WorldWideScience

Sample records for human compound action

  1. Human neural tuning estimated from compound action potentials in normal hearing human volunteers

    Science.gov (United States)

    Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

    2015-12-01

    The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

  2. The action of sennosides and related compounds on human colon and rectum 1

    Science.gov (United States)

    Hardcastle, J. D.; Wilkins, J. L.

    1970-01-01

    The direct action of intraluminal senna and related compounds on the human colon and rectum has been investigated. Motility was recorded by balloon kymography with recording units inserted into well established transverse colostomies or into the rectum. The motility of the colon was not changed by intraluminal senna glycosides but the introduction of senna previously incubated with faeces or Esch. coli stimulated the colon to peristalt. The peristalsis was similar to that stimulated by rheinanthrone, an oxanthrone produced by chemical hydrolysis and reduction of senna. Both activated senna and rheinanthrone appeared to act in the colon by contact stimulation. No peristaltic response was stimulated in the rectum, either with activated senna or with rheinanthrone. PMID:4929273

  3. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocitie...... effort and attention to theory and practical detail that may be time consuming....

  4. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocities...... dispersion over increasing conduction distance is greater for the SNAP than CMAP, and demonstration of conduction block is therefore difficult. In addition, the effect of temporal dispersion on amplitude and shape is strongly dependent on the number of conducting fibers and their distribution, and......, with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers...

  5. [Loudness optimized registration of compound action potential in cochlear implant recipients].

    Science.gov (United States)

    Berger, Klaus; Hocke, Thomas; Hessel, Horst

    2017-11-01

    Background Postoperative measurements of compound action potentials are not always possible due to the insufficient acceptance of the CI-recipients. This study investigated the impact of different parameters on the acceptance of the measurements. Methods Compound action potentials of 16 CI recipients were measured with different pulse-widths. Recipients performed a loudness rating at the potential thresholds with the different sequences. Results Compound action potentials obtained with higher pulse-widths were rated softer than those obtained with smaller pulse-widths. Conclusions Compound action potentials measured with higher pulse-widths generate a gap between loudest acceptable presentation level and potential threshold. This gap contributes to a higher acceptance of postoperative measurements. Georg Thieme Verlag KG Stuttgart · New York.

  6. The Kinetics Human Action Video Dataset

    OpenAIRE

    Kay, Will; Carreira, Joao; Simonyan, Karen; Zhang, Brian; Hillier, Chloe; Vijayanarasimhan, Sudheendra; Viola, Fabio; Green, Tim; Back, Trevor; Natsev, Paul; Suleyman, Mustafa; Zisserman, Andrew

    2017-01-01

    We describe the DeepMind Kinetics human action video dataset. The dataset contains 400 human action classes, with at least 400 video clips for each action. Each clip lasts around 10s and is taken from a different YouTube video. The actions are human focussed and cover a broad range of classes including human-object interactions such as playing instruments, as well as human-human interactions such as shaking hands. We describe the statistics of the dataset, how it was collected, and give some ...

  7. Everyday robotic action: Lessons from human action control

    Directory of Open Access Journals (Sweden)

    Roy eDe Kleijn

    2014-03-01

    Full Text Available Robots are increasingly capable of performing everyday human activities such as cooking, cleaning, and doing the laundry. This requires the real-time planning and execution of complex, temporally-extended sequential actions under high degrees of uncertainty, which provides many challenges to traditional approaches to robot action control. We argue that important lessons in this respect can be learned from research on human action control. We provide a brief overview of available psychological insights into this issue and focus on four principles that we think could be particularly beneficial for robot control: the integration of symbolic and subsymbolic planning of action sequences, the integration of feedforward and feedback control, the clustering of complex actions into subcomponents, and the contextualization of action-control structures through goal representations.

  8. Action recognition using mined hierarchical compound features.

    Science.gov (United States)

    Gilbert, Andrew; Illingworth, John; Bowden, Richard

    2011-05-01

    The field of Action Recognition has seen a large increase in activity in recent years. Much of the progress has been through incorporating ideas from single-frame object recognition and adapting them for temporal-based action recognition. Inspired by the success of interest points in the 2D spatial domain, their 3D (space-time) counterparts typically form the basic components used to describe actions, and in action recognition the features used are often engineered to fire sparsely. This is to ensure that the problem is tractable; however, this can sacrifice recognition accuracy as it cannot be assumed that the optimum features in terms of class discrimination are obtained from this approach. In contrast, we propose to initially use an overcomplete set of simple 2D corners in both space and time. These are grouped spatially and temporally using a hierarchical process, with an increasing search area. At each stage of the hierarchy, the most distinctive and descriptive features are learned efficiently through data mining. This allows large amounts of data to be searched for frequently reoccurring patterns of features. At each level of the hierarchy, the mined compound features become more complex, discriminative, and sparse. This results in fast, accurate recognition with real-time performance on high-resolution video. As the compound features are constructed and selected based upon their ability to discriminate, their speed and accuracy increase at each level of the hierarchy. The approach is tested on four state-of-the-art data sets, the popular KTH data set to provide a comparison with other state-of-the-art approaches, the Multi-KTH data set to illustrate performance at simultaneous multiaction classification, despite no explicit localization information provided during training. Finally, the recent Hollywood and Hollywood2 data sets provide challenging complex actions taken from commercial movie sequences. For all four data sets, the proposed hierarchical

  9. Intracellular Diagnostics: Hunting for the Mode of Action of Redox-Modulating Selenium Compounds in Selected Model Systems

    Directory of Open Access Journals (Sweden)

    Dominika Mániková

    2014-08-01

    Full Text Available Redox-modulating compounds derived from natural sources, such as redox active secondary metabolites, are currently of considerable interest in the field of chemoprevention, drug and phytoprotectant development. Unfortunately, the exact and occasionally even selective activity of such products, and the underlying (bio-chemical causes thereof, are often only poorly understood. A combination of the nematode- and yeast-based assays provides a powerful platform to investigate a possible biological activity of a new compound and also to explore the “redox link” which may exist between its activity on the one side and its chemistry on the other. Here, we will demonstrate the usefulness of this platform for screening several selenium and tellurium compounds for their activity and action. We will also show how the nematode-based assay can be used to obtain information on compound uptake and distribution inside a multicellular organism, whilst the yeast-based system can be employed to explore possible intracellular mechanisms via chemogenetic screening and intracellular diagnostics. Whilst none of these simple and easy-to-use assays can ultimately substitute for in-depth studies in human cells and animals, these methods nonetheless provide a first glimpse on the possible biological activities of new compounds and offer direction for more complicated future investigations. They may also uncover some rather unpleasant biochemical actions of certain compounds, such as the ability of the trace element supplement selenite to induce DNA strand breaks.

  10. Action Mechanism of Iridoid Compounds on Guinea-pig Right Atrium Specimens

    OpenAIRE

    齊藤, 久美子; 酒井 淳一; 堀田 芳弘

    2016-01-01

     We examined the actions of iridoid compounds (aucubin (Auc), geniposidic acid (GA)) and a noniridoid compound (chlorogenic acid (CA)) contained in Eucommia leaves [1] [2], which show blood pressure-lowering effects, on the heart using right atrial specimens isolated from guinea pigs. These 3 compounds showed negative inotropic effects (NIE) and negative chronotropic effects (NCE) at a final concentration of 10 -5 or 10 -4 M in an experiment using right atrial specimens. Furthermore, pretreat...

  11. Human Actions Made Tangible

    DEFF Research Database (Denmark)

    Buur, Jacob; Caglio, Agnese; Jensen, Lars Christian

    2014-01-01

    , a method developed to engage people from different backgrounds in collaboratively analysing videos with the help of physical objects. We will present one of these tools, Action Scrabble, for analysing temporal organisation of human actions. We work with a case of skilled forklift truck driving...

  12. Mechanisms of action of phenolic compounds in olive.

    Science.gov (United States)

    Rafehi, Haloom; Ververis, Katherine; Karagiannis, Tom C

    2012-06-01

    Olive oil, an oil rich in monounsaturated fatty acids (MUFCs) and minor constituents including phenolic compounds, is a major component of the Mediterranean diet. The potential health benefits of the Mediterranean diet were highlighted by the seminal Seven Countries Study, and more contemporary research has identified olive oil as a major element responsible for these effects. It is emerging that the phenolic compounds are the most likely candidates accounting for the cardioprotective and cancer preventative effects of extra virgin olive oil (EVOO). In particular, the phenolic compound, hydroxytyrosol has been identified as one of the most potent antioxidants found in olive oil. This review will briefly consider historical aspects of olive oil research and the biological properties of phenolic compounds in olive oil will be discussed. The focus of the discussion will be related to the mechanisms of action of hydroxytyrosol. Studies have demonstrated that hydroxytyrosol induces apoptosis and cell cycle arrest in cancer cells. Further, research has shown that hydroxytyrosol can prevent cardiovascular disease by reducing the expression of adhesion molecules on endothelial cells and preventing the oxidation of low-density lipoprotein (LDL). The molecular mechanisms accounting for these effects are reviewed.

  13. Synthesis of sulfenamides, derivatives of morpholine, 4-aminomorpholine and thiomorpholine as compounds of potential radioprotective action

    Energy Technology Data Exchange (ETDEWEB)

    Strzelczyk, M.; Kucharski, A. (Wojskowa Akademia Medyczna, Lodz (Poland))

    1979-01-01

    Sulfenamides belong to the group of compounds displaying radioprotective action. Their mechanism of action is based mainly on the protection against oxygenation. Six compounds were synthetized four of which i.e. 3-nitrophenylothiomorpholine, 2,4-dinitrophenylothiomorpholine, 2,4-dinitrophenylothio-4-aminomorpholine and 2,4-dinitrophenylothiothiomorpholine were to date not described in the literature. The structure of the synthetized compounds was confirmed by elementary and infrared spectral analysis.

  14. Observed Human Actions, and Not Mechanical Actions, Induce Searching Errors in Infants

    Directory of Open Access Journals (Sweden)

    Yusuke Moriguchi

    2012-01-01

    Full Text Available Recent neurophysiological studies have shown that several human brain regions involved in executing actions are activated by merely observing such actions via a human, and not by a mechanical hand. At a behavioral level, observing a human’s movements, but not those of a robot, significantly interferes with ongoing executed movements. However, it is unclear whether the biological tuning in the observation/execution matching system are functional during infancy. The present study examines whether a human’s actions, and not a mechanical action, influence infants’ execution of the same actions due to the observation/execution matching system. Twelve-month-old infants were given a searching task. In the tasks, infants observed an object hidden at location A, after which either a human hand (human condition or a mechanical one (mechanical condition searched the object correctly. Next, the object was hidden at location B and infants were allowed to search the object. We examined whether infants searched the object at location B correctly. The results revealed that infants in the human condition were more likely to search location A than those in the mechanical condition. Moreover, the results suggested that infants’ searching behaviors were affected by their observations of the same actions by a human, but not a mechanical hand. Thus, it may be concluded that the observation/execution matching system may be biologically tuned during infancy.

  15. Spatio-Temporal Layout of Human Actions for Improved Bag-of-Words Action Detection

    NARCIS (Netherlands)

    Burghouts, G.J.; Schutte, K.

