP{sup +}) toxicity at <= 5 muM, but resistant to the parental compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The high homogeneity and purity of the cultures allowed the detection of metabolic changes during the degeneration. Cellular ATP dropped in two phases after 24 and 48 h; cellular glutathione (GSH) decreased continuously, paralleled by an increase in lipid peroxidation. These events were accompanied by a time-dependent degeneration of neurites. Block of the dopamine transporter by GBR 12909 or mazindol completely abrogated MPP{sup +} toxicity. Inhibition of de novo dopamine synthesis by alpha-methyl-L-tyrosine or 3-iodo-L-tyrosine attenuated toxicity, but did not reduce the initial drop in ATP. Inhibition of mixed lineage kinases by CEP1347 completely prevented the MPP{sup +}-induced loss of viability and intracellular GSH, but failed to attenuate the initial drop of ATP. For the quantitative assessment of neurite degeneration, an automated imaging-based high content screening approach was applied and confirmed the findings made by pharmacological interventions in this study. Our data indicate that inhibition of mitochondrial ATP synthesis is not sufficient to trigger cell death in MPP{sup +}-treated LUHMES.

  18. Vesicular stomatitis virus glycoprotein- and Venezuelan equine encephalitis virus-derived glycoprotein-pseudotyped lentivirus vectors differentially transduce corneal endothelium, trabecular meshwork, and human photoreceptors.

    PubMed

    Lipinski, Daniel M; Barnard, Alun R; Charbel Issa, Peter; Singh, Mandeep S; De Silva, Samantha R; Trabalza, Antonio; Eleftheriadou, Ioanna; Ellison, Stuart M; Mazarakis, Nicholas D; MacLaren, Robert E

    2014-01-01

    The ability to deliver a large transgene efficiently to photoreceptors using viral vectors remains problematic and yet is critical for the future therapy of inherited retinal diseases such as Stargardt's and Usher's 1B. Herein, we examine the ocular tropism of a HIV-1-based lentivirus vector pseudotyped with Venezuelan equine encephalitis virus-derived glycoprotein (VEEV-G) after intraocular delivery to the posterior and anterior chambers of C57BL/6 wild-type mice. Reporter gene (EGFP) expression was evaluated using in vivo fluorescence imaging followed by postmortem immunohistochemistry and retinal function assessed by electroretinography. Intracameral administration of VEEV-G and vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped vectors resulted in robust transgene expression in the corneal endothelium and trabecular meshwork. After subretinal administration, onset of transgene expression was observed in the retinal pigment epithelium (RPE) 1 day postinjection with both VEEV-G and control VSV-G pseudotypes, but no significant photoreceptor transduction was apparent. Substantial degeneration of the outer nuclear layer was observed with VEEV-G-pseudotyped vector, which corresponded to ablation of retinal function. Subretinal administration of VSV-G was observed to result in significant suppression of electrophysiological function compared with buffer-injected and uninjected control eyes. Suppression of the c-wave amplitude, in addition to reduced RPE65 expression, indicated potential RPE dysfunction. Ex vivo tropism of VSV-G was assessed using organotypic culture of explanted retina harvested from wild-type mice and human patients undergoing retinal detachment surgery to examine the prevention of transduction by physical barriers and species differences in tropism.

  19. Potentiation of epidermal growth factor receptor-mediated oncogenesis by c-Src: implications for the etiology of multiple human cancers.

    PubMed Central

    Maa, M C; Leu, T H; McCarley, D J; Schatzman, R C; Parsons, S J

    1995-01-01

    c-Src is a nontransforming tyrosine kinase that participates in signaling events mediated by a variety of polypeptide growth factor receptors, including the epidermal growth factor receptor (EGFR). Overexpression and continual ligand stimulation of the EGFR results in morphological transformation of cells in vitro and tumor development in vivo. Elevated levels of c-Src and the EGFR are found in a variety of human malignancies, raising the question of whether c-Src can functionally cooperate with the EGFR during tumorigenesis. To address this issue, we generated c-Src/EGFR double overexpressors and compared their proliferative and biochemical characteristics to those of single overexpressors and control cells. We found that in cells expressing high levels of receptor, c-Src potentiated DNA synthesis, growth in soft agar, and tumor formation in nude mice. Growth potentiation was associated with the formation of a heterocomplex between c-Src and activated EGFR, the appearance of a distinct tyrosyl phosphorylation on the receptor, and an enhancement of receptor substrate phosphorylation. These findings indicate that c-Src is capable of potentiating receptor-mediated tumorigenesis and suggest that synergism between c-Src and the EGFR may contribute to a more aggressive phenotype in multiple human tumors. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7542783

  20. Initial slope of radiation survival curves is characteristic of the origin of primary and established cultures of human tumor cells and fibroblasts

    SciTech Connect

    Malaise, E.P.; Fertil, B.; Deschavanne, P.J.; Chavaudra, N.; Brock, W.A.

    1987-08-01

    The published survival curves of 110 human tumor cell lines and 147 nontransformed human fibroblast strains have been reanalyzed using three different statistical methods: the single hit multitarget model, the linear-quadratic model, and the mean inactivation dose. The 110 tumor cell lines were classified in two ways: (a) into three categories defined by clinical radiocurability criteria, and (b) into seven categories based on histopathology. The 147 fibroblast strains were divided into eight genetic groups. Differences in the radiosensitivities of both the tumor cell and fibroblast groups could be demonstrated only by parameters that describe the slopes of the initial part of the survival curves. The capacity of the survival level to identify significant differences between groups was dose dependent over the range 1 to 6 Gy. This relationship showed a bell-shaped curve with a maximum at 1.5 Gy for the tumor cell lines and 3 Gy for the fibroblasts. Values for intrinsic radiosensitivity for a number of groups of tumors have also been obtained by primary culture of tumor cells. These values are strictly comparable to those obtained by clonogenic methods. This confirms that intrinsic radiosensitivity is a determinant of the response of tumor cells to radiotherapy and suggests that tissue culture methods may be used as a predictive assay.

  1. Cross-Analysis of Gene and miRNA Genome-Wide Expression Profiles in Human Fibroblasts at Different Stages of Transformation

    PubMed Central

    Ostano, Paola; Bione, Silvia; Belgiovine, Cristina; Chiodi, Ilaria; Ghimenti, Chiara; Scovassi, A. Ivana; Chiorino, Giovanna

    2012-01-01

    Abstract We have developed a cellular system constituted of human telomerase immortalized fibroblasts that gradually underwent neoplastic transformation during propagation in culture. We exploited this cellular system to investigate gene and miRNA transcriptional programs in cells at different stages of propagation, representing five different phases along the road to transformation, from non-transformed cells up to tumorigenic and metastatic ones. Here we show that gene and miRNA expression profiles were both able to divide cells according to their transformation phase. We identified more than 1,700 genes whose expression was highly modulated in cells at at least one propagation stage and we found that the number of modulated genes progressively increased at successive stages of transformation. These genes identified processes significantly deregulated in tumorigenic cells, such as cell differentiation, cell movement and extracellular matrix remodeling, cell cycle and apoptosis, together with upregulation of several cancer testis antigens. Alterations in cell cycle, apoptosis, and cancer testis antigen expression were particular hallmarks of metastatic cells. A parallel deregulation of a panel of 43 miRNAs strictly connected to the p53 and c-Myc pathways and with oncogenic/oncosuppressive functions was also found. Our results indicate that cen3tel cells can be a useful model for human fibroblast neoplastic transformation, which appears characterized by complex and peculiar alterations involving both genetic and epigenetic reprogramming, whose elucidation could provide useful insights into regulatory networks underlying cancerogenesis. PMID:22321013

  2. Cross-analysis of gene and miRNA genome-wide expression profiles in human fibroblasts at different stages of transformation.

    PubMed

    Ostano, Paola; Bione, Silvia; Belgiovine, Cristina; Chiodi, Ilaria; Ghimenti, Chiara; Scovassi, A Ivana; Chiorino, Giovanna; Mondello, Chiara

    2012-01-01

    We have developed a cellular system constituted of human telomerase immortalized fibroblasts that gradually underwent neoplastic transformation during propagation in culture. We exploited this cellular system to investigate gene and miRNA transcriptional programs in cells at different stages of propagation, representing five different phases along the road to transformation, from non-transformed cells up to tumorigenic and metastatic ones. Here we show that gene and miRNA expression profiles were both able to divide cells according to their transformation phase. We identified more than 1,700 genes whose expression was highly modulated in cells at at least one propagation stage and we found that the number of modulated genes progressively increased at successive stages of transformation. These genes identified processes significantly deregulated in tumorigenic cells, such as cell differentiation, cell movement and extracellular matrix remodeling, cell cycle and apoptosis, together with upregulation of several cancer testis antigens. Alterations in cell cycle, apoptosis, and cancer testis antigen expression were particular hallmarks of metastatic cells. A parallel deregulation of a panel of 43 miRNAs strictly connected to the p53 and c-Myc pathways and with oncogenic/oncosuppressive functions was also found. Our results indicate that cen3tel cells can be a useful model for human fibroblast neoplastic transformation, which appears characterized by complex and peculiar alterations involving both genetic and epigenetic reprogramming, whose elucidation could provide useful insights into regulatory networks underlying cancerogenesis.

  3. Functional consequences of anti-sense RNA-mediated inhibition of CD8 surface expression in a human T cell clone

    PubMed Central

    1988-01-01

    An experimental approach for defining the function of CD8 has been developed by linking anti-sense RNA mutagenesis and T cell cloning technologies. We have transfected an anti-sense CD8 episomal expression vector into a CD8+ nontransformed human T cell clone that is specific for the human class I alloantigen HLA-B35. Expression of CD8 on this T cell clone, JH.ARL.1, was selectively and efficiently inhibited. Stimulation of this CD8- variant with specific alloantigen resulted in a marked loss of a number of functional responses, including cytotoxicity, proliferation, IL-2 secretion, and IL-2-R expression. However, these same functional responses could be elicited with stimuli that do not require antigen recognition to activate the T cell (anti- CD3 mAbs, PHA). The results of our study support the hypothesis that CD8 is required for recognition of class I MHC alloantigens that results in activation of T cell functional responses. PMID:2459296

  4. The ETS Transcription Factor ESE-1 Transforms MCF-12A Human Mammary Epithelial Cells via a Novel Cytoplasmic Mechanism

    PubMed Central

    Prescott, Jason D.; Koto, Karen S. N.; Singh, Meenakshi; Gutierrez-Hartmann, Arthur

    2004-01-01

    Several different transcription factors, including estrogen receptor, progesterone receptor, and ETS family members, have been implicated in human breast cancer, indicating that transcription factor-induced alterations in gene expression underlie mammary cell transformation. ESE-1 is an epithelium-specific ETS transcription factor that contains two distinguishing domains, a serine- and aspartic acid-rich (SAR) domain and an AT hook domain. ESE-1 is abundantly expressed in human breast cancer and trans-activates epithelium-specific gene promoters in transient transfection assays. While it has been presumed that ETS factors transform mammary epithelial cells via their nuclear transcriptional functions, here we show (i) that ESE-1 protein is cytoplasmic in human breast cancer cells; (ii) that stably expressed green fluorescent protein-ESE-1 transforms MCF-12A human mammary epithelial cells; and (iii) that the ESE-1 SAR domain, acting in the cytoplasm, is necessary and sufficient to mediate this transformation. Deletion of transcriptional regulatory or nuclear localization domains does not impair ESE-1-mediated transformation, whereas fusing the simian virus 40 T-antigen nuclear localization signal to various ESE-1 constructs, including the SAR domain alone, inhibits their transforming capacity. Finally, we show that the nuclear localization of ESE-1 protein induces apoptosis in nontransformed mammary epithelial cells via a transcription-dependent mechanism. Together, our studies reveal two distinct ESE-1 functions, apoptosis and transformation, where the ESE-1 transcription activation domain contributes to apoptosis and the SAR domain mediates transformation via a novel nonnuclear, nontranscriptional mechanism. These studies not only describe a unique ETS factor transformation mechanism but also establish a new paradigm for cell transformation in general. PMID:15169914

  5. Barriers to Infection of Human Cells by Feline Leukemia Virus: Insights into Resistance to Zoonosis.

    PubMed

    Terry, Anne; Kilbey, Anna; Naseer, Asif; Levy, Laura S; Ahmad, Shamim; Watts, Ciorsdaidh; Mackay, Nancy; Cameron, Ewan; Wilson, Sam; Neil, James C

    2017-03-01

    The human genome displays a rich fossil record of past gammaretrovirus infections, yet no current epidemic is evident, despite environmental exposure to viruses that infect human cells in vitro Feline leukemia viruses (FeLVs) rank high on this list, but neither domestic nor workplace exposure has been associated with detectable serological responses. Nonspecific inactivation of gammaretroviruses by serum factors appears insufficient to explain these observations. To investigate further, we explored the susceptibilities of primary and established human cell lines to FeLV-B, the most likely zoonotic variant. Fully permissive infection was common in cancer-derived cell lines but was also a feature of nontransformed keratinocytes and lung fibroblasts. Cells of hematopoietic origin were generally less permissive and formed discrete groups on the basis of high or low intracellular protein expression and virion release. Potent repression was observed in primary human blood mononuclear cells and a subset of leukemia cell lines. However, the early steps of reverse transcription and integration appear to be unimpaired in nonpermissive cells. FeLV-B was subject to G→A hypermutation with a predominant APOBEC3G signature in partially permissive cells but was not mutated in permissive cells or in nonpermissive cells that block secondary viral spread. Distinct cellular barriers that protect primary human blood cells are likely to be important in protection against zoonotic infection with FeLV.IMPORTANCE Domestic exposure to gammaretroviruses such as feline leukemia viruses (FeLVs) occurs worldwide, but the basis of human resistance to infection remains incompletely understood. The potential threat is evident from the human genome sequence, which reveals many past epidemics of gammaretrovirus infection, and from recent cross-species jumps of gammaretroviruses from rodents to primates and marsupials. This study examined resistance to infection at the cellular level with the most

  6. Barriers to Infection of Human Cells by Feline Leukemia Virus: Insights into Resistance to Zoonosis

    PubMed Central

    Terry, Anne; Kilbey, Anna; Naseer, Asif; Levy, Laura S.; Ahmad, Shamim; Watts, Ciorsdaidh; Mackay, Nancy; Cameron, Ewan; Wilson, Sam

    2016-01-01

    ABSTRACT The human genome displays a rich fossil record of past gammaretrovirus infections, yet no current epidemic is evident, despite environmental exposure to viruses that infect human cells in vitro. Feline leukemia viruses (FeLVs) rank high on this list, but neither domestic nor workplace exposure has been associated with detectable serological responses. Nonspecific inactivation of gammaretroviruses by serum factors appears insufficient to explain these observations. To investigate further, we explored the susceptibilities of primary and established human cell lines to FeLV-B, the most likely zoonotic variant. Fully permissive infection was common in cancer-derived cell lines but was also a feature of nontransformed keratinocytes and lung fibroblasts. Cells of hematopoietic origin were generally less permissive and formed discrete groups on the basis of high or low intracellular protein expression and virion release. Potent repression was observed in primary human blood mononuclear cells and a subset of leukemia cell lines. However, the early steps of reverse transcription and integration appear to be unimpaired in nonpermissive cells. FeLV-B was subject to G→A hypermutation with a predominant APOBEC3G signature in partially permissive cells but was not mutated in permissive cells or in nonpermissive cells that block secondary viral spread. Distinct cellular barriers that protect primary human blood cells are likely to be important in protection against zoonotic infection with FeLV. IMPORTANCE Domestic exposure to gammaretroviruses such as feline leukemia viruses (FeLVs) occurs worldwide, but the basis of human resistance to infection remains incompletely understood. The potential threat is evident from the human genome sequence, which reveals many past epidemics of gammaretrovirus infection, and from recent cross-species jumps of gammaretroviruses from rodents to primates and marsupials. This study examined resistance to infection at the cellular level

  7. Proteasome-Dependent Degradation of Daxx by the Viral E1B-55K Protein in Human Adenovirus-Infected Cells ▿

    PubMed Central

    Schreiner, Sabrina; Wimmer, Peter; Sirma, Hüseyin; Everett, Roger D.; Blanchette, Paola; Groitl, Peter; Dobner, Thomas

    2010-01-01

    The death-associated protein Daxx found in PML (promyelocytic leukemia protein) nuclear bodies (PML-NBs) is involved in transcriptional regulation and cellular intrinsic antiviral resistence against incoming viruses. We found that knockdown of Daxx in a nontransformed human hepatocyte cell line using RNA interference (RNAi) techniques results in significantly increased adenoviral (Ad) replication, including enhanced viral mRNA synthesis and viral protein expression. This Daxx restriction imposed upon adenovirus growth is counteracted by early protein E1B-55K (early region 1B 55-kDa protein), a multifunctional regulator of cell-cycle-independent Ad5 replication. The viral protein binds to Daxx and induces its degradation through a proteasome-dependent pathway. We show that this process is independent of Ad E4orf6 (early region 4 open reading frame 6), known to promote the proteasomal degradation of cellular p53, Mre11, DNA ligase IV, and integrin α3 in combination with E1B-55K. These results illustrate the importance of the PML-NB-associated factor Daxx in virus growth restriction and suggest that E1B-55K antagonizes innate antiviral activities of Daxx and PML-NBs to stimulate viral replication at a posttranslational level. PMID:20484509

  8. Low cytotoxicity of inorganic nanotubes and fullerene-like nanostructures in human bronchial epithelial cells: relation to inflammatory gene induction and antioxidant response.

    PubMed

    Pardo, Michal; Shuster-Meiseles, Timor; Levin-Zaidman, Smadar; Rudich, Assaf; Rudich, Yinon

    2014-03-18

    The cytotoxicity of tungsten disulfide nano tubes (INT-WS2) and inorganic fullerene-like molybdenum disulfide (IF-MoS2) nanoparticles (NPs) used in industrial and medical applications was evaluated in comparison to standard environmental particulate matter. The IF-MoS2 and INT-WS2 reside in vesicles/inclusion bodies, suggestive of endocytic vesicles. In cells representing the respiratory, immune and metabolic systems, both IF-MoS2 and INT-WS2 NPs remained nontoxic compared to equivalent concentrations (up to 100 μg/mL in the medium) of silica dioxide (SiO2), diesel engine-derived and carbon black NPs, which induced cell death. Associating with this biocompatibility of IF-MoS2\\INT-WS2, we demonstrate in nontransformed human bronchial cells (NL-20) relative low induction of the pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α. Moreover, IF-MoS2 and INT-WS2 activated antioxidant response as measured by the antioxidant response element (ARE) using a luciferase reporter, and induced Nrf2-mediated Phase II detoxification genes. Collectively, our findings suggest that the lower cytotoxicity of IF-MoS2 and INT-WS2 NPs does not reflect general biological inertness. Rather, compared to other NP's, it likely results from decreased pro-inflammatory activation, but a comparable significant capacity to induce protective antioxidant/detoxification defense mechanisms.

  9. A high-affinity and specific carrier-mediated mechanism for uptake of thiamine pyrophosphate by human colonic epithelial cells.

    PubMed

    Nabokina, Svetlana M; Said, Hamid M

    2012-08-01

    All mammals require exogenous sources of thiamine (vitamin B1), as they lack the ability to synthesize the vitamin. These sources are dietary and bacterial (the latter is in reference to the vitamin, which is synthesized by the normal microflora of the large intestine). Bacterially generated thiamine exists in the free, as well as the pyrophosphorylated [thiamine pyrophosphate (TPP)], form. With no (or very little) phosphatase activity in the colon, we hypothesized that the bacterially generated TPP can also be taken up by colonocytes. To test this hypothesis, we examined [(3)H]TPP uptake in the human-derived, nontransformed colonic epithelial NCM460 cells and purified apical membrane vesicles isolated from the colon of human organ donors. Uptake of TPP by NCM460 cells occurred without metabolic alterations in the transported substrate and 1) was pH- and Na(+)-independent, but energy-dependent, 2) was saturable as a function of concentration (apparent K(m) = 0.157 ± 0.028 μM), 3) was highly specific for TPP and not affected by free thiamine (or its analogs) or by thiamine monophosphate and unrelated folate derivatives, 4) was adaptively regulated by extracellular substrate (TPP) level via what appears to be a transcriptionally mediated mechanism(s), and 5) appeared to be influenced by an intracellular Ca(2+)/calmodulin-mediated regulatory pathway. These findings suggest the involvement of a carrier-mediated mechanism for TPP uptake by colonic NCM460 cells, which was further confirmed by results from studies of native human colonic apical membrane vesicles. The results also suggest that the bacterially synthesized TPP in the large intestine is bioavailable and may contribute to overall body homeostasis of vitamin B1 and, especially, to the cellular nutrition of the local colonocytes.

  10. Human Development, Human Evolution.

    ERIC Educational Resources Information Center

    Smillie, David

    One of the truly remarkable events in human evolution is the unprecedented increase in the size of the brain of "Homo" over a brief span of 2 million years. It would appear that some significant selective pressure or opportunity presented itself to this branch of the hominid line and caused a rapid increase in the brain, introducing a…

  11. Humanizing the Humanities.

    ERIC Educational Resources Information Center

    Peters, Dennis

    1983-01-01

    Reviews some of the steps taken at Shoreline Community College to develop cooperative programs involving vocational and academic faculty, including the creation of a Humanities Advisory Council. Briefly describes some of the cooperative programs, e.g., symposia on critical issues in higher education, guest lectures, and high school outreach. (AYC)

  12. Humanity and human DNA.

    PubMed

    Mattei, Jean-François

    2012-10-01

    Genetics has marked the second half of the 20th century by addressing such formidable problems as the identification of our genes and their role, their interaction with the environment, and even their therapeutic uses. The identification of genes raises questions about differences between humans and non-humans, as well as about the evolution towards trans-humanism and post-humanism. In practise, however, the main question concerns the limits of prenatal genetic diagnosis, not only on account of the seriousness of the affections involved but also because of the choice to be made between following-up the medical indication and engaging in a systematic public health strategy aimed at eliminating children with certain handicaps. History reminds us that genetic science has already been misused by political forces influenced by the ideas of eugenics, particularly in the Nazi period. We may wonder whether it is reasonable to formulate a judgement on the life of a child yet to be born, merely on the basis of a DNA analysis. My experience as a practising geneticist and my involvement in French politics forces me to stress the dangers of a new eugenics hiding behind a medical mask. As demonstrated by epigenetics, human beings cannot be reduced to their DNA alone. In our society, one of the problems concerns individuals whose lives may be considered by some as simply not worth living. Another problem is the place and the social significance of the handicapped amongst us. Fortunately, recent progresses in gene therapy, biotherapy, and even pharmacology, appear to be opening up promising therapeutic perspectives. We should bear in mind that the chief vocation of medical genetics, which fully belongs to the art of medicine, is to heal and to cure. This is precisely where genetics should concentrate its efforts software.

  13. CHR-2797: an antiproliferative aminopeptidase inhibitor that leads to amino acid deprivation in human leukemic cells.

    PubMed

    Krige, David; Needham, Lindsey A; Bawden, Lindsay J; Flores, Nicolas; Farmer, Hannah; Miles, Lauren E C; Stone, Erica; Callaghan, Juliana; Chandler, Stephen; Clark, Vanessa L; Kirwin-Jones, Patricia; Legris, Valérie; Owen, Jo; Patel, Thakor; Wood, Steve; Box, Gary; Laber, David; Odedra, Rajesh; Wright, Annette; Wood, L Michael; Eccles, Suzanne A; Bone, Elisabeth A; Ayscough, Andrew; Drummond, Alan H

    2008-08-15

    CHR-2797 is a novel metalloenzyme inhibitor that is converted into a pharmacologically active acid product (CHR-79888) inside cells. CHR-79888 is a potent inhibitor of a number of intracellular aminopeptidases, including leucine aminopeptidase. CHR-2797 exerts antiproliferative effects against a range of tumor cell lines in vitro and in vivo and shows selectivity for transformed over nontransformed cells. Its antiproliferative effects are at least 300 times more potent than the prototypical aminopeptidase inhibitor, bestatin. However, the mechanism by which inhibition of these enzymes leads to proliferative changes is not understood. Gene expression microarrays were used to profile changes in mRNA expression levels in the human promyelocytic leukemia cell line HL-60 treated with CHR-2797. This analysis showed that CHR-2797 treatment induced a transcriptional response indicative of amino acid depletion, the amino acid deprivation response, which involves up-regulation of amino acid synthetic genes, transporters, and tRNA synthetases. These changes were confirmed in other leukemic cell lines sensitive to the antiproliferative effects of CHR-2797. Furthermore, CHR-2797 treatment inhibited phosphorylation of mTOR substrates and reduced protein synthesis in HL-60 cells, both also indicative of amino acid depletion. Treatment with CHR-2797 led to an increase in the concentration of intracellular small peptides, the substrates of aminopeptidases. It is suggested that aminopeptidase inhibitors, such as CHR-2797 and bestatin, deplete sensitive tumor cells of amino acids by blocking protein recycling, and this generates an antiproliferative effect. CHR-2797 is orally bioavailable and currently undergoing phase II clinical investigation in the treatment of myeloid leukemia.

  14. Human cell toxicogenomic analysis linking reactive oxygen species to the toxicity of monohaloacetic acid drinking water disinfection byproducts.

    PubMed

    Pals, Justin; Attene-Ramos, Matias S; Xia, Menghang; Wagner, Elizabeth D; Plewa, Michael J

    2013-01-01

    Chronic exposure to drinking water disinfection byproducts has been linked to adverse health risks. The monohaloacetic acids (monoHAAs) are generated as byproducts during the disinfection of drinking water and are cytotoxic, genotoxic, mutagenic, and teratogenic. Iodoacetic acid toxicity was mitigated by antioxidants, suggesting the involvement of oxidative stress. Other monoHAAs may share a similar mode of action. Each monoHAA generated a significant concentration-response increase in the expression of a β-lactamase reporter under the control of the antioxidant response element (ARE). The monoHAAs generated oxidative stress with a rank order of iodoacetic acid (IAA) > bromoacetic acid (BAA) ≫ chloroacetic acid (CAA); this rank order was observed with other toxicological end points. Toxicogenomic analysis was conducted with a nontransformed human intestinal epithelial cell line (FHs 74 Int). Exposure to the monoHAAs altered the transcription levels of multiple oxidative stress responsive genes, indicating that each exposure generated oxidative stress. The transcriptome profiles showed an increase in thioredoxin reductase 1 (TXNRD1) and sulfiredoxin (SRXN1), suggesting peroxiredoxin proteins had been oxidized during monoHAA exposures. Three possible sources of reactive oxygen species were identified, the hypohalous acid generating peroxidase enzymes lactoperoxidase (LPO) and myeloperoxidase (MPO), nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase 5 (NOX5), and PTGS2 (COX-2) mediated arachidonic acid metabolism. Each monoHAA exposure caused an increase in COX-2 mRNA levels. These data provide a functional association between monoHAA exposure and adverse health outcomes such as oxidative stress, inflammation, and cancer.

  15. Discoidin Domain Receptor 2 Mediates Collagen-Induced Activation of Membrane-Type 1 Matrix Metalloproteinase in Human Fibroblasts.

    PubMed

    Majkowska, Iwona; Shitomi, Yasuyuki; Ito, Noriko; Gray, Nathanael S; Itoh, Yoshifumi

    2017-03-07

    Membrane-Type 1 Matrix Metalloproteinase (MT1-MMP) is a membrane-bound MMP that is highly expressed in cells with invading capacity including fibroblasts and invasive cancer cell. A potential physiological stimulus for MT1-MMP expression is fibrillar collagen, and it has been shown that it upregulates both MT1-MMP gene and functions in various cell types. However, the mechanisms of collagen-mediated MT1-MMP activation is not clearly understood. In this study we identified discoidin domain receptor 2 (DDR2) as a crucial receptor that mediates this process in human fibroblasts. Knocking down DDR2, but not β1 integrin subunit, a common subunit for all collagen-binding integrins, inhibited collagen-induced activation of proMMP-2 and upregulation of MT1-MMP at the gene and protein level. Interestingly DDR2 knockdown or pharmacological inhibition of DDR2 also inhibited MT1-MMP-dependent cellular degradation of collagen film, suggesting that cell surface collagen degradation by MT1-MMP involves DDR2-mediated collagen signalling. This DDR2-mediated mechanism is only present in non-transformed mesenchymal cells, as collagen-induced MT1-MMP activation in HT1080 fibrosarcoma cells and MT1-MMP function in MDA-MB231 breast cancer cells were not affected by DDR kinase inhibition. DDR2 activation was found to be noticeably more effective when cells were stimulated by collagen without non-helical telopeptides region compared to intact collagen fibrils. Those data suggest that DDR2 is a microenvironmental sensor that regulates fibroblasts migration in collagen-rich environment.

  16. Expression of 11β-hydroxysteroid dehydrogenase enzymes in human osteosarcoma: potential role in pathogenesis and as targets for treatments.

    PubMed

    Patel, Pushpa; Hardy, Rowan; Sumathi, Vaiyapuri; Bartle, Gillian; Kindblom, Lars-Gunnar; Grimer, Robert; Bujalska, Iwona; Stewart, Paul M; Rabbitt, Elizabeth; Gittoes, Neil J L; Cooper, Mark S

    2012-08-01

    Osteosarcoma (OS) is a primary malignant tumour of bone occurring predominantly in children and young adults. Despite chemotherapy, relapse is common and mortality remains high. Non-transformed osteoblasts are highly sensitive to glucocorticoids, which reduce proliferation and induce apoptosis. Previously, we observed that OS cells, but not normal osteoblasts, express 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme inactivates cortisol (active) to cortisone (inactive) and expression of 11β-HSD2 renders OS cells resistant to glucocorticoids. By contrast, the related enzyme 11β-HSD1 converts cortisone to cortisol and reduces OS cell proliferation in vitro. Some synthetic glucocorticoids (e.g. dehydrodexamethasone (DHD), inactive counterpart of dexamethasone (DEX)) have been reported to be activated by 11β-HSD2. We therefore investigated expression and enzymatic activity of 11β-HSD isozymes in human OS tissue, determined whether 11β-HSD expression has prognostic value in the response to therapy, and evaluated the potential use of synthetic glucocorticoids to selectively target OS cells. OS samples expressed both 11β-HSD1 and 11β-HSD2. 11β-HSD1 expression in pretreatment biopsy specimens positively correlated with primary tumour size. Expression and activity of 11β-HSD1 in post-treatment biopsies were unrelated to the degree of tumour necrosis following chemotherapy. However, high 11β-HSD2 expression in post-treatment biopsies correlated with a poor response to therapy. OS cells that expressed 11β-HSD2 inactivated endogenous glucocorticoids; but these cells were also able to generate DEX from DHD. These results suggest that OS treatment response is related to 11β-HSD2 enzyme expression. Furthermore, OS cells expressing this enzyme could be targeted by treatment with synthetic glucocorticoids that are selectively reactivated by the enzyme.

  17. A tumor-promoting mechanism mediated by retrotransposon-encoded reverse transcriptase is active in human transformed cell lines

    PubMed Central

    Sciamanna, Ilaria; Gualtieri, Alberto; Cossetti, Cristina; Osimo, Emanuele Felice; Ferracin, Manuela; Macchia, Gianfranco; Aricò, Eleonora; Prosseda, Gianni; Vitullo, Patrizia; Misteli, Tom; Spadafora, Corrado

    2013-01-01

    LINE-1 elements make up the most abundant retrotransposon family in the human genome. Full-length LINE-1 elements encode a reverse transcriptase (RT) activity required for their own retrotranpsosition as well as that of non-autonomous Alu elements. LINE-1 are poorly expressed in normal cells and abundantly in cancer cells. Decreasing RT activity in cancer cells, by either LINE-1-specific RNA interference, or by RT inhibitory drugs, was previously found to reduce proliferation and promote differentiation and to antagonize tumor growth in animal models. Here we have investigated how RT exerts these global regulatory functions. We report that the RT inhibitor efavirenz (EFV) selectively downregulates proliferation of transformed cell lines, while exerting only mild effects on non-transformed cells; this differential sensitivity matches a differential RT abundance, which is high in the former and undetectable in the latter. Using CsCl density gradients, we selectively identify Alu and LINE-1 containing DNA:RNA hybrid molecules in cancer but not in normal cells. Remarkably, hybrid molecules fail to form in tumor cells treated with EFV under the same conditions that repress proliferation and induce the reprogramming of expression profiles of coding genes, microRNAs (miRNAs) and ultraconserved regions (UCRs). The RT-sensitive miRNAs and UCRs are significantly associated with Alu sequences. The results suggest that LINE-1-encoded RT governs the balance between single-stranded and double-stranded RNA production. In cancer cells the abundant RT reverse-transcribes retroelement-derived mRNAs forming RNA:DNA hybrids. We propose that this impairs the formation of double-stranded RNAs and the ensuing production of small regulatory RNAs, with a direct impact on gene expression. RT inhibition restores the ‘normal’ small RNA profile and the regulatory networks that depend on them. Thus, the retrotransposon-encoded RT drives a previously unrecognized mechanism crucial to the

  18. A tumor-promoting mechanism mediated by retrotransposon-encoded reverse transcriptase is active in human transformed cell lines.

    PubMed

    Sciamanna, Ilaria; Gualtieri, Alberto; Cossetti, Cristina; Osimo, Emanuele Felice; Ferracin, Manuela; Macchia, Gianfranco; Aricò, Eleonora; Prosseda, Gianni; Vitullo, Patrizia; Misteli, Tom; Spadafora, Corrado

    2013-12-01

    LINE-1 elements make up the most abundant retrotransposon family in the human genome. Full-length LINE-1 elements encode a reverse transcriptase (RT) activity required for their own retrotranpsosition as well as that of non-autonomous Alu elements. LINE-1 are poorly expressed in normal cells and abundantly in cancer cells. Decreasing RT activity in cancer cells, by either LINE-1-specific RNA interference, or by RT inhibitory drugs, was previously found to reduce proliferation and promote differentiation and to antagonize tumor growth in animal models. Here we have investigated how RT exerts these global regulatory functions. We report that the RT inhibitor efavirenz (EFV) selectively downregulates proliferation of transformed cell lines, while exerting only mild effects on non-transformed cells; this differential sensitivity matches a differential RT abundance, which is high in the former and undetectable in the latter. Using CsCl density gradients, we selectively identify Alu and LINE-1 containing DNA:RNA hybrid molecules in cancer but not in normal cells. Remarkably, hybrid molecules fail to form in tumor cells treated with EFV under the same conditions that repress proliferation and induce the reprogramming of expression profiles of coding genes, microRNAs (miRNAs) and ultraconserved regions (UCRs). The RT-sensitive miRNAs and UCRs are significantly associated with Alu sequences. The results suggest that LINE-1-encoded RT governs the balance between single-stranded and double-stranded RNA production. In cancer cells the abundant RT reverse-transcribes retroelement-derived mRNAs forming RNA:DNA hybrids. We propose that this impairs the formation of double-stranded RNAs and the ensuing production of small regulatory RNAs, with a direct impact on gene expression. RT inhibition restores the 'normal' small RNA profile and the regulatory networks that depend on them. Thus, the retrotransposon-encoded RT drives a previously unrecognized mechanism crucial to the

  19. The effect of neighboring cells on the stiffness of cancerous and non-cancerous human mammary epithelial cells

    NASA Astrophysics Data System (ADS)

    Guo, Xinyi; Bonin, Keith; Scarpinato, Karin; Guthold, Martin

    2014-10-01

    Using an Atomic Force Microscope (AFM) with a 5.3 μm diameter spherical probe, we determined mechanical properties of individual human mammary epithelial cells. The cells were derived from a pair of cell lines that mimic cell progression through four phases of neoplastic transformation: normal (non-transformed), immortal, tumorigenic, and metastatic. Measurements on cells in all four phases were taken over both the cytoplasmic and nuclear regions. Moreover, the measurements were made for cells in different microenvironments as related to cell-cell contacts: isolated cells; cells residing on the periphery of a contiguous cell monolayer; and cells on the inside of a contiguous cell monolayer. By fitting the AFM force versus indentation curves to a Hertz model, we determined the pseudo-elastic Young’s modulus, E. Combining all data for the cellular subregions (over nucleus and cytoplasm) and the different cell microenvironments, we obtained stiffness values for normal, immortal, tumorigenic, and metastatic cells of 870 Pa, 870 Pa, 490 Pa, and 580 Pa, respectively. That is, cells become softer as they advance to the tumorigenic phase and then stiffen somewhat in the final step to metastatic cells. We also found a distinct contrast in the influence of a cell’s microenvironment on cell stiffness. Normal mammary epithelial cells inside a monolayer are stiffer than peripheral cells, which are stiffer than isolated cells. However, the microenvironment had a slight, opposite effect on tumorigenic and little effect on immortal and metastatic cell stiffness. Thus, the stiffness of cancer cells is less sensitive to the microenvironment than normal cells. Our results show that the mechanical properties of a cell can depend on cancer progression and microenvironment (cell-cell interactions).

  20. Human Augmentics: augmenting human evolution.

    PubMed

    Kenyon, Robert V; Leigh, Jason

    2011-01-01

    Human Augmentics (HA) refers to technologies for expanding the capabilities, and characteristics of humans. One can think of Human Augmentics as the driving force in the non-biological evolution of humans. HA devices will provide technology to compensate for human biological limitations either natural or acquired. The strengths of HA lie in its applicability to all humans. Its interoperability enables the formation of ecosystems whereby augmented humans can draw from other realms such as "the Cloud" and other augmented humans for strength. The exponential growth in new technologies portends such a system but must be designed for interaction through the use of open-standards and open-APIs for system development. We discuss the conditions needed for HA to flourish with an emphasis on devices that provide non-biological rehabilitation.

