Effects of External Loads on Human Head Movement Control Systems

Science.gov (United States)

Nam, M. H.; Choi, O. M.

1984-01-01

The central and reflexive control strategies underlying movements were elucidated by studying the effects of external loads on human head movement control systems. Some experimental results are presented on dynamic changes weigh the addition of aviation helmet (SPH4) and lead weights (6 kg). Intended time-optimal movements, their dynamics and electromyographic activity of neck muscles in normal movements, and also in movements made with external weights applied to the head were measured. It was observed that, when the external loads were added, the subject went through complex adapting processes and the head movement trajectory and its derivatives reached steady conditions only after transient adapting period. The steady adapted state was reached after 15 to 20 seconds (i.e., 5 to 6 movements).

Radiation-induced gene amplification in rodent and human cells

International Nuclear Information System (INIS)

Luecke-Huhle, C.; Gloss, B.; Herrlich, P.

1990-01-01

Ionizing and UV radiations induce amplification of SV40 DNA sequences integrated in the genome of Chinese hamster cells and increase amplification of the dihydrofolate reductase (DHFR) gene during methotrexate selection in human skin fibroblasts of a patient with ataxia telangiectasia. Various types of external (60-Co-γ-rays, 241-Am-α-particles, UV) or internal radiation (caused by the decay of 125 I incorporated into DNA in form of I-UdR) were applied. By cell fusion experiments it could be shown that SV40 gene amplification is mediated by one or several diffusible trans-acting factors induced or activated in a dose dependent manner by all types of radiation. One of these factors binds to a 10 bp sequence within the minimal origin of replication of SV40. In vivo competition with an excess of a synthetic oligonucleotide comprising this sequence blocks radiation-induced amplification. (author) 25 refs.; 8 figs

Health-related external cost assessment in Europe: methodological developments from ExternE to the 2013 Clean Air Policy Package.

Science.gov (United States)

van der Kamp, Jonathan; Bachmann, Till M

2015-03-03

"Getting the prices right" through internalizing external costs is a guiding principle of environmental policy making, one recent example being the EU Clean Air Policy Package released at the end of 2013. It is supported by impact assessments, including monetary valuation of environmental and health damages. For over 20 years, related methodologies have been developed in Europe in the Externalities of Energy (ExternE) project series and follow-up activities. In this study, we aim at analyzing the main methodological developments over time from the 1990s until today with a focus on classical air pollution-induced human health damage costs. An up-to-date assessment including the latest European recommendations is also applied. Using a case from the energy sector, we identify major influencing parameters: differences in exposure modeling and related data lead to variations in damage costs of up to 21%; concerning risk assessment and monetary valuation, differences in assessing long-term exposure mortality risks together with assumptions on particle toxicity explain most of the observed changes in damage costs. These still debated influencing parameters deserve particular attention when damage costs are used to support environmental policy making.

Combined effects of external electric and magnetic fields on electromagnetically induced transparency of a two-dimensional quantum dot

International Nuclear Information System (INIS)

Rezaei, Gh.; Shojaeian Kish, S.; Avazpour, A.

2012-01-01

In this article effects of external electric and magnetic fields on the electromagnetically induced transparency of a hydrogenic impurity confined in a two-dimensional quantum dot are investigated. To do this the probe absorption, group velocity and refractive index of the medium in the presence of external electric and magnetic fields are discussed. It is found that, electromagnetically induced transparency occurs in the system and its frequency, transparency window and group velocity of the probe field strongly depend on the external fields. In comparison with atomic system, one may control the electromagnetically induced transparency and the group velocity of light in nano structures with the dot size and confinement potential.

Histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells.

Science.gov (United States)

Semeraro, F; Ammollo, C T; Esmon, N L; Esmon, C T

2014-10-01

Extracellular histones exert part of their prothrombotic activity through the stimulation of blood cells. Besides platelets, histones can bind to red blood cells (RBCs), which are important contributors to thrombogenesis, but little is known about the functional consequences of this interaction. To evaluate the effect of histones on the procoagulant potential of human RBCs with particular regard to the expression of surface phosphatidylserine (PS). PS exposure on human RBCs treated with a natural mixture of histones or recombinant individual histones was evaluated with fluorescein isothiocyanate-annexin-V binding and measured with flow cytometry. Calcium influx in RBCs loaded with the calcium-sensitive fluorophore Fluo-4 AM was assessed with flow cytometry. The procoagulant potential of histone-treated RBCs was evaluated with a purified prothrombinase assay and a one-stage plasma recalcification clotting test. Natural histones induced PS exposure on RBCs in a dose-dependent manner, and neutralization or cleavage of histones by heparin or activated protein C, respectively, abolished PS externalization. H4 was mainly responsible for the stimulating activity of histones, whereas the other subtypes were almost ineffective. Similarly, natural histones and H4 induced influx of calcium into RBCs, whereas the other individual histones did not. Histone-induced exposure of PS on RBCs translated into increased prothrombinase complex-mediated prothrombin activation and accelerated fibrin formation in plasma. Histones induce RBCs to express a procoagulant phenotype through the externalization of PS. This finding provides new insights into the prothrombotic activity of extracellular histones. © 2014 International Society on Thrombosis and Haemostasis.

Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance.

Science.gov (United States)

Violante, Ines R; Li, Lucia M; Carmichael, David W; Lorenz, Romy; Leech, Robert; Hampshire, Adam; Rothwell, John C; Sharp, David J

2017-03-14

Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.

Expressing air pollution-induced health-related externalities in physical terms with the help of DALYs.

Science.gov (United States)

Bachmann, Till M; van der Kamp, Jonathan

2017-06-01

The unintended impacts of industrial activity on human health and the environment have regularly been assessed and monetised (referred to as "external costs"). External costs are, however, a rather abstract aggregate so that decision makers cannot easily relate them to tangible impacts. At the same time, physical health impact indicators have different units that cannot readily be compared and communicated in a joint way. To support better informed decisions at policy or company level, we propose and demonstrate a way to facilitate communication on non-monetized, that is, physical health indicators quantified in studies. The concept Disability-Adjusted Life Year (DALY) is chosen as metric due to its widespread use. We establish a comprehensive and consistent set of six health endpoints caused by particles and ozone, and derive related up-to-date DALYs. Further we apply the DALY values to a French smart grid demonstration project. Owing to its size, the gains in terms of reduced DALYs are however small. In contrast to external cost assessments, in the frame of which morbidity endpoints usually contribute to around 10-15%, they are found to be insubstantial in the overall DALY score (i.e. below 1%). This is because DALYs only consider time losses weighted by severity while external costs also factor in further welfare effects, i.e. combining resource, disutility and opportunity costs of illness. As a result, methodological limitations, mainly existing for the morbidity-related DALY values, appear to be less of concern. Overall, using the DALYs with and without morbidity impacts is justifiable. Either choice in the communication of health-related physical externalities induces the need to explain the limitations in terms of the treatment of morbidity endpoints (notably their definition and the disability weights used) or their complete disregard. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dielectric-spectroscopy approach to ferrofluid nanoparticle clustering induced by an external electric field.

Science.gov (United States)

Rajnak, Michal; Kurimsky, Juraj; Dolnik, Bystrik; Kopcansky, Peter; Tomasovicova, Natalia; Taculescu-Moaca, Elena Alina; Timko, Milan

2014-09-01

An experimental study of magnetic colloidal particles cluster formation induced by an external electric field in a ferrofluid based on transformer oil is presented. Using frequency domain isothermal dielectric spectroscopy, we study the influence of a test cell electrode separation distance on a low-frequency relaxation process. We consider the relaxation process to be associated with an electric double layer polarization taking place on the particle surface. It has been found that the relaxation maximum considerably shifts towards lower frequencies when conducting the measurements in the test cells with greater electrode separation distances. As the electric field intensity was always kept at a constant value, we propose that the particle cluster formation induced by the external ac electric field accounts for that phenomenon. The increase in the relaxation time is in accordance with the Schwarz theory of electric double layer polarization. In addition, we analyze the influence of a static electric field generated by dc bias voltage on a similar shift in the relaxation maximum position. The variation of the dc electric field for the hysteresis measurements purpose provides understanding of the development of the particle clusters and their decay. Following our results, we emphasize the utility of dielectric spectroscopy as a simple, complementary method for detection and study of clusters of colloidal particles induced by external electric field.

Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas.

Science.gov (United States)

Lee, Andrew S; Tang, Chad; Hong, Wan Xing; Park, Sujin; Bazalova-Carter, Magdalena; Nelson, Geoff; Sanchez-Freire, Veronica; Bakerman, Isaac; Zhang, Wendy; Neofytou, Evgenios; Connolly, Andrew J; Chan, Charles K; Graves, Edward E; Weissman, Irving L; Nguyen, Patricia K; Wu, Joseph C

2017-08-01

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs), have great potential as an unlimited donor source for cell-based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein, we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present evidence that EBRT is effective in arresting growth of hESC-derived teratomas in vivo at day 28 post-implantation by using a microCT irradiator capable of targeted treatment in small animals. Within several days of irradiation, teratomas derived from injection of undifferentiated hESCs and hiPSCs demonstrated complete growth arrest lasting several months. In addition, EBRT reduced reseeding potential of teratoma cells during serial transplantation experiments, requiring irradiated teratomas to be seeded at 1 × 10 3 higher doses to form new teratomas. We demonstrate that irradiation induces teratoma cell apoptosis, senescence, and growth arrest, similar to established radiobiology mechanisms. Taken together, these results provide proof of concept for the use of EBRT in the treatment of existing teratomas and highlight a strategy to increase the safety of stem cell-based therapies. Stem Cells 2017;35:1994-2000. © 2017 AlphaMed Press.

Human Sound Externalization in Reverberant Environments

DEFF Research Database (Denmark)

Catic, Jasmina

In everyday environments, listeners perceive sound sources as externalized. In listening conditions where the spatial cues that are relevant for externalization are not represented correctly, such as when listening through headphones or hearing aids, a degraded perception of externalization may...... occur. In this thesis, the spatial cues that arise from a combined effect of filtering due to the head, torso, and pinna and the acoustic environment were analysed and the impact of such cues for the perception of externalization in different frequency regions was investigated. Distant sound sources...... were simulated via headphones using individualized binaural room impulse responses (BRIRs). An investigation of the influence of spectral content of a sound source on externalization showed that effective externalization cues are present across the entire frequency range. The fluctuation of interaural...

N-Acetyl-L-cysteine protects thyroid cells against DNA damage induced by external and internal irradiation.

Science.gov (United States)

Kurashige, Tomomi; Shimamura, Mika; Nagayama, Yuji

2017-11-01

We evaluated the effect of the antioxidant N-acetyl-L-cysteine (NAC) on the levels of reactive oxygen species (ROS), DNA double strand breaks (DSB) and micronuclei (MN) induced by internal and external irradiation using a rat thyroid cell line PCCL3. In internal irradiation experiments, ROS and DSB levels increased immediately after 131 I addition and then gradually declined, resulting in very high levels of MN at 24 and 48 h. NAC administration both pre- and also post- 131 I addition suppressed ROS, DSB and MN. In external irradiation experiments with a low dose (0.5 Gy), ROS and DSB increased shortly and could be prevented by NAC administration pre-, but not post-irradiation. In contrast, external irradiation with a high dose (5 Gy) increased ROS and DSB in a bimodal way: ROS and DSB levels increased immediately after irradiation, quickly returned to the basal levels and gradually rose again after >24 h. The second phase was in parallel with an increase in 4-hydroxy-2-nonenal. The number of MN induced by the second wave of ROS/DSB elevations was much higher than that by the first peak. In this situation, NAC administered pre- and post-irradiation comparably suppressed MN induced by a delayed ROS elevation. In conclusion, a prolonged ROS increase during internal irradiation and a delayed ROS increase after external irradiation with a high dose caused serious DNA damage, which were efficiently prevented by NAC. Thus, NAC administration even both after internal or external irradiation prevents ROS increase and eventual DNA damage.

Comorbidity in illness-induced posttraumatic stress disorder versus posttraumatic stress disorder due to external events in a nationally representative study.

Science.gov (United States)

Sommer, Jordana L; Mota, Natalie; Edmondson, Donald; El-Gabalawy, Renée

2018-05-10

The current study compared physical and mental health characteristics and quality of life of illness-induced posttraumatic stress disorder (PTSD) versus those with PTSD due to external traumatic events in a population-based sample. PTSD was assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-5) using DSM-5 criteria in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions. Participants with past-year PTSD (n = 1779) were categorized into two groups: illness-induced (6.5%) and other trauma-induced PTSD (92.9%) based on index trauma. Group differences in physical health, mental health, and quality of life were estimated using multiple logistic and linear regressions with adjustment for demographics and medical morbidity. Compared to PTSD due to external events, illness-induced PTSD had higher rates of life-threatening illness in the past year. Illness-induced PTSD compared to PTSD due to external events was associated with reduced odds of depressive/bipolar disorders and antisocial personality disorder, but increased odds of cannabis use disorder. The groups did not differ on quality of life after accounting for medical morbidity. Illness-induced PTSD is common among American adults and has a similar impact on quality of life as PTSD due to external events, but may have distinct mental health correlates. Copyright © 2018 Elsevier Inc. All rights reserved.

Large-scale, near-Earth, magnetic fields from external sources and the corresponding induced internal field

Science.gov (United States)

Langel, R. A.; Estes, R. H.

1983-01-01

Data from MAGSAT analyzed as a function of the Dst index to determine the first degree/order spherical harmonic description of the near-Earth external field and its corresponding induced field. The analysis was done separately for data from dawn and dusk. The MAGSAT data was compared with POGO data. A local time variation of the external field persists even during very quiet magnetic conditions; both a diurnal and 8-hour period are present. A crude estimate of Sq current in the 45 deg geomagnetic latitude range is obtained for 1966 to 1970. The current strength, located in the ionosphere and induced in the Earth, is typical of earlier determinations from surface data, although its maximum is displaced in local time from previous results.

Influence of external magnetic field on laser-induced gold nanoparticles fragmentation

International Nuclear Information System (INIS)

Serkov, A. A.; Rakov, I. I.; Simakin, A. V.; Kuzmin, P. G.; Shafeev, G. A.; Mikhailova, G. N.; Antonova, L. Kh.; Troitskii, A. V.; Kuzmin, G. P.

2016-01-01

Laser-assisted fragmentation is an efficient method of the nanoparticles size and morphology control. However, its exact mechanisms are still under consideration. One of the remaining problems is the plasma formation, inevitably occurring upon the high intensity laser irradiation. In this Letter, the role of the laser-induced plasma is studied via introduction of high-intensity external magnetic field (up to 7.5 T). Its presence is found to cause the plasma emission to start earlier regarding to a laser pulse, also increasing the plume luminosity. Under these conditions, the acceleration of nanoparticles fragmentation down to a few nanometers is observed. Laser-induced plasma interaction with magnetic field and consequent energy transfer from plasma to nanoparticles are discussed.

Vacuum energy induced by an external magnetic field in a curved space

International Nuclear Information System (INIS)

Sitenko, Yu.A.; Rakityansky, D.G.

1998-01-01

The asymptotic expansion of the product of an operator raised to an arbitrary power and an exponential function of this operator is obtained. With the aid of this expansion, the density of vacuum energy induced by a static external magnetic field of an Abelian or a non-Abelian nature is expressed in terms of the DeWitt-Seeley-Gilkey coefficients

External field-induced chaos in classical and quantum Hamiltonian systems

International Nuclear Information System (INIS)

Lin, W.C.

1986-01-01

Classical nonlinear nonintegrable systems exhibit dense sets of resonance zones in phase space. Global chaotic motion appears when neighboring resonance zones overlap. The chaotic motion signifies the destruction of a quasi constant of motion. The motion of a particle, trapped in one of the wells of a sinusoidal, potential driven by a monochromatic external field was studied. Global chaotic behavior sets in when the amplitude of the external field reaches a critical value. The particle then escapes the well. The critical values are found to be in good agreement with a resonance overlap criterion rather than a renormalization-group scheme. A similar system was then studied, but with the particle being confined in an infinite square well potential instead. A stochastic layer is found in the low-energy part of the phase space. The resonance zone structure is found to be in excellent agreement with predictions. The critical values for the onset of global chaotic behavior are found to be in excellent agreement with the renormalization group scheme. The quantum version of the second model above was then considered. In a similar fashion, the external field induces quantum resonance zones. The spectral statistics were computed, and a transition of statistics from Poissonian to Wigner-like was found as overlap of quantum resonances occurs. This also signifies the destruction of a quasi-constant of motion

External apical root resorption diagnosis by using FII human dentine fraction and salivary IGg.

Science.gov (United States)

Da-Costa, Tânia Maris Pedrini Soares; Hidalgo, Mirian Marubayashi; Consolaro, Alberto; Lima, Carlos Eduardo de Oliveira; Tanaka, Evelise Ono; Itano, Eiko Nakagawa

2018-06-01

External apical root resorption as a consequence of orthodontic treatment is an inflammatory pathological process that results in permanent loss of tooth structure from the root apex. This study aimed to investigate the diagnostic potential of human dentine fractions and salivary IgG in external apical root resorption. Saliva samples were collected from 10 patients before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of orthodontic treatment. The total dentinal extract, obtained from human third molars, was fractioned by gel filtration chromatography in three fractions denominated FI, FII and FIII. The root resorption analysis of the upper central incisors was performed by digital image subtraction method. Reactivity of salivary IgG to antigenic fractions of dentine was determined by enzyme-linked immunosorbent assay (Elisa). Regardless of treatment, FI dentin fraction with high MM (root resorptions were detected. Our results suggest that FII human dentine fraction and salivary IgG have potential to be used in diagnosis and monitoring of external apical root resorption. The development of a practical and accessible biochemical test using saliva and FII dentine fraction may help in the prevention of severe root resorption. Copyright © 2018. Published by Elsevier Masson SAS.

The effect of internal and external fields of view on visually induced motion sickness

NARCIS (Netherlands)

Bos, J.E.; Vries, S.C. de; Emmerik, M.L. van; Groen, E.L.

2010-01-01

Field of view (FOV) is said to affect visually induced motion sickness. FOV, however, is characterized by an internal setting used by the graphics generator (iFOV) and an external factor determined by screen size and viewing distance (eFOV). We hypothesized that especially the incongruence between

External main-induced events in relation to nuclear power plant siting

International Nuclear Information System (INIS)

1981-01-01

This safety Guide recomments procedures and provides information for use in implementing that part of the code of safety in Nuclear Power Plant Siting (IAEA Safety Series No. 50-C-S) which concerns man-induced events external to the plant, up to the evaluation of corresponding design basis parameters. Like the code, the Guide forms part of the IAEA's programme, referred to as the NUSS programme, for establishing codes of practice and safety Guides relating to land-based stationary thermal neutron power plants

Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

International Nuclear Information System (INIS)

Li, Chao; Ruan, Jing; Yang, Meng; Pan, Fei; Gao, Guo; Qu, Su; Shen, You-Lan; Dang, Yong-Jun; Wang, Kan; Jin, Wei-Lin; Cui, Da-Xiang

2015-01-01

Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer

Quasi-static electric field in a cylindrical volume conductor induced by external coils.

Science.gov (United States)

Esselle, K P; Stuchly, M A

1994-02-01

An expansion technique based on modified Bessel functions is used to obtain an analytical solution for the electric field induced in a homogeneous cylindrical volume conductor by an external coil. The current in the coil is assumed to be changing slowly so that quasi-static conditions can be justified. Valid for any coil type, this solution is ideal for fast computation of the induced electric field at a large number of points. Efficient implementation of this method in a computer code is described and numerical results are presented for a perpendicular circular coil and a tangential double-square coil.

Human-induced geomorphic change across environmental gradients

Science.gov (United States)

Vanacker, V.; Molina, A.; Bellin, N.; Christl, M.

2016-12-01

Human-induced land cover changes are causing important adverse effects on the ecological services rendered by mountain ecosystems, and the number of case-studies of the impact of humans on soil erosion and sediment yield has mounted rapidly. Anthropogenic disturbance of natural vegetation can profoundly alter the physical, chemical and biological processes within soils. Rapid removal of topsoil during intense farming can result in an imbalance between soil production through chemical weathering and physical soil erosion, with direct implications on nutrient cycling, soil fertility and agricultural production. In this study, we present a conceptual model for assessing human-induced erosion for a wide variety of environmental settings and pose that human-induced geomorphic change cannot be assessed solely based on modern erosion rates as natural or baseline erosion rates can be important in e.g. mountainous terrain. As such, we assess the vulnerability of a given ecosystem to human-induced land cover change by quantifying the change in catchment-wide erosion rates resulting from anthropogenic changes in vegetation cover. Human-induced erosion is here approximated by the ratio of the total specific sediment yield to the natural erosional mass flux, and is dimensionless. The conceptual model is applied to three contrasting environmental settings where data on soil production, physical soil erosion and long-term denudation are available: the tropical Andes, subtropical southern Brazil, and semi-arid Spanish Cordillera. The magnitude of human-induced geomorphic change strongly differs between the three regions. The data suggest that the sensitivity to human-induced erosion is ecosystem dependent, and related to soil erosivity and potential vegetation cover disturbances as a result of human impact. It may therefore be expected that the potential for erosion regulation is larger in well-vegetated ecosystem where strong differences may exist in vegetation cover between

Propagation of the state change induced by external forces in local interactions

Science.gov (United States)

Lu, Jianjun; Tokinaga, Shozo

2016-10-01

This paper analyses the propagation of the state changes of agents that are induced by external forces applied to a plane. In addition, we propose two models for the behavior of the agents placed on a lattice plane, both of which are affected by local interactions. We first assume that agents are allowed to move to another site to maximise their satisfaction. Second, we utilise a model in which the agents choose activities on each site. The results show that the migration (activity) patterns of agents in both models achieve stability without any external forces. However, when we apply an impulsive external force to the state of the agents, we then observe the propagation of the changes in the agents' states. Using simulation studies, we show the conditions for the propagation of the state changes of the agents. We also show the propagation of the state changes of the agents allocated in scale-free networks and discuss the estimation of the agents' decisions in real state changes. Finally, we discuss the estimation of the agents' decisions in real state temporal changes using economic and social data from Japan and the United States.

STAT6-Dependent Collagen Synthesis in Human Fibroblasts Is Induced by Bovine Milk.

Directory of Open Access Journals (Sweden)

Stefan Kippenberger

Full Text Available Since the domestication of the urus, 10.000 years ago, mankind utilizes bovine milk for different purposes. Besides usage as a nutrient also the external application of milk on skin has a long tradition going back to at least the ancient Aegypt with Cleopatra VII as a great exponent. In order to test whether milk has impact on skin physiology, cultures of human skin fibroblasts were exposed to commercial bovine milk. Our data show significant induction of proliferation by milk (max. 2,3-fold, EC50: 2,5% milk without toxic effects. Surprisingly, bovine milk was identified as strong inducer of collagen 1A1 synthesis at both, the protein (4-fold, EC50: 0,09% milk and promoter level. Regarding the underlying molecular pathways, we show functional activation of STAT6 in a p44/42 and p38-dependent manner. More upstream, we identified IGF-1 and insulin as key factors responsible for milk-induced collagen synthesis. These findings show that bovine milk contains bioactive molecules that act on human skin cells. Therefore, it is tempting to test the herein introduced concept in treatment of atrophic skin conditions induced e.g. by UV light or corticosteroids.

Altered expression of long non-coding RNAs during genotoxic stress-induced cell death in human glioma cells.

Science.gov (United States)

Liu, Qian; Sun, Shanquan; Yu, Wei; Jiang, Jin; Zhuo, Fei; Qiu, Guoping; Xu, Shiye; Jiang, Xuli

2015-04-01

Long non-coding RNAs (lncRNAs), a recently discovered class of non-coding genes, are transcribed throughout the genome. Emerging evidence suggests that lncRNAs may be involved in modulating various aspects of tumor biology, including regulating gene activity in response to external stimuli or DNA damage. No data are available regarding the expression of lncRNAs during genotoxic stress-induced apoptosis and/or necrosis in human glioma cells. In this study, we detected a change in the expression of specific candidate lncRNAs (neat1, GAS5, TUG1, BC200, Malat1, MEG3, MIR155HG, PAR5, and ST7OT1) during DNA damage-induced apoptosis in human glioma cell lines (U251 and U87) using doxorubicin (DOX) and resveratrol (RES). We also detected the expression pattern of these lncRNAs in human glioma cell lines under necrosis induced using an increased dose of DOX. Our results reveal that the lncRNA expression patterns are distinct between genotoxic stress-induced apoptosis and necrosis in human glioma cells. The sets of lncRNA expressed during genotoxic stress-induced apoptosis were DNA-damaging agent-specific. Generally, MEG3 and ST7OT1 are up-regulated in both cell lines under apoptosis induced using both agents. The induction of GAS5 is only clearly detected during DOX-induced apoptosis, whereas the up-regulation of neat1 and MIR155HG is only found during RES-induced apoptosis in both cell lines. However, TUG1, BC200 and MIR155HG are down regulated when necrosis is induced using a high dose of DOX in both cell lines. In conclusion, our findings suggest that the distinct regulation of lncRNAs may possibly involve in the process of cellular defense against genotoxic agents.

Attributable Human-Induced Changes in the Likelihood and Magnitude of the Observed Extreme Precipitation during Hurricane Harvey

OpenAIRE

Risser, MD; Wehner, MF

2017-01-01

©2017. American Geophysical Union. All Rights Reserved. Record rainfall amounts were recorded during Hurricane Harvey in the Houston, Texas, area, leading to widespread flooding. We analyze observed precipitation from the Global Historical Climatology Network with a covariate-based extreme value statistical analysis, accounting for both the external influence of global warming and the internal influence of El Niño–Southern Oscillation. We find that human-induced climate change likely increase...

Carcinogenesis--a synopsis of human experience with external exposure in medicine

International Nuclear Information System (INIS)

Boice, J.D. Jr.

1988-01-01

Studies in the 1980s of medically irradiated populations have increased our knowledge of radiation carcinogenesis. (1) Investigations of prenatal x-ray exposures, especially in twins, provide evidence that very low doses of ionizing radiation may cause cancer in humans. (2) Fractionated doses appear as effective as single exposures of the same total dose in causing breast cancer, but seem less effective for lung cancer. (3) Excess breast cancers can occur among women exposed under age 10, indicating that the immature breast is susceptible to the carcinogenic action of radiation. (4) Moderate doses on the order of 1 Gy to the brains of children can cause tumors later in life; moderately high doses to the skin can cause cancer when followed by frequent exposure to ultraviolet light. (5) Radiotherapy for cervical cancer can increase the rate of subsequent leukemia with the best fitting dose-response functions including a negative exponential term to account for cell-killing. (6) Low-dose exposures of about 10 cGy may increase the risk of thyroid cancer. (7) Second cancers following radiotherapy for a variety of cancers occur primarily among long-term survivors. (8) Radiotherapy may not significantly increase the risk of leukemia following childhood cancer, whereas chemotherapy with alkylating agents is a major risk factor. (9) Bone cancer occurs after high-dose radiotherapy for childhood cancer, but children with retinoblastoma are not more susceptible to radiation-induced disease than children with other malignancies. (10) High-dose external beam therapy can cause thyroid cancer. (11) Studies of cervical cancer patients indicate that the risk of radiation-induced second malignancies follows a time-response model consistent with a constant multiplication of the underlying background incidence. 83 references

Enhanced stimulus-induced gamma activity in humans during propofol-induced sedation.

Directory of Open Access Journals (Sweden)

Neeraj Saxena

Full Text Available Stimulus-induced gamma oscillations in the 30-80 Hz range have been implicated in a wide number of functions including visual processing, memory and attention. While occipital gamma-band oscillations can be pharmacologically modified in animal preparations, pharmacological modulation of stimulus-induced visual gamma oscillations has yet to be demonstrated in non-invasive human recordings. Here, in fifteen healthy humans volunteers, we probed the effects of the GABAA agonist and sedative propofol on stimulus-related gamma activity recorded with magnetoencephalography, using a simple visual grating stimulus designed to elicit gamma oscillations in the primary visual cortex. During propofol sedation as compared to the normal awake state, a significant 60% increase in stimulus-induced gamma amplitude was seen together with a 94% enhancement of stimulus-induced alpha suppression and a simultaneous reduction in the amplitude of the pattern-onset evoked response. These data demonstrate, that propofol-induced sedation is accompanied by increased stimulus-induced gamma activity providing a potential window into mechanisms of gamma-oscillation generation in humans.

Comparison of the external physical damages between laser-assisted and mechanical immobilized human sperm using scanning electronic microscopy.

Directory of Open Access Journals (Sweden)

David Y L Chan

Full Text Available We aim to visualize the external physical damages and distinct external phenotypic effects between mechanical and laser-assisted immobilized human spermatozoa using scanning electronic microscopy (SEM. Human spermatozoa were immobilized mechanically or with laser assistance for SEM examination and the membrane integrities were checked on both types of immobilized spermatozoa. We found evidence of external damages at SEM level on mechanically kinked sperm, but not on laser-assisted immobilized sperm. Although no external damage was found on laser-assist immobilized sperm, there were two distinct types of morphological changes when spermatozoa were stricken by infra-red laser. Coiled tails were immediately formed when Laser pulse was applied to the sperm end piece area, whereas laser applied to the sperm principal piece area resulted in a sharp bend of sperm tails. Sperm immobilized by laser did not exhibit any morphological change if the laser did not hit within the on-screen central target zone or if the laser hit the sperm mid piece or head. Our modified membrane integrity assay revealed that the external membrane of more than half of the laser-assisted immobilized sperm remained intact. In conclusion, mechanical immobilization produced membrane damages whilst laser-assisted immobilization did not result in any external membrane damages besides morphological changes at SEM level.

How does stochastic resonance work within the human brain? - Psychophysics of internal and external noise

International Nuclear Information System (INIS)

Aihara, Takatsugu; Kitajo, Keiichi; Nozaki, Daichi; Yamamoto, Yoshiharu

2010-01-01

We review how research on stochastic resonance (SR) in neuroscience has evolved and point out that the previous studies have overlooked the interaction between internal and external noise. We propose a new psychometric function incorporating SR effects, and show that a Bayesian adaptive method applied to the function efficiently estimates the parameters of the function. Using this procedure in visual detection experiments, we provide significant insight into the relationship between internal and external noise in SR within the human brain.

An examination of human factors in external beam radiation therapy: Findings and implications

International Nuclear Information System (INIS)

Henriksen, K.; Kaye, R.D.; Jones, R.E. Jr.; Morisseau, D.S.; Persensky, J.J.

1994-01-01

To better understand the contributing factors to human error in external beam radiation therapy, the US Nuclear Regulatory Commission has undertaken a series of human factors evaluations. A team of human factors specialists, assisted by a panel of radiation oncologists, medical physicists, and radiation technologists, conducted visits to 24 radiation oncology departments at community hospitals, university centers, and free-standing clinics. A function and task analysis was initially performed to guide subsequent evaluations in the areas of human-system interfaces, procedures, training and qualifications, and organizational policies and practices. Representative findings and implications for improvement are discussed within the context of a dynamic model which holds that misadministration likely results from the unanticipated interaction of several necessary but singly insufficient conditions

The external cruising costs of parking

NARCIS (Netherlands)

Inci, E.; van Ommeren, J.N.; Kobus, Martijn

2017-01-01

Existing work emphasizes the importance of traffic congestion externalities, but typically ignores cruising-for-parking externalities. We estimate the marginal external cruising costs of parking—that is, the time costs that an additional parked car imposes on drivers by inducing them to cruise for

ExternE: Externalities of energy Vol. 2. Methodology

International Nuclear Information System (INIS)

Berry, J.; Holland, M.; Watkiss, P.

1995-01-01

This report describes the methodology used by the ExternE Project of the European Commission (DGXII) JOULE Programme for assessment of the external costs of energy. It is one of a series of reports describing analysis of nuclear, fossil and renewable fuel cycles for assessment of the externalities associated with electricity generation. Part I of the report deals with analysis of impacts, and Part II with the economic valuation of those impacts. Analysis is conducted on a marginal basis, to allow the effect of an incremental investment in a given technology to be quantified. Attention has been paid to the specificity of results with respect to the location of fuel cycle activities, the precise technologies used, and the type and source of fuel. The main advantages of this detailed approach are as follows: It takes full and proper account of the variability of impacts that might result from different power projects; It is more transparent than analysis based on hypothetically 'representative' cases for each of the different fuel cycles; It provides a framework for consistent comparison between fuel cycles. A wide variety of impacts have been considered. These include the effects of air pollution on the natural and human environment, consequences of accidents in the workplace, impacts of noise and visual intrusion on amenity, and the effects of climate change arising from the release of greenhouse gases. Wherever possible we have used the 'impact pathway' or 'damage function' approach to follow the analysis from identification of burdens (e.g. emissions) through to impact assessment and then valuation in monetary terms. This has required a detailed knowledge of the technologies involved, pollutant dispersion, analysis of effects on human and environmental health, and economics. In view of this the project brought together a multi-disciplinary team with experts from many European countries and the USA. The spatial and temporal ranges considered in the analysis are

Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli

KAUST Repository

Sakata, Katsumi

2016-10-24

Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state–space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical “external stimulus-induced information loss” model of biological systems.

Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli

KAUST Repository

Sakata, Katsumi; Saito, Toshiyuki; Ohyanagi, Hajime; Okumura, Jun; Ishige, Kentaro; Suzuki, Harukazu; Nakamura, Takuji; Komatsu, Setsuko

2016-01-01

Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state–space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical “external stimulus-induced information loss” model of biological systems.

ExternE National Implementation Finland

Energy Technology Data Exchange (ETDEWEB)

Pingoud, K; Maelkki, H; Wihersaari, M; Pirilae, P [VTT Energy, Espoo (Finland); Hongisto, M [Imatran Voima Oy, Vantaa (Finland); Siitonen, S [Ekono Energy Ltd, Espoo (Finland); Johansson, M [Finnish Environment Institute, Helsinki (Finland)

1999-07-01

ExternE National Implementation is a continuation of the ExternE Project, funded in part by the European Commission's Joule III Programme. This study is the result of the ExternE National Implementation Project for Finland. Three fuel cycles were selected for the Finnish study: coal, peat and wood-derived biomass, which together are responsible for about 40% of total electricity generation in Finland and about 75% of the non-nuclear fuel based generation. The estimated external costs or damages were dominated by the global warming (GW) impacts in the coal and peat fuel cycles, but knowledge of the true GW impacts is still uncertain. From among other impacts that were valued in monetary terms the human health damages due to airborne emissions dominated in all the three fuel cycles. Monetary valuation for ecosystem impacts is not possible using the ExternE methodology at present. The Meri-Pori power station representing the coal fuel cycle is one of the world's cleanest and most efficient coal-fired power plants with a condensing turbine. The coal is imported mainly from Poland. The estimated health damages were about 4 mECU/kWh, crop damages an order of magnitude lower and damages caused to building materials two orders of magnitude lower. The power stations of the peat and biomass fuel cycles are of CHP type, generating electricity and heat for the district heating systems of two cities. Their fuels are of domestic origin. The estimated health damages allocated to electricity generation were about 5 and 6 mECU/kWh, respectively. The estimates were case-specific and thus an generalisation of the results to the whole electricity generation in Finland is unrealistic. Despite the uncertainties and limitations of the methodology, it is a promising tool in the comparison of similar kinds of fuel cycles, new power plants and pollution abatement technologies and different plant locations with each other. (orig.)

ExternE National Implementation Finland

Energy Technology Data Exchange (ETDEWEB)

Pingoud, K.; Maelkki, H.; Wihersaari, M.; Pirilae, P. [VTT Energy, Espoo (Finland); Hongisto, M. [Imatran Voima Oy, Vantaa (Finland); Siitonen, S. [Ekono Energy Ltd, Espoo (Finland); Johansson, M. [Finnish Environment Institute, Helsinki (Finland)

1999-07-01

ExternE National Implementation is a continuation of the ExternE Project, funded in part by the European Commission's Joule III Programme. This study is the result of the ExternE National Implementation Project for Finland. Three fuel cycles were selected for the Finnish study: coal, peat and wood-derived biomass, which together are responsible for about 40% of total electricity generation in Finland and about 75% of the non-nuclear fuel based generation. The estimated external costs or damages were dominated by the global warming (GW) impacts in the coal and peat fuel cycles, but knowledge of the true GW impacts is still uncertain. From among other impacts that were valued in monetary terms the human health damages due to airborne emissions dominated in all the three fuel cycles. Monetary valuation for ecosystem impacts is not possible using the ExternE methodology at present. The Meri-Pori power station representing the coal fuel cycle is one of the world's cleanest and most efficient coal-fired power plants with a condensing turbine. The coal is imported mainly from Poland. The estimated health damages were about 4 mECU/kWh, crop damages an order of magnitude lower and damages caused to building materials two orders of magnitude lower. The power stations of the peat and biomass fuel cycles are of CHP type, generating electricity and heat for the district heating systems of two cities. Their fuels are of domestic origin. The estimated health damages allocated to electricity generation were about 5 and 6 mECU/kWh, respectively. The estimates were case-specific and thus an generalisation of the results to the whole electricity generation in Finland is unrealistic. Despite the uncertainties and limitations of the methodology, it is a promising tool in the comparison of similar kinds of fuel cycles, new power plants and pollution abatement technologies and different plant locations with each other. (orig.)

ExternE National Implementation Finland

International Nuclear Information System (INIS)

Pingoud, K.; Maelkki, H.; Wihersaari, M.; Pirilae, P.; Hongisto, M.; Siitonen, S.; Johansson, M.

1999-01-01

ExternE National Implementation is a continuation of the ExternE Project, funded in part by the European Commission's Joule III Programme. This study is the result of the ExternE National Implementation Project for Finland. Three fuel cycles were selected for the Finnish study: coal, peat and wood-derived biomass, which together are responsible for about 40% of total electricity generation in Finland and about 75% of the non-nuclear fuel based generation. The estimated external costs or damages were dominated by the global warming (GW) impacts in the coal and peat fuel cycles, but knowledge of the true GW impacts is still uncertain. From among other impacts that were valued in monetary terms the human health damages due to airborne emissions dominated in all the three fuel cycles. Monetary valuation for ecosystem impacts is not possible using the ExternE methodology at present. The Meri-Pori power station representing the coal fuel cycle is one of the world's cleanest and most efficient coal-fired power plants with a condensing turbine. The coal is imported mainly from Poland. The estimated health damages were about 4 mECU/kWh, crop damages an order of magnitude lower and damages caused to building materials two orders of magnitude lower. The power stations of the peat and biomass fuel cycles are of CHP type, generating electricity and heat for the district heating systems of two cities. Their fuels are of domestic origin. The estimated health damages allocated to electricity generation were about 5 and 6 mECU/kWh, respectively. The estimates were case-specific and thus an generalisation of the results to the whole electricity generation in Finland is unrealistic. Despite the uncertainties and limitations of the methodology, it is a promising tool in the comparison of similar kinds of fuel cycles, new power plants and pollution abatement technologies and different plant locations with each other. (orig.)

Entrepreneurial Team: How Human and Social Capital Influence Entrepreneurial Opportunity Identification and Mobilization of External Resources

Directory of Open Access Journals (Sweden)

Ahlem Omri

2015-01-01

Full Text Available Entrepreneurial teams play an extremely important role in the development of any country, especially in developing countries. To understand entrepreneurial teams that operate in a low-technology industry, we rely on the network and human perspective on entrepreneurship. In this paper, we investigate how the social and human capital of entrepreneurial team members influences their ability to identify entrepreneurial opportunities and mobilize external resources. We extend prior research in two ways. First, by using the ordered probit method to measure the identified entrepreneurial opportunities number at the level of entrepreneurial teams. Second, to our knowledge, there is a very small number of studies that have theoretically and empirically investigated the mobilization of external resources, especially at the level of entrepreneurial teams.

Analysis of external events - Nuclear Power Plant Dukovany

International Nuclear Information System (INIS)

Hladky, Milan

2000-01-01

PSA of external events at level 1 covers internal events, floods, fires, other external events are not included yet. Shutdown PSA takes into account internal events, floods, fires, heavy load drop, other external events are not included yet. Final safety analysis report was conducted after 10 years of operation for all Dukovany operational units. Probabilistic approach was used for analysis of aircraft drop and external man-induced events. The risk caused by man-induced events was found to be negligible and was accepted by State Office for Nuclear Safety (SONS)

Some Ethical Concerns About Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Zheng, Yue Liang

2016-10-01

Human induced pluripotent stem cells can be obtained from somatic cells, and their derivation does not require destruction of embryos, thus avoiding ethical problems arising from the destruction of human embryos. This type of stem cell may provide an important tool for stem cell therapy, but it also results in some ethical concerns. It is likely that abnormal reprogramming occurs in the induction of human induced pluripotent stem cells, and that the stem cells generate tumors in the process of stem cell therapy. Human induced pluripotent stem cells should not be used to clone human beings, to produce human germ cells, nor to make human embryos. Informed consent should be obtained from patients in stem cell therapy.

Mercury-Induced Externalization of Phosphatidylserine and Caspase 3 Activation in Human Liver Carcinoma (HepG2 Cells

Directory of Open Access Journals (Sweden)

Paul B. Tchounwou

2006-03-01

Full Text Available Apoptosis arises from the active initiation and propagation of a series of highly orchestrated specific biochemical events leading to the demise of the cell. It is a normal physiological process, which occurs during embryonic development as well as in the maintenance of tissue homeostasis. Diverse groups of molecules are involved in the apoptosis pathway and it functions as a mechanism to eliminate unwanted or irreparably damaged cells. However, inappropriate induction of apoptosis by environmental agents has broad ranging pathologic implications and has been associated with several diseases including cancer. The toxicity of several heavy metals such as mercury has been attributed to their high affinity to sulfhydryl groups of proteins and enzymes, and their ability to disrupt cell cycle progression and/or apoptosis in various tissues. The aim of this study was to assess the potential for mercury to induce early and late-stage apoptosis in human liver carcinoma (HepG2 cells. The Annexin-V and Caspase 3 assays were performed by flow cytometric analysis to determine the extent of phosphatidylserine externalization and Caspase 3 activation in mercury-treated HepG2 cells. Cells were exposed to mercury for 10 and 48 hours respectively at doses of 0, 1, 2, and 3 μg/mL based on previous cytotoxicity results in our laboratory indicating an LD50 of 3.5 ± 0.6 μg/mL for mercury in HepG2 cells. The study data indicated a dose response relationship between mercury exposure and the degree of early and late-stage apoptosis in HepG2 cells. The percentages of cells undergoing early apoptosis were 0.03 ± 0.03%, 5.19 ± 0.04%, 6.36 ± 0.04%, and 8.84 ± 0.02% for 0, 1, 2, and 3 μg/mL of mercury respectively, indicating a gradual increase in apoptotic cells with increasing doses of mercury. The percentages of Caspase 3 positive cells undergoing late apoptosis were 3.58 ± 0.03%, 17.06 ± 0

The effect of the external medium on the gravity-induced polarity of cytoplasmic streaming in Chara corallina (Characeae)

Science.gov (United States)

Staves, M. P.; Wayne, R.; Leopold, A. C.

1997-01-01

Gravity induces a polarity of cytoplasmic streaming in vertical internodal cells of Chara such that the downwardly directed stream moves faster than the upwardly directed stream. In order to determine whether the statolith theory (in which intracellular sedimenting particles are responsible for gravity sensing) or the gravitational pressure theory (in which the entire protoplast acts as the gravity sensor) best explain the gravity response in Chara internodal cells, we controlled the physical properties of the external medium, including density and osmolarity, with impermeant solutes and examined the effect on the polarity of cytoplasmic streaming. As the density of the external medium is increased, the polarity of cytoplasmic streaming decreases and finally disappears when the density of the external medium is equal to that of the cell (1015 kg/m3). A further increase in the density of the external medium causes a reversal of the gravity response. These results are consistent with the gravitational pressure theory of gravity sensing since the buoyancy of the protoplast is dependent on the difference between the density of the protoplast and the external medium, and are inconsistent with the statolith theory since the buoyancy of intracellular particles are unaffected by changes in the external medium.

External man-induced events in relation to nuclear power plant design

International Nuclear Information System (INIS)

1982-01-01

This Guide deals with the basic design requirements for nuclear power plants, and presents a general design approach for protection against the effects of man-induced events. Section 2 discusses the general design approach. Section 3 outlines the development of the basic information necessary for an evaluation of the adequacy of a design against the effects of aircraft crashes, fires, explosions, and the release of toxic gases or corrosive substances. Section 4 outlines the design logic for protection against external man-induced events. It indicates possible methods of ensuring overall plant safety, including protection against possible secondary effects. Included for each event are: a methodology for calculating the design input parameters from the data generated in the siting study, system protection considerations from the effects of this man-induced event, and criteria for judging the adequacy of the protection provided. Specific design guidance related to acts of sabotage is not provided in this Guide. It should be recognized, however, that for certain situations such acts can be important to safety and could constitute the controlling postulated initiating event for design. The list of events covered is not necessarily complete. However, important events on which enough work has already been done in various Member States to enable their effects to be converted into generally accepted design parameters are included. In addition, other man-induced events such as dam ruptures, ship collisions, construction accidents and the like are identified but no general guidelines for design can be specified for these at present. These events need to be considered on an ad hoc basis, in order to arrive at design input parameters for them

Roles of effective helical ripple rates in nonlinear stability of externally induced magnetic islands

Energy Technology Data Exchange (ETDEWEB)

Nishimura, Seiya, E-mail: n-seiya@kobe-kosen.ac.jp [Kobe City College of Technology, Kobe, Hyogo 651-2194 (Japan)

2015-02-15

Magnetic islands are externally produced by resonant magnetic perturbations (RMPs) in toroidal plasmas. Spontaneous annihilation of RMP-induced magnetic islands called self-healing has been observed in helical systems. A possible mechanism of the self-healing is shielding of RMP penetration by helical ripple-induced neoclassical flows, which give rise to neoclassical viscous torques. In this study, effective helical ripple rates in multi-helicity helical systems are revisited, and a multi-helicity effect on the self-healing is investigated, based on a theoretical model of rotating magnetic islands. It is confirmed that effective helical ripple rates are sensitive to magnetic axis positions. It is newly found that self-healing thresholds also strongly depend on magnetic axis positions, which is due to dependence of neoclassical viscous torques on effective helical ripple rates.

Behavioural responses to human-induced environmental change.

Science.gov (United States)

Tuomainen, Ulla; Candolin, Ulrika

2011-08-01

The initial response of individuals to human-induced environmental change is often behavioural. This can improve the performance of individuals under sudden, large-scale perturbations and maintain viable populations. The response can also give additional time for genetic changes to arise and, hence, facilitate adaptation to new conditions. On the other hand, maladaptive responses, which reduce individual fitness, may occur when individuals encounter conditions that the population has not experienced during its evolutionary history, which can decrease population viability. A growing number of studies find human disturbances to induce behavioural responses, both directly and by altering factors that influence fitness. Common causes of behavioural responses are changes in the transmission of information, the concentration of endocrine disrupters, the availability of resources, the possibility of dispersal, and the abundance of interacting species. Frequent responses are alterations in habitat choice, movements, foraging, social behaviour and reproductive behaviour. Behavioural responses depend on the genetically determined reaction norm of the individuals, which evolves over generations. Populations first respond with individual behavioural plasticity, whereafter changes may arise through innovations and the social transmission of behavioural patterns within and across generations, and, finally, by evolution of the behavioural response over generations. Only a restricted number of species show behavioural adaptations that make them thrive in severely disturbed environments. Hence, rapid human-induced disturbances often decrease the diversity of native species, while facilitating the spread of invasive species with highly plastic behaviours. Consequently, behavioural responses to human-induced environmental change can have profound effects on the distribution, adaptation, speciation and extinction of populations and, hence, on biodiversity. A better understanding of

Trace elements in human, cattle and swine teeth, measured by external beam PIXE-PIGE setup

International Nuclear Information System (INIS)

Tabacniks, M.H.; Rizzutto, M.A.; Added, N.; Liguori Neto, R.; Acquadro, J.C.; Vilela, M.; Oliveira, T.R.C.F.; Markarian, R.A.; Mori, M.

2001-01-01

The use of animal teeth to replace human teeth in dentistry school classes and to test chemicals and fillings, motivated for a better characterization of the elementary composition of their enamel, since some of the chemical properties, adhesion and chemical compatibility may depend on these parameters. Cattle, swine and human teeth were collected by dentists of the University of Sao Paulo. These teeth came primarily from Sao Paulo region and were analyzed for trace elements at the Open Nuclear Physics Laboratory, using a high energy external proton beam, PIXE-PIGE setup

Radiation-induced instability of human genome

International Nuclear Information System (INIS)

Ryabchenko, N.N.; Demina, Eh.A.

2014-01-01

A brief review is dedicated to the phenomenon of radiation-induced genomic instability where the increased level of genomic changes in the offspring of irradiated cells is characteristic. Particular attention is paid to the problems of genomic instability induced by the low-dose radiation, role of the bystander effect in formation of radiation-induced instability, and its relationship with individual radiosensitivity. We believe that in accordance with the paradigm of modern radiobiology the increased human individual radiosensitivity can be formed due to the genome instability onset and is a significant risk factor for radiation-induced cancer

Application of declarative modeling approaches for external events

International Nuclear Information System (INIS)

Anoba, R.C.

2005-01-01

Probabilistic Safety Assessments (PSAs) are increasingly being used as a tool for supporting the acceptability of design, procurement, construction, operation, and maintenance activities at Nuclear Power Plants. Since the issuance of Generic Letter 88-20 and subsequent IPE/IPEEE assessments, the NRC has issued several Regulatory Guides such as RG 1.174 to describe the use of PSA in risk-informed regulation activities. Most PSA have the capability to address internal events including internal floods. As the more demands are being placed for using the PSA to support risk-informed applications, there has been a growing need to integrate other eternal events (Seismic, Fire, etc.) into the logic models. Most external events involve spatial dependencies and usually impact the logic models at the component level. Therefore, manual insertion of external events impacts into a complex integrated fault tree model may be too cumbersome for routine uses of the PSA. Within the past year, a declarative modeling approach has been developed to automate the injection of external events into the PSA. The intent of this paper is to introduce the concept of declarative modeling in the context of external event applications. A declarative modeling approach involves the definition of rules for injection of external event impacts into the fault tree logic. A software tool such as the EPRI's XInit program can be used to interpret the pre-defined rules and automatically inject external event elements into the PSA. The injection process can easily be repeated, as required, to address plant changes, sensitivity issues, changes in boundary conditions, etc. External event elements may include fire initiating events, seismic initiating events, seismic fragilities, fire-induced hot short events, special human failure events, etc. This approach has been applied at a number of US nuclear power plants including a nuclear power plant in Romania. (authors)

ISS External Contamination Environment for Space Science Utilization

Science.gov (United States)

Soares, Carlos; Mikatarian, Ron; Steagall, Courtney; Huang, Alvin; Koontz, Steven; Worthy, Erica

2014-01-01

(1) The International Space Station is the largest and most complex on-orbit platform for space science utilization in low Earth orbit, (2) Multiple sites for external payloads, with exposure to the associated natural and induced environments, are available to support a variety of space science utilization objectives, (3) Contamination is one of the induced environments that can impact performance, mission success and science utilization on the vehicle, and (4)The ISS has been designed, built and integrated with strict contamination requirements to provide low levels of induced contamination on external payload assets.

Flow-induced vibration of steam generator helical tubes subjected to external liquid cross flow and internal two-phase flow

International Nuclear Information System (INIS)

Jong Chull Jo; Myung Jo Jhung; Woong Sik Kim; Hho Jung Kim

2005-01-01

Full text of publication follows: This paper addresses the potential flow-induced vibration problems in a helically-coiled tube steam generator of integral-type nuclear reactor, of which the tubes are subjected to liquid cross flow externally and multi-phase flow externally. The thermal-hydraulic conditions of both tube side and shell side flow fields are predicted using a general purpose computational fluid dynamics code employing the finite volume element modeling. To get the natural frequency and corresponding mode shape of the helical type tubes with various conditions, a finite element analysis code is used. Based on the results of both helical coiled tube steam generator thermal-hydraulic and coiled tube modal analyses, turbulence-induced vibration and fluid-elastic instability analyses are performed. And then the potential for damages on the tubes due to either turbulence-induced vibration or fluid-elastic instability is assessed. In the assessment, special emphases are put on the detailed investigation for the effects of support conditions, coil diameter, and helix pitch on the modal, vibration amplitude and instability characteristics of tubes, from which a technical information and basis needed for designers and regulatory reviewers can be derived. (authors)

External and internal geometry of European adults.

Science.gov (United States)

Bertrand, Samuel; Skalli, Wafa; Delacherie, Laurent; Bonneau, Dominique; Kalifa, Gabriel; Mitton, David

2006-12-15

The primary objective of the study was to bring a deeper knowledge of the human anthropometry, investigating the external and internal body geometry of small women, mid-sized men and tall men. Sixty-four healthy European adults were recruited. External measurements were performed using classical anthropometric instruments. Internal measurements of the trunk bones were performed using a stereo-radiographic 3D reconstruction technique. Besides the original procedure presented in this paper for performing in vivo geometrical data acquisition on numerous volunteers, this study provides an extensive description of both external and internal (trunk skeleton) human body geometry for three morphotypes. Moreover, this study proposes a global external and internal geometrical description of 5th female 50th male and 95th male percentile subjects. This study resulted in a unique geometrical database enabling improvement for numerical models of the human body for crash test simulation and offering numerous possibilities in the anthropometry field.