    2013-01-01

    We investigate how human action recognition can be improved by considering spatio-temporal layout of actions. From literature, we adopt a pipeline consisting of STIP features, a random forest to quantize the features into histograms, and an SVM classifier. Our goal is to detect 48 human actions,

  16. Closure Report for Corrective Action Unit 566: EMAD Compound, Nevada National Security Site, Nevada with ROTC-1, Revision 0

    Energy Technology Data Exchange (ETDEWEB)

    Mark Krauss

    2011-06-01

    This Closure Report (CR) presents information supporting the closure of Corrective Action Unit (CAU) 566: EMAD Compound, Nevada National Security Site, Nevada. Corrective Action Unit 566 comprises Corrective Action Site (CAS) 25-99-20, EMAD Compound, located within Area 25 of the Nevada National Security Site. The purpose of this CR is to provide documentation supporting the completed corrective actions and provide data confirming that the closure objectives for CAU 566 were met. To achieve this, the following actions were performed: • Review the current site conditions, including the concentration and extent of contamination. • Implement any corrective actions necessary to protect human health and the environment. • Properly dispose of corrective action and investigation wastes. • Document Notice of Completion and closure of CAU 566 issued by the Nevada Division of Environmental Protection. From October 2010 through May 2011, closure activities were performed as set forth in the Streamlined Approach for Environmental Restoration Plan for CAU 566: EMAD Compound, Nevada National Security Site, Nevada. The purposes of the activities as defined during the data quality objectives process were as follows: • Determine whether contaminants of concern (COCs) are present. • If COCs are present, determine their nature and extent, implement appropriate corrective actions, and properly dispose of wastes. Analytes detected during the closure activities were evaluated against final action levels (FALs) to determine COCs for CAU 566. Assessment of the data from collected soil samples, and from radiological and visual surveys of the site, indicates the FALs were exceeded for polychlorinated biphenyls (PCBs), semivolatile organic compounds (SVOCs), and radioactivity. Corrective actions were implemented to remove the following: • Radiologically contaminated soil assumed greater than FAL at two locations • Radiologically contaminated soil assumed greater than FAL with

  17. In vitro assessment of antiproliferative action selectivity of dietary isothiocyanates for tumor versus normal human cells

    Directory of Open Access Journals (Sweden)

    Konić-Ristić Aleksandra

    2016-01-01

    Full Text Available Background/Aim. Numerous epidemiological studies have shown beneficial effects of cruciferous vegetables consumption in cancer chemoprevention. Biologically active compounds of different Brassicaceae species with antitumor potential are isothiocyanates, present in the form of their precursors - glucosinolates. The aim of this study was to determine the selectivity of antiproliferative action of dietary isothiocyanates for malignant versus normal cells. Methods. Antiproliferative activity of three isothiocyanates abundant in human diet: sulforaphane, benzyl isothiocyanate (BITC and phenylethyl isothiocyanate, on human cervix carcinoma cell line - HeLa, melanoma cell line - Fem-x, and colon cancer cell line - LS 174, and on peripheral blood mononuclear cells (PBMC, with or without mitogen, were determined by MTT colorimetric assay 72 h after their continuous action. Results. All investigated isothiocyanates inhibited the proliferation of HeLa, Fem-x and LS 174 cells. On all cell lines treated, BITC was the most potent inhibitor of cell proliferation with half-maximum inhibitory concentration (IC50 values of 5.04 mmoL m-3 on HeLa cells, 2.76 mmol m-3 on Fem-x, and 14.30 mmol m-3 on LS 174 cells. Antiproliferative effects on human PBMC were with higher IC50 than on malignant cells. Indexes of selectivity, calculated as a ratio between IC50 values obtained on PBMC and malignant cells, were between 1.12 and 16.57, with the highest values obtained for the action of BITC on melanoma Fem-x cells. Conclusion. Based on its antiproliferative effects on malignant cells, as well as the selectivity of the action to malignant vs normal cells, benzyl isothiocyanate can be considered as a promising candidate in cancer chemoprevention. In general, the safety of investigated compounds, in addition to their antitumor potential, should be considered as an important criterion in cancer chemoprevention. Screening of selectivity is a plausible approach to the evaluation

  18. Human action recognition using trajectory-based representation

    Directory of Open Access Journals (Sweden)

    Haiam A. Abdul-Azim

    2015-07-01

    Full Text Available Recognizing human actions in video sequences has been a challenging problem in the last few years due to its real-world applications. A lot of action representation approaches have been proposed to improve the action recognition performance. Despite the popularity of local features-based approaches together with “Bag-of-Words” model for action representation, it fails to capture adequate spatial or temporal relationships. In an attempt to overcome this problem, a trajectory-based local representation approaches have been proposed to capture the temporal information. This paper introduces an improvement of trajectory-based human action recognition approaches to capture discriminative temporal relationships. In our approach, we extract trajectories by tracking the detected spatio-temporal interest points named “cuboid features” with matching its SIFT descriptors over the consecutive frames. We, also, propose a linking and exploring method to obtain efficient trajectories for motion representation in realistic conditions. Then the volumes around the trajectories’ points are described to represent human actions based on the Bag-of-Words (BOW model. Finally, a support vector machine is used to classify human actions. The effectiveness of the proposed approach was evaluated on three popular datasets (KTH, Weizmann and UCF sports. Experimental results showed that the proposed approach yields considerable performance improvement over the state-of-the-art approaches.

  19. Understanding human action: integrating meanings, mechanisms, causes, and contexts

    NARCIS (Netherlands)

    Keestra, M.; Repko, A.F.; Newell, W.H.; Szostak, R.

    2012-01-01

    Humans are capable of understanding an incredible variety of actions performed by other humans. Even though these range from primary biological actions like eating and fleeing, to acts in parliament or in poetry, humans generally can make sense of each other’s actions. Understanding other people’s

  20. Human action analysis with randomized trees

    CERN Document Server

    Yu, Gang; Liu, Zicheng

    2014-01-01

    This book will provide a comprehensive overview on human action analysis with randomized trees. It will cover both the supervised random trees and the unsupervised random trees. When there are sufficient amount of labeled data available, supervised random trees provides a fast method for space-time interest point matching. When labeled data is minimal as in the case of example-based action search, unsupervised random trees is used to leverage the unlabelled data. We describe how the randomized trees can be used for action classification, action detection, action search, and action prediction.

  1. Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Poulet, Claire; Diness, Jonas Goldin

    2014-01-01

    (+) currents by ∼15% and prolonged action potential duration (APD), but no effect was observed in myocytes from AF patients. In trabeculae muscle strips from right atrial appendages of SR patients, both compounds increased APD and effective refractory period, and depolarized the resting membrane potential......, while only NS8593 induced these effects in tissue from AF patients. SK channel inhibition did not alter any electrophysiological parameter in human interventricular septum tissue. CONCLUSIONS: SK channels are present in human atria where they participate in repolarization. SK2 and SK3 were down...

  2. Episodic Reasoning for Vision-Based Human Action Recognition

    Directory of Open Access Journals (Sweden)

    Maria J. Santofimia

    2014-01-01

    Full Text Available Smart Spaces, Ambient Intelligence, and Ambient Assisted Living are environmental paradigms that strongly depend on their capability to recognize human actions. While most solutions rest on sensor value interpretations and video analysis applications, few have realized the importance of incorporating common-sense capabilities to support the recognition process. Unfortunately, human action recognition cannot be successfully accomplished by only analyzing body postures. On the contrary, this task should be supported by profound knowledge of human agency nature and its tight connection to the reasons and motivations that explain it. The combination of this knowledge and the knowledge about how the world works is essential for recognizing and understanding human actions without committing common-senseless mistakes. This work demonstrates the impact that episodic reasoning has in improving the accuracy of a computer vision system for human action recognition. This work also presents formalization, implementation, and evaluation details of the knowledge model that supports the episodic reasoning.

  3. Mode of action of Organotins in Immune cells

    NARCIS (Netherlands)

    Hendriksen, P.J.M.; Schmeits, P.C.J.; Loveren, van H.; Shao, J.; Peijnenburg, A.A.C.M.

    2015-01-01

    This chapter focuses mainly on the effects of organotin compounds in various human and animal models and describes the research performed to elucidate the immunotoxic mechanism of action of organotin compounds. Both dibutyltin (DBT) and tributyltins (TBT) organotin compounds can cause atrophy of the

  4. Life cycle responses of the midge Chironomus riparius to compounds with different modes of action.

    NARCIS (Netherlands)

    Marinkovic, M.; Verweij, R.A.; Nummerdor, G.A.; Jonker, M.J.; Kraak, M.H.S.; Admiraal, W.

    2011-01-01

    Compounds with different modes of action may affect life cycles of biota differently. The aim of the present study was therefore to investigate the impact of four chemicals with different modes of action, including the essential metal copper, the nonessential metal cadmium, the organometal

  5. Life cycle responses of the midge Chironomus riparius to compounds with different modes of action

    NARCIS (Netherlands)

    Marinkovic, M.; Verweij, R.A.; Nummerdor, G.A.; Jonker, M.J.; Kraak, M.H.S.; Admiraal, W.

    2011-01-01

    Compounds with different modes of action may affect life cycles of biota differently. The aim of the present study was therefore to investigate the impact of four chemicals with different modes of action, including the essential metal copper, the nonessential metal cadmium, the organometal

  6. Herbal Remedies for Coccidiosis Control: A Review of Plants, Compounds, and Anticoccidial Actions

    Directory of Open Access Journals (Sweden)

    Thangarasu Muthamilselvan

    2016-01-01

    Full Text Available Coccidiosis is the bane of the poultry industry causing considerable economic loss. Eimeria species are known as protozoan parasites to cause morbidity and death in poultry. In addition to anticoccidial chemicals and vaccines, natural products are emerging as an alternative and complementary way to control avian coccidiosis. In this review, we update recent advances in the use of anticoccidial phytoextracts and phytocompounds, which cover 32 plants and 40 phytocompounds, following a database search in PubMed, Web of Science, and Google Scholar. Four plant products commercially available for coccidiosis are included and discussed. We also highlight the chemical and biological properties of the plants and compounds as related to coccidiosis control. Emphasis is placed on the modes of action of the anticoccidial plants and compounds such as interference with the life cycle of Eimeria, regulation of host immunity to Eimeria, growth regulation of gut bacteria, and/or multiple mechanisms. Biological actions, mechanisms, and prophylactic/therapeutic potential of the compounds and extracts of plant origin in coccidiosis are summarized and discussed.

  7. Application of optical action potentials in human induced pluripotent stem cells-derived cardiomyocytes to predict drug-induced cardiac arrhythmias.

    Science.gov (United States)

    Lu, H R; Hortigon-Vinagre, M P; Zamora, V; Kopljar, I; De Bondt, A; Gallacher, D J; Smith, G

    2017-09-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were digitized at 10kHz and the records subsequently analyzed off-line. Cells were exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound) that were blinded to the investigating laboratory. Action potential parameters were measured, including rise time (T rise ) of the optical action potential duration (oAPD). Significant effects on oAPD were sensitively detected with 11 QT-prolonging drugs, while oAPD shortening was observed with I Ca -antagonists, I Kr -activator or ATP-sensitive K + channel (K ATP )-opener. Additionally, the assay detected varied effects induced by 6 different sodium channel blockers. The detection threshold for these drug effects was at or below the published values of free effective therapeutic plasma levels or effective concentrations by other studies. The results of this blinded study indicate that OAP is a sensitive method to accurately detect drug-induced effects (i.e., duration/QT-prolongation, shortening, beat rate, and incidence of early after depolarizations) in hiPS-CMs; therefore, this technique will potentially be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Adaboost-based algorithm for human action recognition

    KAUST Repository

    Zerrouki, Nabil

    2017-11-28

    This paper presents a computer vision-based methodology for human action recognition. First, the shape based pose features are constructed based on area ratios to identify the human silhouette in images. The proposed features are invariance to translation and scaling. Once the human body features are extracted from videos, different human actions are learned individually on the training frames of each class. Then, we apply the Adaboost algorithm for the classification process. We assessed the proposed approach using the UR Fall Detection dataset. In this study six classes of activities are considered namely: walking, standing, bending, lying, squatting, and sitting. Results demonstrate the efficiency of the proposed methodology.