  1. Human Rights/Human Needs.

    ERIC Educational Resources Information Center

    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)

  2. Up-regulation of early growth response gene 1 (EGR-1) via ERK1/2 signals attenuates sulindac sulfide-mediated cytotoxicity in the human intestinal epithelial cells

    SciTech Connect

    Moon, Yuseok Yang, Hyun; Kim, Yung Bu

    2007-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are used to relieve pain and inflammation and have also received considerable attention because of their preventive effects against human cancer. However, the drug application is sometimes limited by the severe gastrointestinal ulcers and mucosal complications. In the present study, NSAID sulindac sulfide was investigated for the cytotoxic injury in the intestinal epithelial cells in association with an immediate inducible factor, early growth response gene 1 (EGR-1). Previously we reported that sulindac sulfide can suppress tumor cell invasion by inducing EGR-1. Extending the previous study, EGR-1 induction by sulindac sulfide was observed both in the non-transformed and transformed human intestinal epithelial cell lines. In terms of signaling pathway, ERK1/2 MAP kinases and its substrate Elk-1 transcription factor were involved in the sulindac sulfide-induced EGR-1 gene expression. Moreover, sulindac sulfide stimulated the nuclear translocation of the transcription factor EGR-1, which was also mediated by ERK1/2 signaling pathway. The roles of EGR-1 signals in the apoptotic cell death were assessed in the intestinal epithelial cells. Suppression of EGR-1 expression retarded cellular growth and colony forming activity in the intestinal epithelial cells. Moreover, induced EGR-1 ameliorated sulindac sulfide-mediated apoptotic cell death and enhanced the cellular survival. Taken all together, sulindac sulfide activated ERK1/2 MAP kinases which then mediated EGR-1 induction and nuclear translocation, all of which played important roles in the cellular survival from NSAID-mediated cytotoxicity in the human intestinal epithelial cells, implicating the protective roles of EGR-1 in the NSAID-mediated mucosal injuries.

  3. Teaching humanism.

    PubMed

    Stern, David T; Cohen, Jordan J; Bruder, Ann; Packer, Barbara; Sole, Allison

    2008-01-01

    As the "passion that animates authentic professionalism," humanism must be infused into medical education and clinical care as a central feature of medicine's professionalism movement. In this article, we discuss a current definition of humanism in medicine. We will also provide detailed descriptions of educational programs intended to promote humanism at a number of medical schools in the United States (and beyond) and identify the key factors that make these programs effective. Common elements of programs that effectively teach humanism include: (1) opportunities for students to gain perspective in the lives of patients; (2) structured time for reflection on those experiences; and (3) focused mentoring to ensure that these events convert to positive, formative learning experiences. By describing educational experiences that both promote and sustain humanism in doctors, we hope to stimulate the thinking of other medical educators and to disseminate the impact of these innovative educational programs to help the profession meet its obligation to provide the public with humanistic physicians.

  4. Human cloning and human dignity.

    PubMed

    Birnbacher, Dieter

    2005-03-01

    Judging from the official documents dealing with the moral and legal aspects of human reproductive cloning there seems to be a nearly worldwide consensus that reproductive cloning is incompatible with human dignity. The certainty of this judgement is, however, not matched by corresponding arguments. Is the incompatibility of reproductive with human dignity an ultimate moral intuition closed to further argument? The paper considers several ways by which the intuition might be connected with more familiar applications of the concept of human dignity, and argues that there is no such connection. It concludes that the central objections to human reproductive cloning are not objections relating to dignity but objections relating to risk, especially the risks imposed on children born in the course of testing the method's safety.

  5. Human rights

    PubMed Central

    Powell, J Enoch

    1977-01-01

    What are human rights? In this article Enoch Powell, MP (a former Conservative Minister of Health), approaches this question through a critical discussion of Article 25 (I) of the United Nations Universal Declaration of Human Rights. Professor R S Downie in his accompanying commentary analyses Mr Powell's statements and takes up in particular Mr Powell's argument that claiming rights for one person entails compulsion on another person. In Professor Downie's view there is nothing in Article 25 (I) that cannot embody acceptable moral rights, the commonly accepted interpretation of that Article of the UN Universal Declaration of Human Rights which many people think is wholly acceptable. PMID:604483

  6. Human Cytochrome P450 2W1 Is Not Expressed in Adrenal Cortex and Is Only Rarely Expressed in Adrenocortical Carcinomas

    PubMed Central

    Nolé, Paola; Duijndam, Britt; Stenman, Adam; Juhlin, C. Christofer; Kozyra, Mikael; Larsson, Catharina; Ingelman-Sundberg, Magnus

    2016-01-01

    Human cytochome P450 2W1 (CYP2W1) enzyme is expressed in fetal colon and in colon tumors. The level of expression is higher in colon metastases than in the parent tumors and the enzyme is a possible drug target for treatment of colorectal cancer, as demonstrated in mouse xenograft studies. A previous study published in this journal reported that CYP2W1 is highly expressed in normal and transformed adrenal tissue. However, adrenal expression of CYP2W1 protein was not seen in previous studies in our research group. To clarify this inconsistency, we have used qRT-PCR and Western blotting with CYP2W1-specific antibodies to probe a panel of 27 adrenocortical carcinomas and 35 normal adrenal cortex samples. CYP2W1 mRNA expression is seen in all samples. However, significant CYP2W1 protein expression was found in only one tumor sample (a testosterone-producing adrenocortical carcinoma) and not in any normal tissue. Differences in the specificity of the CYP2W1 antibodies used in the two studies may explain the apparent discrepancy. We conclude that normal adrenal tissue lacks P450 2W1 enzyme expression; also, adrenocortical carcinomas generally do not express the enzyme. This information thus underline the colon cancer specificity of CYP2W1 enzyme expression and has implications for the development of anti-colon cancer therapies based on CYP2W1 as a drug target, since 2W1-dependent bioactivation of prodrugs for CYP2W1 will not take place in normal adrenal tissue or other non-transformed tissues. PMID:27598485

  7. Human Infrastructure & Human Activity Detection

    DTIC Science & Technology

    2007-07-01

    researchers are developing sensors systems that detect footfalls (or gait ) [1, 2], speech, the spectral response of human skin, etc [3]. Little work has...cone shaped field of view. • Visible imagers can capture color or grayscale video for human gait detection and object recognition. • Infrared...his/her gait produces a unique signature [13]. Indirect means of detecting personnel include the usage of acoustic, seismic, magnetic, passive

  8. Human monkeypox.

    PubMed

    McCollum, Andrea M; Damon, Inger K

    2014-01-01

    Human monkeypox is a zoonotic Orthopoxvirus with a presentation similar to smallpox. Clinical differentiation of the disease from smallpox and varicella is difficult. Laboratory diagnostics are principal components to identification and surveillance of disease, and new tests are needed for a more precise and rapid diagnosis. The majority of human infections occur in Central Africa, where surveillance in rural areas with poor infrastructure is difficult but can be accomplished with evidence-guided tools and educational materials to inform public health workers of important principles. Contemporary epidemiological studies are needed now that populations do not receive routine smallpox vaccination. New therapeutics and vaccines offer hope for the treatment and prevention of monkeypox; however, more research must be done before they are ready to be deployed in an endemic setting. There is a need for more research in the epidemiology, ecology, and biology of the virus in endemic areas to better understand and prevent human infections.

  9. Human Interface to Netcentricity

    DTIC Science & Technology

    2006-06-01

    to human communication involves communications initiated by applications or devices for human consumption. Examples include intelligent agents...AKO) are all examples of human to machine communication. • Human to Human: Human to human communication in a net-centric environment can be...the discussion will center on providing options for improving human to human communication . It is our position that an emphasis on human to human

  10. Human Trafficking

    ERIC Educational Resources Information Center

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  11. Classical Humanities

    ERIC Educational Resources Information Center

    Goodwin, Donn; And Others

    1975-01-01

    This article reports on a pilot course in humanities team-taught by three teachers, two from a senior high-school and one from a junior high-school, in Brookfield, Wisconsin. The specific subject matter is Greek and Roman culture. The curriculum is outlined and the basic reading list is included. (CLK)

  12. Humanizing Calculus

    ERIC Educational Resources Information Center

    Cirillo, Michelle

    2007-01-01

    In this article, the author explores the history and the mathematics used by Newton and Leibniz in their invention of calculus. The exploration of this topic is intended to show students that mathematics is a human invention. Suggestions are made to help teachers incorporate the mathematics and the history into their own lessons. (Contains 3…

  13. Nothing Human

    ERIC Educational Resources Information Center

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  14. Human Rights in the Humanities

    ERIC Educational Resources Information Center

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  15. Human Locomotion

    PubMed Central

    Inman, Verne T.

    1966-01-01

    The development of bipedal plantigrade progression is a purely human, and apparently learned, accomplishment. Experimental findings confirm the hypothesis that the human body will integrate the motion of various segments of the body and control the activity of muscles to minimize energy expenditure. Movements which are integrated for this purpose include vertical displacement of the body, horizontal rotation of the pelvis, mediolateral pelvic tilt, flexion of the knee, plantar flexion of the ankle and foot, lateral displacement of the torso and rotation of the shoulder girdle. Raising and lowering the body results in gains and losses of potential energy, and acceleration and deceleration result in gains and losses of kinetic energy. The motions are so co-ordinated that a transfer of energy back and forth from kinetic to potential occurs during walking, which tends to minimize total energy expenditure as well as muscle work. ImagesFig. 1 PMID:5942660

  16. Humane reproduction.

    PubMed

    1974-03-01

    Discusses social, economic, and humane considerations in population control. Mental health aspects of controlled fertility are considered in relation to the family's psychosocial and material resources, the effects of reproduction on the individual the family, and community, and the advantages and disadvantages of controlled reproduction. A distinction between family planning and population control is outlined. It is suggested that there is hardly a single more effective tool for preventing psychological disorders than the prevention of unwanted pregnancies. Analyses of educational and medical services and methods of birth control are presented. A comprehensive neighborhood health station, which would consolidate these services, is suggested. It is concluded that humane programs of reproduction would lead to a reconciliation of biological drives with a responsible concern for the quality of life.

  17. Human genetics

    SciTech Connect

    Carlson, E.A.

    1984-01-01

    This text provides full and balanced coverage of the concepts requisite for a thorough understanding of human genetics. Applications to both the individual and society are integrated throughout the lively and personal narrative, and the essential principles of heredity are clearly presented to prepare students for informed participation in public controversies. High-interest, controversial topics, including recombinant DNA technology, oncogenes, embryo transfer, environmental mutagens and carcinogens, IQ testing, and eugenics encourage understanding of important social issues.

  18. Human Metapneumovirus.

    PubMed

    Schuster, Jennifer E; Williams, John V

    2014-10-01

    Human metapneumovirus (HMPV), a paramyxovirus identified in 2001, is a leading cause of respiratory tract infections in both children and adults. Seroprevalence studies demonstrate that the primary infection occurs before the age of 5 years, and humans are reinfected throughout life. The four subgroups of HMPV occur with year-to-year variability, and infection with one subgroup confers some serologic cross-protection. Experimental vaccines elicit a humoral response in both animal and human models and have been used to identify antigenic determinants. The main target of protective antibodies is the fusion (F) protein, although many of the remaining eight proteins are immunogenic. Monoclonal antibodies (mAbs) targeting the F protein are both protective and therapeutic in animal models. Most recently, the identification of broadly neutralizing antibodies against HMPV and respiratory syncytial virus demonstrates that common epitopes are present between the two viruses. Broadly neutralizing mAbs have significant clinical implications for prophylaxis and treatment of high-risk hosts as well as vaccine development.

  19. Human evolution.

    PubMed

    Wood, B

    1996-12-01

    The common ancestor of modern humans and the great apes is estimated to have lived between 5 and 8 Myrs ago, but the earliest evidence in the human, or hominid, fossil record is Ardipithecus ramidus, from a 4.5 Myr Ethiopian site. This genus was succeeded by Australopithecus, within which four species are presently recognised. All combine a relatively primitive postcranial skeleton, a dentition with expanded chewing teeth and a small brain. The most primitive species in our own genus, Homo habilis and Homo rudolfensis, are little advanced over the australopithecines and with hindsight their inclusion in Homo may not be appropriate. The first species to share a substantial number of features with later Homo is Homo ergaster, or 'early African Homo erectus', which appears in the fossil record around 2.0 Myr. Outside Africa, fossil hominids appear as Homo erectus-like hominids, in mainland Asia and in Indonesia close to 2 Myr ago; the earliest good evidence of 'archaic Homo' in Europe is dated at between 600-700 Kyr before the present. Anatomically modern human, or Homo sapiens, fossils are seen first in the fossil record in Africa around 150 Kyr ago. Taken together with molecular evidence on the extent of DNA variation, this suggests that the transition from 'archaic' to 'modern' Homo may have taken place in Africa.

  20. Human suffering.

    PubMed

    1992-12-01

    10 measures of quality of life are used to rank 141 countries in the International Human Suffering Index (HSI). The Index differentiates between extreme, high, moderate, and minimal levels of human suffering. Social welfare is the sum of 10 measures: life expectancy, daily caloric intake, clean drinking water, infant immunization, secondary school enrollment, gross national product per capita, the rate of inflation, communication technology (i.e., telephones), political freedom, and civil rights. Each measure is ranked between 0 and 10. The highest score indicates the greatest country stress, with the worst possible score being 100. About 1 billion people live in desperate poverty. Living conditions are the worst in Mozambique (93), followed by Somalia, Afghanistan, Haiti, and Sudan. Most of these countries also have high population growth. The most comfortable countries are Denmark (1), the Netherlands, Belgium, Switzerland, and Canada, which have low population growth. Total scores of 75 or greater (extreme human suffering) occur in 27 countries (20 in Africa, 16 in Asia, and Haiti) with 8% of the world's population (432 million people). High human suffering scores range between 50 and 74 and include 56 countries (24 in Africa, 16 in Asia, 15 in the Western Hemisphere, and 1 in Oceania) with 3.5 billion people. The number of countries in this grouping increased from 44 countries with 58% of world population in 1987. Moderate suffering scores range from 25-49. Countries with moderate suffering number 34 countries (9 in Europe, 13 in Asia, 8 in the Western Hemisphere, and 2 in Oceania and 2 in Africa) with 11.8% of world population (636 million). Over the preceding 5-year period the number of countries increased from 29 countries with 10% of world population. Minimal human suffering occurs in 24 countries (17 in Europe, Israel and Japan in Asia; Canada, the US, and Barbados in the Western Hemisphere; and Australia and New Zealand in Oceania) with 14.8% of world

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

    ERIC Educational Resources Information Center

    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. Human Heredity: Genetic Mechanisms in Humans.

    ERIC Educational Resources Information Center

    Blank, C. E.

    1988-01-01

    Discussed are some of the uncertainties in human genetic mechanisms that are often presented as dogma in Biology textbooks. Presented is a brief historical background and illustrations involving chromosome abnormality in humans and linkage studies in humans. (CW)

  3. Human Astroviruses

    PubMed Central

    Pintó, Rosa M.; Guix, Susana

    2014-01-01

    SUMMARY Human astroviruses (HAtVs) are positive-sense single-stranded RNA viruses that were discovered in 1975. Astroviruses infecting other species, particularly mammalian and avian, were identified and classified into the genera Mamastrovirus and Avastrovirus. Through next-generation sequencing, many new astroviruses infecting different species, including humans, have been described, and the Astroviridae family shows a high diversity and zoonotic potential. Three divergent groups of HAstVs are recognized: the classic (MAstV 1), HAstV-MLB (MAstV 6), and HAstV-VA/HMO (MAstV 8 and MAstV 9) groups. Classic HAstVs contain 8 serotypes and account for 2 to 9% of all acute nonbacterial gastroenteritis in children worldwide. Infections are usually self-limiting but can also spread systemically and cause severe infections in immunocompromised patients. The other groups have also been identified in children with gastroenteritis, but extraintestinal pathologies have been suggested for them as well. Classic HAstVs may be grown in cells, allowing the study of their cell cycle, which is similar to that of caliciviruses. The continuous emergence of new astroviruses with a potential zoonotic transmission highlights the need to gain insights on their biology in order to prevent future health threats. This review focuses on the basic virology, pathogenesis, host response, epidemiology, diagnostic assays, and prevention strategies for HAstVs. PMID:25278582

  4. Human schistosomiasis

    PubMed Central

    Colley, Daniel G; Bustinduy, Amaya L; Secor, W Evan; King, Charles H

    2015-01-01

    Human schistosomiasis—or bilharzia—is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination. PMID:24698483

  5. Human schistosomiasis.

    PubMed

    Colley, Daniel G; Bustinduy, Amaya L; Secor, W Evan; King, Charles H

    2014-06-28

    Human schistosomiasis--or bilharzia--is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination.

  6. The Digital Humanities as a Humanities Project

    ERIC Educational Resources Information Center

    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,…

  7. NATO Human View Architecture and Human Networks

    NASA Technical Reports Server (NTRS)

    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.

  8. Building artificial humans to understand humans.

    PubMed

    Ishiguro, Hiroshi; Nishio, Shuichi

    2007-01-01

    If we could build an android as a very humanlike robot, how would we humans distinguish a real human from an android? The answer to this question is not so easy. In human-android interaction, we cannot see the internal mechanism of the android, and thus we may simply believe that it is a human. This means that a human can be defined from two perspectives: one by organic mechanism and the other by appearance. Further, the current rapid progress in artificial organs makes this distinction confusing. The approach discussed in this article is to create artificial humans with humanlike appearances. The developed artificial humans, an android and a geminoid, can be used to improve understanding of humans through psychological and cognitive tests conducted using the artificial humans. We call this new approach to understanding humans android science.

  9. Human Rhinoviruses

    PubMed Central

    Lamson, Daryl M.; St. George, Kirsten; Walsh, Thomas J.

    2013-01-01

    Human rhinoviruses (HRVs), first discovered in the 1950s, are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical visits and missed days of work. Advances in molecular methods have enhanced our understanding of the genomic structure of HRV and have led to the characterization of three genetically distinct HRV groups, designated groups A, B, and C, within the genus Enterovirus and the family Picornaviridae. HRVs are traditionally associated with upper respiratory tract infection, otitis media, and sinusitis. In recent years, the increasing implementation of PCR assays for respiratory virus detection in clinical laboratories has facilitated the recognition of HRV as a lower respiratory tract pathogen, particularly in patients with asthma, infants, elderly patients, and immunocompromised hosts. Cultured isolates of HRV remain important for studies of viral characteristics and disease pathogenesis. Indeed, whether the clinical manifestations of HRV are related directly to viral pathogenicity or secondary to the host immune response is the subject of ongoing research. There are currently no approved antiviral therapies for HRVs, and treatment remains primarily supportive. This review provides a comprehensive, up-to-date assessment of the basic virology, pathogenesis, clinical epidemiology, and laboratory features of and treatment and prevention strategies for HRVs. PMID:23297263

  10. Human Factors in Human-Systems Integration

    NASA Technical Reports Server (NTRS)

    Fitts, David J.; Sandor, Aniko; Litaker, Harry L., Jr.; Tillman, Barry

    2008-01-01

    Any large organization whose mission is to design and develop systems for humans, and train humans needs a well-developed integration and process plan to deal with the challenges that arise from managing multiple subsystems. Human capabilities, skills, and needs must be considered early in the design and development process, and must be continuously considered throughout the development lifecycle. This integration of human needs within system design is typically formalized through a Human-Systems Integration (HSI) program. By having an HSI program, an institution or organization can reduce lifecycle costs and increase the efficiency, usability, and quality of its products because human needs have been considered from the beginning.

  11. Humane Education: An Overview.

    ERIC Educational Resources Information Center

    Whitlock, Eileen S.; Westerlund, Stuart R.

    This booklet traces the historical development of human education as it has been instilled into the young people of America from colonial times to the present and provides a future prognosis of humaneness in the schools. Humane education promotes humane behavior and is an important part of the humane movement in the United States, although until…

  12. Human Research Risk Management

    NASA Video Gallery

    Crew health and performance is critical to successful human exploration beyond low Earth orbit. The Human Research Program (HRP) investigates and mitigates the highest risks to human health and per...

  13. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. . Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  14. Human-machine interactions

    DOEpatents

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.

    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.

  15. What Are the Humanities?

    ERIC Educational Resources Information Center

    Broderick, Francis

    A working definition of the humanities and characteristics of a liberally educated person are specified. The humanities embrace areas of human knowledge that possess these elements: central concern for human beings rather than for the processes of nature or the structures of society; primary focus on the individual rather than on the group;…

  16. Cooperation in human teaching.

    PubMed

    Kruger, Ann Cale

    2015-01-01

    Kline's evolutionary analysis of teaching provides welcome reframing for cross-species comparisons. However, theory based on competition cannot explain the transmission of human cultural elements that were collectively created. Humans evolved in a cultural niche and teaching-learning coevolved to transmit culture. To study human cultural variation in teaching, we need a more articulated theory of this distinctively human engagement.

  17. Visualizing Humans by Computer.

    ERIC Educational Resources Information Center

    Magnenat-Thalmann, Nadia

    1992-01-01

    Presents an overview of the problems and techniques involved in visualizing humans in a three-dimensional scene. Topics discussed include human shape modeling, including shape creation and deformation; human motion control, including facial animation and interaction with synthetic actors; and human rendering and clothing, including textures and…

  18. Special Section: Human Rights

    ERIC Educational Resources Information Center

    Frydenlund, Knut; And Others

    1978-01-01

    Eleven articles examine human rights in Europe. Topics include unemployment, human rights legislation, role of the Council of Europe in promoting human rights, labor unions, migrant workers, human dignity in industralized societies, and international violence. Journal available from Council of Europe, Directorate of Press and Information, 67006…

  19. Human Research Program Opportunities

    NASA Technical Reports Server (NTRS)

    Kundrot, Craig E.

    2014-01-01

    The goal of HRP is to provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. The Human Research Program was designed to meet the needs of human space exploration, and understand and reduce the risk to crew health and performance in exploration missions.

  20. ISS Payload Human Factors

    NASA Technical Reports Server (NTRS)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  1. Preference for human eyes in human infants.

    PubMed

    Dupierrix, Eve; de Boisferon, Anne Hillairet; Méary, David; Lee, Kang; Quinn, Paul C; Di Giorgio, Elisa; Simion, Francesca; Tomonaga, Masaki; Pascalis, Olivier

    2014-07-01

    Despite evidence supporting an early attraction to human faces, the nature of the face representation in neonates and its development during the first year after birth remain poorly understood. One suggestion is that an early preference for human faces reflects an attraction toward human eyes because human eyes are distinctive compared with other animals. In accord with this proposal, prior empirical studies have demonstrated the importance of the eye region in face processing in adults and infants. However, an attraction for the human eye has never been shown directly in infants. The current study aimed to investigate whether an attraction for human eyes would be present in newborns and older infants. With the use of a preferential looking time paradigm, newborns and 3-, 6-, 9-, and 12-month-olds were simultaneously presented with a pair of nonhuman primate faces (chimpanzees and Barbary macaques) that differed only by the eyes, thereby pairing a face with original nonhuman primate eyes with the same face in which the eyes were replaced by human eyes. Our results revealed that no preference was observed in newborns, but a preference for nonhuman primate faces with human eyes emerged from 3months of age and remained stable thereafter. The findings are discussed in terms of how a preference for human eyes may emerge during the first few months after birth.

  2. Economics of human trafficking.

    PubMed

    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. Mice with human livers.

    PubMed

    Grompe, Markus; Strom, Stephen

    2013-12-01

    Animal models are used to study many aspects of human disease and to test therapeutic interventions. However, some very important features of human biology cannot be replicated in animals, even in nonhuman primates or transgenic rodents engineered with human genes. Most human microbial pathogens do not infect animals and the metabolism of many xenobiotics is different between human beings and animals. The advent of transgenic immune-deficient mice has made it possible to generate chimeric animals harboring human tissues and cells, including hepatocytes. The liver plays a central role in many human-specific biological processes and mice with humanized livers can be used to model human metabolism, liver injury, gene regulation, drug toxicity, and hepatotropic infections.

  4. Human dignity, bioethics, and human rights.

    PubMed

    Häyry, Matti; Takala, Tuija

    2005-09-01

    The authors analyse and assess the Universal Draft Declaration on Bioethics and Human Rights published by UNESCO. They argue that the Draft has two main weaknesses. It unnecessarily confines the scope of bioethics to life sciences and their practical applications. And it fails to spell out the intended role of human dignity in international ethical regulation.

  5. Human Papillomavirus (HPV) Vaccines

    MedlinePlus

    ... Directory Cancer Prevention Overview Research Human Papillomavirus (HPV) Vaccines On This Page What are human papillomaviruses? Which ... infections? Can HPV infections be prevented? What HPV vaccines are available? Who should get the HPV vaccines? ...

  6. Telling the Human Story.

    ERIC Educational Resources Information Center

    Richardson, Miles

    1987-01-01

    Proposes that one of the fundamental human attributes is telling stories. Explores the debate on whether Neanderthals possessed language ability. Discusses the role of the "human story" in teaching anthropology. (DH)

  7. Mining human antibody repertoires

    PubMed Central

    2010-01-01

    Human monoclonal antibodies (mAbs) have become drugs of choice for the management of an increasing number of human diseases. Human antibody repertoires provide a rich source for human mAbs. Here we review the characteristics of natural and non-natural human antibody repertoires and their mining with non-combinatorial and combinatorial strategies. In particular, we discuss the selection of human mAbs from naïve, immune, transgenic and synthetic human antibody repertoires using methods based on hybridoma technology, clonal expansion of peripheral B cells, single-cell PCR, phage display, yeast display and mammalian cell display. Our reliance on different strategies is shifting as we gain experience and refine methods to the efficient generation of human mAbs with superior pharmacokinetic and pharmacodynamic properties. PMID:20505349

  8. The Growing Human Population.

    ERIC Educational Resources Information Center

    Keyfitz, Nathan

    1989-01-01

    Discusses the issue of human population. Illustrates the projections of the growing human population in terms of developed and less developed countries. Describes the family planning programs in several countries. Lists three references for further reading. (YP)

  9. Human genomic variation

    PubMed Central

    Disotell, Todd R

    2000-01-01

    The recent completion and assembly of the first draft of the human genome, which combines samples from several ethnically diverse males and females, provides preliminary data on the extent of human genetic variation. PMID:11178257

  10. Indicators: Human Disturbance

    EPA Pesticide Factsheets

    Human disturbance is a measure of the vulnerability of aquatic resources to a variety of harmful human activities such as tree removal, road building, construction near shorelines/streambanks, and artificial hardening of lakeshores with retaining walls.

  11. Human assisted robotic exploration

    NASA Astrophysics Data System (ADS)

    Files, B. T.; Canady, J.; Warnell, G.; Stump, E.; Nothwang, W. D.; Marathe, A. R.

    2016-05-01

    In support of achieving better performance on autonomous mapping and exploration tasks by incorporating human input, we seek here to first characterize humans' ability to recognize locations from limited visual information. Such a characterization is critical to the design of a human-in-the-loop system faced with deciding whether and when human input is useful. In this work, we develop a novel and practical place-recognition task that presents humans with video clips captured by a navigating ground robot. Using this task, we find experimentally that human performance does not seem to depend on factors such as clip length or familiarity with the scene and also that there is significant variability across subjects. Moreover, we find that humans significantly outperform a state-of-the-art computational solution to this problem, suggesting the utility of incorporating human input in autonomous mapping and exploration techniques.

  12. Human Papillomavirus (HPV) Vaccine

    MedlinePlus

    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  13. Human Melioidosis, Malawi, 2011

    PubMed Central

    Katangwe, Thembi; Purcell, Janet; Bar-Zeev, Naor; Denis, Brigitte; Montgomery, Jacqui; Alaerts, Maaike; Heyderman, Robert Simon; Dance, David A.B.; Kennedy, Neil; Feasey, Nicholas

    2013-01-01

    A case of human melioidosis caused by a novel sequence type of Burkholderia pseudomallei occurred in a child in Malawi, southern Africa. A literature review showed that human cases reported from the continent have been increasing. PMID:23735189

  14. Human bites (image)

    MedlinePlus

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  15. Pathfinder: Humans in space

    NASA Technical Reports Server (NTRS)

    Anderson, John L.

    1988-01-01

    Viewgraphs are presented on the Pathfinder program. Information is given on human exploration of the solar system, technical requirements interfaces, program objectives, space suits, human performance, man-machine systems, space habitats, life support systems, and artificial gravity

  16. Human productivity program definition

    NASA Technical Reports Server (NTRS)

    Cramer, D. B.

    1985-01-01

    The optimization of human productivity on the space station within the existing resources and operational constraints is the aim of the Human Productivity Program. The conceptual objectives of the program are as follows: (1) to identify long lead technology; (2) to identify responsibility for work elements; (3) to coordinate the development of crew facilities and activities; and (4) to lay the foundation for a cost effective approach to improving human productivity. Human productivity work elements are also described and examples are presented.

  17. Human Rights Resource Catalogue.

    ERIC Educational Resources Information Center

    Zambrano, Elias, Comp.

    This document provides information about 25 programs/brochures which focus on human rights topics. Specific topics include: (1) counselor preparation; (2) multicultural awareness; (3) abuse and neglect; (4) Acquired Immune Deficiency Syndrome; (5) self-awareness; (6) human rights awareness and human rights of students; (7) cultural diversity; (8)…

  18. The Virtual Physiological Human

    PubMed Central

    Coveney, Peter V.; Diaz, Vanessa; Hunter, Peter; Kohl, Peter; Viceconti, Marco

    2011-01-01

    The Virtual Physiological Human is synonymous with a programme in computational biomedicine that aims to develop a framework of methods and technologies to investigate the human body as a whole. It is predicated on the transformational character of information technology, brought to bear on that most crucial of human concerns, our own health and well-being.

  19. Robotics of human movements.

    PubMed

    van der Smagt, Patrick; Grebenstein, Markus; Urbanek, Holger; Fligge, Nadine; Strohmayr, Michael; Stillfried, Georg; Parrish, Jonathon; Gustus, Agneta

    2009-01-01

    The construction of robotic systems that can move the way humans do, with respect to agility, stability and precision, is a necessary prerequisite for the successful integration of robotic systems in human environments. We explain human-centered views on robotics, based on the three basic ingredients (1) actuation; (2) sensing; and (3) control, and formulate detailed examples thereof.

  20. Whose Human Rights?

    ERIC Educational Resources Information Center

    Rendel, Margherita

    During the last 50 years, principles, institutions, and policies of human rights have been developed worldwide. This book brings together European and international conventions on human rights, the rights of women, and the users and uses of education, and places them in their wider context. It examines issues in how human rights work, the ways in…

  1. [Eugenics and human cloning].

    PubMed

    Boloz, W

    2001-01-01

    Because of legislative bans there are still no reports of human cloning. However eager public debate is currently running, concerning medical, legal, social and ethical aspects of human cloning. Arguments for and against human cloning are presented. An important argument against cloning is the danger of eugenic tendencies connected with cloning, which could lead to genetic discrimination.

  2. Humanities in the Community.

    ERIC Educational Resources Information Center

    Vendler, Helen

    1982-01-01

    In order that the humanities survive in America and that they find a place in the American community, learning should begin with arts. It is by the natural reciprocity between the arts and the humanities that the humanities can be made most accessible in the community. (MLW)

  3. Production Of Human Antibodies

    NASA Technical Reports Server (NTRS)

    Sammons, David W.; Neil, Garry A.

    1993-01-01

    Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

  4. A Human Rights Glossary.

    ERIC Educational Resources Information Center

    Flowers, Nancy

    1998-01-01

    Presents a human rights glossary that includes definitions of basic terms, treaties, charters, and groups/organizations that have been featured in previous articles in this edition of "Update on Law-Related Education"; the human rights terms have been compiled as part of the celebration of the Universal Declaration of Human Rights…

  5. Humanism in emergency medicine.

    PubMed

    Rosenzweig, S

    1993-09-01

    Emergency medicine has not yet appropriated "humanism" as a term of its own. Medical humanism needs to be interpreted in a way that is consistent with the practical goals of emergency medicine. In this essay, humanism in emergency medicine is defined by identifying the dehumanizing aspects of sudden illness and exploring of ways for sustaining the humanity of emergency department patients. Excerpts from Dr Oliver Sacks' autobiographical work A Leg to Stand On give voice to the human needs created by sudden illness and its treatment.

  6. Human Mitochondrial Protein Database

    National Institute of Standards and Technology Data Gateway

    SRD 131 Human Mitochondrial Protein Database (Web, free access)   The Human Mitochondrial Protein Database (HMPDb) provides comprehensive data on mitochondrial and human nuclear encoded proteins involved in mitochondrial biogenesis and function. This database consolidates information from SwissProt, LocusLink, Protein Data Bank (PDB), GenBank, Genome Database (GDB), Online Mendelian Inheritance in Man (OMIM), Human Mitochondrial Genome Database (mtDB), MITOMAP, Neuromuscular Disease Center and Human 2-D PAGE Databases. This database is intended as a tool not only to aid in studying the mitochondrion but in studying the associated diseases.

  7. Biological Races in Humans

    PubMed Central

    Templeton, Alan R.

    2013-01-01

    Races may exist in humans in a cultural sense, but biological concepts of race are needed to access their reality in a non-species-specific manner and to see if cultural categories correspond to biological categories within humans. Modern biological concepts of race can be implemented objectively with molecular genetic data through hypothesis-testing. Genetic data sets are used to see if biological races exist in humans and in our closest evolutionary relative, the chimpanzee. Using the two most commonly used biological concepts of race, chimpanzees are indeed subdivided into races but humans are not. Adaptive traits, such as skin color, have frequently been used to define races in humans, but such adaptive traits reflect the underlying environmental factor to which they are adaptive and not overall genetic differentiation, and different adaptive traits define discordant groups. There are no objective criteria for choosing one adaptive trait over another to define race. As a consequence, adaptive traits do not define races in humans. Much of the recent scientific literature on human evolution portrays human populations as separate branches on an evolutionary tree. A tree-like structure among humans has been falsified whenever tested, so this practice is scientifically indefensible. It is also socially irresponsible as these pictorial representations of human evolution have more impact on the general public than nuanced phrases in the text of a scientific paper. Humans have much genetic diversity, but the vast majority of this diversity reflects individual uniqueness and not race. PMID:23684745

  8. Human Milk Banking.

    PubMed

    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.

  9. Human rights and bioethics.

    PubMed

    Barilan, Y M; Brusa, M

    2008-05-01

    In the first part of this article we survey the concept of human rights from a philosophical perspective and especially in relation to the "right to healthcare". It is argued that regardless of meta-ethical debates on the nature of rights, the ethos and language of moral deliberation associated with human rights is indispensable to any ethics that places the victim and the sufferer in its centre. In the second part we discuss the rise of the "right to privacy", particularly in the USA, as an attempt to make the element of personal free will dominate over the element of basic human interest within the structure of rights and when different rights seem to conflict. We conclude by discussing the relationship of human rights with moral values beyond the realm of rights, mainly human dignity, free will, human rationality and response to basic human needs.

  10. Human research subjects as human research workers.

    PubMed

    Lynch, Holly Fernandez

    2014-01-01

    Biomedical research involving human subjects has traditionally been treated as a unique endeavor, presenting special risks and demanding special protections. But in several ways, the regulatory scheme governing human subjects research is counter-intuitively less protective than the labor and employment laws applicable to many workers. This Article relies on analogical and legal reasoning to demonstrate that this should not be the case; in a number of ways, human research subjects ought to be fundamentally recast as human research workers. Like other workers protected under worklaw, biomedical research subjects often have interests that diverge from those in positions of control but little bargaining power for change. Bearing these important similarities in mind, the question becomes whether there is any good reason to treat subjects and protected workers differently as a matter of law. With regard to unrestricted payment, eligibility for a minimum wage, compensation for injury, and rights to engage in concerted activity, the answer is no and human subjects regulations ought to be revised accordingly.

  11. Integrated Environmental Modelling: human decisions, human challenges

    USGS Publications Warehouse

    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.

  12. [The embryo, the human and the humanized].

    PubMed

    Roa, A

    1992-03-01

    Since the moment of fecundation the human embryo is endowed with the properties of unity and uniqueness and its existence is therefore inviolable. Disputing arguments against this thesis are analyzed. Recent views of some biologists negate the human character to the embryo since the essence of a human being would be its cultural nature and ability to communicate. However, the embryo contains all the genetic information that will allow him to develop the ability to communicate. Any attempt to separate the 3 moments of time, past present and future is a definitive violation of ethics. A basic foundation of ethics is that present and future are implicit in the past and vice-versa. Finally, the idea that the unwanted child is not a cultural being should be discarded.

  13. Chimeras and human dignity.

    PubMed

    de Melo-Martín, Inmaculada

    2008-12-01

    Discussions about whether new biomedical technologies threaten or violate human dignity are now common. Indeed, appeals to human dignity have played a central role in national and international debates about whether to allow particular kinds of biomedical investigations. The focus of this paper is on chimera research. I argue here that both those who claim that particular types of human-nonhuman chimera research threaten human dignity and those who argue that such threat does not exist fail to make their case. I first introduce some of the arguments that have been offered supporting the claim that the creation of certain sorts of chimeras threatens or violates human dignity. I next present opponents' assessments of such arguments. Finally I critically analyze both the critics' and the supporters' claims about whether chimera research threatens human dignity.

  14. Human Performance in Space

    NASA Technical Reports Server (NTRS)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration -- from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of long-duration spaceflight) affects crew performance, and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculo-skeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from NASA.

  15. [Human physiology: kidney].

    PubMed

    Natochin, Iu V

    2010-01-01

    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  16. Robotics for Human Exploration

    NASA Technical Reports Server (NTRS)

    Fong, Terrence; Deans, Mathew; Bualat, Maria

    2013-01-01

    Robots can do a variety of work to increase the productivity of human explorers. Robots can perform tasks that are tedious, highly repetitive or long-duration. Robots can perform precursor tasks, such as reconnaissance, which help prepare for future human activity. Robots can work in support of astronauts, assisting or performing tasks in parallel. Robots can also perform "follow-up" work, completing tasks designated or started by humans. In this paper, we summarize the development and testing of robots designed to improve future human exploration of space.