ExternE: Externalities of energy Vol. 4. Oil and gas

International Nuclear Information System (INIS)

Friedrich, R.; Krewitt, W.; Mayerhofer, P.

1995-01-01

Awareness of the environmental damage resulting from human activity, particularly commencing energy use, has grown greatly in recent years. Effects such as global warming, ozone depletion and acid rain are now the subjects of much research and public debate. It is now known that these and other effects damage a wide range of receptors, including human health, forests, crops, freshwater ecosystems and buildings. Such damages are typically not accounted for by the producers and consumers of the good in question (in this case energy). They are thus referred to as 'external costs' or 'externalities', to distinguish them from the private costs which account for the construction of plant, cost of fuel, wages, etc. In recent years there has been a growing interest in the assessment of the environmental and health impacts of energy, and the related external costs. This concern is driven by a number of different factors: the need to integrate environmental concerns in decision making over the choice between different fuels and energy technologies; the need to evaluate the costs and benefits of stricter environmental standards; increased attention to the use of economic instruments for environmental policy, the need to develop overall indicators of environmental performance of different technologies; major changes in the energy sector, including privatisation, liberalisation of markets, reduction of subsidies, etc. An agreed methodology for calculation and integration of external costs has not been established. Earlier work is typically of a preliminary nature and tends to be deficient with respect to both the methods employed and the quality of models and data used. In consequence of this a collaborative project, the EC/US Fuel Cycles Study, was established between Directorate General XLI (Science, Research and Technology) of the European Commission and the United States Department of Energy. This ran for the period 1991 to 1993, and good agreement on a variety of

Hexavalent chromium induces chromosome instability in human urothelial cells

Energy Technology Data Exchange (ETDEWEB)

Wise, Sandra S. [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Holmes, Amie L. [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Department of Radiation Oncology, Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Liou, Louis [Department of Pathology, Boston University School of Medicine, 670 Albany St., Boston, MA 02118 (United States); Adam, Rosalyn M. [Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Wise, John Pierce Sr., E-mail: john.wise@louisville.edu [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States)

2016-04-01

Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. - Highlights: • Hexavalent chromium is genotoxic to human urothelial cells. • Hexavalent chromium induces aneuploidy in human urothelial cells. • hTERT-immortalized human urothelial cells model the effects seen in primary urothelial cells. • Hexavalent chromium has a strong likelihood of being carcinogenic for bladder tissue.

Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs.

Science.gov (United States)

Muñoz-Islas, Enriqueta; González-Hernández, Abimael; Lozano-Cuenca, Jair; Ramírez-Rosas, Martha Beatríz; Medina-Santillán, Roberto; Centurión, David; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

2015-10-01

During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine. Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1-C3) for infusions of 5-HT. The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT. Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action. © International Headache Society 2015.

RELATIVECONTRIBUTIONS OF THE NIGERIAN CAPITALMARKETTO THE GROWTH OF EXTERNAL RESERVES (2005-2014

Directory of Open Access Journals (Sweden)

Akaninyene Udo Akpan

2015-01-01

Full Text Available Virtually all aspects of human endeavour entail the use of money either selfgenerated or borrowed. In capital market, the stock in trade is money which couldbe raised through various instruments under well governed rules and regulationscarefully administered and followed by different institutions or market operators.External reserves constitute an integral part of the wealth of the nation such thatthe lack of it brings worry to most nations and can limit the ability of the countryto make foreign currency denominated payments and limits its spending abroad.Hence,countries are induced to hold reserves to allow monetary authorities tointervene in markets to control the exchange rate and inflation. Adequate reservesalso allow the country to borrow from abroad and to hedge against instability anduncertainty of external capital flows.Therefore, the objective of this paper is toaccess the relative contribution of the Nigerian capital market if any to the growthof her external reserve.The methodology used is purely descriptive and narrative and the data used is secondary. The evidence provided in the study based on thestatistical analysis, revealed that the Nigerian capital market can induce thegrowthof external reserve but it has not contributed to the growth of externalreserve in Nigeria. Furthermore, the study recommendedamong otherstheneedfor availability of more investment instruments such as derivatives, futures,swaps, options in the market and theexpansion of the Nigerian capital Market bythe government creating an enabling investable environment that will increaseboth the volume of transactions and number of securities traded in the market.This will improve their ability to mobilize resources and efficiently allocate themto the most productive sectors of the economy hence, contributing its portion tothe growth of her external reserve.

International Space Station External Contamination Environment for Space Science Utilization

Science.gov (United States)

Soares, Carlos E.; Mikatarian, Ronald R.; Steagall, Courtney A.; Huang, Alvin Y.; Koontz, Steven; Worthy, Erica

2014-01-01

The International Space Station (ISS) is the largest and most complex on-orbit platform for space science utilization in low Earth orbit. Multiple sites for external payloads, with exposure to the associated natural and induced environments, are available to support a variety of space science utilization objectives. Contamination is one of the induced environments that can impact performance, mission success and science utilization on the vehicle. The ISS has been designed, built and integrated with strict contamination requirements to provide low levels of induced contamination on external payload assets. This paper addresses the ISS induced contamination environment at attached payload sites, both at the requirements level as well as measurements made on returned hardware, and contamination forecasting maps being generated to support external payload topology studies and science utilization.

Radiation-induced external ear canal cholesteatoma-like disease

Energy Technology Data Exchange (ETDEWEB)

Ishihara, Akiko; Okuno, Hideji; Noguchi, Keisuke; Komatsuzaki, Atsushi [Tokyo Medical and Dental Univ. (Japan). School of Medicine

1999-06-01

Three cases of cholesteatoma-like disease in the ear canals after radiation therapy for head and neck tumor were reported. Effect of irradiation on bone and soft tissue including skin brings about pathological reaction to the external ear canal as well. Two types of disease resembling cholesteatomas have been recognized: keratosis obturans (KO) and external auditory canal cholesteatoma (EACC). KO appears to be derived from disease of canal skin involved with keratinization, creating a widning of the canal. EACC, on the other hand, seems to develop in the disease of bony canal where a localized absorption of its bone with invasion of squamous epithelium takes place. (author)

Vitamin D fails to prevent serum starvation- or staurosporine-induced apoptosis in human and rat osteosarcoma-derived cell lines

International Nuclear Information System (INIS)

Witasp, Erika; Gustafsson, Ann-Catrin; Cotgreave, Ian; Lind, Monica; Fadeel, Bengt

2005-01-01

Previous studies have suggested that 1,25(OH) 2 D 3 , the active form of vitamin D 3 , may increase the survival of bone-forming osteoblasts through an inhibition of apoptosis. On the other hand, vitamin D 3 has also been shown to trigger apoptosis in human cancer cells, including osteosarcoma-derived cell lines. In the present study, we show that 1,25(OH) 2 D 3 induces a time- and dose-dependent loss of cell viability in the rat osteosarcoma cell line, UMR-106, and the human osteosarcoma cell line, TE-85. We were unable, however, to detect nuclear condensation, phosphatidylserine externalization, or other typical signs of apoptosis in this model. Moreover, 1,25(OH) 2 D 3 failed to protect against apoptosis induced by serum starvation or incubation with the protein kinase inhibitor, staurosporine. These in vitro findings are thus at variance with several previous reports in the literature and suggest that induction of or protection against apoptosis of bone-derived cells may not be a primary function of vitamin D 3

Inducing and manipulating magnetization in 2D zinc–oxide by strain and external voltage

Science.gov (United States)

Taivansaikhan, P.; Tsevelmaa, T.; Rhim, S. H.; Hong, S. C.; Odkhuu, D.

2018-04-01

Two-dimensional (2D) structures that exhibit intriguing magnetic phenomena such as perpendicular magnetic anisotropy and its switchable feature are of great interests in spintronics research. Herein, the density functional theory studies reveal the critical impacts of strain and external gating on vacancy-induced magnetism and its spin direction in a graphene-like single layer of zinc oxide (ZnO). In contrast to the pristine and defective ZnO with an O-vacancy, the presence of a Zn-vacancy induces significant magnetic moments to its first neighboring O and Zn atoms due to the charge deficit. We further predict that the direction of magnetization easy axis reverses from an in-plane to perpendicular orientation under a practically achievable biaxial compressive strain of only ~1–2% or applying an electric field by means of the charge density modulation. This magnetization reversal is mainly driven by the strain- and electric-field-induced changes in the spin–orbit coupled d states of the first-neighbor Zn atom to a Zn-vacancy. These findings open interesting prospects for exploiting strain and electric field engineering to manipulate magnetism and magnetization orientation of 2D materials.

THE ESTIMATION OF HUMAN-OPERATOR CYBERNETIC ABILITIES DURING THE IMPACT OF DESTABILIZING FACTORS OF EXTERNAL ENVIRONMENT

Directory of Open Access Journals (Sweden)

Sergii T. Polishchuk

2009-04-01

Full Text Available  The method of estimation of human-operator cybernetics abilities during of the impacting of destabilizing factors of external environment is suggested. It was proved that up-to-date biomedical approach for periodical health examination of pilots in civil aviation isn’t guarantees theirs cybernetics abilities in cases of influence of destabilizing factors.

Gain with and without population inversion via vacuum-induced coherence in a V-type atom without external coherent driving

International Nuclear Information System (INIS)

Xu Weihua; Wu Jinhui; Gao Jinyue

2006-01-01

In a three-level V-type atomic system without any external coherent driving, owing to the coherence that results from the vacuum of the radiation field, both the probe gain with and without population inversion can be achieved with very weak incoherent pumping. The gain is achieved in the absence of any external coherent driving field, so it is different from the gain without inversion in ordinary laser-driven schemes where a coherent driving field is necessary to create the coherence. The gain is also different from the conventional lasing gain because the population inversion is achieved via vacuum-induced coherence, which is dependent on the atomic coherence

Verocytotoxin-induced apoptosis of human microvascular endothelial cells.

Science.gov (United States)

Pijpers, A H; van Setten, P A; van den Heuvel, L P; Assmann, K J; Dijkman, H B; Pennings, A H; Monnens, L A; van Hinsbergh, V W

2001-04-01

The pathogenesis of the epidemic form of hemolytic uremic syndrome is characterized by endothelial cell damage. In this study, the role of apoptosis in verocytotoxin (VT)-mediated endothelial cell death in human glomerular microvascular endothelial cells (GMVEC), human umbilical vein endothelial cells, and foreskin microvascular endothelial cells (FMVEC) was investigated. VT induced apoptosis in GMVEC and human umbilical vein endothelial cells when the cells were prestimulated with the inflammatory mediator tumor necrosis factor-alpha (TNF-alpha). FMVEC displayed strong binding of VT and high susceptibility to VT under basal conditions, which made them suitable for the study of VT-induced apoptosis without TNF-alpha interference. On the basis of functional (flow cytometry and immunofluorescence microscopy using FITC-conjugated annexin V and propidium iodide), morphologic (transmission electron microscopy), and molecular (agarose gel electrophoresis of cellular DNA fragments) criteria, it was documented that VT induced programmed cell death in microvascular endothelial cells in a dose- and time-dependent manner. Furthermore, whereas partial inhibition of protein synthesis by VT was associated with a considerable number of apoptotic cells, comparable inhibition of protein synthesis by cycloheximide was not. This suggests that additional pathways, independent of protein synthesis inhibition, may be involved in VT-mediated apoptosis in microvascular endothelial cells. Specific inhibition of caspases by Ac-Asp-Glu-Val-Asp-CHO, but not by Ac-Tyr-Val-Ala-Asp-CHO, was accompanied by inhibition of VT-induced apoptosis in FMVEC and TNF-alpha-treated GMVEC. These data indicate that VT can induce apoptosis in human microvascular endothelial cells.

Human internal and external exposure to PBDEs--a review of levels and sources

DEFF Research Database (Denmark)

Frederiksen, Marie; Vorkamp, Katrin; Thomsen, Marianne

2009-01-01

This paper reviews the existing literature on human exposure to polybrominated diphenyl ethers (PBDEs), with particular focus on external exposure routes (e.g. dust, diet, and air) and the resulting internal exposure to PBDEs (e.g. breast milk and blood). Being lipophilic and persistent organic...... ingest more dust than adults. Infants are also exposed to PBDEs via breast milk. Internal human exposure has generally been found to be one order of magnitude larger in North America than in Europe and Asia. These differences cannot solely be explained by the dietary intake as meat products are the only...... food group where some differences has been observed. However, indoor air and dust concentrations have been found to be approximately one order of magnitude higher in North America than in Europe, possibly a result of different fire safety standards. Within Europe, higher PBDE concentrations in dust...

Evaluation of the Induced Activity in Air by the External Proton Beam in the Target Room of the Proton Accelerator Facility of Proton Engineering Frontier Project

International Nuclear Information System (INIS)

Lee, Cheol Woo; Lee, Young Ouk; Cho, Young Sik; Ahn, So Hyun

2007-01-01

One of the radiological concerns is the worker's exposure level and the concentration of the radionuclides in the air after shutdown, for the safety analysis on the proton accelerator facility. Although, the primary radiation source is the protons accelerated up to design value, all of the radio-nuclide is produced from the secondary neutron and photon induced reaction in air. Because, the protons don't penetrate the acceleration equipment like the DTL tank wall or BTL wall, secondary neutrons or photons are only in the air in the accelerator tunnel building because of the short range of the proton in the materials. But, for the case of the target rooms, external proton beams are occasionally used in the various experiments. When these external proton beams travel through air from the end of the beam transport line to the target, they interact directly with air and produce activation products from the proton induced reaction. The external proton beam will be used in the target rooms in the accelerator facility of the Proton Accelerator Frontier Project (PEFP). In this study, interaction characteristics of the external proton beam with air and induced activity in air from the direct interaction of the proton beam were evaluated

External Events PSA for the Paks NPP

International Nuclear Information System (INIS)

Bareith, Attila; Karsa, Zoltan; Siklossy, Tamas; Vida, Zoltan

2014-01-01

quantification and interpretation of results. The risk of core damage induced by natural external hazards was quantified to the extent seen feasible. In addition to risk quantification, unresolved issues and necessary follow-on analyses were identified and proposed. At present an action plan is being developed for these analyses. Core damage risk has been assessed quantitatively for wind, snow and frost hazards. Detailed importance, sensitivity and uncertainty analyses were conducted. Moreover the main risk contributors induced by these external events were also identified. Additional follow-on analyses were proposed to enable an improved risk quantification by means of reducing uncertainties, establishing a better technical basis for the applied analytical assumptions, or decreasing unnecessarily high conservatism. Based on the findings of hazard assessment and plant response analysis, the core damage risk induced by extreme rainfall and lightning was found to be insignificant. However, some follow-on analyses were proposed and safety enhancement measures were conceptualised to fully underpin this conclusion. Due to lack of appropriate data and supporting analysis on the capacity of plant systems and components no PSA model has been developed yet for extreme temperatures. Follow-on analyses necessary for quantifying the risk of core damage induced by extreme temperatures have been identified. (authors)

Human-induced Arctic moistening.

Science.gov (United States)

Min, Seung-Ki; Zhang, Xuebin; Zwiers, Francis

2008-04-25

The Arctic and northern subpolar regions are critical for climate change. Ice-albedo feedback amplifies warming in the Arctic, and fluctuations of regional fresh water inflow to the Arctic Ocean modulate the deep ocean circulation and thus exert a strong global influence. By comparing observations to simulations from 22 coupled climate models, we find influence from anthropogenic greenhouse gases and sulfate aerosols in the space-time pattern of precipitation change over high-latitude land areas north of 55 degrees N during the second half of the 20th century. The human-induced Arctic moistening is consistent with observed increases in Arctic river discharge and freshening of Arctic water masses. This result provides new evidence that human activity has contributed to Arctic hydrological change.

N-Acetylcysteine Amide Protects Against Oxidative Stress–Induced Microparticle Release From Human Retinal Pigment Epithelial Cells

Science.gov (United States)

Carver, Kyle A.; Yang, Dongli

2016-01-01

Purpose Oxidative stress is a major factor involved in retinal pigment epithelium (RPE) apoptosis that underlies AMD. Drusen, extracellular lipid- and protein-containing deposits, are strongly associated with the development of AMD. Cell-derived microparticles (MPs) are small membrane-bound vesicles shed from cells. The purpose of this study was to determine if oxidative stress drives MP release from RPE cells, to assess whether these MPs carry membrane complement regulatory proteins (mCRPs: CD46, CD55, and CD59), and to evaluate the effects of a thiol antioxidant on oxidative stress–induced MP release. Methods Retinal pigment epithelium cells isolated from human donor eyes were cultured and treated with hydrogen peroxide (H2O2) to induce oxidative stress. Isolated MPs were fixed for transmission electron microscopy or processed for component analysis by flow cytometry, Western blot analysis, and confocal microscopy. Results Transmission electron microscopy showed that MPs ranged in diameter from 100 to 1000 nm. H2O2 treatment led to time- and dose-dependent elevations in MPs with externalized phosphatidylserine and phosphatidylethanolamine, known markers of MPs. These increases were strongly correlated to RPE apoptosis. Oxidative stress significantly increased the release of mCRP-positive MPs, which were prevented by a thiol antioxidant, N-acetylcysteine amide (NACA). Conclusions This is the first evidence that oxidative stress induces cultured human RPE cells to release MPs that carry mCRPs on their surface. The levels of released MPs are strongly correlated with RPE apoptosis. N-acetylcysteine amide prevents oxidative stress–induced effects. Our findings indicate that oxidative stress reduces mCRPs on the RPE surface through releasing MPs. PMID:26842754

Activated human mast cells induce LOX-1-specific scavenger receptor expression in human monocyte-derived macrophages.

Directory of Open Access Journals (Sweden)

Mervi Alanne-Kinnunen

Full Text Available Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs.Components released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1 mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α, and transforming growth factor beta (TGF-β1, which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell -induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages.Mast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis.

Proteomic approach in human health and disease: Preventive and cure studies

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Khaled MM Koriem

2018-01-01

Full Text Available Proteomic is a branch of science that deals with various numbers of proteins where proteins are essential human constituents. Proteomic has a lot of functions inside the human and animal living organisms. This review helps to make a thought on the importance of proteomic application in human health and disease with special reference to preventive and cure studies. The human health can be divided into physical and mental health. The physical health relates to keeping human body state in a good health and to nutritional type and environmental factors. The mental health correlates to human psychological state. The main factors that affect the status of human health are human diet, exercise and sleep. The healthy diet is very important and needs to maintain the human health. The training program exercise improves human fitness and overall health and wellness. The sleep is a vital factor to sustain the human health. The human disease indicates abnormal human condition which influences the specific human part or the whole human body. There are external and internal factors which induce human disease. The external factors include pathogens while internal factors include allergies and autoimmunity. There are 4 principle types of human diseases: (1 infectious disease, (2 deficiency disease, (3 genetic disease and (4 physiological disease. There are many and various external microbes' factors that induce human infectious disease and these agents include viruses, bacteria, fungi and protozoa. The lack of necessary and vital dietary rudiments such as vitamins and minerals is the main cause of human deficiency disease. The genetic disease is initiated by hereditary disturbances that occur in the human genetic map. The physiological disease occurs when the normal human function body is affected due to human organs become malfunction. In conclusion, proteomic plays a vital and significant role in human health and disease.

External fixation of femoral defects in athymic rats: Applications for human stem cell implantation and bone regeneration

Directory of Open Access Journals (Sweden)

Terasa Foo

2013-01-01

Full Text Available An appropriate animal model is critical for the research of stem/progenitor cell therapy and tissue engineering for bone regeneration in vivo. This study reports the design of an external fixator and its application to critical-sized femoral defects in athymic rats. The external fixator consists of clamps and screws that are readily available from hardware stores as well as Kirschner wires. A total of 35 rats underwent application of the external fixator with creation of a 6-mm bone defect in one femur of each animal. This model had been used in several separate studies, including implantation of collagen gel, umbilical cord blood mesenchymal stem cells, endothelial progenitor cells, or bone morphogenetic protein-2. One rat developed fracture at the proximal pin site and two rats developed deep tissue infection. Pin loosening was found in nine rats, but it only led to the failure of external fixation in two animals. In 8 to 10 weeks, various degrees of bone growth in the femoral defects were observed in different study groups, from full repair of the bone defect with bone morphogenetic protein-2 implantation to fibrous nonunion with collagen gel implantation. The external fixator used in these studies provided sufficient mechanical stability to the bone defects and had a comparable complication rate in athymic rats as in immunocompetent rats. The external fixator does not interfere with the natural environment of a bone defect. This model is particularly valuable for investigation of osteogenesis of human stem/progenitor cells in vivo.

External Contamination Control of Attached Payloads on the International Space Station

Science.gov (United States)

Soares, Carlos E.; Mikatarian, Ronald R.; Olsen, Randy L.; Huang, Alvin Y.; Steagall, Courtney A.; Schmidl, William D.; Wright, Bruce D.; Koontz, Steven

2012-01-01

The International Space Station (ISS) is an on-orbit platform for science utilization in low Earth orbit with multiple sites for external payloads with exposure to the natural and induced environments. Contamination is one of the induced environments that can impact performance, mission success and science utilization on the vehicle. This paper describes the external contamination control requirements and integration process for externally mounted payloads on the ISS. The external contamination control requirements are summarized and a description of the integration and verification process is detailed to guide payload developers in the certification process of attached payloads on the vehicle. A description of the required data certification deliverables covers the characterization of contamination sources. Such characterization includes identification, usage and operational data for each class of contamination source. Classes of external contamination sources covered are vacuum exposed materials, sources of leakage, vacuum venting and thrusters. ISS system level analyses are conducted by the ISS Space Environments Team to certify compliance with external contamination control requirements. This paper also addresses the ISS induced contamination environment at attached payload sites, both at the requirements level as well as measurements made on ISS.

Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum

International Nuclear Information System (INIS)

Inouye, Minoru; Yamamura, Hideki; Nakano, Atsuhiro.

1995-01-01

Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 μmol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 μg/g at the time of irradiation and remaining at more than 40 μg/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositide-mediated signaling systems regulate radiation-induced apoptosis. (author)

Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum.

Science.gov (United States)

Inouye, M; Yamamura, H; Nakano, A

1995-09-01

Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 mumol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 micrograms/g at the time of irradiation and remaining at more than 40 micrograms/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositidemediated signaling systems regulate radiation-induced apoptosis.

Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum

Energy Technology Data Exchange (ETDEWEB)

Inouye, Minoru; Yamamura, Hideki [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine; Nakano, Atsuhiro

1995-09-01

Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 {mu}mol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 {mu}g/g at the time of irradiation and remaining at more than 40 {mu}g/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositide-mediated signaling systems regulate radiation-induced apoptosis. (author).

Simple wealth distribution model causing inequality-induced crisis without external shocks

Science.gov (United States)

Benisty, Henri

2017-05-01

We address the issue of the dynamics of wealth accumulation and economic crisis triggered by extreme inequality, attempting to stick to most possibly intrinsic assumptions. Our general framework is that of pure or modified multiplicative processes, basically geometric Brownian motions. In contrast with the usual approach of injecting into such stochastic agent models either specific, idiosyncratic internal nonlinear interaction patterns or macroscopic disruptive features, we propose a dynamic inequality model where the attainment of a sizable fraction of the total wealth by very few agents induces a crisis regime with strong intermittency, the explicit coupling between the richest and the rest being a mere normalization mechanism, hence with minimal extrinsic assumptions. The model thus harnesses the recognized lack of ergodicity of geometric Brownian motions. It also provides a statistical intuition to the consequences of Thomas Piketty's recent "r >g " (return rate > growth rate) paradigmatic analysis of very-long-term wealth trends. We suggest that the "water-divide" of wealth flow may define effective classes, making an objective entry point to calibrate the model. Consistently, we check that a tax mechanism associated to a few percent relative bias on elementary daily transactions is able to slow or stop the build-up of large wealth. When extreme fluctuations are tamed down to a stationary regime with sizable but steadier inequalities, it should still offer opportunities to study the dynamics of crisis and the inner effective classes induced through external or internal factors.

External dose estimation of the human associated with companion animals under veterinary nuclear medical diagnosis

International Nuclear Information System (INIS)

Ito, Nobuhiko; Hanawa, Asumi; Suzuki, Kanan

2004-01-01

This study was performed in order to make a safety guideline for veterinary nuclear medicine in Japan. Well often used radionuclides ( 18 F and 99 mTc) were employed for evaluating the external radiation exposures of veterinarians, animal owners, and the public. The human external radiation exposure from radiation sources in phantom likened to animal was considered by comparing the results of computer simulation and the actually measured exposure. The computer simulation was performed by using macro program of Microsoft Visual Basic for Applications (VBA). In this simulation calculation process, radiation absorption and buildup were taken into consideration with the gamma ray emitted from radioactive materials in the body of the animal. Both corresponded well though the simulation result tended to be overvalued from the actual measurement value. Therefore, it is thought that this system can be applied to the estimation of human's external exposure. When the calculation was done on the condition that the radioactive substance exists only in internal organs (heart, liver, kidneys, and bladder), the unequal distribution of the dose rate was found near the animal body. External radiation exposure estimation to the veterinarian, the animal owner and the public was performed under consideration of the actual working condition, the distance from the source, and the time of exposure. In the calculation, the radiation dose of the animal owner and the public did not exceed the dose limit (5 mSv/yr for the animal owner, and 1 mSv/yr for the general public: International Commission of Radiological Protection (ICRP) 1990) in the release after 24 hours of the radiopharmaceutical administering. The calculation condition used in this study was actually more excessive. So the authors consider these exposures would cause no significant issue by starting the veterinary nuclear medicine in Japan. Moreover, since injected radiopharmaceutical is excreted out of the body actually, the

Small--radiation-amplitude dynamical voltage model of an irradiated, externally unbiased Josephson tunnel junction

International Nuclear Information System (INIS)

McAdory, R.T. Jr.

1988-01-01

A theory is presented for the nonequilibrium voltage states of an irradiated Josephson junction shunted by an external resistor but with no external current or voltage biasing. This device, referred to as a free-running Josephson junction, is modeled in a small--radiation-amplitude, deterministic regime extending the previous work of Shenoy and Agarwal. The time-averaged induced voltage is treated as a dynamical variable, the external radiation is modeled as a current source, and the induced junction-radiation vector potential, with and without a mode structure, is treated to first order in the driving currents. A dynamical equation for the time-averaged induced voltage yields a (nonequilibrium) steady-state relation between the time-averaged induced voltage and the incident radiation amplitude valid for a wide range of voltages, including zero. Regions of bistability occur in the voltage--versus--incident-amplitude curves, some of which are dependent on the external resistor. The zero-voltage state breaks down, as the external radiation amplitude is increased, at a critical value of the incident-radiation amplitude inversely proportional to the external resistance

21 CFR 870.1750 - External programmable pacemaker pulse generator.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External programmable pacemaker pulse generator. 870.1750 Section 870.1750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker...

Radiation-Induced Differentiation in Human Lung Fibroblast

International Nuclear Information System (INIS)

Park, Sa-Rah; Ahn, Ji-Yeon; Han, Young-Soo; Shim, Jie-Young; Yun, Yeon-Sook; Song, Jie-Young

2007-01-01

One of the most common tumors in many countries is lung cancer and patients with lung cancer may take radiotherapy. Although radiotherapy may have its own advantages, it can also induce serious problems such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of α-SMA and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-β), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are related to fibrosis. Among them TGF-β with Smad signaling is known to be the main stream and other signaling molecules such as MAPK, ERK and JNK (3) also participates in the process. In addition to those above factors, it is thought that more diverse and complicate mechanisms may involve in the radiationinduced fibrosis. Therefore, to investigate the underlying mechanisms in radiation induced fibrosis, first of all, we confirmed whether radiation induces trans differentiation in human normal lung fibroblasts. Here, we suggest that not only TGF-β but also radiation can induce trans differentiation in human lung fibroblast WI-38 and IMR-90

The effect of internal and external fields of view on visually induced motion sickness.

Science.gov (United States)

Bos, Jelte E; de Vries, Sjoerd C; van Emmerik, Martijn L; Groen, Eric L

2010-07-01

Field of view (FOV) is said to affect visually induced motion sickness. FOV, however, is characterized by an internal setting used by the graphics generator (iFOV) and an external factor determined by screen size and viewing distance (eFOV). We hypothesized that especially the incongruence between iFOV and eFOV would lead to sickness. To that end we used a computer game environment with different iFOV and eFOV settings, and found the opposite effect. We speculate that the relative large differences between iFOV and eFOV used in this experiment caused the discrepancy, as may be explained by assuming an observer model controlling body motion. Copyright 2009 Elsevier Ltd. All rights reserved.

Effect of External Use of Sesame Oil in the Prevention of Chemotherapy-Induced Phlebitis

Science.gov (United States)

Nekuzad, Nilufar; Ashke Torab, Tahereh; Mojab, Faraz; Alavi-Majd, Hamid; Azadeh, Payam; Ehtejab, Gholamreza

2012-01-01

Intravenous chemotherapy is an important mean for the treatment of cancers. Infusion phlebitis (Ph) is a common and acute complication of chemotherapy. The frequency of Ph is about 70% in patients undergoing chemotherapeutic management. It can induce the pain, increase the risk of thrombophlebitis, lead to incomplete follow-up, and thereby, affect the patient’s health status. Respecting the great importance of these issues, it is essential to prevent Ph. This study conducted to determine the effect of external use of Sesame Oil (SO) in the prevention of Ph. Sixty patients with colon or rectum cancer, who admitted for chemotherapeutic management, enrolled in clinical trial and were randomly divided into two equal groups: Control and Intervention. Ten drops of SO was applied twice a day for 14 days externally in intervention group, whereas the control group received nothing. Incidence and grade of Ph was measured in both groups. Data was analyzed through independent t-test, Χ2, Fisher’s exact test, Mann-Whitney, and Lagrange survival using SPSS 16. The incidence of Ph was 10% and 80% in intervention group and control group, respectively.There was a significant difference between two groups (p < 0.05). Ph was 8 times more frequent in control group (R R = 8; AR R = 70%). In addition, there was statistically significant difference between the grade and incidence of Ph with SO and control group (p < 0.05). According to these results, it seems that external use of SO is effective, safe and well-tolerated for prophylaxis from Ph. Therefore, it can be suggested as a selected prevention method for reducing the complication. PMID:24250538

Controlled transport of solitons and bubbles using external perturbations

International Nuclear Information System (INIS)

Gonzalez, J.A.; Marcano, A.; Mello, B.A.; Trujillo, L.

2006-01-01

We investigate generalized soliton-bearing systems in the presence of external perturbations. We show the possibility of the transport of solitons using external waves, provided the waveform and its velocity satisfy certain conditions. We also investigate the stabilization and transport of bubbles using external perturbations in 3D-systems. We also present the results of real experiments with laser-induced vapor bubbles in liquids

Ginsenoside Rg3 induces DNA damage in human osteosarcoma cells and reduces MNNG-induced DNA damage and apoptosis in normal human cells.

Science.gov (United States)

Zhang, Yue-Hui; Li, Hai-Dong; Li, Bo; Jiang, Sheng-Dan; Jiang, Lei-Sheng

2014-02-01

Panax ginseng is a Chinese medicinal herb. Ginsenosides are the main bioactive components of P. ginseng, and ginsenoside Rg3 is the primary ginsenoside. Ginsenosides can potently kill various types of cancer cells. The present study was designed to evaluate the potential genotoxicity of ginsenoside Rg3 in human osteosarcoma cells and the protective effect of ginsenoside Rg3 with respect to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced DNA damage and apoptosis in a normal human cell line (human fibroblasts). Four human osteosarcoma cell lines (MG-63, OS732, U-2OS and HOS cells) and a normal human cell line (human fibroblasts) were employed to investigate the cytotoxicity of ginsenosides Rg3 by MTT assay. Alkaline comet assay and γH2AX focus staining were used to detect the DNA damage in MG-63 and U-2OS cells. The extent of cell apoptosis was determined by flow cytometry and a DNA ladder assay. Our results demonstrated that the cytotoxicity of ginsenoside Rg3 was dose-dependent in the human osteosarcoma cell lines, and MG-63 and U-2OS cells were the most sensitive to ginsenoside Rg3. As expected, compared to the negative control, ginsenoside Rg3 significantly increased DNA damage in a concentration-dependent manner. In agreement with the comet assay data, the percentage of γH2AX-positive MG-63 and U-2OS cells indicated that ginsenoside Rg3 induced DNA double-strand breaks in a concentration-dependent manner. The results also suggest that ginsenoside Rg3 reduces the extent of MNNG-induced DNA damage and apoptosis in human fibroblasts.

Human cytomegalovirus (HCMV) induces human endogenous retrovirus (HERV) transcription.

Science.gov (United States)

Assinger, Alice; Yaiw, Koon-Chu; Göttesdorfer, Ingmar; Leib-Mösch, Christine; Söderberg-Nauclér, Cecilia

2013-11-12

Emerging evidence suggests that human cytomegalovirus (HCMV) is highly prevalent in tumours of different origin. This virus is implied to have oncogenic and oncomodulatory functions, through its ability to control host gene expression. Human endogenous retroviruses (HERV) are also frequently active in tumours of different origin, and are supposed to contribute as cofactors to cancer development. Due to the high prevalence of HCMV in several different tumours, and its ability to control host cell gene expression, we sought to define whether HCMV may affect HERV transcription. Infection of 3 established cancer cell lines, 2 primary glioblastoma cells, endothelial cells from 3 donors and monocytes from 4 donors with HCMV (strains VR 1814 or TB40/F) induced reverse transcriptase (RT) activity in all cells tested, but the response varied between donors. Both, gammaretrovirus-related class I elements HERV-T, HERV-W, HERV-F and ERV-9, and betaretrovirus-related class II elements HML-2 - 4 and HML-7 - 8, as well as spuma-virus related class III elements of the HERV-L group were up-regulated in response to HCMV infection in GliNS1 cells. Up-regulation of HERV activity was more pronounced in cells harbouring active HCMV infection, but was also induced by UV-inactivated virus. The effect was only slightly affected by ganciclovir treatment and was not controlled by the IE72 or IE86 HCMV genes. Within this brief report we show that HCMV infection induces HERV transcriptional activity in different cell types.

Agonist-induced desensitization of human β3-adrenoceptors expressed in human embryonic kidney cells

NARCIS (Netherlands)

Michel-Reher, Martina B.; Michel, Martin C.

2013-01-01

β3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β3-adrenoceptor desensitization in HEK cells.

External gamma irradiation-induced effects in early-life stages of zebrafish, Danio rerio

International Nuclear Information System (INIS)

Gagnaire, B.; Cavalié, I.; Pereira, S.; Floriani, M.; Dubourg, N.; Camilleri, V.; Adam-Guillermin, C.

2015-01-01

Highlights: • The present study aimed to evaluate the effects of gamma rays on zebrafish larvae. • Different techniques were used: gene expression, biochemistry, microscopy and macroscopical observations. • The results showed that gamma irradiation can alter embryo-larval development at several levels of organization. - Abstract: In the general context of validation of tools useful for the characterization of ecological risk linked to ionizing radiation, the effects of an external gamma irradiation were studied in zebrafish larvae irradiated for 96 h with two dose rates: 0.8 mGy/d, which is close to the level recommended to protect ecosystems from adverse effects of ionizing radiation (0.24 mGy/d) and a higher dose rate of 570 mGy/d. Several endpoints were investigated, such as mortality, hatching, and some parameters of embryo-larval development, immunotoxicity, apoptosis, genotoxicity, neurotoxicity and histological alterations. Results showed that an exposure to gamma rays induced an acceleration of hatching for both doses and a decrease of yolk bag diameter for the highest dose, which could indicate an increase of global metabolism. AChE activity decreased with the low dose rate of gamma irradiation and alterations were also shown in muscles of irradiated larvae. These results suggest that gamma irradiation can induce damages on larval neurotransmission, which could have repercussions on locomotion. DNA damages, basal ROS production and apoptosis were also induced by irradiation, while ROS stimulation index and EROD biotransformation activity were decreased and gene expression of acetylcholinesterase, choline acetyltransferase, cytochrome p450 and myeloperoxidase increased. These results showed that ionizing radiation induced an oxidative stress conducting to DNA damages. This study characterized further the modes of action of ionizing radiation in fish.

External gamma irradiation-induced effects in early-life stages of zebrafish, Danio rerio

Energy Technology Data Exchange (ETDEWEB)

Gagnaire, B., E-mail: beatrice.gagnaire@irsn.fr [Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115 (France); Cavalié, I. [Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115 (France); Pereira, S. [Neolys Diagnostics, Lyon 69373 (France); Floriani, M.; Dubourg, N.; Camilleri, V.; Adam-Guillermin, C. [Institut de Radioprotection et de Sureté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115 (France)

2015-12-15

Highlights: • The present study aimed to evaluate the effects of gamma rays on zebrafish larvae. • Different techniques were used: gene expression, biochemistry, microscopy and macroscopical observations. • The results showed that gamma irradiation can alter embryo-larval development at several levels of organization. - Abstract: In the general context of validation of tools useful for the characterization of ecological risk linked to ionizing radiation, the effects of an external gamma irradiation were studied in zebrafish larvae irradiated for 96 h with two dose rates: 0.8 mGy/d, which is close to the level recommended to protect ecosystems from adverse effects of ionizing radiation (0.24 mGy/d) and a higher dose rate of 570 mGy/d. Several endpoints were investigated, such as mortality, hatching, and some parameters of embryo-larval development, immunotoxicity, apoptosis, genotoxicity, neurotoxicity and histological alterations. Results showed that an exposure to gamma rays induced an acceleration of hatching for both doses and a decrease of yolk bag diameter for the highest dose, which could indicate an increase of global metabolism. AChE activity decreased with the low dose rate of gamma irradiation and alterations were also shown in muscles of irradiated larvae. These results suggest that gamma irradiation can induce damages on larval neurotransmission, which could have repercussions on locomotion. DNA damages, basal ROS production and apoptosis were also induced by irradiation, while ROS stimulation index and EROD biotransformation activity were decreased and gene expression of acetylcholinesterase, choline acetyltransferase, cytochrome p450 and myeloperoxidase increased. These results showed that ionizing radiation induced an oxidative stress conducting to DNA damages. This study characterized further the modes of action of ionizing radiation in fish.

Agent-based simulation for human-induced hazard analysis.

Science.gov (United States)

Bulleit, William M; Drewek, Matthew W

2011-02-01

Terrorism could be treated as a hazard for design purposes. For instance, the terrorist hazard could be analyzed in a manner similar to the way that seismic hazard is handled. No matter how terrorism is dealt with in the design of systems, the need for predictions of the frequency and magnitude of the hazard will be required. And, if the human-induced hazard is to be designed for in a manner analogous to natural hazards, then the predictions should be probabilistic in nature. The model described in this article is a prototype model that used agent-based modeling (ABM) to analyze terrorist attacks. The basic approach in this article of using ABM to model human-induced hazards has been preliminarily validated in the sense that the attack magnitudes seem to be power-law distributed and attacks occur mostly in regions where high levels of wealth pass through, such as transit routes and markets. The model developed in this study indicates that ABM is a viable approach to modeling socioeconomic-based infrastructure systems for engineering design to deal with human-induced hazards. © 2010 Society for Risk Analysis.

External costs of electricity production: case study Croatia

International Nuclear Information System (INIS)

Bozicevic Vrhovcak, Maja; Tomsic, Zeljko; Debrecin, Nenad

2005-01-01

Because electricity production is one of the major sources of pollution, and at the same time is the most centralised one, environmental issues in power system operation and planning are gaining ever-increasing attention. It is very difficult to compare environmental impacts of various electricity generation technologies and fuel types because they are extremely divergent. The most widely accepted common denominator today is the so-called external cost by which a monetary value is associated with environmental damage. In this paper, damages to human health resulting from Croatian thermal power plants annual operation are presented. Stack emissions have been translated into ambient concentrations by atmospheric dispersion modelling. Existing data on relations between human health degradation and ground concentrations of the analysed pollutants have been used. Geographic information software has been used in order to account for spatially dependent data. Monetary values have been assigned to the estimated human health damage. External costs resulting from impact of Croatian thermal power plants airborne emissions on human health have been calculated. The total Croatian thermal power system external costs, resulting from impacts on human health, are presented and discussed

Protection against UVB-induced oxidative stress in human skin cells and skin models by methionine sulfoxide reductase A.

Science.gov (United States)

Pelle, Edward; Maes, Daniel; Huang, Xi; Frenkel, Krystyna; Pernodet, Nadine; Yarosh, Daniel B; Zhang, Qi

2012-01-01

Environmental trauma to human skin can lead to oxidative damage of proteins and affect their activity and structure. When methionine becomes oxidized to its sulfoxide form, methionine sulfoxide reductase A (MSRA) reduces it back to methionine. We report here the increase in MSRA in normal human epidermal keratinocytes (NHEK) after ultraviolet B (UVB) radiation, as well as the reduction in hydrogen peroxide levels in NHEK pre-treated with MSRA after exposure. Further, when NHEK were pre-treated with a non-cytotoxic pentapeptide containing methionine sulfoxide (metSO), MSRA expression increased by 18.2%. Additionally, when the media of skin models were supplemented with the metSO pentapeptide and then exposed to UVB, a 31.1% reduction in sunburn cells was evident. We conclude that the presence of MSRA or an externally applied peptide reduces oxidative damage in NHEK and skin models and that MSRA contributes to the protection of proteins against UVB-induced damage in skin.

Neutrophil-induced human bronchial hyperresponsiveness in vitro--pharmacological modulation.

Science.gov (United States)

Hughes, J M; McKay, K O; Johnson, P R; Tragoulias, S; Black, J L; Armour, C L

1993-04-01

Although it has been postulated that inflammatory cells cause the bronchial hyperresponsiveness which is diagnostic of asthma, until recently there has been little direct evidence of such a link. We have recently shown that calcium ionophore-activated human neutrophils and eosinophils can induce a state of human airway hyperresponsiveness in vitro. In this study we have shown that the anti-inflammatory agent nedocromil sodium, 10(-7) M, inhibited the hyperresponsiveness induced by products released from ionophore activated neutrophils but did not inhibit the release of leukotriene B4 from the same cells. Neutrophil-induced bronchial hyperresponsiveness was also inhibited by pre-treatment of the bronchial tissues with a thromboxane A2 and prostaglandin receptor antagonist, GR32191, 10(-7) M. These findings indicate that cyclooxygenase products are involved in bronchial hyperresponsiveness induced by inflammatory cell products in vitro and that their release can be inhibited by nedocromil sodium.

Does Acute Normobaric Hypoxia Induce Anapyrexia in Adult Humans?

Science.gov (United States)

Seo, Yongsuk; Gerhart, Hayden D; Vaughan, Jeremiah; Kim, Jung-Hyun; Glickman, Ellen L

2017-06-01

Seo, Yongsuk, Hayden D. Gerhart, Jeremiah Vaughan, Jung-Hyun Kim, and Ellen L. Glickman. Does acute normobaric hypoxia induce anapyrexia in adult humans? High Alt Med Biol. 18:185-190, 2017.-Exposure to hypoxia is known to induce a reduction in core body temperature as a protective mechanism, which has been shown in both animals and humans. The purpose of this study was to test if acute exposure to normobaric hypoxia (NH) induces anapyrexia in adult humans in association with decreased peripheral oxygen saturation (SpO 2 ). Ten healthy male subjects were seated in atmospheres of normobaric normoxia 21% (NN21), NH 17% (NH17), and 13% (NH13) O 2 for 60 minutes in a counterbalanced manner. Rectal temperature (Tre) was continuously monitored together with the quantification of metabolic heat production (MHP) and body heat storage (S). Baseline physiological measurements showed no differences between the three conditions. SpO 2 was significantly decreased in NH17 and NH13 compared with NN21 (p ≤ 0.001). Tre decreased following 60 minutes of resting in all conditions, but, independent of the conditions, showed no association between Tre and levels of hypoxic SpO 2 . There was also no significant difference in either MHP or S between conditions. The present results showed no evidence of hypoxia-induced anapyrexia in adult humans during 1 hour of resting after exposure to NH either at 13% or 17% O 2 .

Effect of external volume expansion on the survival of fat grafts

Directory of Open Access Journals (Sweden)

Raghuveer Reddy

2016-01-01

Full Text Available Introduction: External volume expansion (EVE is one method, which has been utilised for increasing the survival of adipose tissue grafts. EVE releases positive pressure from the graft and also induces intense levels of edema that decreases diffusion of metabolites essential for graft survival initially. The ideal timing of external volume expansion in relation to the injection of the fat to facilitate survival is not yet clear. Aims and Objectives: This study was undertaken to evaluate and compare the efficacy of external volume expansion applied at variable time points in relation to the injection of the fat. Materials and Methods: Athymic mouse was the animal model and human lipo-aspirate mixed with PRP was used as graft. An indigenous dome shaped silicone device was fabricated to deliver a negative pressure of -30 mm of Hg. The EVE was applied at variable time intervals. At the end of 4 weeks visual, histological and radiological features of the injected fat were compared. The adipose tissue was stained with human vimentin to ascertain the origin of the retained fat. Results: All the grafts, which had EVE, had significantly better volume retention and vascularity. The groups which underwent a delayed EVE or prior expansion followed by concomitant graft injection and expansion showed the most optimal vascularity and graft retention. Conclusions: A delayed EVE or prior expansion followed by concomitant graft injection and expansion may be the most ideal combinations to optimize graft take. However, on account of the relatively small sample size, there was a limitation in drawing statistically significant conclusions for certain variables.

Pathological studies on carcinoma of the lung in rats induced by external x-ray irradiation

International Nuclear Information System (INIS)

Kodama, Tetsuro

1978-01-01

Lung tumors in Wistar rats were induced by administration of various doses of external irradiation through the anterior chest wall. Pulmonary fibrosis following external irradiation was observed in 13 of 17 rats (76.4%) in Group I (800R/day for 5 days), in 26 of 36 rats (78.8%) in Group II (800R/WK for 5 WKs), and in 6 of 18 rats (35.3%) in Group III (500R/WK for 4 WKs). The degree of pulmonary fibrosis was greater each time in the rats given 4,000R than in the rats given 2,000R. In Groups I and II 5 pulmonary tumors (2 squamous cell carcinomas, 1 adenocarcinoma, and 2 adenomas) were observed in 3 of 16 rats (17.6%), and 10 pulmonary tumors (4 squamous cell carcinomas, 1 adenocarcinoma, 4 adenomas, and 1 fibrosarcoma) were observed in 9 of 33 rats (24.2%), respectively. In Group III only 1 case of pulmonary adenoma was observed among 17 rats (6.8%). The first case of epithelial tumor of the lung was found in a rat in Group I. Histological findings during the course of the experiment revealed that the earliest changes following irradiation were those of radiation pneuminitis, characterized by engorged capillaries and edema in collapsed alveoli, with lymphocytic and plasma cell infiltrations. In addition, the nuclei of the lining cells of the alveoli and bronchioles were enlarged and atypical. From the 10th through the 20th experimental week, fibrosis of the alveolar septum and adenomatous hyperplasia of the alveolar lining became extensive, particularly in the bronchiolo-alveolar areas of the periphery of the lung. Atypical adenomatous hyperplasia occurred within the fibrotic lesion or in proximity to it. It was frequently followed by carcinoma, suggesting that carcinoma in the present experiment arose in atypical epithelium, induced by irradiation of the bronchiolo-alveolar epithelial lining

Pathological studies on carcinoma of the lung in rats induced by external x-ray irradiation

Energy Technology Data Exchange (ETDEWEB)

Kodama, T [Hiroshima Univ. (Japan). School of Medicine

1978-08-01

Lung tumors in Wistar rats were induced by administration of various doses of external irradiation through the anterior chest wall. Pulmonary fibrosis following external irradiation was observed in 13 of 17 rats (76.4%) in Group I (800R/day for 5 days), in 26 of 36 rats (78.8%) in Group II (800R/WK for 5 WKs), and in 6 of 18 rats (35.3%) in Group III (500R/WK for 4 WKs). The degree of pulmonary fibrosis was greater each time in the rats given 4,000R than in the rats given 2,000R. In Groups I and II 5 pulmonary tumors (2 squamous cell carcinomas, 1 adenocarcinoma, and 2 adenomas) were observed in 3 of 16 rats (17.6%), and 10 pulmonary tumors (4 squamous cell carcinomas, 1 adenocarcinoma, 4 adenomas, and 1 fibrosarcoma) were observed in 9 of 33 rats (24.2%), respectively. In Group III only 1 case of pulmonary adenoma was observed among 17 rats (6.8%). The first case of epithelial tumor of the lung was found in a rat in Group I. Histological findings during the course of the experiment revealed that the earliest changes following irradiation were those of radiation pneuminitis, characterized by engorged capillaries and edema in collapsed alveoli, with lymphocytic and plasma cell infiltrations. In addition, the nuclei of the lining cells of the alveoli and bronchioles were enlarged and atypical. From the 10th through the 20th experimental week, fibrosis of the alveolar septum and adenomatous hyperplasia of the alveolar lining became extensive, particularly in the bronchiolo-alveolar areas of the periphery of the lung. Atypical adenomatous hyperplasia occurred within the fibrotic lesion or in proximity to it. It was frequently followed by carcinoma, suggesting that carcinoma in the present experiment arose in atypical epithelium, induced by irradiation of the bronchiolo-alveolar epithelial lining.

Arsenic exposure induces the Warburg effect in cultured human cells

Energy Technology Data Exchange (ETDEWEB)

Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T., E-mail: klimecki@pharmacy.arizona.edu

2013-08-15

Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect.

Arsenic exposure induces the Warburg effect in cultured human cells

International Nuclear Information System (INIS)

Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T.

2013-01-01

Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect

Evaluation of the induced electric field and compliance procedure for a wireless power transfer system in an electrical vehicle

International Nuclear Information System (INIS)

Laakso, Ilkka; Hirata, Akimasa

2013-01-01

In this study, an induced electric field in a human body is evaluated for the magnetic field leaked from a wireless power transfer system for charging an electrical vehicle. The magnetic field from the wireless power transfer system is modelled computationally, and its effectiveness is confirmed by comparison with the field measured in a previous study. The induced electric field in a human standing around the vehicle is smaller than the allowable limit prescribed in international guidelines, although the magnetic field strength in the human body is locally higher than the allowable external field strength. Correlation between the external magnetic field and the induced electric field is confirmed to be reasonable at least in the standing posture, which is the case discussed in the international standard. Based on this finding, we discussed and confirmed the applicability of a three-point magnetic field measurement at heights of 0.5, 1.0, and 1.5 m for safety compliance. (paper)

Evaluation of the induced electric field and compliance procedure for a wireless power transfer system in an electrical vehicle.

Science.gov (United States)

Laakso, Ilkka; Hirata, Akimasa

2013-11-07

In this study, an induced electric field in a human body is evaluated for the magnetic field leaked from a wireless power transfer system for charging an electrical vehicle. The magnetic field from the wireless power transfer system is modelled computationally, and its effectiveness is confirmed by comparison with the field measured in a previous study. The induced electric field in a human standing around the vehicle is smaller than the allowable limit prescribed in international guidelines, although the magnetic field strength in the human body is locally higher than the allowable external field strength. Correlation between the external magnetic field and the induced electric field is confirmed to be reasonable at least in the standing posture, which is the case discussed in the international standard. Based on this finding, we discussed and confirmed the applicability of a three-point magnetic field measurement at heights of 0.5, 1.0, and 1.5 m for safety compliance.

Hodgkin's disease: thyroid dysfunction following external irradiation

International Nuclear Information System (INIS)

Tamura, K.; Shimaoka, K.

1981-01-01

The thyroid gland is commonly included in the field of radiation therapy for patients with malignant lymphoma and with head and neck tumors. The radiation dose for malignant diseases varies considerably depending on the purpose of treatment and the institutional policies. A substantial number of these patients are developing subclinical and clinical hypothyroidism. The risk of developing hypothyroidism after a moderate radiation dose of 2000 to 4500 rads has been reported to be 10 to 20 percent. In addition, subclinical hypothyroidism is induced further in one third of the patients. There are also suggestions that external irradiation of the thyroid gland in patients with malignant lymphomas, as well as internal irradiation with radioiodine of the normal and hyperthyroid human thyroid glands, would induce elevations of serum antithyroid autoantibody titers. However, only a few cases of Graves disease following irradiation to the thyroid gland have been reported. We encountered a young woman who received radiation therapy to the mantle field for her Hodgkin's disease and developed hypothyroxinemia without overt signs and symptoms of hypothyroidism, followed by appearance of nodular goiter and then full-blown Graves disease

ExternE: Externalities of energy Vol. 3. Coal and lignite

International Nuclear Information System (INIS)

Berry, J.; Holland, M.; Lee, D.