  9. Adaboost-based algorithm for human action recognition

    KAUST Repository

    Zerrouki, Nabil; Harrou, Fouzi; Sun, Ying; Houacine, Amrane

    2017-01-01

    This paper presents a computer vision-based methodology for human action recognition. First, the shape based pose features are constructed based on area ratios to identify the human silhouette in images. The proposed features are invariance to translation and scaling. Once the human body features are extracted from videos, different human actions are learned individually on the training frames of each class. Then, we apply the Adaboost algorithm for the classification process. We assessed the proposed approach using the UR Fall Detection dataset. In this study six classes of activities are considered namely: walking, standing, bending, lying, squatting, and sitting. Results demonstrate the efficiency of the proposed methodology.

  10. Analysis of electrically evoked compound action potential of the auditory nerve in children with bilateral cochlear implants.

    Science.gov (United States)

    Caldas, Fernanda Ferreira; Cardoso, Carolina Costa; Barreto, Monique Antunes de Souza Chelminski; Teixeira, Marina Santos; Hilgenberg, Anacléia Melo da Silva; Serra, Lucieny Silva Martins; Bahmad Junior, Fayez

    2016-01-01

    The cochlear implant device has the capacity to measure the electrically evoked compound action potential of the auditory nerve. The neural response telemetry is used in order to measure the electrically evoked compound action potential of the auditory nerve. To analyze the electrically evoked compound action potential, through the neural response telemetry, in children with bilateral cochlear implants. This is an analytical, prospective, longitudinal, historical cohort study. Six children, aged 1-4 years, with bilateral cochlear implant were assessed at five different intervals during their first year of cochlear implant use. There were significant differences in follow-up time (p=0.0082) and electrode position (p=0.0019) in the T-NRT measure. There was a significant difference in the interaction between time of follow-up and electrode position (p=0.0143) when measuring the N1-P1 wave amplitude between the three electrodes at each time of follow-up. The electrically evoked compound action potential measurement using neural response telemetry in children with bilateral cochlear implants during the first year of follow-up was effective in demonstrating the synchronized bilateral development of the peripheral auditory pathways in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  11. Impact of androgenic/antiandrogenic compounds (AAC) on human sex steroid metabolizing key enzymes

    International Nuclear Information System (INIS)

    Allera, A.; Lo, S.; King, I.; Steglich, F.; Klingmueller, D.

    2004-01-01

    Various pesticides, industrial pollutants and synthetic compounds, to which human populations are exposed, are known or suspected to interfere with endogenous sex hormone functions. Such interference potentially affect the development and expression of the male and female reproductive system or both. Chemicals in this class are thus referred to as endocrine disruptors (ED). This emphazises on the relevance of screening ED for a wide range of sex hormone-mimicking effects. These compounds are believed to exert influence on hormonal actions predominantly by (i) interfering with endogenous steroids in that they functionally interact with plasma membrane-located receptors as well as with nuclear receptors both for estrogens and androgens or (ii) affecting the levels of sex hormones as a result of their impact on steroid metabolizing key enzymes. Essential sex hormone-related enzymes within the endocrine system of humans are aromatase, 5α-reductase 2 as well as specific sulfotransferases and sulfatases (so-called phase I and phase II enzymes, respectively). Using suitable human tissues and human cancer cell lines (placenta, prostate, liver and JEG-3, lymph node carcinoma of prostate (LnCaP) cells) we investigated the impact of 10 widely used chemicals suspected of acting as ED with androgenic or antiandrogenic activity (so-called AAC) on the activity of these sex hormone metabolizing key enzymes in humans. In addition, the respective effects of six substances were also studied as positive controls due to their well-known specific hormonal agonistic/antagonistic activities. The aim of this report and subsequent investigations is to improve human health risk assessment for AAC and other ED

  12. Contamination levels of human pharmaceutical compounds in French surface and drinking water.

    Science.gov (United States)

    Mompelat, S; Thomas, O; Le Bot, B

    2011-10-01

    The occurrence of 20 human pharmaceutical compounds and metabolites from 10 representative therapeutic classes was analysed from resource and drinking water in two catchment basins located in north-west France. 98 samples were analysed from 63 stations (surface water and drinking water produced from surface water). Of the 20 human pharmaceutical compounds selected, 16 were quantified in both the surface water and drinking water, with 22% of the values above the limit of quantification for surface water and 14% for drinking water). Psychostimulants, non-steroidal anti-inflammatory drugs, iodinated contrast media and anxiolytic drugs were the main therapeutic classes of human pharmaceutical compounds detected in the surface water and drinking water. The results for surface water were close to results from previous studies in spite of differences in prescription rates of human pharmaceutical compounds in different countries. The removal rate of human pharmaceutical compounds at 11 water treatment units was also determined. Only caffeine proved to be resistant to drinking water treatment processes (with a minimum rate of 5%). Other human pharmaceutical compounds seemed to be removed more efficiently (average elimination rate of over 50%) by adsorption onto activated carbon and oxidation/disinfection with ozone or chlorine (not taking account of the disinfection by-products). These results add to the increasing evidence of the occurrence of human pharmaceutical compounds in drinking water that may represent a threat to human beings exposed to a cocktail of human pharmaceutical compounds and related metabolites and by-products in drinking water.

  13. A word in the hand: action, gesture and mental representation in humans and non-human primates

    Science.gov (United States)

    Cartmill, Erica A.; Beilock, Sian; Goldin-Meadow, Susan

    2012-01-01

    The movements we make with our hands both reflect our mental processes and help to shape them. Our actions and gestures can affect our mental representations of actions and objects. In this paper, we explore the relationship between action, gesture and thought in both humans and non-human primates and discuss its role in the evolution of language. Human gesture (specifically representational gesture) may provide a unique link between action and mental representation. It is kinaesthetically close to action and is, at the same time, symbolic. Non-human primates use gesture frequently to communicate, and do so flexibly. However, their gestures mainly resemble incomplete actions and lack the representational elements that characterize much of human gesture. Differences in the mirror neuron system provide a potential explanation for non-human primates' lack of representational gestures; the monkey mirror system does not respond to representational gestures, while the human system does. In humans, gesture grounds mental representation in action, but there is no evidence for this link in other primates. We argue that gesture played an important role in the transition to symbolic thought and language in human evolution, following a cognitive leap that allowed gesture to incorporate representational elements. PMID:22106432

  14. The Action of Chain Extenders in Nylon-6, PET, and Model Compounds

    NARCIS (Netherlands)

    Loontjens, T.; Pauwels, K.; Derks, F.; Neilen, M.; Sham, C.K.; Serné, M.

    1997-01-01

    The action of two complementary chain extenders is studied in model systems as well as in poly(ethylene terephthalate) (PET) and nylon–6. Chain extenders are low molecular weight compounds that can be used to increase the molecular weight of polymers in a short time. The reaction must preferably be

  15. Human action recognition based on estimated weak poses

    Science.gov (United States)

    Gong, Wenjuan; Gonzàlez, Jordi; Roca, Francesc Xavier

    2012-12-01

    We present a novel method for human action recognition (HAR) based on estimated poses from image sequences. We use 3D human pose data as additional information and propose a compact human pose representation, called a weak pose, in a low-dimensional space while still keeping the most discriminative information for a given pose. With predicted poses from image features, we map the problem from image feature space to pose space, where a Bag of Poses (BOP) model is learned for the final goal of HAR. The BOP model is a modified version of the classical bag of words pipeline by building the vocabulary based on the most representative weak poses for a given action. Compared with the standard k-means clustering, our vocabulary selection criteria is proven to be more efficient and robust against the inherent challenges of action recognition. Moreover, since for action recognition the ordering of the poses is discriminative, the BOP model incorporates temporal information: in essence, groups of consecutive poses are considered together when computing the vocabulary and assignment. We tested our method on two well-known datasets: HumanEva and IXMAS, to demonstrate that weak poses aid to improve action recognition accuracies. The proposed method is scene-independent and is comparable with the state-of-art method.

  16. The Natural Antiangiogenic Compound AD0157 Induces Caspase-Dependent Apoptosis in Human Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Melissa García-Caballero

    2017-11-01

    Full Text Available Evasion of apoptosis is a hallmark of cancer especially relevant in the development and the appearance of leukemia drug resistance mechanisms. The development of new drugs that could trigger apoptosis in aggressive hematological malignancies, such as AML and CML, may be considered a promising antileukemic strategy. AD0157, a natural marine pyrrolidinedione, has already been described as a compound that inhibits angiogenesis by induction of apoptosis in endothelial cells. The crucial role played by defects in the apoptosis pathways in the pathogenesis, progression and response to conventional therapies of several forms of leukemia, moved us to analyze the effect of this compound on the growth and death of leukemia cells. In this work, human myeloid leukemia cells (HL60, U937 and KU812F were treated with AD0157 ranging from 1 to 10 μM and an experimental battery was applied to evaluate its apoptogenic potential. We report here that AD0157 was highly effective to inhibit cell growth by promotion of apoptosis in human myeloid leukemia cells, and provide evidence of its mechanisms of action. The apoptogenic activity of AD0157 on leukemia cells was verified by an increased chromatin condensation and DNA fragmentation, and confirmed by an augmentation in the apoptotic subG1 population, translocation of the membrane phosphatidylserine from the inner face of the plasma membrane to the cell surface and by cleavage of the apoptosis substrates PARP and lamin-A. In addition, AD0157 in the low micromolar range significantly enhanced the activities of the initiator caspases-8 and -9, and the effector caspases-3/-7 in a dose-dependent manner. Results presented here throw light on the apoptogenic mechanism of action of AD0157, mediated through caspase-dependent cascades, with an especially relevant role played by mitochondria. Altogether, these results suggest the therapeutic potential of this compound for the treatment of human myeloid leukemia.

  17. Recognition and Prediction of Human Actions for Safe Human-Robot Collaboration

    DEFF Research Database (Denmark)

    Andersen, Rasmus Skovgaard; Bøgh, Simon; Ceballos, Iker

    Collaborative industrial robots are creating new opportunities for collaboration between humans and robots in shared workspaces. In order for such collaboration to be efficient, robots - as well as humans - need to have an understanding of the other's intentions and current ongoing action....... In this work, we propose a method for learning, classifying, and predicting actions taken by a human. Our proposed method is based on the human skeleton model from a Kinect. For demonstration of our approach we chose a typical pick-and-place scenario. Therefore, only arms and upper body are considered......; in total 15 joints. Based on trajectories on these joints, different classes of motion are separated using partitioning around medoids (PAM). Subsequently, SVM is used to train the classes to form a library of human motions. The approach allows run-time detection of when a new motion has been initiated...