  17. BNST neurocircuitry in humans

    PubMed Central

    Avery, Suzanne N.; Clauss, Jacqueline A.; Winder, Danny G.; Woodward, Neil; Heckers, Stephan; Blackford, Jennifer Urbano

    2014-01-01

    Anxiety and addiction disorders are two of the most common mental disorders in the United States, and are typically chronic, disabling, and comorbid. Emerging evidence suggests the bed nucleus of the stria terminalis (BNST) mediates both anxiety and addiction through connections with other brain regions, including the amygdala and nucleus accumbens. Although BNST structural connections have been identified in rodents and a limited number of structural connections have been verified in non-human primates, BNST connections have yet to be described in humans. Neuroimaging is a powerful tool for identifying structural and functional circuits in vivo. In this study, we examined BNST structural and functional connectivity in a large sample of humans. The BNST has structural and functional connections with multiple subcortical regions, including limbic, thalamic, and basal ganglia structures, confirming structural findings in rodents. We describe two novel connections in the human brain that have not been previously reported in rodents or non-human primates, including structural connections with the temporal pole, and functional connections with the paracingulate gyrus. The findings of this study provide a map of the BNST’s structural and functional connectivity across brain in healthy humans. In large part, the BNST neurocircuitry in humans is similar to findings from rodents and non-human primates; however, several connections are unique to humans. Future explorations of BNST neurocircuitry in anxiety and addiction disorders have the potential to reveal novel mechanisms underlying these disabling psychiatric illnesses. PMID:24444996

  18. Artificial human vision camera

    NASA Astrophysics Data System (ADS)

    Goudou, J.-F.; Maggio, S.; Fagno, M.

    2014-10-01

    In this paper we present a real-time vision system modeling the human vision system. Our purpose is to inspire from human vision bio-mechanics to improve robotic capabilities for tasks such as objects detection and tracking. This work describes first the bio-mechanical discrepancies between human vision and classic cameras and the retinal processing stage that takes place in the eye, before the optic nerve. The second part describes our implementation of these principles on a 3-camera optical, mechanical and software model of the human eyes and associated bio-inspired attention model.

  19. Human target acquisition performance

    NASA Astrophysics Data System (ADS)

    Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

    2012-06-01

    The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

  20. The psychology of humanness.

    PubMed

    Haslam, Nick; Loughnan, Steve; Holland, Elise

    2013-01-01

    This chapter explores the ways in which the concept of "humanness" illuminates a wide and fascinating variety of psychological phenomena. After introducing the concept--everyday understandings of what it is to be human--we present a model of the diverse ways in which humanness can be denied to people. According to this model people may be perceived as lacking uniquely human characteristics, and thus likened to animals, or as lacking human nature, and thus likened to inanimate objects. Both of these forms of dehumanization occur with varying degrees of subtlety, from the explicit uses of derogatory animal metaphors, to stereotypes that ascribe lesser humanness or simpler minds to particular groups, to nonconscious associations between certain humans and nonhumans. After reviewing research on dehumanization through the lens of our model we examine additional topics that the psychology of humanness clarifies, notably the perception of nonhuman animals and the objectification of women. Humanness emerges as a concept that runs an integrating thread through a variety of research literatures.

  1. Competent human research personnel.

    PubMed

    Arford, Patricia H; Knowles, Marilyn B; Sneed, Nancee V

    2008-12-01

    The process of conducting human research is highly regulated, rigorous, detailed oriented, potentially harmful, and, hopefully, beneficial. Health professionals learn how to critique, design, analyze, and apply human research but have minimal education in how to conduct human research. Successful completion of a 24-hour course was mandated for research support personnel to enhance the protection of human subjects, improve the integrity of data collected, and ensure cost-effective results. Routine audits demonstrated that the course substantially improved the documentation of the informed consent process, source documentation, protocol adherence, and regulatory compliance.

  2. Developing Human Resources through Actualizing Human Potential

    ERIC Educational Resources Information Center

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  3. Human Mind Maps

    ERIC Educational Resources Information Center

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  4. IMMUNOASSAY HUMAN EXPOSURE STUDIES

    EPA Science Inventory

    The Human Exposure Research Branch has developed several enzyme-linked immunosorbent assay (ELISA) methods to support human exposure assessment studies. Immunoassays to detect low levels (<10 ng/mL) of chlorpyrifos in food, track-in dirt and house dust have been applied to sam...

  5. Quantification of human responses

    NASA Technical Reports Server (NTRS)

    Steinlage, R. C.; Gantner, T. E.; Lim, P. Y. W.

    1992-01-01

    Human perception is a complex phenomenon which is difficult to quantify with instruments. For this reason, large panels of people are often used to elicit and aggregate subjective judgments. Print quality, taste, smell, sound quality of a stereo system, softness, and grading Olympic divers and skaters are some examples of situations where subjective measurements or judgments are paramount. We usually express what is in our mind through language as a medium but languages are limited in available choices of vocabularies, and as a result, our verbalizations are only approximate expressions of what we really have in mind. For lack of better methods to quantify subjective judgments, it is customary to set up a numerical scale such as 1, 2, 3, 4, 5 or 1, 2, 3, ..., 9, 10 for characterizing human responses and subjective judgments with no valid justification except that these scales are easy to understand and convenient to use. But these numerical scales are arbitrary simplifications of the complex human mind; the human mind is not restricted to such simple numerical variations. In fact, human responses and subjective judgments are psychophysical phenomena that are fuzzy entities and therefore difficult to handle by conventional mathematics and probability theory. The fuzzy mathematical approach provides a more realistic insight into understanding and quantifying human responses. This paper presents a method for quantifying human responses and subjective judgments without assuming a pattern of linear or numerical variation for human responses. In particular, quantification and evaluation of linguistic judgments was investigated.

  6. Human Simulated Diving Experiments.

    ERIC Educational Resources Information Center

    Bruce, David S.; Speck, Dexter F.

    1979-01-01

    This report details several simulated divinq experiments on the human. These are suitable for undergraduate or graduate laboratories in human or environmental physiology. The experiment demonstrates that a diving reflex is precipitated by both facial cooling and apnea. (Author/RE)

  7. Introduction to human factors

    SciTech Connect

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  8. The great human expansion.

    PubMed

    Henn, Brenna M; Cavalli-Sforza, L L; Feldman, Marcus W

    2012-10-30

    Genetic and paleoanthropological evidence is in accord that today's human population is the result of a great demic (demographic and geographic) expansion that began approximately 45,000 to 60,000 y ago in Africa and rapidly resulted in human occupation of almost all of the Earth's habitable regions. Genomic data from contemporary humans suggest that this expansion was accompanied by a continuous loss of genetic diversity, a result of what is called the "serial founder effect." In addition to genomic data, the serial founder effect model is now supported by the genetics of human parasites, morphology, and linguistics. This particular population history gave rise to the two defining features of genetic variation in humans: genomes from the substructured populations of Africa retain an exceptional number of unique variants, and there is a dramatic reduction in genetic diversity within populations living outside of Africa. These two patterns are relevant for medical genetic studies mapping genotypes to phenotypes and for inferring the power of natural selection in human history. It should be appreciated that the initial expansion and subsequent serial founder effect were determined by demographic and sociocultural factors associated with hunter-gatherer populations. How do we reconcile this major demic expansion with the population stability that followed for thousands years until the inventions of agriculture? We review advances in understanding the genetic diversity within Africa and the great human expansion out of Africa and offer hypotheses that can help to establish a more synthetic view of modern human evolution.

  9. Human Powered Centrifuge

    NASA Technical Reports Server (NTRS)

    Mulenburg, Gerald M. (Inventor); Vernikos, Joan (Inventor)

    1997-01-01

    A human powered centrifuge has independently established turntable angular velocity and human power input. A control system allows excess input power to be stored as electric energy in a battery or dissipated as heat through a resistors. In a mechanical embodiment, the excess power is dissipated in a friction brake.

  10. HUMAN HEALTH RESEARCH STRATEGY

    EPA Science Inventory

    The mission of the U.S. Environmental Protection Agency (EPA) is to protect public health and safeguard the environment. Risk assessment is an integral part of this mission in that it identifies and characterizes environmentally related human health problems. The Human Health Re...

  11. Annotated Humanities Programs.

    ERIC Educational Resources Information Center

    Adler, Richard R.; Applebee, Arthur

    The humanities programs offered in 1968 by 227 United States secondary schools are listed alphabetically by state, including almost 100 new programs not annotated in the 1967 listing (see TE 000 224). Each annotation presents a brief description of the approach to study used in the particular humanities course (e.g., American Studies, Culture…

  12. English and "Humanities"

    ERIC Educational Resources Information Center

    Lindley, David

    1973-01-01

    Defends English instruction against the current trend of integrating such classes into humanities programs, arguing for the uniqueness and unpredictability of all experience and the human capacity to recreate, share, and evaluate experience as is taught in English. (Author/RB)

  13. Investigating the Human Experience

    ERIC Educational Resources Information Center

    Ducote, Richard L.; Peterson, Robert E.

    1975-01-01

    A project entitled "Investigating the Human Experience," which was funded by the National Endowment for the Humanities, enables the College of DuPage to conduct a series of free films in various off-campus facilities. Documentaries and recent TV specials are shown, followed by a group discussion moderated by an instructor from the…

  14. Being Human in Sport.

    ERIC Educational Resources Information Center

    Allen, Dorothy J.; Fahey, Brian W.

    The structure of humanness as the unique and essential being of the individual, constantly emerging through experience and the actualization of human potential within the sports environment, is the central theme of this book. Sport is defined broadly to include all forms of physical activity experiences. Each chapter represents an inquiry unique…

  15. Methods in human cytogenetics

    SciTech Connect

    1993-12-31

    Chapter 4, discusses the various techniques used in the study human cytogenetics. The methods are discussed in historical order, from direct methods to tissue culture techniques, prenatal studies, meiotic studies, sex chromatin techniques, banding techniques, prophase banding and replication studies. Nomenclature of human chromosomes and quantitative methods are also mentioned. 60 refs., 3 figs.

  16. Assessment of Human Factors

    NASA Technical Reports Server (NTRS)

    Mount, Frances; Foley, Tico

    1999-01-01

    Human Factors Engineering, often referred to as Ergonomics, is a science that applies a detailed understanding of human characteristics, capabilities, and limitations to the design, evaluation, and operation of environments, tools, and systems for work and daily living. Human Factors is the investigation, design, and evaluation of equipment, techniques, procedures, facilities, and human interfaces, and encompasses all aspects of human activity from manual labor to mental processing and leisure time enjoyments. In spaceflight applications, human factors engineering seeks to: (1) ensure that a task can be accomplished, (2) maintain productivity during spaceflight, and (3) ensure the habitability of the pressurized living areas. DSO 904 served as a vehicle for the verification and elucidation of human factors principles and tools in the microgravity environment. Over six flights, twelve topics were investigated. This study documented the strengths and limitations of human operators in a complex, multifaceted, and unique environment. By focusing on the man-machine interface in space flight activities, it was determined which designs allow astronauts to be optimally productive during valuable and costly space flights. Among the most promising areas of inquiry were procedures, tools, habitat, environmental conditions, tasking, work load, flexibility, and individual control over work.

  17. Environment and the Humanities.

    ERIC Educational Resources Information Center

    Allen, Rodney F., Ed.; And Others

    As a conference report, the booklet is primarily devoted to abstracts of papers presented at a Conference on Environment and Humanities held in Tallahassee, Florida, April 25-27, 1976. Dr. Huston Smith of Syracuse University, the main speaker, addressed the issue of "Humanities and Environmental Awareness." Other topics discussed…

  18. Humane Education Projects Handbook.

    ERIC Educational Resources Information Center

    Junior League of Ogden, UT.

    This handbook was developed to promote interest in humane education and to encourage the adoption of humane education projects. Although specifically designed to assist Junior Leagues in developing such projects, the content should prove valuable to animal welfare organizations, zoos, aquariums, nature centers, and other project-oriented groups…

  19. Human Dignity Through History.

    ERIC Educational Resources Information Center

    Satterlie, Arthur L.

    A major educational need, as assessed by a committee of teachers, students, and community members, is to recognize acceptance of human dignity as the ultimate value in decision making. This concept provides a basis for the elementary and secondary social studies program. Although the concept of human dignity was promoted with the signing of the…

  20. Manage "Human Capital" Strategically

    ERIC Educational Resources Information Center

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  1. Human gene therapy.

    PubMed

    Sandhu, J S; Keating, A; Hozumi, N

    1997-01-01

    Human gene therapy and its application for the treatment of human genetic disorders, such as cystic fibrosis, cancer, and other diseases, are discussed. Gene therapy is a technique in which a functioning gene is inserted into a human cell to correct a genetic error or to introduce a new function to the cell. Many methods, including retroviral vectors and non-viral vectors, have been developed for both ex vivo and in vivo gene transfer into cells. Vectors need to be developed that efficiently transfer genes to target cells, and promoter systems are required that regulate gene expression according to physiologic needs of the host cell. There are several safety and ethical issues related to manipulating the human genome that need to be resolved. Current gene therapy efforts focus on gene insertion into somatic cells only. Gene therapy has potential for the effective treatment of genetic disorders, and gene transfer techniques are being used for basic research, for example, in cancer, to examine the underlying mechanism of disease. There are still many technical obstacles to be overcome before human gene therapy can become a routine procedure. The current human genome project provides the sequences of a vast number of human genes, leading to the identification, characterization, and understanding of genes that are responsible for many human diseases.

  2. [Human science and medicine].

    PubMed

    Caporale, Maria

    2005-01-01

    Objective of Human Science teaching is to develop Knowledge and ability for rational analysis of bio-medical problems. The relationship between doctor and patient must be founded on dialogue, cooperation, understanding, on respect of human rights: life, health, physical integrity, privacy, autonomy, freedom and liability to guide ethical choices in clinical experience and rediscover anthropological significance of Medicine.

  3. Humanism within Globalization

    ERIC Educational Resources Information Center

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  4. Human vaccines & immunotherapeutics: news.

    PubMed

    Riedmann, Eva M

    2013-10-01

    Infant rotavirus vaccination provides for herd immunity Nonreplicating sporozoite vaccine protects humans against malaria Personalized brain cancer vaccine enters phase 2 trial Novel implantable therapeutic cancer vaccine to be tested in humans Clostridium difficile vaccine candidate successful in phase 1 CDC reports strong uptake of HPV vaccine in boys Whooping cough outbreak in Texas.

  5. The Humanities' Value

    ERIC Educational Resources Information Center

    Harpham, Geoffrey Galt

    2009-01-01

    Why should society support the humanities when so many people are suffering from the effects of the economic crisis? What claim do the humanities, or scholarship generally, have on increasingly limited resources? Shouldn't such pursuits be considered luxuries at a time when people should be focusing on essentials? The alleviation of human…

  6. Incorporating Human Interindividual Biotransformation ...

    EPA Pesticide Factsheets

    The protection of sensitive individuals within a population dictates that measures other than central tendencies be employed to estimate risk. The refinement of human health risk assessments for chemicals metabolized by the liver to reflect data on human variability can be accomplished through (1) the characterization of enzyme expression in large banks of human liver samples, (2) the employment of appropriate techniques for the quantification and extrapolation of metabolic rates derived in vitro, and (3) the judicious application of physiologically based pharmacokinetic (PBPK) modeling. While in vitro measurements of specific biochemical reactions from multiple human samples can yield qualitatively valuable data on human variance, such measures must be put into the perspective of the intact human to yield the most valuable predictions of metabolic differences among humans. For quantitative metabolism data to be the most valuable in risk assessment, they must be tied to human anatomy and physiology, and the impact of their variance evaluated under real exposure scenarios. For chemicals metabolized in the liver, the concentration of parent chemical in the liver represents the substrate concentration in the MichaelisMenten description of metabolism. Metabolic constants derived in vitro may be extrapolated to the intact liver, when appropriate conditions are met. Metabolic capacity Vmax; the maximal rate of the reaction) can be scaled directly to the concentration

  7. Portraits of Human Greatness.

    ERIC Educational Resources Information Center

    Saint Anselm's Coll., Manchester, NH.

    Examined is the Humanities Program at St. Anselm College, a two-year program of readings and lectures ordered chronologically from ancient to contemporary times--from the age of Classical Greek thought and the Old Testament to the twentieth century. The first year of the Humanities Program is organized in eight units on general modes of…

  8. Vaccination against human papillomavirus

    PubMed Central

    Mello, Claudia Figueiredo

    2013-01-01

    ABSTRACT Human papillomavirus infection is common and causes different manifestations. This infection is a public health concern because it has been associated with genital tract malignant diseases among men and women. Currently two vaccines are available to prevent the human papillomavirus infection and its associated diseases. PMID:24488402

  9. Evaluating the Humanities

    ERIC Educational Resources Information Center

    Brody, Howard

    2013-01-01

    How can one measure the value of teaching the humanities? The problem of assessment and accountability is prominent today, of course, in secondary and higher education. It is perhaps even more acute for those who teach the humanities in nontraditional settings, such as medical and other professional schools. The public assumes that academes can…

  10. Human-System Technology

    DTIC Science & Technology

    2005-11-10

    Computing, this multidisciplinary field exploits advances in cognitive research together with those in computer science and related areas to optimize the...deep understanding of human cognition, perception, and/or locomotion; the relevant areas of computer science ; and the nature of the human activity to be

  11. Human Space Flight

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara; Mount, Frances

    2004-01-01

    The first human space flight, in the early 1960s, was aimed primarily at determining whether humans could indeed survive and function in micro-gravity. Would eating and sleeping be possible? What mental and physical tasks could be performed? Subsequent programs increased the complexity of the tasks the crew performed. Table 1 summarizes the history of U.S. space flight, showing the projects, their dates, crew sizes, and mission durations. With over forty years of experience with human space flight, the emphasis now is on how to design space vehicles, habitats, and missions to produce the greatest returns to human knowledge. What are the roles of the humans in space flight in low earth orbit, on the moon, and in exploring Mars?

  12. Beliefs about Human Extinction

    SciTech Connect

    Tonn, Bruce Edward

    2009-11-01

    This paper presents the results of a web-based survey about futures issues. Among many questions, respondents were asked whether they believe humans will become extinct. Forty-five percent of the almost 600 respondents believe that humans will become extinct. Many of those holding this believe felt that humans could become extinct within 500-1000 years. Others estimated extinction 5000 or more years into the future. A logistic regression model was estimated to explore the bases for this belief. It was found that people who describe themselves a secular are more likely to hold this belief than people who describe themselves as being Protestant. Older respondents and those who believe that humans have little control over their future also hold this belief. In addition, people who are more apt to think about the future and are better able to imagine potential futures tend to also believe that humans will become extinct.

  13. Dogs catch human yawns.

    PubMed

    Joly-Mascheroni, Ramiro M; Senju, Atsushi; Shepherd, Alex J

    2008-10-23

    This study is the first to demonstrate that human yawns are possibly contagious to domestic dogs (Canis familiaris). Twenty-nine dogs observed a human yawning or making control mouth movements. Twenty-one dogs yawned when they observed a human yawning, but control mouth movements did not elicit yawning from any of them. The presence of contagious yawning in dogs suggests that this phenomenon is not specific to primate species and may indicate that dogs possess the capacity for a rudimentary form of empathy. Since yawning is known to modulate the levels of arousal, yawn contagion may help coordinate dog-human interaction and communication. Understanding the mechanism as well as the function of contagious yawning between humans and dogs requires more detailed investigation.

  14. Implications for human health.

    PubMed Central

    Golberg, L

    1979-01-01

    To analyze the implications for human health, the toxicologist requires four sets of data: the results of toxicity and other studies in animals; quantitative data on actual or potential human exposure; whatever information is available on effects of exposure in man; and the statistical extrapolations from the dose-response relationships in animals to the (usually) much lower levels of human exposure. Professional expertise in toxicology is essential to assess the nature and severity of the toxic effects observed in animals, including such characteristics as potential for progression, irreversibility and production of incapacity. Given sufficient data, an estimate can be arrived at of the likelihood that such effects will be elicited in human populations of differing susceptibilities. The criteria by which the overall implications for human health can be judged comprise both the direct effects on man, as well as the indirect consequences stemming from environmental impacts. PMID:540600

  15. Mars Human Exploration Objectives

    NASA Technical Reports Server (NTRS)

    Briggs, Geoff

    1998-01-01

    This paper reviews the objectives and other considerations of Human exploration of Mars. The objectives of human exploration of Mars are: (1) to learn how Mars is similar to, and different from, Earth; (2) to explore possible life, past and present; (3) to discover what Mars is like now from the perspective of Geoscience and geologic history; and (4) how did Mars form and how did its formation differ from Earth. Considerations of human Martian exploration involve: (1) having a capable base laboratory; (2) having long range transportation; (3) having operational autonomy of the crew, and the requirement of the crew to possess a range of new cognitive processes along with easy communications with terrestrial colleagues; and finally (4) creating the human habitat along with human factors which involve more than just survivability.

  16. Archaea on Human Skin

    PubMed Central

    Probst, Alexander J.; Auerbach, Anna K.; Moissl-Eichinger, Christine

    2013-01-01

    The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin. PMID:23776475

  17. Human fetal thyroid function.

    PubMed

    Polak, Michel

    2014-01-01

    The early steps of thyroid development that lead to its function in the human fetus and subsequently the further maturation that allows the human fetus to secrete thyroxine (T4) in a significant amount are reviewed here. We underline the importance of the transfer of T4 from the pregnant woman to her fetus, which contributes at all stages of the pregnancy to fetal thyroid function and development. In the first trimester of pregnancy, the temporal and structural correlation of thyroid hormone synthesis with folliculogenesis supported the concept that structural and functional maturations are closely related. Human thyroid terminal differentiation follows a precisely timed gene expression program. The crucial role of the sodium/iodine symporter for the onset of thyroid function in the human fetus is shown. Fetal T4 is detected by the eleventh week of gestation and progressively increases throughout. The pattern of thyroid hormones and thyroid-stimulating hormone levels in the course of pregnancy is given from fetal blood sampling data, and the mechanisms governing this maturation in the human fetus are discussed. Finally an example of primary human fetal thyroid dysfunction, such as in Down syndrome, is given. The understanding of the physiology of the human fetal thyroid function is the basis for fetal medicine in the field of thyroidology.

  18. Archaea on human skin.

    PubMed

    Probst, Alexander J; Auerbach, Anna K; Moissl-Eichinger, Christine

    2013-01-01

    The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin.

  19. Human Space Exploration

    NASA Technical Reports Server (NTRS)

    Jeevarajan, Antony

    2014-01-01

    The Mars probe, launched by India a few months ago, is on its way to Mars. At this juncture, it is appropriate to talk about the opportunities presented to us for the Human Exploration of Mars. I am planning to highlight some of the challenges to take humans to Mars, descend, land, stay, ascend and return home safely. The logistics of carrying the necessary accessories to stay at Mars will be delivered in multiple stages using robotic missions. The primary ingredients for human survival is air, water, food and shelter and the necessity to recycle the primary ingredients will be articulated. Humans have to travel beyond the van Allen radiation belt under microgravity condition during this inter-planetary travel for about 6 months minimum one way. The deconditioning of human system under microgravity conditions and protection of humans from Galactic cosmic radiation during the travel should be taken into consideration. The multi-disciplinary effort to keep the humans safe and functional during this journey will be addressed.

  20. Human Plasma Protein C

    PubMed Central

    Kisiel, Walter

    1979-01-01

    Protein C is a vitamin K-dependent protein, which exists in bovine plasma as a precursor of a serine protease. In this study, protein C was isolated to homogeneity from human plasma by barium citrate adsorption and elution, ammonium sulfate fractionation, DEAE-Sephadex chromatography, dextran sulfate agarose chromatography, and preparative polyacrylamide gel electrophoresis. Human protein C (Mr = 62,000) contains 23% carbohydrate and is composed of a light chain (Mr = 21,000) and a heavy chain (Mr = 41,000) held together by a disulfide bond(s). The light chain has an amino-terminal sequence of Ala-Asn-Ser-Phe-Leu- and the heavy chain has an aminoterminal sequence of Asp-Pro-Glu-Asp-Gln. The residues that are identical to bovine protein C are underlined. Incubation of human protein C with human α-thrombin at an enzyme to substrate weight ratio of 1:50 resulted in the formation of activated protein C, an enzyme with serine amidase activity. In the activation reaction, the apparent molecular weight of the heavy chain decreased from 41,000 to 40,000 as determined by gel electrophoresis in the presence of sodium dodecyl sulfate. No apparent change in the molecular weight of the light chain was observed in the activation process. The heavy chain of human activated protein C also contains the active-site serine residue as evidenced by its ability to react with radiolabeled diisopropyl fluorophosphate. Human activated protein C markedly prolongs the kaolin-cephalin clotting time of human plasma, but not that of bovine plasma. The amidolytic and anticoagulant activities of human activated protein C were completely obviated by prior incubation of the enzyme with diisopropyl fluorophosphate. These results indicate that human protein C, like its bovine counterpart, exists in plasma as a zymogen and is converted to a serine protease by limited proteolysis with attendant anticoagulant activity. Images PMID:468991

  1. Human Computer Interaction

    NASA Astrophysics Data System (ADS)

    Bhagwani, Akhilesh; Sengar, Chitransh; Talwaniper, Jyotsna; Sharma, Shaan

    2012-08-01

    The paper basically deals with the study of HCI (Human computer interaction) or BCI(Brain-Computer-Interfaces) Technology that can be used for capturing brain signals and translating them into commands that allow humans to control (just by thinking) devices such as computers, robots, rehabilitation technology and virtual reality environments. The HCI is based as a direct communication pathway between the brain and an external device. BCIs are often aimed at assisting, augmenting, or repairing human cognitive or sensory-motor functions.The paper also deals with many advantages of BCI Technology along with some of its applications and some major drawbacks.

  2. Aluminium in human sweat.

    PubMed

    Minshall, Clare; Nadal, Jodie; Exley, Christopher

    2014-01-01

    It is of burgeoning importance that the human body burden of aluminium is understood and is measured. There are surprisingly few data to describe human excretion of systemic aluminium and almost no reliable data which relate to aluminium in sweat. We have measured the aluminium content of sweat in 20 healthy volunteers following mild exercise. The concentration of aluminium ranged from 329 to 5329μg/L. These data equate to a daily excretion of between 234 and 7192μg aluminium and they strongly suggest that perspiration is the major route of excretion of systemic aluminium in humans.

  3. Human exposure to aluminium.

    PubMed

    Exley, Christopher

    2013-10-01

    Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

  4. Introduction to human factors.

    PubMed

    Bergman, Eric

    2012-03-01

    This paper provides an introduction to "human factors engineering," an applied science that seeks to optimize usability and safety of systems. Human factors engineering pursues this goal by aligning system design with the perceptual, cognitive, and physical capabilities of users. Human factors issues loom large in the diabetes management domain because patients and health care professionals interact with a complex variety of systems, including medical device hardware and software, which are themselves embedded within larger systems of institutions, people, and processes. Usability considerations must be addressed in these systems and devices to ensure safe and effective diabetes management.

  5. Human Resource Accounting.

    DTIC Science & Technology

    1984-12-01

    I AD-RI54 787 HUMAN RESOURCE ACCOUNTING (U) NAVAL POSTGRADUATE SCHOOL 1/2 F MONTEREY CR J C MARTINS DEC 84 1UNCLASSIFIED /G 5/9 NL -~~ .. 2. . L...Monterey, California JUN1im THESISG HUMAN RESOURCE ACCOUNTING by Joaquim C. Martins LLJ.. December 1984 Thesis Advisor: R.A. McGonigal Approved for...REPORT & PECRI00 COVERED Master’s Thesis; Human Resource Accounting Dcme 94- ’ 6. PERFORMING ORG. REPORT NUMBER 7. AUTOR(*) . CONTRACT OR GRANT NUMBER

  6. Human pancreas development.

    PubMed

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

  7. Human Genome Project

    SciTech Connect

    Block, S.; Cornwall, J.; Dally, W.; Dyson, F.; Fortson, N.; Joyce, G.; Kimble, H. J.; Lewis, N.; Max, C.; Prince, T.; Schwitters, R.; Weinberger, P.; Woodin, W. H.

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  8. Sulfatases and human disease.

    PubMed

    Diez-Roux, Graciana; Ballabio, Andrea

    2005-01-01

    Sulfatases are a highly conserved family of proteins that cleave sulfate esters from a wide range of substrates. The importance of sulfatases in human metabolism is underscored by the presence of at least eight human monogenic diseases caused by the deficiency of individual sulfatases. Sulfatase activity requires a unique posttranslational modification, which is impaired in patients with multiple sulfatase deficiency (MSD) due to a mutation of the sulfatase modifying factor 1 (SUMF1). Here we review current knowledge and future perspectives on the evolution of the sulfatase gene family, on the role of these enzymes in human metabolism, and on new developments in the therapy of sulfatase deficiencies.

  9. Shugoshin-1 balances Aurora B kinase activity via PP2A to promote chromosome bi-orientation.

    PubMed

    Meppelink, Amanda; Kabeche, Lilian; Vromans, Martijn J M; Compton, Duane A; Lens, Susanne M A

    2015-04-28

    Correction of faulty kinetochore-microtubule attachments is essential for faithful chromosome segregation and dictated by the opposing activities of Aurora B kinase and PP1 and PP2A phosphatases. How kinase and phosphatase activities are appropriately balanced is less clear. Here, we show that a centromeric pool of PP2A-B56 counteracts Aurora B T-loop phosphorylation and is recruited to centromeres through Shugoshin-1 (Sgo1). In non-transformed RPE-1 cells, Aurora B, Sgo1, and PP2A-B56 are enriched on centromeres and levels diminish as chromosomes establish bi-oriented attachments. Elevating Sgo1 levels at centromeres recruits excess PP2A-B56, and this counteracts Aurora B kinase activity, undermining efficient correction of kinetochore-microtubule attachment errors. Conversely, Sgo1-depleted cells display reduced centromeric localization of Aurora B, whereas the remaining kinase is hyperactive due to concomitant reduction of centromeric PP2A-B56. Our data suggest that Sgo1 can tune the stability of kinetochore-microtubule attachments through recruitment of PP2A-B56 that balances Aurora B activity at the centromere.

  10. Mitotic entry: Non-genetic heterogeneity exposes the requirement for Plk1.

    PubMed

    Aspinall, Claire F; Zheleva, Daniella; Tighe, Anthony; Taylor, Stephen S

    2015-11-03

    The quest to develop novel antimitotic chemotherapy agents has led to the generation of several small molecule inhibitors targeting Plk1, a protein kinase required for multiple aspects of cell division. Previous studies have shown that upon exposure to Plk1 inhibitors, cells enter mitosis, delay briefly in prophase and then arrest in mitosis due to an inability to undergo centrosome separation. Here, we show that four different classes of Plk1 inhibitor block mitotic entry in several cancer cell lines and non-transformed RPE-1 cells. The proportion of cells that arrest in G2 is cell line and concentration dependent, and is subject to non-genetic heterogeneity. Following inhibitor washout, the G2 block is alleviated and cells enter mitosis but then fail to complete cell division indicating that most Plk1 inhibitors are not fully reversible. An exception is CYC140844; in contrast to five other inhibitors examined here, this novel Plk1 inhibitor is fully reversible. We discuss the implications for developing Plk1 inhibitors as chemotherapy agents and research tools.

  11. Approaches to Human Communication.

    ERIC Educational Resources Information Center

    Budd, Richard W., Ed.; Ruben, Brent D., Ed.

    This anthology of essays approaches human communication from the points of view of: anthropology, art biology, economics, encounter groups, semantics, general system theory, history, information theory, international behavior, journalism, linguistics, mass media, neurophysiology, nonverbal behavior, organizational behavior, philosophy, political…

  12. Human Computers 1947

    NASA Technical Reports Server (NTRS)

    1947-01-01

    Langley's human computers at work in 1947. The female presence at Langley, who performed mathematical computations for male staff. Photograph published in Winds of Change, 75th Anniversary NASA publication (page 48), by James Schultz.

  13. Human Systems Integration Introduction

    NASA Video Gallery

    This lecture provides an overview of Human Systems Integration (HSI), its implementation cost and return on investment, HSI domains, how HSI fits into the NASA organization structure, HSI roles and...

  14. Teaching about Human Geography.

    ERIC Educational Resources Information Center

    Schlene, Vickie J.

    1991-01-01

    Presents a sampling of items from the ERIC database concerning the teaching of human geography. Includes documents dealing with Africa, Asia, the United States, Canada, Antarctica, and geographic concepts. Explains how to obtain ERIC documents. (SG)

  15. Will Technology Humanize Us?

    ERIC Educational Resources Information Center

    Snider, Robert C.

    1972-01-01

    The author considers the question of whether technology will cause humanization or dehumanization in the schools. He concludes that we can not stop tecchnology; we can only give it direction and purpose. (Author/MS)

  16. The Human Hazard.

    ERIC Educational Resources Information Center

    Tickell, Crispin

    1995-01-01

    Examines the plight of environmental refugees and the adequacy of political responses to the situation. Discusses the consequences of accelerated environmental change, particularly the impact of global warming on human migration. (LZ)

  17. Human Biomass Consumption

    NASA Video Gallery

    Humans are using an increasing amount of Earth’s annual production of plants. Research shows that, from 1995 to 2005, consumption rose from 20 to 25 percent of the planet's annual production. Wha...

  18. Statement on Human Cloning

    MedlinePlus

    ... form Search American Association for the Advancement of Science Statement on Human Cloning Tweet The American Association for the Advancement of Science (AAAS) recognizes the intense debates within our society ...

  19. Viruses and human cancer

    SciTech Connect

    Gallo, R.C.; Haseltine, W.; Klein, G.; Zur Hausen, H.

    1987-01-01

    This book contains papers on the following topics: Immunology and Epidemiology, Biology and Pathogenesis, Models of Pathogenesis and Treatment, Simian and Bovine Retroviruses, Human Papilloma Viruses, EBV and Herpesvirus, and Hepatitis B Virus.

  20. HPV (Human Papillomavirus)

    MedlinePlus

    ... Ask your doctor if you should get the HPV Vaccine. What else can I do to lower my ... the body. To Learn More About HPV Human Papillomavirus Vaccine More in For Women Medication Safety for Women ¡ ...

  1. Human X chromosome

    SciTech Connect

    1993-12-31

    Chapter 21, describes in detail the human X chromosome. X chromatin (or Barr body) formation, inactivation and reactivation of the X chromosome, X;Y translocations, and sex reversal are discussed. 30 refs., 3 figs.

  2. Uniquely human social cognition.

    PubMed

    Saxe, Rebecca

    2006-04-01

    Recent data identify distinct components of social cognition associated with five brain regions. In posterior temporal cortex, the extrastriate body area is associated with perceiving the form of other human bodies. A nearby region in the posterior superior temporal sulcus is involved in interpreting the motions of a human body in terms of goals. A distinct region at the temporo-parietal junction supports the uniquely human ability to reason about the contents of mental states. Medial prefrontal cortex is divided into at least two subregions. Ventral medial prefrontal cortex is implicated in emotional empathy, whereas dorsal medial prefrontal cortex is implicated in the uniquely human representation of triadic relations between two minds and an object, supporting shared attention and collaborative goals.

  3. Pesticides and Human Health

    MedlinePlus

    ... Active Ingredients Other/Inert Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure ... toxic products , and those that are natural or organic , can cause health problems if someone is exposed ...

  4. Human Reliability Program Overview

    SciTech Connect

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  5. Aerospace Human Factors

    NASA Technical Reports Server (NTRS)

    Jordan, Kevin

    1999-01-01

    The following contains the final report on the activities related to the Cooperative Agreement between the human factors research group at NASA Ames Research Center and the Psychology Department at San Jose State University. The participating NASA Ames division has been, as the organization has changed, the Aerospace Human Factors Research Division (ASHFRD and Code FL), the Flight Management and Human Factors Research Division (Code AF), and the Human Factors Research and Technology Division (Code IH). The inclusive dates for the report are November 1, 1984 to January 31, 1999. Throughout the years, approximately 170 persons worked on the cooperative agreements in one capacity or another. The Cooperative Agreement provided for research personnel to collaborate with senior scientists in ongoing NASA ARC research. Finally, many post-MA/MS and post-doctoral personnel contributed to the projects. It is worth noting that 10 former cooperative agreement personnel were hired into civil service positions directly from the agreements.

  6. Creativity: The Human Resource.

    ERIC Educational Resources Information Center

    Lewis, Richard W.

    1979-01-01

    The author discusses an exhibition entitled "Creativity--The Human Resource." The exhibition examines the work of 15 Americans, such as designer Buckminster Fuller and artist Judy Chicago, who have contributed in special ways to the arts and sciences. (PHR)

  7. Visible Human Project

    MedlinePlus

    ... Toxicology Health Services Research & Public Health Health Information Technology NLM for You Grants & Funding Meaningful Use Tools Training & Outreach Network of Medical Libraries Regional Activities Careers @ NLM Mobile Gallery Site Navigation Home The Visible Human Project ® ...

  8. Human Resource Planning

    ERIC Educational Resources Information Center

    Hoffman, W. H.; Wyatt, L. L.

    1977-01-01

    By using the total resource approach, we have focused attention on the need to integrate human resource planning with other business plans and highlighted the importance of a productivity strategy. (Author)

  9. Bridging Humanism and Behaviorism.

    ERIC Educational Resources Information Center

    Chu, Lily

    1980-01-01

    Humanistic behaviorism may provide the necessary bridge between behaviorism and humanism. Perhaps the most humanistic approach to teaching is to learn how certain changes will help students and how these changes can be accomplished. (Author/MLF)

  10. Humanism vs. Behaviorism

    ERIC Educational Resources Information Center

    Hunter, Madeline

    1977-01-01

    Author argues that humanism and behaviorism are not necessarily exclusive of one another, and that principles of behaviorism, when thoughtfully applied, can lead to the achievement of humanistic goals. (RW)

  11. Habitability and Human Factors Contributions to Human Space Flight

    NASA Technical Reports Server (NTRS)

    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.

  12. Pushing Human Frontiers

    NASA Technical Reports Server (NTRS)

    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.

  13. Human Assisted Assembly Processes

    SciTech Connect

    CALTON,TERRI L.; PETERS,RALPH R.