1995-01-01

Awareness of the environmental damage resulting from human activity, particularly concerning energy use, has grown greatly in recent years. Effects such as global warming, ozone depletion and acid rain are now the subjects of much research and public debate. It is now known that these and other effects damage a wide range of receptors, including human health, forests, crops, freshwater ecosystems and buildings. Such damages are typically not accounted for by the producers and consumers of the good in question (in this case energy). They are thus referred to as 'external costs' or 'externalities', to distinguish them from the private costs which account for the construction of plant, cost of fuel, wages, etc. In recent years there has been a growing interest in the assessment of the environmental and health impacts of energy, and the related external costs. This concern is driven by a number of different factors: the need to integrate environmental concerns in decision making over the choice between different fuels and energy technologies; the need to evaluate the costs and benefits of stricter environmental standards; increased attention to the use of economic instruments for environmental policy; the need to develop overall indicators of environmental performance of different technologies; major changes in the energy sector, including privatisation, liberalisation of markets, reduction of subsidies, etc. An agreed methodology for calculation and integration of external costs has not been established. Earlier work is typically of a preliminary nature and tends to be deficient with respect to both the methods employed and the quality of models and data used. In consequence of this a collaborative project, the EC/US Fuel Cycles Study, was established between Directorate General XII (Science, Research and Technology) of the European Commission and the United States Department of Energy. This ran for the period 1991 to 1993, and good agreement on a variety of

induced acute cytotoxicity in human cervical epithelial carcinoma cells

African Journals Online (AJOL)

Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

21 CFR 868.5935 - External negative pressure ventilator.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External negative pressure ventilator. 868.5935 Section 868.5935 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... ventilator. (a) Identification. An external negative pressure ventilator (e.g., iron lung, cuirass) is a...

Job Demands and Job Resources in Human Service Managerial Work An External Assessment ThroughWork Content Analysis

Directory of Open Access Journals (Sweden)

Linda Corin

2016-12-01

Full Text Available Managers’ psychosocial working conditions are important for managerial sustainability in the public sector. The job demands-resources (JD-R model is a widely applied and well-recognized framework for measuring psychosocial working conditions. However, there is still a need for methodological contributions including more objective as well as qualitative ways to assess these conditions. In this study, job demands and job resources as well as the balance between them was qualitatively and externally assessed for first-line human service managers using a work content analysis method. Conditions and actions were focused upon with an external perspective. Special attention was paid to concrete examples and consequences of work characteristics with predefined criteria and cut-off points to guide the assessments. The results reveal an imbalance for human service managers between high levels of job demands and the lack of job resources available to meet these demands. Work overload, conflicting and unclear goals and tasks, emotional demands, restricted control, and lack of supervisory and organizational support generally characterized the managerial assignment. The analysis provided concrete explanations of the current work strain in this group of employees, thereby giving both short-term and long-term possibilities for improvement of managerial work and sustainability.

Hesperetin induces melanin production in adult human epidermal melanocytes.

Science.gov (United States)

Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

2015-06-01

One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p melanin production in human melanocyte cultures could be reproduced on human skin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis.

Science.gov (United States)

Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S

1991-04-01

A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

The cytotoxic effect of oxybuprocaine on human corneal epithelial cells by inducing cell cycle arrest and mitochondria-dependent apoptosis.

Science.gov (United States)

Fan, W-Y; Wang, D-P; Wen, Q; Fan, T-J

2017-08-01

Oxybuprocaine (OBPC) is a widely used topical anesthetic in eye clinic, and prolonged and repeated usage of OBPC might be cytotoxic to the cornea, especially to the outmost corneal epithelium. In this study, we characterized the cytotoxic effect of OBPC on human corneal epithelial (HCEP) cells and investigated its possible cellular and molecular mechanisms using an in vitro model of non-transfected HCEP cells. Our results showed that OBPC at concentrations ranging from 0.025% to 0.4% had a dose- and time-dependent cytotoxicity to HCEP cells. Moreover, OBPC arrested the cells at S phase and induced apoptosis of these cells by inducing plasma membrane permeability, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation. Furthermore, OBPC could trigger the activation of caspase-2, -3, and -9, downregulate the expression of Bcl-xL, upregulate the expression of Bax along with the cytoplasmic amount of mitochondria-released apoptosis-inducing factor, and disrupt mitochondrial transmembrane potential. Our results suggest that OBPC has a dose- and time-dependent cytotoxicity to HCEP cells by inducing cell cycle arrest and cell apoptosis via a death receptor-mediated mitochondria-dependent proapoptotic pathway, and this novel finding provides new insights into the acute cytotoxicity and its toxic mechanisms of OBPC on HCEP cells.

Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

Directory of Open Access Journals (Sweden)

McIver Lauren J

2009-12-01

Full Text Available Abstract Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level.

Evolution of external genitalia: insights from reptilian development.

Science.gov (United States)

Gredler, Marissa L; Larkins, Christine E; Leal, Francisca; Lewis, A Kelsey; Herrera, Ana M; Perriton, Claire L; Sanger, Thomas J; Cohn, Martin J

2014-01-01

External genitalia are found in each of the major clades of amniotes. The phallus is an intromittent organ that functions to deliver sperm into the female reproductive tract for internal fertilization. The cellular and molecular genetic mechanisms of external genital development have begun to be elucidated from studies of the mouse genital tubercle, an embryonic appendage adjacent to the cloaca that is the precursor of the penis and clitoris. Progress in this area has improved our understanding of genitourinary malformations, which are among the most common birth defects in humans, and created new opportunities for comparative studies of other taxa. External genitalia evolve rapidly, which has led to a striking diversity of anatomical forms. Within the past year, studies of external genital development in non-mammalian amniotes, including birds, lizards, snakes, alligators, and turtles, have begun to shed light on the molecular and morphogenetic mechanisms underlying the diversification of phallus morphology. Here, we review recent progress in the comparative developmental biology of external genitalia and discuss the implications of this work for understanding external genital evolution. We address the question of the deep homology (shared common ancestry) of genital structures and of developmental mechanisms, and identify new areas of investigation that can be pursued by taking a comparative approach to studying development of the external genitalia. We propose an evolutionary interpretation of hypospadias, a congenital malformation of the urethra, and discuss how investigations of non-mammalian species can provide novel perspectives on human pathologies.

DEEP code to calculate dose equivalents in human phantom for external photon exposure by Monte Carlo method

International Nuclear Information System (INIS)

Yamaguchi, Yasuhiro

1991-01-01

The present report describes a computer code DEEP which calculates the organ dose equivalents and the effective dose equivalent for external photon exposure by the Monte Carlo method. MORSE-CG, Monte Carlo radiation transport code, is incorporated into the DEEP code to simulate photon transport phenomena in and around a human body. The code treats an anthropomorphic phantom represented by mathematical formulae and user has a choice for the phantom sex: male, female and unisex. The phantom can wear personal dosimeters on it and user can specify their location and dimension. This document includes instruction and sample problem for the code as well as the general description of dose calculation, human phantom and computer code. (author)

Vincristine-induced bystander effect in human lymphocytes

International Nuclear Information System (INIS)

Testi, Serena; Azzarà, Alessia; Giovannini, Caterina; Lombardi, Sara; Piaggi, Simona; Facioni, Maria Sole; Scarpato, Roberto

2016-01-01

Highlights: • We studied whether or not vincristine induced a bystander response in human lymphocytes. • Vincristine significantly increased MN frequencies in mononucleated recipient cells. • ROS or soluble proteins (IL-32 and TGF-β) may account for the observed response. - Abstract: Bystander effect is a known radiobiological effect, widely described using ionizing radiations and which, more recently, has also been related to chemical mutagens. In this study, we aimed to assess whether or not a bystander response can be induced in cultured human peripheral lymphocytes by vincristine, a chemotherapeutic mutagen acting as spindle poison, and by mitomycin-C, an alkylating agent already known to induce this response in human lymphoblastoid cells. Designing a modified ad hoc protocol for the cytokinesis blocked micronucleus (MN) assay, we detected the presence of a dose-dependent bystander response in untreated cultures receiving the conditioned medium (CM) from mitomycin-C (MMC) or vincristine (VCR) treated cultures. In the case of MMC, MN frequencies, expressed as micronucleated binucleates, were: 13.5 ± 1.41 at 6 μM, 22 ± 2.12 at 12 μM or 28.25 ± 5.13 at 15 μM vs. a control value of 4.75 ± 1.59. MN levels for VCR, expressed as micronucleated mononucleates were: 2.75 ± 0.88 at 0.0 μM, 27.25 ± 2.30 at 0.4 μM, 46.25 ± 1.94 at 0.8 μM, 98.25 ± 7.25 at 1.6 μM. To verify that no mutagen residual was transferred to recipient cultures together with the CM, we evaluated MN levels in cultures receiving the medium immediately after three washings following the chemical treatment (unconditioned medium). We further confirmed these results using a cell-mixing approach where untreated lymphocytes were co-cultured with donor cells treated with an effect-inducing dose of MMC or VCR. A distinct production pattern of both reactive oxygen species and soluble mediator proteins by treated cells may account for the differences observed in the manifestation of the

Vincristine-induced bystander effect in human lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Testi, Serena; Azzarà, Alessia; Giovannini, Caterina; Lombardi, Sara [Unità di Genetica, Dipartimento di Biologia, Pisa University, Via Derna 1, 56126 Pisa (Italy); Piaggi, Simona [Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Pisa University, Via Savi 10, 56126 Pisa (Italy); Facioni, Maria Sole [Unità di Genetica, Dipartimento di Biologia, Pisa University, Via Derna 1, 56126 Pisa (Italy); Scarpato, Roberto, E-mail: roberto.scarpato@unipi.it [Unità di Genetica, Dipartimento di Biologia, Pisa University, Via Derna 1, 56126 Pisa (Italy); Research Center of Nutraceuticals and Food for Health, University of Pisa, Pisa (Italy)

2016-07-15

Highlights: • We studied whether or not vincristine induced a bystander response in human lymphocytes. • Vincristine significantly increased MN frequencies in mononucleated recipient cells. • ROS or soluble proteins (IL-32 and TGF-β) may account for the observed response. - Abstract: Bystander effect is a known radiobiological effect, widely described using ionizing radiations and which, more recently, has also been related to chemical mutagens. In this study, we aimed to assess whether or not a bystander response can be induced in cultured human peripheral lymphocytes by vincristine, a chemotherapeutic mutagen acting as spindle poison, and by mitomycin-C, an alkylating agent already known to induce this response in human lymphoblastoid cells. Designing a modified ad hoc protocol for the cytokinesis blocked micronucleus (MN) assay, we detected the presence of a dose-dependent bystander response in untreated cultures receiving the conditioned medium (CM) from mitomycin-C (MMC) or vincristine (VCR) treated cultures. In the case of MMC, MN frequencies, expressed as micronucleated binucleates, were: 13.5 ± 1.41 at 6 μM, 22 ± 2.12 at 12 μM or 28.25 ± 5.13 at 15 μM vs. a control value of 4.75 ± 1.59. MN levels for VCR, expressed as micronucleated mononucleates were: 2.75 ± 0.88 at 0.0 μM, 27.25 ± 2.30 at 0.4 μM, 46.25 ± 1.94 at 0.8 μM, 98.25 ± 7.25 at 1.6 μM. To verify that no mutagen residual was transferred to recipient cultures together with the CM, we evaluated MN levels in cultures receiving the medium immediately after three washings following the chemical treatment (unconditioned medium). We further confirmed these results using a cell-mixing approach where untreated lymphocytes were co-cultured with donor cells treated with an effect-inducing dose of MMC or VCR. A distinct production pattern of both reactive oxygen species and soluble mediator proteins by treated cells may account for the differences observed in the manifestation of the

Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency

Science.gov (United States)

Cacchiarelli, Davide; Trapnell, Cole; Ziller, Michael J.; Soumillon, Magali; Cesana, Marcella; Karnik, Rahul; Donaghey, Julie; Smith, Zachary D.; Ratanasirintrawoot, Sutheera; Zhang, Xiaolan; Ho Sui, Shannan J.; Wu, Zhaoting; Akopian, Veronika; Gifford, Casey A.; Doench, John; Rinn, John L.; Daley, George Q.; Meissner, Alexander; Lander, Eric S.; Mikkelsen, Tarjei S.

2015-01-01

Summary Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered reactivation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. PMID:26186193

Induced pluripotent stem cell-derived neuron as a human model for testing environmentally induced developmental neurotoxicity

Science.gov (United States)

Induced pluripotent stem cell-derived neurons as a human model for testing environmentally induced developmental neurotoxicity Ingrid L. Druwe1, Timothy J. Shafer2, Kathleen Wallace2, Pablo Valdivia3 ,and William R. Mundy2. 1University of North Carolina, Curriculum in Toxicology...

A Study Of The Effect Of Human Soul On External Objects : Between Copenhagen School And Mulla Sadra

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Ali Arshad Riahi

2015-06-01

Full Text Available Abstract : The theory of the effects of all human souls on external objects, from the viewpoint of Copenhagen School (in Quantum Physics, has made physicists deny the existence of two separate realms of the observer and the observed; they claim that causality is meaningless and profess that it is impossible to recognize the object. While, on the other hand, Mulla Ṣadra believes that the effect of soul on external objects is limited to the souls of prophets as well as saints and, barring evil eye or supplications, there is no such effect in others. In this article we argue that, based on Mulla Ṣadra’s teachings and philosophical doctrine, it is actually possible to generalize this effect to other human souls. Consequently, it is impossible to have an accurate recognition of the causes of events if causality is considered meaningless. In addition, it is feasible to have cognition about these causes of events through gnostic intuition.Keywords : human soul, external objects, Copenhagen School, Mulla Ṣadra, unity, causality Abstrak :  Teori tentang efek jiwa seluruh manusia terhadap objek-objek eksternal, dari sudut pandang Madzhab Copenhagen (dalam Fisika Kuantum, telah membuat para fisikawan mengingkari keterpisahan dua alam, yaitu subjek dan objek; berdasarkan keyakinan ini, mereka mengklaim bahwa [hukum] kausalitas menjadi gugur dan tidak berguna, dan mereka juga percaya bahwa mengetahui sepenuhnya objek adalah tidak mungkin. Sementara, di tempat lain, Mulla Ṣadra meyakini bahwa jiwa yang berefek terhadap objek-objek eksternal terbatas pada jiwa para nabi dan orang-orang suci. Ia juga meyakini bahwa tidak berefeknya jiwa-jiwa manusia biasa kecuali pada perbuatan-perbuatan seperti yang ia sebut sebagai ‘evil eye’ dan doa. Dalam artikel ini, kami berupaya membuktikan bahwa, berdasarkan ajaran dan doktrin filsafat Mulla Ṣadra, pengaruh (efek jiwa manusia dapat digeneralisir. Dengan demikian tidak mungkin untuk mengetahui secara

External flood probabilistic safety analysis of a coastal NPP

International Nuclear Information System (INIS)

Pisharady, Ajai S.; Chakraborty, M.K.; Acharya, Sourav; Roshan, A.D.; Bishnoi, L.R.

2015-01-01

External events pose a definitive challenge to safety of NPP, solely due to their ability to induce common cause failures. Flooding incidents at Le Blayais NPP, France, Fort Calhoun NPP, USA and Fukushima Daiichi have pointed to the importance of external flooding as an important contributor to NPP risk. A methodology developed for external flood PSA of a coastal NPP vulnerable to flooding due to tsunami, cyclonic storm and intense local precipitation is presented in this paper. Different tasks for EFPSA has been identified along with general approach for completing each task

The Difference Between Ice Cream and Nazis: Moral Externalization and the Evolution of Human Cooperation.

Science.gov (United States)

Stanford, P Kyle

2017-07-06

A range of empirical findings are first used to more precisely characterize our distinctive tendency to objectify or externalize moral demands, and it is then argued that this salient feature of our moral cognition represents a profound puzzle for evolutionary approaches to human moral psychology that existing proposals do not help to resolve. It is then proposed that such externalization facilitated a broader shift to a vastly more cooperative form of social life by establishing and maintaining a connection between the extent to which an agent is herself motivated by a given moral norm and the extent to which she uses conformity to that same norm as a criterion in evaluating candidate partners in social interaction generally. This connection ensures the correlated interaction necessary to protect those prepared to adopt increasingly cooperative, altruistic, and other prosocial norms of interaction from exploitation, especially as such norms were applied in novel ways and/or to novel circumstances and as the rapid establishment of new norms allowed us to reap still greater rewards from hypercooperation. A wide range of empirical findings are then used to support this hypothesis, showing why the status we ascribe to moral demands and considerations exhibits the otherwise puzzling combination of objective and subjective elements that it does as well as showing how the need to effectively advertise our externalization of particular moral commitments generates features of our social interaction so familiar that they rarely strike us as standing in need of any explanation in the first place.

Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells

DEFF Research Database (Denmark)

Pasarica, Magdalena; Mashtalir, Nazar; McAllister, Emily J

2008-01-01

Human adenovirus Ad-36 is causatively and correlatively linked with animal and human obesity, respectively. Ad-36 enhances differentiation of rodent preadipocytes, but its effect on adipogenesis in humans is unknown. To indirectly assess the role of Ad-36-induced adipogenesis in human obesity......, the effect of the virus on commitment, differentiation, and lipid accumulation was investigated in vitro in primary human adipose-derived stem/stromal cells (hASC). Ad-36 infected hASC in a time- and dose-dependent manner. Even in the presence of osteogenic media, Ad-36-infected hASC showed significantly...... greater lipid accumulation, suggestive of their commitment to the adipocyte lineage. Even in the absence of adipogenic inducers, Ad-36 significantly increased hASC differentiation, as indicated by a time-dependent expression of genes within the adipogenic cascade-CCAAT/Enhancer binding protein...

Investigation of thermoelastic stresses induced at high altitudes on aircraft external fuel tanks

Science.gov (United States)

Mousseau, Stephanie Lynn Steber

As composite technology has grown over the past several decades, the use of composite materials in military applications has become more feasible and widely accepted. Although composite materials provide many benefits, including strength optimization and reduced weight, damage and repair of these materials creates an additional challenge, especially when operating in a marine environment, such as on a carrier deck. This is evident within the Navy, as excessive damage often leads to the scrapping of F/A-18 External Fuel Tanks. This damage comes in many forms, the most elusive of which is delamination. Often the delamination found on the tanks is beyond repairable limits and the cause unknown, making it difficult to predict and prevent. The purpose of this investigation was to study the structure of the Navy's 330 gallon External Fuel Tanks and investigate one potential cause of delamination, stresses induced at high altitudes by cold temperatures. A stress analysis was completed using finite element software, and validation of the model was accomplished through testing of a scale model specimen. Due to the difficulties in modeling and predicting delamination, such as unknown presence of voids and understanding failure criteria, delamination was not modeled in Abaqus, rather stresses were observed and characteristics were studied to understand the potential for delamination within the layup. In addition, studies were performed to understand the effect of material properties and layup sequence on the stress distribution within the tank. Alternative design solutions are presented which could reduce the radial stresses within the tank, and recommendations are made for further study to understand the trade-offs between stress, cost, and manufacturability.

Coherent polarization driven by external electromagnetic fields

International Nuclear Information System (INIS)

Apostol, M.; Ganciu, M.

2010-01-01

The coherent interaction of the electromagnetic radiation with an ensemble of polarizable, identical particles with two energy levels is investigated in the presence of external electromagnetic fields. The coupled non-linear equations of motion are solved in the stationary regime and in the limit of small coupling constants. It is shown that an external electromagnetic field may induce a macroscopic occupation of both the energy levels of the particles and the corresponding photon states, governed by a long-range order of the quantum phases of the internal motion (polarization) of the particles. A lasing effect is thereby obtained, controlled by the external field. Its main characteristics are estimated for typical atomic matter and atomic nuclei. For atomic matter the effect may be considerable (for usual external fields), while for atomic nuclei the effect is extremely small (practically insignificant), due to the great disparity in the coupling constants. In the absence of the external field, the solution, which is non-analytic in the coupling constant, corresponds to a second-order phase transition (super-radiance), which was previously investigated.

Fast-ion losses induced by ELMs and externally applied magnetic perturbations in the ASDEX Upgrade tokamak

International Nuclear Information System (INIS)

Garcia-Munoz, M; Rodriguez-Ramos, M; Äkäslompolo, S; De Marne, P; Dunne, M G; Dux, R; Fietz, S; Fuchs, C; Geiger, B; Herrmann, A; Hoelzl, M; Kurzan, B; McDermott, R M; Strumberger, E; Evans, T E; Ferraro, N M; Pace, D C; Lazanyi, N; Nocente, M; Shinohara, K

2013-01-01

Phase-space time-resolved measurements of fast-ion losses induced by edge localized modes (ELMs) and ELM mitigation coils have been obtained in the ASDEX Upgrade tokamak by means of multiple fast-ion loss detectors (FILDs). Filament-like bursts of fast-ion losses are measured during ELMs by several FILDs at different toroidal and poloidal positions. Externally applied magnetic perturbations (MPs) have little effect on plasma profiles, including fast-ions, in high collisionality plasmas with mitigated ELMs. A strong impact on plasma density, rotation and fast-ions is observed, however, in low density/collisionality and q 95 plasmas with externally applied MPs. During the mitigation/suppression of type-I ELMs by externally applied MPs, the large fast-ion bursts observed during ELMs are replaced by a steady loss of fast-ions with a broad-band frequency and an amplitude of up to an order of magnitude higher than the neutral beam injection (NBI) prompt loss signal without MPs. Multiple FILD measurements at different positions, indicate that the fast-ion losses due to static 3D fields are localized on certain parts of the first wall rather than being toroidally/poloidally homogeneously distributed. Measured fast-ion losses show a broad energy and pitch-angle range and are typically on banana orbits that explore the entire pedestal/scrape-off-layer (SOL). Infra-red measurements are used to estimate the heat load associated with the MP-induced fast-ion losses. The heat load on the FILD detector head and surrounding wall can be up to six times higher with MPs than without 3D fields. When 3D fields are applied and density pump-out is observed, an enhancement of the fast-ion content in the plasma is typically measured by fast-ion D-alpha (FIDA) spectroscopy. The lower density during the MP phase also leads to a deeper beam deposition with an inward radial displacement of ≈2 cm in the maximum of the beam emission. Orbit simulations are used to test different models for 3D

14 CFR 29.865 - External loads.

Science.gov (United States)

2010-01-01

... 200 volts per meter. (iii) Be protected against any failure that could be induced by a failure mode of... operational envelope without hazard to the rotorcraft during normal flight conditions. In addition, these...-load combinations to be used for nonhuman external cargo except for the failure of critical structural...

Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

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Amie L. Holmes

2013-11-01

Full Text Available Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration- and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D. Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent manner. Thus, chronic exposure to particulate nickel induces genotoxicity and cellular transformation in human lung epithelial cells.

Streptococcus gordonii lipoproteins induce IL-8 in human periodontal ligament cells.

Science.gov (United States)

Kim, A Reum; Ahn, Ki Bum; Kim, Hyun Young; Seo, Ho Seong; Kum, Kee-Yeon; Yun, Cheol-Heui; Han, Seung Hyun

2017-11-01

Streptococcus gordonii, a Gram-positive oral bacterium, is a life-threatening pathogen that causes infective endocarditis. It is frequently isolated from the periapical lesions of patients with apical periodontitis and has thus been implicated in inflammatory responses. However, little is known about the virulence factors of S. gordonii responsible for the induction of inflammatory responses in the periapical areas. Here, we investigated the role of S. gordonii cell wall-associated virulence factors on interleukin (IL)-8 induction in human periodontal ligament (PDL) cells using ethanol-inactivated wild-type S. gordonii, a lipoteichoic acid (LTA)-deficient mutant (ΔltaS), and a lipoprotein-deficient mutant (Δlgt). Wild-type S. gordonii induced IL-8 expression at both the protein and mRNA levels in human PDL cells in a dose- and time-dependent manner. A transient transfection and reporter gene assay demonstrated that wild-type S. gordonii activated Toll-like receptor 2 (TLR2). Additionally, IL-8 production induced by wild-type S. gordonii was substantially inhibited by anti-TLR2-neutralizing antibodies. Both wild-type S. gordonii and the ΔltaS mutant induced IL-8 production; however, this response was not observed when cells were stimulated with the Δlgt mutant. Interestingly, lipoproteins purified from S. gordonii induced IL-8 production, whereas purified LTA did not. In addition, purified lipoproteins stimulated TLR2 more potently than LTA. Furthermore, S. gordonii-induced IL-8 expression was specifically inhibited by blocking p38 kinase, while lipoprotein-induced IL-8 expression was inhibited by blocking p38 kinase, ERK, or JNK. Of particular note, exogenous addition of purified S. gordonii lipoproteins enhanced Δlgt-induced IL-8 production in human PDL cells to an extent similar to that induced by the wild-type strain. Collectively, these results suggest that lipoproteins are an important component of S. gordonii for the induction of IL-8 production in human

Pathway of deoxynivalenol-induced apoptosis in human colon carcinoma cells

International Nuclear Information System (INIS)

Bensassi, Fatma; El Golli-Bennour, Emna; Abid-Essefi, Salwa; Bouaziz, Chayma; Hajlaoui, Mohamed Rabeh; Bacha, Hassen

2009-01-01

The mycotoxin, deoxynivalenol (DON), is generally detected in cereal grains and grain-based food products worldwide. Therefore, DON has numerous toxicological effects on animals and humans. The present investigation was conducted to determine the molecular aspects of DON toxicity on human colon carcinoma cells (HT 29). To this aim, we have monitored the effects of DON on (i) cell viability, (ii) Heat shock protein expressions as a parameter of protective and adaptive response, (iii) oxidative damage and (iv) cell death signalling pathway. Our results clearly showed that DON treatment inhibits cell proliferation, did not induce Hsp 70 protein expression and reactive oxygen species generation. We have also demonstrated that this toxin induced a DNA fragmentation followed by p53 and caspase-3 activations. Finally, our findings suggested that oxidative damage is not the major contributor to DON toxicity. This mycotoxin induces direct DNA lesions and could be considered by this fact as a genotoxic agent inducing cell death via an apoptotic process.

Regional programme on quality control of radioimmunoassay: Development of human resources and external quality assessments

International Nuclear Information System (INIS)

Quiroga, S.; Torres, M.; Mendizabal, A.F.; Farinati, Z.; Galanternik, A.

1986-01-01

Since 1978 the authors have been concerned with helping to standardize radioimmunoassay (RIA) methodology in Argentina and other Latin American countries by: (1) developing human resources through courses on quality control of RIA and training of fellows, and (2) developing four external quality assessment (EQA) schemes to evaluate the performance of laboratories in determining several analytes by RIA. The number of collaborating laboratories increased between the first and fourth schemes. The average analytical performance achieved by the participants in each scheme was estimated by the average between-laboratory variation. Thyroxine, cortisol and tri-iodothyronine were measured the most accurately. Different problems were evident in the RIAs of thyrotrophin, luteinizing hormone, follicle stimulating hormone, prolactin, testosterone, progesterone, cortisol, immunoglobulin E and human growth hormone. RIA of oestradiol showed the worst accuracy. Analysis of the results showed an increasing interest in RIA quality control as it was found to improve the reliability of RIA. (author)

Development and Commissioning of an External Beam Facility in the Union College Ion Beam Analysis Laboratory

Science.gov (United States)

Yoskowitz, Joshua; Clark, Morgan; Labrake, Scott; Vineyard, Michael

2015-10-01

We have developed an external beam facility for the 1.1-MV tandem Pelletron accelerator in the Union College Ion Beam Analysis Laboratory. The beam is extracted from an aluminum pipe through a 1 / 4 ' ' diameter window with a 7.5- μm thick Kapton foil. This external beam facility allows us to perform ion beam analysis on samples that cannot be put under vacuum, including wet samples and samples too large to fit into the scattering chamber. We have commissioned the new facility by performing proton induced X-ray emission (PIXE) analysis of several samples of environmental interest. These include samples of artificial turf, running tracks, and a human tooth with an amalgam filling. A 1.7-MeV external proton beam was incident on the samples positioned 2 cm from the window. The resulting X-rays were measured using a silicon drift detector and were analyzed using GUPIX software to determine the concentrations of elements in the samples. The results on the human tooth indicate that while significant concentrations of Hg, Ag, and Sn are present in the amalgam filling, only trace amounts of Hg appear to have leached into the tooth. The artificial turf and running tracks show rather large concentrations of a broad range of elements and trace amounts of Pb in the turf infill.

Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

Directory of Open Access Journals (Sweden)

Leonardo D'Aiuto

Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

Evaluation of human-induced vibration of continuous footbridges

OpenAIRE

El-Robaa Ahmed; Gaawan Sameh; Malek Charles

2015-01-01

With the development of construction materials and the introduction of high strength steel and concrete, the human-induced vibration became a dominant criterion for the design of pedestrian bridges. Currently, longer spans and lightweight bridges have been comprised in most of design trends. This leads to lower the natural frequencies of the system which have a great effect on the dynamic performance of bridges subjected to human activities. Although the design of steel footbridges could reac...

Induction of Skin-Derived Precursor Cells from Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Sugiyama-Nakagiri, Yoriko; Fujimura, Tsutomu; Moriwaki, Shigeru

2016-01-01

The generation of full thickness human skin from dissociated cells is an attractive approach not only for treating skin diseases, but also for treating many systemic disorders. However, it is currently not possible to obtain an unlimited number of skin dermal cells. The goal of this study was to develop a procedure to produce skin dermal stem cells from induced pluripotent stem cells (iPSCs). Skin-derived precursor cells (SKPs) were isolated as adult dermal precursors that could differentiate into both neural and mesodermal progenies and could reconstitute the dermis. Thus, we attempted to generate SKPs from iPSCs that could reconstitute the skin dermis. Human iPSCs were initially cultured with recombinant noggin and SB431542, an inhibitor of activin/nodal and TGFβ signaling, to induce neural crest progenitor cells. Those cells were then treated with SKP medium that included CHIR99021, a WNT signal activator. The induction efficacy from neural crest progenitor cells to SKPs was more than 97%. No other modifiers tested were able to induce those cells. Those human iPSC-derived SKPs (hiPSC-SKPs) showed a similar gene expression signature to SKPs isolated from human skin dermis. Human iPSC-SKPs differentiated into neural and mesodermal progenies, including adipocytes, skeletogenic cell types and Schwann cells. Moreover, they could be induced to follicular type keratinization when co-cultured with human epidermal keratinocytes. We here provide a new efficient protocol to create human skin dermal stem cells from hiPSCs that could contribute to the treatment of various skin disorders.

ETHICS IN HEALTH CARE: INDUCEMENT AND HUMAN SUBJECTS

Directory of Open Access Journals (Sweden)

MUNIR HOSSAIN TALUKDER

2011-05-01

Full Text Available Currently, most health researchers or donor organizations considerinducement as a vital part in promoting research. They propose benefits, such as post research free medical treatment, food, insurance facilities, or even cash, in order to meet sufficient number of subjects. So, inducement may influence one to participate in a research. Is it ethical to offer inducement to human subjects? What are the risks in such practice? What will happen if the donor agencies use subjects by hiding possible risks from them? When an inducement can satisfy ethical criteria? The CIOMS, FDA, and other ethical guidelines hold that inducement is unethical because it involves enough risk for voluntary informed consent. Supporting this position, a group of ethicists has argued that inducement undermines voluntariness especially when subjects are poor and vulnerable, and thus, unethical. In contrast to them, others argue that inducement contributes to discover new knowledge which can improve miserable condition of the poor. In their view, an inducement maintains all ethical criteria including subject’s autonomy, and therefore, morally permissible. The paper focuses this debate and analyzes both types ofargument. It examines whether inducement invalidate informed consent.Even if inducement may not violate the basic components of informedconsent, the paper concludes, subjects may claim a prima facie right to enjoy research outcomes.

Human-Induced Effects on RSS Ranging Measurements for Cooperative Positioning

DEFF Research Database (Denmark)

Della Rosa, Francescantonio; Pelosi, Mauro; Nurmi, Jari

2012-01-01

of human-induced perturbations for enhancing the final positioning accuracy through cooperative schemes has been assessed. It has been proved that the effect of cooperation is very limited if human factors are not taken into account when performing experimental activities.......We present experimental evaluations of human-induced perturbations on received-signal-strength-(RSS-) based ranging measurements for cooperative mobile positioning. To the best of our knowledge, this work is the first attempt to gain insight and understand the impact of both body loss and hand grip...... on the RSS for enhancing proximity measurements among neighbouring devices in cooperative scenarios. Our main contribution is represented by experimental investigations. Analysis of the errors introduced in the distance estimation using path-loss-based methods has been carried out. Moreover, the exploitation...

Gallic Acid Induces Apoptosis in Human Gastric Adenocarcinoma Cells.

Science.gov (United States)

Tsai, Chung-Lin; Chiu, Ying-Ming; Ho, Tin-Yun; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Wu, Yi-Ying

2018-04-01

Gastric cancer is one of the most common malignant cancers with a poor prognosis and high mortality rate worldwide. Current treatment of gastric cancer includes surgery and chemotherapy as the main modalities, but the potentially severe side-effects of chemotherapy present a considerable challenge. Gallic acid is a trihydroxybenzoic acid found to exert an anticancer effect against a variety of cancer cells. The purpose of this study was to determine the anti-cancer activity of Galla chinensis and its main component gallic acid on human gastric adenocarcinoma cells. MTT assay and cell death ELISA were used to determine the apoptotic effect of Gallic Chinensis and gallic acid on human gastric adenocarcinoma cells. To determine the pathway and relevant components by which gallic acid-induced apoptosis is mediated through, cells were transfected with siRNA (Fas, FasL, DR5, p53) using Lipofectamine 2000. Reults: Gallic Chinensis and gallic acid induced apoptosis of human gastric adenocarcinoma cells. Gallic acid induced up-regulation of Fas, FasL, and DR5 expression in AGS cells. Transfection of cells with Fas, FasL, or DR5 siRNA reduced gallic acid-induced cell death. In addition, p53 was shown to be involved in gallic acid-mediated Fas, FasL, and DR5 expression as well as cell apoptosis in AGS cells. These results suggest that gallic acid has a potential role in the treatment of gastric cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Externalities of energy. Swedish implementation of the ExternE methodology

International Nuclear Information System (INIS)

Nilsson, Maans; Gullberg, M.

1998-01-01

The growing interest for developing economic instruments for efficient environmental policies has opened up a large area of multi-disciplinary research. ExternE is an example of this research, combining disciplines such as engineering, ecology, immunology and economics expertise to create new knowledge about how environmental pressures from energy production affect our nature and society. The ExternE Project aims to identify and, as far as possible quantify the externalities of energy production in Europe. The Stockholm Environment Institute has carried out a preliminary aggregation: -Coal Fuel Cycle: centred around Vaesteraas Kraftvaermeverk, Vaesteraas. This is the largest co-generation plant in Sweden, with four blocks and a maximum co-generation output of 520 MW electricity and 950 MW heat. The analysis is carried out on boiler B4. -Biomass Fuel Cycle: centred around Haendeloeverket, Norrkoeping. This plant predominately burns forestry residues, but a variety of fuels are combusted. Haendeloeverket has an installed capacity of 100 MW electricity and 375 MW heat, in a total of three boilers and two back-pressure turbines. The analysis is carried out on boiler P13. -Hydro Fuel Cycle: Klippens Kraftstation, Storuman. Built in 1990-1994, it is the youngest hydro power station in Sweden. It has been designed and built with significant efforts to account for and protect environmental values. Installed capacity is 28 MW. The environmental impact assessment from the construction of this plant is carried out, but the evaluation is still not finalized. The preliminary aggregation aimed to test whether ExternE results could be used to make estimates for the entire Swedish electricity production system. Hence, national results as well as results from other partner countries in ExternE has been applied

Human induced pluripotent stem cells on autologous feeders.

Directory of Open Access Journals (Sweden)

Kazutoshi Takahashi

Full Text Available BACKGROUND: For therapeutic usage of induced Pluripotent Stem (iPS cells, to accomplish xeno-free culture is critical. Previous reports have shown that human embryonic stem (ES cells can be maintained in feeder-free condition. However, absence of feeder cells can be a hostile environment for pluripotent cells and often results in karyotype abnormalities. Instead of animal feeders, human fibroblasts can be used as feeder cells of human ES cells. However, one still has to be concerned about the existence of unidentified pathogens, such as viruses and prions in these non-autologous feeders. METHODOLOGY/PRINCIPAL FINDINGS: This report demonstrates that human induced Pluripotent Stem (iPS cells can be established and maintained on isogenic parental feeder cells. We tested four independent human skin fibroblasts for the potential to maintain self-renewal of iPS cells. All the fibroblasts tested, as well as their conditioned medium, were capable of maintaining the undifferentiated state and normal karyotypes of iPS cells. Furthermore, human iPS cells can be generated on isogenic parental fibroblasts as feeders. These iPS cells carried on proliferation over 19 passages with undifferentiated morphologies. They expressed undifferentiated pluripotent cell markers, and could differentiate into all three germ layers via embryoid body and teratoma formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that autologous fibroblasts can be not only a source for iPS cells but also be feeder layers. Our results provide a possibility to solve the dilemma by using isogenic fibroblasts as feeder layers of iPS cells. This is an important step toward the establishment of clinical grade iPS cells.

Helium induces preconditioning in human endothelium in vivo

NARCIS (Netherlands)

Smit, Kirsten F.; Oei, Gezina T. M. L.; Brevoord, Daniel; Stroes, Erik S.; Nieuwland, Rienk; Schlack, Wolfgang S.; Hollmann, Markus W.; Weber, Nina C.; Preckel, Benedikt

2013-01-01

Helium protects myocardium by inducing preconditioning in animals. We investigated whether human endothelium is preconditioned by helium inhalation in vivo. Forearm ischemia-reperfusion (I/R) in healthy volunteers (each group n = 10) was performed by inflating a blood pressure cuff for 20 min.

Probabilistic analysis of external events with focus on the Fukushima event

International Nuclear Information System (INIS)

Kollasko, Heiko; Jockenhoevel-Barttfeld, Mariana; Klapp, Ulrich

2014-01-01

External hazards are those natural or man-made hazards to a site and facilities that are originated externally to both the site and its processes, i.e. the duty holder may have very little or no control over the hazard. External hazards can have the potential of causing initiating events at the plant, typically transients like e.g., loss of offsite power. Simultaneously, external events may affect safety systems required to control the initiating event and, where applicable, also back-up systems implemented for risk-reduction. The plant safety may especially be threatened when loads from external hazards exceed the load assumptions considered in the design of safety-related systems, structures and components. Another potential threat is given by hazards inducing initiating events not considered in the safety demonstration otherwise. An example is loss of offsite power combined with prolonged plant isolation. Offsite support, e.g., delivery of diesel fuel oil, usually credited in the deterministic safety analysis may not be possible in this case. As the Fukushima events have shown, the biggest threat is likely given by hazards inducing both effects. Such hazards may well be dominant risk contributors even if their return period is very high. In order to identify relevant external hazards for a certain Nuclear Power Plant (NPP) location, a site specific screening analysis is performed, both for single events and for combinations of external events. As a result of the screening analysis, risk significant and therefore relevant (screened-in) single external events and combinations of them are identified for a site. The screened-in events are further considered in a detailed event tree analysis in the frame of the Probabilistic Safety Analysis (PSA) to calculate the core damage/large release frequency resulting from each relevant external event or from each relevant combination. Screening analyses of external events performed at AREVA are based on the approach provided

Training-induced changes in membrane transport proteins of human skeletal muscle

DEFF Research Database (Denmark)

Juel, C.

2006-01-01

Training improves human physical performance by inducing structural and cardiovascular changes, metabolic changes, and changes in the density of membrane transport proteins. This review focuses on the training-induced changes in proteins involved in sarcolemmal membrane transport. It is concluded...

Characterization of human septic sera induced gene expression modulation in human myocytes

Science.gov (United States)

Hussein, Shaimaa; Michael, Paul; Brabant, Danielle; Omri, Abdelwahab; Narain, Ravin; Passi, Kalpdrum; Ramana, Chilakamarti V.; Parrillo, Joseph E.; Kumar, Anand; Parissenti, Amadeo; Kumar, Aseem

2009-01-01

To gain a better understanding of the gene expression changes that occurs during sepsis, we have performed a cDNA microarray study utilizing a tissue culture model that mimics human sepsis. This study utilized an in vitro model of cultured human fetal cardiac myocytes treated with 10% sera from septic patients or 10% sera from healthy volunteers. A 1700 cDNA expression microarray was used to compare the transcription profile from human cardiac myocytes treated with septic sera vs normal sera. Septic sera treatment of myocytes resulted in the down-regulation of 178 genes and the up-regulation of 4 genes. Our data indicate that septic sera induced cell cycle, metabolic, transcription factor and apoptotic gene expression changes in human myocytes. Identification and characterization of gene expression changes that occur during sepsis may lead to the development of novel therapeutics and diagnostics. PMID:19684886

Global Assessment of Human-induced Soil Degradation (GLASOD)

NARCIS (Netherlands)

Oldeman, L.R.; Hakkeling, R.T.A.; Sombroek, W.G.; Batjes, N.H.

2014-01-01

The GLASOD project (1987-1990) has produced a world map of human-induced soil degradation. Data were complied in cooperation with a large number of soil scientists throughout the world, using uniform Guidelines and international correlation. The status of soil degradation was mapped within loosely

Environmental external effects from wind power based on the EU ExternE methodology

DEFF Research Database (Denmark)

Ibsen, Liselotte Schleisner; Nielsen, Per Sieverts

1998-01-01

of the Danish part of the project is to implement the framework for externality evaluation, for three different power plants located in Denmark. The paper will focus on the assessment of the impacts of the whole fuel cycles for wind, natural gas and biogas. Priority areas for environmental impact assessment......The European Commission has launched a major study project, ExternE, to develop a methodology to quantify externalities. A “National Implementation Phase”, was started under the Joule II programme with the purpose of implementing the ExternE methodology in all member states. The main objective...

Epstein–Barr Virus-Induced Metabolic Rearrangements in Human B-Cell Lymphomas

Directory of Open Access Journals (Sweden)

Pier P. Piccaluga

2018-06-01

Full Text Available Tumor metabolism has been the object of several studies in the past, leading to the pivotal observation of a consistent shift toward aerobic glycolysis (so-called Warburg effect. More recently, several additional investigations proved that tumor metabolism is profoundly affected during tumorigenesis, including glucose, lipid and amino-acid metabolism. It is noticeable that metabolic reprogramming can represent a suitable therapeutic target in many cancer types. Epstein–Barr virus (EBV was the first virus linked with cancer in humans when Burkitt lymphoma (BL was described. Besides other well-known effects, it was recently demonstrated that EBV can induce significant modification in cell metabolism, which may lead or contribute to neoplastic transformation of human cells. Similarly, virus-induced tumorigenesis is characterized by relevant metabolic abnormalities directly induced by the oncoviruses. In this article, the authors critically review the most recent literature concerning EBV-induced metabolism alterations in lymphomas.

Nonlinear dynamics of mushy layers induced by external stochastic fluctuations.

Science.gov (United States)

Alexandrov, Dmitri V; Bashkirtseva, Irina A; Ryashko, Lev B

2018-02-28

The time-dependent process of directional crystallization in the presence of a mushy layer is considered with allowance for arbitrary fluctuations in the atmospheric temperature and friction velocity. A nonlinear set of mushy layer equations and boundary conditions is solved analytically when the heat and mass fluxes at the boundary between the mushy layer and liquid phase are induced by turbulent motion in the liquid and, as a result, have the corresponding convective form. Namely, the 'solid phase-mushy layer' and 'mushy layer-liquid phase' phase transition boundaries as well as the solid fraction, temperature and concentration (salinity) distributions are found. If the atmospheric temperature and friction velocity are constant, the analytical solution takes a parametric form. In the more common case when they represent arbitrary functions of time, the analytical solution is given by means of the standard Cauchy problem. The deterministic and stochastic behaviour of the phase transition process is analysed on the basis of the obtained analytical solutions. In the case of stochastic fluctuations in the atmospheric temperature and friction velocity, the phase transition interfaces (mushy layer boundaries) move faster than in the deterministic case. A cumulative effect of these noise contributions is revealed as well. In other words, when the atmospheric temperature and friction velocity fluctuate simultaneously due to the influence of different external processes and phenomena, the phase transition boundaries move even faster. This article is part of the theme issue 'From atomistic interfaces to dendritic patterns'.This article is part of the theme issue 'From atomistic interfaces to dendritic patterns'. © 2018 The Author(s).

Electronic properties of phosphorene/graphene heterostructures: Effect of external electric field

Energy Technology Data Exchange (ETDEWEB)

Kaur, Sumandeep; Srivastava, Sunita; Tankeshwar, K. [Department of Physics, Panjab University, Chandigarh-160014 (India); Kumar, Ashok [Centre for Physical Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, India 151001 (India)

2016-05-23

We report the electronic properties of electrically gated heterostructures of black and blue phosphorene with graphene. The heterostructure of blue phosphorene with graphene is energetically more favorable than black phospherene/graphene. However, both are bonded by weak interlayer interactions. Graphene induces the Dirac cone character in both heterostructure which shows tunabilities with external electric field. It is found that Dirac cone get shifted depending on the polarity of external electric field that results into the so called self induced p-type or n-type doping effect. These features have importance in the fabrication of nano-electronic devices based on the phosphorene/graphene heterostructures.

Regional Externalities

NARCIS (Netherlands)

Heijman, W.J.M.

2007-01-01

The book offers practical and theoretical insights in regional externalities. Regional externalities are a specific subset of externalities that can be defined as externalities where space plays a dominant role. This class of externalities can be divided into three categories: (1) externalities

Microtubule Abnormalities Underlying Gulf War Illness in Neurons from Human-Induced Pluripotent Cells

Science.gov (United States)

2016-09-01

cells derived from human induced pluripotent stem cells (hiPSCs), originating from GW...AWARD NUMBER: W81XWH-15-1-0433 TITLE: Microtubule Abnormalities Underlying Gulf War Illness in Neurons from Human- Induced Pluripotent Cells ...A simple blood sample is taken from the soldier, and then transduced, using reliable established methods , to make the cells pluripotent .

Evaluation of nefazodone-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes

Energy Technology Data Exchange (ETDEWEB)

Lee, Sujeong, E-mail: crystalee@gmail.com [Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-343 (Korea, Republic of); Lee, Hyang-Ae, E-mail: hyangaelee@gmail.com [Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-343 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 110-799 (Korea, Republic of); Human and Environmental Toxicology Program, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-350 (Korea, Republic of); Choi, Sung Woo, E-mail: djmaya@snu.ac.kr [Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 110-799 (Korea, Republic of); Kim, Sung Joon, E-mail: sjoonkim@snu.ac.kr [Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 110-799 (Korea, Republic of); Kim, Ki-Suk, E-mail: idkks00@gmail.com [Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-343 (Korea, Republic of); Human and Environmental Toxicology Program, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-350 (Korea, Republic of)

2016-04-01

The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), which express the major cardiac ion channels and recapitulate spontaneous mechanical and electrical activities, may provide a possible solution for the lack of in vitro human-based cardiotoxicity testing models. Cardiotoxicity induced by the antidepressant nefazodone was previously revealed to cause an acquired QT prolongation by hERG channel blockade. To elucidate the cellular mechanisms underlying the cardiotoxicity of nefazodone beyond hERG, its effects on cardiac action potentials (APs) and ion channels were investigated using hiPSC-CMs with whole-cell patch clamp techniques. In a proof of principle study, we examined the effects of cardioactive channel blockers on the electrophysiological profile of hiPSC-CMs in advance of the evaluation of nefazodone. Nefazodone dose-dependently prolonged the AP duration at 90% (APD{sub 90}) and 50% (APD{sub 50}) repolarization, reduced the maximum upstroke velocity (dV/dt{sub max}) and induced early after depolarizations. Voltage-clamp studies of hiPSC-CMs revealed that nefazodone inhibited various voltage-gated ion channel currents including I{sub Kr}, I{sub Ks}, I{sub Na}, and I{sub Ca}. Among them, I{sub Kr} and I{sub Na} showed relatively higher sensitivity to nefazodone, consistent with the changes in the AP parameters. In summary, hiPSC-CMs enabled an integrated approach to evaluate the complex interactions of nefazodone with cardiac ion channels. These results suggest that hiPSC-CMs can be an effective model for detecting drug-induced arrhythmogenicity beyond the current standard assay of heterologously expressed hERG K{sup +} channels. - Highlights: • Nefazodone prolonged APD and decreased upstroke velocity of APs in hiPSC-CMs. • Nefazodone inhibited cardiac ion channels, especially I{sub Kr} and I{sub Na}, in hiPSC-CMs. • Nefazodone-induced AP changes are mainly the result of I{sub Kr} and I{sub Na} inhibition

l-Serine Enhances Light-Induced Circadian Phase Resetting in Mice and Humans.

Science.gov (United States)

Yasuo, Shinobu; Iwamoto, Ayaka; Lee, Sang-Il; Ochiai, Shotaro; Hitachi, Rina; Shibata, Satomi; Uotsu, Nobuo; Tarumizu, Chie; Matsuoka, Sayuri; Furuse, Mitsuhiro; Higuchi, Shigekazu

2017-12-01

Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 l-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before l-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of l-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: l-Serine administration enhanced light-induced phase shifts in mice (1.86-fold; P light-dark cycle by 6 h, l-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, l-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-l-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances. © 2017 American Society for Nutrition.

Cytogenetic and molecular characterization of human radio-induced tumours

International Nuclear Information System (INIS)

Lefevre, S.

2002-09-01

After a brief recall of some fundamentals regarding radiobiology, this research thesis discusses some epidemiological aspects of radio carcinogenesis, based on epidemiological studies performed on people having survived to Hiroshima, Nagasaki and Chernobyl, but also performed on people submitted to domestic or professional exposures to radon, or to medicine-related exposures. The author highlights some predispositions to radio-induced cancers. Then, she discusses the genetic mechanisms of radio-induced carcinogenesis and the genetic alterations observed in human radio-induced tumours. She discusses and comments the genomic instability, its mechanisms and some models observed on mice, and describes the various forms of radio-induced genomic instability. After a discussion of all these aspects, the author draws some perspectives for future research works

Externalities - an analysis using the EU ExternE-results

International Nuclear Information System (INIS)

2003-10-01

The EU project ExternE quantified the externalities for the different energy technologies. In this work, the ExternE results are used in a MARKAL-analysis for the Nordic countries. The analysis does not go into detail, but gives some interesting indications: The external costs are not fully covered in the Nordic energy systems, the present taxes and charges are not high enough. The emissions from the energy systems would be strongly reduced, if taxes/environmental charges were set at the level ExternE calculate. The emissions from power production would be reduced most. Renewable energy sources and natural gas dominate the energy systems in the ExternE case

ExternE: Externalities of energy Vol. 1. Summary

International Nuclear Information System (INIS)

Holland, M.; Berry, J.

1995-01-01

There is a growing requirement for policy analysts to take account of the environment in their decision making and to undertake the specified cost-benefit analysis. Within the European Union this is reflected in the 5th Environmental Action Programme, and the Commission's White Paper entitled 'Growth, competitiveness, employment and the ways forward to the 21st century'. This has led to a need for evaluation of environmental externalities. The ExternE Project commenced in 1991 as the European part of a collaborative study between the European Commission and the US Department of Energy. It aims to be the first systematic approach to the evaluation of external costs of a wide range of different fuel cycles. The project will result in an operational accounting framework for the quantification and monetarisation of priority environmental and other externalities. This framework will allow the calculation of the marginal external costs and benefits for specific power plants, at specific sites using specified technologies. There are three major phases in the project. Phase 1 was undertaken in collaboration with the US Department of Energy. In this phase the teams jointly developed the conceptual approach and methodology and shared scientific information for application to a number of fuel cycles. On the European side work concentrated on the nuclear and coal fuel cycles which together were expected to raise many of the fundamental issues in fuel cycle analysis. The project is currently nearing completion of Phase 2. During this phase the methodology has been applied to a wide range of different fossil, nuclear and renewable fuel cycles for power generation and energy conservation options. Also a series of National Implementation Programmes is underway in which the methodology and accounting framework are being applied to reference sites throughout Europe. In addition the general methodology is being extended to address the evaluation of externalities associated with

Mechanisms of acetaminophen-induced cell death in primary human hepatocytes

Energy Technology Data Exchange (ETDEWEB)

Xie, Yuchao; McGill, Mitchell R.; Dorko, Kenneth [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

2014-09-15

Acetaminophen (APAP) overdose is the most prevalent cause of drug-induced liver injury in western countries. Numerous studies have been conducted to investigate the mechanisms of injury after APAP overdose in various animal models; however, the importance of these mechanisms for humans remains unclear. Here we investigated APAP hepatotoxicity using freshly isolated primary human hepatocytes (PHH) from either donor livers or liver resections. PHH were exposed to 5 mM, 10 mM or 20 mM APAP over a period of 48 h and multiple parameters were assessed. APAP dose-dependently induced significant hepatocyte necrosis starting from 24 h, which correlated with the clinical onset of human liver injury after APAP overdose. Interestingly, cellular glutathione was depleted rapidly during the first 3 h. APAP also resulted in early formation of APAP-protein adducts (measured in whole cell lysate and in mitochondria) and mitochondrial dysfunction, indicated by the loss of mitochondrial membrane potential after 12 h. Furthermore, APAP time-dependently triggered c-Jun N-terminal kinase (JNK) activation in the cytosol and translocation of phospho-JNK to the mitochondria. Both co-treatment and post-treatment (3 h) with the JNK inhibitor SP600125 reduced JNK activation and significantly attenuated cell death at 24 h and 48 h after APAP. The clinical antidote N-acetylcysteine offered almost complete protection even if administered 6 h after APAP and a partial protection when given at 15 h. Conclusion: These data highlight important mechanistic events in APAP toxicity in PHH and indicate a critical role of JNK in the progression of injury after APAP in humans. The JNK pathway may represent a therapeutic target in the clinic. - Highlights: • APAP reproducibly causes cell death in freshly isolated primary human hepatocytes. • APAP induces adduct formation, JNK activation and mitochondrial dysfunction in PHH. • Mitochondrial adducts and JNK translocation are delayed in PHH compared to

Trigeminal induced arousals during human sleep.