  18. Skeleton-based human action recognition using multiple sequence alignment

    Science.gov (United States)

    Ding, Wenwen; Liu, Kai; Cheng, Fei; Zhang, Jin; Li, YunSong

    2015-05-01

    Human action recognition and analysis is an active research topic in computer vision for many years. This paper presents a method to represent human actions based on trajectories consisting of 3D joint positions. This method first decompose action into a sequence of meaningful atomic actions (actionlets), and then label actionlets with English alphabets according to the Davies-Bouldin index value. Therefore, an action can be represented using a sequence of actionlet symbols, which will preserve the temporal order of occurrence of each of the actionlets. Finally, we employ sequence comparison to classify multiple actions through using string matching algorithms (Needleman-Wunsch). The effectiveness of the proposed method is evaluated on datasets captured by commodity depth cameras. Experiments of the proposed method on three challenging 3D action datasets show promising results.

  19. Botanical compounds and their regulation of nuclear receptor action: the case of traditional Chinese medicine.

    Science.gov (United States)

    Li, Ling; Bonneton, François; Chen, Xiao Yong; Laudet, Vincent

    2015-02-05

    Nuclear receptors (NRs) are major pharmacological targets that allow an access to the mechanisms controlling gene regulation. As such, some NRs were identified as biological targets of active compounds contained in herbal remedies found in traditional medicines. We aim here to review this expanding literature by focusing on the informative articles regarding the mechanisms of action of traditional Chinese medicines (TCMs). We exemplified well-characterized TCM action mediated by NR such as steroid receptors (ER, GR, AR), metabolic receptors (PPAR, LXR, FXR, PXR, CAR) and RXR. We also provided, when possible, examples from other traditional medicines. From these, we draw a parallel between TCMs and phytoestrogens or endocrine disrupting chemicals also acting via NR. We define common principle of action and highlight the potential and limits of those compounds. TCMs, by finely tuning physiological reactions in positive and negative manners, could act, in a subtle but efficient way, on NR sensors and their transcriptional network. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Carcinogenicity assessment of water-soluble nickel compounds.

    Science.gov (United States)

    Goodman, Julie E; Prueitt, Robyn L; Dodge, David G; Thakali, Sagar

    2009-01-01

    IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.

  1. Human action perspectives based on individual plant examination results

    International Nuclear Information System (INIS)

    Forester, J.; Thompson, C.; Drouin, M.; Lois, E.

    1996-01-01

    This paper provides perspectives on human actions gained from reviewing 76 individual plant examination (IPE) submittals. Human actions found to be important in boiling water reactors (BWRs) and in pressurized water reactors (PWRs) are presented and the events most frequently found important are discussed. Since there are numerous factors that can influence the quantification of human error probabilities (HEPs) and introduce significant variability in the resulting HEPs (which in turn can influence which events are found to be important), the variability in HEPs for similar events across IPEs is examined to assess the extent to which variability in results is due to real versus artifactual differences. Finally, similarities and differences in human action observations across BWRs and PWRs are examined

  2. The dependence level analysis between the human actions in NPP Operation

    International Nuclear Information System (INIS)

    Farcasiu, M.; Nitoi, M.; Apostol, M.; Florescu, G.; Prisecaru, Ilie

    2009-01-01

    The Human Reliability Analysis (HRA) is an important method in Probabilistic Safety Assessment (PSA) studies and offers desirability for concrete improvement of the man - machine - organization interfaces, reliability and safety. An important step in HRA is the dependence level analysis between the human actions performed by the same person or between the actions performed by different persons, step in quantitative analysis of the human errors probabilities. The purpose of this paper is to develop a model to analyze the dependence level between human actions for Nuclear Power Plant (NPP) operation. The model estimates the conditional human error probabilities (CHEP) and joint human error probabilities (JHEP). The achieved sensitivity analyses determine human performance sensibility to systematic variations for dependence level between human actions. The human error probabilities estimated in this paper are adequate values for integration both in HRA and in PSA realized for NPP. This type of analysis helps in finding and analyzing the ways of reducing the likelihood of human errors, so that the impact of human factor to systems availability, reliability and safety can be realistically estimated. In order to demonstrate the usability of this model an analysis is performed upon the dependences between the necessary human actions in mitigating the consequences of LOCA events, particularly for the case of Cernavoda NPP. (authors)

  3. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  4. Multi-class Mode of Action Classification of Toxic Compounds Using Logic Based Kernel Methods.

    Science.gov (United States)

    Lodhi, Huma; Muggleton, Stephen; Sternberg, Mike J E

    2010-09-17

    Toxicity prediction is essential for drug design and development of effective therapeutics. In this paper we present an in silico strategy, to identify the mode of action of toxic compounds, that is based on the use of a novel logic based kernel method. The technique uses support vector machines in conjunction with the kernels constructed from first order rules induced by an Inductive Logic Programming system. It constructs multi-class models by using a divide and conquer reduction strategy that splits multi-classes into binary groups and solves each individual problem recursively hence generating an underlying decision list structure. In order to evaluate the effectiveness of the approach for chemoinformatics problems like predictive toxicology, we apply it to toxicity classification in aquatic systems. The method is used to identify and classify 442 compounds with respect to the mode of action. The experimental results show that the technique successfully classifies toxic compounds and can be useful in assessing environmental risks. Experimental comparison of the performance of the proposed multi-class scheme with the standard multi-class Inductive Logic Programming algorithm and multi-class Support Vector Machine yields statistically significant results and demonstrates the potential power and benefits of the approach in identifying compounds of various toxic mechanisms. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. When Humanoid Robots Become Human-Like Interaction Partners: Corepresentation of Robotic Actions

    Science.gov (United States)

    Stenzel, Anna; Chinellato, Eris; Bou, Maria A. Tirado; del Pobil, Angel P.; Lappe, Markus; Liepelt, Roman

    2012-01-01

    In human-human interactions, corepresenting a partner's actions is crucial to successfully adjust and coordinate actions with others. Current research suggests that action corepresentation is restricted to interactions between human agents facilitating social interaction with conspecifics. In this study, we investigated whether action…

  6. Educational actions in human communication health: telehealth contributions in primary care

    Directory of Open Access Journals (Sweden)

    Gabriela Guedes de Sá Leitão

    Full Text Available ABSTRACT Objective: to characterize educational actions related to human communication health produced at the Tele-Health Center for health professionals in primary care. Methods: a cross-sectional study was conducted at the Tele-Health Center at the Federal University of Pernambuco Clinical Hospital. Educational actions produced by tele-consultants between 2008 and 2014 linked to the health of human communication were considered. Data collection was conducted in two phases. In the first phase, the data were explored and educational actions were selected based on the title and the relationship with human communication. In the second phase, each action was observed and evaluated for content. The data were analyzed using descriptive statistics. Results: a few educational actions related to human communication health were concentrated in 2014. Throughout the period analyzed, the actions were restricted to the field of language and concentrated on the education issue as well as the strategic area of child and adolescent health. The most frequent occupational category among the tele-consultants was nursing. Conclusion: a small number of educational actions addressing the health of human communication was produced and the participation of speech therapists remains incipient.

  7. Humanities for the Environment—A Manifesto for Research and Action

    Directory of Open Access Journals (Sweden)

    Poul Holm

    2015-12-01

    Full Text Available Human preferences, practices and actions are the main drivers of global environmental change in the 21st century. It is crucial, therefore, to promote pro-environmental behavior. In order to accomplish this, we need to move beyond rational choice and behavioral decision theories, which do not capture the full range of commitments, assumptions, imaginaries, and belief systems that drive those preferences and actions. Humanities disciplines, such as philosophy, history, religious studies, gender studies, language and literary studies, psychology, and pedagogics do offer deep insights into human motivations, values, and choices. We believe that the expertise of such fields for transforming human preferences, practices and actions is ignored at society’s peril. We propose an agenda that focuses global humanities research on stepping up to the challenges of planetary environmental change. We have established Environmental Humanities Observatories through which to observe, explore and enact the crucial ways humanistic disciplines may help us understand and engage with global ecological problems by providing insight into human action, perceptions, and motivation. We present this Manifesto as an invitation for others to join the “Humanities for the Environment” open global consortium of humanities observatories as we continue to develop a shared research agenda.

  8. A Systems Biology Approach to Understanding the Mechanisms of Action of an Alternative Anticancer Compound in Comparison to Cisplatin

    Science.gov (United States)

    Wright, Elise P.; Padula, Matthew P.; Higgins, Vincent J.; Aldrich-Wright, Janice R.; Coorssen, Jens R.

    2014-01-01

    Many clinically available anticancer compounds are designed to target DNA. This commonality of action often yields overlapping cellular response mechanisms and can thus detract from drug efficacy. New compounds are required to overcome resistance mechanisms that effectively neutralise compounds like cisplatin and those with similar chemical structures. Studies have shown that 56MESS is a novel compound which, unlike cisplatin, does not covalently bind to DNA, but is more toxic to many cell lines and active against cisplatin-resistant cells. Furthermore, a transcriptional study of 56MESS in yeast has implicated iron and copper metabolism as well as the general yeast stress response following challenge with 56MESS. Beyond this, the cytotoxicity of 56MESS remains largely uncharacterised. Here, yeast was used as a model system to facilitate a systems-level comparison between 56MESS and cisplatin. Preliminary experiments indicated that higher concentrations than seen in similar studies be used. Although a DNA interaction with 56MESS had been theorized, this work indicated that an effect on protein synthesis/ degradation was also implicated in the mechanism(s) of action of this novel anticancer compound. In contrast to cisplatin, the different mechanisms of action that are indicated for 56MESS suggest that this compound could overcome cisplatin resistance either as a stand-alone treatment or a synergistic component of therapeutics. PMID:28250393

  9. Neurotoxic effects of perfluoroalkylated compounds: mechanisms of action and environmental relevance.

    Science.gov (United States)

    Mariussen, Espen

    2012-09-01

    Perfluoroalkylated compounds (PFCs) are used in fire-fighting foams, treatment of clothes, carpets and leather products, and as lubricants, pesticides, in paints and medicine. Recent developments in chemical analysis have revealed that fluorinated compounds have become ubiquitously spread and are regarded as a potential threats to the environment. Due to the carbon-fluorine bond, which has a very high bond strength, these chemicals are extremely persistent towards degradation and some PFCs have a potential for bioaccumulation in organisms. Of particular concern has been the developmental toxicity of PFOS and PFOA, which has been manifested in rodent studies as high mortality of prenatally exposed newborn rats and mice within 24 h after delivery. The nervous system appears to be one of the most sensitive targets of environmental contaminants. The serious developmental effects of PFCs have lead to the upcoming of studies that have investigated neurotoxic effects of these substances. In this review the major findings of the neurotoxicity of the main PFCs and their suggested mechanisms of action are presented. The neurotoxic effects are discussed in light of other toxic effects of PFCs to indicate the significance of PFCs as neurotoxicants. The main findings are that PFCs may induce neurobehavioral effects, particularly in developmentally exposed animals. The effects are, however, subtle and inconclusive and are often induced at concentrations where other toxic effects also are expected. Mechanistic studies have shown that PFCs may affect the thyroid system, influence the calcium homeostasis, protein kinase C, synaptic plasticity and cellular differentiation. Compared to other environmental toxicants the human blood levels of PFCs are high and of particular concern is that susceptible groups may be exposed to a cocktail of substances that in combination reach harmful concentrations.