    2000-01-01

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative

  14. Alcohol in human history.

    PubMed

    Vallee, B L

    1994-01-01

    The role of ethanol in the history of human development is here summarized under seven topics: I. Alcohol: the substitute for water as the major human beverage; II. Alcohol as a component of the diet and source of calories; III. Alcohol, concentration by distillation; IV. The Reformation, Temperance and Prohibition; V. Potable nonalcoholic beverages: Boiled water (coffee, tea); VI. Purification and sanitation of water; VII. The present and future.

  15. Meeting human needs

    NASA Technical Reports Server (NTRS)

    Nicogossian, Arnauld E.

    1992-01-01

    The degree of autonomy of future long duration manned missions will emphasize interactions between human operators and automated systems aimed at the most effective allocations of tasks between humans and machines. Knowledge of crewmembers' physical status, encompassing both capabilities and limitations, will also be critical during EVA and planetary roving missions; psychological evaluation and support, with a view to both individual health and group cohesion and productivity, may become a critical consideration. Attention is here given to crewmembers' medical and psychological vulnerabilities.

  16. Evolution and human sexuality.

    PubMed

    Gray, Peter B

    2013-12-01

    The aim of this review is to put core features of human sexuality in an evolutionary light. Toward that end, I address five topics concerning the evolution of human sexuality. First, I address theoretical foundations, including recent critiques and developments. While much traces back to Darwin and his view of sexual selection, more recent work helps refine the theoretical bases to sex differences and life history allocations to mating effort. Second, I consider central models attempting to specify the phylogenetic details regarding how hominin sexuality might have changed, with most of those models honing in on transitions from a possible chimpanzee-like ancestor to the slightly polygynous and long-term bonded sociosexual partnerships observed among most recently studied hunter-gatherers. Third, I address recent genetic and physiological data contributing to a refined understanding of human sexuality. As examples, the availability of rapidly increasing genomic information aids comparative approaches to discern signals of selection in sexuality-related phenotypes, and neuroendocrine studies of human responses to sexual stimuli provide insight into homologous and derived mechanisms. Fourth, I consider some of the most recent, large, and rigorous studies of human sexuality. These provide insights into sexual behavior across other national samples and on the Internet. Fifth, I discuss the relevance of a life course perspective to understanding the evolution of human sexuality. Most research on the evolution of human sexuality focuses on young adults. Yet humans are sexual beings from gestation to death, albeit in different ways across the life course, and in ways that can be theoretically couched within life history theory.

  17. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1990-01-01

    This paper describes several case studies of human space exploration, considered by the NASA's Office of Exploration in 1988. Special attention is given to the mission scenarios, the critical technology required in these expeditions, and the extraterrestrial power requirements of significant system elements. The cases examined include a manned expedition to Phobos, the inner Martian moon; a human expedition to Mars; the Lunar Observatory; and a lunar outpost to early Mars evolution.

  18. Mapping the human genome

    SciTech Connect

    Annas, G.C.; Elias, S.

    1992-01-01

    This article is a review of the book Mapping the Human Genome: Using Law and Ethics as Guides, edited by George C. Annas and Sherman Elias. The book is a collection of essays on the subject of using ethics and laws as guides to justify human gene mapping. It addresses specific issues such problems related to eugenics, patents, insurance as well as broad issues such as the societal definitions of normality.

  19. Humans in space.

    PubMed

    White, R J; Averner, M

    2001-02-22

    Many successful space missions over the past 40 years have highlighted the advantages and necessity of humans in the exploration of space. But as space travel becomes ever more feasible in the twenty-first century, the health and safety of future space explorers will be paramount. In particular, understanding the risks posed by exposure to radiation and extended weightlessness will be crucial if humans are to travel far from Earth.

  20. The great human expansion

    PubMed Central

    Henn, Brenna M.; Cavalli-Sforza, L. L.; Feldman, Marcus W.

    2012-01-01

    Genetic and paleoanthropological evidence is in accord that today’s human population is the result of a great demic (demographic and geographic) expansion that began approximately 45,000 to 60,000 y ago in Africa and rapidly resulted in human occupation of almost all of the Earth’s habitable regions. Genomic data from contemporary humans suggest that this expansion was accompanied by a continuous loss of genetic diversity, a result of what is called the “serial founder effect.” In addition to genomic data, the serial founder effect model is now supported by the genetics of human parasites, morphology, and linguistics. This particular population history gave rise to the two defining features of genetic variation in humans: genomes from the substructured populations of Africa retain an exceptional number of unique variants, and there is a dramatic reduction in genetic diversity within populations living outside of Africa. These two patterns are relevant for medical genetic studies mapping genotypes to phenotypes and for inferring the power of natural selection in human history. It should be appreciated that the initial expansion and subsequent serial founder effect were determined by demographic and sociocultural factors associated with hunter-gatherer populations. How do we reconcile this major demic expansion with the population stability that followed for thousands years until the inventions of agriculture? We review advances in understanding the genetic diversity within Africa and the great human expansion out of Africa and offer hypotheses that can help to establish a more synthetic view of modern human evolution. PMID:23077256

  1. The human oncogenic viruses

    SciTech Connect

    Luderer, A.A.; Weetall, H.H

    1986-01-01

    This book contains eight selections. The titles are: Cytogenetics of the Leukemias and Lymphomas; Cytogenetics of Solid Tumors: Renal Cell Carcinoma, Malignant Melanoma, Retinoblastoma, and Wilms' Tumor; Elucidation of a Normal Function for a Human Proto-Oncogene; Detection of HSV-2 Genes and Gene Products in Cervical Neoplasia; Papillomaviruses in Anogennital Neoplasms; Human Epstein-Barr Virus and Cancer; Hepatitis B Virus and Hepatocellular Carcinoma; and Kaposi's Sarcoma: Acquired Immunodeficiency Syndrome (AIDS) and Associated Viruses.

  2. The Human Relations School.

    ERIC Educational Resources Information Center

    Fox, Robert S.; Lippitt, Ronald

    As an expansion of ED 026 320, the model for a Human Relations School sketched in this document is an attempt to answer these questions: What would it be like if a school were to see itself as a laboratory for living and learning in which the test that is known about human interaction were utilized? How would it be organized? What would be its…

  3. Human ocular anatomy.

    PubMed

    Kels, Barry D; Grzybowski, Andrzej; Grant-Kels, Jane M

    2015-01-01

    We review the normal anatomy of the human globe, eyelids, and lacrimal system. This contribution explores both the form and function of numerous anatomic features of the human ocular system, which are vital to a comprehensive understanding of the pathophysiology of many oculocutaneous diseases. The review concludes with a reference glossary of selective ophthalmologic terms that are relevant to a thorough understanding of many oculocutaneous disease processes.

  4. Potentiality and human embryos.

    PubMed

    Lizza, John P

    2007-09-01

    Consideration of the potentiality of human embryos to develop characteristics of personhood, such as intellect and will, has figured prominently in arguments against abortion and the use of human embryos for research. In particular, such consideration was the basis for the call of the US President's Council on Bioethics for a moratorium on stem cell research on human embryos. In this paper, I critique the concept of potentiality invoked by the Council and offer an alternative account. In contrast to the Council's view that an embryo's potentiality is determined by definition and is not affected by external conditions that may prevent certain possibilities from ever being realized, I propose an empirically grounded account of potentiality that involves an assessment of the physical and decisional conditions that may restrict an embryo's possibilities. In my view, some human embryos lack the potentiality to become a person that other human embryos have. Assuming for the sake of argument that the potential to become a person gives a being special moral status, it follows that some human embryos lack this status. This argument is then used to support Gene Outka's suggestion that it is morally permissible to experiment on 'spare' frozen embryos that are destined to be destroyed.

  5. Human Factors Review Plan

    SciTech Connect

    Paramore, B.; Peterson, L.R.

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  6. Glycobiology of human milk.

    PubMed

    Newburg, D S

    2013-07-01

    Glycans are characteristic components of milk, and each species has unique patterns of specific carbohydrates. Human milk is unusually rich in glycans, with the major components being lactose and oligosaccharides, representing approximately 6.8 and 1% of the milk, respectively. Other sources of glycans in human milk include monosaccharides, mucins, glycosaminoglycans, glycoproteins, glycopeptides, and glycolipids. In human milk, the presence and patterns of these glycans vary depending upon the stage of lactation and the maternal genes and their genetic polymorphisms that control glycosyl transferases. The synthesis of milk glycans utilizes a significant portion of the metabolic energy that the mother expends when producing her milk, but other than lactose, these glycans contribute little to the nutritional needs of the infant. The data herein support several functions. 1) Many human milk glycans inhibit pathogens from binding to the intestinal mucosa. 2) Human milk glycans attenuate inflammation. 3) Glycans also directly stimulate the growth of beneficial (mutualist) bacteria of the microbiota (formerly considered commensal microflora of the intestine); these mutualists and their fermentation products can, in turn, (a) inhibit pathogens, (b) modulate signaling and inflammation, and (c) the fermentation products can be absorbed and utilized as a source of dietary calories. These functions can help direct and support intestinal postnatal growth, development, and ontogeny of colonization. The many functions of the milk glycans may synergistically protect infants from disease. Hence, human milk glycans and their homologs may serve as novel prophylactic or therapeutic agents for a diverse range of deleterious conditions.

  7. Human behavior and human performance: Psychomotor demands

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The results of several experiments are presented in abstract form. These studies are critical for the interpretation and acceptance of flight based science to be conducted by the Behavior and Performance project. Some representative titles are as follow: External audio for IBM/PC compatible computers; A comparative assessment of psychomotor performance (target prediction by humans and macaques); Response path (a dependent measure for computer maze solving and other tasks); Behavioral asymmetries of psychomotor performance in Rhesus monkey (a dissociation between hand preference and skill); Testing primates with joystick based automated apparatus; and Environmental enrichment and performance assessment for ground or flight based research with primates;

  8. Microtubule organization during human parthenogenesis.

    PubMed

    Terada, Yukihiro; Hasegawa, Hisataka; Ugajin, Tomohisa; Murakami, Takashi; Yaegashi, Nobuo; Okamura, Kunihiro

    2009-04-01

    In human fertilization, the sperm centrosome plays a crucial role as a microtubule organizing center (MTOC). We studied microtubule organization during human parthenogenesis, which occurs when a human egg undergoes cleavage without a sperm centrosome. Multiple cytoplasmic asters were organized in the human oocyte after parthenogenetic activation, indicating that multiple MTOC are present in the human oocyte cytoplasm and function like a human sperm centrosome during parthenogenesis.

  9. Developing Human Performance Measures

    SciTech Connect

    Jeffrey Joe; Bruce Hallbert; Larry Blackwood; Donald Dudehoeffer; Kent Hansen

    2006-05-01

    Through the reactor oversight process (ROP), the U.S. Nuclear Regulatory Commission (NRC) monitors the performance of utilities licensed to operate nuclear power plants. The process is designed to assure public health and safety by providing reasonable assurance that licensees are meeting the cornerstones of safety and designated crosscutting elements. The reactor inspection program, together with performance indicators (PIs), and enforcement activities form the basis for the NRC’s risk-informed, performance based regulatory framework. While human performance is a key component in the safe operation of nuclear power plants and is a designated cross-cutting element of the ROP, there is currently no direct inspection or performance indicator for assessing human performance. Rather, when human performance is identified as a substantive cross cutting element in any 1 of 3 categories (resources, organizational or personnel), it is then evaluated for common themes to determine if follow-up actions are warranted. However, variability in human performance occurs from day to day, across activities that vary in complexity, and workgroups, contributing to the uncertainty in the outcomes of performance. While some variability in human performance may be random, much of the variability may be attributed to factors that are not currently assessed. There is a need to identify and assess aspects of human performance that relate to plant safety and to develop measures that can be used to successfully assure licensee performance and indicate when additional investigation may be required. This paper presents research that establishes a technical basis for developing human performance measures. In particular, we discuss: 1) how historical data already gives some indication of connection between human performance and overall plant performance, 2) how industry led efforts to measure and model human performance and organizational factors could serve as a data source and basis for a

  10. Human Milk Fortification.

    PubMed

    Simmer, Karen

    2015-01-01

    Human milk is the feed of choice for preterm infants. However, human milk does not provide enough nutrition, especially protein, for preterm infants to achieve target growth rates similar to those in utero (15-20 g/kg per day). Fortifiers for human milk, manufactured from bovine milk, are commercially available and routinely used for patients born <32 weeks' gestation prior to discharge home. Recent recommended dietary intakes (RDI) have been revised. Up to 4.2 g of protein and 135 kcal/kg per day is recommended for infants born very preterm. Additional supplements are needed to current commercial fortifiers to achieve these RDI and reduce the incidence of ex-uterine growth failure. A human milk fortifier that is manufactured from donor human milk is available in some developed countries and may confer some clinical benefits, including a reduction in necrotizing enterocolitis. Fortification can be added in a standardized protocol as per manufacturers' instructions. Human milk composition can be analyzed and fortification individualized to take into account the large variation from mother to mother. Alternatively, fortification can be increased in a stepwise manner based on assumed composition while monitoring blood urea levels for safety. The current aim is to prevent preterm infants dropping percentiles and falling below the 10th percentile at 36 weeks' corrected gestational age or discharge home. More data are required on how best to fortify human milk for preterm infants to achieve optimal growth, development and health outcomes in the long term. There is an urgent need for well-designed and informed randomized clinical trials in this vulnerable preterm population.

  11. Meeting human needs

    NASA Technical Reports Server (NTRS)

    Nicogossian, Arnauld E.

    1992-01-01

    Manned space flight can be viewed as an interaction of three general elements: the human crewmember, spacecraft systems, and the environment. While the human crewmember is a crucial element in the system, certain physiological, psychological, environ- mental and spacecraft systems factors can compromise human performance in space. These factors include atmospheric pressure, physiology, uncertainties associated with space radiation, the potential for exposure to toxic materials in the closed environment, and spacecraft habitability. Health protection in space, for current and future missions, relies on a philosophy of risk reduction, which in the space program is achieved in four ways-through health maintenance, health care, design criteria, an selection and training. Emphasis is place upon prevention, through selection criteria and careful screening. Spacecraft health care systems must be absolutely reliable, and they will be automated and computerized to the maximum extent possible, but still designed with the human crewmember's capabilities in mind. The autonomy and technological sophistication of future missions will require a greater emphasis on high-level interaction between the human operator and automated systems, with effective allocation of tasks between humans and machines. Performance in space will include complex tasks during extravehicular activity (EVA) and on planetary surfaces, and knowledge of crewmembers' capability and limitations during such operations will be critical to mission success. Psychological support will become increasingly important on space missions, as crews spend long periods in remote and potentially hazardous environments. The success of future missions will depend on both individual psychological health and group cohesion and productivity, particularly as crew profiles become more heterogeneous. Thus, further human factors are needed in the area of small-group dynamics and performance.

  12. Spaceflight Human System Standards

    NASA Technical Reports Server (NTRS)

    Holubec, Keith; Tillman, Barry; Connolly, Jan

    2009-01-01

    NASA created a new approach for human system integration and human performance standards. NASA created two documents a standard and a reference handbook. The standard is titled NASA Space Flight Human-System Standard (SFHSS) and consists of two-volumes: Volume 1- Crew Health This volume covers standards needed to support astronaut health (medical care, nutrition, sleep, exercise, etc.) Volume 2 Human Factors, Habitability and Environmental Health This volume covers the standards for system design that will maintain astronaut performance (ie., environmental factors, design of facilities, layout of workstations, and lighting requirements). It includes classic human factors requirements. The new standards document is written in terms so that it is applicable to a broad range of present and future NASA systems. The document states that all new programs prepare system-specific requirements that will meet the general standards. For example, the new standard does not specify a design should accommodate specific percentiles of a defined population. Rather, NASA-STD-3001, Volume 2 states that all programs shall prepare program-specific requirements that define the user population and their size ranges. The design shall then accommodate the full size range of those users. The companion reference handbook, Human Integration Design Handbook (HIDH), was developed to capture the design consideration information from NASA-STD-3000, and adds spaceflight lessons learned, gaps in knowledge, example solutions, and suggests research to further mature specific disciplines. The HIDH serves two major purposes: HIDH is the reference document for writing human factors requirements for specific systems. HIDH contains design guidance information that helps insure that designers create systems which safely and effectively accommodate the capabilities and limitations of space flight crews.

  13. Infants' Responses to Real Humans and Representations of Humans

    ERIC Educational Resources Information Center

    Heron, Michelle; Slaughter, Virginia

    2010-01-01

    Infants' responses to typical and scrambled human body shapes were assessed in relation to the realism of the human body stimuli presented. In four separate experiments, infants were familiarized to typical human bodies and then shown a series of scrambled human bodies on the test. Looking behaviour was assessed in response to a range of different…

  14. Inhaled human insulin.

    PubMed

    Strack, Thomas R

    2006-04-01

    The benefit of subcutaneous insulin therapy in patients with diabetes is frequently limited due to difficulty in convincing patients of the importance of multiple daily insulin injections to cope effectively with meal-associated glycemic changes. Thus, the aim of achieving tight glycemic control, which is critical for reducing the risk of long-term diabetes-related complications, frequently remains elusive. The successful development of an inhalable insulin as a noninvasive alternative promises to change the management of diabetes. The first product to become available to patients is inhaled human insulin, a dry-powder formulation packaged into discrete blisters containing 1 or 3 mg of dry-powder human insulin and administered via a unique pulmonary inhaler device. It has recently been approved in both the United States and the European Union for the control of hyperglycemia in adult patients with type 1 or type 2 diabetes. The pharmacokinetic profile of inhaled human insulin closely mimics the natural pattern of insulin secretion, and resembles that of rapid-acting subcutaneous analogs. Similarly to rapid-acting subcutaneous analogs, inhaled human insulin has a more rapid onset of glucose-lowering activity compared to subcutaneous regular insulin, allowing it to be administered shortly before meals. It has a duration of glucose-lowering activity comparable to subcutaneous regular insulin and longer than rapid-acting insulin analogs. Inhaled human insulin effectively controls postprandial glucose concentrations in patients with type 1 or type 2 diabetes without increasing the risk of hypoglycemia, and even improves fasting glucose levels compared to subcutaneous insulin. Inhaled human insulin has an overall favorable safety profile. There are small reductions in lung function (1-1.5% of total lung forced expiratory volume in the first second [FEV1] capacity) after onset of treatment that are reversible in most patients if treatment is discontinued. Inhaled human

  15. Why Geo-Humanities

    NASA Astrophysics Data System (ADS)

    Graells, Robert Casals i.; Sibilla, Anna; Bohle, Martin

    2016-04-01

    Anthropogenic global change is a composite process. It consists of societal processes (in the 'noosphere') and natural processes (in the 'bio-geosphere'). The 'noosphere' is the ensemble of social, cultural or political insights ('shared subjective mental concepts') of people. Understanding the composite of societal and natural processes ('human geo-biosphere intersections'), which shapes the features of anthropogenic global change, would benefit from a description that draws equally on natural sciences, social sciences and humanities. To that end it is suggested to develop a concept of 'geo-humanities': This essay presents some aspects of its scope, discussing "knowledge that is to manage", "intentions that are to shape", "choices that are to justify" and "complexity that is to handle". Managing knowledge: That people understand anthropogenic global change requires their insights into how 'human geosphere intersections' function. Insights are formed ('processed') in the noosphere by means of interactions between people. Understanding how 'human geosphere intersections' functions combines scientific, engineering and economic studies with studies of the dynamics of the noosphere. Shaping intentions: During the last century anthropogenic global change developed as the collateral outcome of humankind's accumulated actions. It is caused by the number of people, the patterns of their consumption of resources, and the alterations of their environments. Nowadays, anthropogenic global chance is either an intentional negligence or a conscious act. Justifying choices: Humanity has alternatives how to alter Earth at planetary scale consciously. For example, there is a choice to alter the geo-biosphere or to adjust the noosphere. Whatever the choice, it will depend on people's world-views, cultures and preferences. Thus beyond issues whether science and technology are 'sound' overarching societal issues are to tackle, such as: (i) how to appropriate and distribute natural

  16. [Human cloning or cannibalism].

    PubMed

    Sokolowski, L M

    2001-01-01

    In this article I develop the idea presented in my previous work that human cloning would be of little practical use since almost any aim that one would like to attain by multiple cloning of a concrete man or a group of people, are unattainable or it might be achieved by easier, cheaper and more efficient traditional methods. For this reason cloning of a man is unlikely to occur on a larger scale and only few people will decide to clone themselves. In this sense no social effects of human cloning will be disastrous for the human population. Yet investigations in human genetics are very important since they may provide medical applications far more important than human cloning. It is argued that the main trend of modern medicine: organ transplantation from an alien donor, will become socially dangerous in near future since the number of donors will be drastically smaller than the number of potential patients waiting for transplantations. This in turn may cause social conflicts and a form of medical cannibalism may arise. These problems and conflicts will be avoided if organ transplantation from an alien donor is replaced by organ cloning, i.e. by transplanting an organ developed from the patient.

  17. Human HOX gene disorders.

    PubMed

    Quinonez, Shane C; Innis, Jeffrey W

    2014-01-01

    The Hox genes are an evolutionarily conserved family of genes, which encode a class of important transcription factors that function in numerous developmental processes. Following their initial discovery, a substantial amount of information has been gained regarding the roles Hox genes play in various physiologic and pathologic processes. These processes range from a central role in anterior-posterior patterning of the developing embryo to roles in oncogenesis that are yet to be fully elucidated. In vertebrates there are a total of 39 Hox genes divided into 4 separate clusters. Of these, mutations in 10 Hox genes have been found to cause human disorders with significant variation in their inheritance patterns, penetrance, expressivity and mechanism of pathogenesis. This review aims to describe the various phenotypes caused by germline mutation in these 10 Hox genes that cause a human phenotype, with specific emphasis paid to the genotypic and phenotypic differences between allelic disorders. As clinical whole exome and genome sequencing is increasingly utilized in the future, we predict that additional Hox gene mutations will likely be identified to cause distinct human phenotypes. As the known human phenotypes closely resemble gene-specific murine models, we also review the homozygous loss-of-function mouse phenotypes for the 29 Hox genes without a known human disease. This review will aid clinicians in identifying and caring for patients affected with a known Hox gene disorder and help recognize the potential for novel mutations in patients with phenotypes informed by mouse knockout studies.

  18. The Human Serum Metabolome

    PubMed Central

    Psychogios, Nikolaos; Hau, David D.; Peng, Jun; Guo, An Chi; Mandal, Rupasri; Bouatra, Souhaila; Sinelnikov, Igor; Krishnamurthy, Ramanarayan; Eisner, Roman; Gautam, Bijaya; Young, Nelson; Xia, Jianguo; Knox, Craig; Dong, Edison; Huang, Paul; Hollander, Zsuzsanna; Pedersen, Theresa L.; Smith, Steven R.; Bamforth, Fiona; Greiner, Russ; McManus, Bruce; Newman, John W.; Goodfriend, Theodore; Wishart, David S.

    2011-01-01

    Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca. PMID:21359215

  19. Human hybrid hybridoma

    SciTech Connect

    Tiebout, R.F.; van Boxtel-Oosterhof, F.; Stricker, E.A.M.; Zeijlemaker, W.P.

    1987-11-15

    Hybrid hybridomas are obtained by fusion of two cells, each producing its own antibody. Several authors have reported the construction of murine hybrid hybridomas with the aim to obtain bispecific monoclonal antibodies. The authors have investigated, in a model system, the feasibility of constructing a human hybrid hybridoma. They fused two monoclonal cell lines: an ouabain-sensitive and azaserine/hypoxanthine-resistant Epstein-Barr virus-transformed human cell line that produces an IgG1kappa antibody directed against tetanus toxiod and an azaserine/hypoxanthine-sensitive and ouabain-resistant human-mouse xenohybrid cell line that produces a human IgG1lambda antibody directed against hepatitis-B surface antigen. Hybrid hybridoma cells were selected in culture medium containing azaserine/hypoxanthine and ouabain. The hybrid nature of the secreted antibodies was analyzed by means of two antigen-specific immunoassay. The results show that it is possible, with the combined use of transformation and xenohybridization techniques, to construct human hybrid hybridomas that produce bispecific antibodies. Bispecific antibodies activity was measured by means of two radioimmunoassays.

  20. Healthy human gut phageome

    PubMed Central

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; van der Oost, John; de Vos, Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20–50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health. PMID:27573828

  1. Human occupancy detection

    NASA Astrophysics Data System (ADS)

    Brown, David A.

    1994-10-01

    In the area of security and surveillance technologies, the problem of the arrival in Canada of illegal and undesirable ship and truck cargo loads is steadily increasing. As the volumes of cargo arrivals increase so do the Immigration and Customs problems related to the determination of the validity of those cargo contents. Of special concern to Immigration Control Authorities around the world is the emerging and increasing trend of illegal smuggling of human beings hidden inside of shipping containers. Beginning in 1992, Immigration Control Authorities in Canada observed an escalation of alien people smuggling through the use of cargo shipping containers arriving in the Port of Montreal. This paper will present to the audience the recently completed Immigration Canada Human Occupancy Detection project by explaining the design, development and testing of human occupancy detectors. The devices are designed to electronically detect the presence of persons hiding inside of shipping containers, without the requirement of opening the container doors. The human occupancy detection concepts are based upon the presence of carbon dioxide or other human waste characteristics commonly found inside of shipping containers.

  2. The Human Genome Program

    SciTech Connect

    Bell, G.I.

    1989-01-01

    Early in 1986, Charles DeLisi, then head of the Office of Health and Environmental Research at the Department of Energy (DOE) requested the Los Alamos National Laboratory (LANL) to organize a workshop charged with inquiring whether the state of technology and potential payoffs in biological knowledge and medical practice were such as to justify an organized program to map and sequence the human genome. The DOE's interest arose from its mission to assess the effects of radiation and other products of energy generation on human health in general and genetic material in particular. The workshop concluded that the technology was ripe, the benefits would be great, and a national program should be promptly initiated. Later committees, reporting to DOE, to the NIH, to the Office of Technology Assessment of the US Congress, and to the National Academy of Science have reviewed these issues more deliberately and come to the same conclusion. As a consequence, there has been established in the United States, a Human Genome Program, with funding largely from the NIH and the DOE, as indicated in Table 1. Moreover, the Program has attracted international interest, and Great Britain, France, Italy, and the Soviet Union, among other countries, have been reported to be starting human genome initiatives. Coordination of these programs, clearly in the interests of each, remains to be worked out, although an international Human Genome Organization (HUGO) is considering such coordination. 5 refs., 1 fig., 2 tabs.

  3. Human herpesvirus 6.

    PubMed Central

    Braun, D K; Dominguez, G; Pellett, P E

    1997-01-01

    Human herpesvirus 6 variant A (HHV-6A) and human herpesvirus 6 variant B (HHV-6B) are two closely related yet distinct viruses. These visuses belong to the Roseolovirus genus of the betaherpesvirus subfamily; they are most closely related to human herpesvirus 7 and then to human cytomegalovirus. Over 95% of people older than 2 years of age are seropositive for either or both HHV-6 variants, and current serologic methods are incapable of discriminating infection with one variant from infection with the other. HHV-6A has not been etiologically linked to any human disease, but such an association will probably be found soon. HHV-6B is the etiologic agent of the common childhood illness exanthem subitum (roseola infantum or sixth disease) and related febrile illnesses. These viruses are frequently active and associated with illness in immunocompromised patients and may play a role in the etiology of Hodgkin's disease and other malignancies. HHV-6 is a commensal inhabitant of brains; various neurologic manifestations, including convulsions and encephalitis, can occur during primary HHV-6 infection or in immunocompromised patients. HHV-6 and distribution in the central nervous system are altered in patients with multiple sclerosis; the significance of this is under investigation. PMID:9227865

  4. The Exploration of Mars by Humans: Why Mars? Why Humans?

    NASA Technical Reports Server (NTRS)

    Levine, Joel S.

    2011-01-01

    As we commemorate the 50th anniversary of Yuri Gagarin's historic flight in 1961, the first flight of a human in space, plans are underway for another historic human mission. Plans are being developed for a human mission to Mars. Once we reach Mars, the human species will become the first two-planet species. Both the Bush Administration (in 2004) and the Obama Administration (in 2010) proposed a human mission to Mars as a national goal of the United States.

  5. Human Modeling For Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    Tran, Donald; Stambolian, Damon; Henderson, Gena; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over that last few years using human modeling for human factors engineering analysis for design of spacecraft and launch vehicles. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the different types of human modeling used currently and in the past at Kennedy Space Center (KSC) currently, and to explain the future plans for human modeling for future spacecraft designs.

  6. Human Modeling for Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    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

  7. Human immune system variation

    PubMed Central

    Brodin, Petter; Davis, Mark M.

    2017-01-01

    The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual’s immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases. PMID:27916977

  8. Reflections on humanizing biomedicine.

    PubMed

    Marcum, James A

    2008-01-01

    Although biomedicine is responsible for the "miracles" of modern medicine, paradoxically it has also led to a quality-of-care crisis in which many patients feel disenfranchised from the health-care industry. To address this crisis, several medical commentators make an appeal for humanizing biomedicine, which has led to shifts in the philosophical boundaries of medical knowledge and practice. In this paper, the metaphysical, epistemological, and ethical boundaries of biomedicine and its humanized versions are investigated and compared to one another. Biomedicine is founded on a metaphysical position of mechanistic monism, an epistemology of objective knowing, and an ethic of emotionally detached concern. In humanizing modern medicine, these boundaries are often shifted to a metaphysical position of dualism/holism, an epistemology of subject knowing, and an ethic of empathic care. In a concluding section, the question is discussed whether these shifts in the philosophical boundaries are adequate to resolve the quality-of-care crisis.

  9. Abortion and human rights.

    PubMed

    Shaw, Dorothy

    2010-10-01

    Abortion has been a reality in women's lives since the beginning of recorded history, typically with a high risk of fatal consequences, until the last century when evolutions in the field of medicine, including techniques of safe abortion and effective methods of family planning, could have ended the need to seek unsafe abortion. The context of women's lives globally is an important but often ignored variable, increasingly recognised in evolving human rights especially related to gender and reproduction. International and regional human rights instruments are being invoked where national laws result in violations of human rights such as health and life. The individual right to conscientious objection must be respected and better understood, and is not absolute. Health professional organisations have a role to play in clarifying responsibilities consistent with national laws and respecting reproductive rights. Seeking common ground using evidence rather than polarised opinion can assist the future focus.

  10. Human nutrition: evolutionary perspectives.

    PubMed

    Barnicot, N A

    2005-01-01

    In recent decades, much new evidence relating to the ape forerunners of modern humans has come to hand and diet appears to be an important factor. At some stage, there must have been a transition from a largely vegetarian ape diet to a modern human hunting economy providing significant amounts of meat. On an even longer evolutionary time scale the change was more complex. The mechanisms of evolutionary change are now better understood than they were in Darwin's time, thanks largely to great advances in genetics, both experimental and theoretical. It is virtually certain that diet, as a major component of the human environment, must have exerted evolutionary effects, but researchers still have little good evidence.

  11. Human-Robot Interaction

    NASA Technical Reports Server (NTRS)

    Rochlis-Zumbado, Jennifer; Sandor, Aniko; Ezer, Neta

    2012-01-01

    Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI) is a new Human Research Program (HRP) risk. HRI is a research area that seeks to understand the complex relationship among variables that affect the way humans and robots work together to accomplish goals. The DRP addresses three major HRI study areas that will provide appropriate information for navigation guidance to a teleoperator of a robot system, and contribute to the closure of currently identified HRP gaps: (1) Overlays -- Use of overlays for teleoperation to augment the information available on the video feed (2) Camera views -- Type and arrangement of camera views for better task performance and awareness of surroundings (3) Command modalities -- Development of gesture and voice command vocabularies

  12. Teleoperator Human Factors Study

    NASA Technical Reports Server (NTRS)

    1986-01-01

    An investigation of the spectrum of space teleoperation activities likely in the 1985 to 1995 decade focused on the resolution of critical human engineering issues and characterization of the technology effect on performance of remote human operators. The study began with the identification and documentation of a set of representative reference teleoperator tasks. For each task, technology, development, and design options, issues, and alternatives that bear on human operator performance were defined and categorized. A literature survey identified existing studies of man/machine issues. For each teleoperations category, an assessment was made of the state of knowledge on a scale from adequate to void. The tests, experiments, and analyses necessary to provide the missing elements of knowledge were then defined. A limited set of tests were actually performed, including operator selection, baseline task definition, control mode study, lighting study, camera study, and preliminary time delay study.

  13. Preparing for Human Exploration

    NASA Technical Reports Server (NTRS)

    Drake, Bret G.; Joosten, B. Kent

    1998-01-01

    NASA's Human Exploration and Development of Space (HEDS) Enterprise is defining architectures and requirements for human exploration that radically reduce the costs of such missions through the use of advanced technologies, commercial partnerships and innovative systems strategies. In addition, the HEDS Enterprise is collaborating with the Space Science Enterprise to acquire needed early knowledge about Mars and to demonstrate critical technologies via robotic missions. This paper provides an overview of the technological challenges facing NASA as it prepares for human exploration. Emphasis is placed on identifying the key technologies including those which will provide the most return in terms of reducing total mission cost and/or reducing potential risk to the mission crew. Top-level requirements are provided for those critical enabling technology options currently under consideration.

  14. Helicopter human factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  15. Cardiovascular Deconditioning in Humans: Human Studies Core

    NASA Technical Reports Server (NTRS)

    Williams, Gordon

    1999-01-01

    Major cardiovascular problems, secondary to cardiovascular deconditioning, may occur on extended space missions. While it is generally assumed that the microgravity state is the primary cause of cardiovascular deconditioning, sleep deprivation and disruption of diurnal rhythms may also play an important role. Factors that could be modified by either or both of these perturbations include: autonomic function and short-term cardiovascular reflexes, vasoreactivity, circadian rhythm of cardiovascular hormones (specifically the renin-angiotensin system) and renal sodium handling and hormonal influences on that process, venous compliance, cardiac mass, and cardiac conduction processes. The purpose of the Human Studies Core is to provide the infrastructure to conduct human experiments which will allow for the assessment of the likely role of such factors in the space travel associated cardiovascular deconditioning process and to develop appropriate countermeasures. The Core takes advantage of a newly-created Intensive Physiologic Monitoring (IPM) Unit at the Brigham and Women's Hospital, Boston, MA, to perform these studies. The Core includes two general experimental protocols. The first protocol involves a head down tilt bed-rest study to simulate microgravity. The second protocol includes the addition of a disruption of circadian rhythms to the simulated microgravity environment. Before and after each of these environmental manipulations, the subjects will undergo acute stressors simulating changes in volume and/or stress, which could occur in space and on return to Earth. The subjects are maintained in a rigidly controlled environment with fixed light/dark cycles, activity pattern, and dietary intake of nutrients, fluids, ions and calories.

  16. The Human Centrifuge

    NASA Astrophysics Data System (ADS)

    van Loon, Jack J. W. A.

    2009-01-01

    Life on Earth has developed at unit gravity, 9.81 m/s2, which was a major factor especially when vertebrates emerged from water onto land in the late Devonian, some 375 million years ago. But how would nature have evolved on a larger planet? We are able to address this question simply in experiments using centrifuges. Based on these studies we have gained valuable insights in the physiological process in plants and animals. They adapt to a new steady state suitable for the high-g environments applied. Information on mammalian adaptations to hyper-g is interesting or may be even vital for human space exploration programs. It has been shown in long duration animal hypergravity studies, ranging from snails, rats to primates, that various structures like muscles, bones, neuro-vestibular, or the cardio-vascular system are affected. However, humans have never been exposed to a hyper-g environment for long durations. Centrifuge studies involving humans are mostly in the order of hours. The current work on human centrifuges are all focused on short arm systems to apply short periods of artificial gravity in support of long duration space missions in ISS or to Mars. In this paper we will address the possible usefulness of a large human centrifuge on Earth. In such a centrifuge a group of humans can be exposed to hypergravity for, in principle, an unlimited period of time like living on a larger planet. The input from a survey under scientists working in the field of gravitational physiology, but also other disciplines, will be discussed.

  17. Human dignity and human tissue: a meaningful ethical relationship?

    PubMed

    Kirchhoffer, David G; Dierickx, Kris

    2011-09-01

    Human dignity has long been used as a foundational principle in policy documents and ethical guidelines intended to govern various forms of biomedical research. Despite the vast amount of literature concerning human dignity and embryonic tissues, the majority of biomedical research uses non-embryonic human tissue. Therefore, this contribution addresses a notable lacuna in the literature: the relationship, if any, between human dignity and human tissue. This paper first elaborates a multidimensional understanding of human dignity that overcomes many of the shortcomings associated with the use of human dignity in other ethical debates. Second, it discusses the relationship between such an understanding of human dignity and 'non-embryonic' human tissue. Finally, it considers the implications of this relationship for biomedical research and practice involving human tissue. The contribution demonstrates that while human tissue cannot be said to have human dignity, human dignity is nevertheless implicated by human tissue, making what is done with human tissue and how it is done worthy of moral consideration.

  18. Ayahuasca and human destiny.

    PubMed

    McKenna, Dennis J

    2005-06-01

    In this essay, the author shares his personal reflections gleaned from a lifetime of research with ayahuasca, and speculates on the societal, political, planetary, and evolutionary implications of humanity's aeons-old symbiosis with this shamanic plant. The thesis is developed that at this critical historical juncture, ayahuasca has developed a strategy to broadcast its message to a wider world--a reflection of the urgent need to avert global ecological catastrophe. While ayahuasca has much to teach us, the critical question is, will humanity hear it, and heed it, in time?

  19. Human MSH2 protein

    DOEpatents

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    1997-01-01

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  20. Human MSH2 protein

    DOEpatents

    Chapelle, A. de la; Vogelstein, B.; Kinzler, K.W.

    1997-01-07

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error{sup +} (RER{sup +}) tumor cells. 19 figs.