Science.gov (United States)

Heiser, Clemens; Baja, Jan; Lenz, Franziska; Sommer, J Ulrich; Hörmann, Karl; Herr, Raphael M; Stuck, Boris A

2015-05-01

Arousals caused by external stimuli during human sleep have been studied for most of the sensorial systems. It could be shown that a pure nasal trigeminal stimulus leads to arousals during sleep. The frequency of arousals increases dependent on the stimulus concentration. The aim of the study was to evaluate the influence of different stimulus durations on arousal frequency during different sleep stages. Ten young healthy volunteers with 20 nights of polysomnography were included in the study. Pure trigeminal stimulation with both different concentrations of CO2 (0, 10, 20, 40% v/v) and different stimulus durations (1, 3, 5, and 10 s) were applied during different sleep stages to the volunteers using an olfactometer. The application was performed during different sleep stages (light sleep, deep sleep, REM sleep). The number of arousals increased with rising stimulus duration and stimulus concentration during each sleep stage. Trigeminal stimuli during sleep led to arousals in dose- and time-dependent manner.

Dissection of pathways leading to antigen receptor-induced and Fas/CD95-induced apoptosis in human B cells

NARCIS (Netherlands)

Lens, S. M.; den Drijver, B. F.; Pötgens, A. J.; Tesselaar, K.; van Oers, M. H.; van Lier, R. A.

1998-01-01

To dissect intracellular pathways involved in B cell Ag receptor (BCR)-mediated and Fas-induced human B cell death, we isolated clones of the Burkitt lymphoma cell line Ramos with different apoptosis sensitivities. Selection for sensitivity to Fas-induced apoptosis also selected for clones with

External cervical resorption: diagnostic and treatment tips

Directory of Open Access Journals (Sweden)

Alberto Consolaro

Full Text Available ABSTRACT External cervical resorption is caused, almost exclusively, by dental trauma - especially those characterized by concussion - and is a dental disease to be diagnosed and treated accurately by endodontists. However, the vast majority of the cases is initially diagnosed by an orthodontist, due to the imaging possibilities in standardized documentations. Among the causes of external cervical resorption, it is common to mistakenly attribute it to orthodontic treatment, traumatic occlusion or even to chronic inflammatory periodontal disease. External cervical resorption is associated to dental trauma in several situations mentioned in this paper. In old cases, and eventually still nowadays, it may have been induced by internal tooth bleaching, which is increasingly less frequent in endodontically treated teeth. There are some tips to be followed and some care that must be taken during the diagnosis and treatment of external cervical resorption clinical cases. The present study lists foundations that will allow the professional to perform safely and accurately in each specific case. Some of these tips and care measures are of orthodontic nature.

Human Immunodeficiency virus and invasive external otitis- A case ...

African Journals Online (AJOL)

Acute invasive external otitis is an uncommon life-threatening infection of the exteernal auditory canal (EAC), most often affecting the elderly diabetic patients. Although few reports have been made in HIV-positive/Aids patients among the caucasians. We present here a 25 year old nursing mother with a month history of ...

French regulations for countering external violent forces affecting nuclear power stations

International Nuclear Information System (INIS)

Dupraz, B.

1986-01-01

This article describes the general principles underlying nuclear safety regulations to counter external violent forces to which plants can be exposed. It then examines the statutory directives concerning external violences connected with human activities or originating from natural phenomena. 3 refs [fr

External PIXE analysis of old inks and papers

International Nuclear Information System (INIS)

Hassanzadeh, A.; Lamehi-Rachti, M.; Oliaiy, P.; Rahighi, J.; Shokouhi, F.

1999-01-01

Proton Induced X-ray Emission, PIXE is a very well established analytical method. This technique of analysis can equally be applied both in vacuum, internal PIXE, and in atmosphere, external PIXE. External PIXE has been applied to material analysis in Van de Graaff laboratory at AEOI using filters and funny filters. Advantages of using these filters have been studied when analysing ancient written documents such as envelopes, inks, and newspapers. This technique clearly demonstrated the differences between new and old inks and papers. More data is needed to show other features of this technique. (author)

Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

Energy Technology Data Exchange (ETDEWEB)

Wang, Xin; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China 201203 (China); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China 201203 (China)

2017-04-01

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD-induced

Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

International Nuclear Information System (INIS)

Wang, Xin; Xu, Mei; Frank, Jacqueline A.; Ke, Zun-ji; Luo, Jia

2017-01-01

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD-induced

External auditory exostoses in the Xuchang and Xujiayao human remains: Patterns and implications among eastern Eurasian Middle and Late Pleistocene crania.

Science.gov (United States)

Trinkaus, Erik; Wu, Xiu-Jie

2017-01-01

In the context of Middle and Late Pleistocene eastern Eurasian human crania, the external auditory exostoses (EAE) of the late archaic Xuchang 1 and 2 and the Xujiayao 15 early Late Pleistocene human temporal bones are described. Xujiayao 15 has small EAE (Grade 1), Xuchang 1 presents bilateral medium EAE (Grade 2), and Xuchang 2 exhibits bilaterally large EAE (Grade 3), especially on the right side. These cranial remains join the other eastern Eurasian later Pleistocene humans in providing frequencies of 61% (N = 18) and 58% (N = 12) respectively for archaic and early modern human samples. These values are near the upper limits of recent human frequencies, and they imply frequent aquatic exposure among these Pleistocene humans. In addition, the medial extents of the Xuchang 1 and 2 EAE would have impinged on their tympanic membranes, and the large EAE of Xuchang 2 would have resulted in cerumen impaction. Both effects would have produced conductive hearing loss, a serious impairment in a Pleistocene foraging context.

External costs related to power production technologies. ExternE national implementation for Denmark

Energy Technology Data Exchange (ETDEWEB)

Schleisner, L; Sieverts Nielsen, P [eds.

1997-12-01

The objective of the ExternE National Implementation project has been to establish a comprehensive and comparable set of data on externalities of power generation for all EU member states and Norway. The tasks include the application of the ExternE methodology to the most important fuel cycles for each country as well as to update the already existing results, to aggregate these site- and technology-specific results to more general figures. The current report covers the detailed information concerning the ExternE methodology. Importance is attached to the computer system used in the project and the assessment of air pollution effects on health, materials and ecological effects. Also the assessment of global warming damages are described. Finally the report covers the detailed information concerning the national implementation for Denmark for an offshore wind farm and a wind farm on land, a decentralised CHP plant based on natural gas and a decentralised CHP plant base on biogas. (au) EU-JOULE 3. 79 tabs., 11 ills., 201 refs.

External costs related to power production technologies. ExternE national implementation for Denmark

International Nuclear Information System (INIS)

Schleisner, L.; Sieverts Nielsen, P.

1997-12-01

The objective of the ExternE National Implementation project has been to establish a comprehensive and comparable set of data on externalities of power generation for all EU member states and Norway. The tasks include the application of the ExternE methodology to the most important fuel cycles for each country as well as to update the already existing results, to aggregate these site- and technology-specific results to more general figures. The current report covers the detailed information concerning the ExternE methodology. Importance is attached to the computer system used in the project and the assessment of air pollution effects on health, materials and ecological effects. Also the assessment of global warming damages are described. Finally the report covers the detailed information concerning the national implementation for Denmark for an offshore wind farm and a wind farm on land, a decentralised CHP plant based on natural gas and a decentralised CHP plant base on biogas. (au) EU-JOULE 3. 79 tabs., 11 ills., 201 refs

Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

OpenAIRE

Hayato Fukusumi; Tomoko Shofuda; Yohei Bamba; Atsuyo Yamamoto; Daisuke Kanematsu; Yukako Handa; Keisuke Okita; Masaya Nakamura; Shinya Yamanaka; Hideyuki Okano; Yonehiro Kanemura

2016-01-01

Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPS...

Attributable Human-Induced Changes in the Likelihood and Magnitude of the Observed Extreme Precipitation during Hurricane Harvey

Science.gov (United States)

Risser, Mark D.; Wehner, Michael F.

2017-12-01

Record rainfall amounts were recorded during Hurricane Harvey in the Houston, Texas, area, leading to widespread flooding. We analyze observed precipitation from the Global Historical Climatology Network with a covariate-based extreme value statistical analysis, accounting for both the external influence of global warming and the internal influence of El Niño-Southern Oscillation. We find that human-induced climate change likely increased the chances of the observed precipitation accumulations during Hurricane Harvey in the most affected areas of Houston by a factor of at least 3.5. Further, precipitation accumulations in these areas were likely increased by at least 18.8% (best estimate of 37.7%), which is larger than the 6-7% associated with an attributable warming of 1°C in the Gulf of Mexico and Clausius-Clapeyron scaling. In a Granger causality sense, these statements provide lower bounds on the impact of climate change and motivate further attribution studies using dynamical climate models.

FOXL2-induced follistatin attenuates activin A-stimulated cell proliferation in human granulosa cell tumors

Energy Technology Data Exchange (ETDEWEB)

Cheng, Jung-Chien; Chang, Hsun-Ming; Qiu, Xin; Fang, Lanlan; Leung, Peter C.K., E-mail: peter.leung@ubc.ca

2014-01-10

Highlights: •Activin A stimulates cell proliferation in KGN human granulosa cell tumor-derived cell line. •Cyclin D2 mediates activin A-induced KGN cell proliferation. •FOXL2 induces follistatin expression in KGN cells. •FOXL2-induced follistatin attenuates activin A-stimulated KGN cell proliferation. -- Abstract: Human granulosa cell tumors (GCTs) are rare, and their etiology remains largely unknown. Recently, the FOXL2 402C > G (C134W) mutation was found to be specifically expressed in human adult-type GCTs; however, its function in the development of human GCTs is not fully understood. Activins are members of the transforming growth factor-beta superfamily, which has been shown to stimulate normal granulosa cell proliferation; however, little is known regarding the function of activins in human GCTs. In this study, we examined the effect of activin A on cell proliferation in the human GCT-derived cell line KGN. We show that activin A treatment stimulates KGN cell proliferation. Treatment with the activin type I receptor inhibitor SB431542 blocks activin A-stimulated cell proliferation. In addition, our results show that cyclin D2 is induced by treatment with activin A and is involved in activin A-stimulated cell proliferation. Moreover, the activation of Smad signaling is required for activin A-induced cyclin D2 expression. Finally, we show that the overexpression of the wild-type FOXL2 but not the C134W mutant FOXL2 induced follistatin production. Treatment with exogenous follistatin blocks activin A-stimulated cell proliferation, and the overexpression of wild-type FOXL2 attenuates activin A-stimulated cell proliferation. These results suggest that FOXL2 may act as a tumor suppressor in human adult-type GCTs by inducing follistatin expression, which subsequently inhibits activin-stimulated cell proliferation.

Stability properties of a toroidal z-pinch in an external magnetic multipole field

International Nuclear Information System (INIS)

Eriksson, H.G.

1987-01-01

MHD stability of m=1, axisymmetric, external modes of a toroidal z-pinch immersed in an external multipole field (Extrap configuration) is studied. The description includes the effects of a weak toroidicity, a non-circular plasma cross-section and the influence of induced currents in the external conductors. It is found that the non-circularity of the plasma cross-section always has a destabilizing effect but that the m=1 mode can be stabilized by the external feedback if the non-circularity is small. (author)

Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells.

Science.gov (United States)

Zeng, Wei; Xiao, Tao; Cai, Anlie; Cai, Weiliang; Liu, Huanhuan; Liu, Jingling; Li, Jie; Tan, Miduo; Xie, Li; Liu, Ying; Yang, Xiangcheng; Long, Yi

2017-01-01

Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy. We show that salidroside induced significant apoptosis in the human chondrosarcoma cell line SW1353. In addition, we demonstrate that salidroside-induced an autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II and downregulation of P62. Moreover, pharmacological or genetic blocking of autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced TFEB (Ser142) dephosphorylation, subsequently to activated TFEB nuclear translocation and increase of TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes. Importantly, we found that salidroside triggered the generation of ROS in SW1353 cells. Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB-dependent autophagy. These data demonstrate that salidroside increased TFEB-dependent autophagy by activating ROS signaling pathways in human chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent autophagy to enhance the activity of salidroside warrants further attention in treatment of human chondrosarcoma cells. © 2017 The Author(s). Published by S. Karger AG, Basel.

Generation of functional podocytes from human induced pluripotent stem cells

Directory of Open Access Journals (Sweden)

Osele Ciampi

2016-07-01

Full Text Available Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, α-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro.

Roles of CDX2 and EOMES in human induced trophoblast progenitor cells

Energy Technology Data Exchange (ETDEWEB)

Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Wang, Kai [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Gong, Yun Guo; Khoo, Sok Kean [Genomic Microarray Core Facility, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Leach, Richard, E-mail: Richard.Leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group, Grand Rapids, MI 49503 (United States)

2013-02-08

Highlights: ► CDX2 and EOMES play critical roles in human induced trophoblast progenitors (iTP). ► iTP cells directly transformed from fibroblasts. ► Differentiation of iTP cells into extravillous trophoblasts and syncytiotrophoblasts. -- Abstract: Abnormal trophoblast lineage proliferation and differentiation in early pregnancy have been associated with the pathogenesis of placenta diseases of pregnancy. However, there is still a gap in understanding the molecular mechanisms of early placental development due to the limited primary trophoblast cultures and fidelity of immortalized trophoblast lines. Trophoblasts stem (TS) cells, an in vitro model of trophectoderm that can differentiate into syncytiotrophoblasts and extravillous trophoblasts, can be an attractive tool for early pregnancy research. TS cells are well established in mouse but not in humans due to insufficient knowledge of which trophoblast lineage-specific transcription factors are involved in human trophectoderm (TE) proliferation and differentiation. Here, we applied induced pluripotent stem cell technique to investigate the human trophoblast lineage-specific transcription factors. We established human induced trophoblast progenitor (iTP) cells by direct reprogramming the fibroblasts with a pool of mouse trophoblast lineage-specific transcription factors consisting of CDX2, EOMES, and ELF5. The human iTP cells exhibit epithelial morphology and can be maintained in vitro for more than 2 months. Gene expression profile of these cells was tightly clustered with human trophectoderm but not with human neuron progenitor cells, mesenchymal stem cells, or endoderm cells. These cells are capable of differentiating into cells with an invasive capacity, suggesting extravillous trophoblasts. They also form multi-nucleated cells which secrete human chorionic gonadotropin and estradiol, consistent with a syncytiotrophoblast phenotype. Our results provide the evidence that transcription factors CDX2 and

Tungsten-induced carcinogenesis in human bronchial epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Laulicht, Freda; Brocato, Jason; Cartularo, Laura; Vaughan, Joshua; Wu, Feng; Kluz, Thomas; Sun, Hong [Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987 (United States); Oksuz, Betul Akgol [Genome Technology Center, New York University Langone Medical Center, New York, NY 10016 (United States); Shen, Steven [Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY 10016 (United States); Peana, Massimiliano; Medici, Serenella; Zoroddu, Maria Antonietta [Department of Chemistry and Pharmacy, University of Sassari, Sassari (Italy); Costa, Max, E-mail: Max.Costa@nyumc.org [Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987 (United States)

2015-10-01

Metals such as arsenic, cadmium, beryllium, and nickel are known human carcinogens; however, other transition metals, such as tungsten (W), remain relatively uninvestigated with regard to their potential carcinogenic activity. Tungsten production for industrial and military applications has almost doubled over the past decade and continues to increase. Here, for the first time, we demonstrate tungsten's ability to induce carcinogenic related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer-related pathways in transformed clones as determined by RNA sequencing. Human bronchial epithelial cell line (Beas-2B) exposed to tungsten developed carcinogenic properties. In a soft agar assay, tungsten-treated cells formed more colonies than controls and the tungsten-transformed clones formed tumors in nude mice. RNA-sequencing data revealed that the tungsten-transformed clones altered the expression of many cancer-associated genes when compared to control clones. Genes involved in lung cancer, leukemia, and general cancer genes were deregulated by tungsten. Taken together, our data show the carcinogenic potential of tungsten. Further tests are needed, including in vivo and human studies, in order to validate tungsten as a carcinogen to humans. - Highlights: • Tungsten (W) induces cell transformation and increases migration in vitro. • W increases xenograft growth in nude mice. • W altered the expression of cancer-related genes such as those involved in leukemia. • Some of the dysregulated leukemia genes include, CD74, CTGF, MST4, and HOXB5. • For the first time, data is presented that demonstrates tungsten's carcinogenic potential.

Externalities of fuel cycles 'ExternE' project. Coal fuel cycle. Estimation of physical impacts and monetary valuation for priority impact pathways

International Nuclear Information System (INIS)

Berry, J.E.; Holland, M.R.; Watkiss, P.R.

1994-01-01

Background to the ExternE Project Awareness of the environmental damage resulting from human activity, particularly concerning energy use, has grown greatly in recent years. Effects such as global warming, ozone depletion and acid rain are now the subjects of much research and public debate. It is now known that these and other effects damage a wide range of receptors, including human health, forests, crops, freshwater ecosystems and buildings. Such damages are typically not accounted for by the producers and consumers of the good in question (in this case energy). They are thus referred to as 'external costs' or 'externalities', to distinguish them from the private costs which account for the construction of plant, cost of fuel, wages, etc. In recent years there has been a growing interest in the assessment of the environmental and health impacts of energy, and the related external costs. This concern is driven by a number of different factors; The need to integrate environmental concerns in decision making over the choice between different fuels and energy technologies. The need to evaluate the costs and benefits of stricter environmental standards. Increased attention to the use of economic instruments for environmental policy. The need to develop overall indicators of environmental performance of different technologies. Major changes in the energy sector, including privatisation, liberalisation of markets, reduction of subsidies, etc. An agreed methodology for calculation and integration of external costs has not been established. Earlier work is typically of a preliminary nature and tends to be deficient with respect to both the methods employed and the quality of models and data used. In consequence of this a collaborative project, the EC/US Fuel Cycles Study, was established between Directorate General XII (Science, Research and Technology) of the European Commission and the United States Department of Energy. This ran for the period 1991 to 1993, and good

Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

Science.gov (United States)

Kim, Albert H.; Wakabayashi, Ken T.; Baumann, Michael H.; Shaham, Yavin

2014-01-01

MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed “rave” parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22−23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ∼1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues. PMID:24899699

Ultraviolet B irradiation of human leukaemia HL-60 cells in vitro induces apoptosis

International Nuclear Information System (INIS)

Martin, S.J.; Cotter, T.G.

1991-01-01

UV radiation is known to be a potent agent for the induction of programmed cell death (apoptosis) in human skin. However, the mechanistic aspects of UV-induced apoptosis remain ill-defined. In this study the effects of varying periods of UV-irradiation on the human leukaemia HL-60 cell line and on five other human cell lines were investigated.HL-60 cells were found to rapidly undergo apoptosis en masse after short periods of UV-irradiation whereas prolonged exposure of these cells to this form of radiation induced a more rapid form of cell death which was suggestive of necrosis, the pathological mode of cell death. UV-induced apoptosis in cell lines was characterized by morphological changes as well as DNA fragmentation into unit multiples of ∼ 200 bp, which was indicative of endogenous endonuclease activation. This DNA fragmentation pattern was not detected in cells immediately after UV-irradiation, and was therefore not the result of direct UV-induced DNA damage. UV-induced apoptosis of the HL-60 cell line was found to require extracellular calcium and to be inhibited in a dose-dependent way by zinc added to the culture medium. (author)

Evaluation of human-induced vibration of continuous footbridges

Directory of Open Access Journals (Sweden)

El-Robaa Ahmed

2015-01-01

Full Text Available With the development of construction materials and the introduction of high strength steel and concrete, the human-induced vibration became a dominant criterion for the design of pedestrian bridges. Currently, longer spans and lightweight bridges have been comprised in most of design trends. This leads to lower the natural frequencies of the system which have a great effect on the dynamic performance of bridges subjected to human activities. Although the design of steel footbridges could reach the optimum level of design in terms of strength criterion, it might not reach the acceptance level for vibration condition. This will enforce the designer to choose section profiles with higher inertia to enhance stiffness of the whole system. This paper presents an overall assessment for floor vibration problem due to pedestrian induced vertical forces on continuous composite footbridges. The footfall method presented by concrete centre “CCIP-016” is adopted in this study to evaluate the response factor and acceleration of pedestrian bridges using a FEA software package “Robot Structural Analysis”.

External auditory canal leech: a rare case report of paediatric ...

African Journals Online (AJOL)

Leeches are blood sucking organism feed on human blood. While human bites are common, they rarely cause human internal infestation. We describe a rare case of a parasitic leech infestation of the External Auditory Canal (EAC). A two month old child presented to the Emergency department with a seven day history of ...

Externalities of fuel cycles 'ExternE' project. Summary report

International Nuclear Information System (INIS)

Holland, M.; Berry, J.

1994-01-01

There is a growing requirement for policy analysts to take account of the environment in their decision making and to undertake the specified cost-benefit analysis. Within the European Union this is reflected in the 5th Environmental Action Programme, and the Commission's White Paper entitled 'Growth, competitiveness, employment and the ways forward to the 21st century'. This has led to a need for evaluation of environmental externalities. The ExternE Project commenced in 1991 as the European part of a collaborative study between the European Commission and the US Department of Energy. It aims to be the first systematic approach to the evaluation of external costs of a wide range of different fuel cycles. The project will result in an operational accounting framework for the quantification and monetarisation of priority environmental and other externalities. This framework will allow the calculation of the marginal external costs and benefits for specific power plants, at specific sites using specified technologies. There are three major phases in the project. Phase I was undertaken in collaboration with the US Department of Energy. In this phase the teams jointly developed the conceptual approach and methodology and shared scientific information for application to a number of fuel cycles. On the European side work concentrated on the nuclear and coal fuel cycles which together were expected to raise many of the fundamental issues in fuel cycle analysis. The project is currently nearing completion of Phase 2. During this phase the methodology has been applied to a wide range of different fossil, nuclear and renewable fuel cycles for power generation and energy conservation options. Also a series of National Implementation Programmes are underway in which the methodology and accounting framework are being applied to reference sites throughout Europe. In addition the general methodology is being extended to address the evaluation of externalities associated with

Molecular analysis of formaldehyde-induced mutations in human lymphoblasts and E. coli

International Nuclear Information System (INIS)

Crosby, R.M.; Richardson, K.K.; Craft, T.R.; Benforado, K.B.; Liber, H.L.; Skopek, T.R.

1988-01-01

The molecular nature of formaldehyde (HCHO)-induced mutations was studied in both human lymphoblasts and E. coli. Thirty HPRT - human lymphoblast colonies induced by eight repetitive 150 μM HCHO treatments were characterized by Southern blot analysis. Fourteen of these mutants (47%) had visible deletions of some or all of the X-linked HPRT bands, indicating that HCHO can induce large losses of DNA in human lymphoblasts. In E. coli., DNA alterations induced by HCHO were characterized with use of the xanthine guanine phosphoribosyl transferase (gpt) gene as the genetic target. Exposure of E. coli to 4 mM HCHO for 1 hr induced large insertions (41%), large deletions (18%), and point mutations (41%). Dideoxy DNA sequencing revealed that most of the point mutations were transversions at GC base pairs. In contrast, exposure of E. coli to 40 mM HCHO for 1 hr produced 92% point mutations, 62% of which were transitions at a single AT base pair in the gene. Therefore, HCHO is capable of producing different genetic alterations in E. coli at different concentrations, suggesting fundamental differences in the mutagenic mechanisms operating at the two concentrations used. Naked pSV2gpt plasmid DNA was exposed to 3.3 or 10 mM HCHO and transformed into E. coli. Most of the resulting mutations were frameshifts, again suggesting a different mutagenic mechanism

Impact of training state on fasting-induced regulation of adipose tissue metabolism in humans

DEFF Research Database (Denmark)

Bertholdt, Lærke; Gudiksen, Anders; Stankiewicz, Tomasz

2018-01-01

Recruitment of fatty acids from adipose tissue is essential during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore, the aim of the present study was to investig......Recruitment of fatty acids from adipose tissue is essential during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore, the aim of the present study...... was to investigate 1) fasting-induced regulation of lipolysis and glyceroneogenesis in human adipose tissue as well as 2) the impact of training state on basal oxidative capacity and fasting-induced metabolic regulation in human adipose tissue. Untrained (VO2max 55ml......RNA content were higher in trained subjects than untrained subjects. In addition, trained subjects had higher adipose tissue hormone sensitive lipase Ser660 phosphorylation and adipose triglyceride lipase protein content as well as higher plasma free fatty acids concentration than untrained subjects during...

The Externe project. Assessment of the external costs of the natural gas fuel cycle

International Nuclear Information System (INIS)

Holland, M.R.

1997-01-01

A detailed bottom-up methodology for assessment of the external costs of energy has been developed by a multi-disciplinary, pan-European team as part of the European Commissions's JOULE Programme. The consequences of the generation of electricity from fossil, nuclear and renewable technologies, in terms of damages to human health, buildings and the wider environment, have been assessed within a consistent framework. The potential application of the results in cost-benefit analysis, power system optimisation, emissions charging, etc. is also now under investigation. The analysis starts with definition of the fuel cycle, and specification of the technologies and locations to be considered. Results to date show that for typical modern examples of power plants burning different fossil fuels, externalities (including possible global warming effects) are lowest for gas-burning plant. (R.P.)

Formaldehyde sensor based on Ni-doped tetrapod-shaped ZnO nanopowder induced by external magnetic field

Science.gov (United States)

Bai, Zikui; Xie, Changsheng; Hu, Mulin; Zhang, Shunping

2008-12-01

The sensors based on Ni-doped ZnO nanopowder with tetrapod-shape (T-ZnO) were fabricated by screen-printing technique with external magnetic field in different direction. The morphologies and crystal structures of the thick film were characterized by X-ray diffraction (XRD) and field-emission scanning electron microscopy (FE-SEM), respectively. Gas-sensing property of sensors responded to 100 ppm formaldehyde was also detected. The results show that the direction of magnetic field has crucial effect on the sensor sensitivity. The sensors based on 5 wt% Ni-doped T-ZnO induced by magnetic field in parallel direction to the thick film surface, has the optimization sensitivity, the shortest response and recovery time, which are 10.6, 16 and 15 s, respectively. The magnetic-field induction model and the gas-sensing mechanism of the Ni-doped T-ZnO are proposed.

Spaceflight induced changes in the human proteome.

Science.gov (United States)

Kononikhin, Alexey S; Starodubtseva, Natalia L; Pastushkova, Lyudmila Kh; Kashirina, Daria N; Fedorchenko, Kristina Yu; Brhozovsky, Alexander G; Popov, Igor A; Larina, Irina M; Nikolaev, Evgeny N

2017-01-01

Spaceflight is one of the most extreme conditions encountered by humans: Individuals are exposed to radiation, microgravity, hypodynamia, and will experience isolation. A better understanding of the molecular processes induced by these factors may allow us to develop personalized countermeasures to minimize risks to astronauts. Areas covered: This review is a summary of literature searches from PubMed, NASA, Roskosmos and the authors' research experiences and opinions. The review covers the available proteomic data on the effects of spaceflight factors on the human body, including both real space missions and ground-based model experiments. Expert commentary: Overall, the authors believe that the present background, methodology and equipment improvements will enhance spaceflight safety and support accumulation of new knowledge on how organisms adapt to extreme conditions.

The effect of childhood malnutrition on externalizing behavior.

Science.gov (United States)

Liu, Jianghong; Raine, Adrian

2006-10-01

Childhood externalizing behavior (aggression, hyperactivity, and conduct disorder) has been increasingly viewed as a public health problem because of its etiology and outcome. The association between malnutrition and externalizing behavior has begun to receive attention. This review summarizes recent empirical findings on malnutrition as a risk factor for the development of externalizing behavior, with an emphasis on micronutrient deficiency, and explores brain dysfunction as a possible mechanism. Externalizing behavior is associated with both macromalnutrition (e.g. protein) and micromalnutrition (e.g. iron and zinc). Both prenatal and postnatal malnutrition is implicated. The long-term effects of malnutrition on behavior could be reversible. The effects of docosahexaenoic acid/omega-3 long-chain essential fatty acid on externalizing behavior are more mixed. From animal and human findings, it is hypothesized that malnutrition impairs neurocognitive functioning by reducing neurons, alternating neurotransmitter functioning, and increasing neurotoxicity, and that such neurocognitive impairments predispose to externalizing behavior. Different lines of evidence support the view that poor nutrition contributes to the development of child behavior problems. More randomized, controlled trials that manipulate nutritional intake and evaluate behavior in children are needed to evaluate the etiological role of nutrition in externalizing behavior in order to inform intervention and prevention efforts.

Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

Science.gov (United States)

Dettmar, Anne K.; Binder, Elisabeth; Greiner, Friederike R.; Liebau, Max C.; Kurschat, Christine E.; Jungraithmayr, Therese C.; Saleem, Moin A.; Schmitt, Claus-Peter; Feifel, Elisabeth; Orth-Höller, Dorothea; Kemper, Markus J.; Pepys, Mark; Würzner, Reinhard

2014-01-01

Hemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)-producing Escherichia coli. Proteinuria can occur in the early phase of the disease, and its persistence determines the renal prognosis. Stx2 may injure podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member of the pentraxin family, has been shown to protect against Stx2-induced lethality in mice in vivo, presumably by specific binding to the toxin. We therefore tested the hypothesis that SAP can protect against Stx2-induced injury of human podocytes. To elucidate the mechanisms underlying podocyte injury in HUS-associated proteinuria, we assessed Stx2-induced activation of mitogen-activated protein kinases (MAPKs) and apoptosis in immortalized human podocytes and evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2-binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was internalized and then activated p38α MAPK and c-Jun N-terminal kinase (JNK), important signaling steps in cell differentiation and apoptosis. Stx2 also activated caspase 3, resulting in an increased level of apoptosis. Coincubation of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a target of Stx2 and that SAP protects podocytes against Stx2-induced injury. SAP may therefore be a useful therapeutic option. PMID:24566618

Thermographic venous blood flow characterization with external cooling stimulation

Science.gov (United States)

Saxena, Ashish; Ng, E. Y. K.; Raman, Vignesh

2018-05-01

Experimental characterization of blood flow in a human forearm is done with the application of continuous external cooling based active thermography method. Qualitative and quantitative detection of the blood vessel in a thermal image is done, along with the evaluation of blood vessel diameter, blood flow direction, and velocity in the target blood vessel. Subtraction based image manipulation is performed to enhance the feature contrast of the thermal image acquired after the removal of external cooling. To demonstrate the effect of occlusion diseases (obstruction), an external cuff based occlusion is applied after the removal of cooling and its effect on the skin rewarming is studied. Using external cooling, a transit time method based blood flow velocity estimation is done. From the results obtained, it is evident that an external cooling based active thermography method can be used to develop a diagnosis tool for superficial blood vessel diseases.

Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive.

Science.gov (United States)

Marsden, Karen E; Ma, Wei Ji; Deci, Edward L; Ryan, Richard M; Chiu, Pearl H

2015-06-01

The duration and quality of human performance depend on both intrinsic motivation and external incentives. However, little is known about the neuroscientific basis of this interplay between internal and external motivators. Here, we used functional magnetic resonance imaging to examine the neural substrates of intrinsic motivation, operationalized as the free-choice time spent on a task when this was not required, and tested the neural and behavioral effects of external reward on intrinsic motivation. We found that increased duration of free-choice time was predicted by generally diminished neural responses in regions associated with cognitive and affective regulation. By comparison, the possibility of additional reward improved task accuracy, and specifically increased neural and behavioral responses following errors. Those individuals with the smallest neural responses associated with intrinsic motivation exhibited the greatest error-related neural enhancement under the external contingency of possible reward. Together, these data suggest that human performance is guided by a "tonic" and "phasic" relationship between the neural substrates of intrinsic motivation (tonic) and the impact of external incentives (phasic).

Sphingosine-1-phosphate prevents chemotherapy-induced human primordial follicle death.

Science.gov (United States)

Li, Fang; Turan, Volkan; Lierman, Sylvie; Cuvelier, Claude; De Sutter, Petra; Oktay, Kutluk

2014-01-01

Can Sphingosine-1-phosphate (S1P), a ceramide-induced death pathway inhibitor, prevent cyclophosphamide (Cy) or doxorubicin (Doxo) induced apoptotic follicle death in human ovarian xenografts? S1P can block human apoptotic follicle death induced by both drugs, which have differing mechanisms of cytotoxicity. S1P has been shown to decrease the impact of chemotherapy and radiation on germinal vesicle oocytes in animal studies but no human translational data exist. Experimental human ovarian xenografting to test the in vivo protective effect of S1P on primordial follicle survival in the chemotherapy setting. The data were validated by assessing the same protective effect in the ovaries of xenografted mice in parallel. Xenografted mice were treated with Cy (75 mg/kg), Cy+S1P (200 μM), Doxo (10 mg/kg), Doxo+S1P or vehicle only (Control). S1P was administered via continuous infusion using a mini-osmotic pump beginning 24 h prior to and ending 72 h post-chemotherapy. Grafts were then recovered and stained with anti-caspase 3 antibody for the detection of apoptosis in primordial follicles. The percentage of apoptotic to total primordial follicles was calculated in each group. Both Cy and Doxo resulted in a significant increase in apoptotic follicle death in human ovarian xenografts compared with controls (62.0 ± 3.9% versus 25.7 ± 7.4%, P 0.05). The findings from the ovaries of the severe combined immunodeficient mice mirrored the findings with human tissue. The functionality of the rescued human ovarian follicles needs to be evaluated in future studies though the studies in rodents showed that rescued oocytes can result in healthy offspring. In addition, the impact of S1P on cancer cells should be further studied. S1P and its future analogs hold promise for preserving fertility by pharmacological means for patients undergoing chemotherapy. This research is supported by NIH's NICHD and NCI (5R01HD053112-06 and 5R21HD061259-02) and the Flemish Foundation for Scientific

Human albumin prevents 6-hydroxydopamine-induced loss of tyrosine hydroxylase in in vitro and in vivo.

Directory of Open Access Journals (Sweden)

Li-Juan Zhang

Full Text Available Human albumin has recently been demonstrated to protect brain neurons from injury in rat ischemic brain. However, there is no information available about whether human albumin can prevent loss of tyrosine hydroxylase (TH expression of dopaminergic (DA neurons induced by 6-hydroxydopamine (6-OHDA toxicity that is most commonly used to create a rat model of Parkinson's disease (PD. In the present study, two microliters of 1.25% human albumin were stereotaxically injected into the right striatum of rats one day before or 7 days after the 6-OHDA lesion in the same side. D-Amphetamine-induced rotational asymmetry was measured 7 days, 3 and 10 weeks after 6-OHDA lesion. We observed that intrastriatal administration of human albumin significantly reduced the degree of rotational asymmetry. The number of TH-immunoreactive neurons present in the substantia nigra was greater in 6-OHDA lesioned rats following human albumin-treatment than non-human albumin treatment. TH-immunoreactivity in the 6-OHDA-lesioned striatum was also significantly increased in the human albumin-treated rats. To examine the mechanisms underlying the effects of human albumin, we challenged PC12 cells with 6-OHDA as an in vitro model of PD. Incubation with human albumin prevented 6-OHDA-induced reduction of cell viability in PC12 cell cultures, as measured by MTT assay. Furthermore, human albumin reduced 6-OHDA-induced formation of reactive oxygen species (ROS and apoptosis in cultured PC12 cells, as assessed by flow cytometry. Western blot analysis showed that human albumin inhibited 6-OHDA-induced activation of JNK, c-Jun, ERK, and p38 mitogen-activated protein kinases (MAPK signaling in PC12 cultures challenged with 6-OHDA. Human albumin may protect against 6-OHDA toxicity by influencing MAPK pathway followed by anti-ROS formation and anti-apoptosis.

Human Albumin Prevents 6-Hydroxydopamine-Induced Loss of Tyrosine Hydroxylase in In Vitro and In Vivo

Science.gov (United States)

Zhang, Li-Juan; Xue, Yue-Qiang; Yang, Chun; Yang, Wei-Hua; Chen, Long; Zhang, Qian-Jin; Qu, Ting-Yu; Huang, Shile; Zhao, Li-Ru; Wang, Xiao-Min; Duan, Wei-Ming

2012-01-01

Human albumin has recently been demonstrated to protect brain neurons from injury in rat ischemic brain. However, there is no information available about whether human albumin can prevent loss of tyrosine hydroxylase (TH) expression of dopaminergic (DA) neurons induced by 6-hydroxydopamine (6-OHDA) toxicity that is most commonly used to create a rat model of Parkinson's disease (PD). In the present study, two microliters of 1.25% human albumin were stereotaxically injected into the right striatum of rats one day before or 7 days after the 6-OHDA lesion in the same side. D-Amphetamine-induced rotational asymmetry was measured 7 days, 3 and 10 weeks after 6-OHDA lesion. We observed that intrastriatal administration of human albumin significantly reduced the degree of rotational asymmetry. The number of TH-immunoreactive neurons present in the substantia nigra was greater in 6-OHDA lesioned rats following human albumin-treatment than non-human albumin treatment. TH-immunoreactivity in the 6-OHDA-lesioned striatum was also significantly increased in the human albumin-treated rats. To examine the mechanisms underlying the effects of human albumin, we challenged PC12 cells with 6-OHDA as an in vitro model of PD. Incubation with human albumin prevented 6-OHDA-induced reduction of cell viability in PC12 cell cultures, as measured by MTT assay. Furthermore, human albumin reduced 6-OHDA-induced formation of reactive oxygen species (ROS) and apoptosis in cultured PC12 cells, as assessed by flow cytometry. Western blot analysis showed that human albumin inhibited 6-OHDA-induced activation of JNK, c-Jun, ERK, and p38 mitogen-activated protein kinases (MAPK) signaling in PC12 cultures challenged with 6-OHDA. Human albumin may protect against 6-OHDA toxicity by influencing MAPK pathway followed by anti-ROS formation and anti-apoptosis. PMID:22815976

Physiological correlates of stress-induced decrements in human perceptual performance.

Science.gov (United States)

1993-11-01

Stress-induced changes in human performance have been thought to result from alterations in the "multidimensional arousal state" of the individual, as indexed by alterations in the physiological and psychological mechanisms controlling performance. I...

Anticipated chaos in a nonsymmetric coupled external-cavity-laser system

International Nuclear Information System (INIS)

Rees, Paul; Spencer, Paul S.; Pierce, Iestyn; Sivaprakasam, S.; Shore, K. Alan

2003-01-01

We explain how the anticipation of chaos in a coupled external cavity laser system described by Sivaprakasam, Shahverdiev, Spencer, and Shore [Phys. Rev. Lett. 87, 154101 (2001)] is obtained. We show that the external cavity induces the required symmetry breaking necessary for the existence of a time delay between the synchronized output of the two laser diodes. The inclusion of a detuning between the two lasers causes one laser to anticipate the chaotic dynamics of the other

Correlation of Vitamin D status and orthodontic-induced external apical root resorption.

Science.gov (United States)

Tehranchi, Azita; Sadighnia, Azin; Younessian, Farnaz; Abdi, Amir H; Shirvani, Armin

2017-01-01

Adequate Vitamin D is essential for dental and skeletal health in children and adult. The purpose of this study was to assess the correlation of serum Vitamin D level with external-induced apical root resorption (EARR) following fixed orthodontic treatment. In this cross-sectional study, the prevalence of Vitamin D deficiency (defined by25-hydroxyvitamin-D) was determined in 34 patients (23.5% male; age range 12-23 years; mean age 16.63 ± 2.84) treated with fixed orthodontic treatment. Root resorption of four maxillary incisors was measured using before and after periapical radiographs (136 measured teeth) by means of a design-to-purpose software to optimize data collection. Teeth with a maximum percentage of root resorption (%EARR) were indicated as representative root resorption for each patient. A multiple linear regression model and Pearson correlation coefficient were used to assess the association of Vitamin D status and observed EARR. P 0.05). This study suggests that Vitamin D level is not among the clinical variables that are potential contributors for EARR. The prevalence of Vitamin D deficiency does not differ in patients with higher EARR. These data suggest the possibility that Vitamin D insufficiency may not contribute to the development of more apical root resorption although this remains to be confirmed by further longitudinal cohort studies.

IRAK1 variant is protective for orthodontic-induced external apical root resorption.

Science.gov (United States)

Pereira, S; Nogueira, L; Canova, F; Lopez, M; Silva, H C

2016-10-01

Interleukin-1 beta (IL1B) pathway is a key player in orthodontic-induced external apical root resorption (EARR). The aim of this work was to identify the genes related to the IL1 pathway as possible candidate genes for EARR, which might be included in an integrative predictive model of this complex phenotype. Using a stepwise multiple linear regression model, 195 patients who had undergone orthodontic treatment were assessed for clinical and genetic factors associated with %EARRmax (maximum %EARR value obtained for each patient). The four maxillary incisors and the two maxillary canines were assessed. Three functional single nucleotide polymorphisms (SNPs) were genotyped: rs1143634 in IL1B gene, rs315952 in IL1RN gene, and rs1059703 in X-linked IRAK1 gene. The model showed that four of the nine clinical variables and one SNP explained 30% of the %EARRmax variability. The most significant unique contributions to the model were gender (P = 0.001), treatment duration (P < 0.001), premolar extractions (P = 0.003), Hyrax appliance (P < 0.001), and homozygosity/hemizygosity for variant C from IRAK1 gene (P = 0.018), which proved to be a protective factor. IRAK1 polymorphism is proposed as a protective variant for EARR. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

External costs of energy - do the answers match the questions? Looking back at 10 years of ExternE

International Nuclear Information System (INIS)

Krewitt, W.

2002-01-01

While the claim for 'getting prices right' is quite popular in conceptual policy papers, the implementation of appropriate internalisation strategies is still hampered by a lack of reliable external cost data. Great expectations were set into the ExternE project, a major research programme launched by the European Commission at the beginning of the 1990s to provide a scientific basis for the quantification of energy related externalities and to give guidance supporting the design of internalisation measures. After more than a decade of research, the ExternE label became a well recognised standard source for external cost data. Looking back into the ExternE history, the paper pursues how emerging new scientific insights and changing background assumptions affected external cost estimates and related recommendations to policy over time. Based on ExternE results, the usefulness and inherent limitations of external cost estimates for impact categories like climate change or nuclear waste disposal is discussed. The paper also gives examples on how external costs in spite of remaining uncertainties are successfully used to support environmental policy. (Author)

Environmental stress induces trinucleotide repeat mutagenesis in human cells.

Science.gov (United States)

Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A; Yotnda, Patricia; Wilson, John H

2015-03-24

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.

Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells

OpenAIRE

Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

2016-01-01

Progesterone plays critical roles in maintaining a successful pregnancy at the early embryonic stage. Human chorionic gonadotropin (hCG) rapidly induces amphiregulin (AREG) expression. However, it remains unknown whether AREG mediates hCG-induced progesterone production. Thus, the objective of this study was to investigate the role of AREG in hCG-induced progesterone production and the underlying molecular mechanism in human granulosa cells; primary cells were used as the experimental model. ...

Findings Brief External Review of the Ecosystem Approaches to ...

International Development Research Centre (IDRC) Digital Library (Canada)

External Review of the Ecosystem Approaches to Human. Health Program ... Improved understanding of social, political, economic, and ecological interactions and .... global learning, communication among partners and others stakeholders.

Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives

Science.gov (United States)

Gajbhiye, Virendra; Escalante, Leah; Chen, Guojun; Laperle, Alex; Zheng, Qifeng; Steyer, Benjamin; Gong, Shaoqin; Saha, Krishanu

2013-12-01

Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained higher fibroblast proliferation levels and MMP activity. The results demonstrate that the PEG-H40-DXC nanoparticle system provides an effective tool to controlling gene expression in human stem cell derivatives.Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained

Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

International Nuclear Information System (INIS)

Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana; Klegeris, Andis; Little, Jonathan P.

2014-01-01

Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes

Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

Energy Technology Data Exchange (ETDEWEB)

Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana [School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC (Canada); Klegeris, Andis [Department of Biology, University of British Columbia Okanagan, Kelowna, BC (Canada); Little, Jonathan P., E-mail: jonathan.little@ubc.ca [School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC (Canada)

2014-03-28

Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observed link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.

Recombinant human bone morphogenetic protein induces bone formation

International Nuclear Information System (INIS)

Wang, E.A.; Rosen, V.; D'Alessandro, J.S.; Bauduy, M.; Cordes, P.; Harada, T.; Israel, D.I.; Hewick, R.M.; Kerns, K.M.; LaPan, P.; Luxenberg, D.P.; McQuaid, D.; Moutsatsos, I.K.; Nove, J.; Wozney, J.M.

1990-01-01

The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans

Rhein Induces Apoptosis in Human Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Ching-Yao Chang

2012-01-01

Full Text Available Human breast cancers cells overexpressing HER2/neu are more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2 and control vector MCF-7 (MCF-7/VEC cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

Dipole nano-laser: the effect of an external electric field

Energy Technology Data Exchange (ETDEWEB)

Ghannam, T, E-mail: gtalal@hotmail.co [KAIN Institute for Nano-Technology, King Saud University, PO Box 2454, Riyadh 11451 (Saudi Arabia)

2010-08-14

Using the Langevin formalism we study the effects an external electromagnetic field induces in a system made of a pumped two-level system (TLS) and a metallic nano-particle (NP) that interact together via their near-fields. The surface plasmons of the NP greatly enhance the scattered light. With the absence of the external EM field the spectral width of the scattered light is broader than that of the system, covering almost the entire optical range. However, with the inclusion the external EM field, a reduction in the spectral width of the scattered light of order of 10-50 times below that of the system is observed for certain parameter regimes.This system exhibits also bistability in the population difference of the TLS with the external field acting as an order parameter, but only for certain values of the noise quanta.

Estimating parameters of chaotic systems synchronized by external driving signal

International Nuclear Information System (INIS)

Wu Xiaogang; Wang Zuxi

2007-01-01

Noise-induced synchronization (NIS) has evoked great research interests recently. Two uncoupled identical chaotic systems can achieve complete synchronization (CS) by feeding a common noise with appropriate intensity. Actually, NIS belongs to the category of external feedback control (EFC). The significance of applying EFC in secure communication lies in fact that the trajectory of chaotic systems is disturbed so strongly by external driving signal that phase space reconstruction attack fails. In this paper, however, we propose an approach that can accurately estimate the parameters of the chaotic systems synchronized by external driving signal through chaotic transmitted signal, driving signal and their derivatives. Numerical simulation indicates that this approach can estimate system parameters and external coupling strength under two driving modes in a very rapid manner, which implies that EFC is not superior to other methods in secure communication

Human FcγRIIA induces anaphylactic and allergic reactions.

Science.gov (United States)

Jönsson, Friederike; Mancardi, David A; Zhao, Wei; Kita, Yoshihiro; Iannascoli, Bruno; Khun, Huot; van Rooijen, Nico; Shimizu, Takao; Schwartz, Lawrence B; Daëron, Marc; Bruhns, Pierre

2012-03-15

IgE and IgE receptors (FcεRI) are well-known inducers of allergy. We recently found in mice that active systemic anaphylaxis depends on IgG and IgG receptors (FcγRIIIA and FcγRIV) expressed by neutrophils, rather than on IgE and FcεRI expressed by mast cells and basophils. In humans, neutrophils, mast cells, basophils, and eosinophils do not express FcγRIIIA or FcγRIV, but FcγRIIA. We therefore investigated the possible role of FcγRIIA in allergy by generating novel FcγRIIA-transgenic mice, in which various models of allergic reactions induced by IgG could be studied. In mice, FcγRIIA was sufficient to trigger active and passive anaphylaxis, and airway inflammation in vivo. Blocking FcγRIIA in vivo abolished these reactions. We identified mast cells to be responsible for FcγRIIA-dependent passive cutaneous anaphylaxis, and monocytes/macrophages and neutrophils to be responsible for FcγRIIA-dependent passive systemic anaphylaxis. Supporting these findings, human mast cells, monocytes and neutrophils produced anaphylactogenic mediators after FcγRIIA engagement. IgG and FcγRIIA may therefore contribute to allergic and anaphylactic reactions in humans.

Nuclear DNA damage-triggered NLRP3 inflammasome activation promotes UVB-induced inflammatory responses in human keratinocytes

Energy Technology Data Exchange (ETDEWEB)

Hasegawa, Tatsuya, E-mail: tatsuya.hasegawa@to.shiseido.co.jp; Nakashima, Masaya; Suzuki, Yoshiharu

2016-08-26

Ultraviolet (UV) radiation in sunlight can result in DNA damage and an inflammatory reaction of the skin commonly known as sunburn, which in turn can lead to cutaneous tissue disorders. However, little has been known about how UV-induced DNA damage mediates the release of inflammatory mediators from keratinocytes. Here, we show that UVB radiation intensity-dependently increases NLRP3 gene expression and IL-1β production in human keratinocytes. Knockdown of NLRP3 with siRNA suppresses UVB-induced production of not only IL-1β, but also other inflammatory mediators, including IL-1α, IL-6, TNF-α, and PGE{sub 2}. In addition, inhibition of DNA damage repair by knockdown of XPA, which is a major component of the nucleotide excision repair system, causes accumulation of cyclobutane pyrimidine dimer (CPD) and activation of NLRP3 inflammasome. In vivo immunofluorescence analysis confirmed that NLRP3 expression is also elevated in UV-irradiated human epidermis. Overall, our findings indicate that UVB-induced DNA damage initiates NLRP3 inflammasome activation, leading to release of various inflammatory mediators from human keratinocytes. - Highlights: • UVB radiation induces NLRP3 inflammasome activation in human keratinocytes. • NLRP3 knockdown suppresses production of UVB-induced inflammatory mediators. • UVB-induced DNA damage triggers NLRP3 inflammasome activation. • NLRP3 expression in human epidermis is elevated in response to UV radiation.

Nuclear DNA damage-triggered NLRP3 inflammasome activation promotes UVB-induced inflammatory responses in human keratinocytes

International Nuclear Information System (INIS)

Hasegawa, Tatsuya; Nakashima, Masaya; Suzuki, Yoshiharu

2016-01-01

Ultraviolet (UV) radiation in sunlight can result in DNA damage and an inflammatory reaction of the skin commonly known as sunburn, which in turn can lead to cutaneous tissue disorders. However, little has been known about how UV-induced DNA damage mediates the release of inflammatory mediators from keratinocytes. Here, we show that UVB radiation intensity-dependently increases NLRP3 gene expression and IL-1β production in human keratinocytes. Knockdown of NLRP3 with siRNA suppresses UVB-induced production of not only IL-1β, but also other inflammatory mediators, including IL-1α, IL-6, TNF-α, and PGE_2. In addition, inhibition of DNA damage repair by knockdown of XPA, which is a major component of the nucleotide excision repair system, causes accumulation of cyclobutane pyrimidine dimer (CPD) and activation of NLRP3 inflammasome. In vivo immunofluorescence analysis confirmed that NLRP3 expression is also elevated in UV-irradiated human epidermis. Overall, our findings indicate that UVB-induced DNA damage initiates NLRP3 inflammasome activation, leading to release of various inflammatory mediators from human keratinocytes. - Highlights: • UVB radiation induces NLRP3 inflammasome activation in human keratinocytes. • NLRP3 knockdown suppresses production of UVB-induced inflammatory mediators. • UVB-induced DNA damage triggers NLRP3 inflammasome activation. • NLRP3 expression in human epidermis is elevated in response to UV radiation.

Rationale for a GRAVSAT-MAGSAT mission: A perspective on the problem of external/internal transient field effects

Science.gov (United States)

Hermance, J. F.

1985-01-01

The Earth's magnetic field at MAGSAT altitudes not only has contributions from the Earth's core and static magnetization in the lithosphere, but also from external electric current systems in the ionosphere and magnetosphere, along with induced electric currents flowing in the conducting earth. Hermance assessed these last two contributions; the external time-varying fields and their associated internal counter-parts which are electromagnetically induced. It is readily recognized that during periods of magnetic disturbance, external currents often contribute from 10's to 100's of nanoteslas (gammas) to observations of the Earth's field. Since static anomalies from lithospheric magnetization are of this same magnitude or less, these external source fields must be taken into account when attempting to delineate gross structural features in the crust.

Endogenous cannabinoid receptor ligand induces the migration of human natural killer cells.

Science.gov (United States)

Kishimoto, Seishi; Muramatsu, Mayumi; Gokoh, Maiko; Oka, Saori; Waku, Keizo; Sugiura, Takayuki

2005-02-01

2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors (CB1 and CB2). Evidence is gradually accumulating which shows that 2-arachidonoylglycerol plays important physiological roles in several mammalian tissues and cells, yet the details remain ambiguous. In this study, we first examined the effects of 2-arachidonoylglycerol on the motility of human natural killer cells. We found that 2-arachidonoylglycerol induces the migration of KHYG-1 cells (a natural killer leukemia cell line) and human peripheral blood natural killer cells. The migration of natural killer cells induced by 2-arachidonoylglycerol was abolished by treating the cells with SR144528, a CB2 receptor antagonist, suggesting that the CB2 receptor is involved in the 2-arachidonoylglycerol-induced migration. In contrast to 2-arachidonoylglycerol, anandamide, another endogenous cannabinoid receptor ligand, did not induce the migration. Delta9-tetrahydrocannabinol, a major psychoactive constituent of marijuana, also failed to induce the migration; instead, the addition of delta9-tetrahydrocannabinol together with 2-arachidonoylglycerol abolished the migration induced by 2-arachidonoylglycerol. It is conceivable that the endogenous ligand for the cannabinoid receptor, that is, 2-arachidonoylglycerol, affects natural killer cell functions such as migration, thereby contributing to the host-defense mechanism against infectious viruses and tumor cells.