  10. Human action recognition with depth cameras

    CERN Document Server

    Wang, Jiang; Wu, Ying

    2014-01-01

    Action recognition technology has many real-world applications in human-computer interaction, surveillance, video retrieval, retirement home monitoring, and robotics. The commoditization of depth sensors has also opened up further applications that were not feasible before. This text focuses on feature representation and machine learning algorithms for action recognition from depth sensors. After presenting a comprehensive overview of the state of the art, the authors then provide in-depth descriptions of their recently developed feature representations and machine learning techniques, includi

  11. Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets

    Science.gov (United States)

    Siles-Lucas, Mar; Casulli, Adriano; Cirilli, Roberto

    2018-01-01

    Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways. PMID:29677189

  12. Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets.

    Directory of Open Access Journals (Sweden)

    Mar Siles-Lucas

    2018-04-01

    Full Text Available Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways.

  13. Rational Emotive Behavior Therapy: Humanism in Action.

    Science.gov (United States)

    Hill, Larry K.

    1996-01-01

    Claims that humanism, in both concept and philosophy, is encased in a literature that is predominantly abstract, making humanism difficult to translate into tangible day-to-day action. Argues that rational emotive behavior therapy (REBT), however, provides a detailed method for translating humanist concepts into humanist behavior. (RJM)

  14. Multi-task learning with group information for human action recognition

    Science.gov (United States)

    Qian, Li; Wu, Song; Pu, Nan; Xu, Shulin; Xiao, Guoqiang

    2018-04-01

    Human action recognition is an important and challenging task in computer vision research, due to the variations in human motion performance, interpersonal differences and recording settings. In this paper, we propose a novel multi-task learning framework with group information (MTL-GI) for accurate and efficient human action recognition. Specifically, we firstly obtain group information through calculating the mutual information according to the latent relationship between Gaussian components and action categories, and clustering similar action categories into the same group by affinity propagation clustering. Additionally, in order to explore the relationships of related tasks, we incorporate group information into multi-task learning. Experimental results evaluated on two popular benchmarks (UCF50 and HMDB51 datasets) demonstrate the superiority of our proposed MTL-GI framework.

  15. A survey on vision-based human action recognition

    NARCIS (Netherlands)

    Poppe, Ronald Walter

    Vision-based human action recognition is the process of labeling image sequences with action labels. Robust solutions to this problem have applications in domains such as visual surveillance, video retrieval and human–computer interaction. The task is challenging due to variations in motion

  16. Antimicrobial compounds targeting Gram-negative bacteria in food: Their mode of action and combinational effects

    DEFF Research Database (Denmark)

    Hyldgaard, Morten

    2015-01-01

    compromising food shelf-life or safety. Natural antimicrobial compounds have therefore gained increased interest as a label-friendly alternative that can be added directly to food products. Although natural antimicrobials constitute an interesting source of compounds, it is often not understood how...... they interact with bacterial cells to exert their mechanism of inhibition or killing. Furthermore, natural antimicrobials are often not potent enough as single compounds, and may cause unwanted sensory side-effects, which limit the quantities that can be applied to food. These problems might be circumvented...... by combining antimicrobials to decrease the concentrations needed without compromising their antimicrobial activity. The work described in this dissertation presents two projects concerning the mechanism of action of selected natural antimicrobial compounds primarily against Gram-negative bacteria, and two...

  17. Review of pulmonary toxicity of indium compounds to animals and humans

    International Nuclear Information System (INIS)

    Tanaka, Akiyo; Hirata, Miyuki; Kiyohara, Yutaka; Nakano, Makiko; Omae, Kazuyuki; Shiratani, Masaharu; Koga, Kazunori

    2010-01-01

    Due to the increased production of ITO, the potential health hazards arising from occupational exposure to this material have attracted much attention. This review consists of three parts: 1) toxic effects of indium compounds on animals, 2) toxic effects of indium compounds on humans, and 3) recommendations for preventing exposure to indium compounds in the workplace. Available data have indicated that insoluble form of indium compounds, such as ITO, indium arsenide (InAs) and indium phosphide (InP), can be toxic to animals. Furthermore, InP has demonstrated clear evidence of carcinogenic potential in long-term inhalation studies using experimental animals. As for the dangers to humans, some data are available concerning adverse health effects to workers who have been exposed to indium-containing particles. The Japan Society for Occupational Health recommended the value of 3 μg/L of indium in serum as the occupational exposure limit based on biological monitoring to preventing adverse health effects in workers resulting from occupational exposure to indium compounds. Accordingly, it is essential that much greater attention is focused on human exposure to indium compounds, and precautions against possible exposure to indium compounds are most important with regard to health management among indium-handling workers.

  18. Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Deming Xu

    2007-06-01

    Full Text Available Candida albicans is a prevalent fungal pathogen amongst the immunocompromised population, causing both superficial and life-threatening infections. Since C. albicans is diploid, classical transmission genetics can not be performed to study specific aspects of its biology and pathogenesis. Here, we exploit the diploid status of C. albicans by constructing a library of 2,868 heterozygous deletion mutants and screening this collection using 35 known or novel compounds to survey chemically induced haploinsufficiency in the pathogen. In this reverse genetic assay termed the fitness test, genes related to the mechanism of action of the probe compounds are clearly identified, supporting their functional roles and genetic interactions. In this report, chemical-genetic relationships are provided for multiple FDA-approved antifungal drugs (fluconazole, voriconazole, caspofungin, 5-fluorocytosine, and amphotericin B as well as additional compounds targeting ergosterol, fatty acid and sphingolipid biosynthesis, microtubules, actin, secretion, rRNA processing, translation, glycosylation, and protein folding mechanisms. We also demonstrate how chemically induced haploinsufficiency profiles can be used to identify the mechanism of action of novel antifungal agents, thereby illustrating the potential utility of this approach to antifungal drug discovery.

  19. Phenolic compounds apigenin, hesperidin and kaempferol reduce in vitro lipid accumulation in human adipocytes.

    Science.gov (United States)

    Gómez-Zorita, Saioa; Lasa, Arrate; Abendaño, Naiara; Fernández-Quintela, Alfredo; Mosqueda-Solís, Andrea; Garcia-Sobreviela, Maria Pilar; Arbonés-Mainar, Jose M; Portillo, Maria P

    2017-11-21

    Adipocytes derived from human mesenchymal stem cells (MSCs) are widely used to investigate adipogenesis. Taking into account both the novelty of these MSCs and the scarcity of studies focused on the effects of phenolic compounds, the aim of the present study was to analyze the effect of apigenin, hesperidin and kaempferol on pre-adipocyte and mature adipocytes derived from this type of cells. In addition, the expression of genes involved in TG accumulation was also measured. Pre-adipocytes were cultured from day 0 to day 8 and mature adipocytes for 48 h with the polyphenols at doses of 1, 10 and 25 µM. Apigenin did not show an anti-adipogenic action. Pre-adipocytes treated with hesperidin and kaempferol showed reduced TG content at the three experimental doses. Apigenin did not modify the expression of the main adipogenic genes (c/ebpβ, c/ebpα, pparγ and srebp1c), hesperidin inhibited genes involved in the three phases of adipogenesis (c/ebpβ, srebp1c and perilipin) and kaempferol reduced c/ebpβ. In mature adipocytes, the three polyphenols reduced TG accumulation at the dose of 25 µM, but not at lower doses. All compounds increased mRNA levels of atgl. Apigenin and hesperidin decreased fasn expression. The present study shows the anti-adipogenic effect and delipidating effects of apigenin, hesperidin and kaempferol in human adipocytes derived from hMSCs. While hesperidin blocks all the stages of adipogenesis, kaempferol only inhibits the early stage. Regarding mature adipocytes, the three compounds reduce TG accumulation by activating, at least in part, lipolysis, and in the case of hesperidin and apigenin, also by reducing lipogenesis. The present study shows for the first time the anti-adipogenic effect and delipidating effect of apigenin, hesperidin and kaempferol in human adipocytes derived from MSCs for the first time.

  20. Rosewood oil induces sedation and inhibits compound action potential in rodents.

    Science.gov (United States)

    de Almeida, Reinaldo Nóbrega; Araújo, Demétrius Antonio Machado; Gonçalves, Juan Carlos Ramos; Montenegro, Fabrícia Costa; de Sousa, Damião Pergentino; Leite, José Roberto; Mattei, Rita; Benedito, Marco Antonio Campana; de Carvalho, José Gilberto Barbosa; Cruz, Jader Santos; Maia, José Guilherme Soares

    2009-07-30

    Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.

  1. Signed language and human action processing: evidence for functional constraints on the human mirror-neuron system.

    Science.gov (United States)

    Corina, David P; Knapp, Heather Patterson

    2008-12-01

    In the quest to further understand the neural underpinning of human communication, researchers have turned to studies of naturally occurring signed languages used in Deaf communities. The comparison of the commonalities and differences between spoken and signed languages provides an opportunity to determine core neural systems responsible for linguistic communication independent of the modality in which a language is expressed. The present article examines such studies, and in addition asks what we can learn about human languages by contrasting formal visual-gestural linguistic systems (signed languages) with more general human action perception. To understand visual language perception, it is important to distinguish the demands of general human motion processing from the highly task-dependent demands associated with extracting linguistic meaning from arbitrary, conventionalized gestures. This endeavor is particularly important because theorists have suggested close homologies between perception and production of actions and functions of human language and social communication. We review recent behavioral, functional imaging, and neuropsychological studies that explore dissociations between the processing of human actions and signed languages. These data suggest incomplete overlap between the mirror-neuron systems proposed to mediate human action and language.

  2. Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative

    Directory of Open Access Journals (Sweden)

    Marcin Mączyński

    2018-06-01

    Full Text Available This work describes the synthesis of a new series of isoxazole derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10 was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The isoxazole derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA-induced proliferation of peripheral blood mononuclear cells (PBMCs to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenylmethylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3 compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS-induced tumor necrosis factor (TNF α production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models.

  3. Social interaction enhances motor resonance for observed human actions.

    Science.gov (United States)

    Hogeveen, Jeremy; Obhi, Sukhvinder S

    2012-04-25

    Understanding the neural basis of social behavior has become an important goal for cognitive neuroscience and a key aim is to link neural processes observed in the laboratory to more naturalistic social behaviors in real-world contexts. Although it is accepted that mirror mechanisms contribute to the occurrence of motor resonance (MR) and are common to action execution, observation, and imitation, questions remain about mirror (and MR) involvement in real social behavior and in processing nonhuman actions. To determine whether social interaction primes the MR system, groups of participants engaged or did not engage in a social interaction before observing human or robotic actions. During observation, MR was assessed via motor-evoked potentials elicited with transcranial magnetic stimulation. Compared with participants who did not engage in a prior social interaction, participants who engaged in the social interaction showed a significant increase in MR for human actions. In contrast, social interaction did not increase MR for robot actions. Thus, naturalistic social interaction and laboratory action observation tasks appear to involve common MR mechanisms, and recent experience tunes the system to particular agent types.

  4. Compound stimulus extinction reduces spontaneous recovery in humans

    OpenAIRE

    Coelho, Cesar A.O.; Dunsmoor, Joseph E.; Phelps, Elizabeth A.

    2015-01-01

    Fear-related behaviors are prone to relapse following extinction. We tested in humans a compound extinction design (“deepened extinction”) shown in animal studies to reduce post-extinction fear recovery. Adult subjects underwent fear conditioning to a visual and an auditory conditioned stimulus (CSA and CSB, respectively) separately paired with an electric shock. The target CS (CSA) was extinguished alone followed by compound presentations of the extinguished CSA and nonextinguished CSB. Reco...