  1. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1989-01-01

    The nation's efforts to expand human presence and activity beyond Earth orbit into the solar system was given renewed emphasis in January of 1988 when the Presidential Directive on National Space Policy was signed into effect. The expansion of human presence into the solar system has particular significance, in that it defines long-range goals for NASA's future missions. To embark and achieve such ambitious ventures is a significant undertaking, particularly compared to past space activities. Missions to Mars, the Moon, and Phobos, as well as an observatory based on the dark side of the Moon are discussed.

  2. We Are Human Beings.

    PubMed

    McGee, Andrew

    2016-04-01

    In this paper, I examine Jeff McMahan's arguments for his claim that we are not human organisms, and the arguments of Derek Parfit to the same effect in a recent paper. McMahan uses these arguments to derive conclusions concerning the moral status of embryos and permanent vegetative state (PVS) patients. My claim will be that neither thinker has successfully shown that we are not human beings, and therefore these arguments do not establish the ethical conclusions that McMahan has sought to draw from the arguments in respect of the moral status of embryos and PVS patients.

  3. Defining the Human Microbiome

    PubMed Central

    Ursell, Luke K; Metcalf, Jessica L; Parfrey, Laura Wegener; Knight, Rob

    2012-01-01

    Rapidly developing sequencing methods and analytical techniques are enhancing our ability to understand the human microbiome, and, indeed, how we define the microbiome and its constituents. In this review we highlight recent research that expands our ability to understand the human microbiome on different spatial and temporal scales, including daily timeseries datasets spanning months. Furthermore, we discuss emerging concepts related to defining operational taxonomic units, diversity indices, core versus transient microbiomes and the possibility of enterotypes. Additional advances in sequencing technology and in our understanding of the microbiome will provide exciting prospects for exploiting the microbiota for personalized medicine. PMID:22861806

  4. Human Factors Model

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  5. On human health.

    PubMed

    van Spijk, Piet

    2015-05-01

    If it is true that health is a priority objective of medicine, then medical practice can only be successful if the meaning of the term "health" is known. Various attempts have been made over the years to define health. This paper proposes a new definition. In addition to current health concepts, it also takes into account the distinction between specifically human (great) health and health as the absence of disease and illness-i.e. small health. The feeling of leading a life that makes sense plays a key role in determining specifically human great health.

  6. Disorders of Human Hemoglobin

    NASA Astrophysics Data System (ADS)

    Bank, Arthur; Mears, J. Gregory; Ramirez, Francesco

    1980-02-01

    Studies of the human hemoglobin system have provided new insights into the regulation of expression of a group of linked human genes, the γ -δ -β globin gene complex in man. In particular, the thalassemia syndromes and related disorders of man are inherited anemias that provide mutations for the study of the regulation of globin gene expression. New methods, including restriction enzyme analysis and cloning of cellular DNA, have made it feasible to define more precisely the structure and organization of the globin genes in cellular DNA. Deletions of specific globin gene fragments have already been found in certain of these disorders and have been applied in prenatal diagnosis.

  7. We Are Human Beings

    PubMed Central

    McGee, Andrew

    2016-01-01

    In this paper, I examine Jeff McMahan’s arguments for his claim that we are not human organisms, and the arguments of Derek Parfit to the same effect in a recent paper. McMahan uses these arguments to derive conclusions concerning the moral status of embryos and permanent vegetative state (PVS) patients. My claim will be that neither thinker has successfully shown that we are not human beings, and therefore these arguments do not establish the ethical conclusions that McMahan has sought to draw from the arguments in respect of the moral status of embryos and PVS patients. PMID:26810918

  8. Mapping Human Epigenomes

    PubMed Central

    Rivera, Chloe M.; Ren, Bing

    2013-01-01

    As the second dimension to the genome, the epigenome contains key information specific to every type of cells. Thousands of human epigenome maps have been produced in recent years thanks to rapid development of high throughput epigenome mapping technologies. In this review, we discuss the current epigenome mapping toolkit and utilities of epigenome maps. We focus particularly on mapping of DNA methylation, chromatin modification state and chromatin structures, and emphasize the use of epigenome maps to delineate human gene regulatory sequences and developmental programs. We also provide a perspective on the progress of the epigenomics field and challenges ahead. PMID:24074860

  9. Sacred Sounds in the Humanities.

    ERIC Educational Resources Information Center

    Kelly, Robert A.

    To see literature as a sign and a symbol simply reasserts the view of the humanities as the embodiment of the highest aspirations of human nature. Human beings are sign givers and symbol makers as they look for the sacred meaning in their lives. Through a college humanities course, some of the symbols that artists employ in fiction, poetry, drama,…

  10. Human Challenges in Exploration Missions

    NASA Technical Reports Server (NTRS)

    Lloyd, Charles W.

    2007-01-01

    This viewgraph presents an overview using pictures some of the history of human exploration of the new frontiers of Earth and then examines some of the challenges to human exploration of space. Particular attention is given to the environmental factors and to the social and human factors that effect humans in space environments.

  11. Human Rights: The Essential Reference.

    ERIC Educational Resources Information Center

    Devine, Carol; Hansen, Carol Rae; Wilde, Ralph; Bronkhorst, Daan; Moritz, Frederic A.; Rolle, Baptiste; Sherman, Rebecca; Southard, Jo Lynn; Wilkinson, Robert; Poole, Hilary, Ed.

    This reference work documents the history of human rights theory, explains each article of the Universal Declaration of Human Rights, explores the contemporary human rights movement, and examines the major human rights issues facing the world today. This book is the first to combine historical and contemporary perspectives on these critical…

  12. Making IBM's Computer, Watson, Human

    ERIC Educational Resources Information Center

    Rachlin, Howard

    2012-01-01

    This essay uses the recent victory of an IBM computer (Watson) in the TV game, "Jeopardy," to speculate on the abilities Watson would need, in addition to those it has, to be human. The essay's basic premise is that to be human is to behave as humans behave and to function in society as humans function. Alternatives to this premise are considered…

  13. ANTHROPOMETRY AND HUMAN ENGINEERING.

    DTIC Science & Technology

    de l’armee de l’air francaise; Sheldon types and success in flight performance; Adapting the aeroplane to the pilot; Instrument dials, instrument...establishment of a longitudinal study of the medical and psychological aspects of the U.S. naval aviator; Somatotyping ; Human factors in aircraft design.

  14. Who Hung the Humanities?

    ERIC Educational Resources Information Center

    Lambert, David

    2013-01-01

    This paper is partly based on a lecture given at the AGTA conference in Perth in January 2013. It argues for a progressive subject based curriculum in which geography plays an essential part. This is based on an analysis of why and how subjects like geography, as part of the humanities, have been undermined and diminished in recent times. In a way…

  15. Occupying the Digital Humanities

    ERIC Educational Resources Information Center

    Rice, Jeff

    2013-01-01

    This essay questions the digital humanities' dependence on interpretation and critique as strategies for reading and responding to texts. Instead, the essay proposes suggestion as a digital rhetorical practice, one that does not replace hermeneutics, but instead offers alternative ways to respond to texts. The essay uses the Occupy movement as an…

  16. The Humanities, Unraveled

    ERIC Educational Resources Information Center

    Berube, Michael

    2013-01-01

    Graduate education in the humanities is in crisis. Every aspect, from the most specific details of the curriculum to the broadest questions about its purpose, is in crisis. It is a seamless garment of crisis: If one pulls on any one thread, the entire thing unravels. It is therefore exceptionally difficult to discuss any one aspect of graduate…

  17. Neurobiology and the Humanities

    PubMed Central

    Zeki, Semir

    2014-01-01

    Can the arts and humanities contribute significantly to the study of the brain? Similar brain processes are involved in humanistic and scientific inference, and in this essay, I argue that conclusions reached by one are relevant to the other. PMID:25277451

  18. Radar: Human Safety Net

    ERIC Educational Resources Information Center

    Ritz, John M.

    2016-01-01

    Radar is a technology that can be used to detect distant objects not visible to the human eye. A predecessor of radar, called the telemobiloscope, was first used to detect ships in the fog in 1904 off the German coast. Many scientists have worked on the development and refinement of radar (Hertz with electromagnetic waves; Popov with determining…

  19. Negative Human Interaction

    ERIC Educational Resources Information Center

    Brannan, John M.

    1972-01-01

    This study is an effort to examine man's most negative experiences as he perceives them. The results indicated that teachers were involved more often than any other person in the most negative experience reported. Improved human relations skills are clearly indicated for those in higher education as well as in public schools. (Author)

  20. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

  1. The Humanities and Leadership.

    ERIC Educational Resources Information Center

    Gardner, John W.; And Others

    1985-01-01

    Five individuals discuss the relationship of the humanities and leadership in different contexts: the liberal arts (John W. Gardner); the sculpting of a statue of James Madison (Walker Hancock); the Kennedy years (Thomas R. West), our civic culture (Bruce Adams); and liberal education (Gregory S. Prince, Jr.). (MSE)

  2. Humanizing the Workplace.

    ERIC Educational Resources Information Center

    Fairfield, Roy P., Ed.

    A series of essays discussing ideas about humanizing work are presented in the document. Three major sections divide the essays, and each includes a preface with comments suggesting the central focus and questions with which the authors are concerned. The first section deals with the history, philosophy, and issues related to work and contains…

  3. Medicine and the Humanities.

    ERIC Educational Resources Information Center

    Pabst, Diana

    1992-01-01

    Discusses a Pennsylvania State University seminar program designed to help medical professionals explore aspects of medical treatment through readings in the humanities. Argues that the program is broader in vision and scope that other medical ethics courses. Suggests that the effort can refresh and deepen doctors' work with patients. (SG)

  4. Humanizing the Secondary School.

    ERIC Educational Resources Information Center

    Hamilton, Norman K., Ed.; Saylor, J. Galen, Ed.

    These papers, presented during ASCD-sponsored conference, confront educators with issues in and alternatives for making secondary schools a more humanizing experience for students. The contributors and their articles are: Norman K. Hamilton, "Alternatives in Secondary Education"; Thornton B. Monez and Norman L. Bussiere, "The High School in Human…

  5. Human Babesiosis, Bolivia, 2013

    PubMed Central

    Gabrielli, Simona; Totino, Valentina; Macchioni, Fabio; Zuñiga, Freddy; Rojas, Patricia; Lara, Yuni; Roselli, Mimmo; Cancrini, Gabriella

    2016-01-01

    To investigate human babesiosis in the Bolivian Chaco, in 2013 we tested blood samples from 271 healthy persons living in 2 rural communities in this region. Microscopy and PCR indicated that 3.3% of persons were positive for Babesia microti parasites (US lineage); seroprevalence was 45.7%. Appropriate screening should mitigate the risk for transfusion-associated babesiosis. PMID:27434696

  6. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  7. Human Development Student Modules.

    ERIC Educational Resources Information Center

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This set of 61 student learning modules deals with various topics pertaining to human development. The modules, which are designed for use in performance-based vocational education programs, each contain the following components: an introduction for the student, a performance objective, a variety of learning activities, content information, a…

  8. Human chromosome 8.

    PubMed Central

    Wood, S

    1988-01-01

    The role of human chromosome 8 in genetic disease together with the current status of the genetic linkage map for this chromosome is reviewed. Both hereditary genetic disease attributed to mutant alleles at gene loci on chromosome 8 and neoplastic disease owing to somatic mutation, particularly chromosomal translocations, are discussed. PMID:3070042

  9. Animal and Human Communication.

    ERIC Educational Resources Information Center

    Rummel, Lynda

    Several misconceptions regarding the status of human communication systems relative to the systems of other animals are discussed in this paper. Arguments are offered supporting the expansion of the communication discipline to include the study of the communication systems of other species. The "communicative continuity" view which ranks…

  10. Futures of Human Communication.

    ERIC Educational Resources Information Center

    Harms, L. S.

    There are several research areas basic to the long-range future of human communications. Telecommunication and transportation offer the possiblity of two worldwide communications networks whose interrelationships need to be explored in terms of the needs of the individual, the community, and the world at large. Expanding possibilities of…

  11. Humans as Lie Detectors.

    ERIC Educational Resources Information Center

    DePaulo, Bella; And Others

    1980-01-01

    Discusses several studies of whether and how well humans can detect lies. Examines the accuracy of such persons as well as the process of how they actually detect lies, how they think they detect lies, and whether the actual and perceived processes of lie detection correspond to one another. (JMF)

  12. Humanism in Education

    ERIC Educational Resources Information Center

    Armstrong, Michael

    2015-01-01

    This is the text of Michael Armstrong's address to the Brian Simon Centenary conference, held at the Institute of Education on 26 March 2015. Michael Armstrong celebrates the humanism that underlay Brian's belief in a common system of education, democratic and non-selective, and finds its counterpart in the creative practice of school children.

  13. Humanizing science education

    NASA Astrophysics Data System (ADS)

    Donnelly, James F.

    2004-09-01

    This paper argues that the diverse curriculum reform agendas associated with science education are strongly and critically associated with the educational characteristics of the humanities. The article begins with a survey of interpretations of the distinctive contribution which the humanities make to educational purposes. From this survey four general characteristics of the humanities are identified: an appeal to an autonomous self with the right and capacity to make independent judgements and interpretations; indeterminacy in the subject matter of these judgements and interpretations; a focus on meaning, in the context of human responses, actions, and relationships, and especially on the ethical, aesthetic, and purposive; and finally, the possibility of commonality in standards of judgement and interpretation, under conditions of indeterminacy. Inquiry and science technology and society (STS) orientated curriculum development agendas within science education are explored in the light of this analysis. It is argued that the four characteristics identified are central to the educational purposes of these and other less prominent modes of curriculum development in science, though not unproblematically so. In the light of this discussion the prognosis and challenges for science curriculum development are explored.

  14. Biotechnologies and Human Dignity

    ERIC Educational Resources Information Center

    Sweet, William; Masciulli, Joseph

    2011-01-01

    In this article, the authors review some contemporary cases where biotechnologies have been employed, where they have had global implications, and where there has been considerable debate. The authors argue that the concept of dignity, which lies at the center of such documents as the 2005 Universal Declaration on Bioethics and Human Rights, the…

  15. Human Learning and Memory

    ERIC Educational Resources Information Center

    Lieberman, David A.

    2012-01-01

    This innovative textbook is the first to integrate learning and memory, behaviour, and cognition. It focuses on fascinating human research in both memory and learning (while also bringing in important animal studies) and brings the reader up to date with the latest developments in the subject. Students are encouraged to think critically: key…

  16. Human Memory: The Basics

    ERIC Educational Resources Information Center

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  17. The Human Toxome Project

    EPA Science Inventory

    The Human Toxome project, funded as an NIH Transformative Research grant 2011--‐ 2016, is focused on developing the concepts and the means for deducing, validating, and sharing molecular Pathways of Toxicity (PoT). Using the test case of estrogenic endocrine disruption, the respo...

  18. Marketing Human Resource Development.

    ERIC Educational Resources Information Center

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  19. Fighting for Human Rights

    ERIC Educational Resources Information Center

    Ong, Bao

    2011-01-01

    Speak Truth To Power consists of 17 teacher-developed lessons based on the stories of rights advocates from all over the world. The lessons were created for sixth-through 12th-grade students, and have come to New York schools thanks to the Robert F. Kennedy Center for Justice and Human Rights and the New York State United Teachers union. Speak…

  20. Predictors of human rotation.

    PubMed

    Stochl, Jan; Croudace, Tim

    2013-01-01

    Why some humans prefer to rotate clockwise rather than anticlockwise is not well understood. This study aims to identify the predictors of the preferred rotation direction in humans. The variables hypothesised to influence rotation preference include handedness, footedness, sex, brain hemisphere lateralisation, and the Coriolis effect (which results from geospatial location on the Earth). An online questionnaire allowed us to analyse data from 1526 respondents in 97 countries. Factor analysis showed that the direction of rotation should be studied separately for local and global movements. Handedness, footedness, and the item hypothesised to measure brain hemisphere lateralisation are predictors of rotation direction for both global and local movements. Sex is a predictor of the direction of global rotation movements but not local ones, and both sexes tend to rotate clockwise. Geospatial location does not predict the preferred direction of rotation. Our study confirms previous findings concerning the influence of handedness, footedness, and sex on human rotation; our study also provides new insight into the underlying structure of human rotation movements and excludes the Coriolis effect as a predictor of rotation.

  1. Parasites and human evolution.

    PubMed

    Perry, George H

    2014-01-01

    Our understanding of human evolutionary and population history can be advanced by ecological and evolutionary studies of our parasites. Many parasites flourish only in the presence of very specific human behaviors and in specific habitats, are wholly dependent on us, and have evolved with us for thousands or millions of years. Therefore, by asking when and how we first acquired those parasites, under which environmental and cultural conditions we are the most susceptible, and how the parasites have evolved and adapted to us and we in response to them, we can gain considerable insight into our own evolutionary history. As examples, the tapeworm life cycle is dependent on our consumption of meat, the divergence of body and head lice may have been subsequent to the development of clothing, and malaria hyperendemicity may be associated with agriculture. Thus, the evolutionary and population histories of these parasites are likely intertwined with critical aspects of human biology and culture. Here I review the mechanics of these and multiple other parasite proxies for human evolutionary history and discuss how they currently complement our fossil, archeological, molecular, linguistic, historical, and ethnographic records. I also highlight potential future applications of this promising model for the field of evolutionary anthropology.

  2. Antihumanism in the Humanities.

    ERIC Educational Resources Information Center

    Schwartz, Joel

    1990-01-01

    Analyzes the antihumanistic elements of Jacques Derrida's theory of deconstruction. Argues that the modern French intellectuals, including Foucault, Derrida, and Lacan, have had an antihumanistic effect on the American social sciences and humanities by rejecting the existence of truth, morality, and rationality. (FMW)

  3. Human Social Genomics

    PubMed Central

    Cole, Steven W.

    2014-01-01

    A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA) characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural “social signal transduction” pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving. PMID:25166010

  4. Learning to Be Human

    ERIC Educational Resources Information Center

    Macmurray, John

    2012-01-01

    This article presents "Learning to be Human", which John Macmurray delivered on 5 May 1958 as the annual public lecture at Moray House College of Education, now part of Edinburgh University. The key themes of the paper are ones to which Macmurray returned again and again in both his educational and his philosophical writing for over 40 years and…

  5. Human Ecology: Curriculum Review.

    ERIC Educational Resources Information Center

    Bybee, Rodger W.

    1984-01-01

    Describes nine commercially available programs which represent one aspect or a portion of the human ecology theme. Other information supplied for each program includes: program objectives; methods of instruction; specific subjects, grade, and ability levels; materials produced and purchasable; program implementation; teacher preparation; program…

  6. Human Balance System

    MedlinePlus

    ... and vision problems, and difficulty with concentration and memory. What is balance? Balance is the ability to maintain the body’s center of mass over its base of support. 1 A properly functioning balance system allows humans to see clearly while moving, identify orientation with ...

  7. Human perspiration measurement.

    PubMed

    Ohhashi, T; Sakaguchi, M; Tsuda, T

    1998-11-01

    We review various methods developed for human perspiration measurement and their physiological applications, with special reference to the performance and application of a new home-made ratemeter and instrumentation with a microscope. Many kinds of humidity sensor based on humidity-sensitive electrical properties have been investigated and placed on the market. Recently a capacitive thin-film humidity sensor was constructed and confirmed to be one of the best humidity sensors for accurately and quickly detecting changes in the relative humidity of gas-flow perfused through a ventilated chamber for human perspiration measurement. In this paper we also introduce a new home-made ratemeter with a capacitive humidity sensor, the electrical output of which is not disturbed by changes in ambient temperature, and new instrumentation for directly observing drops of sweat secreted from eccrine glands in human skin and simultaneously measuring the change in amount of perspiration at the same area of skin. Finally, we review physiological applications of the methods for measuring human palmar perspiration including emotional sweating.

  8. Food Affects Human Behavior.

    ERIC Educational Resources Information Center

    Kolata, Gina

    1982-01-01

    A conference on whether food and nutrients affect human behavior was held on November 9, 1982 at the Massachusetts Institute of Technology. Various research studies on this topic are reviewed, including the effects of food on brain biochemistry (particularly sleep) and effects of tryptophane as a pain reducer. (JN)

  9. Humane Treatment of Animals.

    ERIC Educational Resources Information Center

    Dawson, Joan Smithey

    This booklet is designed to give teachers resource information about the humane treatment of and care for animals. The topics are presented as springboards for discussion and class activity. Topics include the care of dogs, cats, birds, horses, and fish; wildlife and ecological relationships; and careers with animals. Illustrations on some pages…

  10. Tackling Human Rights

    ERIC Educational Resources Information Center

    McLester, Susan

    2005-01-01

    In 2003, four high school students from the Tashkent International School in the capital city confronted the issue of their nation's human rights problems head on by researching the topic and publishing their findings on the Web. The site, "Uzbekistan: Opaque Reality," was created as an entry for the non-profit Global SchoolNet's Doors…

  11. Fighting for the Humanities

    ERIC Educational Resources Information Center

    Nelson, Cary

    2012-01-01

    The question, "Who will bankroll poetry?", succinctly embodies what is now a widespread recognition that the humanities may have more to lose in the current budget wars than either the sciences or a number of technical fields. The only budget war that can unite individuals, rather than divide them, is one arguing that too much is being…

  12. Designers of Human Settlements

    ERIC Educational Resources Information Center

    Cliff, Ursula

    1976-01-01

    Reviewed herein are the ideas of nine men who have addressed themselves to the problems of human settlements in this century. The ideas reviewed include those of Arnold Toynbee, Lewis Mumford, Hassan Fathy, Buckminster Fuller, Constantinos Doxiadis, Charles Correa, Paul Mwaluko, Robert McNamara and John F. C. Turner. (BT)

  13. "Healthy" Human Development Indices

    ERIC Educational Resources Information Center

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  14. Lessons in Human Relations.

    ERIC Educational Resources Information Center

    Glenn, Joanne Lozar

    2003-01-01

    Explores the importance of relationship literacy--the ability to create good relationships with others--in the next economy and offers perspectives on how business education instructors can help students develop and improve their human relations skills for business success. (Author/JOW)

  15. The human genome project.

    PubMed Central

    Olson, M V

    1993-01-01

    The Human Genome Project in the United States is now well underway. Its programmatic direction was largely set by a National Research Council report issued in 1988. The broad framework supplied by this report has survived almost unchanged despite an upheaval in the technology of genome analysis. This upheaval has primarily affected physical and genetic mapping, the two dominant activities in the present phase of the project. Advances in mapping techniques have allowed good progress toward the specific goals of the project and are also providing strong corollary benefits throughout biomedical research. Actual DNA sequencing of the genomes of the human and model organisms is still at an early stage. There has been little progress in the intrinsic efficiency of DNA-sequence determination. However, refinements in experimental protocols, instrumentation, and project management have made it practical to acquire sequence data on an enlarged scale. It is also increasingly apparent that DNA-sequence data provide a potent means of relating knowledge gained from the study of model organisms to human biology. There is as yet little indication that the infusion of technology from outside biology into the Human Genome Project has been effectively stimulated. Opportunities in this area remain large, posing substantial technical and policy challenges. PMID:8506271

  16. Human Biology: Experimental.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Bureau of Curriculum Development.

    Education is a process of adapting to change, and the rate of change is especially rapid in science today. This curriculum in human biology is an alternative to the New York State courses in general and Regents biology, and it has been designed to focus on change from the standpoint of the urban student. It is designed to provide students with…

  17. Technologies for Human Exploration

    NASA Technical Reports Server (NTRS)

    Drake, Bret G.

    2014-01-01

    Access to Space, Chemical Propulsion, Advanced Propulsion, In-Situ Resource Utilization, Entry, Descent, Landing and Ascent, Humans and Robots Working Together, Autonomous Operations, In-Flight Maintenance, Exploration Mobility, Power Generation, Life Support, Space Suits, Microgravity Countermeasures, Autonomous Medicine, Environmental Control.

  18. Human Aggression and Suicide

    ERIC Educational Resources Information Center

    Brown, Gerald L.; Goodwin, Frederick K

    1986-01-01

    The central nervous system transmitter serontonin may be altered in aggressive/impulsive and suicidal behaviors in humans. These reports are largely consistent with animal data, and constitute one of the most highly replicated set of findings in biological psychiatry. Suggests that some suicidal behavior may be a special kind of aggressive…

  19. Have we overestimated the benefit of human(ized) antibodies?

    PubMed Central

    Getts, Meghann T; McCarthy, Derrick P; Chastain, Emily ML; Miller, Stephen D

    2010-01-01

    The infusion of animal-derived antibodies has been known for some time to trigger the generation of antibodies directed at the foreign protein as well as adverse events including cytokine release syndrome. These immunological phenomena drove the development of humanized and fully human monoclonal antibodies. The ability to generate human(ized) antibodies has been both a blessing and a curse. While incremental gains in the clinical efficacy and safety for some agents have been realized, a positive effect has not been observed for all human(ized) antibodies. Many human(ized) antibodies trigger the development of anti-drug antibody responses and infusion reactions. The current belief that antibodies need to be human(ized) to have enhanced therapeutic utility may slow the development of novel animal-derived monoclonal antibody therapeutics for use in clinical indications. In the case of murine antibodies, greater than 20% induce tolerable/negligible immunogenicity, suggesting that in these cases humanization may not offer significant gains in therapeutic utility. Furthermore, humanization of some murine antibodies may reduce their clinical effectiveness. The available data suggest that the utility of human(ized) antibodies needs to be evaluated on a case-by-case basis, taking a cost-benefit approach, taking both biochemical characteristics and the targeted therapeutic indication into account. PMID:20935511

  20. Human-Robot Interaction

    NASA Technical Reports Server (NTRS)

    Sandor, Aniko; Cross, E. Vincent, II; Chang, Mai Lee

    2015-01-01

    Human-robot interaction (HRI) is a discipline investigating the factors affecting the interactions between humans and robots. It is important to evaluate how the design of interfaces affect the human's ability to perform tasks effectively and efficiently when working with a robot. By understanding the effects of interface design on human performance, workload, and situation awareness, interfaces can be developed to appropriately support the human in performing tasks with minimal errors and with appropriate interaction time and effort. Thus, the results of research on human-robot interfaces have direct implications for the design of robotic systems. For efficient and effective remote navigation of a rover, a human operator needs to be aware of the robot's environment. However, during teleoperation, operators may get information about the environment only through a robot's front-mounted camera causing a keyhole effect. The keyhole effect reduces situation awareness which may manifest in navigation issues such as higher number of collisions, missing critical aspects of the environment, or reduced speed. One way to compensate for the keyhole effect and the ambiguities operators experience when they teleoperate a robot is adding multiple cameras and including the robot chassis in the camera view. Augmented reality, such as overlays, can also enhance the way a person sees objects in the environment or in camera views by making them more visible. Scenes can be augmented with integrated telemetry, procedures, or map information. Furthermore, the addition of an exocentric (i.e., third-person) field of view from a camera placed in the robot's environment may provide operators with the additional information needed to gain spatial awareness of the robot. Two research studies investigated possible mitigation approaches to address the keyhole effect: 1) combining the inclusion of the robot chassis in the camera view with augmented reality overlays, and 2) modifying the camera

  1. Making Human Beings Human: Bioecological Perspectives on Human Development. The SAGE Program on Applied Developmental Science

    ERIC Educational Resources Information Center

    Bronfenbrenner, Urie, Ed.

    2004-01-01

    To a greater extent than any other species, human beings create the environments that, in turn, shape their own development. This book endeavors to demonstrate that human beings can also develop those environments to optimize their most constructive genetic potentials. What makes human beings human, therefore, is both the potential to shape their…

  2. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    PubMed

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  3. Helicopter Human Factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  4. The Universal Declaration on the Human Genome and Human Rights.

    PubMed

    Mayor, Federico

    2003-01-01

    Since 1985, UNESCO studies ethical questions arising in genetics. In 1992, I established the International Bioethics Committee at UNESCO with the mission to draft the Universal Declaration on the Human Genome and Human Rights, which was adopted by UNESCO in 1997 and the United Nations in 1998. The Declaration relates the human genome with human dignity, deals with the rights of the persons concerned by human genome research and provides a reference legal framework for both stimulating the ethical debate and the harmonization of the law worldwide, favouring useful developments that respect human dignity.

  5. Zygomycetes in Human Disease

    PubMed Central

    Ribes, Julie A.; Vanover-Sams, Carolyn L.; Baker, Doris J.

    2000-01-01

    The Zygomycetes represent relatively uncommon isolates in the clinical laboratory, reflecting either environmental contaminants or, less commonly, a clinical disease called zygomycosis. There are two orders of Zygomycetes containing organisms that cause human disease, the Mucorales and the Entomophthorales. The majority of human illness is caused by the Mucorales. While disease is most commonly linked to Rhizopus spp., other organisms are also associated with human infection, including Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces, and Syncephalastrum spp. Although Mortierella spp. do cause disease in animals, there is no longer sufficient evidence to suggest that they are true human pathogens. The spores from these molds are transmitted by inhalation, via a variety of percutaneous routes, or by ingestion of spores. Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns. Zygomycosis occurs only rarely in immunocompetent hosts. The disease manifestations reflect the mode of transmission, with rhinocerebral and pulmonary diseases being the most common manifestations. Cutaneous, gastrointestinal, and allergic diseases are also seen. The Mucorales are associated with angioinvasive disease, often leading to thrombosis, infarction of involved tissues, and tissue destruction mediated by a number of fungal proteases, lipases, and mycotoxins. If the diagnosis is not made early, dissemination often occurs. Therapy, if it is to be effective, must be started early and requires combinations of antifungal drugs, surgical intervention, and reversal of the underlying risk

  6. Human Integration Design Processes (HIDP)

    NASA Technical Reports Server (NTRS)

    Boyer, Jennifer

    2014-01-01

    The purpose of the Human Integration Design Processes (HIDP) document is to provide human-systems integration design processes, including methodologies and best practices that NASA has used to meet human systems and human rating requirements for developing crewed spacecraft. HIDP content is framed around human-centered design methodologies and processes in support of human-system integration requirements and human rating. NASA-STD-3001, Space Flight Human-System Standard, is a two-volume set of National Aeronautics and Space Administration (NASA) Agency-level standards established by the Office of the Chief Health and Medical Officer, directed at minimizing health and performance risks for flight crews in human space flight programs. Volume 1 of NASA-STD-3001, Crew Health, sets standards for fitness for duty, space flight permissible exposure limits, permissible outcome limits, levels of medical care, medical diagnosis, intervention, treatment and care, and countermeasures. Volume 2 of NASASTD- 3001, Human Factors, Habitability, and Environmental Health, focuses on human physical and cognitive capabilities and limitations and defines standards for spacecraft (including orbiters, habitats, and suits), internal environments, facilities, payloads, and related equipment, hardware, and software with which the crew interfaces during space operations. The NASA Procedural Requirements (NPR) 8705.2B, Human-Rating Requirements for Space Systems, specifies the Agency's human-rating processes, procedures, and requirements. The HIDP was written to share NASA's knowledge of processes directed toward achieving human certification of a spacecraft through implementation of human-systems integration requirements. Although the HIDP speaks directly to implementation of NASA-STD-3001 and NPR 8705.2B requirements, the human-centered design, evaluation, and design processes described in this document can be applied to any set of human-systems requirements and are independent of reference

  7. Human evolution. Y-chromosome clues to human ancestry.

    PubMed

    Brookfield, J F

    1995-10-01

    The case for a recent expansion of modern humans from Africa has been strengthened by the finding of monomorphism in part of a Y-linked gene, consistent with the low variability seen in human mitochondrial DNAs.

  8. Monogenic human skin disorders.

    PubMed

    Lemke, Johannes R; Kernland-Lang, Kristin; Hörtnagel, Konstanze; Itin, Peter

    2014-01-01

    Human genodermatoses represent a broad and partly confusing spectrum of countless rare diseases with confluent and overlapping phenotypes often impeding a precise diagnosis in an affected individual. High-throughput sequencing techniques have expedited the identification of novel genes and have dramatically simplified the establishment of genetic diagnoses in such heterogeneous disorders. The precise genetic diagnosis of a skin disorder is crucial for the appropriate counselling of patients and their relatives regarding the course of the disease, prognosis and recurrence risks. Understanding the underlying pathophysiology is a prerequisite to understanding the disease and developing specific, targeted or individualized therapeutic approaches. We aimed to create a comprehensive overview of human genodermatoses and their respective genetic aetiology known to date. We hope this may represent a useful tool in guiding dermatologists towards genetic diagnoses, providing patients with individual knowledge on the respective disorder and applying novel research findings to clinical practice.

  9. [PALEOPATHOLOGY OF HUMAN REMAINS].

    PubMed

    Minozzi, Simona; Fornaciari, Gino

    2015-01-01

    Many diseases induce alterations in the human skeleton, leaving traces of their presence in ancient remains. Paleopathological examination of human remains not only allows the study of the history and evolution of the disease, but also the reconstruction of health conditions in the past populations. This paper describes the most interesting diseases observed in skeletal samples from the Roman Imperial Age necropoles found in urban and suburban areas of Rome during archaeological excavations in the last decades. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumours, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, the palaeopathological study allowed to highlight the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population.

  10. Ancient human microbiomes

    PubMed Central

    Warinner, Christina; Speller, Camilla; Collins, Matthew J.; Lewis, Cecil M.

    2015-01-01

    Very recently, we discovered a vast new microbial self: the human microbiome. Our native microbiota interface with our biology and culture to influence our health, behavior, and quality of life, and yet we know very little about their origin, evolution, or ecology. With the advent of industrialization, globalization, and modern sanitation, it is intuitive that we have changed our relationship with microbes, but we have little information about the ancestral state of our microbiome, and therefore, we lack a foundation for characterizing this change. High-throughput sequencing has opened up new opportunities in the field of paleomicrobiology, allowing us to investigate the evolution of the complex microbial ecologies that inhabit our bodies. By focusing on recent coprolite and dental calculus research, we explore how emerging research on ancient human microbiomes is changing the way we think about ancient disease and how archaeological studies can contribute to a medical understanding of health and nutrition today. PMID:25559298

  11. Posthumanism: beyond humanism?

    PubMed

    Valera, Luca

    2014-01-01

    The focal point of posthumanism consists not as such in an a-critical acceptance of the technological promises - like there is for transhumanism - but in a total contamination and hybridization of human beings with other living beings and machines (these are the two main forms of contamination). The change of perspective untaken by posthumanism would be, thus, a paradigmatic shift in anthropology. As with ecologism, posthumanism, in order to obtain total contamination and man's openness to otherness, proposes the elimination and the fluidification of boundaries, thus even denying man's identity, and, with it, the very possibility of openness. However, by denying the identity, one denies the condition of possibility of thought, just as it has been manifested in history until now: hence we understand how, primarily, posthumanism is not configured as an adequate philosophical reflection, but as a narrative that takes origin from certain requirements, which are eminently human, and that discloses its deeply anthropogenic roots.

  12. Sleep and Human Aging.

    PubMed

    Mander, Bryce A; Winer, Joseph R; Walker, Matthew P

    2017-04-05

    Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need?

  13. MIS - The Human Connection

    PubMed Central

    Bush, Ian E.

    1980-01-01

    The lessons of the 70's with MIS were largely painful, often the same as those of the 60's, and were found in different phases on two continents. On examination this turns out to be true for many non-medical fields, true for systems programming, and thus a very general phenomenon. It is related to the functional complexity rather than to the sheer size of the software required, and above all to the relative neglect of human factors at all levels of software and hardware design. Simple hierarchical theory is a useful tool for analyzing complex systems and restoring the necessary dominance of common sense human factors. An example shows the very large effects of neglecting these factors on costs and benefits of MIS and their sub-systems.

  14. Human factors workplace considerations

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1988-01-01

    Computer workstations assume many different forms and play different functions today. In order for them to assume the effective interface role which they should play they must be properly designed to take into account the ubiguitous human factor. In addition, the entire workplace in which they are used should be properly configured so as to enhance the operational features of the individual workstation where possible. A number of general human factors workplace considerations are presented. This ongoing series of notes covers such topics as achieving comfort and good screen visibility, hardware issues (e.g., mouse maintenance), screen symbology features (e.g., labels, cursors, prompts), and various miscellaneous subjects. These notes are presented here in order to: (1) illustrate how one's workstation can be used to support telescience activities of many other people working within an organization, and (2) provide a single complete set of considerations for future reference.

  15. Epidemiology of human listeriosis.

    PubMed Central

    Schuchat, A; Swaminathan, B; Broome, C V

    1991-01-01

    During the 1980s, investigation of several large epidemics of listeriosis confirmed that transmission of L. monocytogenes in food causes human disease. Progress in laboratory detection and subtyping of the organism has enhanced our ability to compare human and environmental isolates of L. monocytogenes. Transmission by foodborne organisms is now recognized as causing both epidemic and sporadic listeriosis. Continued study of dietary risk factors associated with listeriosis is needed in order to develop dietary recommendations for the expanding population at increased risk of disease. Current research application of new molecular methods to the study of L. monocytogenes may improve the ability to diagnose pregnancy-associated disease and permit the rapid detection and control of L. monocytogenes in the food supply. PMID:1906370

  16. Secure Distributed Human Computation

    NASA Astrophysics Data System (ADS)

    Gentry, Craig; Ramzan, Zulfikar; Stubblebine, Stuart

    In Peha’s Financial Cryptography 2004 invited talk, he described the Cyphermint PayCash system (see www.cyphermint.com), which allows people without bank accounts or credit cards (a sizeable segment of the U.S. population) to automatically and instantly cash checks, pay bills, or make Internet transactions through publicly-accessible kiosks. Since PayCash offers automated financial transactions and since the system uses (unprotected) kiosks, security is critical. The kiosk must decide whether a person cashing a check is really the person to whom the check was made out, so it takes a digital picture of the person cashing the check and transmits this picture electronically to a central office, where a human worker compares the kiosk’s picture to one that was taken when the person registered with Cyphermint. If both pictures are of the same person, then the human worker authorizes the transaction.

  17. Hyaluronan in human malignancies

    SciTech Connect

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

    2011-02-15

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

  18. Human waves in stadiums

    NASA Astrophysics Data System (ADS)

    Farkas, I.; Helbing, D.; Vicsek, T.