LIF is a contraction-induced myokine stimulating human myocyte proliferation

DEFF Research Database (Denmark)

Broholm, Christa; Laye, Matthew J; Brandt, Claus

2011-01-01

in skeletal muscle, but LIF was not detectable in plasma of the subjects. However, electrically stimulated cultured human myotubes produced and secreted LIF, suggesting that LIF is a myokine with local effects. The well-established exercise-induced signaling molecules PI3K, Akt and mTor contributed...... to the regulation of LIF in cultured human myotubes as chemical inhibition of PI3K and mTor and siRNA knockdown of Akt1 were independently sufficient to down regulate LIF. Human myoblast proliferation was increased by recombinant exogenous LIF and decreased by siRNA knockdown of the endogenous LIF receptor. Finally...

PPARγ ligand ciglitazone inhibits TNFα-induced ICAM-1 in human airway smooth muscle cells

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Chien-Da Huang

2014-08-01

Full Text Available Background: Modification of human airway smooth muscle (ASM function by proinflammatory cytokines has been regarded as a potential mechanism underlying bronchial hyperresponsiveness in asthma. Human ASM cells express intercellular adhesion molecule (ICAM-1 in response to cytokines. Synthetic ligands for peroxisome proliferator-activated receptor (PPARγ reportedly possess anti-inflammatory and immunomodulatory properties. In this study, we examined whether ciglitazone, a synthetic PPARγ ligand, can modulate the basal and tumor necrosis factor (TNFα-induced ICAM1 gene expression in human ASM cells. Methods: Human ASM cells were treated with TNFα. ICAM-1 expression was assessed by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR analysis. PPARγ activity was inhibited by target-specific small interfering (si RNA targeting PPARγ and GW9662, a PPARγ antagonist. Activity of nuclear factor (NF-κB was assessed by using immunoblot analysis, immune-confocal images, and electrophoretic mobility shift assay (EMSA. Results: By flow cytometry, ciglitazone alone had no effect on ICAM-1 expression in ASM cells, but inhibited ICAM-1 expression in response to TNFα (10 ng/ml in a dose-dependent manner (1-10 μM. It also inhibited TNFα-induced ICAM1 gene expression by RT-PCR analysis. Knockdown of PPARγ gene by target-specific siRNA targeting PPARγ enhanced ICAM-1 expression and the inhibitory effect of ciglitazone on TNFα-induced ICAM-1 expression was reversed by PPARγ siRNA and GW9662. SN-50 (10 μg/ml, an inhibitor for nuclear translocation of NF-κB, inhibited TNFα-induced ICAM-1 expression. Ciglitazone did not prevent TNFα-induced degradation of the cytosolic inhibitor of NF-κB (IκB, but inhibited the nuclear translocation of p65 induced by TNFα and suppressed the NF-κB/DNA binding activity. Conclusion: These findings suggest that ciglitazone inhibits TNFα-induced ICAM1 gene expression in human ASM cells through

Intermedilysin induces EGR-1 expression through calcineurin/NFAT pathway in human cholangiocellular carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Susilowati, Heni [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Okamura, Hirohiko [Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Hirota, Katsuhiko, E-mail: hirota@dent.tokushima-u.ac.jp [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Shono, Masayuki [Support Center for Advanced Medical Sciences, The University of Tokushima, Tokushima 770-8504 (Japan); Yoshida, Kaya [Department of Fundamental Oral Health Science, School of Oral Health and Welfare, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Murakami, Keiji [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Tabata, Atsushi; Nagamune, Hideaki [Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima 770-8506 (Japan); Haneji, Tatsuji [Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Miyake, Yoichiro [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan)

2011-01-07

Research highlights: {yields} ILY leads to the accumulation of [Ca{sup 2+}]i in the nucleus in HuCCT1 cells. {yields} ILY induced activation of NFAT1 through a calcineurin-dependent pathway. {yields} Calcineuri/NFAT pathway is involved in EGR-1 expression in response to ILY treatment. -- Abstract: Intermedilysin (ILY) is a cholesterol-dependent cytolysin produced by Streptococcus intermedius, which is associated with human brain and liver abscesses. Although intrahepatic bile duct cells play a valuable role in the pathogenesis of liver abscess, the molecular mechanism of ILY-treated intrahepatic bile duct cells remains unknown. In this study, we report that ILY induced a nuclear accumulation of intracellular calcium ([Ca{sup 2+}]i) in human cholangiocellular cells HuCCT1. We also demonstrate that 10 ng/ml ILY induced NFAT1 dephosphorylation and its nuclear translocation in HuCCT1 cells. In contrast to the result that ILY induced NF-{kappa}B translocation in human hepatic HepG2 cells, ILY did not affect NF-{kappa}B localization in HuCCT1 cells. Dephosphorylation and nuclear translocation of NFAT1 caused by ILY were prevented by [Ca{sup 2+}]i calcium chelator, BAPTA/AM, and calcineurin inhibitors, cyclosporine A and tacrolimus. ILY induced early growth response-1 (EGR-1) expression and it was inhibited by the pre-treatment with cyclosporine A, indicating that the calcineurin/NFAT pathway was involved in EGR-1 expression in response to ILY. ILY-induced calcineurin/NFAT1 activation and sequential EGR-1 expression might be related to the pathogenesis of S. intermedius in human bile duct cells.

Intermedilysin induces EGR-1 expression through calcineurin/NFAT pathway in human cholangiocellular carcinoma cells

International Nuclear Information System (INIS)

Susilowati, Heni; Okamura, Hirohiko; Hirota, Katsuhiko; Shono, Masayuki; Yoshida, Kaya; Murakami, Keiji; Tabata, Atsushi; Nagamune, Hideaki; Haneji, Tatsuji; Miyake, Yoichiro

2011-01-01

Research highlights: → ILY leads to the accumulation of [Ca 2+ ]i in the nucleus in HuCCT1 cells. → ILY induced activation of NFAT1 through a calcineurin-dependent pathway. → Calcineuri/NFAT pathway is involved in EGR-1 expression in response to ILY treatment. -- Abstract: Intermedilysin (ILY) is a cholesterol-dependent cytolysin produced by Streptococcus intermedius, which is associated with human brain and liver abscesses. Although intrahepatic bile duct cells play a valuable role in the pathogenesis of liver abscess, the molecular mechanism of ILY-treated intrahepatic bile duct cells remains unknown. In this study, we report that ILY induced a nuclear accumulation of intracellular calcium ([Ca 2+ ]i) in human cholangiocellular cells HuCCT1. We also demonstrate that 10 ng/ml ILY induced NFAT1 dephosphorylation and its nuclear translocation in HuCCT1 cells. In contrast to the result that ILY induced NF-κB translocation in human hepatic HepG2 cells, ILY did not affect NF-κB localization in HuCCT1 cells. Dephosphorylation and nuclear translocation of NFAT1 caused by ILY were prevented by [Ca 2+ ]i calcium chelator, BAPTA/AM, and calcineurin inhibitors, cyclosporine A and tacrolimus. ILY induced early growth response-1 (EGR-1) expression and it was inhibited by the pre-treatment with cyclosporine A, indicating that the calcineurin/NFAT pathway was involved in EGR-1 expression in response to ILY. ILY-induced calcineurin/NFAT1 activation and sequential EGR-1 expression might be related to the pathogenesis of S. intermedius in human bile duct cells.

Human Capital and Knowledge Emergence. Induced Effects of the Global Crisis on Human capital and Innovation

Directory of Open Access Journals (Sweden)

Simona Buta

2014-12-01

Full Text Available In the global crisis context crossed by organizations and countries in the past six years we assist also at conflicting measures in which regards knowledge, innovation and human capital; for example, countries such as England and France have reduced their costs for education, while Germany and other countries (Australia, Austria, Canada and Norway maintained the same allocations for education. What will be the effects of such measures on human capital in the near future? What are the best human resources policies in companies in the crisis context? Given that the subject of the research is "knowledge and human capital", in this paper we refer to the induced effects of the crisis on human capital and innovation. We will also identify the key steps that can be taken during crisis, and not only, to stimulate human capital.

Prolactin-inducible proteins in human breast cancer cells

International Nuclear Information System (INIS)

Shiu, R.P.; Iwasiow, B.M.

1985-01-01

The mechanism of action of prolactin in target cells and the role of prolactin in human breast cancer are poorly understood phenomena. The present study examines the effect of human prolactin (hPRL) on the synthesis of unique proteins by a human breast cancer cell line, T-47D, in serum-free medium containing bovine serum albumin. [ 35 S]Methionine-labeled proteins were analysed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis and fluorography. Treatment of cells with hPRL (1-1000 ng/ml) and hydrocortisone (1 microgram/ml) for 36 h or longer resulted in the synthesis and secretion of three proteins having molecular weights of 11,000, 14,000, and 16,000. Neither hPRL nor hydrocortisone alone induced these proteins. Of several other peptide hormones tested, only human growth hormone, a hormone structurally and functionally similar to hPRL, could replace hPRL in causing protein induction. These three proteins were, therefore, referred to as prolactin-inducible proteins (PIP). Each of the three PIPs was purified to homogeneity by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and specific antibodies were generated to them in rabbits. By immunoprecipitation and immunoblotting (Western blot) of proteins secreted by T-47D cells, it was demonstrated that the three PIPs were immunologically identical to one another. In addition, the 16-kDa and 14-kDa proteins (PIP-16 and PIP-14), and not the 11-kDa protein (PIP-11), incorporated [ 3 H]glycosamine. Furthermore, 2-deoxyglucose (2 mM) and tunicamycin (0.5 micrograms/ml), two compounds known to inhibit glycosylation, blocked the production of PIP-16 and PIP-14, with a concomitant increase in the accumulation of PIP-11

The ExternE project: methodology, objectives and limitations

International Nuclear Information System (INIS)

Rabl, A.; Spadaro, J.V.

2002-01-01

This paper presents a summary of recent studies on external costs of energy systems, in particular the ExternE (External Costs of Energy) Project of the European Commission. To evaluate the impact and damage cost of a pollutant, one needs to carry out an impact pathway analysis; this involves the calculation of increased pollutant concentrations in all affected regions due to an incremental emission (e.g. μg/m 3 of particles, using models of atmospheric dispersion and chemistry), followed by the calculation of physical impacts (e.g. number of cases of asthma due to these particles, using a dose-response function). The entire so-called fuel chain (or fuel cycle) is evaluated and compared on the basis of delivered end use energy. Even though the uncertainties are large, the results provide substantial evidence that the classical air pollutants (particles, NO x and SO x ) from the combustion of fossil fuels impose a heavy toll, in addition to the cost of global warming. The external costs are especially large for coal; even for 'good current technology' they may be comparable to the price of electricity. For natural gas the external costs are about a third to a half of coal. The external costs of nuclear are small compared to the price of electricity (at most a few %), and so are the external costs of most renewable energy systems. (authors)

Evolution of External Consultant Involvement in Human Resource Management in Eastern Europe (1990-2007

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József Poór

2015-03-01

Full Text Available This paper aims to analyze the evolution of Human Resources (HR consulting in transitional economies of Eastern Europe (EE from the political changes till the economic crisis (2008. This article provides insights into the specific socio-economic environment and HR practice of the region.  Following Markham's model (1999 we analyze specific characteristics of four typical ways of external consultant involvement: informative-becnhmarking, design, change and organizational learning consulting.  in this region. In general, before the political changes at the end of the 1980's, in most EE countries , consulting service was redendered by sector  research institutes, controlled by the state or by the different minsitries. Consulting approach in EE countries  were predominant similar to the school of scientific management. HR consulting hardly existed that time. Since changes in the regime's consulting linked to privatization, firm restructuring, and development has been developing significantly in all countries of the region. HR consulting underwent a significant development in the region.

Network and external perturbation induce burst synchronisation in cat cerebral cortex

Science.gov (United States)

Lameu, Ewandson L.; Borges, Fernando S.; Borges, Rafael R.; Batista, Antonio M.; Baptista, Murilo S.; Viana, Ricardo L.

2016-05-01

The brain of mammals are divided into different cortical areas that are anatomically connected forming larger networks which perform cognitive tasks. The cat cerebral cortex is composed of 65 areas organised into the visual, auditory, somatosensory-motor and frontolimbic cognitive regions. We have built a network of networks, in which networks are connected among themselves according to the connections observed in the cat cortical areas aiming to study how inputs drive the synchronous behaviour in this cat brain-like network. We show that without external perturbations it is possible to observe high level of bursting synchronisation between neurons within almost all areas, except for the auditory area. Bursting synchronisation appears between neurons in the auditory region when an external perturbation is applied in another cognitive area. This is a clear evidence that burst synchronisation and collective behaviour in the brain might be a process mediated by other brain areas under stimulation.

Saponin B, a novel cytostatic compound purified from Anemone taipaiensis, induces apoptosis in a human glioblastoma cell line.

Science.gov (United States)

Wang, Yuangang; Tang, Haifeng; Zhang, Yun; Li, Juan; Li, Bo; Gao, Zhenhui; Wang, Xiaoyang; Cheng, Guang; Fei, Zhou

2013-11-01

Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors. Saponin B, a novel compound isolated from the medicinal plant, Anemone taipaiensis, has been found to have a strong time- and dose-dependent cytostatic effect on human glioma cells and to suppress the growth of U87MG GBM cells. In this study, we investigated whether saponin B induces the apoptosis of glioblastoma cells and examined the underlying mechanism(s) of action of saponin B. Saponin B significantly suppressed U87MG cell proliferation. Flow cytometric analysis of DNA in the U87MG cells confirmed that saponin B blocked the cell cycle at the S phase. Furthermore, treatment of the U87MG cells with saponin B induced chromatin condensation and led to the formation of apoptotic bodies, as observed under a fluorescence microscope, and Annexin V/PI assay further suggested that phosphatidylserine (PS) externalization was apparent at higher drug concentrations. Treatment with saponin B activated the receptor-mediated pathway of apoptosis, as western blot analysis revealed the activation of Fas-l. Saponin B increased the Bax and caspase-3 ratio and decreased the protein expression of Bcl-2. The results from the present study demonstrate that the novel compound, saponin B, effectively induces the apoptosis of GBM cells and inhibits glioma cell growth and survival. Therefore, saponin B may be a potential candidate for the development of novel cancer therapeutics with antitumor activity against gliomas.

Late biological effects from internal and external exposure

International Nuclear Information System (INIS)

Adams, W.H.

1985-01-01

Information on late biological effects of radiation was obtained from the long-term medical followup of a small population of Marshallese accidentally exposed to radioactive fallout from a thermonuclear test in 1954. Endocrine data are compatible with a sequence of nonstochastic radiation effects. The ingestion of radioisotopes of iodine produced clinical thyroid hypofunction in children, biochemical evidence of thyroid dysfunction in some adults, thyroid adenomatous module formation, and, as a possible indirect effect of thyroid damage, at least two cases of pituitary adenoma. In contrast, the only evidence of a stochastic effect has been a real increase in thyroid cancers among the more highly exposed people of Rongelap, none of whom have evidence of residual disease. While three nonthyroidal cancers which are known to be inducible in humans by external irradiation have been documented in the exposed population, three similar cancers have occurred in an unexposed comparison population of Marshallese. Nonstochastic effects of radiation exposure may be common but subtle. In the Marshallese experience the morbidity of delayed nonstochastic effects far exceeds that of the stochastic. 20 refs., 5 figs., 1 tab

Generation of Oligodendrogenic Spinal Neural Progenitor Cells From Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Khazaei, Mohamad; Ahuja, Christopher S; Fehlings, Michael G

2017-08-14

This unit describes protocols for the efficient generation of oligodendrogenic neural progenitor cells (o-NPCs) from human induced pluripotent stem cells (hiPSCs). Specifically, detailed methods are provided for the maintenance and differentiation of hiPSCs, human induced pluripotent stem cell-derived neural progenitor cells (hiPS-NPCs), and human induced pluripotent stem cell-oligodendrogenic neural progenitor cells (hiPSC-o-NPCs) with the final products being suitable for in vitro experimentation or in vivo transplantation. Throughout, cell exposure to growth factors and patterning morphogens has been optimized for both concentration and timing, based on the literature and empirical experience, resulting in a robust and highly efficient protocol. Using this derivation procedure, it is possible to obtain millions of oligodendrogenic-NPCs within 40 days of initial cell plating which is substantially shorter than other protocols for similar cell types. This protocol has also been optimized to use translationally relevant human iPSCs as the parent cell line. The resultant cells have been extensively characterized both in vitro and in vivo and express key markers of an oligodendrogenic lineage. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley and Sons, Inc.

Human induced pluripotent stem cells: A disruptive innovation.

Science.gov (United States)

De Vos, J; Bouckenheimer, J; Sansac, C; Lemaître, J-M; Assou, S

2016-01-01

This year (2016) will mark the 10th anniversary of the discovery of induced pluripotent stem cells (iPSCs). The finding that the transient expression of four transcription factors can radically remodel the epigenome, transcriptome and metabolome of differentiated cells and reprogram them into pluripotent stem cells has been a major and groundbreaking technological innovation. In this review, we discuss the major applications of this technology that we have grouped in nine categories: a model to study cell fate control; a model to study pluripotency; a model to study human development; a model to study human tissue and organ physiology; a model to study genetic diseases in a dish; a tool for cell rejuvenation; a source of cells for drug screening; a source of cells for regenerative medicine; a tool for the production of human organs in animals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Bisphenol A and Bisphenol S Induce Distinct Transcriptional Profiles in Differentiating Human Primary Preadipocytes.

Directory of Open Access Journals (Sweden)

Jonathan G Boucher

Full Text Available Bisphenol S (BPS is increasingly used as a replacement plasticizer for bisphenol A (BPA but its effects on human health have not been thoroughly examined. Recent evidence indicates that both BPA and BPS induce adipogenesis, although the mechanisms leading to this effect are unclear. In an effort to identify common and distinct mechanisms of action in inducing adipogenesis, transcriptional profiles of differentiating human preadipocytes exposed to BPA or BPS were compared. Human subcutaneous primary preadipocytes were differentiated in the presence of either 25 μM BPA or BPS for 2 and 4 days. Poly-A RNA-sequencing was used to identify differentially expressed genes (DEGs. Functional analysis of DEGs was undertaken in Ingenuity Pathway Analysis. BPA-treatment resulted in 472 and 176 DEGs on days 2 and 4, respectively, affecting pathways such as liver X receptor (LXR/retinoid X receptor (RXR activation, hepatic fibrosis and cholestasis. BPS-treatment resulted in 195 and 51 DEGs on days 2 and 4, respectively, revealing enrichment of genes associated with adipogenesis and lipid metabolism including the adipogenesis pathway and cholesterol biosynthesis. Interestingly, the transcription repressor N-CoR was identified as a negative upstream regulator in both BPA- and BPS-treated cells. This study presents the first comparison of BPA- and BPS-induced transcriptional profiles in human differentiating preadipocytes. While we previously showed that BPA and BPS both induce adipogenesis, the results from this study show that BPS affects adipose specific transcriptional changes earlier than BPA, and alters the expression of genes specifically related to adipogenesis and lipid metabolism. The findings provide insight into potential BPS and BPA-mediated mechanisms of action in inducing adipogenesis in human primary preadipocytes.

External costs related to power production technologies. ExternE national implementation for Denmark

International Nuclear Information System (INIS)

Schleisner, L.; Sieverts Nielsen, P.

1997-12-01

The objective of the ExternE National Implementation project has been to establish a comprehensive and comparable set of data on externalities of power generation for all EU member states and Norway. The tasks include the application of the ExternE methodology to the most important fuel cycles for each country as well as to update the already existing results; to aggregate these site- and technology-specific results to more general figures. The current report covers the results of the national implementation for Denmark. Three different fuel cycles have been chosen as case studies. These are fuel cycles for an offshore wind farm and a wind farm on land, a decentralised CHP plant based on natural gas and a decentralised CHP plant based on biogas. The report covers all the details of the application of the methodology to these fuel cycles aggregation to a national level. (au) EU-JOULE 3. 59 tabs., 25 ills., 61 refs

External costs related to power production technologies. ExternE national implementation for Denmark

Energy Technology Data Exchange (ETDEWEB)

Schleisner, L; Sieverts Nielsen, P

1997-12-01

The objective of the ExternE National Implementation project has been to establish a comprehensive and comparable set of data on externalities of power generation for all EU member states and Norway. The tasks include the application of the ExternE methodology to the most important fuel cycles for each country as well as to update the already existing results; to aggregate these site- and technology-specific results to more general figures. The current report covers the results of the national implementation for Denmark. Three different fuel cycles have been chosen as case studies. These are fuel cycles for an offshore wind farm and a wind farm on land, a decentralised CHP plant based on natural gas and a decentralised CHP plant based on biogas. The report covers all the details of the application of the methodology to these fuel cycles aggregation to a national level. (au) EU-JOULE 3. 59 tabs., 25 ills., 61 refs.

Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells.

Science.gov (United States)

Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

2016-04-26

Progesterone plays critical roles in maintaining a successful pregnancy at the early embryonic stage. Human chorionic gonadotropin (hCG) rapidly induces amphiregulin (AREG) expression. However, it remains unknown whether AREG mediates hCG-induced progesterone production. Thus, the objective of this study was to investigate the role of AREG in hCG-induced progesterone production and the underlying molecular mechanism in human granulosa cells; primary cells were used as the experimental model. We demonstrated that the inhibition of EGFR and the knockdown of AREG abolished hCG-induced steroidogenic acute regulatory protein (StAR) expression and progesterone production. Importantly, follicular fluid AREG levels were positively correlated with progesterone levels in the follicular fluid and serum. Treatment with AREG increased StAR expression and progesterone production, and these stimulatory effects were abolished by EGFR inhibition. Moreover, activation of ERK1/2, but not PI3K/Akt, signaling was required for the AREG-induced up-regulation of StAR expression and progesterone production. Our results demonstrate that AREG mediates hCG-induced StAR expression and progesterone production in human granulosa cells, providing novel evidence for the role of AREG in the regulation of steroidogenesis.

Environmental externalities related to power production on biogas and natural gas based on the EU ExternE methodology

DEFF Research Database (Denmark)

Nielsen, Per Sieverts; Ibsen, Liselotte Schleisner

1998-01-01

This paper assesses the environmental impacts and external costs from selected electricity generation systems in Denmark. The assessment is carried out as part of the ExternE National Implementation, which is the second phase of the ExternE project and involves case studies from all Western...... European countries. The project use a “bottom-up” methodology to evaluate the external costs associated with a wide range of different fuel cycles. The project has identified priority impacts, where most are impacts from air emissions. Externalities due to atmospheric emissions are calculated through...

An external standard method for quantification of human cytomegalovirus by PCR

International Nuclear Information System (INIS)

Rongsen, Shen; Liren, Ma; Fengqi, Zhou; Qingliang, Luo

1997-01-01

An external standard method for PCR quantification of HCMV was reported. [α- 32 P]dATP was used as a tracer. 32 P-labelled specific amplification product was separated by agarose gel electrophoresis. A gel piece containing the specific product band was excised and counted in a plastic scintillation counter. Distribution of [α- 32 P]dATP in the electrophoretic gel plate and effect of separation between the 32 P-labelled specific product and free [α- 32 P]dATP were observed. A standard curve for quantification of HCMV by PCR was established and detective results of quality control templets were presented. The external standard method and the electrophoresis separation effect were appraised. The results showed that the method could be used for relative quantification of HCMV. (author)

The protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis

Directory of Open Access Journals (Sweden)

Xue - Fang Chen

2013-06-01

Full Text Available AIM: To investigate the protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis. METHODS:Subcultured human lens epithelial cell line, ultraviolet induced cell apoptosis, 20μmol/L resveratrol pretreated cell, the indicators change was observed: rate of apoptosis was detected by flow cytometry and apoptosis-related factors of caspses-3 and caspase-9 were detected by colorimetric detection, ultrastructure changes were observed under transmission electron microscope. RESULTS: Flow cytometry instrument testing found that resveratrol can suppress the apoptosis induced by ultraviolet irradiation, caspses-3 and caspase-9 content in positive control group were significantly higher than that of the negative control group at the same time period, the difference was statistically significant(P<0.05; caspses-3 and caspase-9 content in experimental group were lower than that in the positive control group at the same time, the difference was statistically significant(P<0.05. In addition, the damage of human lens epithelial cells was alleviated with the incubation time of resveratrol elongated. CONCLUSION:Resveratrol may inhibit ultraviolet-induced apoptosis of human lens epithelial cells, it has preventive function against radioactive cataract, and it can provide reliable evidence for pursuing effective medicine to prevent and treat cataract.

Ketamine Causes Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Neurons

Science.gov (United States)

Ito, Hiroyuki; Uchida, Tokujiro; Makita, Koshi

2015-01-01

Purpose Ketamine toxicity has been demonstrated in nonhuman mammalian neurons. To study the toxic effect of ketamine on human neurons, an experimental model of cultured neurons from human induced pluripotent stem cells (iPSCs) was examined, and the mechanism of its toxicity was investigated. Methods Human iPSC-derived dopaminergic neurons were treated with 0, 20, 100 or 500 μM ketamine for 6 and 24 h. Ketamine toxicity was evaluated by quantification of caspase 3/7 activity, reactive oxygen species (ROS) production, mitochondrial membrane potential, ATP concentration, neurotransmitter reuptake activity and NADH/NAD+ ratio. Mitochondrial morphological change was analyzed by transmission electron microscopy and confocal microscopy. Results Twenty-four-hour exposure of iPSC-derived neurons to 500 μM ketamine resulted in a 40% increase in caspase 3/7 activity (P ketamine (100 μM) decreased the ATP level (22%, P ketamine concentration, which suggests that mitochondrial dysfunction preceded ROS generation and caspase activation. Conclusions We established an in vitro model for assessing the neurotoxicity of ketamine in iPSC-derived neurons. The present data indicate that the initial mitochondrial dysfunction and autophagy may be related to its inhibitory effect on the mitochondrial electron transport system, which underlies ketamine-induced neural toxicity. Higher ketamine concentration can induce ROS generation and apoptosis in human neurons. PMID:26020236

Arsenite-induced autophagy is associated with proteotoxicity in human lymphoblastoid cells

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Bolt, Alicia M.; Zhao, Fei; Pacheco, Samantha; Klimecki, Walter T., E-mail: klimecki@pharmacy.arizona.edu

2012-10-15

Epidemiological studies of arsenic-exposed populations have provided evidence that arsenic exposure in humans is associated with immunosuppression. Previously, we have reported that arsenite-induced toxicity is associated with the induction of autophagy in human lymphoblastoid cell lines (LCL). Autophagy is a cellular process that functions in the degradation of damaged cellular components, including protein aggregates formed by misfolded or damaged proteins. Accumulation of misfolded or damaged proteins in the endoplasmic reticulum (ER) lumen causes ER stress and activates the unfolded protein response (UPR). In an effort to investigate the mechanism of autophagy induction by arsenite in the LCL model, we examined the potential contribution of ER stress and activation of the UPR. LCL exposed to sodium arsenite for 8-days induced expression of UPR-activated genes, including CHOP and GRP78, at the RNA and the protein level. Evidence for activation of the three arms of the UPR was observed. The arsenite-induced activation of the UPR was associated with an accumulation of protein aggregates containing p62 and LC3, proteins with established roles in the sequestration and autophagic clearance of protein aggregates. Taken together, these data provide evidence that arsenite-induced autophagy is associated with the generation of ER stress, activation of the UPR, and formation of protein aggregates that may be targeted to the lysosome for degradation. -- Highlights: ► Arsenite induces endoplasmic reticulum stress and the unfolded protein response. ► Arsenite induces the formation of protein aggregates that contain p62 and LC3-II. ► Time-course data suggests that arsenite-induced autophagy precedes ER stress.

Internal phase transition induced by external forces in Finsler geometric model for membranes

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Koibuchi, Hiroshi; Shobukhov, Andrey

2016-10-01

In this paper, we numerically study an anisotropic shape transformation of membranes under external forces for two-dimensional triangulated surfaces on the basis of Finsler geometry. The Finsler metric is defined by using a vector field, which is the tangential component of a three-dimensional unit vector σ corresponding to the tilt or some external macromolecules on the surface of disk topology. The sigma model Hamiltonian is assumed for the tangential component of σ with the interaction coefficient λ. For large (small) λ, the surface becomes oblong (collapsed) at relatively small bending rigidity. For the intermediate λ, the surface becomes planar. Conversely, fixing the surface with the boundary of area A or with the two-point boundaries of distance L, we find that the variable σ changes from random to aligned state with increasing of A or L for the intermediate region of λ. This implies that an internal phase transition for σ is triggered not only by the thermal fluctuations, but also by external mechanical forces. We also find that the frame (string) tension shows the expected scaling behavior with respect to A/N (L/N) at the intermediate region of A (L) where the σ configuration changes between the disordered and ordered phases. Moreover, we find that the string tension γ at sufficiently large λ is considerably smaller than that at small λ. This phenomenon resembles the so-called soft-elasticity in the liquid crystal elastomer, which is deformed by small external tensile forces.

Human Induced Pluripotent Stem Cell-Derived Macrophages for Unraveling Human Macrophage Biology.

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Zhang, Hanrui; Reilly, Muredach P

2017-11-01

Despite a substantial appreciation for the critical role of macrophages in cardiometabolic diseases, understanding of human macrophage biology has been hampered by the lack of reliable and scalable models for cellular and genetic studies. Human induced pluripotent stem cell (iPSC)-derived macrophages (IPSDM), as an unlimited source of subject genotype-specific cells, will undoubtedly play an important role in advancing our understanding of the role of macrophages in human diseases. In this review, we summarize current literature in the differentiation and characterization of IPSDM at phenotypic, functional, and transcriptomic levels. We emphasize the progress in differentiating iPSC to tissue resident macrophages, and in understanding the ontogeny of in vitro differentiated IPSDM that resembles primitive hematopoiesis, rather than adult definitive hematopoiesis. We review the application of IPSDM in modeling both Mendelian genetic disorders and host-pathogen interactions. Finally, we highlighted the potential areas of research using IPSDM in functional validation of coronary artery disease loci in genome-wide association studies, functional genomic analyses, drug testing, and cell therapeutics in cardiovascular diseases. © 2017 American Heart Association, Inc.

Low-wealth Entrepreneurs and Access to External Financing

DEFF Research Database (Denmark)

Frid, Casey J.; Wyman, David M.; Gartner, Bill

2016-01-01

Purpose: -The purpose of this paper is to explore the relationship between low-wealth business founders in the USA and external startup funding. Specifically, the authors test whether a founders’ low personal net worth is correlated with a lower probability of acquiring funding from outside sources...... demonstrates the importance of personal wealth as a factor in acquiring external startup financing compared to human capital, industry, or personal characteristics. Social implications: -If the ability to acquire external funding is significantly constrained, the quality of the opportunity and the skill...... endowments at the outset. Originality/value: -Unlike prior studies, the data used are not subject to survivor bias or an underrepresentation of self-employment. The statistical model jointly estimates acquisition of financing and the amount received. This resolves selection and censoring problems. Finally...

Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.

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Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm

2015-01-01

Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential. Copyright© Ferrata Storti Foundation.

Interaction of the superconducting domains induced by external electric field with electromagnetic waves

International Nuclear Information System (INIS)

Shapiro, B.Y.

1992-01-01

The behavior of a superconductor in time-independent electric field perpendicular to the surface and in the external electromagnetic wave is theoretically investigated. A new type of the resonance interaction between superconducting domains localized along the magnetic field (if the superconducting phase transition takes place in the external magnetic field perpendicular to the surface) and electromagnetic waves is predicted. The surface impedance of the superconductor with domains is calculated. It is shown that the real part of the impedance has a saturation if the skin length equals the domain size. (orig.)

Inhibitory Effect of Endostar on Specific Angiogenesis Induced by Human Hepatocellular Carcinoma

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Qing Ye

2015-01-01

Full Text Available To investigate the effect of endostar on specific angiogenesis induced by human hepatocellular carcinoma, this research systematically elucidated the inhibitory effect on HepG2-induced angiogenesis by endostar from 50 ng/mL to 50000 ng/mL. We employed fluorescence quantitative Boyden chamber analysis, wound-healing assay, flow cytometry examination using a coculture system, quantitative analysis of tube formation, and in vivo Matrigel plug assay induced by HCC conditioned media (HCM and HepG2 compared with normal hepatocyte conditioned media (NCM and L02. Then, we found that endostar as a tumor angiogenesis inhibitor could potently inhibit human umbilical vein endothelial cell (HUVEC migration in response to HCM after four- to six-hour action, inhibit HCM-induced HUVEC migration to the lesion part in a dose-dependent manner between 50 ng/mL and 5000 ng/mL at 24 hours, and reduce HUVEC proliferation in a dose-dependent fashion. Endostar inhibited HepG2-induced tube formation of HUVECs which peaked at 50 ng/mL. In vivo Matrigel plug formation was also significantly reduced by endostar in HepG2 inducing system rather than in L02 inducing system. It could be concluded that, at cell level, endostar inhibited the angiogenesis-related biological behaviors of HUVEC in response to HCC, including migration, adhesion proliferation, and tube formation. At animal level, endostar inhibited the angiogenesis in response to HCC in Matrigel matrix.

Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells.

Science.gov (United States)

Wang, Xin; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Luo, Jia

2017-04-01

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Improvement in the performance of external quality assessment in Korean HIV clinical laboratories using unrecalcified human plasma.

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Wang, Jin-Sook; Kee, Mee-Kyung; Choi, Byeong-Sun; Kim, Chan-Wha; Kim, Hyon-Suk; Kim, Sung Soon

2012-01-01

The external quality assessment schemes (EQAS) organizer provides a suitable program to monitor and improve the quality of human immunodeficiency virus (HIV) testing laboratories with EQAS panels prepared under various conditions. The aim of the current study was to investigate the effects of human plasma samples on the EQAS results of HIV obtained from hospital-based clinical laboratories. From 2007 to 2009, HIV EQAS panels consisted of four to six samples that consisted of undiluted positive and negative samples and were provided to laboratories twice per year. Up until the first half EQAS in 2008, EQAS panel materials were obtained by converting acid citrate dextrose treated plasma to serum via chemical treatment with CaCl2. Beginning with the second EQAS in 2008, all materials were prepared without the defibrination process. Approximately 300 HIV clinical laboratories participated in this program. The overall performance of clinical laboratories was shown to be improved when using unrecalcified plasma panels compared with recalcified panels. Significant differences were observed in EIA analyses of plasma for both positive (plaboratories.

Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

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Hayato Fukusumi

2016-01-01

Full Text Available Human neural progenitor cells (hNPCs have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi. Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

Photobiological implications of melanin photoprotection after UVB-induced tanning of human skin but not UVA-induced tanning.

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Coelho, Sergio G; Yin, Lanlan; Smuda, Christoph; Mahns, Andre; Kolbe, Ludger; Hearing, Vincent J

2015-03-01

Repetitive suberythemal UVA and/or UVB exposures were used to generate comparable UV-induced tans in human skin over the course of 2 weeks. To evaluate the potential photoprotective values of those UVA- and/or UVB- induced tans and to avoid the confounding issue of residual UV-induced DNA damage, we waited 1 week before challenging those areas with a 1.5 MED of UVA+UVB after which we measure DNA damage. The results show that the type of UV used to induce skin pigmentation affects the redistribution of melanin in the skin and/or de novo melanin synthesis. The UVA-induced tans failed to even provide a minimal SPF of 1.5, which suggests that producing a tan with UVA-rich sunlamps prior to a holiday or vacation is completely counterproductive. Published 2014. This article is a US Government work and is in the public domain in the USA.

An analysis of critical heat flux on the external surface of the reactor vessel lower head

International Nuclear Information System (INIS)

Yang, Soo Hyung; Baek, Won Pil; Chang, Soon Heung

1999-01-01

CHF (Critical heat flux) on the external surface of the reactor vessel lower head is major key in the evaluation on the feasibility of IVR-EVC (In-Vessel Retention through External Vessel Cooling) concept. To identify the CHF on the external surface, considerable works have been performed. Through the review on the previous works related to the CHF on the external surface, liquid subcooling, induced flow along the external surface, ICI (In-Core Instrument) nozzle and minimum gap are identified as major parameters. According to the present analysis, the effects of the ICI nozzle and minimum gap on CHF are pronounced at the upstream of test vessel: on the other hand, the induced flow considerably affects the CHF at downstream of test vessel. In addition, the subcooling effect is shown at all of test vessel, and decreases with the increase in the elevation of test vessel. In the real application of the IVR-EVC concept, vertical position is known as a limiting position, at which thermal margin is the minimum. So, it is very important to precisely predict the CHF at vertical position in a viewpoint of gaining more thermal margins. However, the effects of the liquid subcooling and induced flow do not seem to be adequately included in the CHF correlations suggested by previous works, especially at the downstream positions

Molecular mechanism implicated in Pemetrexed-induced apoptosis in human melanoma cells

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Buqué Aitziber

2012-04-01

Full Text Available Abstract Background Metastatic melanoma is a lethal skin cancer and its incidence is rising every year. It represents a challenge for oncologist, as the current treatment options are non-curative in the majority of cases; therefore, the effort to find and/or develop novel compounds is mandatory. Pemetrexed (Alimta®, MTA is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. It is currently used in the treatment of mesothelioma and non-small cell lung cancer (NSCLC, and has shown clinical activity in other tumors such as breast, colorectal, bladder, cervical, gastric and pancreatic cancer. However, its effect in human melanoma has not been studied yet. Results In the current work we studied the effect of MTA on four human melanoma cell lines A375, Hs294T, HT144 and MeWo and in two NSCLC cell lines H1299 and Calu-3. We have found that MTA induces DNA damage, S-phase cell cycle arrest, and caspase- dependent and –independent apoptosis. We show that an increment of the intracellular reactive oxygen species (ROS and p53 is required for MTA-induced cytotoxicity by utilizing N-Acetyl-L-Cysteine (NAC to blockage of ROS and p53-defective H1299 NSCLC cell line. Pretreatment of melanoma cells with NAC significantly decreased the DNA damage, p53 up-regulation and cytotoxic effect of MTA. MTA was able to induce p53 expression leading to up-regulation of p53-dependent genes Mcl-1 and PIDD, followed by a postranscriptional regulation of Mcl-1 improving apoptosis. Conclusions We found that MTA induced DNA damage and mitochondrial-mediated apoptosis in human melanoma cells in vitro and that the associated apoptosis was both caspase-dependent and –independent and p53-mediated. Our data suggest that MTA may be of therapeutic relevance for the future treatment of human malignant melanoma.

External noise distinguishes attention mechanisms.

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Lu, Z L; Dosher, B A

1998-05-01

We developed and tested a powerful method for identifying and characterizing the effect of attention on performance in visual tasks as due to signal enhancement, distractor exclusion, or internal noise suppression. Based on a noisy Perceptual Template Model (PTM) of a human observer, the method adds increasing amounts of external noise (white gaussian random noise) to the visual stimulus and observes the effect on performance of a perceptual task for attended and unattended stimuli. The three mechanisms of attention yield three "signature" patterns of performance. The general framework for characterizing the mechanisms of attention is used here to investigate the attentional mechanisms in a concurrent location-cued orientation discrimination task. Test stimuli--Gabor patches tilted slightly to the right or left--always appeared on both the left and the right of fixation, and varied independently. Observers were cued on each trial to attend to the left, the right, or evenly to both stimuli, and decide the direction of tilt of both test stimuli. For eight levels of added external noise and three attention conditions (attended, unattended, and equal), subjects' contrast threshold levels were determined. At low levels of external noise, attention affected threshold contrast: threshold contrasts for non-attended stimuli were systematically higher than for equal attention stimuli, which were, in turn, higher than for attended stimuli. Specifically, when the rms contrast of the external noise is below 10%, there is a consistent 17% elevation of contrast threshold from attended to unattended condition across all three subjects. For higher levels of external noise, attention conditions did not affect threshold contrast values at all. These strong results are characteristic of a signal enhancement, or equivalently, an internal additive noise reduction mechanism of attention.

Mechanisms of palmitate-induced cell death in human osteoblasts

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Gunaratnam, Krishanthi; Vidal, Christopher; Boadle, Ross; Thekkedam, Chris; Duque, Gustavo

2013-01-01

Summary Lipotoxicity is an overload of lipids in non-adipose tissues that affects function and induces cell death. Lipotoxicity has been demonstrated in bone cells in vitro using osteoblasts and adipocytes in coculture. In this condition, lipotoxicity was induced by high levels of saturated fatty acids (mostly palmitate) secreted by cultured adipocytes acting in a paracrine manner. In the present study, we aimed to identify the underlying mechanisms of lipotoxicity in human osteoblasts. Palmitate induced autophagy in cultured osteoblasts, which was preceded by the activation of autophagosomes that surround palmitate droplets. Palmitate also induced apoptosis though the activation of the Fas/Jun kinase (JNK) apoptotic pathway. In addition, osteoblasts could be protected from lipotoxicity by inhibiting autophagy with the phosphoinositide kinase inhibitor 3-methyladenine or by inhibiting apoptosis with the JNK inhibitor SP600125. In summary, we have identified two major molecular mechanisms of lipotoxicity in osteoblasts and in doing so we have identified a new potential therapeutic approach to prevent osteoblast dysfunction and death, which are common features of age-related bone loss and osteoporosis. PMID:24285710

Chill-inducing music enhances altruism in humans

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Hajime eFukui

2014-10-01

Full Text Available Music is a universal feature of human cultures, and it has both fascinated and troubled many researchers. In this paper we show through the Dictator Game that an individual’s listening to preferred chill-inducing music may promote altruistic behavior that extends beyond the bounds of kin selection or reciprocal altruism. Participants were 22 undergraduate and postgraduate students who were divided into two groups, the In-group (IG and the Out-group (OG, and they acted as dictators. The dictators listened to their own preferred chill-inducing music, to music they disliked, or to silence, and then played the Dictator Game. In this hypothetical experiment, the dictators were given real money (which they did not keep and were asked to distribute it to the recipients, who were presented as stylized images of men and women displayed on a computer screen. The dictators played the Dictator Game both before and after listening to the music. Both male and female dictators gave more money after listening to their preferred music and less after listening to the music they disliked, whereas silence had no effect on the allocated amounts. The group to which the recipient belonged did not influence these trends. The results suggest that listening to preferred chill-inducing music promotes altruistic behavior.

Chill-inducing music enhances altruism in humans.

Science.gov (United States)

Fukui, Hajime; Toyoshima, Kumiko

2014-01-01

Music is a universal feature of human cultures, and it has both fascinated and troubled many researchers. In this paper we show through the dictator game (DG) that an individual's listening to preferred "chill-inducing" music may promote altruistic behavior that extends beyond the bounds of kin selection or reciprocal altruism. Participants were 22 undergraduate and postgraduate students who were divided into two groups, the in-group and the out-group, and they acted as dictators. The dictators listened to their own preferred "chill-inducing" music, to music they disliked, or to silence, and then played the DG. In this hypothetical experiment, the dictators were given real money (which they did not keep) and were asked to distribute it to the recipients, who were presented as stylized images of men and women displayed on a computer screen. The dictators played the DG both before and after listening to the music. Both male and female dictators gave more money after listening to their preferred music and less after listening to the music they disliked, whereas silence had no effect on the allocated amounts. The group to which the recipient belonged did not influence these trends. The results suggest that listening to preferred "chill-inducing" music promotes altruistic behavior.

Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

International Nuclear Information System (INIS)

Su, Chen-Ming; Wang, Shih-Wei; Lee, Tzong-Huei; Tzeng, Wen-Pei; Hsiao, Che-Jen; Liu, Shih-Chia; Tang, Chih-Hsin

2013-01-01

Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress is involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.

Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells

Energy Technology Data Exchange (ETDEWEB)

Su, Chen-Ming [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Wang, Shih-Wei [Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (China); Lee, Tzong-Huei [Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan (China); Tzeng, Wen-Pei [Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan (China); Hsiao, Che-Jen [School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Liu, Shih-Chia [Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan (China); Tang, Chih-Hsin, E-mail: chtang@mail.cmu.edu.tw [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan (China)

2013-10-15

Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress. - Highlights: • Trichodermin induces chondrosarcoma apoptosis. • ER stress is involved in trichodermin-induced cell death. • Trichodermin induces chondrosarcoma death in vivo.

Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells

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Mohamad Hafizi Abu Bakar

2015-05-01

Full Text Available Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.

Gemcitabine inhibits proliferation and induces apoptosis in human pancreatic cancer PANC-1 cells.

Science.gov (United States)

Yong-Xian, Gui; Xiao-Huan, Li; Fan, Zhang; Guo-Fang, Tian

2016-10-01

The aim of the study is to investigate the underlying molecular mechanisms by which gemcitabine (gem) inhibits proliferation and induces apoptosis in human pancreatic cancer PANC-1 cells in vitro. After PANC-1 cells had been treated by indicated concentration (0, 5, and 25 mg/L) of gem for 48 h, cell proliferation was evaluated by 3'-(4, 5 dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay; cell morphology was observed by transmission electron microscopy; Expression of c-IAP2 and Bcl-2 proteins was analyzed by Western blot; the activity of caspase-3 and -9 was detected by spectrophotometry. Gem significantly inhibited cell proliferation and could induce apoptosis of human pancreatic cancer PANC-1 cells, with a dose-dependent manner. Western blot analysis showed that gem significantly reduced c-IAP2 and Bcl-2 proteins expression level (P PANC-1 cells. Gem could induce apoptosis of human pancreatic cancer PANC-1 cells, probably through downregulating c-IAP2 and Bcl-2 expression levels, and at the same time activating caspase-3 and -9.

Effects of Er, Cr:YSGG laser irradiation on external adaptation of restorations in caries-affected cavities

International Nuclear Information System (INIS)

Tonetto, Mateus Rodrigues; Saad, José Roberto Cury; Campos, Edson Alves de; Neto, Sizenando de Toledo Porto; De Andrade, Marcelo Ferrarezi; Bandéca, Matheus Coelho; Borges, Alvaro Henrique; Pinto, Shelon Cristina Souza

2013-01-01

This study evaluated the effect of Er,Cr:YSGG laser irradiation on the external adaptation of composite resin restorations in caries-affected cavities. Mixed class V cavity preparations were performed in 36 intact human third molars, in half of which caries was artificially induced. Both healthy and carious dentin were etched with 35% phosphoric acid (Ultradent Products Inc., South Jordan, Utah, USA), and the teeth were divided into three groups, i.e., (a) untreated etched dentin, (b) application of the Er, Cr:YSGG laser and (c) use of chlorhexidine as an adjunct in the bonding process. Restorations were fabricated with Z350 XT FiltekTM composite resin (3M ESPE) and subsequently the specimens were subjected to thermocycling to simulate artificial ageing. Quantitative analysis of external adaptation was performed by scanning electron microscopy in both healthy and affected dentin using epoxy resin replicas. It was concluded that the application of laser and chlorhexidine did not affect the percentages of marginal adaptation of class V restorations. Furthermore, thermocycling may influence adaptation values. (letter)

Differentiation of human-induced pluripotent stem cells into insulin-producing clusters.

Science.gov (United States)

Shaer, Anahita; Azarpira, Negar; Vahdati, Akbar; Karimi, Mohammad Hosein; Shariati, Mehrdad

2015-02-01

In diabetes mellitus type 1, beta cells are mostly destroyed; while in diabetes mellitus type 2, beta cells are reduced by 40% to 60%. We hope that soon, stem cells can be used in diabetes therapy via pancreatic beta cell replacement. Induced pluripotent stem cells are a kind of stem cell taken from an adult somatic cell by "stimulating" certain genes. These induced pluripotent stem cells may be a promising source of cell therapy. This study sought to produce isletlike clusters of insulin-producing cells taken from induced pluripotent stem cells. A human-induced pluripotent stem cell line was induced into isletlike clusters via a 4-step protocol, by adding insulin, transferrin, and selenium (ITS), N2, B27, fibroblast growth factor, and nicotinamide. During differentiation, expression of pancreatic β-cell genes was evaluated by reverse transcriptase-polymerase chain reaction; the morphologic changes of induced pluripotent stem cells toward isletlike clusters were observed by a light microscope. Dithizone staining was used to stain these isletlike clusters. Insulin produced by these clusters was evaluated by radio immunosorbent assay, and the secretion capacity was analyzed with a glucose challenge test. Differentiation was evaluated by analyzing the morphology, dithizone staining, real-time quantitative polymerase chain reaction, and immunocytochemistry. Gene expression of insulin, glucagon, PDX1, NGN3, PAX4, PAX6, NKX6.1, KIR6.2, and GLUT2 were documented by analyzing real-time quantitative polymerase chain reaction. Dithizone-stained cellular clusters were observed after 23 days. The isletlike clusters significantly produced insulin. The isletlike clusters could increase insulin secretion after a glucose challenge test. This work provides a model for studying the differentiation of human-induced pluripotent stem cells to insulin-producing cells.

Generation of human induced pluripotent stem cell lines from human dermal fibroblasts using a non-integration system

Directory of Open Access Journals (Sweden)

Kyung-Ok Uhm

2017-05-01

Full Text Available We generated human induced pluripotent stem cells (hiPSCs from dermal fibroblasts using a Sendai virus (SeV-based gene delivery method. The generated hiPSC line, KSCBi002-A, has a normal karyotype (46,XY. The pluripotency and differentiation capacity were characterized by comparison with those of a human embryonic stem cell line. This cell line is registered and available from the National Stem Cell Bank, Korea National Institute of Health.

Directed motion generated by heat bath nonlinearly driven by external noise

International Nuclear Information System (INIS)

Chaudhuri, J Ray; Barik, D; Banik, S K

2007-01-01

Based on the heat bath system approach where the bath is nonlinearly modulated by an external Gaussian random force, we propose a new microscopic model to study directed motion in the overdamped limit for a nonequilibrium open system. Making use of the coupling between the heat bath and the external modulation as a small perturbation, we construct a Langevin equation with multiplicative noise- and space-dependent dissipation and the corresponding Fokker-Planck-Smoluchowski equation in the overdamped limit. We examine the thermodynamic consistency condition and explore the possibility of observing a phase-induced current as a consequence of state-dependent diffusion and, necessarily, nonlinear driving of the heat bath by the external noise

Directed motion generated by heat bath nonlinearly driven by external noise

Energy Technology Data Exchange (ETDEWEB)

Chaudhuri, J Ray [Department of Physics, Katwa College, Katwa, Burdwan 713 130, West Bengal (India); Barik, D [Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032 (India); Banik, S K [Department of Physics, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0435 (United States)

2007-12-07

Based on the heat bath system approach where the bath is nonlinearly modulated by an external Gaussian random force, we propose a new microscopic model to study directed motion in the overdamped limit for a nonequilibrium open system. Making use of the coupling between the heat bath and the external modulation as a small perturbation, we construct a Langevin equation with multiplicative noise- and space-dependent dissipation and the corresponding Fokker-Planck-Smoluchowski equation in the overdamped limit. We examine the thermodynamic consistency condition and explore the possibility of observing a phase-induced current as a consequence of state-dependent diffusion and, necessarily, nonlinear driving of the heat bath by the external noise.

PHA-induced cytotoxicity of human lymphocytes against adherent hela-cells

NARCIS (Netherlands)

Huges-Law, G.; de Gast, G. C.; The, T. Hauw

The conditions for a phytohaemagglutinin(PHA)-induced cytotoxicity test of human peripheral blood lymphocytes were investigated. [3H]thymidine prelabelled HeLa cells were used as target cells. Stimulation with 10 μl PHA/ml during 24 h gave the best measure of lymphocyte cytotoxic capacity.

RECOMBINANT HUMAN INTERLEUKIN-6 INDUCES A RAPID AND REVERSIBLE ANEMIA IN CANCER-PATIENTS

NARCIS (Netherlands)

NIEKEN, J; MULDER, NH; VELLENGA, E; LIMBURG, PC; PIERS, DA; DEVRIES, EGE

1995-01-01

Initial studies have shown that recombinant human interleukin-6 (rhIL-6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II

Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice

International Nuclear Information System (INIS)

Giavazzi, R.; Garofalo, A.; Bani, M.R.; Abbate, M.; Ghezzi, P.; Boraschi, D.; Mantovani, A.; Dejana, E.