  5. Vision-based Human Action Classification Using Adaptive Boosting Algorithm

    KAUST Repository

    Zerrouki, Nabil; Harrou, Fouzi; Sun, Ying; Houacine, Amrane

    2018-01-01

    Precise recognition of human action is a key enabler for the development of many applications including autonomous robots for medical diagnosis and surveillance of elderly people in home environment. This paper addresses the human action recognition based on variation in body shape. Specifically, we divide the human body into five partitions that correspond to five partial occupancy areas. For each frame, we calculated area ratios and used them as input data for recognition stage. Here, we consider six classes of activities namely: walking, standing, bending, lying, squatting, and sitting. In this paper, we proposed an efficient human action recognition scheme, which takes advantages of superior discrimination capacity of AdaBoost algorithm. We validated the effectiveness of this approach by using experimental data from two publicly available databases fall detection databases from the University of Rzeszow’s and the Universidad de Málaga fall detection datasets. We provided comparisons of the proposed approach with state-of-the-art classifiers based on the neural network, K-nearest neighbor, support vector machine and naïve Bayes and showed that we achieve better results in discriminating human gestures.

  6. Vision-based Human Action Classification Using Adaptive Boosting Algorithm

    KAUST Repository

    Zerrouki, Nabil

    2018-05-07

    Precise recognition of human action is a key enabler for the development of many applications including autonomous robots for medical diagnosis and surveillance of elderly people in home environment. This paper addresses the human action recognition based on variation in body shape. Specifically, we divide the human body into five partitions that correspond to five partial occupancy areas. For each frame, we calculated area ratios and used them as input data for recognition stage. Here, we consider six classes of activities namely: walking, standing, bending, lying, squatting, and sitting. In this paper, we proposed an efficient human action recognition scheme, which takes advantages of superior discrimination capacity of AdaBoost algorithm. We validated the effectiveness of this approach by using experimental data from two publicly available databases fall detection databases from the University of Rzeszow’s and the Universidad de Málaga fall detection datasets. We provided comparisons of the proposed approach with state-of-the-art classifiers based on the neural network, K-nearest neighbor, support vector machine and naïve Bayes and showed that we achieve better results in discriminating human gestures.

  7. Robotic situational awareness of actions in human teaming

    Science.gov (United States)

    Tahmoush, Dave

    2015-06-01

    When robots can sense and interpret the activities of the people they are working with, they become more of a team member and less of just a piece of equipment. This has motivated work on recognizing human actions using existing robotic sensors like short-range ladar imagers. These produce three-dimensional point cloud movies which can be analyzed for structure and motion information. We skeletonize the human point cloud and apply a physics-based velocity correlation scheme to the resulting joint motions. The twenty actions are then recognized using a nearest-neighbors classifier that achieves good accuracy.

  8. Design, synthesis, antiviral activity and mode of action of phenanthrene-containing N-heterocyclic compounds inspired by the phenanthroindolizidine alkaloid antofine.

    Science.gov (United States)

    Yu, Xiuling; Wei, Peng; Wang, Ziwen; Liu, Yuxiu; Wang, Lizhong; Wang, Qingmin

    2016-02-01

    The phenanthroindolizidine alkaloid antofine and its analogues have excellent antiviral activity against tobacco mosaic virus (TMV). To simplify the structure and the synthesis of the phenanthroindolizidine alkaloid, a series of phenanthrene-containing N-heterocyclic compounds (compounds 1 to 33) were designed and synthesised, based on the intermolecular interaction of antofine and TMV RNA, and systematically evaluated for their anti-TMV activity. Most of these compounds exhibited good to reasonable anti-TMV activity. The optimum compounds 5, 12 and 21 displayed higher activity than the lead compound antofine and commercial ribavirin. Compound 12 was chosen for field trials of antiviral efficacy against TMV, and was found to exhibit better activity than control plant virus inhibitors. Compounds 5 and 12 were chosen for mode of action studies. The changes in fluorescence intensity of compounds 5 and 12 on separated TMV RNA showed that these small molecules can also bind to TMV RNA, but the mode is very different from that of antofine. The compounds combining phenanthrene and an N-heterocyclic ring could maintain the anti-TMV activity of phenanthroindolizidines, but their modes of action are different from that of antofine. The present study lays a good foundation for us to find more efficient anti-plant virus reagents. © 2015 Society of Chemical Industry.

  9. Action Search: Learning to Search for Human Activities in Untrimmed Videos

    KAUST Repository

    Alwassel, Humam

    2017-06-13

    Traditional approaches for action detection use trimmed data to learn sophisticated action detector models. Although these methods have achieved great success at detecting human actions, we argue that huge information is discarded when ignoring the process, through which this trimmed data is obtained. In this paper, we propose Action Search, a novel approach that mimics the way people annotate activities in video sequences. Using a Recurrent Neural Network, Action Search can efficiently explore a video and determine the time boundaries during which an action occurs. Experiments on the THUMOS14 dataset reveal that our model is not only able to explore the video efficiently but also accurately find human activities, outperforming state-of-the-art methods.

  10. Vanadium Compounds as PTP Inhibitors

    Directory of Open Access Journals (Sweden)

    Elsa Irving

    2017-12-01

    Full Text Available Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs and protein tyrosine phosphatases (PTPs. Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought to inhibit PTPs, thus acting as a pan-inhibitor of this enzyme superfamily. We discuss recent developments in the biological and biochemical actions of more complex vanadium derivatives, including decavanadate and in particular the growing number of oxidovanadium compounds with organic ligands. Pre-clinical studies involving these compounds are discussed in the anti-diabetic and anti-cancer contexts. Although in many cases PTP inhibition has been implicated, it is also clear that many such compounds have further biochemical effects in cells. There also remain concerns surrounding off-target toxicities and long-term use of vanadium compounds in vivo in humans, hindering their progress through clinical trials. Despite these current misgivings, interest in these chemicals continues and many believe they could still have therapeutic potential. If so, we argue that this field would benefit from greater focus on improving the delivery and tissue targeting of vanadium compounds in order to minimize off-target toxicities. This may then harness their full therapeutic potential.

  11. Predicting human activities in sequences of actions in RGB-D videos

    Science.gov (United States)

    Jardim, David; Nunes, Luís.; Dias, Miguel

    2017-03-01

    In our daily activities we perform prediction or anticipation when interacting with other humans or with objects. Prediction of human activity made by computers has several potential applications: surveillance systems, human computer interfaces, sports video analysis, human-robot-collaboration, games and health-care. We propose a system capable of recognizing and predicting human actions using supervised classifiers trained with automatically labeled data evaluated in our human activity RGB-D dataset (recorded with a Kinect sensor) and using only the position of the main skeleton joints to extract features. Using conditional random fields (CRFs) to model the sequential nature of actions in a sequence has been used before, but where other approaches try to predict an outcome or anticipate ahead in time (seconds), we try to predict what will be the next action of a subject. Our results show an activity prediction accuracy of 89.9% using an automatically labeled dataset.

  12. Six coordination compounds: mode of cytotoxic action and biological evaluation

    Directory of Open Access Journals (Sweden)

    ali aydin

    2016-09-01

    Full Text Available This study describes the biological and anticancer properties of followed coordination compounds. IR spectra, magnetic properties, thermal analyses and crystal structures of six cyanido-complexes derivatives with [MII(CN4]2- (MII= Ni and Pd and [Co(CN6]3- anions and N-bishydeten (N,N-bis(2-hydroxyethylethylenediamine as a capping ligand have been previously reported. Here, we investigated these complexes denoted as[Ni(N-bishydetenNi(CN4] (C1, [Zn2(N-bishydeten2Ni(CN4] (C2, [Ni(N-bishydetenPd(CN4] (C3, [Cd(N-bishydeten2][Pd(CN4] (C4, [Ni2(N-bishydeten2Co(CN6].3H2O (C5 and K[Cd(N-bishydetenCo(CN6].1.5H2O (C6, which were tested for their anti-proliferative activity against human cervical cancer (HeLa, human colon cancer (HT29, rat glioma (C6 and African green monkey kidney (Vero cell lines. The DNA/BSA binding affinities of these compounds were also elucidated by spectroscopic titrations, displacement experiments and electrophoresis measurements. Studies on cancerous cells revealed that C1, C2, C4 and C6 exhibited significant antitumor activity and inhibited tumor progression in testing cell lines and showed high solubility in the solvent. Absorbance and emission spectra data results revealed that the complexes interact with the DNA via groove binding mode of interaction. Overall, these compounds have been found to demonstrate effective anti-proliferative activity against the cancer cell lines, indicating that they are a potent candidate for preclinical or clinical study.

  13. Action Search: Learning to Search for Human Activities in Untrimmed Videos

    KAUST Repository

    Alwassel, Humam; Heilbron, Fabian Caba; Ghanem, Bernard

    2017-01-01

    Traditional approaches for action detection use trimmed data to learn sophisticated action detector models. Although these methods have achieved great success at detecting human actions, we argue that huge information is discarded when ignoring

  14. Exemplar-based human action pose correction.

    Science.gov (United States)

    Shen, Wei; Deng, Ke; Bai, Xiang; Leyvand, Tommer; Guo, Baining; Tu, Zhuowen

    2014-07-01

    The launch of Xbox Kinect has built a very successful computer vision product and made a big impact on the gaming industry. This sheds lights onto a wide variety of potential applications related to action recognition. The accurate estimation of human poses from the depth image is universally a critical step. However, existing pose estimation systems exhibit failures when facing severe occlusion. In this paper, we propose an exemplar-based method to learn to correct the initially estimated poses. We learn an inhomogeneous systematic bias by leveraging the exemplar information within a specific human action domain. Furthermore, as an extension, we learn a conditional model by incorporation of pose tags to further increase the accuracy of pose correction. In the experiments, significant improvements on both joint-based skeleton correction and tag prediction are observed over the contemporary approaches, including what is delivered by the current Kinect system. Our experiments for the facial landmark correction also illustrate that our algorithm can improve the accuracy of other detection/estimation systems.

  15. An action selection architecture for autonomous virtual humans in persistent worlds

    OpenAIRE

    Sevin, Etienne de; Thalmann, Daniel

    2007-01-01

    Nowadays, virtual humans such as non-player characters in computer games need to have a strong autonomy in order to live their own life in persistent virtual worlds. When designing autonomous virtual humans, the action selection problem needs to be considered, as it is responsible for decision making at each moment in time. Indeed action selection architectures for autonomous virtual humans need to be reactive, proactive, motivational, and emotional to obtain a high degree of autonomy and ind...

  16. Antioxidative Effects of Phenolic Compounds of Mushroom Mycelia in Simulated Regions of the Human Colon, In Vitro Study

    Directory of Open Access Journals (Sweden)

    Vamanu Emanuel

    2018-03-01

    Full Text Available Many compounds in mushrooms are biologically active; however, the in vivo actions of their metabolites are poorly understood. An in vitro system, GIS1, was used to simulate the fermentation action of microbiota in each colon region. We used MycoPo, a natural product obtained from the lyophilized mycelia of different Pleurotus ostreatus species to determine the biological effects in human-colon regions. Controls (Lentinula edodes mycelia; dried basidia of Agaricus brunnescens were chosen to confirm the biological activity of P. ostreatus mycelia in vitro. We measured total antioxidant capacity and ferric ion-reducing antioxidant power (FRAP in simulated colon regions to identify antioxidant compounds, and undertook in vitro gastrointestinal simulation and microbiological analyses. The highest FRAP was found for the ascending colon, and the antioxidant effect was higher when MycoPo was administered. A. brunnescens consumption resulted in low total antioxidant capacity. Polyphenol content was correlated with the antioxidant status and microbial composition of microbiota. Total polyphenolic content was higher after A. brunnescens consumption, and four types of polyphenols were identified by high-performance liquid chromatography. Major phenolic acids were gentisic acid, homogentisic acid, and small amounts of caffeic acid. The Enterobacteriaceae species populations varied greatly across the three parts of the colon. We noted a significant (p0.85. These data suggest a direct relationship between favorable bacterial strains and availability of bioactive compounds, with specificity for each colon region.