    2003-12-01

    Mexican wave first widely broadcasted during the 1986 World Cup held in Mexico, is a human wave moving along the stands of stadiums as one section of spectators stands up, arms lifting, then sits down as the next section does the same. Here we use variants of models originally developed for the description of excitable media to demonstrate that this collective human behaviour can be quantitatively interpreted by methods of statistical physics. Adequate modelling of reactions to triggering attempts provides a deeper insight into the mechanisms by which a crowd can be stimulated to execute a particular pattern of behaviour and represents a possible tool of control during events involving excited groups of people. Interactive simulations, video recordings and further images are available at the webpage dedicated to this work: http://angel.elte.hu/wave.

  19. Ancient human microbiomes.

    PubMed

    Warinner, Christina; Speller, Camilla; Collins, Matthew J; Lewis, Cecil M

    2015-02-01

    Very recently, we discovered a vast new microbial self: the human microbiome. Our native microbiota interface with our biology and culture to influence our health, behavior, and quality of life, and yet we know very little about their origin, evolution, or ecology. With the advent of industrialization, globalization, and modern sanitation, it is intuitive that we have changed our relationship with microbes, but we have little information about the ancestral state of our microbiome, and we therefore lack a foundation for characterizing this change. High-throughput sequencing has opened up new opportunities in the field of paleomicrobiology, allowing us to investigate the evolution of the complex microbial ecologies that inhabit our bodies. By focusing on recent coprolite and dental calculus research, we explore how emerging research on ancient human microbiomes is changing the way we think about ancient disease and how archaeological studies can contribute to a medical understanding of health and nutrition today.

  20. Human herpesvirus 8 – A novel human pathogen

    PubMed Central

    Edelman, Daniel C

    2005-01-01

    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. PMID:16138925

  1. Artificial intelligence: Human effects

    SciTech Connect

    Yazdani, M.; Narayanan, A.

    1984-01-01

    This book presents an up-to-date study of the interaction between the fast-growing discipline of artificial intelligence and other human endeavors. The volume explores the scope and limitations of computing, and presents a history of the debate on the possibility of machines achieving intelligence. The authors offer a state-of-the-art survey of Al, concentrating on the ''mind'' (language understanding) and the ''body'' (robotics) of intelligent computing systems.

  2. Networks of Human Culture

    NASA Astrophysics Data System (ADS)

    Csermely, Peter

    Now that you are back from the zoo, where you tried in vain to shake the six hands of all the ants for several hours,1 it is time to start our fifth trip into Netland. Let us go and see what those macroscopic ants known as human beings can achieve. I will show you what type of networks we have figured out to support the last variety of social networks from the previous chapter.

  3. [Patenting human genes].

    PubMed

    Brdicka, R

    2002-05-10

    The problem of patenting of human genes, which was discussed at the Workshop organized by OECD, has become very actual due to granted patents that concern testing of genetic disposition for breast cancer. Companies that had made large investments into this research clearly support patenting of their discoveries. But such patents can reduce general accessibility of genetic testing. Existing laws, and namely the Directive of the European Council unfortunately are not unambiguous and allow rather free explanation.

  4. Multichannel Human Body Communication

    NASA Astrophysics Data System (ADS)

    Przystup, Piotr; Bujnowski, Adam; Wtorek, Jerzy

    2016-01-01

    Human Body Communication is an attractive alternative for traditional wireless communication (Bluetooth, ZigBee) in case of Body Sensor Networks. Low power, high data rates and data security makes it ideal solution for medical applications. In this paper, signal attenuation for different frequencies, using FR4 electrodes, has been investigated. Performance of single and multichannel transmission with frequency modulation of analog signal has been tested. Experiment results show that HBC is a feasible solution for transmitting data between BSN nodes.

  5. Human mapping databases.

    PubMed

    Talbot, C; Cuticchia, A J

    2001-05-01

    This unit concentrates on the data contained within two human genome databasesGDB (Genome Database) and OMIM (Online Mendelian Inheritance in Man)and includes discussion of different methods for submitting and accessing data. An understanding of electronic mail, FTP, and the use of a World Wide Web (WWW) navigational tool such as Netscape or Internet Explorer is a prerequisite for utilizing the information in this unit.

  6. Ecotoxicology of human pharmaceuticals.

    PubMed

    Fent, Karl; Weston, Anna A; Caminada, Daniel

    2006-02-10

    Low levels of human medicines (pharmaceuticals) have been detected in many countries in sewage treatment plant (STP) effluents, surface waters, seawaters, groundwater and some drinking waters. For some pharmaceuticals effects on aquatic organisms have been investigated in acute toxicity assays. The chronic toxicity and potential subtle effects are only marginally known, however. Here, we critically review the current knowledge about human pharmaceuticals in the environment and address several key questions. What kind of pharmaceuticals and what concentrations occur in the aquatic environment? What is the fate in surface water and in STP? What are the modes of action of these compounds in humans and are there similar targets in lower animals? What acute and chronic ecotoxicological effects may be elicited by pharmaceuticals and by mixtures? What are the effect concentrations and how do they relate to environmental levels? Our review shows that only very little is known about long-term effects of pharmaceuticals to aquatic organisms, in particular with respect to biological targets. For most human medicines analyzed, acute effects to aquatic organisms are unlikely, except for spills. For investigated pharmaceuticals chronic lowest observed effect concentrations (LOEC) in standard laboratory organisms are about two orders of magnitude higher than maximal concentrations in STP effluents. For diclofenac, the LOEC for fish toxicity was in the range of wastewater concentrations, whereas the LOEC of propranolol and fluoxetine for zooplankton and benthic organisms were near to maximal measured STP effluent concentrations. In surface water, concentrations are lower and so are the environmental risks. However, targeted ecotoxicological studies are lacking almost entirely and such investigations are needed focusing on subtle environmental effects. This will allow better and comprehensive risk assessments of pharmaceuticals in the future.

  7. Neanderthals and Modern Humans

    NASA Astrophysics Data System (ADS)

    Finlayson, Clive

    2004-04-01

    The Neanderthals were a people native to Europe during the Pleistocene period, who became extinct between forty and thirty thousand years ago. Challenging the commonly held view that extinction was caused by the arrival of our ancestors, Clive Finlayson provides evidence that their extinction actually occurred because the Neanderthals could not adapt fast enough to changing ecological and environmental conditions, not their relationship with modern humans.

  8. Isolation of Human Basophils.

    PubMed

    Schroeder, John T; Bieneman, Anja P

    2016-02-02

    Isolating human basophils from blood has long been hampered by the fact that these granulocytes represent just 1% or less of the circulating leukocyte population. We describe herein laboratory protocols that have been refined over the past ∼25 years that now enable investigators to prepare basophils for use in a variety of assays to assess the in vitro biology of these immune cells, both in IgE -dependent and -independent responses.

  9. Human viruses and cancer.

    PubMed

    Morales-Sánchez, Abigail; Fuentes-Pananá, Ezequiel M

    2014-10-23

    The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt's lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers.

  10. Human liver nucleolar antigens.

    PubMed

    Busch, R K; Busch, H

    1981-10-01

    In an extension of previous studies on the antigens in rat liver nucleoli (R. K. Busch, R. C. Reddy, D. H. Henning, and H. Busch, Proc. Soc. Exp. Biol. Med. 160, 185 (1979); R. K. Busch and H. Busch, Tumori 63, 347 (1977); F. M. Davis, R. K. Busch, L. C. Yeoman, and H. Busch, Cancer Res. 38, 1906 (1978), rabbit antibodies were elicited to human liver nucleoli isolated by the sucrose--Mg2+ method (10). Fluorescent nucleoli were found in liver cryostat sections treated with rabbit anti-human liver nucleolar antibodies followed by fluorescein-conjugated goat anti-rabbit antibodies. In HeLa cells, fluorescence was distributed throughout the nucleus and in a nuclear network but was not localized to the nucleolus. In placental cryostat sections, an overall nuclear fluorescence was observed with some localization to nucleoli. Immunodiffusion analysis revealed two immunoprecipitin bands which appeared to be liver specific. Other immunoprecipitin bands were common to liver, placenta, and HeLa nuclear extracts. Rocket immunoelectrophoresis revealed two liver-specific antigens, one migrating to the cathode and the other to the anode Other rockets exhibited identity to antigens of other nuclear extracts. These results demonstrate the presence of human liver nucleolar-specific antigens which were not found in the HeLa and placental cells.

  11. Cocoa and human health.

    PubMed

    Ellam, Samantha; Williamson, Gary

    2013-01-01

    Cocoa is a dry, powdered, nonfat component product prepared from the seeds of the Theobroma cacao L. tree and is a common ingredient of many food products, particularly chocolate. Nutritionally, cocoa contains biologically active substances that may affect human health: flavonoids (epicatechin and oligomeric procyanidins), theobromine, and magnesium. Theobromine and epicatechin are absorbed efficiently in the small intestine, and the nature of their conjugates and metabolites are now known. Oligomeric procyanidins are poorly absorbed in the small intestine, but catabolites are very efficiently absorbed after microbial biotransformation in the colon. A significant number of studies, using in vitro and in vivo approaches, on the effects of cocoa and its constituent flavonoids have been conducted. Most human intervention studies have been performed on cocoa as an ingredient, whereas many in vitro studies have been performed on individual components. Approximately 70 human intervention studies have been carried out on cocoa and cocoa-containing products over the past 12 years, with a variety of endpoints. These studies indicate that the most robust biomarkers affected are endothelial function, blood pressure, and cholesterol level. Mechanistically, supporting evidence shows that epicatechin affects nitric oxide synthesis and breakdown (via inhibition of nicotinamide adenine di-nucleotide phosphate oxidase) and the substrate arginine (via inhibition of arginase), among other targets. Evidence further supports cocoa as a biologically active ingredient with potential benefits on biomarkers related to cardiovascular disease. However, the calorie and sugar content of chocolate and its contribution to the total diet should be taken into account in intervention studies.

  12. Unusual infections in humans.

    PubMed Central

    Neafie, R C; Marty, A M

    1993-01-01

    Nine cases of unusual infections in humans are presented. In each case, we present the clinical history, histopathologic changes (if indicated), morphologic features of the causative organism, diagnosis, discussion, differential diagnosis, therapy, and current literature. All of the cases are illustrated with pertinent photographs. The nine cases are as follows: (i) acanthocephaliasis, the first acquired human infection by Moniliformis moniliformis in the United States; (ii) dipylidiasis, an uncommon infection caused by the dog tapeworm, Dipylidium caninum; (iii) granulomatous amebic encephalitis, caused by the recently identified leptomyxid group of amebae; (iv) schistosomiasis, a dual infection of the urinary bladder with the rare presentation of both adult worms and eggs of Schistosoma haematobium and Schistosoma mansoni in tissue sections; (v) syphilitic gastritis, an uncommon presentation of Treponema pallidum infection, in a patient with an additional incidental infection by Helicobacter pylori; (vi) microsporidiosis, the only infection caused by a Pleistophora sp. in humans; (vii) sporotrichosis, a rare disseminated infection caused by Sporothrix schenckii with numerous yeast cells in the scrotum; (viii) angiostrongyliasis, the first and only infection caused by Angiostrongylus costaricensis acquired in either Puerto Rico or the United States; and (ix) botryomycosis of the skin and subcutaneous tissue, caused by gram-positive cocci with an unusually large number of granules. Images PMID:8457979

  13. Immunology of human schistosomiasis

    PubMed Central

    Colley, D G; Secor, W E

    2014-01-01

    There is a wealth of immunologic studies that have been carried out in experimental and human schistosomiasis that can be classified into three main areas: immunopathogenesis, resistance to reinfection and diagnostics. It is clear that the bulk of, if not all, morbidity due to human schistosomiasis results from immune-response-based inflammation against eggs lodged in the body, either as regulated chronic inflammation or resulting in fibrotic lesions. However, the exact nature of these responses, the antigens to which they are mounted and the mechanisms of the critical regulatory responses are still being sorted out. It is also becoming apparent that protective immunity against schistosomula as they develop into adult worms develops slowly and is hastened by the dying of adult worms, either naturally or when they are killed by praziquantel. However, as with anti-egg responses, the responsible immune mechanisms and inducing antigens are not clearly established, nor are any potential regulatory responses known. Finally, a wide variety of immune markers, both cellular and humoral, can be used to demonstrate exposure to schistosomes, and immunologic measurement of schistosome antigens can be used to detect, and thus diagnose, active infections. All three areas contribute to the public health response to human schistosome infections. PMID:25142505

  14. Mapping the human genome

    SciTech Connect

    Cantor, Charles R.

    1989-06-01

    The following pages aim to lay a foundation for understanding the excitement surrounding the ''human genome project,'' as well as to convey a flavor of the ongoing efforts and plans at the Human Genome Center at the Lawrence Berkeley Laboratory. Our own work, of course, is only part of a broad international effort that will dramatically enhance our understanding of human molecular genetics before the end of this century. In this country, the bulk of the effort will be carried out under the auspices of the Department of Energy and the National Institutes of Health, but significant contributions have already been made both by nonprofit private foundations and by private corporation. The respective roles of the DOE and the NIH are being coordinated by an inter-agency committee, the aims of which are to emphasize the strengths of each agency, to facilitate cooperation, and to avoid unnecessary duplication of effort. The NIH, for example, will continue its crucial work in medical genetics and in mapping the genomes of nonhuman species. The DOE, on the other hand, has unique experience in managing large projects, and its national laboratories are repositories of expertise in physics, engineering, and computer science, as well as the life sciences. The tools and techniques the project will ultimately rely on are thus likely to be developed in multidisciplinary efforts at laboratories like LBL. Accordingly, we at LBL take great pride in this enterprise -- an enterprise that will eventually transform our understanding of ourselves.

  15. Human milk banking.

    PubMed

    O'Hare, Esther Marie; Wood, Angela; Fiske, Elizabeth

    2013-01-01

    Forms of human milk banking and donation have been present for more than a century worldwide, but, since 1985, the Human Milk Banking Association of North America (HM BANA) has established guidelines to make the use of donor's breast milk safe and the second best form of feeding to maternal breast milk for a neonatal intensive care unit (NICU) infant. The Indiana Mother's Human Milk Bank provides an extensive and meticulous process of selecting breast milk donors. The process begins with a phone interview with a potential donor and includes the review of the donor's medical records, blood laboratory screening, medication and dietary intake, as well as consent from the donor's pediatrician. The milk bank follows steps of collecting, storing, and receiving the breast milk in accordance with the guidelines of the HM BANA. Pasteurization is the method used to ensure the proper heating and cooling of breast milk. Despite the rigorous pasteurization method, the donor's breast milk will not lose most of the important beneficial components needed for sick or ill NICU infants. Every batch of pasteurized breast milk will be cultured for any possible contamination and shipped to NICUs after it has been cleared by laboratory testing.

  16. Human metapneumovirus in adults.

    PubMed

    Haas, Lenneke E M; Thijsen, Steven F T; van Elden, Leontine; Heemstra, Karen A

    2013-01-08

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination.

  17. The human papillomaviruses.

    PubMed

    Orth, G; Jablonska, S; Breitburd, F; Favre, M; Croissant, O

    1978-01-01

    Recent biochemical and serological studies have shown the existence of at least four distinct types of human papillomaviruses (HPVs) causing benign skin lesions. These viruses show hardly no antigenic relationships; their DNAs differ by their sensitivity to restriction endonucleases, and show little, if any, sequence homology, as detected by molecular hybridization using complementary RNAs transcribed in vitro. Data on the pathogenicity of HPVs are still incomplete but indicate that some types of benign skin lesions (plantar warts, common warts, flat warts) may be preferentially associated with some types of HPV. Most interesting is that epidermodysplasia verruciformis has been found associated with two types of virus, and that malignant conversion of some lesions has been observed in all the patients infected with one of them. This suggests that at least a HPV may have a higher oncogenic potential, as do rabbit (Shope) papillomavirus and bovine alimentary tract papillomavirus. Much remains to be known on human papilloma-viruses and further studies may lead to the characterization of additional types of HPVs, especially in genital condylomata acuminata and laryngeal papillomas whose malignant conversion, although rare, may be observed. Progress in this field has been and remains hampered by the lack of cell culture systems allowing replication of these highly host and tissue specific viruses, and by the widely variable virus content of the different human lesions known to be associated with a papillomavirus. Further studies are warranted by the possible role of these widespread and epitheliotropic viruses in the origin of some carcinomas in man.

  18. Psychophysics of human echolocation.

    PubMed

    Schörnich, Sven; Wallmeier, Ludwig; Gessele, Nikodemus; Nagy, Andreas; Schranner, Michael; Kish, Daniel; Wiegrebe, Lutz

    2013-01-01

    The skills of some blind humans orienting in their environment through the auditory analysis of reflections from self-generated sounds have received only little scientific attention to date. Here we present data from a series of formal psychophysical experiments with sighted subjects trained to evaluate features of a virtual echo-acoustic space, allowing for rigid and fine-grain control of the stimulus parameters. The data show how subjects shape both their vocalisations and auditory analysis of the echoes to serve specific echo-acoustic tasks. First, we show that humans can echo-acoustically discriminate target distances with a resolution of less than 1 m for reference distances above 3.4 m. For a reference distance of 1.7 m, corresponding to an echo delay of only 10 ms, distance JNDs were typically around 0.5 m. Second, we explore the interplay between the precedence effect and echolocation. We show that the strong perceptual asymmetry between lead and lag is weakened during echolocation. Finally, we show that through the auditory analysis of self-generated sounds, subjects discriminate room-size changes as small as 10%.In summary, the current data confirm the practical efficacy of human echolocation, and they provide a rigid psychophysical basis for addressing its neural foundations.

  19. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1989-01-01

    The Office of Exploration has established a process whereby all NASA field centers and other NASA Headquarters offices participate in the formulation and analysis of a wide range of mission strategies. These strategies were manifested into specific scenarios or candidate case studies. The case studies provided a systematic approach into analyzing each mission element. First, each case study must address several major themes and rationale including: national pride and international prestige, advancement of scientific knowledge, a catalyst for technology, economic benefits, space enterprise, international cooperation, and education and excellence. Second, the set of candidate case studies are formulated to encompass the technology requirement limits in the life sciences, launch capabilities, space transfer, automation, and robotics in space operations, power, and propulsion. The first set of reference case studies identify three major strategies: human expeditions, science outposts, and evolutionary expansion. During the past year, four case studies were examined to explore these strategies. The expeditionary missions include the Human Expedition to Phobos and Human Expedition to Mars case studies. The Lunar Observatory and Lunar Outpost to Early Mars Evolution case studies examined the later two strategies. This set of case studies established the framework to perform detailed mission analysis and system engineering to define a host of concepts and requirements for various space systems and advanced technologies. The details of each mission are described and, specifically, the results affecting the advanced technologies required to accomplish each mission scenario are presented.

  20. Human Milk Lipids.

    PubMed

    Koletzko, Berthold

    2016-01-01

    Human milk lipids provide the infant with energy and essential vitamins, polyunsaturated fatty acids, and bioactive components. Adding complex lipids and milk fat globule membranes to vegetable oil-based infant formula has the potential to enhance infant development and reduce infections. Cholesterol provision with breastfeeding modulates infant sterol metabolism and may induce long-term benefits. Some 98-99% of milk lipids are comprised by triacylglycerols, whose properties depend on incorporated fatty acids. Attention has been devoted to the roles of the long-chain polyunsaturated fatty acids docosahexaenoic (DHA) and arachidonic (ARA) acids. Recent studies on gene-diet interaction (Mendelian randomization) show that breastfeeding providing DHA and ARA improves cognitive development and reduces asthma risk at school age particularly in those children with a genetically determined lower activity of DHA and ARA synthesis. It appears prudent to follow the biological model of human milk in the design of infant formula as far as feasible, unless conclusive evidence for the suitability and safety of other choices is available. The recent European Union legislative stipulation of a high formula DHA content without required ARA deviates from this concept, and such a novel formula composition has not been adequately evaluated. Great future opportunities arise with significant methodological progress for example in lipidomic analyses and their bioinformatic evaluation, which should enhance understanding of the biology of human milk lipids. Such knowledge might lead to improved dietary advice to lactating mothers as well as to further opportunities to enhance infant formula composition.

  1. Science and Human Experience

    NASA Astrophysics Data System (ADS)

    Cooper, Leon N.

    2015-01-01

    Part I. Science and Society: 1. Science and human experience; 2. Does science undermine our values?; 3. Can science serve mankind?; 4. Modern science and contemporary discomfort: metaphor and reality; 5. Faith and science; 6. Art and science; 7. Fraud in science; 8. Why study science? The keys to the cathedral; 9. Is evolution a theory? A modest proposal; 10. The silence of the second; 11. Introduction to Copenhagen; 12. The unpaid debt; Part II. Thought and Consciousness: 13. Source and limits of human intellect; 14. Neural networks; 15. Thought and mental experience: the Turing test; 16. Mind as machine: will we rubbish human experience?; 17. Memory and memories: a physicist's approach to the brain; 18. On the problem of consciousness; Part III. On the Nature and Limits of Science: 19. What is a good theory?; 20. Shall we deconstruct science?; 21. Visible and invisible in physical theory; 22. Experience and order; 23. The language of physics; 24. The structure of space; 25. Superconductivity and other insoluble problems; 26. From gravity to light and consciousness: does science have limits?

  2. Science and Human Experience

    NASA Astrophysics Data System (ADS)

    Cooper, Leon N.

    2014-12-01

    Part I. Science and Society: 1. Science and human experience; 2. Does science undermine our values?; 3. Can science serve mankind?; 4. Modern science and contemporary discomfort: metaphor and reality; 5. Faith and science; 6. Art and science; 7. Fraud in science; 8. Why study science? The keys to the cathedral; 9. Is evolution a theory? A modest proposal; 10. The silence of the second; 11. Introduction to Copenhagen; 12. The unpaid debt; Part II. Thought and Consciousness: 13. Source and limits of human intellect; 14. Neural networks; 15. Thought and mental experience: the Turing test; 16. Mind as machine: will we rubbish human experience?; 17. Memory and memories: a physicist's approach to the brain; 18. On the problem of consciousness; Part III. On the Nature and Limits of Science: 19. What is a good theory?; 20. Shall we deconstruct science?; 21. Visible and invisible in physical theory; 22. Experience and order; 23. The language of physics; 24. The structure of space; 25. Superconductivity and other insoluble problems; 26. From gravity to light and consciousness: does science have limits?

  3. Human evolution and cognition.

    PubMed

    Tattersall, Ian

    2010-09-01

    Human beings are distinguished from all other organisms by their symbolic way of processing information about the world. This unique cognitive style is qualitatively different from all the earlier hominid cognitive styles, and is not simply an improved version of them. The hominid fossil and archaeological records show clearly that biological and technological innovations have typically been highly sporadic, and totally out of phase, since the invention of stone tools some 2.5 million years ago. They also confirm that this pattern applied in the arrival of modern cognition: the anatomically recognizable species Homo sapiens was well established long before any population of it began to show indications of behaving symbolically. This places the origin of symbolic thought in the realms of exaptation, whereby new structures come into existence before being recruited to new uses, and of emergence, whereby entire new levels of complexity are achieved through new combinations of attributes unremarkable in themselves. Both these phenomena involve entirely routine evolutionary processes; special as we human beings may consider ourselves, there was nothing special about the way we came into existence. Modern human cognition is a very recent acquisition; and its emergence ushered in an entirely new pattern of technological (and other behavioral) innovation, in which constant change results from the ceaseless exploration of the potential inherent in our new capacity.

  4. Computing human image annotation.

    PubMed

    Channin, David S; Mongkolwat, Pattanasak; Kleper, Vladimir; Rubin, Daniel L

    2009-01-01

    An image annotation is the explanatory or descriptive information about the pixel data of an image that is generated by a human (or machine) observer. An image markup is the graphical symbols placed over the image to depict an annotation. In the majority of current, clinical and research imaging practice, markup is captured in proprietary formats and annotations are referenced only in free text radiology reports. This makes these annotations difficult to query, retrieve and compute upon, hampering their integration into other data mining and analysis efforts. This paper describes the National Cancer Institute's Cancer Biomedical Informatics Grid's (caBIG) Annotation and Image Markup (AIM) project, focusing on how to use AIM to query for annotations. The AIM project delivers an information model for image annotation and markup. The model uses controlled terminologies for important concepts. All of the classes and attributes of the model have been harmonized with the other models and common data elements in use at the National Cancer Institute. The project also delivers XML schemata necessary to instantiate AIMs in XML as well as a software application for translating AIM XML into DICOM S/R and HL7 CDA. Large collections of AIM annotations can be built and then queried as Grid or Web services. Using the tools of the AIM project, image annotations and their markup can be captured and stored in human and machine readable formats. This enables the inclusion of human image observation and inference as part of larger data mining and analysis activities.

  5. On cloning human beings.

    PubMed

    de Melo-Martin, Inmaculada

    2002-06-01

    The purpose of this paper is to show that arguments for and against cloning fail to make their case because of one or both of the following reasons: 1) they take for granted customary beliefs and assumptions that are far from being unquestionable; 2) they tend to ignore the context in which human cloning is developed. I will analyze some of the assumptions underlying the main arguments that have been offered for and against cloning. Once these assumptions are critically analyzed, arguments both rejecting and supporting human cloning seem to lose weight. I will first briefly present the main arguments that have been proposed against cloning and I will argue that they fail to establish their case. In the next section I will evaluate some of the positive arguments that have been offered supporting such technology. This analysis will show that the case for cloning also fails. Finally, I will maintain that because critics and especially supporters of this technology neglect the context in which human cloning is developed and might be implemented, their arguments are far from compelling.

  6. Gas hydrate and humans

    USGS Publications Warehouse

    Kvenvolden, K.A.

    2000-01-01

    The potential effects of naturally occurring gas hydrate on humans are not understood with certainty, but enough information has been acquired over the past 30 years to make preliminary assessments possible. Three major issues are gas hydrate as (1) a potential energy resource, (2) a factor in global climate change, and (3) a submarine geohazard. The methane content is estimated to be between 1015 to 1017 m3 at STP and the worldwide distribution in outer continental margins of oceans and in polar regions are significant features of gas hydrate. However, its immediate development as an energy resource is not likely because there are various geological constraints and difficult technological problems that must be solved before economic recovery of methane from hydrate can be achieved. The role of gas hydrate in global climate change is uncertain. For hydrate methane to be an effective greenhouse gas, it must reach the atmosphere. Yet there are many obstacles to the transfer of methane from hydrate to the atmosphere. Rates of gas hydrate dissociation and the integrated rates of release and destruction of the methane in the geo/hydro/atmosphere are not adequately understood. Gas hydrate as a submarine geohazard, however, is of immediate and increasing importance to humans as our industrial society moves to exploit seabed resources at ever-greater depths in the waters of our coastal oceans. Human activities and installations in regions of gas-hydrate occurrence must take into account the presence of gas hydrate and deal with the consequences of its presence.

  7. Human Metapneumovirus in Adults

    PubMed Central

    Haas, Lenneke E. M.; Thijsen, Steven F. T.; van Elden, Leontine; Heemstra, Karen A.

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  8. History of Human Parasitology

    PubMed Central

    Cox, F. E. G.

    2002-01-01

    Humans are hosts to nearly 300 species of parasitic worms and over 70 species of protozoa, some derived from our primate ancestors and some acquired from the animals we have domesticated or come in contact with during our relatively short history on Earth. Our knowledge of parasitic infections extends into antiquity, and descriptions of parasites and parasitic infections are found in the earliest writings and have been confirmed by the finding of parasites in archaeological material. The systematic study of parasites began with the rejection of the theory of spontaneous generation and the promulgation of the germ theory. Thereafter, the history of human parasitology proceeded along two lines, the discovery of a parasite and its subsequent association with disease and the recognition of a disease and the subsequent discovery that it was caused by a parasite. This review is concerned with the major helminth and protozoan infections of humans: ascariasis, trichinosis, strongyloidiasis, dracunculiasis, lymphatic filariasis, loasis, onchocerciasis, schistosomiasis, cestodiasis, paragonimiasis, clonorchiasis, opisthorchiasis, amoebiasis, giardiasis, African trypanosomiasis, South American trypanosomiasis, leishmaniasis, malaria, toxoplasmosis, cryptosporidiosis, cyclosporiasis, and microsporidiosis. PMID:12364371

  9. Human Viruses and Cancer

    PubMed Central

    Morales-Sánchez, Abigail; Fuentes-Pananá, Ezequiel M.

    2014-01-01

    The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt’s lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers. PMID:25341666

  10. Human African trypanosomiasis.

    PubMed

    Lejon, Veerle; Bentivoglio, Marina; Franco, José Ramon

    2013-01-01

    Human African trypanosomiasis or sleeping sickness is a neglected tropical disease that affects populations in sub-Saharan Africa. The disease is caused by infection with the gambiense and rhodesiense subspecies of the extracellular parasite Trypanosoma brucei, and is transmitted to humans by bites of infected tsetse flies. The disease evolves in two stages, the hemolymphatic and meningoencephalitic stages, the latter being defined by central nervous system infection after trypanosomal traversal of the blood-brain barrier. African trypanosomiasis, which leads to severe neuroinflammation, is fatal without treatment, but the available drugs are toxic and complicated to administer. The choice of medication is determined by the infecting parasite subspecies and disease stage. Clinical features include a constellation of nonspecific symptoms and signs with evolving neurological and psychiatric alterations and characteristic sleep-wake disturbances. Because of the clinical profile variability and insidiously progressive central nervous system involvement, disease staging is currently based on cerebrospinal fluid examination, which is usually performed after the finding of trypanosomes in blood or other body fluids. No vaccine being available, control of human African trypanosomiasis relies on diagnosis and treatment of infected patients, assisted by vector control. Better diagnostic tools and safer, easy to use drugs are needed to facilitate elimination of the disease.

  11. Human Provenancing: It's Elemental…

    NASA Astrophysics Data System (ADS)

    Meier-Augenstein, Wolfram; Kemp

    2009-04-01

    Forensic science already uses a variety of methods often in combination to determine a deceased person's identity if neither personal effects nor next of kin (or close friends) can positively identify the victim. While disciplines such as forensic anthropology are able to work from a blank canvass as it were and can provide information on age, gender and ethnical grouping, techniques such as DNA profiling do rely on finding a match either in a database or a comparative sample presumed to be an ante-mortem sample of the victim or from a putative relation. Chances for either to succeed would be greatly enhanced if information gained from a forensic anthropological examination and, circumstances permitting a facial reconstruction could be linked to another technique that can work from a blank canvass or at least does not require comparison to a subject specific database. With the help of isotope ratio mass spectrometry even the very atoms from which a body is made can be used to say something about a person that will help to focus human identification using traditional techniques such as DNA, fingerprints and odontology. Stable isotope fingerprinting works on the basis that almost all chemical elements and in particular the so-called light elements such as carbon (C) that comprise most of the human body occur naturally in different forms, namely isotopes. 2H isotope abundance values recorded by the human body through food and drink ultimately reflect averaged isotopic composition of precipitation or ground water. Stable isotope analysis of 2H isotopic composition in different human tissue such as hair, nails, bone and teeth enables us to construct a time resolved isotopic profile or ‘fingerprint' that may not necessarily permit direct identification of a murder victim or mass disaster victim but in conjunction with forensic anthropological information will provide sufficient intelligence to construct a profile for intelligence lead identification stating where a

  12. Human Research Program (HRP) Overview

    NASA Video Gallery

    The Human Research Program (HRP) is a major part of the Space Life and Physical Sciences Research and Applications Division within the Human Exploration and Operations Mission Directorate (HEOMD). ...

  13. Fire Control and Human Evolution.

    ERIC Educational Resources Information Center

    Russell, Claire

    1978-01-01

    Briefly outlines some aspects of the discovery of fire control by primitive people, such as the preadaptation for speech, the evolution of the human brain, and natural selection for human nakedness or loss of hair. (CS)

  14. DEMONSTRATION OF HUMAN EXPOSURE TOOLS

    EPA Science Inventory

    The Human Exposure and Atmospheric Sciences Division (HEASD) of the National Exposure Research Laboratory (NERL) conducts research on exposure measurements, human activity patterns, exposure and dose models, and cumulative exposures critical for the Agency to make scientificall...

  15. Oceans and Human Health Center

    MedlinePlus

    ocean and human health science can help prevent disease outbreaks and improve public health through a deeper understanding of the causes ... our Center and the field of oceans and human health science. More Research Learn about the research ...

  16. About Human Parainfluenza Viruses (HPIVs)

    MedlinePlus

    ... Overview Laboratory Diagnosis HPIV Seasons Resources & References About Human Parainfluenza Viruses (HPIVs) Recommend on Facebook Tweet Share ... 6348 Email CDC-INFO U.S. Department of Health & Human Services HHS/Open USA.gov Top

  17. Administrative Aspects of Human Experimentation.

    ERIC Educational Resources Information Center

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  18. Humane Education: A Forgotten Mandate

    ERIC Educational Resources Information Center

    Quinn, Peter J.

    1977-01-01

    Discusses the importance of humane education (i.e., the teaching of the principles of justice, goodwill, and respect for all living creatures) and offers suggestions for integrating humane education in the elementary school curriculum. (JG)

  19. Human Exploration of the Moon

    NASA Technical Reports Server (NTRS)

    Mendell, Wendell W.

    1999-01-01

    Human exploration of the Moon tilde-n or, more generally, human exploration of the solar system tilde-n began with the landing of Apollo 11 Lunar Module on the lunar surface. Human exploration continued with growing capability until the departure of the Apollo 17 lunar module from the lunar surface in 1972. Human exploration is currently experiencing what can be called euphemistically a hiatus.

  20. Rejecting medical humanism: medical humanities and the metaphysics of medicine.

    PubMed

    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.

  1. Human Milk-Treatment and Quality of Banked Human Milk.

    PubMed

    Picaud, Jean-Charles; Buffin, Rachel

    2017-03-01

    The aim of human milk banks is to deliver safe and high quality donor human milk. Treatment of human milk has to destroy most microorganisms while preserving immunological and nutrient components, which is obtained when using low time low temperature pasteurization. However it destroys bile-simulated lipase, reduces lactoferrin, lysozyme, immunoglobulins, and bactericidal capacity of human milk. New methods are under investigation such as high temperature short time pasteurization, high pressure processing, or ultraviolet irradiation. They have been tested in experimental conditions and there are promising results, but they have to be tested in real conditions in human milk bank.

  2. Leadership in a Humane Organization

    ERIC Educational Resources Information Center

    Dimitrov, Danielle

    2015-01-01

    Purpose: The purpose of this paper is to explore the way leadership influences an organization to become humane through its features and behaviors; as well as the organizational circumstances in which humane leadership can be nurtured. The first empirical case study, in the fields of Human Resource Development (HRD) and hospitality management, to…

  3. The Humanities at Triton College.

    ERIC Educational Resources Information Center

    Jacot, Robert E.; Prendergast, Nancy E.

    Designed to assist college personnel in assessing program needs, this report provides an overview of the humanities programs at Triton College. Part I focuses on curricular humanities programs, including discussions of the role and objectives of the School of Arts and Sciences; humanities courses offered in the school; special humanities…

  4. Research Needs for Human Factors.

    ERIC Educational Resources Information Center

    Army Research Inst. for the Behavioral and Social Sciences, Arlington, VA.

    Human factors engineering can be defined as the application of scientific principles, methods, and data drawn from a variety of disciplines to the development of engineering systems in which people play a significant role. Since human factors issues arise in every domain in which humans interact with the products of a technological society, six…

  5. Genes, Environment, and Human Behavior.

    ERIC Educational Resources Information Center

    Bloom, Mark V.; Cutter, Mary Ann; Davidson, Ronald; Dougherty, Michael J.; Drexler, Edward; Gelernter, Joel; McCullough, Laurence B.; McInerney, Joseph D.; Murray, Jeffrey C.; Vogler, George P.; Zola, John

    This curriculum module explores genes, environment, and human behavior. This book provides materials to teach about the nature and methods of studying human behavior, raise some of the ethical and public policy dilemmas emerging from the Human Genome Project, and provide professional development for teachers. An extensive Teacher Background…

  6. A Hierarchy of Human Rights.

    ERIC Educational Resources Information Center

    Brockett, Charles

    To establish an objective conception of human rights, one must first identify basic needs intrinsic to all people and then determine whether these needs are or can be hierarchically ordered. Many scholars have conducted research on the concept of human needs, particularly in the area of human rights. Among these scholars are Abraham H. Maslow…

  7. Community College Humanities Review, 1999.

    ERIC Educational Resources Information Center

    Scheper, George L., Ed.

    1999-01-01

    This special issue of the Community College Humanities Review contains articles generated by National Endowment for the Humanities Summer Institutes, held over several years. The institutes provided opportunities for academics from a variety of humanities disciplines and types of institutions to interact over an extended period of common study of…

  8. NASA Space Human Factors Program

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This booklet briefly and succinctly treats 23 topics of particular interest to the NASA Space Human Factors Program. Most articles are by different authors who are mainly NASA Johnson or NASA Ames personnel. Representative topics covered include mental workload and performance in space, light effects on Circadian rhythms, human sleep, human reasoning, microgravity effects and automation and crew performance.

  9. Literacy as a Human Problem.

    ERIC Educational Resources Information Center

    Raymond, James C., Ed.

    First presented as papers in a symposium on literacy conducted at the University of Alabama, essays in this volume explore three areas of human literacy--law, linguistics, and the English language; testing; and literacy's relation with culture and human consciousness. Following an introduction examining literacy as a human problem, the following…

  10. Gender Aspects of Human Security

    ERIC Educational Resources Information Center

    Moussa, Ghada

    2008-01-01

    The chapter deals with the gender dimensions in human security through focusing on the relationship between gender and human security, first manifested in international declarations and conventions, and subsequently evolving in world women conferences. It aims at analysing the various gender aspects in its relation to different human security…

  11. Office for Human Research Protections

    MedlinePlus

    ... A A A Print Share Office for Human Research Protections The Office for Human Research Protections (OHRP) provides leadership in the protection of ... welfare, and wellbeing of human subjects involved in research conducted or supported by the U.S. Department of ...