1990-01-01

This study has examined the effect of the cytokine interleukin 1 (IL-1) on metastasis formation by the human melanoma A375M in nude mice. We have found that human recombinant IL-1 beta (a single injection greater than 0.01 micrograms per mouse i.v. given before tumor cells) induced an augmentation of experimental lung metastases from the A375M tumor cells in nude mice. This effect was rapidly induced and reversible within 24 h after IL-1 injection. A similar effect was induced by human recombinant IL-1 alpha and human recombinant tumor necrosis factor, but not by human recombinant interleukin 6. 5-[125I]odo-2'-deoxyuridine-radiolabeled A375M tumor cells injected i.v. remained at a higher level in the lungs of nude mice receiving IL-1 than in control mice. In addition, IL-1 injected 1 h, but not 24 h, after tumor cells enhanced lung colonization as well, thus suggesting an effect of IL-1 on the vascular transit of tumor cells. These findings may explain the observation of enhanced secondary localization of tumor cells at inflammatory sites and suggest that modulation of secondary spread should be carefully considered when assessing the ability of this cytokine to complement cytoreductive therapies

Capacity of ultraviolet-induced DNA repair in human glioma cells

Energy Technology Data Exchange (ETDEWEB)

Itoh, Hiroji

1987-04-01

A DNA repair abnormality is likely related to an increased incidence of neoplasms in several autosomal recessive diseases such as xeroderma pigmentosum, Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. In human glioma cells, however, there are only a few reports on DNA repair. In this study, an ultraviolet (UV)-induced DNA repair was examined systematically in many human glioma cells. Two human malignant glioma cell lines (MMG-851, U-251-MG) and 7 human glioma cell strains (4, benign; 3, malignant) of short term culture, in which glial fibrillary acidic protein (GFAP) staining were positive, were used. To investigate the capacity of DNA repair, UV sensitivity was determined by colony formation; excision repair by autoradiography and Cytosine Arabinoside (Ara-C) assay; and post-replication repair by the joining rate of newly synthesized DNA. As a result, the colony-forming abilities of malignant glioma cell lines were lower than those of normal human fibroblasts, but no difference was found between two malignant glioma cell lines. The excision repair of the malignant group (2 cell lines and 3 cell strains) was apparently lower than that of the benign group (4 cell strains). In two malignant glioma cell lines, the excision repair of MMG-851 was lower than that of U-251-MG, and the post-replication repair of MMG-851 was higher than that of U-251-MG. These results were considered to correspond well with colony-forming ability. The results indicate that there are some differences in each human malignant glioma cell in its UV-induced DNA repair mechanism, and that the excision repair of the malignant glioma cells is apparently lower than that of the benign glioma cells. These findings may be useful for diagnosis and treatment.

Communication: Polarizable polymer chain under external electric field in a dilute polymer solution.

Science.gov (United States)

Budkov, Yu A; Kolesnikov, A L; Kiselev, M G

2015-11-28

We study the conformational behavior of polarizable polymer chain under an external homogeneous electric field within the Flory type self-consistent field theory. We consider the influence of electric field on the polymer coil as well as on the polymer globule. We show that when the polymer chain conformation is a coil, application of external electric field leads to its additional swelling. However, when the polymer conformation is a globule, a sufficiently strong field can induce a globule-coil transition. We show that such "field-induced" globule-coil transition at the sufficiently small monomer polarizabilities goes quite smoothly. On the contrary, when the monomer polarizability exceeds a certain threshold value, the globule-coil transition occurs as a dramatic expansion in the regime of first-order phase transition. The developed theoretical model can be applied to predicting polymer globule density change under external electric field in order to provide more efficient processes of polymer functionalization, such as sorption, dyeing, and chemical modification.

ExternE - valuation of hydro power in Klippen. Final report

International Nuclear Information System (INIS)

Nilsson, Maans

1998-08-01

'true' average willingness to pay for these respondents is within these boundaries. The average willingness to pay was 300-700 SEK/year for Swedes, 600-1900 SEK/year for Locals and 500-2000 SEK/year for Tourists. Total national benefits can be estimated from the average willingness to pay for the three categories. With a total production estimated at 5820 GWh, the externalities are estimated to 54-125 mEcu/kWh from the Swede sample, 0.12-0.33 mEcu/kWh for the locals sample and 1.7-7.7 mEcu/kWh for the tourist sample. The question whether decision-makers should use these CV-results as estimates of the damages induced by a specific project cannot be answered in simple way. There are a number of ethical/philosophical questions as well as methodological pitfalls that must be taken very seriously. It is a challenge to communicate adequate information to a lay audience on a complex phenomenon such as the river ecosystems and impacts of hydro power developments. There is a risk that respondents are ill-informed when they are asked to state a willingness to pay. The results from the Swede sample must be interpreted with serious caution as we see a risk of an embedding effect. We have higher confidence in the samples of Locals and Tourists, who are better informed and familiar with the issue 38 refs, 4 figs, 5 tabs, 1 appendix

Light Water Reactor Sustainability Program Industry Application External Hazard Analyses Problem Statement

Energy Technology Data Exchange (ETDEWEB)

Szilard, Ronaldo Henriques [Idaho National Lab. (INL), Idaho Falls, ID (United States); Coleman, Justin [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis L. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Prescott, Steven [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kammerer, Annie [Annie Kammerer Consulting, Rye, NH (United States); Youngblood, Robert [Idaho National Lab. (INL), Idaho Falls, ID (United States); Pope, Chad [Idaho State Univ., Pocatello, ID (United States)

2015-07-01

Risk-Informed Margin Management Industry Application on External Events. More specifically, combined events, seismically induced external flooding analyses for a generic nuclear power plant with a generic site soil, and generic power plant system and structure. The focus of this report is to define the problem above, set up the analysis, describe the methods to be used, tools to be applied to each problem, and data analysis and validation associated with the above.

Diagnosis of West Nile Virus Human Infections: Overview and Proposal of Diagnostic Protocols Considering the Results of External Quality Assessment Studies

Directory of Open Access Journals (Sweden)

Ana Vázquez

2013-09-01

Full Text Available West Nile virus, genus Flavivirus, is transmitted between birds and occasionally other animals by ornithophilic mosquitoes. This virus also infects humans causing asymptomatic infections in about 85% of cases and <1% of clinical cases progress to severe neuroinvasive disease. The virus also presents a threat since most infections remain unapparent. However, the virus contained in blood and organs from asymptomatically infected donors can be transmitted to recipients of these infectious tissues. This paper reviews the presently available methods to achieve the laboratory diagnosis of West Nile virus infections in humans, discussing the most prominent advantages and disadvantages of each in light of the results obtained during four different External Quality Assessment studies carried out by the European Network for ‘Imported’ Viral Diseases (ENIVD.

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

Science.gov (United States)

Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

2016-01-01

The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

Directory of Open Access Journals (Sweden)

Hyunjung Choi

Full Text Available The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH-smoothened (Smo signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Two sides of the same coin? Unraveling subtle differences between human embryonic and induced pluripotent stem cells by Raman spectroscopy.

Science.gov (United States)

Parrotta, Elvira; De Angelis, Maria Teresa; Scalise, Stefania; Candeloro, Patrizio; Santamaria, Gianluca; Paonessa, Mariagrazia; Coluccio, Maria Laura; Perozziello, Gerardo; De Vitis, Stefania; Sgura, Antonella; Coluzzi, Elisa; Mollace, Vincenzo; Di Fabrizio, Enzo Mario; Cuda, Giovanni

2017-11-28

Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, hold enormous promise for many biomedical applications, such as regenerative medicine, drug testing, and disease modeling. Although induced pluripotent stem cells resemble embryonic stem cells both morphologically and functionally, the extent to which these cell lines are truly equivalent, from a molecular point of view, remains controversial. Principal component analysis and K-means cluster analysis of collected Raman spectroscopy data were used for a comparative study of the biochemical fingerprint of human induced pluripotent stem cells and human embryonic stem cells. The Raman spectra analysis results were further validated by conventional biological assays. Raman spectra analysis revealed that the major difference between human embryonic stem cells and induced pluripotent stem cells is due to the nucleic acid content, as shown by the strong positive peaks at 785, 1098, 1334, 1371, 1484, and 1575 cm -1 , which is enriched in human induced pluripotent stem cells. Here, we report a nonbiological approach to discriminate human induced pluripotent stem cells from their native embryonic stem cell counterparts.

Two sides of the same coin? Unraveling subtle differences between human embryonic and induced pluripotent stem cells by Raman spectroscopy

KAUST Repository

Parrotta, Elvira

2017-11-28

Background: Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, hold enormous promise for many biomedical applications, such as regenerative medicine, drug testing, and disease modeling. Although induced pluripotent stem cells resemble embryonic stem cells both morphologically and functionally, the extent to which these cell lines are truly equivalent, from a molecular point of view, remains controversial. Methods: Principal component analysis and K-means cluster analysis of collected Raman spectroscopy data were used for a comparative study of the biochemical fingerprint of human induced pluripotent stem cells and human embryonic stem cells. The Raman spectra analysis results were further validated by conventional biological assays. Results: Raman spectra analysis revealed that the major difference between human embryonic stem cells and induced pluripotent stem cells is due to the nucleic acid content, as shown by the strong positive peaks at 785, 1098, 1334, 1371, 1484, and 1575 cm–1, which is enriched in human induced pluripotent stem cells. Conclusions: Here, we report a nonbiological approach to discriminate human induced pluripotent stem cells from their native embryonic stem cell counterparts.

Two sides of the same coin? Unraveling subtle differences between human embryonic and induced pluripotent stem cells by Raman spectroscopy

KAUST Repository

Parrotta, Elvira; De Angelis, Maria Teresa; Scalise, Stefania; Candeloro, Patrizio; Santamaria, Gianluca; Paonessa, Mariagrazia; Coluccio, Maria Laura; Perozziello, Gerardo; De Vitis, Stefania; Sgura, Antonella; Coluzzi, Elisa; Mollace, Vincenzo; Di Fabrizio, Enzo M.; Cuda, Giovanni

2017-01-01

Background: Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, hold enormous promise for many biomedical applications, such as regenerative medicine, drug testing, and disease modeling. Although induced pluripotent stem cells resemble embryonic stem cells both morphologically and functionally, the extent to which these cell lines are truly equivalent, from a molecular point of view, remains controversial. Methods: Principal component analysis and K-means cluster analysis of collected Raman spectroscopy data were used for a comparative study of the biochemical fingerprint of human induced pluripotent stem cells and human embryonic stem cells. The Raman spectra analysis results were further validated by conventional biological assays. Results: Raman spectra analysis revealed that the major difference between human embryonic stem cells and induced pluripotent stem cells is due to the nucleic acid content, as shown by the strong positive peaks at 785, 1098, 1334, 1371, 1484, and 1575 cm–1, which is enriched in human induced pluripotent stem cells. Conclusions: Here, we report a nonbiological approach to discriminate human induced pluripotent stem cells from their native embryonic stem cell counterparts.

Modeling Treatment Response for Lamin A/C Related Dilated Cardiomyopathy in Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Lee, Yee-Ki; Lau, Yee-Man; Cai, Zhu-Jun; Lai, Wing-Hon; Wong, Lai-Yung; Tse, Hung-Fat; Ng, Kwong-Man; Siu, Chung-Wah

2017-07-28

Precision medicine is an emerging approach to disease treatment and prevention that takes into account individual variability in the environment, lifestyle, and genetic makeup of patients. Patient-specific human induced pluripotent stem cells hold promise to transform precision medicine into real-life clinical practice. Lamin A/C (LMNA)-related cardiomyopathy is the most common inherited cardiomyopathy in which a substantial proportion of mutations in the LMNA gene are of nonsense mutation. PTC124 induces translational read-through over the premature stop codon and restores production of the full-length proteins from the affected genes. In this study we generated human induced pluripotent stem cells-derived cardiomyocytes from patients who harbored different LMNA mutations (nonsense and frameshift) to evaluate the potential therapeutic effects of PTC124 in LMNA -related cardiomyopathy. We generated human induced pluripotent stem cells lines from 3 patients who carried distinctive mutations (R225X, Q354X, and T518fs) in the LMNA gene. The cardiomyocytes derived from these human induced pluripotent stem cells lines reproduced the pathophysiological hallmarks of LMNA -related cardiomyopathy. Interestingly, PTC124 treatment increased the production of full-length LMNA proteins in only the R225X mutant, not in other mutations. Functional evaluation experiments on the R225X mutant further demonstrated that PTC124 treatment not only reduced nuclear blebbing and electrical stress-induced apoptosis but also improved the excitation-contraction coupling of the affected cardiomyocytes. Using cardiomyocytes derived from human induced pluripotent stem cells carrying different LMNA mutations, we demonstrated that the effect of PTC124 is codon selective. A premature stop codon UGA appeared to be most responsive to PTC124 treatment. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The cachectic mediator proteolysis inducing factor activates NF-kappaB and STAT3 in human Kupffer cells and monocytes

NARCIS (Netherlands)

Watchorn, T.M.; Dowidar, N.; Dejong, C.H.; Waddell, I.D.; Garden, O.J.; Ross, J.A.

2005-01-01

A novel proteoglycan, proteolysis inducing factor (PIF), is capable of inducing muscle proteolysis during the process of cancer cachexia, and of inducing an acute phase response in human hepatocytes. We investigated whether PIF is able to activate pro-inflammatory pathways in human Kupffer cells,

Regulating multiple externalities

DEFF Research Database (Denmark)

Waldo, Staffan; Jensen, Frank; Nielsen, Max

2016-01-01

Open access is a well-known externality problem in fisheries causing excess capacity and overfishing. Due to global warming, externality problems from CO2 emissions have gained increased interest. With two externality problems, a first-best optimum can be achieved by using two regulatory instrume......Open access is a well-known externality problem in fisheries causing excess capacity and overfishing. Due to global warming, externality problems from CO2 emissions have gained increased interest. With two externality problems, a first-best optimum can be achieved by using two regulatory...

Membrane damage induced in cultured human skin fibroblasts by UVA irradiation

International Nuclear Information System (INIS)

Gaboriau, F.; Morliere, P.; Marquis, I.; Moysan, A.; Geze, M.; Dubertret, L.

1993-01-01

Irradiation of cultured human skin fibroblasts with ultraviolet light from 320 to 400 nm (UVA) leads to a decrease in the membrane fluidity exemplified by an enhanced fluorescence anisotropy of the lipophilic fluorescent probe 1-[4-trimethylamino)-phenyl]-6-phenylhexa-1,3,5-triene. This UVA-induced decrease in fluidity is associated with lactate dehydrogenase leakage in the supernatant. Vitamin E, an inhibitor of lipid peroxidation, exerts a protective effect on both phenomena. Therefore, this UVA-induced damage in membrane properties may be related to lipid peroxidation processes. Moreover, exponentially growing cells are more sensitive to these UVA-induced alterations than confluent cells. (Author)

Joint probability safety assessment for NPP defense infrastructure against extreme external natural hazards

International Nuclear Information System (INIS)

Guilin, L.; Defu, L.; Huajun, L.; Fengqing, W.; Tao, Z.

2012-01-01

With the increasing tendency of natural hazards, the typhoon, hurricane and tropical Cyclone induced surge, wave, precipitation, flood and wind as extreme external loads menacing Nuclear Power Plants (NPP) in coastal and inland provinces of China. For all of planned, designed And constructed NPP the National Nuclear Safety Administration of China and IAEA recommended Probable Maximum Hurricane /Typhoon/(PMH/T), Probable Maximum Storm Surge (PMSS), Probable Maximum Flood (PMF), Design Basis Flood (DBF) as safety regulations for NPP defense infrastructures. This paper discusses the joint probability analysis of simultaneous occurrence typhoon induced extreme external hazards and compare with IAEA 2006-2009 recommended safety regulation design criteria for some NPP defense infrastructures along China coast. (authors)

A Monoclonal Antibody against Wnt-1 Induces Apoptosis in Human Cancer Cells

Directory of Open Access Journals (Sweden)

Biao He

2004-01-01

Full Text Available Aberrant activation of the Wingless-type (Wnt/β-catenin signaling pathway is associated with a variety of human cancers. Little is known regarding the role that Wnt ligands play in human carcinogenesis. To test whether a Wnt-1 signal is a survival factor in human cancer cells and thus may serve as a potential cancer therapeutic target, we investigated the effect of inhibition of Wnt-1 signaling in a variety of human cancer cell lines, including non small cell lung cancer, breast cancer, mesothelioma, and sarcoma. Both monoclonal antibody and RNA interference (RNAi were used to inhibit Wnt-1 signaling. We found that incubation of a monoclonal anti-Wnt-1 antibody induced apoptosis and caused downstream protein changes in cancer cells overexpressing Wnt-1. In contrast, apoptosis was not detected in cells lacking or having minimal Wnt-1 expression after the antibody incubation. RNAi targeting of Wnt-1 in cancer cells overexpressing Wnt-1 demonstrated similar downstream protein changes and induction of apoptosis. The antibody also suppressed tumor growth in vivo. Our results indicate that both monoclonal anti-Wnt-1 antibody and Wnt-1 siRNA inhibit Wnt-1 signaling and can induce apoptosis in human cancer cells. These findings hold promise as a novel therapeutic strategy for cancer.

Comparison of radioimmunotherapy and external beam radiotherapy in colon cancer xenografts

International Nuclear Information System (INIS)

Buras, R.R.; Wong, J.F.C.; Kuhn, J.A.; Beatty, B.G.; Williams, L.E.; Beatty, J.D.; Wanek, P.M.

1993-01-01

Radioimmunotherapy and external beam radiotherapy were compared in a nude mouse human colon cancer model. Radioimmunotherapy was delivered by intraperitoneal injection of 90 Y-labeled anticarcinoembryonic antigen monoclonal antibody (anti-CEA MAB). Single fraction external beam radiotherapy was delivered using a 60 Co teletherapy unit. Control groups received saline, unlabeled anit-CEA monoclonal antibody and labeled nonspecific monoclonal antibody. Tumor growth suppression was expressed as delay to reach 2g compared to saline controls. Unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody had no effect. External beam radiotherapy of 300, 600, 1000 and 2000 cGy produced growth delays of 3, 12, 17, and 22 days, respectively. Radioimmunotherapy with 120 μCi, 175 μCi, and 225 μCi resulted in growth delays of 20, 34, and 36 days. Estimated absorbed tumor dose was 1750 cGy in the 120 μCi group. Similar comparisons were done with the more radioresistant WiDr human colon carcinoma cell line. External beam radiotherapy doses of 400, 800, 1200, and 1600 cGy resulted in growth delays of 6, 21, 36 and 48 days, respectively. Radioimmunotherapy of 120 μCi and 175 μCi resulted in growth delays of 9 and 19 days, respectively. The 120 μCi dose delivered an estimated absorbed tumor dose of 1080 cGy to WiDr tumors. In summary, for the radiosensitive LS174T line, radioimmunotherapy produced biologic effects that were comparable to a similar dose of single fraction external beam radiotherapy. For the more radioresistant WiDr tumor, radioimmunotherapy produced a biologic effect which was less than a similar dose of single fraction external beam radiotherapy. These studies suggest that a tumor's response to radioimmunotherapy relative to that of external beam radiotherapy is, in part, dependent on tumor radiosensitivity and repair capacity. 23 refs., 5 figs. 4 tabs

Approaches in estimation of external cost for fuel cycles in the ExternE project

International Nuclear Information System (INIS)

Afanas'ev, A.A.; Maksimenko, B.N.

1998-01-01

The purposes, content and main results of studies realized within the frameworks of the International Project ExternE which is the first comprehensive attempt to develop general approach to estimation of external cost for different fuel cycles based on utilization of nuclear and fossil fuels, as well as on renewable power sources are discussed. The external cost of a fuel cycle is treated as social and environmental expenditures which are not taken into account by energy producers and consumers, i.e. these are expenditures not included into commercial cost nowadays. The conclusion on applicability of the approach suggested for estimation of population health hazards and environmental impacts connected with electric power generation growth (expressed in money or some other form) is made

Melatonin suppresses acrolein-induced IL-8 production in human pulmonary fibroblasts.

Science.gov (United States)

Kim, Gun-Dong; Lee, Seung Eun; Kim, Tae-Ho; Jin, Young-Ho; Park, Yong Seek; Park, Cheung-Seog

2012-04-01

Cigarette smoke (CS) causes harmful alterations in the lungs and airway structures and functions that characterize chronic obstructive pulmonary disease (COPD). In addition to COPD, active cigarette smoking causes other respiratory diseases and diminishes health status. Furthermore, recent studies show that, α, β-unsaturated aldehyde acrolein in CS induces the production of interleukin (IL)-8, which is known to be related to bronchitis, rhinitis, pulmonary fibrosis, and asthma. In addition, lung and pulmonary fibroblasts secrete IL-8, which has a chemotactic effect on leukocytes, and which in turn, play a critical role in lung inflammation. On the other hand, melatonin regulates circadian rhythm homeostasis in humans and has many other effects, which include antioxidant and anti-inflammatory effects, as demonstrated by the reduced expressions of iNOS, IL-1β, and IL-6 and increased glutathione (GSH) and superoxide dismutase activities. In this study, we investigated whether melatonin suppresses acrolein-induced IL-8 secretion in human pulmonary fibroblasts (HPFs). It was found that acrolein-induced IL-8 production was accompanied by increased levels of phosphorylation of Akt and extracellular signal-regulated kinases (ERK1/2) in HPFs, and that melatonin suppressed IL-8 production in HPFs. These results suggest that melatonin suppresses acrolein-induced IL-8 production via ERK1/2 and phosphatidylinositol 3-kinase (PI3K)/Akt signal inhibition in HPFs. © 2011 John Wiley & Sons A/S.

Application of Method of Variation to Analyze and Predict Human Induced Modifications of Water Resource Systems

Science.gov (United States)

Dessu, S. B.; Melesse, A. M.; Mahadev, B.; McClain, M.

2010-12-01

Water resource systems have often used gravitational surface and subsurface flows because of their practicality in hydrological modeling and prediction. Activities such as inter/intra-basin water transfer, the use of small pumps and the construction of micro-ponds challenge the tradition of natural rivers as water resource management unit. On the contrary, precipitation is barely affected by topography and plot harvesting in wet regions can be more manageable than diverting from rivers. Therefore, it is indicative to attend to systems where precipitation drives the dynamics while the internal mechanics constitutes spectrum of human activity and decision in a network of plots. The trade-in volume and path of harvested precipitation depends on water balance, energy balance and the kinematics of supply and demand. Method of variation can be used to understand and predict the implication of local excess precipitation harvest and exchange on the natural water system. A system model was developed using the variational form of Euler-Bernoulli’s equation for the Kenyan Mara River basin. Satellite derived digital elevation models, precipitation estimates, and surface properties such as fractional impervious surface area, are used to estimate the available water resource. Four management conditions are imposed in the model: gravitational flow, open water extraction and high water use investment at upstream and downstream respectively. According to the model, the first management maintains the basin status quo while the open source management could induce externality. The high water market at the upstream in the third management offers more than 50% of the basin-wide total revenue to the upper third section of the basin thus may promote more harvesting. The open source and upstream exploitation suggest potential drop of water availability to downstream. The model exposed the latent potential of economic gradient to reconfigure the flow network along the direction where the

Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo

OpenAIRE

Clémence Roux; Clémence Roux; Clémence Roux; Gaëlle Saviane; Gaëlle Saviane; Jonathan Pini; Jonathan Pini; Nourhène Belaïd; Nourhène Belaïd; Gihen Dhib; Gihen Dhib; Christine Voha; Christine Voha; Christine Voha; Lidia Ibáñez

2018-01-01

Despite mesenchymal stromal cells (MSCs) are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited in vitro expansion, absence of a full phenotypic characterization, few insights on their in vivo fate). Standardized MSCs derived in vitro from human-induced pluripotent stem (huIPS) cells, remediating part of these issues, are considered as well as a valuable tool for th...

A study of risk evaluation methodology selection for the external hazards

International Nuclear Information System (INIS)

Kuramoto, Takahiro; Yamaguchi, Akira; Narumiya, Yosiyuki

2014-01-01

Since the accident at Fukushima Daiichi Nuclear Power Plant caused by the Great East Japan Earthquake in March 2011, there has been growing demands for assessing the effects of external hazards, including natural events, such as earthquake and tsunami, and external human behaviors, and taking actions to address those external hazards. The newly established Japanese regulatory requirements claim design considerations associated with external hazards. The primary objective of the risk assessment for external hazards is to establish countermeasures against such hazards rather than grasping the risk figures. Therefore, applying detailed risk assessment methods, such as probabilistic risk assessment (PRA), to all the external hazards is not always the most appropriate. Risk assessment methods can vary in types including qualitative evaluation, hazard analysis (analyzing hazard frequencies or their influence), and margin assessment. To resolve these issues, a process has been established that enables us to identify the external hazards in a comprehensive and systematic manner, which have potential risks leading to core damage and to select an appropriate evaluation method according to the risks associated with each of the external hazards. This paper discusses the comprehensive and systematic identification process for the external hazards which have potential risks leading to core damage, and the approaches of selecting an appropriate evaluation method for each external hazard. This paper also describes some applications of specific risk evaluation methods. (author)

External Beam Radiotherapy of Recurrent Glioma: Radiation Tolerance of the Human Brain

Energy Technology Data Exchange (ETDEWEB)

Sminia, Peter, E-mail: p.sminia@vumc.nl [Department of Radiation Oncology, Radiobiology Section, VU University Medical Center, De Boelelaan 1117, P.O. Box 7057, Amsterdam (Netherlands); Mayer, Ramona [EBG MedAustron GmbH., Viktor Kaplan-Strasse 2, A-2700, Wiener Neustadt (Austria)

2012-04-05

Malignant gliomas relapse in close proximity to the resection site, which is the postoperatively irradiated volume. Studies on re-irradiation of glioma were examined regarding radiation-induced late adverse effects (i.e., brain tissue necrosis), to obtain information on the tolerance dose and treatment volume of normal human brain tissue. The studies were analyzed using the linear-quadratic model to express the re-irradiation tolerance in cumulative equivalent total doses when applied in 2 Gy fractions (EQD2{sub cumulative}). Analysis shows that the EQD2{sub cumulative} increases from conventional re-irradiation series to fractionated stereotactic radiotherapy (FSRT) to LINAC-based stereotactic radiosurgery (SRS). The mean time interval between primary radiotherapy and the re-irradiation course was shortened from 30 months for conventional re-irradiation to 17 and 10 months for FSRT and SRS, respectively. Following conventional re-irradiation, radiation-induced normal brain tissue necrosis occurred beyond an EQD2{sub cumulative} around 100 Gy. With increasing conformality of therapy, the smaller the treatment volume is, the higher the radiation dose that can be tolerated. Despite the dose escalation, no increase in late normal tissue toxicity was reported. On basis of our analysis, the use of particle therapy in the treatment of recurrent gliomas, because of the optimized physical dose distribution in the tumour and surrounding healthy brain tissue, should be considered for future clinical trials.

External Beam Radiotherapy of Recurrent Glioma: Radiation Tolerance of the Human Brain

Directory of Open Access Journals (Sweden)

Peter Sminia

2012-04-01

Full Text Available Malignant gliomas relapse in close proximity to the resection site, which is the postoperatively irradiated volume. Studies on re-irradiation of glioma were examined regarding radiation-induced late adverse effects (i.e., brain tissue necrosis, to obtain information on the tolerance dose and treatment volume of normal human brain tissue. The studies were analyzed using the linear-quadratic model to express the re-irradiation tolerance in cumulative equivalent total doses when applied in 2 Gy fractions (EQD2cumulative. Analysis shows that the EQD2cumulative increases from conventional re-irradiation series to fractionated stereotactic radiotherapy (FSRT to LINAC-based stereotactic radiosurgery (SRS. The mean time interval between primary radiotherapy and the re-irradiation course was shortened from 30 months for conventional re-irradiation to 17 and 10 months for FSRT and SRS, respectively. Following conventional re-irradiation, radiation-induced normal brain tissue necrosis occurred beyond an EQD2cumulative around 100 Gy. With increasing conformality of therapy, the smaller the treatment volume is, the higher the radiation dose that can be tolerated. Despite the dose escalation, no increase in late normal tissue toxicity was reported. On basis of our analysis, the use of particle therapy in the treatment of recurrent gliomas, because of the optimized physical dose distribution in the tumour and surrounding healthy brain tissue, should be considered for future clinical trials.

Thalidomide induces apoptosis in undifferentiated human induced pluripotent stem cells.

Science.gov (United States)

Tachikawa, Saoko; Nishimura, Toshinobu; Nakauchi, Hiromitsu; Ohnuma, Kiyoshi

2017-10-01

Thalidomide, which was formerly available commercially to control the symptoms of morning sickness, is a strong teratogen that causes fetal abnormalities. However, the mechanism of thalidomide teratogenicity is not fully understood; thalidomide toxicity is not apparent in rodents, and the use of human embryos is ethically and technically untenable. In this study, we designed an experimental system featuring human-induced pluripotent stem cells (hiPSCs) to investigate the effects of thalidomide. These cells exhibit the same characteristics as those of epiblasts originating from implanted fertilized ova, which give rise to the fetus. Therefore, theoretically, thalidomide exposure during hiPSC differentiation is equivalent to that in the human fetus. We examined the effects of thalidomide on undifferentiated hiPSCs and early-differentiated hiPSCs cultured in media containing bone morphogenetic protein-4, which correspond, respectively, to epiblast (future fetus) and trophoblast (future extra-embryonic tissue). We found that only the number of undifferentiated cells was reduced. In undifferentiated cells, application of thalidomide increased the number of apoptotic and dead cells at day 2 but not day 4. Application of thalidomide did not affect the cell cycle. Furthermore, immunostaining and flow cytometric analysis revealed that thalidomide exposure had no effect on the expression of specific markers of undifferentiated and early trophectodermal differentiated cells. These results suggest that the effect of thalidomide was successfully detected in our experimental system and that thalidomide eliminated a subpopulation of undifferentiated hiPSCs. This study may help to elucidate the mechanisms underlying thalidomide teratogenicity and reveal potential strategies for safely prescribing this drug to pregnant women.

Novel pathways to erythropoiesis induced by dimerization of intracellular C-Mpl in human hematopoietic progenitors.

Science.gov (United States)

Parekh, Chintan; Sahaghian, Arineh; Kim, William; Scholes, Jessica; Ge, Shundi; Zhu, Yuhua; Asgharzadeh, Shahab; Hollis, Roger; Kohn, Donald; Ji, Lingyun; Malvar, Jemily; Wang, Xiaoyan; Crooks, Gay

2012-04-01

The cytokine thrombopoietin (Tpo) plays a critical role in hematopoiesis by binding to the extracellular domain and inducing homodimerization of the intracellular signaling domain of its receptor, c-Mpl. Mpl homodimerization can also be accomplished by binding of a synthetic ligand to a constitutively expressed fusion protein F36VMpl consisting of a ligand binding domain (F36V) and the intracellular signaling domain of Mpl. Unexpectedly, in contrast to Tpo stimulation, robust erythropoiesis is induced after dimerization of F36VMpl in human CD34+ progenitor cells. The goal of this study was to define the hematopoietic progenitor stages at which dimerization of intracellular Mpl induces erythropoiesis and the downstream molecular events that mediate this unanticipated effect. Dimerization (in the absence of erythropoietin and other cytokines) in human common myeloid progenitors and megakaryocytic erythroid progenitors caused a significant increase in CD34+ cells (p Mpl in human myeloerythroid progenitors induces progenitor expansion and erythropoiesis through molecular mechanisms that are not shared by Tpo stimulation of endogenous Mpl. Copyright © 2012 AlphaMed Press.

Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes

NARCIS (Netherlands)

Tertoolen, L.G.J.; Braam, S. R.; van Meer, B.J.; Passier, R.; Mummery, C. L.

2018-01-01

Multi electrode arrays (MEAs) are increasingly used to detect external field potentials in electrically active cells. Recently, in combination with cardiomyocytes derived from human (induced) pluripotent stem cells they have started to become a preferred tool to examine newly developed drugs for

Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways

International Nuclear Information System (INIS)

Mu, Shumin; Tian, Xingsong; Ruan, Yongwei; Liu, Yuantao; Bian, Dezhi; Ma, Chunyan; Yu, Chunxiao; Feng, Mei; Wang, Furong; Gao, Ling; Zhao, Jia-jun

2012-01-01

Highlights: ► Diosgenin induces apoptosis in IGF-1-treated thyrocytes through two caspase pathways. ► Diosgenin inhibits FLIP and activates caspase-8 in FAS related-pathway. ► Diosgenin increases ROS, regulates the ratio of Bax/Bcl-2 in mitochondrial pathway. -- Abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24 h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

Hybrid instrument applied to human reliability study in event of loss of external electric power in a nuclear power plant

International Nuclear Information System (INIS)

Martins, Eduardo Ferraz

2015-01-01

The study projects in highly complex installations involves robust modeling, supported by conceptual and mathematical tools, to carry out systematic research and structured the different risk scenarios that can lead to unwanted events from occurring equipment failures or human errors. In the context of classical modeling, the Probabilistic Safety Analysis (PSA) seeks to provide qualitative and quantitative information about the project particularity and their operational facilities, including the identification of factors or scenarios that contribute to the risk and consequent comparison options for increasing safety. In this context, the aim of the thesis is to develop a hybrid instrument (CPP-HI) innovative, from the integrated modeling techniques of Failure Mode and Effect Analysis (FMEA), concepts of Human Reliability Analysis and Probabilistic Composition of Preferences (PCP). In support of modeling and validation of the CPP-HI, a simulation was performed on a triggering event 'Loss of External Electric Power' - PEEE, in a Nuclear Power plant. The results were simulated in a virtual environment (sensitivity analysis) and are robust to the study of Human Reliability Analysis (HRA) in the context of the PSA. (author)

Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin

NARCIS (Netherlands)

Middelkamp-Hup, Maritza A.; Pathak, Madhu A.; Parrado, Concepcion; Goukassian, David; Rius-Díaz, Francisca; Mihm, Martín C.; Fitzpatrick, Thomas B.; González, Salvador

2004-01-01

BACKGROUND: UV radiation induces damage to human skin. Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL). METHODS: A

External Validity in the Study of Human Development: Theoretical and Methodological Issues

Science.gov (United States)

Hultsch, David F.; Hickey, Tom

1978-01-01

An examination of the concept of external validity from two theoretical perspectives: a traditional mechanistic approach and a dialectical organismic approach. Examines the theoretical and methodological implications of these perspectives. (BD)

Modeling human neurological disorders with induced pluripotent stem cells.

Science.gov (United States)

Imaizumi, Yoichi; Okano, Hideyuki

2014-05-01

Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained

Analysis of External Treatment Methods and Technical Characteristics of External Treatment

Science.gov (United States)

Zhang, Rui; Miao, Mingsan; Bai, Ming

2018-01-01

Chinese medicine external therapy is a treatment method of Chinese medicine with Chinese characteristics. The effect of traditional Chinese medicine external treatment, convenient operation, external treatment and technology has great prospects for development. The traditional Chinese medicine external treatment method and technical characteristics were analyzed.

Methanolic Extracts from Brown Seaweeds Dictyota cilliolata and Dictyota menstrualis Induce Apoptosis in Human Cervical Adenocarcinoma HeLa Cells

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Dayanne Lopes Gomes

2015-04-01

Full Text Available Carcinoma of the uterine cervix is the second most common female tumor worldwide, surpassed only by breast cancer. Natural products from seaweeds evidencing apoptotic activity have attracted a great deal of attention as new leads for alternative and complementary preventive or therapeutic anticancer agents. Here, methanol extracts from 13 species of tropical seaweeds (Rhodophytas, Phaeophyta and Chlorophyta collected from the Northeast of Brazil were assessed as apoptosis-inducing agents on human cervical adenocarcinoma (HeLa. All extracts showed different levels of cytotoxicity against HeLa cells; the most potent were obtained from the brown alga Dictyota cilliolata (MEDC and Dictyota menstrualis (MEDM. In addition, MEDC and MEDM also inhibits SiHa (cervix carcinoma cell proliferation. Studies with these two extracts using flow cytometry and fluorescence microscopy showed that HeLa cells exposed to MEDM and MEDC exhibit morphological and biochemical changes that characterize apoptosis as shown by loss of cell viability, chromatin condensation, phosphatidylserine externalization, and sub-G1 cell cycle phase accumulation, also MEDC induces cell cycle arrest in cell cycle phase S. Moreover, the activation of caspases 3 and 9 by these extracts suggests a mitochondria-dependent apoptosis route. However, other routes cannot be ruled out. Together, these results point out the methanol extracts of the brown algae D. mentrualis and D. cilliolata as potential sources of molecules with antitumor activity.

IRIS Toxicological Review of Methanol (Noncancer) (Revised External Review Draft)

Science.gov (United States)

EPA is seeking additional public comment and external peer review of the scientific basis supporting the human health hazard and dose-response assessment of methanol (noncancer). Teleconference Details: The public may participate in th...

TCDD Induces the Hypoxia-Inducible Factor (HIF-1α Regulatory Pathway in Human Trophoblastic JAR Cells

Directory of Open Access Journals (Sweden)

Tien-Ling Liao

2014-09-01

Full Text Available The exposure to dioxin can compromise pregnancy outcomes and increase the risk of preterm births. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD has been demonstrated to induce placental hypoxia at the end of pregnancy in a rat model, and hypoxia has been suggested to be the cause of abnormal trophoblast differentiation and placental insufficiency syndromes. In this study, we demonstrate that the non-hypoxic stimulation of human trophoblastic cells by TCDD strongly increased hypoxia inducible factor-1 alpha (HIF-1α stabilization. TCDD exposure induced the generation of reactive oxygen species (ROS and nitric oxide. TCDD-induced HIF-1α stabilization and Akt phosphorylation was inhibited by pretreatment with wortmannin (a phosphatidylinositol 3-kinase (PI3K inhibitor or N-acetylcysteine (a ROS scavenger. The augmented HIF-1α stabilization by TCDD occurred via the ROS-dependent activation of the PI3K/Akt pathway. Additionally, a significant increase in invasion and metallomatrix protease-9 activity was found in TCDD-treated cells. The gene expression of vascular endothelial growth factor and placental growth factor was induced upon TCDD stimulation, whereas the protein levels of peroxisome proliferator-activated receptor γ (PPARγ, PPARγ coactivator-1α, mitochondrial transcription factor, and uncoupling protein 2 were decreased. Our results indicate that an activated HIF-1α pathway, elicited oxidative stress, and induced metabolic stress contribute to TCDD-induced trophoblastic toxicity. These findings may provide molecular insight into the TCDD-induced impairment of trophoblast function and placental development.

Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells.

Directory of Open Access Journals (Sweden)

Fangfang Lang

Full Text Available Resveratrol (trans-3,4,5'-trihydroxystilbene is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3 was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.

Characterization of Induced Pluripotent Stem Cell-derived Human Serotonergic Neurons

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Lining Cao

2017-05-01

Full Text Available In the brain, the serotonergic neurons located in the raphe nucleus are the unique resource of the neurotransmitter serotonin, which plays a pivotal role in the regulation of brain development and functions. Dysfunction of the serotonin system is present in many psychiatric disorders. Lack of in vitro functional human model limits the understanding of human central serotonergic system and its related diseases and clinical applications. Previously, we have developed a method generating human serotonergic neurons from induced pluripotent stem cells (iPSCs. In this study, we analyzed the features of these human iPSCs-derived serotonergic neurons both in vitro and in vivo. We found that these human serotonergic neurons are sensitive to the selective neurotoxin 5, 7-Dihydroxytryptamine (5,7-DHT in vitro. After being transplanted into newborn mice, the cells not only expressed their typical molecular markers, but also showed the migration and projection to the host’s cerebellum, hindbrain and spinal cord. The data demonstrate that these human iPSCs-derived neurons exhibit the typical features as the serotonergic neurons in the brain, which provides a solid foundation for studying on human serotonin system and its related disorders.

WE-D-210-04: Radiation-Induced Polymerization of Ultrasound Contrast Agents in View of Non-Invasive Dosimetry in External Beam Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Callens, M; Verboven, E; Van Den Abeele, K [Department of Physics, Wave Propagation and Signal Processing, KU Leuven KULAK, Kortrijk (Belgium); D’Agostino, E [DoseVue NV, Hasselt (Belgium); Pfeiffer, H [Department of Materials Engineering, KU Leuven, Leuven (Belgium); D’hooge, J [Department of Cardiovascular Sciences, Bio-Medical Science Group, KU Leuven, Leuven (Belgium)

2015-06-15

Purpose: Ultrasound contrast agents (UCA’s) based on gas-filled microbubbles encapsulated by an amphiphilic shell are well established as safe and effective echo-enhancers in diagnostic imaging. In view of an alternative application of UCA’s, we investigated the use of targeted microbubbles as radiation sensors for external beam radiation therapy. As radiation induces permanent changes in the microbubble’s physico-chemical properties, a robust measure of these changes can provide a direct or indirect estimate of the applied radiation dose. For instance, by analyzing the ultrasonic dispersion characteristics of microbubble distributions before and after radiation treatment, an estimate of the radiation dose at the location of the irradiated volume can be made. To increase the radiation sensitivity of microbubbles, polymerizable diacetylene molecules can be incorporated into the shell. This study focuses on characterizing the acoustic response and quantifying the chemical modifications as a function of radiation dose. Methods: Lipid/diacetylene microbubbles were irradiated with a 6 MV photon beam using dose levels in the range of 0–150 Gy. The acoustic response of the microbubbles was monitored by ultrasonic through-transmission measurements in the range of 500 kHz to 20 MHz, thereby providing the dispersion relations of the phase velocity, attenuation and nonlinear coefficient. In addition, the radiation-induced chemical modifications were quantified using UV-VIS spectroscopy. Results: UV-VIS spectroscopy measurements indicate that ionizing radiation induces the polymerization of diacetylenes incorporated in the microbubble shell. The polymer yield strongly depends on the shell composition and the radiation-dose. The acoustic response is inherently related to the visco-elastic properties of the shell and is strongly influenced by the shell composition and the physico-chemical changes in the environment. Conclusion: Diacetylene-containing microbubbles are

Aboriginal research coalition externalities associated with energy production: Types, measures and integration

International Nuclear Information System (INIS)

Goodman, I.

1992-01-01

A system that has evolved to determine the environmental externalities associated with energy generation is described. The system involves identification and understanding of the activity being considered (power generation from a specific type of plant), effects such as air pollution, measures such as pollution control that can influence the levels of the preceding effects, the resources affected, impacts on human resource uses, and the values humans place on the use of the resources. Considerations in estimating external costs are then discussed. These include property rights, air emissions, electromagnetic fields, pollution control effectiveness and costs, valuation of air emissions, water quality and quantity, effects on fisheries and recreational activities, and effects of dams and inundation. A least-cost, or integrated management process, selects the combination of electricity supply and demand sources that have the least social cost. Total externality costs are estimated, based on emissions or effects from each source multiplied by unit costs, and control measures selected. The external costs are combined with the usual fixed and variable cost calculations to provide a total social cost measure. This monetization procedure allows a complete accounting of all costs to society on an equal basis. 53 refs., 4 figs

The internal-external respiratory motion correlation is unaffected by audiovisual biofeedback.

Science.gov (United States)

Steel, Harry; Pollock, Sean; Lee, Danny; Keall, Paul; Kim, Taeho

2014-03-01

This study evaluated if an audiovisual (AV) biofeedback causes variation in the level of external and internal correlation due to its interactive intervention in natural breathing. The internal (diaphragm) and external (abdominal wall) respiratory motion signals of 15 healthy human subjects under AV biofeedback and free breathing (FB) were analyzed and measures of correlation and regularity taken. Regularity metrics (root mean square error and spectral power dispersion metric) were obtained and the correlation between these metrics and the internal and external correlation was investigated. For FB and AV biofeedback assisted breathing the mean correlations found between internal and external respiratory motion were 0.96±0.02 and 0.96±0.03, respectively. This means there is no evidence to suggest (p-value=0.88) any difference in the correlation between internal and external respiratory motion with the use of AV biofeedback. Our results confirmed the hypothesis that the internal-external correlation with AV biofeedback is the same as for free breathing. Should this correlation be maintained for patients, AV biofeedback can be implemented in the clinic with confidence as regularity improvements using AV biofeedback with an external signal will be reflected in increased internal motion regularity.

RECENT ADVANCES IN STRATEGIES FOR IMMUNOTHERAPY OF HUMAN PAPILLOMAVIRUS-INDUCED LESIONS

Science.gov (United States)

Kanodia, Shreya; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for “proof of concept” studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. PMID:17973257

External Environment Sensing by a Module on Self-reconfiguration Robot

Science.gov (United States)

Goto, Tomotsugu; Uchida, Masafumi; Onogaki, Hitoshi

In the situation in which a robot and a human work together by collaborating with each other, a robot and a human share one working environment, and each interferes in each other. The boundary of each complex dynamic occupation area changes in the connection movement which is the component of collaborative works at this time. The main restraint condition which relates to the robustness of that connection movement is each physical charactristics, that is, the embodiment. A robot body is variability though the embodiment of a human is almost fixed. Therefore, the safe and the robust connection movement is brought when a robot has the robot body which is well suitable for the embodiment of a human. A purpose for this research is that the colaboration works between the self-reconfiguration robot and a human is realized. To achieve this purpose, sensing function of external environment on a module was examined. A module is a component of the self-reconfiguration robot. A robot body vibrates when a module actuates an arm actively. This vibration is observed by using some acceleration sensors. Measured datas reflects a difference of objects that it touches a robot body. In this paper, the sensing technique of external environment which identifies this difference by using the neural network is proposed.

External cost of coal based electricity generation: A tale of Ahmedabad city

International Nuclear Information System (INIS)

Mahapatra, Diptiranjan; Shukla, Priyadarshi; Dhar, Subash

2012-01-01

Electricity production causes unintended impacts. Their exclusion by the market leads to suboptimal resource allocations. Monetizing and internalizing of external costs, though challenging and debatable, leads to a better allocation of economic resources and welfare. In this paper, a life-cycle analysis (LCA) on the production of electricity from conventional coal based electricity generation system has been performed in order to examine the environmental impacts of coal based electricity generating systems in the twin-city of Ahmedabad and Gandhinagar in western India. By using dose–response functions, we make an attempt to estimate the damages to human health, crops, and building materials resulting from the operation of coal power plants and its associated mines. Further, we use geographic information system to account for spatially dependent data. Finally, monetary values have been assigned to estimate the damage to human health, crops and building materials. This study reveals that the health as well as on non-health impacts of air pollution resulting from coal based electricity generation may not be ignored both in absolute as well as economic value terms. Highlights: ► External cost from coal power generating systems has been calculated. ► We use LCA approach to monetize externalities. ► Geographic information software has been used to account for spatially dependent data. ► This study monetizes damages only to human health, crops, and building materials. ► We finally recommend policy directions to arrest this externality.

Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells Using Sendai Virus.

Science.gov (United States)

Soares, Filipa A C; Pedersen, Roger A; Vallier, Ludovic

2016-01-01

This protocol describes the efficient isolation of peripheral blood mononuclear cells from circulating blood via density gradient centrifugation and subsequent generation of integration-free human induced pluripotent stem cells. Peripheral blood mononuclear cells are cultured for 9 days to allow expansion of the erythroblast population. The erythroblasts are then used to derive human induced pluripotent stem cells using Sendai viral vectors, each expressing one of the four reprogramming factors Oct4, Sox2, Klf4, and c-Myc.

Dispersive FDTD analysis of induced electric field in human models due to electrostatic discharge

International Nuclear Information System (INIS)

Hirata, Akimasa; Nagai, Toshihiro; Koyama, Teruyoshi; Hattori, Junya; Chan, Kwok Hung; Kavet, Robert

2012-01-01

Contact currents flow from/into a charged human body when touching a grounded conductive object. An electrostatic discharge (ESD) or spark may occur just before contact or upon release. The current may stimulate muscles and peripheral nerves. In order to clarify the difference in the induced electric field between different sized human models, the in-situ electric fields were computed in anatomically based models of adults and a child for a contact current in a human body following ESD. A dispersive finite-difference time-domain method was used, in which biological tissue is assumed to obey a four-pole Debye model. From our computational results, the first peak of the discharge current was almost identical across adult and child models. The decay of the induced current in the child was also faster due mainly to its smaller body capacitance compared to the adult models. The induced electric fields in the forefingers were comparable across different models. However, the electric field induced in the arm of the child model was found to be greater than that in the adult models primarily because of its smaller cross-sectional area. The tendency for greater doses in the child has also been reported for power frequency sinusoidal contact current exposures as reported by other investigators. (paper)

Molecular characterization of thymidine kinase mutants of human cells induced by densely ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Kronenberg, A; Little, J B

1989-04-01

In order to characterize the nature of mutants induced by densely ionizing radiations at an autosomal locus, the authors have isolated a series of 99 thymidine kinase (tk) mutants of human TK6 lymphoblastoid cells iraadiated with either fast neutrons or accelerated argon ions. Individual muant clones were examined for alterations in their restriction fragment pattern after hybridization with a human cDNA probe for tk. A restriction fragment length polymorphism (RFLP) allowed identification of the active tk allele. Among the neutron-induced mutants, 34/52 exhibited loss of the previously active allele while 6/52 exhibited intragenic rearrangements. Among the argon-induced mutants 27/46 exhibited allele loses and 10/46 showed rearrangements within the tk locus. The remaining mutants had restriction patterns indistinguishable from the TK6 parent. Each of the mutant clones was further examined for structural alterations within the c-erbAl locus which has been localized to chromosome 17q11-q22, at some unknown distance from the human tk locus at chromosome 17q21-q22. A substantial proportion (54%) of tk mutants induced by densely ionizing radiation showed loss of the c-erb locus on the homologous chromosome, suggesting that the mutations involve large-scale genetic changes. (author). 51 refs.; 2 figs.; 6 tabs.

Dispersive FDTD analysis of induced electric field in human models due to electrostatic discharge.

Science.gov (United States)

Hirata, Akimasa; Nagai, Toshihiro; Koyama, Teruyoshi; Hattori, Junya; Chan, Kwok Hung; Kavet, Robert

2012-07-07

Contact currents flow from/into a charged human body when touching a grounded conductive object. An electrostatic discharge (ESD) or spark may occur just before contact or upon release. The current may stimulate muscles and peripheral nerves. In order to clarify the difference in the induced electric field between different sized human models, the in-situ electric fields were computed in anatomically based models of adults and a child for a contact current in a human body following ESD. A dispersive finite-difference time-domain method was used, in which biological tissue is assumed to obey a four-pole Debye model. From our computational results, the first peak of the discharge current was almost identical across adult and child models. The decay of the induced current in the child was also faster due mainly to its smaller body capacitance compared to the adult models. The induced electric fields in the forefingers were comparable across different models. However, the electric field induced in the arm of the child model was found to be greater than that in the adult models primarily because of its smaller cross-sectional area. The tendency for greater doses in the child has also been reported for power frequency sinusoidal contact current exposures as reported by other investigators.

Infrared A radiation promotes survival of human melanocytes carrying ultraviolet radiation-induced DNA damage.

Science.gov (United States)

Kimeswenger, Susanne; Schwarz, Agatha; Födinger, Dagmar; Müller, Susanne; Pehamberger, Hubert; Schwarz, Thomas; Jantschitsch, Christian

2016-06-01

The link between solar radiation and melanoma is still elusive. Although infrared radiation (IR) accounts for over 50% of terrestrial solar energy, its influence on human skin is not well explored. There is increasing evidence that IR influences the expression patterns of several molecules independently of heat. A previous in vivo study revealed that pretreatment with IR might promote the development of UVR-induced non-epithelial skin cancer and possibly of melanoma in mice. To expand on this, the aim of the present study was to evaluate the impact of IR on UVR-induced apoptosis and DNA repair in normal human epidermal melanocytes. The balance between these two effects is a key factor of malignant transformation. Human melanocytes were exposed to physiologic doses of IR and UVR. Compared to cells irradiated with UVR only, simultaneous exposure to IR significantly reduced the apoptotic rate. However, IR did not influence the repair of UVR-induced DNA damage. IR partly reversed the pro-apoptotic effects of UVR via modification of the expression and activity of proteins mainly of the extrinsic apoptotic pathway. In conclusion, IR enhances the survival of melanocytes carrying UVR-induced DNA damage and thereby might contribute to melanomagenesis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Vulnerability of Earth Systems to Human-Induced Global Change and Strategies for Mitigation

Science.gov (United States)

Watson, R. T.

2002-12-01

Since the IGY, there has been growing evidence that climate is changing in response to human activities. The overwhelming majority of scientific experts, whilst recognizing that scientific uncertainties exist, nonetheless believe that human-induced climate change is inevitable. Indeed, during the last few years, many parts of the world have suffered major heat waves, floods, droughts, fires and extreme weather events leading to significant economic losses and loss of life. While individual events cannot be directly linked to human-induced climate change, the frequency and magnitude of these types of events are predicted to increase in a warmer world. The question is not whether climate will change, but rather how much (magnitude), how fast (the rate of change) and where (regional patterns). It is also clear that climate change and other human-induced modifications to the environment will, in many parts of the world, adversely affect socio-economic sectors, including water resources, agriculture, forestry, fisheries and human settlements, ecological systems (particularly forests and coral reefs), and human health (particularly diseases spread by insects), with developing countries being the most vulnerable. Environmental degradation of all types (i.e., climate change, loss of biodiversity, land degradation, air and water quality) all undermine the challenge of poverty alleviation and sustainable economic growth. One of the major challenges facing humankind is to provide an equitable standard of living for this and future generations: adequate food, water and energy, safe shelter and a healthy environment (e.g., clean air and water). Unfortunately, human-induced climate change, as well as other global environmental issues such as land degradation, loss of biological diversity and stratospheric ozone depletion, threatens our ability to meet these basic human needs. The good news is, however, that the majority of experts believe that significant reductions in net

Molecular and biochemical analyses of spontaneous and X-ray-induced mutants in human lymphoblastoid cells

Energy Technology Data Exchange (ETDEWEB)

Liber, H L; Call, K M; Little, J B

1987-05-01

The authors have isolated a series of 14 spontaneously arising and 28 X-ray-induced mutants at the hypoxanthine-guanine phosphoribosyltransferase (hgprt) locus in human lymphoblastoid cells. Among the spontaneous mutants, 5/14 (36%) had detectable alterations in their restriction fragment pattern after hybridization with a human cDNA probe for hgprt. Of the 10 remaining mutants, 4 had partial HGPRT enzyme activity, which suggested that they contained point mutations. Among the 28 mutants induced by 150 rad of X-rays, 15 (54%) had deletions of part or all of the hgprt gene. Of the remaining 13 (18% overall) 5 had partial HGPRT enzyme activity, which suggested that they contained point mutations. These data imply that in this human cell system, X-rays induce both point mutants which have residual enzyme activity as well as mutations involving relatively large deletions of DNA. 48 reference, 1 figure, 4 tables.