  17. Toxicology of perfluorinated compounds

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, Thorsten [Hessian State Laboratory, Wiesbaden (Germany); Mattern, Daniela; Brunn, Hubertus [Hessian State Laboratory, Giessen (Germany)

    2011-12-15

    Perfluorinated compounds [PFCs] have found a wide use in industrial products and processes and in a vast array of consumer products. PFCs are molecules made up of carbon chains to which fluorine atoms are bound. Due to the strength of the carbon/fluorine bond, the molecules are chemically very stable and are highly resistant to biological degradation; therefore, they belong to a class of compounds that tend to persist in the environment. These compounds can bioaccumulate and also undergo biomagnification. Within the class of PFC chemicals, perfluorooctanoic acid and perfluorosulphonic acid are generally considered reference substances. Meanwhile, PFCs can be detected almost ubiquitously, e.g., in water, plants, different kinds of foodstuffs, in animals such as fish, birds, in mammals, as well as in human breast milk and blood. PFCs are proposed as a new class of 'persistent organic pollutants'. Numerous publications allude to the negative effects of PFCs on human health. The following review describes both external and internal exposures to PFCs, the toxicokinetics (uptake, distribution, metabolism, excretion), and the toxicodynamics (acute toxicity, subacute and subchronic toxicities, chronic toxicity including carcinogenesis, genotoxicity and epigenetic effects, reproductive and developmental toxicities, neurotoxicity, effects on the endocrine system, immunotoxicity and potential modes of action, combinational effects, and epidemiological studies on perfluorinated compounds). (orig.)

  18. Children Perseverate to a Human's Actions but Not to a Robot's Actions

    Science.gov (United States)

    Moriguchi, Yusuke; Kanda, Takayuki; Ishiguro, Hiroshi; Itakura, Shoji

    2010-01-01

    Previous research has shown that young children commit perseverative errors from their observation of another person's actions. The present study examined how social observation would lead children to perseverative tendencies, using a robot. In Experiment 1, preschoolers watched either a human model or a robot sorting cards according to one…

  19. Super agonist actions of clothianidin and related compounds on the SAD beta 2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes.

    Science.gov (United States)

    Ihara, Makoto; Matsuda, Kazuhiko; Shimomura, Masaru; Sattelle, David B; Komai, Koichiro

    2004-03-01

    To compare the actions of clothianidin, a neonicotinoid acting on insect nicotinic acetylcholine receptors, and related compounds with that of imidacloprid, the compounds were tested on the Drosophila SAD-chicken beta2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes using two-electrode voltage-clamp electrophysiology. The maximum response of the SAD beta 2 nicotinic receptor to clothianidin was larger than that observed for acetylcholine. Ring breakage of the imidazolidine ring of imidacloprid resulting in the generation of a guanidine group was critical for this super agonist action.

  20. Compound Stimulus Extinction Reduces Spontaneous Recovery in Humans

    Science.gov (United States)

    Coelho, Cesar A. O.; Dunsmoor, Joseph E.; Phelps, Elizabeth A.

    2015-01-01

    Fear-related behaviors are prone to relapse following extinction. We tested in humans a compound extinction design ("deepened extinction") shown in animal studies to reduce post-extinction fear recovery. Adult subjects underwent fear conditioning to a visual and an auditory conditioned stimulus (CSA and CSB, respectively) separately…

  1. Rebelling against the (Insulin Resistance: A Review of the Proposed Insulin-Sensitizing Actions of Soybeans, Chickpeas, and Their Bioactive Compounds

    Directory of Open Access Journals (Sweden)

    Jaime L. Clark

    2018-03-01

    Full Text Available Insulin resistance is a major risk factor for diseases such as type 2 diabetes and metabolic syndrome. Current methods for management of insulin resistance include pharmacological therapies and lifestyle modifications. Several clinical studies have shown that leguminous plants such as soybeans and pulses (dried beans, dried peas, chickpeas, lentils are able to reduce insulin resistance and related type 2 diabetes parameters. However, to date, no one has summarized the evidence supporting a mechanism of action for soybeans and pulses that explains their ability to lower insulin resistance. While it is commonly assumed that the biological activities of soybeans and pulses are due to their antioxidant activities, these bioactive compounds may operate independent of their antioxidant properties and, thus, their ability to potentially improve insulin sensitivity via alternative mechanisms needs to be acknowledged. Based on published studies using in vivo and in vitro models representing insulin resistant states, the proposed mechanisms of action for insulin-sensitizing actions of soybeans, chickpeas, and their bioactive compounds include increasing glucose transporter-4 levels, inhibiting adipogenesis by down-regulating peroxisome proliferator-activated receptor-γ, reducing adiposity, positively affecting adipokines, and increasing short-chain fatty acid-producing bacteria in the gut. Therefore, this review will discuss the current evidence surrounding the proposed mechanisms of action for soybeans and certain pulses, and their bioactive compounds, to effectively reduce insulin resistance.

  2. Prediction of human population responses to toxic compounds by a collaborative competition.

    Science.gov (United States)

    Eduati, Federica; Mangravite, Lara M; Wang, Tao; Tang, Hao; Bare, J Christopher; Huang, Ruili; Norman, Thea; Kellen, Mike; Menden, Michael P; Yang, Jichen; Zhan, Xiaowei; Zhong, Rui; Xiao, Guanghua; Xia, Menghang; Abdo, Nour; Kosyk, Oksana; Friend, Stephen; Dearry, Allen; Simeonov, Anton; Tice, Raymond R; Rusyn, Ivan; Wright, Fred A; Stolovitzky, Gustavo; Xie, Yang; Saez-Rodriguez, Julio

    2015-09-01

    The ability to computationally predict the effects of toxic compounds on humans could help address the deficiencies of current chemical safety testing. Here, we report the results from a community-based DREAM challenge to predict toxicities of environmental compounds with potential adverse health effects for human populations. We measured the cytotoxicity of 156 compounds in 884 lymphoblastoid cell lines for which genotype and transcriptional data are available as part of the Tox21 1000 Genomes Project. The challenge participants developed algorithms to predict interindividual variability of toxic response from genomic profiles and population-level cytotoxicity data from structural attributes of the compounds. 179 submitted predictions were evaluated against an experimental data set to which participants were blinded. Individual cytotoxicity predictions were better than random, with modest correlations (Pearson's r < 0.28), consistent with complex trait genomic prediction. In contrast, predictions of population-level response to different compounds were higher (r < 0.66). The results highlight the possibility of predicting health risks associated with unknown compounds, although risk estimation accuracy remains suboptimal.

  3. ROBOT LEARNING OF OBJECT MANIPULATION TASK ACTIONS FROM HUMAN DEMONSTRATIONS

    Directory of Open Access Journals (Sweden)

    Maria Kyrarini

    2017-08-01

    Full Text Available Robot learning from demonstration is a method which enables robots to learn in a similar way as humans. In this paper, a framework that enables robots to learn from multiple human demonstrations via kinesthetic teaching is presented. The subject of learning is a high-level sequence of actions, as well as the low-level trajectories necessary to be followed by the robot to perform the object manipulation task. The multiple human demonstrations are recorded and only the most similar demonstrations are selected for robot learning. The high-level learning module identifies the sequence of actions of the demonstrated task. Using Dynamic Time Warping (DTW and Gaussian Mixture Model (GMM, the model of demonstrated trajectories is learned. The learned trajectory is generated by Gaussian mixture regression (GMR from the learned Gaussian mixture model.  In online working phase, the sequence of actions is identified and experimental results show that the robot performs the learned task successfully.

  4. Exposure to perfluorinated compounds and human semen quality in Arctic and European populations

    DEFF Research Database (Denmark)

    Toft, G; Jönsson, B A G; Lindh, C H

    2012-01-01

    Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality.......Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality....

  5. Compound muscle action potential duration in critical illness neuromyopathy.

    Science.gov (United States)

    Kramer, Christopher L; Boon, Andrea J; Harper, C Michel; Goodman, Brent P

    2018-03-01

    We sought to determine the specificity of compound muscle action potential (CMAP) durations and amplitudes in a large critical illness neuromyopathy (CINM) cohort relative to controls with other neuromuscular conditions. Fifty-eight patients with CINM who had been seen over a 17-year period were retrospectively studied. Electrodiagnostic findings of the CINM cohort were compared with patients with axonal peripheral neuropathy and myopathy due to other causes. Mean CMAP durations were prolonged, and mean CMAP amplitudes were severely reduced both proximally and distally in all nerves studied in the CINM cohort relative to the control groups. The specificity of prolonged CMAP durations for CINM approached 100% if they were encountered in more than 1 nerve. Prolonged, low-amplitude CMAPs occur more frequently and with greater severity in CINM patients than in neuromuscular controls with myopathy and axonal neuropathy and are highly specific for the diagnosis of CINM. Muscle Nerve 57: 395-400, 2018. © 2017 Wiley Periodicals, Inc.

  6. Fast programming of peg-in-hole actions by human demonstration

    DEFF Research Database (Denmark)

    Yang, Yang; Lin, Linglong; Song, Y. T.

    2014-01-01

    Peg-in-Hole actions play an important role in industrial assembly. In this paper, we present a system which performs such actions after learning by human demonstration. Strategies for getting robust human-demonstrated PiH trajectories are investigated, and a number of PiH experiments are conducte...... to verify the performance of the proposed approach. The results show that our approach leads to a high PiH success rate and allows the robot to fine-tune the PiH trajectories to achieve faster performance....

  7. Brain-to-brain hyperclassification reveals action-specific motor mapping of observed actions in humans.

    Science.gov (United States)

    Smirnov, Dmitry; Lachat, Fanny; Peltola, Tomi; Lahnakoski, Juha M; Koistinen, Olli-Pekka; Glerean, Enrico; Vehtari, Aki; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri

    2017-01-01

    Seeing an action may activate the corresponding action motor code in the observer. It remains unresolved whether seeing and performing an action activates similar action-specific motor codes in the observer and the actor. We used novel hyperclassification approach to reveal shared brain activation signatures of action execution and observation in interacting human subjects. In the first experiment, two "actors" performed four types of hand actions while their haemodynamic brain activations were measured with 3-T functional magnetic resonance imaging (fMRI). The actions were videotaped and shown to 15 "observers" during a second fMRI experiment. Eleven observers saw the videos of one actor, and the remaining four observers saw the videos of the other actor. In a control fMRI experiment, one of the actors performed actions with closed eyes, and five new observers viewed these actions. Bayesian canonical correlation analysis was applied to functionally realign observers' and actors' fMRI data. Hyperclassification of the seen actions was performed with Bayesian logistic regression trained on actors' data and tested with observers' data. Without the functional realignment, between-subjects accuracy was at chance level. With the realignment, the accuracy increased on average by 15 percentage points, exceeding both the chance level and the accuracy without functional realignment. The highest accuracies were observed in occipital, parietal and premotor cortices. Hyperclassification exceeded chance level also when the actor did not see her own actions. We conclude that the functional brain activation signatures underlying action execution and observation are partly shared, yet these activation signatures may be anatomically misaligned across individuals.