  12. Focus on Teaching the Humanities.

    ERIC Educational Resources Information Center

    Sheridan, Harriet W., Ed.

    1968-01-01

    Six articles on the problems in planning and executing a high school humanities program are collected here. Wallace Kennedy gives a partial listing of Minnesota teachers and schools that offer humanities in grades 11 and 12. Fred E. H. Schroeder takes up the problems of defining "humanities," selecting good teachers, preparing an interdisciplinary…

  13. Humanism and science: a reaction.

    PubMed

    Wampold, Bruce E

    2012-12-01

    Authors in this section have noted that humanism is intrinsic to psychotherapy, although disagreements remain. One of the disagreements is about the role of science in humanism. In this reaction, I contend that humanism, as discussed in these articles, is a legitimate theory to be subjected to scientific scrutiny.

  14. Human Rights and Public Education

    ERIC Educational Resources Information Center

    Bowring, Bill

    2012-01-01

    This article attempts a contrast to the contribution by Hugh Starkey. Rather than his account of the inexorable rise of human rights discourse, and of the implementation of human rights standards, human rights are here presented as always and necessarily scandalous and highly contested. First, I explain why the UK has lagged so far behind its…

  15. The human role in space

    NASA Technical Reports Server (NTRS)

    Hall, S. B.; Vontiesenhausen, G.; Johnson, G. W.

    1982-01-01

    Requirements for the future human role in space are considered. Human tasks were divided into normal scheduled activities, unscheduled activities, and contingency activities. A strawman mission model was developed. Projections were made of crew size, mission duration, pressurized spacecraft volume, and power requirements. Trends of human roles were likewise projected.

  16. Morbilliviruses and human disease.

    PubMed

    Rima, Bertus K; Duprex, W Paul

    2006-01-01

    Morbilliviruses are a group of viruses that belong to the family Paramyxoviridae. The most instantly recognizable member is measles virus (MV) and individuals acutely infected with the virus exhibit a wide range of clinical symptoms ranging from a characteristic mild self-limiting infection to death. Canine distemper virus (CDV) and rinderpest virus (RPV) cause a similar but distinctive pathology in dogs and cattle, respectively, and these, alongside experimental MV infection of primates, have been useful models for MV pathogenesis. Traditionally, viruses were identified because a distinctive disease was observed in man or animals; an infectious agent was subsequently isolated, cultured, and this could be used to recapitulate the disease in an experimentally infected host. Thus, satisfying Koch's postulates has been the norm. More recently, particularly due to the advent of exceedingly sensitive molecular biological assays, many researchers have looked for infectious agents in disease conditions for which a viral aetiology has not been previously established. For these cases, the modified Koch's postulates of Bradford Hill have been developed as criteria to link a virus to a specific disease. Only in a few cases have these conditions been fulfilled. Therefore, many viruses have over the years been definitely and tentatively linked to human diseases and in this respect the morbilliviruses are no different. In this review, human diseases associated with morbillivirus infection have been grouped into three broad categories: (1) those which are definitely caused by the infection; (2) those which may be exacerbated or facilitated by an infection; and (3) those which currently have limited, weak, unsubstantiated or no credible scientific evidence to support any link to a morbillivirus. Thus, an attempt has been made to clarify the published data and separate human diseases actually linked to morbilliviruses from those that are merely anecdotally associated.

  17. Human microsporidial infections.

    PubMed Central

    Weber, R; Bryan, R T; Schwartz, D A; Owen, R L

    1994-01-01

    Microsporidia are obligate intracellular spore-forming protozoal parasites belonging to the phylum Microspora. Their host range is extensive, including most invertebrates and all classes of vertebrates. More than 100 microsporidial genera and almost 1,000 species have now been identified. Five genera (Enterocytozoon spp., Encephalitozoon spp., Septata spp., Pleistophora sp., and Nosema spp.) and unclassified microsporidia (referred to by the collective term Microsporidium) have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. Among persons not infected with human immunodeficiency virus, ten cases of microsporidiosis have been documented. In human immunodeficiency virus-infected patients, on the other hand, over 400 cases of microsporidiosis have been identified, the majority attributed to Enterocytozoon bieneusi, an important cause of chronic diarrhea and wasting. Diagnosis of microsporidiosis currently depends on morphological demonstration of the organisms themselves. Initial detection of microsporidia by light microscopic examination of tissue sections and of more readily obtainable specimens such as stool, duodenal aspirates, urine, sputum, nasal discharge, bronchoalveolar lavage fluid, and conjunctival smears is now becoming routine practice. Definitive species identification is made by using the specific fluorescein-tagged antibody (immunofluorescence) technique or electron microscopy. Treatment options are limited, but symptomatic improvement of Enterocytozoon bieneusi infection may be achieved with the anthelmintic-antiprotozoal drug albendazole. Preliminary observations suggest that Septata intestinalis and Encephalitozoon infections may be cured with albendazole. Progress is being made with respect to in vitro propagation of microsporidia, which is crucial for developing

  18. Mentoring Human Performance - 12480

    SciTech Connect

    Geis, John A.; Haugen, Christian N.

    2012-07-01

    Although the positive effects of implementing a human performance approach to operations can be hard to quantify, many organizations and industry areas are finding tangible benefits to such a program. Recently, a unique mentoring program was established and implemented focusing on improving the performance of managers, supervisors, and work crews, using the principles of Human Performance Improvement (HPI). The goal of this mentoring was to affect behaviors and habits that reliably implement the principles of HPI to ensure continuous improvement in implementation of an Integrated Safety Management System (ISMS) within a Conduct of Operations framework. Mentors engaged with personnel in a one-on-one, or one-on-many dialogue, which focused on what behaviors were observed, what factors underlie the behaviors, and what changes in behavior could prevent errors or events, and improve performance. A senior management sponsor was essential to gain broad management support. A clear charter and management plan describing the goals, objectives, methodology, and expected outcomes was established. Mentors were carefully selected with senior management endorsement. Mentors were assigned to projects and work teams based on the following three criteria: 1) knowledge of the work scope; 2) experience in similar project areas; and 3) perceived level of trust they would have with project management, supervision, and work teams. This program was restructured significantly when the American Reinvestment and Recovery Act (ARRA) and the associated funding came to an end. The program was restructured based on an understanding of the observations, attributed successes and identified shortfalls, and the consolidation of those lessons. Mentoring the application of proven methods for improving human performance was shown effective at increasing success in day-to-day activities and increasing confidence and level of skill of supervisors. While mentoring program effectiveness is difficult to

  19. Human Genome Program

    SciTech Connect

    Not Available

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  20. HUMAN MACHINE COOPERATIVE TELEROBOTICS

    SciTech Connect

    William R. Hamel; Spivey Douglass; Sewoong Kim; Pamela Murray; Yang Shou; Sriram Sridharan; Ge Zhang; Scott Thayer; Rajiv V. Dubey

    2003-06-30

    The remediation and deactivation and decommissioning (D&D) of nuclear waste storage tanks using telerobotics is one of the most challenging tasks faced in environmental cleanup. Since a number of tanks have reached the end of their design life and some of them have leaks, the unstructured, uncertain and radioactive environment makes the work inefficient and expensive. However, the execution time of teleoperation consumes ten to hundred times that of direct contact with an associated loss in quality. Thus, a considerable effort has been expended to improve the quality and efficiency of telerobotics by incorporating into teleoperation and robotic control functions such as planning, trajectory generation, vision, and 3-D modeling. One example is the Robot Task Space Analyzer (RTSA), which has been developed at the Robotics and Electromechanical Systems Laboratory (REMSL) at the University of Tennessee in support of the D&D robotic work at the Oak Ridge National Laboratory and the National Energy Technology Laboratory. This system builds 3-D models of the area of interest in task space through automatic image processing and/or human interactive manual modeling. The RTSA generates a task plan file, which describes the execution of a task including manipulator and tooling motions. The high level controller of the manipulator interprets the task plan file and executes the task automatically. Thus, if the environment is not highly unstructured, a tooling task, which interacts with environment, will be executed in the autonomous mode. Therefore, the RTSA not only increases the system efficiency, but also improves the system reliability because the operator will act as backstop for safe operation after the 3-D models and task plan files are generated. However, unstructured conditions of environment and tasks necessitate that the telerobot operates in the teleoperation mode for successful execution of task. The inefficiency in the teleoperation mode led to the research

  1. Human performance during spaceflight.

    PubMed

    Manzey, D; Lorenz, B

    1999-04-01

    The paper focuses on three different questions: (1) What attributes cause space to be an extreme environment for humans? (2) What do we know about mental performance during spaceflight? (3) What kinds of psychological countermeasures are currently applied and/or conceivable for prolonged spaceflight which might help maintain mental efficiency and stabilize the emotional state of astronauts? Topics discussed include stressors that originate in the space environment, stressors related to the space habitat and its life-support system, stressors related to the mission specific workload of astronauts, stressors that arise from the psychosocial situation in a space habitat, manual performance during spaceflight, and psychological countermeasures for prolonged spaceflight.

  2. THE HUMAN CHROMOSOME

    PubMed Central

    Abuelo, J. G.; Moore, Dorothy E.

    1969-01-01

    Human lymphocytes were grown in short-term tissue culture and were arrested in metaphase with Colcemid. Their chromosomes were prepared by the Langmuir trough-critical point drying technique and were examined under the electron microscope. In addition, some chromosomes were digested with trypsin, Pronase, or DNase. The chromosomes consist entirely of tightly packed, 240 ± 50-A chromatin fibers. Trypsin and Pronase treatments induce relaxation of fiber packing and reveal certain underlying fiber arrangements. Furthermore, trypsin treatment demonstrates that the chromatin fiber has a 25–50 A trypsin-resistant core surrounded by a trypsin-sensitive sheath. DNase digestion suggests that this core contains DNA. PMID:5775795

  3. Investigating human evolutionary history

    PubMed Central

    WOOD, BERNARD

    2000-01-01

    We rely on fossils for the interpretation of more than 95% of our evolutionary history. Fieldwork resulting in the recovery of fresh fossil evidence is an important component of reconstructing human evolutionary history, but advances can also be made by extracting additional evidence for the existing fossil record, and by improving the methods used to interpret the fossil evidence. This review shows how information from imaging and dental microstructure has contributed to improving our understanding of the hominin fossil record. It also surveys recent advances in the use of the fossil record for phylogenetic inference. PMID:10999269

  4. Human detection and tracking

    NASA Astrophysics Data System (ADS)

    Yu, Pengxian; Wei, Yaxun

    2013-10-01

    This paper presents a method to segment moving human bodies. A self-adaptive background model is used to update the background image(so-called reference image). By calculating the Euclidean distance of corresponding points in the current and background image, we can check out the foreground objects. And the shadow can be detected and removed according to the characteristics of the shadow regions shown in HSV space. Finally, target tracking is implemented by calculating the relativity of color histogram between the moving areas in two succeeding images.

  5. Human portable preconcentrator system

    DOEpatents

    Linker, Kevin L.; Bouchier, Francis A.; Hannum, David W.; Rhykerd, Jr., Charles L.

    2003-01-01

    A preconcentrator system and apparatus suited to human portable use wherein sample potentially containing a target chemical substance is drawn into a chamber and through a pervious screen. The screen is adapted to capture target chemicals and then, upon heating, to release those chemicals into the chamber. Chemicals captured and then released in this fashion are then carried to a portable chemical detection device such as a portable ion mobility spectrometer. In the preferred embodiment, the means for drawing sample into the chamber comprises a reversible fan which, when operated in reverse direction, creates a backpressure that facilitates evolution of captured target chemicals into the chamber when the screen is heated.

  6. Human herpes simplex labialis.

    PubMed

    Fatahzadeh, M; Schwartz, R A

    2007-11-01

    Humans are the natural host for eight of more than 80 known herpes viruses. Infections with herpes simplex virus type 1 (HSV-1) are ubiquitous worldwide and highly transmissible. Herpes simplex labialis (HSL) is the best-recognized recrudescent infection of the lips and perioral tissues caused by HSV-1. Facial lesions of HSL may be unsightly, frequent outbreaks unpleasant, and the infection itself more severe locally and systemically in immunocompromised people. This article highlights the pathogenesis, clinical presentation, diagnostic features and management issues for HSL.

  7. Human adaptation to smog

    SciTech Connect

    Evans, G.W. Jacobs, S.V.; Frager, N.B.

    1982-10-01

    This study examined the health effects of human adaptation to photochemical smog. A group of recent arrivals to the Los Angeles air basin were compared to long-term residents of the basin. Evidence for adaptation included greater irritation and respiratory problems among the recent arrivals and desensitization among the long-term residents in their judgments of the severity of the smog problem to their health. There was no evidence for biochemical adaptation as measured by hemoglobin response to oxidant challenge. The results were discussed in terms of psychological adaption to chronic environmental stressors.

  8. Human transposon tectonics.

    PubMed

    Burns, Kathleen H; Boeke, Jef D

    2012-05-11

    Mobile DNAs have had a central role in shaping our genome. More than half of our DNA is comprised of interspersed repeats resulting from replicative copy and paste events of retrotransposons. Although most are fixed, incapable of templating new copies, there are important exceptions to retrotransposon quiescence. De novo insertions cause genetic diseases and cancers, though reliably detecting these occurrences has been difficult. New technologies aimed at uncovering polymorphic insertions reveal that mobile DNAs provide a substantial and dynamic source of structural variation. Key questions going forward include how and how much new transposition events affect human health and disease.

  9. Human exploration of Mars.

    PubMed

    Gwynne, O; McKay, C; Zubrin, R

    1991-06-01

    The human exploration of Mars has the potential to return a rich harvest of scientific information about that planet, its possible past biological history and the prospects for future habitation by Earthly life. The realization of that potential will require new approaches and new technologies--a whole new paradigm in space exploration. Picture yourself exploring the surface of Mars, where your task involves conducting a detailed investigation of features larger than the United States in order to uncover a record of planetary history spanning over four billion years.

  10. Human Exploration of Mars

    NASA Astrophysics Data System (ADS)

    Gwynne, Owen; McKay, Chris; Zubrin, Robert

    1991-06-01

    Novel approaches to the human exploration of Mars are considered with emphasis on a space suit design, extraterrestrial surface mobility, and water supply. A possible way of transporting personnel on the surface of Mars uses a suborbital rocket that will hop from one site to the next, refuelling each time it lands and giving the Martian explorers effective global mobility. Telepresence could be used to avoid limiting the people on Mars to a small exploration area as a result of a lack of transportation infrastructure. Drawings and photographs are included.

  11. [Human brown adipose tissue].

    PubMed

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  12. Photosensitive human syndromes.

    PubMed

    Spivak, Graciela; Hanawalt, Philip C

    2015-06-01

    Photosensitivity in humans can result from defects in repair of light-induced DNA lesions, from photoactivation of chemicals (including certain medications) with sunlight to produce toxic mediators, and by immune reactions to sunlight exposures. Deficiencies in DNA repair and the processing of damaged DNA during replication and transcription may result in mutations and genomic instability. We will review current understanding of photosensitivity to short wavelength ultraviolet light (UV) due to genetic defects in particular DNA repair pathways; deficiencies in some are characterized by an extremely high incidence of cancer in sun-exposed tissues, while in others no cancers have been reported.

  13. [Human castration: historical notes].

    PubMed

    Serarcangeli, C; Rispoli, G

    2001-01-01

    Human castration has been performed from early times for different reasons: to punish and revenge, to display one's religious fanaticism, to protect or to control women, for eunuchs' trade, for therapeutical purposes. In early modern times men were castrated to obtain sopranos voices, or for eugenic or racial reasons. Nowadays chemical castration is used as a therapeutic treatment or as a way to punish rape and other criminal behaviours. Castration is surgical or chemical act that may obviously cause serious physical and psychological consequences.

  14. Magnetic human body communication.

    PubMed

    Park, Jiwoong; Mercier, Patrick P

    2015-01-01

    This paper presents a new human body communication (HBC) technique that employs magnetic resonance for data transfer in wireless body-area networks (BANs). Unlike electric field HBC (eHBC) links, which do not necessarily travel well through many biological tissues, the proposed magnetic HBC (mHBC) link easily travels through tissue, offering significantly reduced path loss and, as a result, reduced transceiver power consumption. In this paper the proposed mHBC concept is validated via finite element method simulations and measurements. It is demonstrated that path loss across the body under various postures varies from 10-20 dB, which is significantly lower than alternative BAN techniques.

  15. Book Review: Human Radiosensitivity

    SciTech Connect

    Morgan, William F.

    2013-11-01

    This well written report reviews the evidence for variation in human sensitivity to ionizing radiation from epidemiological, clinical, animal, and experimental studies. The report also considers the mechanism(s) of radiation sensitivity and the ethical implications of current and potential knowledge that might be gained in the future. The report is concisely written, considers a large number of historical as well as recent studies, and features a ‘ bullet like ’ summary at the end of each chapter that captures the salient points.

  16. Human Transposon Tectonics

    PubMed Central

    Burns, Kathleen H.; Boeke, Jef D.

    2012-01-01

    Mobile DNAs have had a central role in shaping our genome. More than half of our DNA is comprised of interspersed repeats resulting from replicative copy and paste events of retrotransposons. Although most are fixed, incapable of templating new copies, there are important exceptions to retrotransposon quiescence. De novo insertions cause genetic diseases and cancers, though reliably detecting these occurrences has been difficult. New technologies aimed at uncovering polymorphic insertions reveal that mobile DNAs provide a substantial and dynamic source of structural variation. Key questions going forward include the how and how much new transposition events affect human health and disease. PMID:22579280

  17. Human Outreach through Physics

    NASA Astrophysics Data System (ADS)

    Kant Shukla, Padma

    2006-10-01

    In this talk unique methods for human outreach through physics are described. The focus is on identifying young talented researchers and colleagues around the globe and nourish them for the purpose of diffusing physics knowledge. The goal can be achieved through the organization of international conferences, workshops, seminars, and colleagues, at different locations, invite young and experienced researchers to those meetings, invite them to your home institution, in addition to visiting their universities/laboratories for mentoring and exchanging physics knowledge. The scientific part shall deal with collective processes and coherent nonlinear effects in space and laboratory plasmas.

  18. Biological databases for human research.

    PubMed

    Zou, Dong; Ma, Lina; Yu, Jun; Zhang, Zhang

    2015-02-01

    The completion of the Human Genome Project lays a foundation for systematically studying the human genome from evolutionary history to precision medicine against diseases. With the explosive growth of biological data, there is an increasing number of biological databases that have been developed in aid of human-related research. Here we present a collection of human-related biological databases and provide a mini-review by classifying them into different categories according to their data types. As human-related databases continue to grow not only in count but also in volume, challenges are ahead in big data storage, processing, exchange and curation.

  19. Stochastic Models of Human Errors

    NASA Technical Reports Server (NTRS)

    Elshamy, Maged; Elliott, Dawn M. (Technical Monitor)

    2002-01-01

    Humans play an important role in the overall reliability of engineering systems. More often accidents and systems failure are traced to human errors. Therefore, in order to have meaningful system risk analysis, the reliability of the human element must be taken into consideration. Describing the human error process by mathematical models is a key to analyzing contributing factors. Therefore, the objective of this research effort is to establish stochastic models substantiated by sound theoretic foundation to address the occurrence of human errors in the processing of the space shuttle.

  20. [A cyborg is only human].

    PubMed

    Schermer, Maartje H N

    2013-01-01

    New biomedical technologies make it possible to replace parts of the human body or to substitute its functions. Examples include artificial joints, eye lenses and arterial stents. Newer technologies use electronics and software, for example in brain-computer interfaces such as retinal implants and the exoskeleton MindWalker. Gradually we are creating cyborgs: hybrids of man and machine. This raises the question: are cyborgs still humans? It is argued that they are. First, because employing technology is a typically human characteristic. Second, because in western thought the human mind, and not the body, is considered to be the seat of personhood. However, it has been argued by phenomenological philosophers that the body is more than just an object but is also a subject, important for human identity. From this perspective, we can appreciate that a bionic body does not make one less human, but it does influence the experience of being human.

  1. Selection of Recombinant Human Antibodies.

    PubMed

    Tomszak, Florian; Weber, Susanne; Zantow, Jonas; Schirrmann, Thomas; Hust, Michael; Frenzel, André

    2016-01-01

    Since the development of therapeutic antibodies the demand of recombinant human antibodies is steadily increasing. Traditionally, therapeutic antibodies were generated by immunization of rat or mice, the generation of hybridoma clones, cloning of the antibody genes and subsequent humanization and engineering of the lead candidates. In the last few years, techniques were developed that use transgenic animals with a human antibody gene repertoire. Here, modern recombinant DNA technologies can be combined with well established immunization and hybridoma technologies to generate already affinity maturated human antibodies. An alternative are in vitro technologies which enabled the generation of fully human antibodies from antibody gene libraries that even exceed the human antibody repertoire. Specific antibodies can be isolated from these libraries in a very short time and therefore reduce the development time of an antibody drug at a very early stage.In this review, we describe different technologies that are currently used for the in vitro and in vivo generation of human antibodies.

  2. The science of human security.

    PubMed

    Taback, Nathan; Coupland, Robin

    2007-01-01

    During the 1990s medical studies using public health methodologies about injury and death due to weapons in conflict began to appear in the medical literature. The 1990s was also the period when the concept of human security was materialising in the development and humanitarian communities. Nowadays it is common for global organisations, governmental and non-governmental agencies, and academics to conduct scientific studies of human security. Many such studies gather evidence about human insecurity and these in turn lead to policy recommendations pertaining to improving human security. The data-to-policy process applies in this domain. In this article we propose that conceptual developments in human security and methods which generate scientific evidence of human security or insecurity have combined to create a new science: the science of human security. We describe key problems inherent in this new multidisciplinary science, some unique methodological challenges and new scientific opportunities.

  3. Humanized Antibodies for Antiviral Therapy

    NASA Astrophysics Data System (ADS)

    Co, Man Sung; Deschamps, Marguerite; Whitley, Richard J.; Queen, Cary

    1991-04-01

    Antibody therapy holds great promise for the treatment of cancer, autoimmune disorders, and viral infections. Murine monoclonal antibodies are relatively easy to produce but are severely restricted for therapeutic use by their immunogenicity in humans. Production of human monoclonal antibodies has been problematic. Humanized antibodies can be generated by introducing the six hypervariable regions from the heavy and light chains of a murine antibody into a human framework sequence and combining it with human constant regions. We humanized, with the aid of computer modeling, two murine monoclonal antibodies against herpes simplex virus gB and gD glycoproteins. The binding, virus neutralization, and cell protection results all indicate that both humanized antibodies have retained the binding activities and the biological properties of the murine monoclonal antibodies.

  4. Portrait of human tapeworms.

    PubMed

    Flisser, Ana; Viniegra, Ana-Elena; Aguilar-Vega, Laura; Garza-Rodriguez, Adriana; Maravilla, Pablo; Avila, Guillermina

    2004-08-01

    The tapeworms of the genus Taenia that infect human beings are T. solium, T. saginata and T. saginata asiatica. Taenia solium and T. saginata exhibit unequivocal features that characterize them; in contrast, only recent DNA studies, morphological characteristics, and epidemiological and sanitary aspects indicate that T. saginata asiatica is a subspecies of T. saginata. These 3 tapeworms occur in humans in their adult stage, and the intermediate hosts are pigs for T. solium and T. saginata asiatica and cows for T. saginata. Their identification is crucial considering the migratory increase from Asia to the Western Hemisphere and the fact that these tapeworms coexist in the same environment in Asia; furthermore, it is estimated that movement in both directions across the United States-Mexico border exceeds 200 million persons per yr, and thus, opportunities for acquiring and transporting T. solium infections are multiplied. It is not easy to distinguish among these tapeworms; therefore, a comparative diagram of the 3 parasites is shown in this article, which will facilitate their identification. All morphological features, some of which allow for identification, are clear and can be easily distinguished among the 3 tapeworms.

  5. [Mycotoxin research in humans].

    PubMed

    Lazo, Ramón F; Sierra, Gonzalo

    2008-03-01

    This study investigates the occurrence of aflatoxins in Ecuador. Early investigators proved the presence of aflatoxins in human and animal food, but the disturbing data lead to the formation of two research teams at Guayaquil University and the Agrarian University of Ecuador to investigate aflaxotins and other mycotoxins in food and their relationship to human health. Because the concept of mycotoxicosis as a result of the secondary metabolites produced by different species of moulds could cause different clinical patterns, the research team includes Aspergillus metabolites found in the urine of a patient with pulmonary aspergilloma. We considered that the body itself could create secondary metabolites. An ELISA method was used to detect mycotoxins with the specific reactive compounds using a company base assay. This allows the detection quantitative of such metabolites in 24 h collected urine. The patient was treated with itraconazole for nine months, after clinical, radiological and aflatoxins testing. We also investigated three other cases in children with a second level of malnutrition and only with vomitoxins results and in three investigated cases of otomycosis caused by Aspergillus niger only in one case traces of aflatoxins were found.

  6. SARSCEST (human factors)

    NASA Technical Reports Server (NTRS)

    Parsons, H. Mcilvaine

    1988-01-01

    People interact with the processes and products of contemporary technology. Individuals are affected by these in various ways and individuals shape them. Such interactions come under the label 'human factors'. To expand the understanding of those to whom the term is relatively unfamiliar, its domain includes both an applied science and applications of knowledge. It means both research and development, with implications of research both for basic science and for development. It encompasses not only design and testing but also training and personnel requirements, even though some unwisely try to split these apart both by name and institutionally. The territory includes more than performance at work, though concentration on that aspect, epitomized in the derivation of the term ergonomics, has overshadowed human factors interest in interactions between technology and the home, health, safety, consumers, children and later life, the handicapped, sports and recreation education, and travel. Two aspects of technology considered most significant for work performance, systems and automation, and several approaches to these, are discussed.

  7. Adipokines in human reproduction.

    PubMed

    Dupont, Joëlle; Pollet-Villard, Xavier; Reverchon, Maxime; Mellouk, Namya; Levy, Rachel

    2015-10-01

    Adipose tissue communicates with other central and peripheral organs by the synthesis and release of substances called adipokines. The most studied adipokine is leptin but others have been recently identified including resistin, adiponectin, chemerin, omentin and visfatin. These adipokines have a critical role in the development of obesity-related complications and inflammatory conditions. However, they are also involved in other functions in the organism including reproductive functions. Indeed, many groups have demonstrated that adipokine receptors, such as adiponectin and chemerin, but also adipokines themselves (adiponectin, chemerin, resistin, visfatin and omentin) are expressed in human peripheral reproductive tissues and that these adipokines are likely to exert direct effects on these tissues. After a brief description of these new adipokines, an overview of their actions in different human reproductive organs (hypothalamus, pituitary, ovary, testis, uterus and placenta) will be presented. Finally, comments will be made on the eventual alterations of these adipokines in reproductive disorders, with special attention to polycystic ovary syndrome, a disease characterized by dysfunction of gonadal axis and systemic nerve endocrine metabolic network with a prevalence of up to 10% in women of reproductive age.

  8. The human respiratory gate

    NASA Technical Reports Server (NTRS)

    Eckberg, Dwain L.

    2003-01-01

    Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this 'respiratory gating' is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R-R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R-R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.

  9. Globalization and human cooperation

    PubMed Central

    Buchan, Nancy R.; Grimalda, Gianluca; Wilson, Rick; Brewer, Marilynn; Fatas, Enrique; Foddy, Margaret

    2009-01-01

    Globalization magnifies the problems that affect all people and that require large-scale human cooperation, for example, the overharvesting of natural resources and human-induced global warming. However, what does globalization imply for the cooperation needed to address such global social dilemmas? Two competing hypotheses are offered. One hypothesis is that globalization prompts reactionary movements that reinforce parochial distinctions among people. Large-scale cooperation then focuses on favoring one's own ethnic, racial, or language group. The alternative hypothesis suggests that globalization strengthens cosmopolitan attitudes by weakening the relevance of ethnicity, locality, or nationhood as sources of identification. In essence, globalization, the increasing interconnectedness of people worldwide, broadens the group boundaries within which individuals perceive they belong. We test these hypotheses by measuring globalization at both the country and individual levels and analyzing the relationship between globalization and individual cooperation with distal others in multilevel sequential cooperation experiments in which players can contribute to individual, local, and/or global accounts. Our samples were drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. We find that as country and individual levels of globalization increase, so too does individual cooperation at the global level vis-à-vis the local level. In essence, “globalized” individuals draw broader group boundaries than others, eschewing parochial motivations in favor of cosmopolitan ones. Globalization may thus be fundamental in shaping contemporary large-scale cooperation and may be a positive force toward the provision of global public goods. PMID:19255433

  10. Globalization and human cooperation.

    PubMed

    Buchan, Nancy R; Grimalda, Gianluca; Wilson, Rick; Brewer, Marilynn; Fatas, Enrique; Foddy, Margaret

    2009-03-17

    Globalization magnifies the problems that affect all people and that require large-scale human cooperation, for example, the overharvesting of natural resources and human-induced global warming. However, what does globalization imply for the cooperation needed to address such global social dilemmas? Two competing hypotheses are offered. One hypothesis is that globalization prompts reactionary movements that reinforce parochial distinctions among people. Large-scale cooperation then focuses on favoring one's own ethnic, racial, or language group. The alternative hypothesis suggests that globalization strengthens cosmopolitan attitudes by weakening the relevance of ethnicity, locality, or nationhood as sources of identification. In essence, globalization, the increasing interconnectedness of people worldwide, broadens the group boundaries within which individuals perceive they belong. We test these hypotheses by measuring globalization at both the country and individual levels and analyzing the relationship between globalization and individual cooperation with distal others in multilevel sequential cooperation experiments in which players can contribute to individual, local, and/or global accounts. Our samples were drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. We find that as country and individual levels of globalization increase, so too does individual cooperation at the global level vis-à-vis the local level. In essence, "globalized" individuals draw broader group boundaries than others, eschewing parochial motivations in favor of cosmopolitan ones. Globalization may thus be fundamental in shaping contemporary large-scale cooperation and may be a positive force toward the provision of global public goods.

  11. Human kin detection.

    PubMed

    Bressan, Paola; Kramer, Peter

    2015-01-01

    Natural selection has favored the evolution of behaviors that benefit not only one's genes, but also their copies in genetically related individuals. These behaviors include optimal outbreeding (choosing a mate that is neither too closely related, nor too distant), nepotism (helping kin), and spite (hurting non-kin at a personal cost), and all require some form of kin detection or kin recognition. Yet, kinship cannot be assessed directly; human kin detection relies on heuristic cues that take into account individuals' context (whether they were reared by our mother, or grew up in our home, or were given birth by our spouse), appearance (whether they smell or look like us), and ability to arouse certain feelings (whether we feel emotionally close to them). The uncertainties of kin detection, along with its dependence on social information, create ample opportunities for the evolution of deception and self-deception. For example, babies carry no unequivocal stamp of their biological father, but across cultures they are passionately claimed to resemble their mother's spouse; to the same effect, 'neutral' observers are greatly influenced by belief in relatedness when judging resemblance between strangers. Still, paternity uncertainty profoundly shapes human relationships, reducing not only the investment contributed by paternal versus maternal kin, but also prosocial behavior between individuals who are related through one or more males rather than females alone. Because of its relevance to racial discrimination and political preferences, the evolutionary pressure to prefer kin to non-kin has a manifold influence on society at large.

  12. Immunopathogenesis of human schistosomiasis.

    PubMed

    Burke, M L; Jones, M K; Gobert, G N; Li, Y S; Ellis, M K; McManus, D P

    2009-04-01

    Schistosomiasis continues to be a significant cause of parasitic morbidity and mortality worldwide. This review considers the basic features of the pathology and clinical outcomes of hepatointestinal and genitourinary schistosomiasis, presents an overview of the numerous studies on animal models that have clarified many of the immunopathological features, and provides insight into our current understanding of the immunopathogenesis and genetic control of human schistosomiasis. In murine schistosomiasis, pathology is induced by a CD4(+) Th2 driven granulomatous response directed against schistosome eggs lodged in the host liver. The Th2 cytokines IL-4 and IL-13 drive this response, whereas IL-10, IL13Ralpha2, IFN-gamma and a subset of regulatory T-cells act to limit schistosome induced pathology. A variety of cell types including hepatic stellate cells, alternatively activated macrophages and regulatory T-cells have also been implicated in the pathogenesis of schistosomiasis. Current knowledge suggests the immunopathogenic mechanisms underlying human schistosomiasis are likely to be similar. The review also considers the future development of anti-pathology schistosome vaccines. As fibrosis is an important feature of many other diseases such as Crohn's disease and sarcoidosis, a comprehensive understanding of the cellular and molecular mechanisms involved in schistosomiasis may also ultimately contribute to the development an effective disease intervention strategy for other granulofibrotic diseases.

  13. The Human Sweet Tooth

    PubMed Central

    Reed, Danielle R; McDaniel, Amanda H

    2006-01-01

    Humans love the taste of sugar and the word "sweet" is used to describe not only this basic taste quality but also something that is desirable or pleasurable, e.g., la dolce vita. Although sugar or sweetened foods are generally among the most preferred choices, not everyone likes sugar, especially at high concentrations. The focus of my group's research is to understand why some people have a sweet tooth and others do not. We have used genetic and molecular techniques in humans, rats, mice, cats and primates to understand the origins of sweet taste perception. Our studies demonstrate that there are two sweet receptor genes (TAS1R2 and TAS1R3), and alleles of one of the two genes predict the avidity with which some mammals drink sweet solutions. We also find a relationship between sweet and bitter perception. Children who are genetically more sensitive to bitter compounds report that very sweet solutions are more pleasant and they prefer sweet carbonated beverages more than milk, relative to less bitter-sensitive peers. Overall, people differ in their ability to perceive the basic tastes, and particular constellations of genes and experience may drive some people, but not others, toward a caries-inducing sweet diet. Future studies will be designed to understand how a genetic preference for sweet food and drink might contribute to the development of dental caries. PMID:16934118

  14. First human Cerenkography

    NASA Astrophysics Data System (ADS)

    Spinelli, Antonello Enrico; Ferdeghini, Marco; Cavedon, Carlo; Zivelonghi, Emanuele; Calandrino, Riccardo; Fenzi, Alberto; Sbarbati, Andrea; Boschi, Federico

    2013-02-01

    Cerenkov luminescence imaging is an emerging optical preclinical modality based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues with a velocity greater than the speed of light. We present the first human Cerenkography obtained by detecting Cerenkov radiation escaping the thyroid gland of a patient treated for hyperthyroidism. The Cerenkov light was detected using an electron multiplied charge coupled device and a conventional C-mount lens. The system set-up has been tested by using a slab of ex vivo tissue equal to a 1 cm slice of chicken breast in order to simulate optical photons attenuation. We then imaged for 2 min the head and neck region of a patient treated orally 24 h before with 550 MBq of I-131. Co-registration between photographic and Cerenkov images showed a good localization of the Cerenkov light within the thyroid region. In conclusion, we showed that it is possible to obtain a planar image of Cerenkov photons escaping from a human tissue. Cerenkography is a potential novel medical tool to image superficial organs of patients treated with beta minus radiopharmaceuticals and can be extended to the imaging of beta plus emitters.

  15. Superstitious behavior in humans

    PubMed Central

    Ono, Koichi

    1987-01-01

    Twenty undergraduate students were exposed to single response-independent schedules of reinforcer presentation, fixed-time or variable-time, each with values of 30 and 60 s. The reinforcer was a point on a counter accompanied by a red lamp and a brief buzzer. Three color signals were presented, without consistent relation to reinforcer or to the subjects' behavior. Three large levers were available, but the subjects were not asked to perform any particular behavior. Three of the 20 subjects developed persistent superstitious behavior. One engaged in a pattern of lever-pulling responses that consisted of long pulls after a few short pulls; the second touched many things in the experimental booth; the third showed biased responding called sensory superstition. However, most subjects did not show consistent superstitious behavior. Reinforcers can operate effectively on human behavior even in the absence of a response-reinforcer contingency and can, in some cases, shape stable superstitious patterns. However, superstitious behavior is not a consistent outcome of exposure of human subjects to response-independent reinforcer deliveries. PMID:16812480

  16. Human arginase isozymes.

    PubMed

    Grody, W W; Dizikes, G J; Cederbaum, S D

    1987-01-01

    Studies in experimental animals and humans demonstrate the existence of two arginase isozymes. One, designated AI (or A1), has a high pI, is located in the cytosol, is most abundant in liver, and is thought to be primarily responsible for ammonia detoxification as urea. The gene coding for this isozyme is mutated in human hyperargininemia. A second isozyme, designated AII (or A4), has a neutral pI, is located in the mitochondrial matrix, and is thought to be involved primarily in the production of ornithine as a precursor of proline and glutamate. It appears to be expressed in most but not all tissues and in more nearly equal amounts. The two isozymes are immunologically distinct and are coded for by two separate genes. The great similarity in all measured kinetic and some physicochemical properties implies a high degree of structural similarity at the active site, but the lack of immunological cross-reactivity and DNA cross-hybridization implies substantial compositional differences in other parts of the enzyme molecules.

  17. The Human Variome Project.

    PubMed

    Burn, John; Watson, Michael

    2016-06-01

    The practical realization of genomics has meant a growing realization that variant interpretation is a major barrier to practical use of DNA sequence data. The late Professor Dick Cotton devoted his life to innovation in molecular genetics and was a prime mover in the international response to the need to understand the "variome." His leadership resulted in the launch first of the Human Genetic Variation Society and then, in 2006, an international agreement to launch the Human Variome Project (HVP), aimed at data integration enabled by standards and infrastructure of the databases of variants being identified in families with a range of inherited disorders. The project attracted a network of affiliates across 81 countries and earned formal recognition by UNESCO, which now hosts its biennial meetings. It has also signed a Memorandum of Understanding with the World Health Organization. Future progress will depend on longer term secure funding and integration with the efforts of the genomics community where the rapid advances in sequencing technology have enabled variant capture on a previously unimaginable scale. Efforts are underway to integrate the efforts of HVP with those of the Global Alliance for Genomics and Health to provide a lasting legacy of Dick Cotton's vision.