Human retinal pigment epithelial cell-induced apoptosis in activated T cells

DEFF Research Database (Denmark)

Jørgensen, A; Wiencke, A K; la Cour, M

1998-01-01

human retinal pigment epithelial (RPE) cells can induce apoptosis in activated T cells. METHODS: Fas ligand (FasL) expression was detected by flow cytometry and immunohistochemistry. Cultured RPE cells were cocultured with T-cell lines and peripheral blood lymphocytes for 6 hours to 2 days. Induction...... of apoptosis was detected by 7-amino-actinomycin D and annexin V staining. RESULTS: Retinal pigment epithelial cells expressed FasL and induced apoptosis in activated Fas+ T cells. Blocking of Fas-FasL interaction with antibody strongly inhibited RPE-mediated T-cell apoptosis. Retinal pigment epithelial cells...... induced apoptosis in several activated T-cell populations and T-cell lines, including T-cell antigen receptor (TCR)-CD3-negative T-cell lines. In contrast, RPE cells induced little or no apoptosis in resting peripheral T cells. Major histocompatibility complex (MHC) class II monoclonal antibodies, which...

In vivo study of the human skin by the method of laser-induced fluorescence spectroscopy

International Nuclear Information System (INIS)

Borisova, E.; Avramov, L.

2000-01-01

The goals of this study are to perform a preliminary evaluation of the diagnostic potential of noninvasive laser-induced auto-fluorescence spectroscopy (LIAFS) for human skin and optimize of detection and diagnosis of hollow organs and skin. In recent years, there has been growing interest in the use of laser-induced fluorescence to discriminate disease from normal surrounding tissue. The most fluorescence studies have used exogenous fluorophores of this discrimination. The laser-induced auto-fluorescence which is used for diagnosis of tissues in the human body avoids administration of any drugs. In this study a technique for optical biopsy of in vivo human skin is presented. The auto-fluorescence characterization of tissue relies on different spectral properties of tissues. It was demonstrated a differentiation between normal skin and skin with vitiligo. Two main endogenous fluorophores in the human skin account for most of the cellular auto-fluorescence for excitation wavelength 337 nm reduced from of nicotinamide adenine dinucleotide and collagen. The auto-fluorescence spectrum of human skin depend on main internal absorbers which are blood and melanin. In this study was described the effect caused by blood and melanin content on the shape of the auto-fluorescence spectrum of human skin. Human skin fluorescence spectrum might provide dermatologists with important information and such investigations are successfully used now in skin disease diagnostics, in investigation of the environmental factor impact or for evaluation of treatment efficiency. (authors)

Evaluation of the rotenone-induced activation of the Nrf2 pathway in a neuronal model derived from human induced pluripotent stem cells.

Science.gov (United States)

Zagoura, Dimitra; Canovas-Jorda, David; Pistollato, Francesca; Bremer-Hoffmann, Susanne; Bal-Price, Anna

2017-06-01

Human induced pluripotent stem cells (hiPSCs) are considered as a powerful tool for drug and chemical screening and development of new in vitro testing strategies in the field of toxicology, including neurotoxicity evaluation. These cells are able to expand and efficiently differentiate into different types of neuronal and glial cells as well as peripheral neurons. These human cells-based neuronal models serve as test systems for mechanistic studies on different pathways involved in neurotoxicity. One of the well-known mechanisms that are activated by chemically-induced oxidative stress is the Nrf2 signaling pathway. Therefore, in the current study, we evaluated whether Nrf2 signaling machinery is expressed in human induced pluripotent stem cells (hiPSCs)-derived mixed neuronal/glial culture and if so whether it becomes activated by rotenone-induced oxidative stress mediated by complex I inhibition of mitochondrial respiration. Rotenone was found to induce the activation of Nrf2 signaling particularly at the highest tested concentration (100 nM), as shown by Nrf2 nuclear translocation and the up-regulation of the Nrf2-downstream antioxidant enzymes, NQO1 and SRXN1. Interestingly, exposure to rotenone also increased the number of astroglial cells in which Nrf2 activation may play an important role in neuroprotection. Moreover, rotenone caused cell death of dopaminergic neurons since a decreased percentage of tyrosine hydroxylase (TH + ) cells was observed. The obtained results suggest that hiPSC-derived mixed neuronal/glial culture could be a valuable in vitro human model for the establishment of neuronal specific assays in order to link Nrf2 pathway activation (biomarker of oxidative stress) with additional neuronal specific readouts that could be applied to in vitro neurotoxicity evaluation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

Directory of Open Access Journals (Sweden)

Lee Adam Wheeler

2016-05-01

Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

Genital Human Papillomavirus Infection Progression to External Genital Lesions: The HIM Study.

Science.gov (United States)

Sudenga, Staci L; Ingles, Donna J; Pierce Campbell, Christine M; Lin, Hui-Yi; Fulp, William J; Messina, Jane L; Stoler, Mark H; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

2016-01-01

Human papillomavirus (HPV) causes two types of external genital lesions (EGLs) in men: genital warts (condyloma) and penile intraepithelial neoplasia (PeIN). The purpose of this study was to describe genital HPV progression to a histopathologically confirmed HPV-related EGL. A prospective analysis nested within the HPV Infection in Men (HIM) study was conducted among 3033 men. At each visit, visually distinct EGLs were biopsied; the biopsy specimens were subjected to pathologic evaluation and categorized by pathologic diagnoses. Genital swabs and biopsies were used to identify HPV types using the Linear Array genotyping method for swabs and INNO-LiPA for biopsy specimens. EGL incidence was determined among 1788 HPV-positive men, and cumulative incidence rates at 6, 12, and 24 mo were estimated. The proportion of HPV infections that progressed to EGL was also calculated, along with median time to EGL development. Among 1788 HPV-positive men, 92 developed an incident EGL during follow-up (9 PeIN and 86 condyloma). During the first 12 mo of follow-up, 16% of men with a genital HPV 6 infection developed an HPV 6-positive condyloma, and 22% of genital HPV 11 infections progressed to an HPV 11-positive condyloma. During the first 12 mo of follow-up, 0.5% of men with a genital HPV 16 infection developed an HPV 16-positive PeIN. Although we expected PeIN to be a rare event, the sample size for PeIN (n=10) limited the types of analyses that could be performed. Most EGLs develop following infection with HPV 6, 11, or 16, all of which could be prevented with the 4-valent HPV vaccine. In this study, we looked at genital human papillomavirus (HPV) infections that can cause lesions in men. The HPV that we detected within the lesions could be prevented by a vaccine. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

A compact human-powered energy harvesting system

International Nuclear Information System (INIS)

Rao, Yuan; McEachern, Kelly M; Arnold, David P

2013-01-01

This paper presents a fully functional, self-sufficient body-worn energy harvesting system for passively capturing energy from human motion, with the long-term vision of supplying power to portable, wearable, or even implanted electronic devices. The system requires no external power supplies and can bootstrap from zero-state-of-charge to generate electrical energy from walking, jogging and cycling; convert the induced ac voltage to a dc voltage; and then boost and regulate the dc voltage to charge a Li-ion-polymer battery. Tested under normal human activities (walking, jogging, cycling) when worn on different parts of the body, the 70 cm 3 system is shown to charge a 3.7 V rechargeable battery at charge rates ranging from 33 μW to 234 μW

Children's learning of tennis skills is facilitated by external focus instructions

Directory of Open Access Journals (Sweden)

Ricardo Hadler

2014-12-01

Full Text Available The present study examined the effects of instructions promoting external versus internal foci of attention on the learning of a tennis forehand stroke in 11-year old children. Three groups of participants practiced hitting tennis balls at a target. External focus group participants were instructed to direct their attention to the movement of the racquet, while participants in the internal focus group were asked to direct their attention to the movements of their arm. Participants in a control group did not receive attentional focus instructions. Two days after the practice phase (60 trials, learning was assessed in retention and transfer tests. The results showed that the external focus group demonstrated greater accuracy in hitting a target relative to the two other groups in retention, and relative to the internal focus group in transfer. We conclude that instructions inducing an external focus of attention can enhance children's sport skill learning.

ExternE: Externalities of energy Vol. 5. Nuclear

International Nuclear Information System (INIS)

Dreicer, M.; Tort, V.; Manen, P.

1995-01-01

Since the early 1970s, there has been increased interest in the environmental impacts that are caused by the generation of electricity. The comparative risk assessment studies at that time used mainly deaths and injuries as impact indicators. By the end of the 1980s studies changed to the assessment of the costs imposed on society and the environment that were not included in the market price of the energy produced, the so-called external costs. The preliminary studies that were published set the conceptual basis, grounded in neo-classical economics, for the valuation of the health and environmental impacts that could be assessed. As a consequence of the many questions raised by the methodologies employed by these early studies, Directorate General XII (DG XII) of the Commission of the European Communities established a collaborative research programme with the United States Department of Energy to identify an appropriate methodology for this type of work. Following the completion of this collaboration, the DG XII programme has continued as the ExternE project. The main objective of the work carried out at CEPN was to develop an impact pathway methodology for the nuclear fuel cycle that would be consistent with the methodologies developed for other fuel cycles, without loosing the nuclear-specific techniques required for a proper evaluation. In this way, comparisons between the different fuel cycles would be possible. This report presents the methodology and demonstration of the results in the context of the French nuclear fuel cycle. The United States team at Oak Ridge National Laboratory has previously issued a draft report on the results of their assessment. The French fuel cycle was broken down into 8 separate stages. Reference sites and 1990s technology were chosen to represent the total nuclear fuel cycle, as it exists today. In addition, the transportation of material between the sites was considered. The facilities are assessed for routine operation, except

Human herpesvirus 6A induces apoptosis of primary human fetal astrocytes via both caspase-dependent and -independent pathways

Directory of Open Access Journals (Sweden)

Gu Bin

2011-12-01

Full Text Available Abstract Background Human herpesvirus 6 (HHV-6 is a T-lymphtropic and neurotropic virus that can infect various types of cells. Sequential studies reported that apoptosis of glia and neurons induced by HHV-6 might act a potential trigger for some central nervous system (CNS diseases. HHV-6 is involved in the pathogenesis of encephalitis, multiple sclerosis (MS and fatigue syndrome. However, the mechanisms responsible for the apoptosis of infected CNS cells induced by HHV-6 are poorly understood. In this study, we investigated the cell death processes of primary human fetal astrocytes (PHFAs during productive HHV-6A infection and the underlying mechanisms. Results HHV-6A can cause productive infection in primary human fetal astrocytes. Annexin V-PI staining and electron microscopic analysis indicated that HHV-6A was an inducer of apoptosis. The cell death was associated with activation of caspase-3 and cleavage of poly (ADP-ribose polymerase (PARP, which is known to be an important substrate for activated caspase-3. Caspase-8 and -9 were also significantly activated in HHV-6A-infected cells. Moreover, HHV-6A infection led to Bax up-regulation and Bcl-2 down-regulation. HHV-6A infection increased the release of Smac/Diablo, AIF and cytochrome c from mitochondria to cytosol, which induced apoptosis via the caspase-dependent and -independent pathways. In addition, we also found that anti-apoptotic factors such as IAPs and NF-κB decreased in HHV-6A infected PHFAs. Conclusion This is the first demonstration of caspase-dependent and -independent apoptosis in HHV-6A-infected glial cells. These findings would be helpful in understanding the mechanisms of CNS diseases caused by HHV-6.

Bone sarcoma in humans induced by radium: A threshold response?

International Nuclear Information System (INIS)

Rowland, R.E.

1996-01-01

The radium 226 and radium 228 have induced malignancies in the skeleton (primarily bone sarcomas) of humans. They have also induced carcinomas in the paranasal sinuses and mastoid air cells. There is no evidence that any leukemias or any other solid cancers have been induced by internally deposited radium. This paper discuses a study conducted on the dial painter population. This study made a concerted effort to verify, for each of the measured radium cases, the published values of the skeletal dose and the initial intake of radium. These were derived from body content measurements made some 40 years after the radium intake. Corrections to the assumed radium retention function resulted in a considerable number of dose changes. These changes have changed the shape of the dose response function. It now appears that the induction of bone sarcomas is a threshold process

Nitric oxide from both exogenous and endogenous sources activates mitochondria-dependent events and induces insults to human chondrocytes.

Science.gov (United States)

Wu, Gong-Jhe; Chen, Tyng-Guey; Chang, Huai-Chia; Chiu, Wen-Ta; Chang, Chia-Chen; Chen, Ruei-Ming

2007-08-15

During inflammation, overproduction of nitric oxide (NO) can damage chondrocytes. In this study, we separately evaluated the toxic effects of exogenous and endogenous NO on human chondrocytes and their possible mechanisms. Human chondrocytes were exposed to sodium nitroprusside (SNP), an NO donor, or a combination of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) as the exogenous and endogenous sources of NO, respectively. Administration of SNP or a combination of LPS and IFN-gamma in human chondrocytes increased cellular NO levels but decreased cell viability. Exposure to exogenous or endogenous NO significantly induced apoptosis of human chondrocytes. When treated with exogenous or endogenous NO, the mitochondrial membrane potential time-dependently decreased. Exposure to exogenous or endogenous NO significantly enhanced cellular reactive oxygen species (ROS) and cytochrome c (Cyt c) levels. Administration of exogenous or endogenous NO increased caspase-3 activity and consequently induced DNA fragmentation. Suppression of caspase-3 activation by Z-DEVD-FMK decreased NO-induced DNA fragmentation and cell apoptosis. Similar to SNP, exposure of human chondrocytes to S-nitrosoglutathione (GSNO), another NO donor, caused significant increases in Cyt c levels, caspase-3 activity, and DNA fragmentation, and induced cell apoptosis. Pretreatment with N-monomethyl arginine (NMMA), an inhibitor of NO synthase, significantly decreased cellular NO levels, and lowered endogenous NO-induced alterations in cellular Cyt c amounts, caspase-3 activity, DNA fragmentation, and cell apoptosis. Results of this study show that NO from exogenous and endogenous sources can induce apoptotic insults to human chondrocytes via a mitochondria-dependent mechanism.

Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo.

Science.gov (United States)

Roux, Clémence; Saviane, Gaëlle; Pini, Jonathan; Belaïd, Nourhène; Dhib, Gihen; Voha, Christine; Ibáñez, Lidia; Boutin, Antoine; Mazure, Nathalie M; Wakkach, Abdelilah; Blin-Wakkach, Claudine; Rouleau, Matthieu

2017-01-01

Despite mesenchymal stromal cells (MSCs) are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited in vitro expansion, absence of a full phenotypic characterization, few insights on their in vivo fate). Standardized MSCs derived in vitro from human-induced pluripotent stem (huIPS) cells, remediating part of these issues, are considered as well as a valuable tool for therapeutic approaches, but their functions remained to be fully characterized. We generated multipotent MSCs derived from huiPS cells (huiPS-MSCs), and focusing on their immunosuppressive activity, we showed that human T-cell activation in coculture with huiPS-MSCs was significantly reduced. We also observed the generation of functional CD4 + FoxP3 + regulatory T (Treg) cells. Further tested in vivo in a model of human T-cell expansion in immune-deficient NSG mice, huiPS-MSCs immunosuppressive activity prevented the circulation and the accumulation of activated human T cells. Intracytoplasmic labeling of cytokines produced by the recovered T cells showed reduced percentages of human-differentiated T cells producing Th1 inflammatory cytokines. By contrast, T cells producing IL-10 and FoxP3 + -Treg cells, absent in non-treated animals, were detected in huiPS-MSCs treated mice. For the first time, these results highlight the immunosuppressive activity of the huiPS-MSCs on human T-cell stimulation with a concomitant generation of human Treg cells in vivo . They may favor the development of new tools and strategies based on the use of huiPS cells and their derivatives for the induction of immune tolerance.

Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo

Directory of Open Access Journals (Sweden)

Clémence Roux

2018-01-01

Full Text Available Despite mesenchymal stromal cells (MSCs are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited in vitro expansion, absence of a full phenotypic characterization, few insights on their in vivo fate. Standardized MSCs derived in vitro from human-induced pluripotent stem (huIPS cells, remediating part of these issues, are considered as well as a valuable tool for therapeutic approaches, but their functions remained to be fully characterized. We generated multipotent MSCs derived from huiPS cells (huiPS-MSCs, and focusing on their immunosuppressive activity, we showed that human T-cell activation in coculture with huiPS-MSCs was significantly reduced. We also observed the generation of functional CD4+ FoxP3+ regulatory T (Treg cells. Further tested in vivo in a model of human T-cell expansion in immune-deficient NSG mice, huiPS-MSCs immunosuppressive activity prevented the circulation and the accumulation of activated human T cells. Intracytoplasmic labeling of cytokines produced by the recovered T cells showed reduced percentages of human-differentiated T cells producing Th1 inflammatory cytokines. By contrast, T cells producing IL-10 and FoxP3+-Treg cells, absent in non-treated animals, were detected in huiPS-MSCs treated mice. For the first time, these results highlight the immunosuppressive activity of the huiPS-MSCs on human T-cell stimulation with a concomitant generation of human Treg cells in vivo. They may favor the development of new tools and strategies based on the use of huiPS cells and their derivatives for the induction of immune tolerance.

External costs of nuclear-generated electricity

International Nuclear Information System (INIS)

Rotaru, I.; Glodeanu, F.; Popescu, D.; Andrei, V.

2004-01-01

External costs of nuclear power include: future financial liabilities arising from decommissioning and dismantling of nuclear facilities, health and environmental impacts of radioactivity releases in routine operation, radioactive waste disposal and effects of severe accidents. The nuclear energy industry operates under regulations that impose stringent limits to atmospheric emissions and liquid effluents from nuclear facilities as well as requiring the containment and confinement of solid radioactive waste to ensure its isolation from the biosphere as long as it may be harmful for human health and the environment. The capital and operating costs of nuclear power plants and fuel cycle facilities already internalize a major portion of the above-mentioned potential external costs, and these are reflected in the prices paid by consumers of nuclear-generated electricity. The externality related to potential health and environmental impacts of radioactive releases during routine operations have been assessed in a large number of comprehensive studies, in particular the ExternE project that was created in the framework of the European Commission. With regard to effects of severe nuclear accidents, a special legal regime, the third-party liability system, has been implemented to provide limited third party liability coverage in the event of a nuclear accident. The nuclear plant owners are held liable for some specified first substantial part of damages to third parties, and must secure insurance coverage adequate to cover this part. The Government provides coverage for some specified substantial second part of the damages, with any remaining damages to be considered by the national legislation. Thus, the costs of an incident or accident are fully internalized in the costs borne by the nuclear plant owners. Externalities of energy are not limited to environmental and health related impacts, but may result also from macro-economic, policy or strategic factors not reflected

Level of action of cathodal DC polarisation induced inhibition of the human motor cortex.

Science.gov (United States)

Nitsche, Michael A; Nitsche, Maren S; Klein, Cornelia C; Tergau, Frithjof; Rothwell, John C; Paulus, Walter

2003-04-01

To induce prolonged motor cortical excitability reductions by transcranial direct current stimulation in the human. Cathodal direct current stimulation was applied transcranially to the hand area of the human primary motor cortex from 5 to 9 min in separate sessions in twelve healthy subjects. Cortico-spinal excitability was tested by single pulse transcranial magnetic stimulation. Transcranial electrical stimulation and H-reflexes were used to learn about the origin of the excitability changes. Neurone specific enolase was measured before and after the stimulation to prove the safety of the stimulation protocol. Five and 7 min direct current stimulation resulted in motor cortical excitability reductions, which lasted for minutes after the end of stimulation, 9 min stimulation induced after-effects for up to an hour after the end of stimulation, as revealed by transcranial magnetic stimulation. Muscle evoked potentials elicited by transcranial electric stimulation and H-reflexes did not change. Neurone specific enolase concentrations remained stable throughout the experiments. Cathodal transcranial direct current stimulation is capable of inducing prolonged excitability reductions in the human motor cortex non-invasively. These changes are most probably localised intracortically.

Induced mutations for human welfare through agriculture

International Nuclear Information System (INIS)

Patil, S.A.

2009-01-01

pulses and oil seeds. The Groundnut varieties of BARC have spread on more than one million hectares and are providing additional income of more than five hundred crores annually on a continuing basis. These examples prove beyond doubt that induced mutations have played a vital role for human welfare through agriculture

Comparison of gamma radiation - induced effects in two human prostate cancer cells

International Nuclear Information System (INIS)

Vucic, V.; Adzic, M.; Ruzdijic, S.; Radojcic, M.B. . E-mail address of corresponding author: vesnav@vin.bg.ac.yu; Vucic, V.)

2005-01-01

In this study, the effects of gamma radiation on two hormone refractory human prostate cancer cell lines, DU 145 and PC-3, were followed. It was shown that gamma radiation induced significant inhibition of cell proliferation and viability in dose dependent manner. Antiproliferative effects of radiation were similar in both cell lines, and more pronounced than cytotoxic effects. In addition to that, PC-3 cell line was more resistant to radiation -induced cytotoxicity. (author)

External representation of argumentation in CSCL and the management of cognitive load

NARCIS (Netherlands)

Bruggen, J.M.; Kirschner, P.A.; Jochems, W.

2002-01-01

Computer-supported collaborative learning (CSCL) environments, particularly environments where students share external representations, are discussed as an interesting area for the application of cognitive load theory (CLT). CSCL environments share a number of characteristics that will induce

Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways

Energy Technology Data Exchange (ETDEWEB)

Mu, Shumin [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Hospital Affiliated to Shandong Traditional Chinese Medicine University, Jinan 250011 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Tian, Xingsong; Ruan, Yongwei [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Liu, Yuantao [The Second Hospital of Shandong University, Jinan 250033 (China); Bian, Dezhi [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Jining Medical College, Jining 272013 (China); Ma, Chunyan [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Yu, Chunxiao [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Feng, Mei [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Wang, Furong [Shandong University of Traditional Chinese Medicine, Jinan 250011 (China); Gao, Ling [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China); Zhao, Jia-jun, E-mail: jjzhao@medmail.com.cn [Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021 (China)

2012-02-10

Highlights: Black-Right-Pointing-Pointer Diosgenin induces apoptosis in IGF-1-treated thyrocytes through two caspase pathways. Black-Right-Pointing-Pointer Diosgenin inhibits FLIP and activates caspase-8 in FAS related-pathway. Black-Right-Pointing-Pointer Diosgenin increases ROS, regulates the ratio of Bax/Bcl-2 in mitochondrial pathway. -- Abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24 h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.

Involvement of mismatch repair proteins in adaptive responses induced by N-methyl-N'-nitro-N-nitrosoguanidine against {gamma}-induced genotoxicity in human cells

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Ayumi; Sakamoto, Yasuteru; Masumura, Kenichi; Honma, Masamitsu [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Nohmi, Takehiko, E-mail: nohmi@nihs.go.jp [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan)

2011-08-01

Highlights: {yields} Health effects of radiation should be evaluated in combination with chemicals. {yields} Here, we show that MNNG suppresses radiation-induced genotoxicity in human cells. {yields} Mismatch repair proteins play critical roles in the apparent adaptive responses. {yields} Chemical exposure may modulate radiation-induced genotoxicity in humans. - Abstract: As humans are exposed to a variety of chemical agents as well as radiation, health effects of radiation should be evaluated in combination with chemicals. To explore combined genotoxic effects of radiation and chemicals, we examined modulating effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting methylating agent, against genotoxicity of {gamma}-radiation. Human lymphoblastoid TK6 cells and its mismatch-deficient derivative, i.e., MT1 cells, were treated with MNNG for 24 h before they were exposed to {gamma}-irradiation at a dose of 1.0 Gy, and the resulting genotoxicity was examined. In TK6 cells, the pretreatments with MNNG at low doses suppressed frequencies of the thymidine kinase (TK) gene mutation and micronucleus (MN) formation induced by {gamma}-irradiation and thus the dose responses of TK and MN assays were U-shaped along with the pretreatment doses of MNNG. In contrast, the genotoxic effects of MNNG and {gamma}-irradiation were additive in MT1 cells and the frequencies of TK mutations and MN induction increased along with the doses of MNNG. Apoptosis induced by {gamma}-radiation was suppressed by the pretreatments in TK6 cells, but not in MT1 cells. The expression of p53 was induced and cell cycle was delayed at G2/M phase in TK6, but not in MT1 cells, by the treatments with MNNG. These results suggest that pretreatments of MNNG at low doses suppress genotoxicity of {gamma}-radiation in human cells and also that mismatch repair proteins are involved in the apparent adaptive responses.

Estimating Externalities of Natural Gas Fuel Cycles, Report 4

Energy Technology Data Exchange (ETDEWEB)

Barnthouse, L.W.; Cada, G.F.; Cheng, M.-D.; Easterly, C.E.; Kroodsma, R.L.; Lee, R.; Shriner, D.S.; Tolbert, V.R.; Turner, R.S.

1998-01-01

This report describes methods for estimating the external costs (and possibly benefits) to human health and the environment that result from natural gas fuel cycles. Although the concept of externalities is far from simple or precise, it generally refers to effects on individuals' well being, that result from a production or market activity in which the individuals do not participate, or are not fully compensated. In the past two years, the methodological approach that this report describes has quickly become a worldwide standard for estimating externalities of fuel cycles. The approach is generally applicable to any fuel cycle in which a resource, such as coal, hydro, or biomass, is used to generate electric power. This particular report focuses on the production activities, pollution, and impacts when natural gas is used to generate electric power. In the 1990s, natural gas technologies have become, in many countries, the least expensive to build and operate. The scope of this report is on how to estimate the value of externalities--where value is defined as individuals' willingness to pay for beneficial effects, or to avoid undesirable ones. This report is about the methodologies to estimate these externalities, not about how to internalize them through regulations or other public policies. Notwithstanding this limit in scope, consideration of externalities can not be done without considering regulatory, insurance, and other considerations because these institutional factors affect whether costs (and benefits) are in fact external, or whether they are already somehow internalized within the electric power market. Although this report considers such factors to some extent, much analysis yet remains to assess the extent to which estimated costs are indeed external. This report is one of a series of reports on estimating the externalities of fuel cycles. The other reports are on the coal, oil, biomass, hydro, and nuclear fuel cycles, and on general

Spin-lattice dynamics simulation of external field effect on magnetic order of ferromagnetic iron

Directory of Open Access Journals (Sweden)

C. P. Chui

2014-03-01

Full Text Available Modeling of field-induced magnetization in ferromagnetic materials has been an active topic in the last dozen years, yet a dynamic treatment of distance-dependent exchange integral has been lacking. In view of that, we employ spin-lattice dynamics (SLD simulations to study the external field effect on magnetic order of ferromagnetic iron. Our results show that an external field can increase the inflection point of the temperature. Also the model provides a better description of the effect of spin correlation in response to an external field than the mean-field theory. An external field has a more prominent effect on the long range magnetic order than on the short range counterpart. Furthermore, an external field allows the magnon dispersion curves and the uniform precession modes to exhibit magnetic order variation from their temperature dependence.

Heavy metal-induced cytotoxicity to cultured human epidermal keratinocytes and effects of antioxidants.

Science.gov (United States)

Kappus, H; Reinhold, C

1994-04-01

Human epidermal keratinocytes which have been cultured were treated with the heavy metal ions of cadmium, mercury, copper and zinc. Cytotoxicity was measured either by protein estimation or by using the neutral red assay. Antioxidants were added in order to find out whether heavy metal-induced cytotoxicity is related to oxidative stress. All metals used showed considerable cytotoxic effects within 24 h in moderate concentrations. None of the antioxidants vitamin E (alpha-tocopherol), pyrogallol, propyl gallate, BHT or ebselen showed any protective or preventive effect. This indicates that oxidative stress may not be involved in the cytotoxicity induced by heavy metals in human epidermal keratinocytes. The cells used are, however, a valuable tool to study mechanisms of cytotoxicity.

Under-use of body energy and over-use of external energy

Energy Technology Data Exchange (ETDEWEB)

Norgard, Jorgen Stig [Technical Univ. of Denmark, Lyngby (Denmark). Dept. of Civil Engineering

2005-07-01

The world's affluent countries, such as the EU, are facing two severe problems with long-term consequences. One problem is the epidemic-like increase in adverse health effects, which are related to the increasing wealth, primarily appearing as obesity and its associated diseases. This is caused by overeating and under-use of the body energy, due to increased use of mechanized and energy consuming assistance for transport and other daily tasks. This connects to the other problem, namely these countries' excessive use of fossil fuels and other environmentally harmful forms of nature's external energy. This paper illuminates the options for integrated solutions to the two problems by making more use of body energy as a means to reduce the use of nature's external energy. First is listed a human's body energy used for various tasks and occupations, showing that a person's use of external energy is an order of magnitude higher, which can be expressed by the scores of 'energy slaves' each citizen utilizes. An extra health driven physical effort by humans seems to have negligible direct impact on energy consumption. The paper will, however, indicate examples of significant indirect savings of external energy, achieved by healthy extra human efforts. Also, the paper will suggest ways to integrate energy saving policies with health policies for organizing and designing cities and houses to be 'healthy inconvenient', encouraging or pushing people to use their body in their daily doings. This is an enormous challenge to the conventional way of thinking among architects, engineers, planners, as well as individuals in general.

Cisplatin induces protective autophagy through activation of BECN1 in human bladder cancer cells.

Science.gov (United States)

Lin, Ji-Fan; Lin, Yi-Chia; Tsai, Te-Fu; Chen, Hung-En; Chou, Kuang-Yu; Hwang, Thomas I-Sheng

2017-01-01

Cisplatin-based chemotherapy is the first line treatment for several cancers including bladder cancer (BC). Autophagy induction has been implied to contribute to cisplatin resistance in ovarian cancer; and a high basal level of autophagy has been demonstrated in human bladder tumors. Therefore, it is reasonable to speculate that autophagy may account for the failure of cisplatin single treatment in BC. This study investigated whether cisplatin induces autophagy and the mechanism involved using human BC cell lines. Human BC cells (5637 and T24) were used in this study. Cell viability was detected using water soluble tetrazolium-8 reagents. Autophagy induction was detected by monitoring the levels of light chain 3 (LC3)-II and p62 by Western blot, LC3-positive puncta formation by immunofluorescence, and direct observation of the autophagolysosome (AL) formation by transmission electron microscopy. Inhibitors including bafilomycin A1 (Baf A1), chloroquine (CQ), and shRNA-based lentivirus against autophagy-related genes (ATG7 and ATG12) were utilized. Apoptosis level was detected by caspase 3/7 activity and DNA fragmentation. Cisplatin decreased cell viability and induced apoptosis of 5637 and T24 cells in a dose-and time-dependent manner. The increased LC3-II accumulation, p62 clearance, the number of LC3-positive puncta, and ALs in cisplatin-treated cells suggested that cisplatin indeed induces autophagy. Inhibition of cisplatin-induced autophagy using Baf A1, CQ, or ATG7/ATG12 shRNAs significantly enhanced cytotoxicity of cisplatin toward BC cells. These results indicated that cisplatin induced protective autophagy which may contribute to the development of cisplatin resistance and resulted in treatment failure. Mechanistically, upregulation of beclin-1 (BECN1) was detected in cisplatin-treated cells, and knockdown of BECN1 using shRNA attenuated cisplatin-induced autophagy and subsequently enhanced cisplatin-induced apoptosis. Collectively, the study results

Sprint: The first flight demonstration of the external work system robots

Science.gov (United States)

Price, Charles R.; Grimm, Keith

1995-01-01

The External Works Systems (EWS) 'X Program' is a new NASA initiative that will, in the next ten years, develop a new generation of space robots for active and participative support of zero g external operations. The robotic development will center on three areas: the assistant robot, the associate robot, and the surrogate robot that will support external vehicular activities (EVA) prior to and after, during, and instead of space-suited human external activities respectively. The EWS robotics program will be a combination of technology developments and flight demonstrations for operational proof of concept. The first EWS flight will be a flying camera called 'Sprint' that will seek to demonstrate operationally flexible, remote viewing capability for EVA operations, inspections, and contingencies for the space shuttle and space station. This paper describes the need for Sprint and its characteristics.

Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

Science.gov (United States)

Barruet, Emilie; Hsiao, Edward C

2016-01-01

Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

The effect of an Er,Cr:YSGG laser on external adaptation of healthy and decayed cavities

International Nuclear Information System (INIS)

Kabbach, William; Tonetto, Mateus Rodrigues; Campos, Edson Alves; Andrade, Marcelo Ferrarezi; Frizzera, Fausto; Zezéll, Denise Maria; Bandéca, Matheus Coelho; Borges, Alvaro Henrique

2014-01-01

The aim of this study was to evaluate the influence of chlorhexidine and Er,Cr:YSGG laser irradiation on the bond strength and external adaptation in mixed healthy and caries-affected class V cavities before and after thermal cycling. Thirty-six cavity preparations were made in mixed class V buccal human molars, half of them being artificially caries-induced. Any remaining affected dentin was removed from the cavity with a round burr at low speed. The teeth were divided into six groups, according to cleaning agent for both healthy and caries-induced dentin: no treatment, chlorhexidine and erbium, chromium-doped: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) laser irradiation. A Filtek P90 (3M ESPE, St Paul, MN, USA) silorane adhesive restorative system was used. The specimens were subjected to 5000 thermal cycles (5–55 °C 60 min). Epoxy replicas were obtained to characterize the external adaptation under scanning electron microscopy. The average percentages of non-continuous margins were 5.41% and 6.49% in enamel dentin before thermal cycling and 25% and 33.7% after thermal cycling, respectively. The caries-affected and laser irradiated cavities showed higher non-continuous margins. Thermal cycling was able to raise the percentage of non-continuous margin for all groups. Chlorhexidine did not affect the marginal adaptation results, and the Er,Cr: YSGG laser irradiation showed significantly worse results compared with the control group. (paper)

Health Externalities and Heat savings in Energy System Modelling

DEFF Research Database (Denmark)

Zvingilaite, Erika

Energy consumption and production can cause air pollution with global impact, such as CO2, and local/regional air pollutants, such as SO2, NOx and PM2.5, as a result of fuel combustion. Use of fossil fuels leads to global CO2 emissions and causes global warming effects, regardless place or height......-related external costs can be internalised, for instance, in energy system modelling. External costs of global warming and human health damage can be of comparable magnitude.However, in contrast to global CO2 impacts, air pollution damage to human health depends on a number of factors, related to location...... and included in an energy system optimisation model. The performed analysis of the Danish heat and power sector concludes that accounting for spatial variation of health damage costs in heat and power system optimisation model has an effect on the optimal technology mix and distribution of energy plants among...

Tributyltin induces mitochondrial fission through Mfn1 degradation in human induced pluripotent stem cells.

Science.gov (United States)

Yamada, Shigeru; Asanagi, Miki; Hirata, Naoya; Itagaki, Hiroshi; Sekino, Yuko; Kanda, Yasunari

2016-08-01

Organotin compounds, such as tributyltin (TBT), are well-known endocrine disruptors. TBT is also known to cause various forms of cytotoxicity, including neurotoxicity and immunotoxicity. However, TBT toxicity has not been identified in normal stem cells. In the present study, we examined the effects of TBT on cell growth in human induced pluripotent stem cells (iPSCs). We found that exposure to nanomolar concentrations of TBT decreased intracellular ATP levels and inhibited cell viability in iPSCs. Because TBT suppressed energy production, which is a critical function of the mitochondria, we further assessed the effects of TBT on mitochondrial dynamics. Staining with MitoTracker revealed that nanomolar concentrations of TBT induced mitochondrial fragmentation. TBT also reduced the expression of mitochondrial fusion protein mitofusin 1 (Mfn1), and this effect was abolished by knockdown of the E3 ubiquitin ligase membrane-associated RING-CH 5 (MARCH5), suggesting that nanomolar concentrations of TBT could induce mitochondrial dysfunction via MARCH5-mediated Mfn1 degradation in iPSCs. Thus, mitochondrial function in normal stem cells could be used to assess cytotoxicity associated with metal exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

UV-induced DNA-binding proteins in human cells

International Nuclear Information System (INIS)

Glazer, P.M.; Greggio, N.A.; Metherall, J.E.; Summers, W.C.

1989-01-01

To investigate the response of human cells to DNA-damaging agents such as UV irradiation, the authors examined nuclear protein extracts of UV-irradiated HeLa cells for the presence of DNA-binding proteins. Electrophoretically separated proteins were transferred to a nitrocellulose filter that was subsequently immersed in a binding solution containing radioactively labeled DNA probes. Several DNA-binding proteins were induced in HeLa cells after UV irradiation. These included proteins that bind predominantly double-stranded DNA and proteins that bind both double-stranded and single-stranded DNA. The binding proteins were induced in a dose-dependent manner by UV light. Following a dose of 12 J/m 2 , the binding proteins in the nuclear extracts increased over time to a peak in the range of 18 hr after irradiation. Experiments with metabolic inhibitors (cycloheximide and actinomycin D) revealed that de novo synthesis of these proteins is not required for induction of the binding activities, suggesting that the induction is mediated by protein modification

Aqueous Fraction of Nephelium ramboutan-ake Rind Induces Mitochondrial-Mediated Apoptosis in HT-29 Human Colorectal Adenocarcinoma Cells

Directory of Open Access Journals (Sweden)

Muhamad Noor Alfarizal Kamarudin

2012-05-01

Full Text Available The aim of this study was to investigate the cytotoxic and apoptotic effects of Nephelium ramboutan-ake (pulasan rind in selected human cancer cell lines. The crude ethanol extract and fractions (ethyl acetate and aqueous of N. ramboutan-ake inhibited the growth of HT-29, HCT-116, MDA-MB-231, Ca Ski cells according to MTT assays. The N. ramboutan-ake aqueous fraction (NRAF was found to exert the greatest cytotoxic effect against HT-29 in a dose-dependent manner. Evidence of apoptotic cell death was revealed by features such as chromatin condensation, nuclear fragmentation and apoptotic body formation. The result from a TUNEL assay strongly suggested that NRAF brings about DNA fragmentation in HT-29 cells. Phosphatidylserine (PS externalization on the outer leaflet of plasma membranes was detected with annexin V-FITC/PI binding, confirming the early stage of apoptosis. The mitochondrial permeability transition is an important step in the induction of cellular apoptosis, and the results clearly suggested that NRAF led to collapse of mitochondrial transmembrane potential in HT-29 cells. This attenuation of mitochondrial membrane potential (Δψm was accompanied by increased production of ROS and depletion of GSH, an increase of Bax protein expression, and induced-activation of caspase-3/7 and caspase-9. These combined results suggest that NRAF induces mitochondrial-mediated apoptosis.

A schedule to demonstrate radiation-induced sister chromatid exchanges in human lymphocytes

International Nuclear Information System (INIS)

Chaudhuri, J.P.

1982-01-01

The reciprocal interchange between the chromatids of a chromosome, termed sister chromatid exchange (SCE), is considered to be one of the most sensitive and accurate cytogenetic parameters and respond to toxic chemicals at very low doses. But the response of SCE to ionizing radiation is very poor. Human lymphocytes fail to give SCE response when irradiated at G 0 . Probably the primary lesions induced at G 0 do not remain available long enough to find expression as SCEs. Based on this assumption a schedule was developed using caffeine to demonstrate radiation induced SCEs. Following this schedule a dose-dependent increase in the frequency of radiation induced SCEs has been observed. (orig.)

Anti-apoptotic BFL-1 is the major effector in activation-induced human mast cell survival.

Directory of Open Access Journals (Sweden)

Maria Ekoff

Full Text Available Mast cells are best known for their role in allergic reactions, where aggregation of FcεRI leads to the release of mast cell mediators causing allergic symptoms. The activation also induces a survival program in the cells, i.e., activation-induced mast cell survival. The aim of the present study was to investigate how the activation-induced survival is mediated. Cord blood-derived mast cells and the mast cell line LAD-2 were activated through FcεRI crosslinking, with or without addition of chemicals that inhibit the activity or expression of selected Bcl-2 family members (ABT-737; roscovitine. Cell viability was assessed using staining and flow cytometry. The expression and function of Bcl-2 family members BFL-1 and MCL-1 were investigated using real-time quantitative PCR and siRNA treatment. The mast cell expression of Bfl-1 was investigated in skin biopsies. FcεRI crosslinking promotes activation-induced survival of human mast cells and this is associated with an upregulation of the anti-apoptotic Bcl-2 family member Bfl-1. ABT-737 alone or in combination with roscovitine decreases viability of human mast cells although activation-induced survival is sustained, indicating a minor role for Bcl-X(L, Bcl-2, Bcl-w and Mcl-1. Reducing BFL-1 but not MCL-1 levels by siRNA inhibited activation-induced mast cell survival. We also demonstrate that mast cell expression of Bfl-1 is elevated in birch-pollen-provocated skin and in lesions of atopic dermatitis and psoriasis patients. Taken together, our results highlight Bfl-1 as a major effector in activation-induced human mast cell survival.

Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies

OpenAIRE

Payne, Ruth O.; Silk, Sarah E.; Elias, Sean C.; Milne, Kathryn H.; Rawlinson, Thomas A.; Llewellyn, David; Shakri, A. Rushdi; Jin, Jing; Labb?, Genevi?ve M.; Edwards, Nick J.; Poulton, Ian D.; Roberts, Rachel; Farid, Ryan; J?rgensen, Thomas; Alanine, Daniel G.W.

2017-01-01

BACKGROUND: Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the Duffy antigen receptor for chemokines (DARC) and region II of the parasite's Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this interaction associate with clinical immunity, but it is unknown whether these responses can be induced by human vac...

Human induced pluripotent stem cells: a review of the US patent landscape.

Science.gov (United States)

Georgieva, Bilyana P; Love, Jane M

2010-07-01

Human induced pluripotent stem (iPS) cells and human embryonic stem cells are cells that have the ability to differentiate into a variety of cell types. Embryonic stem cells are derived from human embryos; however, by contrast, human iPS cells can be obtained from somatic cells that have undergone a process of 'reprogramming' via genetic manipulation such that they develop pluripotency. Since iPS cells are not derived from human embryos, they are a less complicated source of human pluripotent cells and are considered valuable research tools and potentially useful in therapeutic applications in regenerative medicine. Worldwide, there are only three issued patents concerning iPS cells. Therefore, the patent landscape in this field is largely undefined. This article provides an overview of the issued patents as well as the pending published patent applications in the field.

External-strain-induced semimetallic and metallic phase of chlorographene

Science.gov (United States)

Puri, Shivam; Bhowmick, Somnath

2018-04-01

To overcome the limitations of graphene due to lack of intrinsic band gap, it is generally functionalized with hydrogen or halogen atoms such as fluorine and chlorine. Generally, such functionalization yields a moderate- to high-band-gap material in case of 100% coverage, for example ≈1.5 eV in graphene functionalized with chlorine atoms or chlorographene. In this paper, using ab initio calculations, we report very interesting transformations observed in chlorographene under external strain, driving it to a state with nearly vanishing band gap (under tensile strain) and even converting it to a metal (under compressive strain). We also show the importance of spin-orbit coupling, responsible for the few meV band gap of chlorographene observed under high tensile strain, which would have been a gapless semimetal otherwise.

Comprehensive Understanding of Ductility Loss Mechanisms in Various Steels with External and Internal Hydrogen

Science.gov (United States)

Takakuwa, Osamu; Yamabe, Junichiro; Matsunaga, Hisao; Furuya, Yoshiyuki; Matsuoka, Saburo

2017-11-01

Hydrogen-induced ductility loss and related fracture morphologies are comprehensively discussed in consideration of the hydrogen distribution in a specimen with external and internal hydrogen by using 300-series austenitic stainless steels (Types 304, 316, 316L), high-strength austenitic stainless steels (HP160, XM-19), precipitation-hardened iron-based super alloy (A286), low-alloy Cr-Mo steel (JIS-SCM435), and low-carbon steel (JIS-SM490B). External hydrogen is realized by a non-charged specimen tested in high-pressure gaseous hydrogen, and internal hydrogen is realized by a hydrogen-charged specimen tested in air or inert gas. Fracture morphologies obtained by slow-strain-rate tensile tests (SSRT) of the materials with external or internal hydrogen could be comprehensively categorized into five types: hydrogen-induced successive crack growth, ordinary void formation, small-sized void formation related to the void sheet, large-sized void formation, and facet formation. The mechanisms of hydrogen embrittlement are broadly classified into hydrogen-enhanced decohesion (HEDE) and hydrogen-enhanced localized plasticity (HELP). In the HEDE model, hydrogen weakens interatomic bonds, whereas in the HELP model, hydrogen enhances localized slip deformations. Although various fracture morphologies are produced by external or internal hydrogen, these morphologies can be explained by the HELP model rather than by the HEDE model.

Study of terahertz-radiation-induced DNA damage in human blood leukocytes

Energy Technology Data Exchange (ETDEWEB)

Angeluts, A A; Esaulkov, M N; Kosareva, O G; Solyankin, P M; Shkurinov, A P [International Laser Center, M. V. Lomonosov Moscow State University, Moscow (Russian Federation); Gapeyev, A B; Pashovkin, T N [Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region (Russian Federation); Matyunin, S N [Section of Applied Problems at the Presidium of the Russian Academy of Sciences, Moscow (Russian Federation); Nazarov, M M [Institute on Laser and Information Technologies, Russian Academy of Sciences, Shatura, Moscow Region (Russian Federation); Cherkasova, O P [Institute of Laser Physics, Siberian Branch, Russian Academy of Sciences, Novosibirsk (Russian Federation)

2014-03-28

We have carried out the studies aimed at assessing the effect of terahertz radiation on DNA molecules in human blood leukocytes. Genotoxic testing of terahertz radiation was performed in three different oscillation regimes, the blood leukocytes from healthy donors being irradiated for 20 minutes with the mean intensity of 8 – 200 μW cm{sup -2} within the frequency range of 0.1 – 6.5 THz. Using the comet assay it is shown that in the selected regimes such radiation does not induce a direct DNA damage in viable human blood leukocytes. (biophotonics)

Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells.

Science.gov (United States)

Lin, Chia-Han; Lu, Wei-Cheng; Wang, Che-Wei; Chan, Ya-Chi; Chen, Mu-Kuan

2013-02-25

Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown an anti-proliferative effect on various human cancer cell lines. In contrast, capsaicin has also been considered to promote the growth of cancer cells. Thus, the effects of capsaicin on various cell types need to be explored. The anti-proliferative effects of capsaicin on human KB cancer cells are still unknown. Therefore, we examined the viability, cell cycle progression, and factors associated with apoptosis in KB cells treated with capsaicin. The cell proliferation/viability and cytotoxicity of KB cells exposed to capsaicin were determined by a sulforhodamine B colorimetric assay and trypan blue exclusion. Apoptosis was detected by Hoechst staining and confirmed by western blot analysis of poly-(ADP-ribose) polymerase cleavage. Cell cycle distribution and changes of the mitochondrial membrane potential were analyzed by flow cytometry. Furthermore, the expression of caspase 3, 8 and 9 was evaluated by immunoblotting. We found that treatment of KB cells with capsaicin significantly reduced cell proliferation/viability and induced cell death in a dose-dependent manner compared with that in the untreated control. Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at G2/M phase. Capsaicin-induced growth inhibition of KB cells appeared to be associated with induction of apoptosis. Moreover, capsaicin induced disruption of the mitochondrial membrane potential as well as activation of caspase 9, 3 and poly-(ADP-ribose) polymerase in KB cells. Our data demonstrate that capsaicin modulates cell cycle progression and induces apoptosis in human KB cancer cells through mitochondrial membrane permeabilization and caspase activation. These observations suggest an anti-cancer activity of capsaicin.

Eclalbasaponin II induces autophagic and apoptotic cell death in human ovarian cancer cells

Directory of Open Access Journals (Sweden)

Yoon Jin Cho

2016-09-01

Full Text Available Triterpenoids echinocystic acid and its glycosides, isolated from several Eclipta prostrata, have been reported to possess various biological activities such as anti-inflammatory, anti-bacterial, and anti-diabetic activity. However, the cytotoxicity of the triterpenoids in human cancer cells and their molecular mechanism of action are poorly understood. In the present study, we found that eclalbasaponin II with one glucose moiety has potent cytotoxicity in three ovarian cancer cells and two endometrial cancer cells compared to an aglycone echinocystic acid and eclalbasaponin I with two glucose moiety. Eclalbasaponin II treatment dose-dependently increased sub G1 population. Annexin V staining revealed that eclalbasaponin II induced apoptosis in SKOV3 and A2780 ovarian cancer cells. In addition, eclalbasaponin II-induced cell death was associated with characteristics of autophagy; an increase in acidic vesicular organelle content and elevation of the levels of LC3-II. Interestingly, autophagy inhibitor BaF1 suppressed the eclalbasaponin II-induced apoptosis. Moreover, eclalbasaponin II activated JNK and p38 signaling and inhibited the mTOR signaling. We further demonstrated that pre-treatment with a JNK and p38 inhibitor and mTOR activator attenuated the eclalbasaponin II-induced autophagy. This suggests that eclalbasaponin II induces apoptotic and autophagic cell death through the regulation of JNK, p38, and mTOR signaling in human ovarian cancer cells.

Changes in Gene Expression during G-CSF-Induced Emergency Granulopoiesis in Humans

DEFF Research Database (Denmark)

Pedersen, Corinna C.; Borup, Rehannah; Fischer-Nielsen, Anne

2016-01-01

Emergency granulopoiesis refers to the increased production of neutrophils in bone marrow and their release into circulation induced by severe infection. Several studies point to a critical role for G-CSF as the main mediator of emergency granulopoiesis. However, the consequences of G-CSF...... stimulation on the transcriptome of neutrophils and their precursors have not yet been investigated in humans. In this work, we examine the changes in mRNA expression induced by administration of G-CSF in vivo, as a model of emergency granulopoiesis in humans. Blood samples were collected from healthy...... individuals after 5 d of G-CSF administration. Neutrophil precursors were sorted into discrete stages of maturation by flow cytometry, and RNA was subjected to microarray analysis. mRNA levels were compared with previously published expression levels in corresponding populations of neutrophil precursors...

Human B cells induce dendritic cell maturation and favour Th2 polarization by inducing OX-40 ligand

Science.gov (United States)

Maddur, Mohan S.; Sharma, Meenu; Hegde, Pushpa; Stephen-Victor, Emmanuel; Pulendran, Bali; Kaveri, Srini V.; Bayry, Jagadeesh

2015-01-01

Dendritic cells (DCs) play a critical role in immune homeostasis by regulating the functions of various immune cells, including T and B cells. Notably, DCs also undergo education on reciprocal signalling by these immune cells and environmental factors. Various reports demonstrated that B cells have profound regulatory functions, although only few reports have explored the regulation of human DCs by B cells. Here we demonstrate that activated but not resting B cells induce maturation of DCs with distinct features to polarize Th2 cells that secrete interleukin (IL)-5, IL-4 and IL-13. B-cell-induced maturation of DCs is contact dependent and implicates signalling of B-cell activation molecules CD69, B-cell-activating factor receptor, and transmembrane activator and calcium-modulating cyclophilin ligand interactor. Mechanistically, differentiation of Th2 cells by B-cell-matured DCs is dependent on OX-40 ligand. Collectively, our results suggest that B cells have the ability to control their own effector functions by enhancing the ability of human DCs to mediate Th2 differentiation. PMID:24910129

Effects of external pressure loading on human skin blood flow measured by 133Xe clearance

International Nuclear Information System (INIS)

Holloway, G.A. Jr.; Daly, C.H.; Kennedy, D.; Chimoskey, J.

1976-01-01

Forearm skin blood flow was measured during external pressure loading in normal human subjects using 133 Xe washout from intracutaneous injection sites. Pressures ranging between 5 and 150 mmHg were applied through a 3-cm-diameter disc placed over the site of flow determination. The pressure was maintained constant by a servo-controlled loading mechanism. Flow decreased with pressures from 5 to 10 and 30 to 150 mmHg, but remained constant with pressures from 10 to 30 mmHg. Reactive hyperemia occurred following removal of pressures of 90 mmHg or greater, but did not occur following removal of lower pressures. The pressure-flow curve for parasacral skin of paraplegic subjects closely paralleled the pressure-flow curve of normal skin at pressures tested: 5 to 15 mmHg. These data are interpreted to demonstrate autoregulation of skin blood flow. Autoregulation in parasacral skin of paraplegic subjects suggests a peripheral mechanism. The occurrence of hyperemia at pressures which exceed the ability of skin to autoregulate suggests that both autoregulation and post occlusion hyperemia may have the same mechanism

Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

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Daniel R. Bayzigitov

2016-01-01

Full Text Available Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

Externalities of fuel cycles 'ExternE' project. Natural gas fuel cycle. Estimation of physical impacts and monetary valuation for priority impact pathways

International Nuclear Information System (INIS)

Holland, M.; Watkiss, P.; Berry, J.; Johnson, C.; Lee, D.