  18. Issues on combining human and non-human intelligence

    NASA Technical Reports Server (NTRS)

    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.

  19. Human dignity and human rights in bioethics: the Kantian approach.

    PubMed

    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.

  20. Leptospirosis in Humans

    PubMed Central

    Levett, Paul N.

    2015-01-01

    Leptospirosis is a widespread and potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding. Infection results from direct or indirect exposure to infected reservoir host animals that carry the pathogen in their renal tubules and shed pathogenic leptospires in their urine. Although many wild and domestic animals can serve as reservoir hosts, the brown rat (Rattus norvegicus) is the most important source of human infections. Individuals living in urban slum environments characterized by inadequate sanitation and poor housing are at high risk of rat exposure and leptospirosis. The global burden of leptospirosis is expected to rise with demographic shifts that favor increases in the number of urban poor in tropical regions subject to worsening storms and urban flooding due to climate change. Data emerging from prospective surveillance studies suggest that most human leptospiral infections in endemic areas are mild or asymptomatic. Development of more severe outcomes likely depends on three factors: epidemiological conditions, host susceptibility, and pathogen virulence (Fig. 1). Mortality increases with age, particularly in patients older than 60 years of age. High levels of bacteremia are associated with poor clinical outcomes and, based on animal model and in vitro studies, are related in part to poor recognition of leptospiral LPS by human TLR4. Patients with severe leptospirosis experience a cytokine storm characterized by high levels of IL-6, TNF-alpha, and IL-10. Patients with the HLA DQ6 allele are at higher risk of disease, suggesting a role for lymphocyte stimulation by a leptospiral superantigen. Leptospirosis typically presents as a nonspecific, acute febrile illness characterized by fever, myalgia, and headache and may be confused with other entities such as influenza and dengue fever. Newer diagnostic methods facilitate early diagnosis and antibiotic treatment. Patients progressing to

  1. The Human Urine Metabolome

    PubMed Central

    Bouatra, Souhaila; Aziat, Farid; Mandal, Rupasri; Guo, An Chi; Wilson, Michael R.; Knox, Craig; Bjorndahl, Trent C.; Krishnamurthy, Ramanarayan; Saleem, Fozia; Liu, Philip; Dame, Zerihun T.; Poelzer, Jenna; Huynh, Jessica; Yallou, Faizath S.; Psychogios, Nick; Dong, Edison; Bogumil, Ralf; Roehring, Cornelia; Wishart, David S.

    2013-01-01

    Urine has long been a “favored” biofluid among metabolomics researchers. It is sterile, easy-to-obtain in large volumes, largely free from interfering proteins or lipids and chemically complex. However, this chemical complexity has also made urine a particularly difficult substrate to fully understand. As a biological waste material, urine typically contains metabolic breakdown products from a wide range of foods, drinks, drugs, environmental contaminants, endogenous waste metabolites and bacterial by-products. Many of these compounds are poorly characterized and poorly understood. In an effort to improve our understanding of this biofluid we have undertaken a comprehensive, quantitative, metabolome-wide characterization of human urine. This involved both computer-aided literature mining and comprehensive, quantitative experimental assessment/validation. The experimental portion employed NMR spectroscopy, gas chromatography mass spectrometry (GC-MS), direct flow injection mass spectrometry (DFI/LC-MS/MS), inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) experiments performed on multiple human urine samples. This multi-platform metabolomic analysis allowed us to identify 445 and quantify 378 unique urine metabolites or metabolite species. The different analytical platforms were able to identify (quantify) a total of: 209 (209) by NMR, 179 (85) by GC-MS, 127 (127) by DFI/LC-MS/MS, 40 (40) by ICP-MS and 10 (10) by HPLC. Our use of multiple metabolomics platforms and technologies allowed us to identify several previously unknown urine metabolites and to substantially enhance the level of metabolome coverage. It also allowed us to critically assess the relative strengths and weaknesses of different platforms or technologies. The literature review led to the identification and annotation of another 2206 urinary compounds and was used to help guide the subsequent experimental studies. An online database containing

  2. Human Research Program Requirements Document. Human Research Program Revision E

    NASA Technical Reports Server (NTRS)

    Vargas, Paul

    2011-01-01

    This document defines, documents, and allocates the Human Research Program (HRP) requirements to the HRP Program Elements. It also establishes the flow of requirements from the Human Exploration and Operations Mission Directorate (HEOMD) and the Office of the Chief Health and Medical Officer (OCHMO) down to the various HRP Program Elements to ensure that human research and technology countermeasure investments support the delivery of countermeasures and technologies that satisfy HEOMD's and OCHMO's exploration mission requirements.

  3. Human Dignity and Human Enhancement: A Multidimensional Approach.

    PubMed

    Kirchhoffer, David G

    2017-02-09

    In the debates concerning the ethics of human enhancement through biological or technological modifications, there have been several appeals to the concept of human dignity, both by those favouring such enhancement and by those opposing it. The result is the phenomenon of 'dignity talk', where opposing sides both appeal to the concept of human dignity to ground their arguments resulting in a moral impasse. This article examines the use of the concept of human dignity in the enhancement debates and reveals that the problem of dignity talk arises because proponents of various positions tend to ground human dignity in different features of the human individual. These features include species-membership, possession of a particular capacity, a sense of self-worth, and moral behaviour. The article proposes a solution to this problem by appealing to another feature of human beings, namely their being-in-relationship-over-time. Doing so enables us to understand dignity as a concept that affirms the worth of human individuals as complex, multidimensional wholes, rather than as isolated features. Consequently, the concept of human dignity can serve both a descriptive and a normative function in the enhancement debates. At a descriptive level, asking what advocates of a position mean when they refer to human dignity will reveal what aspects of being human they deem to be most valuable. The debate can then focus on these values. The normative function, although it cannot proscribe or prescribe all enhancement, approves only those enhancements that contribute to the flourishing of human individuals as multidimensional wholes.

  4. Human subjects research handbook: Protecting human research subjects. Second edition

    SciTech Connect

    1996-01-30

    This handbook serves as a guide to understanding and implementing the Federal regulations and US DOE Orders established to protect human research subjects. Material in this handbook is directed towards new and continuing institutional review board (IRB) members, researchers, institutional administrators, DOE officials, and others who may be involved or interested in human subjects research. It offers comprehensive overview of the various requirements, procedures, and issues relating to human subject research today.

  5. Human metabolic atlas: an online resource for human metabolism.

    PubMed

    Pornputtapong, Natapol; Nookaew, Intawat; Nielsen, Jens

    2015-01-01

    Human tissue-specific genome-scale metabolic models (GEMs) provide comprehensive understanding of human metabolism, which is of great value to the biomedical research community. To make this kind of data easily accessible to the public, we have designed and deployed the human metabolic atlas (HMA) website (http://www.metabolicatlas.org). This online resource provides comprehensive information about human metabolism, including the results of metabolic network analyses. We hope that it can also serve as an information exchange interface for human metabolism knowledge within the research community. The HMA consists of three major components: Repository, Hreed (Human REaction Entities Database) and Atlas. Repository is a collection of GEMs for specific human cell types and human-related microorganisms in SBML (System Biology Markup Language) format. The current release consists of several types of GEMs: a generic human GEM, 82 GEMs for normal cell types, 16 GEMs for different cancer cell types, 2 curated GEMs and 5 GEMs for human gut bacteria. Hreed contains detailed information about biochemical reactions. A web interface for Hreed facilitates an access to the Hreed reaction data, which can be easily retrieved by using specific keywords or names of related genes, proteins, compounds and cross-references. Atlas web interface can be used for visualization of the GEMs collection overlaid on KEGG metabolic pathway maps with a zoom/pan user interface. The HMA is a unique tool for studying human metabolism, ranging in scope from an individual cell, to a specific organ, to the overall human body. This resource is freely available under a Creative Commons Attribution-NonCommercial 4.0 International License.

  6. Future of Mechatronics and Human

    NASA Astrophysics Data System (ADS)

    Harashima, Fumio; Suzuki, Satoshi

    This paper mentions circumstance of mechatronics that sustain our human society, and introduces HAM(Human Adaptive Mechatronics)-project as one of research projects to create new human-machine system. The key point of HAM is skill, and analysis of skill and establishment of assist method to enhance total performance of human-machine system are main research concerns. As study of skill is an elucidation of human itself, analyses of human higher function are significant. In this paper, after surveying researches of human brain functions, an experimental analysis of human characteristic in machine operation is shown as one example of our research activities. We used hovercraft simulator as verification system including observation, voluntary motion control and machine operation that are needed to general machine operation. Process and factors to become skilled were investigated by identification of human control characteristics with measurement of the operator's line-of sight. It was confirmed that early switching of sub-controllers / reference signals in human and enhancement of space perception are significant.

  7. Genetics and recent human evolution.

    PubMed

    Templeton, Alan R

    2007-07-01

    Starting with "mitochondrial Eve" in 1987, genetics has played an increasingly important role in studies of the last two million years of human evolution. It initially appeared that genetic data resolved the basic models of recent human evolution in favor of the "out-of-Africa replacement" hypothesis in which anatomically modern humans evolved in Africa about 150,000 years ago, started to spread throughout the world about 100,000 years ago, and subsequently drove to complete genetic extinction (replacement) all other human populations in Eurasia. Unfortunately, many of the genetic studies on recent human evolution have suffered from scientific flaws, including misrepresenting the models of recent human evolution, focusing upon hypothesis compatibility rather than hypothesis testing, committing the ecological fallacy, and failing to consider a broader array of alternative hypotheses. Once these flaws are corrected, there is actually little genetic support for the out-of-Africa replacement hypothesis. Indeed, when genetic data are used in a hypothesis-testing framework, the out-of-Africa replacement hypothesis is strongly rejected. The model of recent human evolution that emerges from a statistical hypothesis-testing framework does not correspond to any of the traditional models of human evolution, but it is compatible with fossil and archaeological data. These studies also reveal that any one gene or DNA region captures only a small part of human evolutionary history, so multilocus studies are essential. As more and more loci became available, genetics will undoubtedly offer additional insights and resolutions of human evolution.

  8. Human Error: A Concept Analysis

    NASA Technical Reports Server (NTRS)

    Hansen, Frederick D.

    2007-01-01

    Human error is the subject of research in almost every industry and profession of our times. This term is part of our daily language and intuitively understood by most people however, it would be premature to assume that everyone's understanding of human error s the same. For example, human error is used to describe the outcome or consequence of human action, the causal factor of an accident, deliberate violations,a nd the actual action taken by a human being. As a result, researchers rarely agree on the either a specific definition or how to prevent human error. The purpose of this article is to explore the specific concept of human error using Concept Analysis as described by Walker and Avant (1995). The concept of human error is examined as currently used in the literature of a variety of industries and professions. Defining attributes and examples of model, borderline, and contrary cases are described. The antecedents and consequences of human error are also discussed and a definition of human error is offered.

  9. A human rights approach to human trafficking for organ removal.

    PubMed

    Budiani-Saberi, Debra; Columb, Seán

    2013-11-01

    Human trafficking for organ removal (HTOR) should not be reduced to a problem of supply and demand of organs for transplantation, a problem of organized crime and criminal justice, or a problem of voiceless, abandoned victims. Rather, HTOR is at once an egregious human rights abuse and a form of human trafficking. As such, it demands a human-rights based approach in analysis and response to this problem, placing the victim at the center of initiatives to combat this phenomenon. Such an approach requires us to consider how various measures impact or disregard victims/potential victims of HTOR and gives us tools to better advocate their interests, rights and freedoms.

  10. Analysis of human emotion in human-robot interaction

    NASA Astrophysics Data System (ADS)

    Blar, Noraidah; Jafar, Fairul Azni; Abdullah, Nurhidayu; Muhammad, Mohd Nazrin; Kassim, Anuar Muhamed

    2015-05-01

    There is vast application of robots in human's works such as in industry, hospital, etc. Therefore, it is believed that human and robot can have a good collaboration to achieve an optimum result of work. The objectives of this project is to analyze human-robot collaboration and to understand humans feeling (kansei factors) when dealing with robot that robot should adapt to understand the humans' feeling. Researches currently are exploring in the area of human-robot interaction with the intention to reduce problems that subsist in today's civilization. Study had found that to make a good interaction between human and robot, first it is need to understand the abilities of each. Kansei Engineering in robotic was used to undergo the project. The project experiments were held by distributing questionnaire to students and technician. After that, the questionnaire results were analyzed by using SPSS analysis. Results from the analysis shown that there are five feelings which significant to the human in the human-robot interaction; anxious, fatigue, relaxed, peaceful, and impressed.

  11. Human Performance Modeling for Dynamic Human Reliability Analysis

    SciTech Connect

    Boring, Ronald Laurids; Joe, Jeffrey Clark; Mandelli, Diego

    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.

  12. Germ-line enhancement of humans and non-humans.

    PubMed

    Loftis, J Robert

    2005-03-01

    The current difference in attitude toward germ-line enhancement in humans and nonhumans is unjustified. Society should be more cautious in modifying the genes of nonhumans and more bold in thinking about modifying our own genome. I identify four classes of arguments pertaining to germ-line enhancement: safety arguments, justice arguments, trust arguments, and naturalness arguments. The first three types are compelling, but do not distinguish between human and nonhuman cases. The final class of argument would justify a distinction between human and nonhuman germ-line enhancement; however, this type of argument fails and, therefore, the discrepancy in attitude toward human and nonhuman germ-line enhancement is unjustified.

  13. Human Thermal Model Evaluation Using the JSC Human Thermal Database

    NASA Technical Reports Server (NTRS)

    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.

  14. Egalitarian motives in humans.

    PubMed

    Dawes, Christopher T; Fowler, James H; Johnson, Tim; McElreath, Richard; Smirnov, Oleg

    2007-04-12

    Participants in laboratory games are often willing to alter others' incomes at a cost to themselves, and this behaviour has the effect of promoting cooperation. What motivates this action is unclear: punishment and reward aimed at promoting cooperation cannot be distinguished from attempts to produce equality. To understand costly taking and costly giving, we create an experimental game that isolates egalitarian motives. The results show that subjects reduce and augment others' incomes, at a personal cost, even when there is no cooperative behaviour to be reinforced. Furthermore, the size and frequency of income alterations are strongly influenced by inequality. Emotions towards top earners become increasingly negative as inequality increases, and those who express these emotions spend more to reduce above-average earners' incomes and to increase below-average earners' incomes. The results suggest that egalitarian motives affect income-altering behaviours, and may therefore be an important factor underlying the evolution of strong reciprocity and, hence, cooperation in humans.

  15. Redesigned Human Metabolic Simulator

    NASA Technical Reports Server (NTRS)

    Duffield, Bruce; Jeng, Frank; Lange, Kevin

    2008-01-01

    A design has been formulated for a proposed improved version of an apparatus that simulates atmospheric effects of human respiration by introducing controlled amounts of carbon dioxide, water vapor, and heat into the air. Denoted a human metabolic simulator (HMS), the apparatus is used for testing life-support equipment when human test subjects are not available. The prior version of the HMS, to be replaced, was designed to simulate the respiratory effects of as many as four persons. It exploits the catalytic combustion of methyl acetate, for which the respiratory quotient (the molar ratio of carbon dioxide produced to oxygen consumed) is very close to the human respiratory quotient of about 0.86. The design of the improved HMS provides for simulation of the respiratory effects of as many as eight persons at various levels of activity. The design would also increase safety by eliminating the use of combustion. The improved HMS (see figure) would include a computer that would exert overall control. The computer would calculate the required amounts of oxygen removal, carbon dioxide addition, water addition, and heat addition by use of empirical equations for metabolic profiles of respiration and heat. A blower would circulate air between the HMS and a chamber containing a life-support system to be tested. With the help of feedback from a mass flowmeter, the blower speed would be adjusted to regulate the rate of flow according to the number of persons to be simulated and to a temperature-regulation requirement (the air temperature would indirectly depend on the rate of flow, among other parameters). Oxygen would be removed from the circulating air by means of a commercially available molecular sieve configured as an oxygen concentrator. Oxygen, argon, and trace amounts of nitrogen would pass through a bed in the molecular sieve while carbon dioxide, the majority of nitrogen, and other trace gases would be trapped by the bed and subsequently returned to the chamber. If

  16. Human-computer interface

    DOEpatents

    Anderson, Thomas G.

    2004-12-21

    The present invention provides a method of human-computer interfacing. Force feedback allows intuitive navigation and control near a boundary between regions in a computer-represented space. For example, the method allows a user to interact with a virtual craft, then push through the windshield of the craft to interact with the virtual world surrounding the craft. As another example, the method allows a user to feel transitions between different control domains of a computer representation of a space. The method can provide for force feedback that increases as a user's locus of interaction moves near a boundary, then perceptibly changes (e.g., abruptly drops or changes direction) when the boundary is traversed.

  17. [Human health sciences].

    PubMed

    Sasada, Masataka; Toichi, Motomi; Yamane, Hiroshi

    2009-01-01

    Medical science and medical practice developed remarkably and economic conditions progressed so much in recent years in Japan. As the result, the average span of life of the Japanese is now the longest in the world and we are well off. The matter of the greatest concern of Japanese people at present is health. In fact, health foods, TV program on health and various matters concerning health overflow around us. It is fairly difficult to define health clearly and correctly. So long as anyone who wants to be in good health, he must be well physically and mentally. It is necessary to pursue the true health, and to investigate theories and techniques to obtain and concrete it, which is called human health sciences.

  18. [Papillomaviruses and human tumors].

    PubMed

    Vonka, V; Hamsíková, E; Sobotková, E; Smahel, M; Kitasato, H; Sainerová, H; Ludvíková, V; Zák, R; Kanka, J; Kolár, Z; Kovarík, J

    2000-12-01

    The report summarizes the main results obtained in the course of our research project. The results of immunological and epidemiological studies provide further proofs that human papillomaviruses (HPV) are the etiological agents in cervical neoplasia. In addition, they raise hopes that immunological methods may be utilized in diagnostics of cervical cancer and for monitoring the clinical course of this disease in the near future. Since the etiological relationship between HPV and cervical carcinoma seems to be proven beyond reasonable doubt, the development of prophylactic and therapeutic vaccines has become the dominant of the contemporary HPV reseach. For studying immune reactions against HPV-induced tumours we developed a model of HPV16-transformed rodent cells.

  19. Human basal body basics.

    PubMed

    Vertii, Anastassiia; Hung, Hui-Fang; Hehnly, Heidi; Doxsey, Stephen

    2016-01-01

    In human cells, the basal body (BB) core comprises a ninefold microtubule-triplet cylindrical structure. Distal and subdistal appendages are located at the distal end of BB, where they play indispensable roles in cilium formation and function. Most cells that arrest in the G0 stage of the cell cycle initiate BB docking at the plasma membrane followed by BB-mediated growth of a solitary primary cilium, a structure required for sensing the extracellular environment and cell signaling. In addition to the primary cilium, motile cilia are present in specialized cells, such as sperm and airway epithelium. Mutations that affect BB function result in cilia dysfunction. This can generate syndromic disorders, collectively called ciliopathies, for which there are no effective treatments. In this review, we focus on the features and functions of BBs and centrosomes in Homo sapiens.

  20. Human physiology in space

    NASA Technical Reports Server (NTRS)

    Vernikos, J.

    1996-01-01

    The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

  1. Human Reliability Program Workshop

    SciTech Connect

    Landers, John; Rogers, Erin; Gerke, Gretchen

    2014-05-18

    A Human Reliability Program (HRP) is designed to protect national security as well as worker and public safety by continuously evaluating the reliability of those who have access to sensitive materials, facilities, and programs. Some elements of a site HRP include systematic (1) supervisory reviews, (2) medical and psychological assessments, (3) management evaluations, (4) personnel security reviews, and (4) training of HRP staff and critical positions. Over the years of implementing an HRP, the Department of Energy (DOE) has faced various challenges and overcome obstacles. During this 4-day activity, participants will examine programs that mitigate threats to nuclear security and the insider threat to include HRP, Nuclear Security Culture (NSC) Enhancement, and Employee Assistance Programs. The focus will be to develop an understanding of the need for a systematic HRP and to discuss challenges and best practices associated with mitigating the insider threat.

  2. Energy and human health.

    PubMed

    Smith, Kirk R; Frumkin, Howard; Balakrishnan, Kalpana; Butler, Colin D; Chafe, Zoë A; Fairlie, Ian; Kinney, Patrick; Kjellstrom, Tord; Mauzerall, Denise L; McKone, Thomas E; McMichael, Anthony J; Schneider, Mycle

    2013-01-01

    Energy use is central to human society and provides many health benefits. But each source of energy entails some health risks. This article reviews the health impacts of each major source of energy, focusing on those with major implications for the burden of disease globally. The biggest health impacts accrue to the harvesting and burning of solid fuels, coal and biomass, mainly in the form of occupational health risks and household and general ambient air pollution. Lack of access to clean fuels and electricity in the world's poor households is a particularly serious risk for health. Although energy efficiency brings many benefits, it also entails some health risks, as do renewable energy systems, if not managed carefully. We do not review health impacts of climate change itself, which are due mostly to climate-altering pollutants from energy systems, but do discuss the potential for achieving near-term health cobenefits by reducing certain climate-related emissions.

  3. Human portable preconcentrator system

    DOEpatents

    Linker, Kevin L.; Brusseau, Charles A.; Hannum, David W.; Puissant, James G.; Varley, Nathan R.

    2003-08-12

    A preconcentrator system and apparatus suited to human portable use wherein sample potentially containing a target chemical substance is drawn into a chamber and through a pervious screen. The screen is adapted to capture target chemicals and then, upon heating, to release those chemicals into the chamber. Chemicals captured and then released in this fashion are then carried to a portable chemical detection device such as a portable ion mobility spectrometer. In the preferred embodiment, the means for drawing sample into the chamber comprises a reversible fan which, when operated in reverse direction, creates a backpressure that facilitates evolution of captured target chemicals into the chamber when the screen is heated. The screen can be positioned directly in front of the detector prior to heating to improve detection capability.

  4. [Management human resources].

    PubMed

    Schena, F P

    2004-01-01

    The management of human resources may follow different models, defined as bureaucratic, technocratic or managerial-entrepreneurial models. The latter being the most used. However, the relationship individual-enterprise is based on both a legal and a psychological contract regardless of the model used. The winning concept considers the personnel as the first and most important customer to be trained, informed and kept updated. For these reasons it is necessary to create a warm working environment, which is the first marketing tool, thus improving the marketing skills (enterprise-customer). The improved results (products, processes and publications) will be achieved by total quality management, which includes training and transformation of the chief's role from the hierarchical management to a coaching approach. This approach will recreativity, personality and competence of the personnel. This new type of leadership is based on the authority recognised by the personnel, service and motivation.

  5. Chromophores in human skin

    NASA Astrophysics Data System (ADS)

    Young, Antony R.

    1997-05-01

    Human skin, especially the epidermis, contains several major solar ultraviolet-radiation- (UVR-) absorbing endogenous chromophores including DNA, urocanic acid, amino acids, melanins and their precursors and metabolites. The lack of solubility of melanins prevents their absorption spectra being defined by routine techniques. Indirect spectroscopic methods show that their spectral properties depend on the stimulus for melanogenesis. The photochemical consequences of UVR absorption by some epidermal chromophores are relatively well understood whereas we lack a detailed understanding of the consequent photobiological and clinical responses. Skin action spectroscopy is not a reliable way of relating a photobiological outcome to a specific chromophore but is important for UVR hazard assessment. Exogenous chromophores may be administered to the skin in combination with UVR exposure for therapeutic benefit, or as sunscreens for the prevention of sunburn and possibly skin cancer.

  6. Endocrinology of human parturition.

    PubMed

    Vannuccini, Silvia; Bocchi, Caterina; Severi, Filiberto M; Challis, John R; Petraglia, Felice

    2016-06-01

    The mechanisms involved in human pregnancy maintenance and parturition are highly complex and involve mother, fetus and placenta. The "final common pathway" to delivery is composed by inflammatory and endocrine interactive paths that tip the balance in favor of coordinated uterine contractility and cervical dilation. These mechanisms involve a shift from progesterone to estrogen dominance, CRH action, increased sensitivity to oxytocin, gap junction formation, and increased prostaglandins activity. Complementary changes in the cervix involve a decrease in progesterone dominance and the actions of prostaglandins and relaxin, via connective tissue alterations, leading to cervical softening and dilation. Neuronal, hormonal, inflammatory and immune pathways participate in initiation of labor and the utero-placental unit plays a major role in the synthesis and release of parturition mediators.

  7. Human physiology in space.

    PubMed

    Vernikos, J

    1996-12-01

    The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

  8. Epigenetics of human papillomaviruses

    SciTech Connect

    Johannsen, Eric; Lambert, Paul F.

    2013-10-15

    Human papilllomaviruses (HPVs) are common human pathogens that infect cutaneous or mucosal epithelia in which they cause warts, self-contained benign lesions that commonly regress. The HPV life cycle is intricately tied to the differentiation of the host epithelium it infects. Mucosotropic HPVs are the most common sexually transmitted pathogen known to mankind. A subset of the mucosotropic HPVs, so-called high risk HPVs, is etiologically associated with numerous cancers of the anogenital tract, most notably the cervix, as well as a growing fraction of head and neck cancers. In these cancers, the HPV genome, which normally exists an a double stranded, circular, nuclear plasmid, is commonly found integrated into the host genome and expresses two viral oncogenes, E6 and E7, that are implicated in the development and maintainance of the cancers caused by these high risk HPVs. Numerous studies, primarily on the high risk HPV16, have documented that the methylation status of the viral genome changes not only in the context of the viral life cycle but also in the context of the progressive neoplastic disease that culminates in cancer. In this article, we summarize the knowledge gained from those studies. We also provide the first analysis of available ChIP-seq data on the occupancy of both epigentically modified histones as well as transcription factors on the high risk HPV18 genome in the context of HeLa cells, a cervical cancer-derived cell line that has been the subject of extensive analyses using this technique. - Highlights: • Methylation status of HPV genomes is dynamic. • Changes are seen in both the viral life cycle and neoplasia. • Histone modification status at LCR is predictive of transcription factor occupancy. • Novel transcription factor binding noted by ChIP-seq.

  9. Human teratogens: update 2010.

    PubMed

    Holmes, Lewis B

    2011-01-01

    A wide variety of human teratogens have been identified. The characteristics of human teratogens can be used in the assessment of apparent "new" teratogens, when postulated. Information is available through online databases, such as TERIS and Reprotox, telephone-based counseling resources (e.g., Organization of Teratogen Information Systems [OTIS] and European Network Teratology Information Services [ENTIS]), reference books, annual meetings of the Teratology Society, and published articles. There are significant deficiencies in the information available: (1) lack of knowledge about the molecular and cellular basis for most teratogenic effects; (2) the inability to genetically identify more susceptible women before pregnancy; (3) little information is available on dermal and airborne exposures during pregnancy; and (4) most clinicians receive little, if any, training in the identification of or counseling for exposure to potential teratogens. There are many current dilemmas in counseling about exposures in pregnancy, including: (1) Is exposure to specific drugs, such as selected serotonin re-uptake inhibitors (SSRIs) and the inhibitors of tumor necrosis factor-alpha, teratogenic in the first trimester of pregnancy? (2) Are the increased risks of birth defects associated with assisted reproductive technology due, in part, to epigenetic effects? (3) What are the "safe" levels of exposure to the plasticizers phthalates during pregnancy? (4) How do we convince busy physicians, nurses, and pharmacists not to use the drug categories A, B, C, D, and X in counseling and to use more accurate sources? There is a need for a national advisory center for pregnancy registries to provide guidance when new registries are being developed.

  10. Voice - How humans communicate?

    PubMed Central

    Tiwari, Manjul; Tiwari, Maneesha

    2012-01-01

    Voices are important things for humans. They are the medium through which we do a lot of communicating with the outside world: our ideas, of course, and also our emotions and our personality. The voice is the very emblem of the speaker, indelibly woven into the fabric of speech. In this sense, each of our utterances of spoken language carries not only its own message but also, through accent, tone of voice and habitual voice quality it is at the same time an audible declaration of our membership of particular social regional groups, of our individual physical and psychological identity, and of our momentary mood. Voices are also one of the media through which we (successfully, most of the time) recognize other humans who are important to us—members of our family, media personalities, our friends, and enemies. Although evidence from DNA analysis is potentially vastly more eloquent in its power than evidence from voices, DNA cannot talk. It cannot be recorded planning, carrying out or confessing to a crime. It cannot be so apparently directly incriminating. As will quickly become evident, voices are extremely complex things, and some of the inherent limitations of the forensic-phonetic method are in part a consequence of the interaction between their complexity and the real world in which they are used. It is one of the aims of this article to explain how this comes about. This subject have unsolved questions, but there is no direct way to present the information that is necessary to understand how voices can be related, or not, to their owners. PMID:22690044

  11. The Human Orrery

    NASA Astrophysics Data System (ADS)

    Bailey, M. E.; Christou, A. A.; Asher, D. J.

    2005-08-01

    The Human Orrery is a dynamic model of the solar system, where people play the role of the moving planets. The users' interactions with the model lead to greater awareness of their place in space and understanding of our planet's changing position with time. It is an innovative concept, the first example in the world to show with precision the elliptical orbits and changing positions of the main bodies in the solar system. It engages the general public in science and mathematics, and introduces key concepts in astronomy and space science in a fun and entertaining way. The model shows the orbits of the six classical planets, a main-belt asteroid (Ceres) and two comets (Halley and Encke) at a scale of 1 metre to 1 AU. It contains more than 200 individually inscribed discs showing the positions of objects at intervals of 16 days or multiples thereof. The region beyond Saturn shows the thirteen ecliptic constellations and directions to more distant objects in the Universe. Activities include `walking the orrery' (moving around the orbits in lockstep from one disc to the next to illustrate Kepler's third law of planetary motion); identifying which planets are visible tonight (or at any other time); and discovering phenomena such as planetary alignments, conjunctions and transits. Younger users can run the orrery; measure the distance between planets or a planet's speed in different parts of its orbit; or use the open space for to create a `dance of the planets'. Advanced users can investigate Kepler's laws by direct measurement; modular arithmetic; properties of ellipses; and calendrical concepts such as leap years and the need for the Gregorian reform. For more information, see http://star.arm.ac.uk/orrery/. The Human Orrery's construction was funded by the Northern Ireland Department of Culture, Arts and Leisure.

  12. Manage your human sigma.

    PubMed

    Fleming, John H; Coffman, Curt; Harter, James K

    2005-01-01

    If sales and service organizations are to improve, they must learn to measure and manage the quality of the employee-customer encounter. Quality improvement methodologies such as Six Sigma are extremely useful in manufacturing contexts, but they're less useful when it comes to human interactions. To address this problem, the authors have developed a quality improvement approach they refer to as Human Sigma. It weaves together a consistent method for assessing the employee-customer encounter and a disciplined process for managing and improving it. There are several core principles for measuring and managing the employee-customer encounter: It's important not to think like an economist or an engineer when assessing interactions because emotions inform both sides' judgments and behavior. The employee-customer encounter must be measured and managed locally, because there are enormous variations in quality at the work-group and individual levels. And to improve the quality of the employee-customer interaction, organizations must conduct both short-term, transactional interventions and long-term, transformational ones. Employee engagement and customer engagement are intimately connected--and, taken together, they have an outsized effect on financial performance. They therefore need to be managed holistically. That is, the responsibility for measuring and monitoring the health of employee-customer relationships must reside within a single organizational structure, with an executive champion who has the authority to initiate and manage change. Nevertheless, the local manager remains the single most important factor in local group performance. A local manager whose work group shows suboptimal performance should be encouraged to conduct interventions, such as targeted training, performance reviews, action learning, and individual coaching.

  13. Genome engineering in human cells.

    PubMed

    Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

    2014-01-01

    Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

  14. Metabolic hypothesis for human altriciality.

    PubMed

    Dunsworth, Holly M; Warrener, Anna G; Deacon, Terrence; Ellison, Peter T; Pontzer, Herman

    2012-09-18

    The classic anthropological hypothesis known as the "obstetrical dilemma" is a well-known explanation for human altriciality, a condition that has significant implications for human social and behavioral evolution. The hypothesis holds that antagonistic selection for a large neonatal brain and a narrow, bipedal-adapted birth canal poses a problem for childbirth; the hominin "solution" is to truncate gestation, resulting in an altricial neonate. This explanation for human altriciality based on pelvic constraints persists despite data linking human life history to that of other species. Here, we present evidence that challenges the importance of pelvic morphology and mechanics in the evolution of human gestation and altriciality. Instead, our analyses suggest that limits to maternal metabolism are the primary constraints on human gestation length and fetal growth. Although pelvic remodeling and encephalization during hominin evolution contributed to the present parturitional difficulty, there is little evidence that pelvic constraints have altered the timing of birth.

  15. Disorder in Complex Human System

    NASA Astrophysics Data System (ADS)

    Akdeniz, K. Gediz

    2011-11-01

    Since the world of human and whose life becomes more and more complex every day because of the digital technology and under the storm of knowledge (media, internet, governmental and non-governmental organizations, etc...) the simulation is rapidly growing in the social systems and in human behaviors. The formation of the body and mutual interactions are left to digital technological, communication mechanisms and coding the techno genetics of the body. Deconstruction begins everywhere. The linear simulation mechanism with modern realities are replaced by the disorder simulation of human behaviors with awareness realities. In this paper I would like to introduce simulation theory of "Disorder Sensitive Human Behaviors". I recently proposed this theory to critique the role of disorder human behaviors in social systems. In this theory the principle of realty is the chaotic awareness of the complexity of human systems inside of principle of modern thinking in Baudrillard's simulation theory. Proper examples will be also considered to investigate the theory.

  16. [Human dignity and Christian ethics].

    PubMed

    Reiter, J

    1993-02-01

    The jurisdiction of most states presumes that human dignity is unconditional. Yet a last reason for this dignity cannot be furnished by a state jurisdiction. Christian ethics for instance argue on a line beyond strictly rational interpretation: human dignity roots in man's affirmation by God. Beyond a simply negative definition it is essential today to define the conditions of human dignity in a positive way.

  17. Research Needs for Human Factors

    DTIC Science & Technology

    1983-01-01

    Research Note 83-07 RESEARCH NEEDS FOR HUMAN FACTORS Conmmittee on Human Factors Cot ittee on Behavioral and Social Sciences and Education National... Research Council IIJanuary 1983 i ~ Approvted for Dublit rellease; distribution unlimited. __ A N- This report, as submitted by the contractor, has...CATALOG NUMBE -- Research Note 83-07 A2{>/)/.2 ? ___ 4. TITLE (e 5110) S. TyPE of REPORT & PERIOD COVERED Renearch Needs for Human Facotrs S. PERFORMING

  18. Transmission risk of human trichinellosis.

    PubMed

    Takumi, Katsuhisa; Teunis, Peter; Fonville, Manoj; Vallee, Isabelle; Boireau, Pascal; Nöckler, Karsten; van der Giessen, Joke

    2009-02-23

    Trichinella is a food-borne parasitic zoonoses and human cases are still reported in Europe mainly due to the consumption of pig meat originating from small backyard farms. Infections originating from industrialized pig farming have not been reported for decades in Europe, due to control measures to prevent the transmission of Trichinella from wildlife by indoor housing and good management practices. Therefore, risk-based monitoring programs might replace individual carcass control in industrialized pig farming as described in EU legislation SANCO 2075/2005. Transmission of Trichinella species between wildlife and the risk that may pose to humans via consumption of contaminated pork meat has not been studied quantitatively. One pathway by which human trichinellosis can occur is the rat-pig-human route. To evaluate the transmission risk though this pathway the dose responses of rat, pig, and human were studied. Experimental T. spiralis infection was performed in rats with doses of as few as 10 parasites and the data set was analysed using a newly developed dose response model that describes larvae per gram (LPG). Experimental T. spiralis infection in pig was analysed in a similar way. Furthermore nine published outbreaks of human trichinellosis were analysed to determine the dose response in humans. The risk of human trichinellosis via the rat-pig-human transmission was simulated by the Monte Carlo method. A pair of female and male parasites representing the lowest infection pressure from the environment, led to the probability of human trichinellosis by consumption of 100g of raw pork meat equal to 5% via the studied rat-pig-human pathway. In the absence of rodent control near the farm, a low infection pressure from wildlife presents a relatively high risk of human trichinellosis via consumption of uncooked pork meat.

  19. Only humans have human placentas: molecular differences between mice and humans.

    PubMed

    Schmidt, André; Morales-Prieto, Diana M; Pastuschek, Jana; Fröhlich, Karolin; Markert, Udo R

    2015-04-01

    The placenta is one of the organs with the highest evolutionary diversity among animal species. In consequence, an animal model that reflects human placentation exactly does not exist. However, the mouse is the most frequently used animal model for placenta and pregnancy research. It possesses a hemochorial placenta, which is similar, but also different from the human placenta. The question whether the similarities are sufficient for the achievement of useful results with regard to human pregnancy was debated recently at the 11th Congress of the European Society for Reproductive Immunology (Budapest, Hungary). Here, we discuss the molecular features of the human placenta that are restricted to primates or even to humans. Many of the primate-specific genetic novelties, e.g., the large microRNA cluster on chromosome 19, have been detected during the last 10-15 years and could not be referred to in earlier discussions. Now, in the light of recent findings and a better understanding of interspecies differences, we conclude that the mouse model is often overvalued. Owing to the increasing number of known human-specific factors in human placentation we consider that many aspects of human placentation can only be understood on the basis of experiments on human cells and tissues in combination with data collections from human subject studies.

  20. 75 FR 6729 - Meetings of Humanities Panel

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-10

    ... DFG/NEH Bilateral Digital Humanities Programs in DFG/NEH Bilateral Digital Humanities Programs... ARTS AND THE HUMANITIES Meetings of Humanities Panel AGENCY: The National Endowment for the Humanities... (Pub. L. 92-463, as amended), notice is hereby given that the following meetings of Humanities...