1994-01-01

This document assesses the progress made in quantifying environmental and health damages associated with the natural gas fuel cycle for electricity generation. The methodology developed in the ExternE Project is described in more detail elsewhere (European Commission, 1994a; 1995, in preparation). The reader is referred to these earlier reports for wider discussion of many of the issues underlying this type of work. The increased desire for economic assessment of environmental damage reflects growing awareness of problems such as global warming, ozone depletion and the acidification and nutrification of ecosystems. A wide range of receptors are affected, including human health, forests, crops, and buildings. Such damages are typically not accounted for by the producers and consumers of the good in question (in this case energy). They are thus referred to as 'external costs' or 'externalities', to distinguish them from the private costs which account for the construction of plant, cost of fuel, wages, etc. At the political level there are a variety of reasons for the growing interest in the quantification of the environmental impacts of energy use and the related external costs. These include the need to integrate environmental concerns when selecting between different fuels and energy technologies and the need to evaluate the costs and benefits of stricter environmental standards. These issues are reflected in European Union policy, through, for example, the Maastricht Treaty, the 5th Environmental Action Programme 'towards sustainability', the European Commission's White Paper 'Growth, competitiveness, employment and ways forward to the 21st century' and the establishment of the European Environmental Agency. The proposal for an Energy-Carbon tax is the first concrete proposal by the European Union for the direct use of economic instruments in environmental policy in the energy sector. An agreed methodology for calculation and integration of external costs has not

Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis.

Science.gov (United States)

Shaw, Catherine A; Webb, David J; Rossi, Adriano G; Megson, Ian L

2009-05-07

Nitric oxide (NO) can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-). In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMvarphi), and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP) is able to limit apoptosis in this cell type. Characterisation of the NO-related species generated by (Z)-1- [2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl)-, chloride (GEA-3162) was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR) spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMvarphi. Resultant MDMvarphi were treated for 24 h with DETA/NO (100 - 1000 muM) or GEA-3162 (10 - 300 muM) in the presence or absence of BAY 41-2272 (1 muM), isobutylmethylxanthine (IBMX; 1 muM), 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 muM) or 8-bromo-cGMP (1 mM). Apoptosis in MDMvarphi was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO) had no effect on cell viability, but ONOO- (GEA-3162) caused a concentration-dependent induction of apoptosis in MDMvarphi. Preconditioning of MDMvarphi with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX), or the NO-independent stimulator of soluble guanylate cyclase, BAY 41-2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner. These results

Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis

Directory of Open Access Journals (Sweden)

Rossi Adriano G

2009-05-01

Full Text Available Abstract Background Nitric oxide (NO can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-. In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMϕ, and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP is able to limit apoptosis in this cell type. Methods Characterisation of the NO-related species generated by (Z-1- [2-(2-aminoethyl-N-(2-ammonioethylamino]diazen-1-ium-1,2-diolate (DETA/NO and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl-, chloride (GEA-3162 was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMϕ. Resultant MDMϕ were treated for 24 h with DETA/NO (100 – 1000 μM or GEA-3162 (10 – 300 μM in the presence or absence of BAY 41–2272 (1 μM, isobutylmethylxanthine (IBMX; 1 μM, 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 μM or 8-bromo-cGMP (1 mM. Apoptosis in MDMϕ was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Results Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO had no effect on cell viability, but ONOO- (GEA-3162 caused a concentration-dependent induction of apoptosis in MDMϕ. Preconditioning of MDMϕ with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX, or the NO-independent stimulator of soluble guanylate cyclase, BAY 41–2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner

Three-dimensional geometric morphometric analysis of the nasopharyngeal boundaries and its functional integration with the face and external basicranium among extant hominoids.

Science.gov (United States)

Pagano, Anthony S; Laitman, Jeffrey T

2015-01-01

The nasopharynx is a centrally located but understudied upper respiratory tract component. This study tested hypotheses related to the functional integration of the nasopharyngeal boundaries with the facial skeleton and external basicranium over the course of development in humans and nonhuman hominoids. It was hypothesized that facial morphology (width, length, and kyphosis) is related to nasopharyngeal width and choanal morphology, whereas relative external basicranial proportions are related to nasopharyngeal depth. Human infants were used as models of extreme orthognathy and external basicranial retroflexion, whereas nonhuman hominoids were used to model greater relative prognathism and external basicranial retroflexion. Both of these groups were contrasted against adult humans, who exhibit both extreme orthognathy and external basicranial flexion. Three-dimensional landmark coordinate data were collected from age-graded series of Homo, Pan, Gorilla, Pongo, and Hylobates. Generalized Procrustes Analysis was performed, and multivariate shape differences were evaluated via principal components analysis. Additionally, linear measures were extracted from the Procrustes-corrected sets of landmark data. Results indicate that human adults are indeed distinct from all groups in possessing a relatively shallow nasopharyngeal roof and shorter, more flexed external basicranial axis. Human adults and infants both exhibit greater relative choanal and nasopharyngeal width. Nonhuman hominoid faces tended to become airorhynch into adulthood, whereas humans exhibited the opposite trend. When pooling all the hominoids, facial width and palate length were strongly correlated with choanal and nasopharyngeal width, whereas facial kyphosis was strongly correlated with choanal orientation. The hypotheses were supported as the results indicated a morphologic relationship among nasopharyngeal boundaries, the facial skeleton, and the external basicranium. © 2014 Wiley Periodicals, Inc.

Is Human-induced Pluripotent Stem Cell the Best Optimal?

OpenAIRE

Feng Wang; Jie Kong; Yi-Yao Cui; Peng Liu; Jian-Yan Wen

2018-01-01

Objective: Since the advent of induced pluripotent stem cell (iPSC) technology a decade ago, enormous progress has been made in stem cell biology and regenerative medicine. Human iPSCs have been widely used for disease modeling, drug discovery, and cell therapy development. In this review, we discuss the progress in applications of iPSC technology that are particularly relevant to drug discovery and regenerative medicine, and consider the remaining challenges and the emerging opportunities in...

The Economics and Ethics of Human Induced Climate Change

OpenAIRE

Spash, Clive L.; Gattringer, Clemens

2016-01-01

Human induced climate change poses a series of ethical challenges to the current political economy, although it has often be regarded by economists as only an ethical issue for those concerned about future generations. The central debate in economics has then concerned the rate at which future costs and benefits should be discounted. Indeed the full range of ethical aspects of climate change are rarely even discussed. Despite recent high profile and lengthy academic papers on t...

Inducible, tunable and multiplex human gene regulation using CRISPR-Cpf1-based transcription factors | Office of Cancer Genomics

Science.gov (United States)

Targeted and inducible regulation of mammalian gene expression is a broadly important research capability that may also enable development of novel therapeutics for treating human diseases. Here we demonstrate that a catalytically inactive RNA-guided CRISPR-Cpf1 nuclease fused to transcriptional activation domains can up-regulate endogenous human gene expression. We engineered drug-inducible Cpf1-based activators and show how this system can be used to tune the regulation of endogenous gene transcription in human cells.

Lipoprotein(a Induces Human Aortic Valve Interstitial Cell Calcification

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Bin Yu, PhD

2017-08-01

Full Text Available Lipoprotein(a, or Lp(a, significantly increased alkaline phosphatase activity, release of phosphate, calcium deposition, hydroxyapatite, cell apoptosis, matrix vesicle formation, and phosphorylation of signal transduction proteins; increased expression of chondro-osteogenic mediators; and decreased SOX9 and matrix Gla protein (p < 0.001. Inhibition of MAPK38 and GSK3β significantly reduced Lp(a-induced calcification of human aortic valve interstitial cells (p < 0.001. There was abundant presence of Lp(a and E06 immunoreactivity in diseased human aortic valves. The present study demonstrates a causal effect for Lp(a in aortic valve calcification and suggests that interfering with the Lp(apathway could provide a novel therapeutic approach in the management of this debilitating disease.

The Efficacy of Dandelion Root Extract in Inducing Apoptosis in Drug-Resistant Human Melanoma Cells

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S. J. Chatterjee

2011-01-01

Full Text Available Notoriously chemoresistant melanoma has become the most prevalent form of cancer for the 25–29 North American age demographic. Standard treatment after early detection involves surgical excision (recurrence is possible, and metastatic melanoma is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE specifically and effectively induces apoptosis in human melanoma cells without inducing toxicity in noncancerous cells. Characteristic apoptotic morphology of nuclear condensation and phosphatidylserine flipping to the outer leaflet of the plasma membrane of A375 human melanoma cells was observed within 48 hours. DRE-induced apoptosis activates caspase-8 in A375 cells early on, demonstrating employment of an extrinsic apoptotic pathway to kill A375 cells. Reactive Oxygen Species (ROS generated from DRE-treated isolated mitochondria indicates that natural compounds in DRE can also directly target mitochondria. Interestingly, the relatively resistant G361 human melanoma cell line responded to DRE when combined with the metabolism interfering antitype II diabetic drug metformin. Therefore, treatment with this common, yet potent extract of natural compounds has proven novel in specifically inducing apoptosis in chemoresistant melanoma, without toxicity to healthy cells.

Inside-out: comparing internally generated and externally generated basic emotions.

Science.gov (United States)

Salas, Christian E; Radovic, Darinka; Turnbull, Oliver H

2012-06-01

A considerable number of mood induction (MI) procedures have been developed to elicit emotion in normal and clinical populations. Although external procedures (e.g., film clips, pictures) are widely used, a number of experiments elicit emotion by using self-generated procedures (e.g., recalling an emotional personal episode). However, no study has directly compared the effectiveness of two types of internal versus external MI across multiple discrete emotions. In the present experiment, 40 undergraduate students watched film clips (external procedure) and recalled personal events (internal procedure) inducing 4 basic emotions (fear, anger, joy, sadness) and later completed a self-report questionnaire. Remarkably, both internal and external procedures elicited target emotions selectively, compared with nontarget emotions. When contrasting the intensity of target emotions, both techniques showed no significant differences, with the exception of Joy, which was more intensely elicited by the internal procedure. Importantly, when considering the overall level of intensity, it was always greater in the internal procedure, for each stimulus. A more detailed investigation of the data suggest that recalling personal events (a type of internal procedure) generates more negative and mixed blends of emotions, which might account for the overall higher intensity of the internal mood induction.

Membrane alterations induced by nonstructural proteins of human norovirus.

Directory of Open Access Journals (Sweden)

Sylvie Y Doerflinger

2017-10-01

Full Text Available Human noroviruses (huNoV are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4 variants. The viral nonstructural (NS proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far about the ultrastructure of these replication organelles or the contribution of individual NS proteins to their biogenesis. We compared the ultrastructural changes induced by expression of norovirus ORF1 polyproteins with those induced upon infection with murine norovirus (MNV. Characteristic membrane alterations induced by ORF1 expression resembled those found in MNV infected cells, consisting of vesicle accumulations likely built from the endoplasmic reticulum (ER which included single membrane vesicles (SMVs, double membrane vesicles (DMVs and multi membrane vesicles (MMVs. In-depth analysis using electron tomography suggested that MMVs originate through the enwrapping of SMVs with tubular structures similar to mechanisms reported for picornaviruses. Expression of GII.4 NS1-2, NS3 and NS4 fused to GFP revealed distinct membrane alterations when analyzed by correlative light and electron microscopy. Expression of NS1-2 induced proliferation of smooth ER membranes forming long tubular structures that were affected by mutations in the active center of the putative NS1-2 hydrolase domain. NS3 was associated with ER membranes around lipid droplets (LDs and induced the formation of convoluted membranes, which were even more pronounced in case of NS4. Interestingly, NS4 was the only GII.4 protein capable of inducing SMV and DMV formation when expressed individually. Our work provides the first ultrastructural analysis of norovirus GII.4 induced vesicle clusters and suggests that their morphology and biogenesis is most similar to picornaviruses. We further identified NS4 as a key factor in the formation of membrane alterations of huNoV and

Perfluorooctane sulfonate (PFOS) induces reactive oxygen species (ROS) production in human microvascular endothelial cells: role in endothelial permeability.

Science.gov (United States)

Qian, Yong; Ducatman, Alan; Ward, Rebecca; Leonard, Steve; Bukowski, Valerie; Lan Guo, Nancy; Shi, Xianglin; Vallyathan, Val; Castranova, Vincent

2010-01-01

Perfluorooctane sulfonate (PFOS) is a member of the perfluoroalkyl acids (PFAA) containing an eight-carbon backbone. PFOS is a man-made chemical with carbon-fluorine bonds that are among the strongest in organic chemistry, and PFOS is widely used in industry. Human occupational and environmental exposure to PFOS occurs globally. PFOS is non-biodegradable and is persistent in the human body and environment. In this study, data demonstrated that exposure of human microvascular endothelial cells (HMVEC) to PFOS induced the production of reactive oxygen species (ROS) at both high and low concentrations. Morphologically, it was found that exposure to PFOS induced actin filament remodeling and endothelial permeability changes in HMVEC. Furthermore, data demonstrated that the production of ROS plays a regulatory role in PFOS-induced actin filament remodeling and the increase in endothelial permeability. Our results indicate that the generation of ROS may play a role in PFOS-induced aberrations of the endothelial permeability barrier. The results generated from this study may provide a new insight into the potential adverse effects of PFOS exposure on humans at the cellular level.

Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells.

Science.gov (United States)

Liao, Wenzhen; Chen, Luying; Ma, Xiang; Jiao, Rui; Li, Xiaofeng; Wang, Yong

2016-05-23

The protective effects of kaempferol against reactive oxygen species (ROS)-induced hemolysis and its antiproliferative activity on human cancer cells were evaluated in this study. Kaempferol exhibited strong cellular antioxidant ability (CAA) with a CAA value of 59.80 ± 0.379 μM of quercetin (QE)/100 μM (EC50 = 7.74 ± 0.049 μM). Pretreatment with kaempferol significantly attenuated the ROS-induced hemolysis of human erythrocyte (87.4% hemolysis suppressed at 100 μg/mL) and reduced the accumulation of toxic lipid peroxidation product malondialdehyde (MDA). The anti-hemolytic activity of kaempferol was mainly through scavenging excessive ROS and preserving the intrinsic antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) activities in normal levels. Additionally, kaempferol showed significant antiproliferative activity on a panel of human cancer cell lines including human breast carcinoma (MCF-7) cells, human stomach carcinoma (SGC-7901) cells, human cervical carcinoma (Hela) cells and human lung carcinoma (A549) cells. Kaemperol induced apoptosis of MCF-7 cells accompanied with nuclear condensation and mitochondria dysfunction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Near Infrared Photoimmunotherapy with Combined Exposure of External and Interstitial Light Sources.

Science.gov (United States)

Maruoka, Yasuhiro; Nagaya, Tadanobu; Sato, Kazuhide; Ogata, Fusa; Okuyama, Shuhei; Choyke, Peter L; Kobayashi, Hisataka

2018-02-21

Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell-specific cancer treatment that induces highly selective necrotic/immunogenic cell death after systemic administration of a photoabsorber antibody conjugate and subsequent NIR light exposure. However, the depth of NIR light penetration in tissue (approximately 2 cm) with external light sources limits the therapeutic effects of NIR-PIT. Interstitial light exposure using cylindrical diffusing optical fibers can overcome this limitation. The purpose in this study was to compare three NIR light delivery methods for treating tumors with NIR-PIT using a NIR laser system at an identical light energy; external exposure alone, interstitial exposure alone, and the combination. Panitumumab conjugated with the photoabsorber IRDye-700DX (pan-IR700) was intravenously administered to mice with A431-luc xenografts which are epithelial growth factor receptor (EGFR) positive. One and 2 days later, NIR light was administered to the tumors using one of three methods. Interstitial exposure alone and in combination with external sources showed the greatest decrease in bioluminescence signal intensity. Additionally, the combination of external and interstitial NIR light exposure showed significantly greater tumor size reduction and prolonged survival after NIR-PIT compared to external exposure alone. This result suggested that the combination of external and interstitial NIR light exposure was more effective than externally applied light alone. Although external exposure is the least invasive means of delivering light, the combination of external and interstitial exposures produces superior therapeutic efficacy in tumors greater than 2 cm in depth from the tissue surface.

Effect of Human Model Height and Sex on Induced Current Dosimetry in Household Induction Heater Users

Science.gov (United States)

Tarao, Hiroo; Hayashi, Noriyuki; Isaka, Katsuo

Induced currents in the high-resolution, anatomical human models are numerically calculated by the impedance method. The human models are supposed to be exposed to highly inhomogeneous 20.9 kHz magnetic fields from a household induction heater (IH). In the case of the adult models, the currents ranging from 5 to 19 mA/m2 are induced for between the shoulder and lower abdomen. Meanwhile, in the case of the child models, the currents ranging from 5 to 21 mA/m2 are induced for between the head and abdomen. In particular, the induced currents near the brain tissue are almost the same as those near the abdomen. When the induced currents in the central nervous system tissues are considered, the induced currents in the child model are 2.1 to 6.9 times as large as those in the adult model under the same B-field exposure environment. These results suggest the importance of further investigation intended for a pregnant female who uses the IH as well as for a child (or the IH users of small standing height).

First branchial cleft fistula associated with external auditory canal stenosis and middle ear cholesteatoma.

Science.gov (United States)

Abdollahi Fakhim, Shahin; Naderpoor, Masoud; Mousaviagdas, Mehrnoosh

2014-10-01

First branchial cleft anomalies manifest with duplication of the external auditory canal. This report features a rare case of microtia and congenital middle ear and canal cholesteatoma with first branchial fistula. External auditory canal stenosis was complicated by middle ear and external canal cholesteatoma, but branchial fistula, opening in the zygomatic root and a sinus in the helical root, may explain this feature. A canal wall down mastoidectomy with canaloplasty and wide meatoplasty was performed. The branchial cleft was excised through parotidectomy and facial nerve dissection. It should be considered that canal stenosis in such cases can induce cholesteatoma formation in the auditory canal and middle ear.

Characterizing human activity induced impulse and slip-pulse excitations through structural vibration

Science.gov (United States)

Pan, Shijia; Mirshekari, Mostafa; Fagert, Jonathon; Ramirez, Ceferino Gabriel; Chung, Albert Jin; Hu, Chih Chi; Shen, John Paul; Zhang, Pei; Noh, Hae Young

2018-02-01

Many human activities induce excitations on ambient structures with various objects, causing the structures to vibrate. Accurate vibration excitation source detection and characterization enable human activity information inference, hence allowing human activity monitoring for various smart building applications. By utilizing structural vibrations, we can achieve sparse and non-intrusive sensing, unlike pressure- and vision-based methods. Many approaches have been presented on vibration-based source characterization, and they often either focus on one excitation type or have limited performance due to the dispersion and attenuation effects of the structures. In this paper, we present our method to characterize two main types of excitations induced by human activities (impulse and slip-pulse) on multiple structures. By understanding the physical properties of waves and their propagation, the system can achieve accurate excitation tracking on different structures without large-scale labeled training data. Specifically, our algorithm takes properties of surface waves generated by impulse and of body waves generated by slip-pulse into account to handle the dispersion and attenuation effects when different types of excitations happen on various structures. We then evaluate the algorithm through multiple scenarios. Our method achieves up to a six times improvement in impulse localization accuracy and a three times improvement in slip-pulse trajectory length estimation compared to existing methods that do not take wave properties into account.

Demonstration of immunochemical identity between the nerve growth factor-inducible large external (NILE) glycoprotein and the cell adhesion molecule L1

DEFF Research Database (Denmark)

Bock, E; Richter-Landsberg, C; Faissner, A

1985-01-01

The nerve growth factor-inducible large external (NILE) glycoprotein and the neural cell adhesion molecule L1 were shown to be immunochemically identical. Immunoprecipitation with L1 and NILE antibodies of [3H]fucose-labeled material from culture supernatants and detergent extracts of NGF......-treated rat PC12 pheochromocytoma cells yielded comigrating bands by SDS-PAGE. NILE antibodies reacted with immunopurified L1 antigen, but not with N-CAM and other L2 epitope-bearing glycoproteins from adult mouse brain. Finally, by sequential immunoprecipitation from detergent extracts of [35S......]methionine-labeled early post-natal cerebellar cell cultures or [3H]fucose-labeled NGF-treated PC12 cells, all immunoreactivity for NILE antibody could be removed by pre-clearing with L1 antibody and vice versa....

Constant external fields in gauge theory and the spin 0, 1/2, 1 path integrals

International Nuclear Information System (INIS)

Reuter, M.; Schmidt, M.G.

1996-10-01

We investigate the usefulness of the ''string-inspired technique'' for gauge theory calculations in a constant external field background. Our approach is based on Strassler's worldline path integral approach to the Bern-Kosower formalism, and on the construction of worldline (super-) Green's functions incorporating external fields as well as internal propagators. The worldline path integral representation of the gluon loop is reexamined in detail. We calculate the two-loop effective actions induced for a constant external field by a scalar and spinor loop, and the corresponding one-loop effective action in the gluon loop case. (orig.)

Portulaca oleracea extracts protect human keratinocytes and fibroblasts from UV-induced apoptosis.

Science.gov (United States)

Lee, Suyeon; Kim, Ki Ho; Park, Changhoon; Lee, Jong-Suk; Kim, Young Heui

2014-10-01

Portulaca oleracea extracts, known as Ma Chi Hyun in the traditional Korean medicine, show a variety of biomedical efficacies including those in anti-inflammation and anti-allergy. In this study, we investigate the protective activity of the P. oleracea extracts against UVB-induced damage in human epithelial keratinocytes and fibroblasts by several apoptosis-related tests. The results suggest that P. oleracea extracts have protective effects from UVB-induced apoptosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Is Human-induced Pluripotent Stem Cell the Best Optimal?

Science.gov (United States)

Wang, Feng; Kong, Jie; Cui, Yi-Yao; Liu, Peng; Wen, Jian-Yan

2018-04-05

Since the advent of induced pluripotent stem cell (iPSC) technology a decade ago, enormous progress has been made in stem cell biology and regenerative medicine. Human iPSCs have been widely used for disease modeling, drug discovery, and cell therapy development. In this review, we discuss the progress in applications of iPSC technology that are particularly relevant to drug discovery and regenerative medicine, and consider the remaining challenges and the emerging opportunities in the field. Articles in this review were searched from PubMed database from January 2014 to December 2017. Original articles about iPSCs and cardiovascular diseases were included and analyzed. iPSC holds great promises for human disease modeling, drug discovery, and stem cell-based therapy, and this potential is only beginning to be realized. However, several important issues remain to be addressed. The recent availability of human cardiomyocytes derived from iPSCs opens new opportunities to build in vitro models of cardiac disease, screening for new drugs and patient-specific cardiac therapy.

Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide

International Nuclear Information System (INIS)

Huang, Chunrong; Zheng, Haichong; He, Wanmei; Lu, Guifang; Li, Xia; Deng, Yubin; Zeng, Mian

2016-01-01

Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI. -- Graphical abstract: Ghrelin ameliorates the human alveolar epithelial A549 cells apoptosis induced by lipopolysaccharide partly through activating the PI3K/Akt and ERK pathway. Display Omitted -- Highlights: •It has been observed that LPS insult significantly increased apoptosis in A549 cells. •Both Akt and ERK signaling are critical adapter molecules to mediate the ghrelin-mediated proliferative effect. •Ghrelin may have a therapeutic effect in the prevention of LPS-induced apoptosis.

Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide

Energy Technology Data Exchange (ETDEWEB)

Huang, Chunrong; Zheng, Haichong; He, Wanmei; Lu, Guifang; Li, Xia [Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Deng, Yubin, E-mail: dengyub@mail.sysu.edu.cn [Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Zeng, Mian, E-mail: zengmian2004@163.com [Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China)

2016-05-20

Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI. -- Graphical abstract: Ghrelin ameliorates the human alveolar epithelial A549 cells apoptosis induced by lipopolysaccharide partly through activating the PI3K/Akt and ERK pathway. Display Omitted -- Highlights: •It has been observed that LPS insult significantly increased apoptosis in A549 cells. •Both Akt and ERK signaling are critical adapter molecules to mediate the ghrelin-mediated proliferative effect. •Ghrelin may have a therapeutic effect in the prevention of LPS-induced apoptosis.

A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

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Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); and others

2014-02-01

Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

International Nuclear Information System (INIS)

Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro

2014-01-01

Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury

Asiaticoside induces cell proliferation and collagen synthesis in human dermal fibroblasts

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Linda Yulianti

2015-08-01

Full Text Available Asiatiocoside, a saponin component isolated from Centella asiatica can improve wound healing by promoting the proliferation of human dermal fibroblasts (HDF and synthesis of collagen. The skin-renewing cells and type I and III collagen synthesis decrease with aging, resulting in the reduction of skin elasticity and delayed wound healing. Usage of natural active compounds from plants in wound healing should be evaluated and compared to retinoic acid as an active agent that regulates wound healing. The aim of this study was to compare and evaluate the effect of asiaticoside and retinoic acid to induce greater cell proliferation and type I and III collagen synthesis in human dermal fibroblast. Methods Laboratory experiments were conducted using human dermal fibroblasts (HDF isolated from human foreskin explants. Seven passages of HDF were treated with asiaticoside and retinoic acid at several doses and incubated for 24 and 48 hours. Cell viability in all groups was tested with the MTT assay to assess HDF proliferation. Type I and III collagen synthesis was examined using the respective ELISA kits. Analysis of variance was performed to compare the treatment groups. Results Asiaticoside had significantly stronger effects on HDF proliferation than retinoic acid (p<0.05. The type III collagen production was significantly greater induction with asiaticoside compared to retinoic acid (p<0.05. Conclusion Asiaticoside induces HDF proliferation and type I and III collagen synthesis in a time- and dose-dependent pattern. Asiaticoside has a similar effect as retinoic acid on type I and type III collagen synthesis.

Depleted uranium induces neoplastic transformation in human lung epithelial cells.

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Xie, Hong; LaCerte, Carolyne; Thompson, W Douglas; Wise, John Pierce

2010-02-15

Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and noncombatants is frequent and widespread. Previous studies have shown that DU has both chemical and radiological toxicity and that the primary route of exposure of DU to humans is through inhalation and ingestion. However, there is limited research information on the potential carcinogenicity of DU in human bronchial cells. Accordingly, we determined the neoplastic transforming ability of particulate DU to human bronchial epithelial cells (BEP2D). We observed the loss of contact inhibition and anchorage independent growth in cells exposed to DU after 24 h. We also characterized these DU-induced transformed cell lines and found that 40% of the cell lines exhibit alterations in plating efficiency and no significant changes in the cytotoxic response to DU. Cytogenetic analyses showed that 53% of the DU-transformed cell lines possess a hypodiploid phenotype. These data indicate that human bronchial cells are transformed by DU and exhibit significant chromosome instability consistent with a neoplastic phenotype.

Moessbauer radiation dynamical diffraction in crystals being subjected to the action of external variable fields

International Nuclear Information System (INIS)

Baryshevskii, V.G.; Skadorov, V.V.

1986-01-01

A dynamical theory is developed of the Moessbauer radiation diffraction by crystals being subjected to an variable external field action. Equations describing the dynamical diffraction by nonstationary crystals are obtained. It is shown that the resonant interaction between Moessbauer radiation and shift field induced in the crystal by a variable external field giving rise to an effective conversion of the incident wave into a wave with changed frequency. (author)

Experimental studies on lung carcinogenesis and their relationship to future research on radiation-induced lung cancer in humans

International Nuclear Information System (INIS)

Cross, F.T.

1991-03-01

The usefulness of experimental systems for studying human lung carcinogenesis lies in the ease of studying components of a total problem. As an example, the main thrust of attack on possible synergistic interactions between radiation, cigarette smoke, and other irritants must be by means of research on animals. Because animals can be serially sacrificed, a systematic search can be made for progressive lung changes, thereby improving our understanding of carcinogenesis. The mechanisms of radiation-induced carcinogenesis have not yet been delineated, but modern concepts of molecular and cellular biology and of radiation dosimetry are being increasingly applied to both in vivo and in vitro exposure to determine the mechanisms of radiation-induced carcinogenesis, to elucidate human data, and to aid in extrapolating experimental animal data to human exposures. In addition, biologically based mathematical models of carcinogenesis are being developed to describe the nature of the events leading to malignancy; they are also an essential part of a rational approach to quantitative cancer risk assessment. This paper summarizes recent experimental and modeling data on radon-induced lung cancer and includes the confounding effects of cigarette-smoke exposures. The applicability of these data to understanding human exposures is emphasized, and areas of future research on human radiation-induced carcinogenesis are discussed. 7 refs., 2 figs., 3 tabs

Cigarette smoke modulates expression of human rhinovirus-induced airway epithelial host defense genes.

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David Proud

Full Text Available Human rhinovirus (HRV infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.

Assessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS).

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Lauenstein, L; Switalla, S; Prenzler, F; Seehase, S; Pfennig, O; Förster, C; Fieguth, H; Braun, A; Sewald, K

2014-06-01

Occupational asthma can be induced by a number of chemicals at the workplace. Risk assessment of potential sensitizers is mostly performed in animal experiments. With increasing public demand for alternative methods, human precision-cut lung slices (PCLS) have been developed as an ex vivo model. Human PCLS were exposed to increasing concentrations of 20 industrial chemicals including 4 respiratory allergens, 11 contact allergens, and 5 non-sensitizing irritants. Local respiratory irritation was characterized and expressed as 75% (EC25) and 50% (EC50) cell viability with respect to controls. Dose-response curves of all chemicals except for phenol were generated. Local respiratory inflammation was quantified by measuring the production of cytokines and chemokines. TNF-α and IL-1α were increased significantly in human PCLS after exposure to the respiratory sensitizers trimellitic anhydride (TMA) and ammonium hexachloroplatinate (HClPt) at subtoxic concentrations, while contact sensitizers and non-sensitizing irritants failed to induce the release of these cytokines to the same extent. Interestingly, significant increases in T(H)1/T(H)2 cytokines could be detected only after exposure to HClPt at a subtoxic concentration. In conclusion, allergen-induced cytokines were observed but not considered as biomarkers for the differentiation between respiratory and contact sensitizers. Our preliminary results show an ex vivo model which might be used for prediction of chemical-induced toxicity, but is due to its complex three-dimensional structure not applicable for a simple screening of functional and behavior changes of certain cell populations such as dendritic cells and T-cells in response to allergens. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Involvement of ERK, Bcl-2 family and caspase 3 in recombinant human activin A-induced apoptosis in A549

International Nuclear Information System (INIS)

Wang Baiding; Feng Yuling; Song Xingbo; Liu Qingqing; Ning Yunye; Ou Xuemei; Yang Jie; Zhang Xiaohong; Wen, Fuqiang

2009-01-01

Background: Activins are members of the transforming growth factor-β (TGF-β) superfamily. Previous studies have shown that activin A may have a central role in regulating both apoptosis and proliferation. However, direct studies of recombination human activin A on human NSCLC A549 cells have not yet been reported. The purpose of this study was to investigate whether activin A could induce apoptosis in A549 cells and the possible mechanisms via which it worked. Methods: Cellular apoptosis induced by activin A was detected by TUNEL assay and the levels of protein expression were detected by western blot. Results: Recombination human activin A induced apoptosis in human NSCLC A549 cells in a concentrate-dependent manner. Activin A-induced A549 apoptosis was accompanied by the up-regulation of Bax, Bad and Bcl-Xs and down-regulation of Bcl-2. Moreover, activin A treatment increased the expression of its typeII receptors, activated ERK and caspase 3 in A549. These results clearly demonstrate that the induction of apoptosis by activin-A involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins and caspase 3 participate in activin A-induced apoptotic process in A549 cells. On the other hand, activin A treatment had little effect on primary human small airway epithelial cells (SAECs). Conclusion: Recombination human activin A induced apoptosis in A549 cells, at least partially, through ERK and mitochondrial pathway. The result that activin A did not affect the normal SAEC revealed activin A might be considered as a potential anticancer agent and worthy of further studies

Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells

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Mishima Satoshi

2009-11-01

Full Text Available Abstract Background Vascular endothelial growth factor (VEGF is a key regulator of pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. Bee products [royal jelly (RJ, bee pollen, and Chinese red propolis] from the honeybee, Apis mellifera, have been used as traditional health foods for centuries. The aim of this study was to investigate the anti-angiogenic effects of bee products using human umbilical vein endothelial cells (HUVECs. Methods In an in vitro tube formation assay, HUVECs and fibroblast cells were incubated for 14 days with VEGF and various concentrations of bee products [RJ, ethanol extract of bee pollen, ethanol extract of Chinese red propolis and its constituent, caffeic acid phenethyl ester (CAPE]. To clarify the mechanism of in vitro angiogenesis, HUVEC proliferation and migration were induced by VEGF with or without various concentrations of RJ, bee pollen, Chinese red propolis, and CAPE. Results RJ, bee pollen, Chinese red propolis, and CAPE significantly suppressed VEGF-induced in vitro tube formation in the descending order: CAPE > Chinese red propolis >> bee pollen > RJ. RJ and Chinese red propolis suppressed both VEGF-induced HUVEC proliferation and migration. In contrast, bee pollen and CAPE suppressed only the proliferation. Conclusion Among the bee products, Chinese red propolis and CAPE in particular showed strong suppressive effects against VEGF-induced angiogenesis. These findings indicate that Chinese red propolis and CAPE may have potential as preventive and therapeutic agents against angiogenesis-related human diseases.

Human Papillomavirus 16 Infection Induces VAP-Dependent Endosomal Tubulation.

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Siddiqa, Abida; Massimi, Paola; Pim, David; Broniarczyk, Justyna; Banks, Lawrence

2018-03-15

Human papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans -Golgi network (TGN) and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation. In addition, we also show a critical requirement for the endoplasmic reticulum (ER)-anchored protein VAP in this process. VAP plays an essential role in actin nucleation and endosome-to-Golgi transport. Indeed, the loss of VAP results in a dramatic decrease in the level of endosomal tubulation induced by incoming HPV-16 virions. This is also accompanied by a marked reduction in virus infectivity. In VAP knockdown cells, we see that the defect in virus trafficking occurs after capsid disassembly but prior to localization at the trans -Golgi network, with the incoming virion-transduced DNA accumulating in Vps29/TGN46-positive hybrid vesicles. Taken together, these studies demonstrate that infection with HPV-16 virions induces marked alterations of endocytic transport pathways, some of which are VAP dependent and required for the endosome-to-Golgi transport of the incoming viral L2/DNA complex. IMPORTANCE Human papillomavirus infectious entry involves multiple interactions with the endocytic transport machinery. In this study, we show that incoming HPV-16 virions induce a dramatic increase in endocytic tubulation. This tubulation requires ER-associated VAP, which plays a critical role in ensuring the delivery of cargoes from the endocytic compartments to the trans -Golgi network. Indeed, the loss of

In Vivo Lipopolysaccharide Exposure of Human Blood Leukocytes Induces Cross-Tolerance to Multiple TLR Ligands

NARCIS (Netherlands)

de Vos, Alex F.; Pater, Jennie M.; van den Pangaart, Petra S.; de Kruif, Martijn D.; van 't Veer, Cornelis; van der Poll, Tom

2009-01-01

In vitro and in vivo experiments in mice have shown that exposure of cells to the TLR4 ligand LPS induces tolerance toward a second exposure to LPS and induces cross-tolerance to certain other TLR ligands. Recently, we found that LPS tolerance in experimental human endotoxemia and Gram-negative

[External cephalic version].

Science.gov (United States)

Navarro-Santana, B; Duarez-Coronado, M; Plaza-Arranz, J

2016-08-01

To analyze the rate of successful external cephalic versions in our center and caesarean sections that would be avoided with the use of external cephalic versions. From January 2012 to March 2016 external cephalic versions carried out at our center, which were a total of 52. We collected data about female age, gestational age at the time of the external cephalic version, maternal body mass index (BMI), fetal variety and situation, fetal weight, parity, location of the placenta, amniotic fluid index (ILA), tocolysis, analgesia, and newborn weight at birth, minor adverse effects (dizziness, hypotension and maternal pain) and major adverse effects (tachycardia, bradycardia, decelerations and emergency cesarean section). 45% of the versions were unsuccessful and 55% were successful. The percentage of successful vaginal delivery in versions was 84% (4% were instrumental) and 15% of caesarean sections. With respect to the variables studied, only significant differences in birth weight were found; suggesting that birth weight it is related to the outcome of external cephalic version. Probably we did not find significant differences due to the number of patients studied. For women with breech presentation, we recommend external cephalic version before the expectant management or performing a cesarean section. The external cephalic version increases the proportion of fetuses in cephalic presentation and also decreases the rate of caesarean sections.

Exercise-induced metallothionein expression in human skeletal muscle fibres

DEFF Research Database (Denmark)

Penkowa, Milena; Keller, Pernille; Keller, Charlotte

2005-01-01

in both type I and II muscle fibres. This is the first report demonstrating that MT-I + II are significantly induced in human skeletal muscle fibres following exercise. As MT-I + II are antioxidant factors that protect various tissues during pathological conditions, the MT-I + II increases post exercise......Exercise induces free oxygen radicals that cause oxidative stress, and metallothioneins (MTs) are increased in states of oxidative stress and possess anti-apoptotic effects. We therefore studied expression of the antioxidant factors metallothionein I and II (MT-I + II) in muscle biopsies obtained...... in response to 3 h of bicycle exercise performed by healthy men and in resting controls. Both MT-I + II proteins and MT-II mRNA expression increased significantly in both type I and II muscle fibres after exercise. Moreover, 24 h after exercise the levels of MT-II mRNA and MT-I + II proteins were still highly...

Indirect effects of human-induced environmental change on offspring production mediated by behavioural responses.

Science.gov (United States)

Candolin, Ulrika; Nieminen, Anne; Nyman, Johanna

2014-01-01

Human-induced rapid environmental changes often cause behavioural alterations in animals. The consequences that these alterations in turn have for the viability of populations are, however, poorly known. We used a population of threespine sticklebacks Gasterosteus aculeatus in the Baltic Sea to investigate the consequences of behavioural responses to human-induced eutrophication for offspring production. The investigated population has been growing during the last decades, and one cause could be increased offspring production. We combined field-based surveys with laboratory-based experiments, and found that an enhanced growth of macroalgae relaxed agonistic interactions among males. This allowed more males to nest, improved hatching success, and increased the number of reproductive cycles that males completed. Thus, the behavioural responses were adaptive at the individual level and increased offspring production. However, a larger proportion of small males of low competitive ability reproduced in dense vegetation. As male size and dominance are heritable, this could influence the genetic composition of the offspring. Together with a higher number of offspring produced, this could influence natural selection and the rate of adaptation to the changing environment. Thus, behavioural responses to a rapid human-induced environmental change can influence offspring production, with potential consequences for population dynamics and evolutionary processes.

cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells.

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Jennifer Paijo

2016-04-01

Full Text Available Human cytomegalovirus (HCMV infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING and thus induces antiviral type I interferon (IFN-I responses. We found that plasmacytoid dendritic cells (pDC as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages.

Molecular biology methods in assessing radiation-induced hereditary risks in humans

International Nuclear Information System (INIS)

Kiuru, A.

2004-12-01

Effort to predict the genetic consequences for humans of exposure to ionising radiation has been one of the most important issues of human genetics over the past 60 years. To date, there has been little experimental knowledge on the genetic risks of human exposure to ionising radiation. Radiation-induced deleterious hereditary effects have not been detected in human populations - not even among the offspring of atomic bomb survivors in Hiroshima and Nagasaki. This does not mean deleterious hereditary effects do not exist in humans, but rather that they are small and/or difficult to detect because the normal incidence of inherited abnormalities is quite high in the human population. Thus, assessment of radiation-induced hereditary risks in humans has been based on the common knowledge of human heredity and on animal experiments. However, recent data have suggested that hyper-variable tandem repeat minisatellite loci provide a useful and sensitive experimental approach for monitoring radiation-induced germline mutations in humans. In order to investigate the feasibility of the minisatellite mutation screening system in assessing radiation-induced hereditary risks in humans, we examined the amount of hereditary minisatellite mutations among the offspring of Estonian Chernobyl cleanup workers. The men studied received a median radiation dose of 109 mSv while working on the cleanup activities after the Chernobyl accident. We compared the minisatellite mutation rates of 155 children born to 147 Estonian Chernobyl cleanup workers after the accident to those of their 148 siblings born prior to it. In addition, 44 Estonian families, where the father had not been exposed to radiation, composed an additional control group. In all of these families, the paternity of the children was ascertained by using 5 minisatellite loci (APOB, HRAS, MCOB19, MCT118, and YNZ-22) in PCR-based analyses. Other 8 minisatellite loci (B6.7, CEB1, CEB15, CEB25, CEB36, MS1, MS31, and MS32) were used

Vitamin D3 analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial cells.

Science.gov (United States)

Tada, Hiroyuki; Shimizu, Takamitsu; Nagaoka, Isao; Takada, Haruhiko

2016-01-01

Maxacalcitol (22-oxacalcitriol: OCT) is a synthetic vitamin D3 analog with a limited calcemic effect. In this study, we investigated whether OCT increases the production of LL-37/CAP-18, a human cathelicidin antimicrobial peptide, in human gingival/oral epithelial cells. A human gingival epithelial cell line (Ca9-22) and human oral epithelial cell lines (HSC-2, HSC-3, and HSC-4) exhibited the enhanced expression of LL-37 mRNA upon stimulation with OCT as well as active metabolites of vitamins D3 and D2. Among the human epithelial cell lines, Ca9-22 exhibited the strongest response to these vitamin D-related compounds. OCT induced the higher production of CAP-18 (ng/mL order) until 6 days time-dependently in Ca9-22 cells in culture. The periodontal pathogen Porphyromonas gingivalis was killed by treatment with the LL-37 peptide. These findings suggest that OCT induces the production of hCAP-18/LL-37 in a manner similar to that induced by the active metabolite of vitamin D3.

Accurate external localization of the left frontal cortex in dogs by using pointer based frameless neuronavigation

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Robrecht Dockx

2017-07-01

Full Text Available Background In humans, non-stereotactic frameless neuronavigation systems are used as a topographical tool for non-invasive brain stimulation methods such as Transcranial Magnetic Stimulation (TMS. TMS studies in dogs may provide treatment modalities for several neuropsychological disorders in dogs. Nevertheless, an accurate non-invasive localization of a stimulation target has not yet been performed in this species. Hypothesis This study was primarily put forward to externally locate the left frontal cortex in 18 healthy dogs by means of a human non-stereotactic neuronavigation system. Secondly, the accuracy of the external localization was assessed. Animals A total of 18 healthy dogs, drawn at random from the research colony present at the faculty of Veterinary Medicine (Ghent University, were used. Methods Two sets of coordinates (X, Y, Z and X″, Y″, Z″ were compared on each dog their tomographical dataset. Results The non-stereotactic neuronavigation system was able to externally locate the frontal cortex in dogs with accuracy comparable with human studies. Conclusion and clinical importance This result indicates that a non-stereotactic neuronavigation system can accurately externally locate the left frontal cortex and paves the way to use guided non-invasive brain stimulation methods as an alternative treatment procedure for neurological and behavioral disorders in dogs. This technique could, in analogy with human guided non-invasive brain stimulation, provide a better treatment outcome for dogs suffering from anxiety disorders when compared to its non-guided alternative.

Apical External Root Resorption and Repair in Orthodontic Tooth Movement: Biological Events.

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Feller, Liviu; Khammissa, Razia A G; Thomadakis, George; Fourie, Jeanine; Lemmer, Johan

2016-01-01

Some degree of external root resorption is a frequent, unpredictable, and unavoidable consequence of orthodontic tooth movement mediated by odontoclasts/cementoclasts originating from circulating precursor cells in the periodontal ligament. Its pathogenesis involves mechanical forces initiating complex interactions between signalling pathways activated by various biological agents. Resorption of cementum is regulated by mechanisms similar to those controlling osteoclastogenesis and bone resorption. Following root resorption there is repair by cellular cementum, but factors mediating the transition from resorption to repair are not clear. In this paper we review some of the biological events associated with orthodontically induced external root resorption.

Apical External Root Resorption and Repair in Orthodontic Tooth Movement: Biological Events

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Liviu Feller

2016-01-01

Full Text Available Some degree of external root resorption is a frequent, unpredictable, and unavoidable consequence of orthodontic tooth movement mediated by odontoclasts/cementoclasts originating from circulating precursor cells in the periodontal ligament. Its pathogenesis involves mechanical forces initiating complex interactions between signalling pathways activated by various biological agents. Resorption of cementum is regulated by mechanisms similar to those controlling osteoclastogenesis and bone resorption. Following root resorption there is repair by cellular cementum, but factors mediating the transition from resorption to repair are not clear. In this paper we review some of the biological events associated with orthodontically induced external root resorption.

Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents

International Nuclear Information System (INIS)

Wan, X. Steven; Ware, Jeffrey H.; Zhou, Zhaozong; Donahue, Jeremiah J.; Guan, Jun; Kennedy, Ann R.

2006-01-01

Purpose: To evaluate the protective effects of antioxidant agents against space radiation-induced oxidative stress in cultured human epithelial cells. Methods and Materials: The effects of selected concentrations of N-acetylcysteine, ascorbic acid, sodium ascorbate, co-enzyme Q10, α-lipoic acid, L-selenomethionine, and vitamin E succinate on radiation-induced oxidative stress were evaluated in MCF10 human breast epithelial cells exposed to radiation with X-rays, γ-rays, protons, or high mass, high atomic number, and high energy particles using a dichlorofluorescein assay. Results: The results demonstrated that these antioxidants are effective in protecting against radiation-induced oxidative stress and complete or nearly complete protection was achieved by treating the cells with a combination of these agents before and during the radiation exposure. Conclusion: The combination of antioxidants evaluated in this study is likely be a promising countermeasure for protection against space radiation-induced adverse biologic effects

Acetyl-CoA Carboxylase-α Inhibitor TOFA Induces Human Cancer Cell Apoptosis

Science.gov (United States)

Wang, Chun; Xu, Canxin; Sun, Mingwei; Luo, Dixian; Liao, Duan-fang; Cao, Deliang

2009-01-01

Acetyl-CoA carboxylase-α (ACCA) is a rate-limiting enzyme in long chain fatty acid synthesis, playing a critical role in cellular energy storage and lipid synthesis. ACCA is upregulated in multiple types of human cancers and small interfering RNA-mediated ACCA silencing in human breast and prostate cancer cells results in oxidative stress and apoptosis. This study reports for the first time that TOFA (5-tetradecyloxy-2-furoic acid), an allosteric inhibitor of ACCA, is cytotoxic to lung cancer cells NCI-H460 and colon carcinoma cells HCT-8 and HCT-15, with an IC50 at approximately 5.0, 5.0, and 4.5 μg/ml, respectively. TOFA at 1.0–20.0 μg/ml effectively blocked fatty acid synthesis and induced cell death in a dose-dependent manner. The cell death was characterized with PARP cleavage, DNA fragmentation, and annexin-V staining, all of which are the features of the apoptosis. Supplementing simultaneously the cells with palmitic acids (100 μM), the end-products of the fatty acid synthesis pathway, prevented the apoptosis induced by TOFA. Taken together, these data suggest that TOFA is a potent cytotoxic agent to lung and colon cancer cells, inducing apoptosis through disturbing their fatty acid synthesis. PMID:19450551

Acetyl-CoA carboxylase-alpha inhibitor TOFA induces human cancer cell apoptosis.

Science.gov (United States)

Wang, Chun; Xu, Canxin; Sun, Mingwei; Luo, Dixian; Liao, Duan-Fang; Cao, Deliang

2009-07-31

Acetyl-CoA carboxylase-alpha (ACCA) is a rate-limiting enzyme in long chain fatty acid synthesis, playing a critical role in cellular energy storage and lipid synthesis. ACCA is upregulated in multiple types of human cancers and small interfering RNA-mediated ACCA silencing in human breast and prostate cancer cells results in oxidative stress and apoptosis. This study reports for the first time that TOFA (5-tetradecyloxy-2-furoic acid), an allosteric inhibitor of ACCA, is cytotoxic to lung cancer cells NCI-H460 and colon carcinoma cells HCT-8 and HCT-15, with an IC(50) at approximately 5.0, 5.0, and 4.5 microg/ml, respectively. TOFA at 1.0-20.0 microg/ml effectively blocked fatty acid synthesis and induced cell death in a dose-dependent manner. The cell death was characterized with PARP cleavage, DNA fragmentation, and annexin-V staining, all of which are the features of the apoptosis. Supplementing simultaneously the cells with palmitic acids (100 microM), the end-products of the fatty acid synthesis pathway, prevented the apoptosis induced by TOFA. Taken together, these data suggest that TOFA is a potent cytotoxic agent to lung and colon cancer cells, inducing apoptosis through disturbing their fatty acid synthesis.

Summary report of already existing guidance on the implementation of External Hazards in extended Level 1 PSA

International Nuclear Information System (INIS)

Klug, J.; Kumar, M.; Prochaska, J.; Brac, P.; Vasseur, D.; Brinkman, H.; Kahia, S.; Nitoi, Mirela; Apostol, M.; Georgescu, G.; Volkanovski, Andrija; Mustoe, J.; Alzbutas, R.; La Rovere, S.

2015-08-01

The report provides a summary of already existing guidance on the implementation of external hazards in extended level 1 PSA. It summarized the lessons learnt from existing standards, existing gaps and possibility for future development within the work-package WP22 'How to introduce hazards in L1 PSA and all possibilities of events combinations'. The report is focused on the four following areas, for several hazards: 1) Impact on the SSCs modelled in L1 PSA event trees; 2) Impact on Human Reliability Assessment modelling in L1 PSA; 3) Site impact modelling in L1 PSA event trees; 4) Link between external initiating events of PSA and NPP design basis conditions. During the review of existing guidance, it appeared that many of the references form a suitable basis to introduce external hazards in L1 PSA including event combination. Available guidelines provide usable recommendations to evaluate failure probabilities of SSCs depending on the influence of single hazard or events combination. The most detailed guidelines are devoted to the seismic events and fires. Even if these guidelines deal only with single event impact, they can be also used for combined events purpose to evaluate particular effects induced by analyzed external hazards. Guidelines provide general systematic framework how to determine the scope of SSCs for extended PSA and failure modes (develop an extended list of components). In general available guidelines provide detailed framework for analysis of seismic event. The other external hazards are not always covered so deeply. This is probably caused by specific site nature of these hazards like external floods, fires etc. In case of HRA, more detailed information and HRA models are available for seismic events or fire events. For the other external hazards, the literature with regard to HRA is not well developed. The PSA for external hazards should take account the potential for human response to be affected by the external event. More realistic Human

Aluminum induces lipid peroxidation and aggregation of human blood platelets

Directory of Open Access Journals (Sweden)

T.J.C. Neiva

1997-05-01

Full Text Available Aluminum (Al3+ intoxication is thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations arising from long-term hemodialysis. Although the metal does not present redox capacity, it can stimulate tissue lipid peroxidation in animal models. Furthermore, in vitro studies have revealed that the fluoroaluminate complex induces diacylglycerol formation, 43-kDa protein phosphorylation and aggregation. Based on these observations, we postulated that Al3+-induced blood platelet aggregation was mediated by lipid peroxidation. Using chemiluminescence (CL of luminol as an index of total lipid peroxidation capacity, we established a correlation between lipid peroxidation capacity and platelet aggregation. Al3+ (20-100 µM stimulated CL production by human blood platelets as well as their aggregation. Incubation of the platelets with the antioxidants nor-dihydroguaiaretic acid (NDGA (100 µM and n-propyl gallate (NPG (100 µM, inhibitors of the lipoxygenase pathway, completely prevented CL and platelet aggregation. Acetyl salicylic acid (ASA (100 µM, an inhibitor of the cyclooxygenase pathway, was a weaker inhibitor of both events. These findings suggest that Al3+ stimulates lipid peroxidation and the lipoxygenase pathway in human blood platelets thereby causing their aggregation

First Branchial Cleft Fistula Associated with External Auditory Canal Stenosis and Middle Ear Cholesteatoma

Science.gov (United States)

Abdollahi fakhim, Shahin; Naderpoor, Masoud; Mousaviagdas, Mehrnoosh

2014-01-01

Introduction: First branchial cleft anomalies manifest with duplication of the external auditory canal. Case Report: This report features a rare case of microtia and congenital middle ear and canal cholesteatoma with first branchial fistula. External auditory canal stenosis was complicated by middle ear and external canal cholesteatoma, but branchial fistula, opening in the zygomatic root and a sinus in the helical root, may explain this feature. A canal wall down mastoidectomy with canaloplasty and wide meatoplasty was performed. The branchial cleft was excised through parotidectomy and facial nerve dissection. Conclusion: It should be considered that canal stenosis in such cases can induce cholesteatoma formation in the auditory canal and middle ear. PMID:25320705

First Branchial Cleft Fistula Associated with External Auditory Canal Stenosis and Middle Ear Cholesteatoma

Directory of Open Access Journals (Sweden)

shahin abdollahi fakhim

2014-10-01