  8. Microencapsulated bitter compounds (from Gentiana lutea) reduce daily energy intakes in humans

    NARCIS (Netherlands)

    Mennella, Ilario; Fogliano, Vincenzo; Ferracane, Rosalia; Arlorio, Marco; Pattarino, Franco; Vitaglione, Paola

    2016-01-01

    Mounting evidence showed that bitter-tasting compounds modulate eating behaviour through bitter taste receptors in the gastrointestinal tract. This study aimed at evaluating the influence of microencapsulated bitter compounds on human appetite and energy intakes. A microencapsulated bitter

  9. Anti-human rhinoviral activity of polybromocatechol compounds isolated from the rhodophyta, Neorhodomela aculeata.

    Science.gov (United States)

    Park, Soon-Hye; Song, Jae-Hyoung; Kim, Taejung; Shin, Woon-Seob; Park, Gab Man; Lee, Seokjoon; Kim, Young-Joo; Choi, Pilju; Kim, Heejin; Kim, Hui-Seong; Kwon, Dur-Han; Choi, Hwa Jung; Ham, Jungyeob

    2012-10-01

    An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1) and five polybromocatechols (2-6) by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC₅₀) of 2.50 μg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC₅₀ of 7.11 μg/mL, and anti-HRV3 activity, with an IC₅₀ of 4.69 μg/mL, without demonstrable cytotoxicity at a concentration of 20 μg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

  10. Human fMRI Reveals That Delayed Action Re-Recruits Visual Perception

    OpenAIRE

    Singhal, Anthony; Monaco, Simona; Kaufman, Liam D.; Culham, Jody C.

    2013-01-01

    Behavioral and neuropsychological research suggests that delayed actions rely on different neural substrates than immediate actions; however, the specific brain areas implicated in the two types of actions remain unknown. We used functional magnetic resonance imaging (fMRI) to measure human brain activation during delayed grasping and reaching. Specifically, we examined activation during visual stimulation and action execution separated by a 18-s delay interval in which subjects had to rememb...

  11. Use of an action-selection framework for human-carnivore conflict in the Bangladesh Sundarbans.

    Science.gov (United States)

    Barlow, Adam C D; Greenwood, Christina J; Ahmad, Ishtiaq U; Smith, James L D

    2010-10-01

    Human-carnivore conflict is manifested in the death of humans, livestock, and carnivores. The resulting negative local attitudes and retribution killings imperil the future of many endangered carnivores. We tailored existing management tools to create a framework to facilitate the selection of actions to alleviate human-carnivore conflict and applied the framework to the human-tiger conflict in the Bangladesh Sundarbans. We identified potential actions that consider previous management efforts, local knowledge, cost-effectiveness, fieldwork experience of authors and project staff, previous research on tiger ecology by the authors, and recommendations from human-carnivore conflict studies in other countries. Our framework includes creation of a profile to improve understanding of the nature of the conflict and its underlying causality. Identified actions include deterrents, education, direct tiger management, and response teams. We ranked actions by their potential to reduce conflict and the monetary cost of their implementation. We ranked tiger-response teams and monitoring problem tigers as the two best actions because both had relatively high impact and cost-effectiveness. We believe this framework could be used under a wide range of human-wildlife conflict situations because it provides a structured approach to selection of mitigating actions. © 2010 Society for Conservation Biology.

  12. Language for action: Motor resonance during the processing of human and robotic voices.

    Science.gov (United States)

    Di Cesare, G; Errante, A; Marchi, M; Cuccio, V

    2017-11-01

    In this fMRI study we evaluated whether the auditory processing of action verbs pronounced by a human or a robotic voice in the imperative mood differently modulates the activation of the mirror neuron system (MNs). The study produced three results. First, the activation pattern found during listening to action verbs was very similar in both the robot and human conditions. Second, the processing of action verbs compared to abstract verbs determined the activation of the fronto-parietal circuit classically involved during the action goal understanding. Third, and most importantly, listening to action verbs compared to abstract verbs produced activation of the anterior part of the supramarginal gyrus (aSMG) regardless of the condition (human and robot) and in the absence of any object name. The supramarginal gyrus is a region considered to underpin hand-object interaction and associated to the processing of affordances. These results suggest that listening to action verbs may trigger the recruitment of motor representations characterizing affordances and action execution, coherently with the predictive nature of motor simulation that not only allows us to re-enact motor knowledge to understand others' actions but also prepares us for the actions we might need to carry out. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Multi-stream CNN: Learning representations based on human-related regions for action recognition

    NARCIS (Netherlands)

    Tu, Zhigang; Xie, Wei; Qin, Qianqing; Poppe, R.W.; Veltkamp, R.C.; Li, Baoxin; Yuan, Junsong

    2018-01-01

    The most successful video-based human action recognition methods rely on feature representations extracted using Convolutional Neural Networks (CNNs). Inspired by the two-stream network (TS-Net), we propose a multi-stream Convolutional Neural Network (CNN) architecture to recognize human actions. We

  14. Antimicrobial Properties of Plant Essential Oils against Human Pathogens and Their Mode of Action: An Updated Review

    Directory of Open Access Journals (Sweden)

    Mallappa Kumara Swamy

    2016-01-01

    Full Text Available A wide range of medicinal and aromatic plants (MAPs have been explored for their essential oils in the past few decades. Essential oils are complex volatile compounds, synthesized naturally in different plant parts during the process of secondary metabolism. Essential oils have great potential in the field of biomedicine as they effectively destroy several bacterial, fungal, and viral pathogens. The presence of different types of aldehydes, phenolics, terpenes, and other antimicrobial compounds means that the essential oils are effective against a diverse range of pathogens. The reactivity of essential oil depends upon the nature, composition, and orientation of its functional groups. The aim of this article is to review the antimicrobial potential of essential oils secreted from MAPs and their possible mechanisms of action against human pathogens. This comprehensive review will benefit researchers who wish to explore the potential of essential oils in the development of novel broad-spectrum key molecules against a broad range of drug-resistant pathogenic microbes.

  15. Antimicrobial Properties of Plant Essential Oils against Human Pathogens and Their Mode of Action: An Updated Review

    Science.gov (United States)

    2016-01-01

    A wide range of medicinal and aromatic plants (MAPs) have been explored for their essential oils in the past few decades. Essential oils are complex volatile compounds, synthesized naturally in different plant parts during the process of secondary metabolism. Essential oils have great potential in the field of biomedicine as they effectively destroy several bacterial, fungal, and viral pathogens. The presence of different types of aldehydes, phenolics, terpenes, and other antimicrobial compounds means that the essential oils are effective against a diverse range of pathogens. The reactivity of essential oil depends upon the nature, composition, and orientation of its functional groups. The aim of this article is to review the antimicrobial potential of essential oils secreted from MAPs and their possible mechanisms of action against human pathogens. This comprehensive review will benefit researchers who wish to explore the potential of essential oils in the development of novel broad-spectrum key molecules against a broad range of drug-resistant pathogenic microbes. PMID:28090211

  16. Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action

    Science.gov (United States)

    Griffin, Michael O.; Ceballos, Guillermo; Villarreal, Francisco

    2010-01-01

    Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The firstt of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline’s multiple mechanisms of action as a means to understand their beneficial effects. PMID:20951211

  17. Human action quality evaluation based on fuzzy logic with application in underground coal mining.

    Science.gov (United States)

    Ionica, Andreea; Leba, Monica

    2015-01-01

    The work system is defined by its components, their roles and the relationships between them. Any work system gravitates around the human resource and the interdependencies between human factor and the other components of it. Researches in this field agreed that the human factor and its actions are difficult to quantify and predict. The objective of this paper is to apply a method of human actions evaluation in order to estimate possible risks and prevent possible system faults, both at human factor level and at equipment level. In order to point out the importance of the human factor influence on all the elements of the working systems we propose a fuzzy logic based methodology for quality evaluation of human actions. This methodology has a multidisciplinary character, as it gathers ideas and methods from: quality management, ergonomics, work safety and artificial intelligence. The results presented refer to a work system with a high degree of specificity, namely, underground coal mining and are valuable for human resources risk evaluation pattern. The fuzzy logic evaluation of the human actions leads to early detection of possible dangerous evolutions of the work system and alarm the persons in charge.

  18. Insulin action in the human brain: evidence from neuroimaging studies.

    Science.gov (United States)

    Kullmann, S; Heni, M; Fritsche, A; Preissl, H

    2015-06-01

    Thus far, little is known about the action of insulin in the human brain. Nonetheless, recent advances in modern neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), have made it possible to investigate the action of insulin in the brain in humans, providing new insights into the pathogenesis of brain insulin resistance and obesity. Using MEG, the clinical relevance of the action of insulin in the brain was first identified, linking cerebral insulin resistance with peripheral insulin resistance, genetic predisposition and weight loss success in obese adults. Although MEG is a suitable tool for measuring brain activity mainly in cortical areas, fMRI provides high spatial resolution for cortical as well as subcortical regions. Thus, the action of insulin can be detected within all eating behaviour relevant regions, which include regions deeply located within the brain, such as the hypothalamus, midbrain and brainstem, as well as regions within the striatum. In this review, we outline recent advances in the field of neuroimaging aiming to investigate the action of insulin in the human brain using different routes of insulin administration. fMRI studies have shown a significant insulin-induced attenuation predominantly in the occipital and prefrontal cortical regions and the hypothalamus, successfully localising insulin-sensitive brain regions in healthy, mostly normal-weight individuals. However, further studies are needed to localise brain areas affected by insulin resistance in obese individuals, which is an important prerequisite for selectively targeting brain insulin resistance in obesity. © 2015 British Society for Neuroendocrinology.

  19. Human Action Recognition Using Ordinal Measure of Accumulated Motion

    Directory of Open Access Journals (Sweden)

    Kim Wonjun

    2010-01-01

    Full Text Available This paper presents a method for recognizing human actions from a single query action video. We propose an action recognition scheme based on the ordinal measure of accumulated motion, which is robust to variations of appearances. To this end, we first define the accumulated motion image (AMI using image differences. Then the AMI of the query action video is resized to a subimage by intensity averaging and a rank matrix is generated by ordering the sample values in the sub-image. By computing the distances from the rank matrix of the query action video to the rank matrices of all local windows in the target video, local windows close to the query action are detected as candidates. To find the best match among the candidates, their energy histograms, which are obtained by projecting AMI values in horizontal and vertical directions, respectively, are compared with those of the query action video. The proposed method does not require any preprocessing task such as learning and segmentation. To justify the efficiency and robustness of our approach, the experiments are conducted on various datasets.

  20. Medical Applications and Toxicities of Gallium Compounds

    Directory of Open Access Journals (Sweden)

    Christopher R. Chitambar

    2010-05-01

    Full Text Available Over the past two to three decades, gallium compounds have gained importance in the fields of medicine and electronics. In clinical medicine, radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti-inflammatory and immunosuppressive activity in animal models of human disease while more recent studies have shown that gallium compounds may function as antimicrobial agents against certain pathogens. In a totally different realm, the chemical properties of gallium arsenide have led to its use in the semiconductor industry. Gallium compounds, whether used medically or in the electronics field, have toxicities. Patients receiving gallium nitrate for the treatment of various diseases may benefit from such therapy, but knowledge of the therapeutic index of this drug is necessary to avoid clinical toxicities. Animals exposed to gallium arsenide display toxicities in certain organ systems suggesting that environmental risks may exist for individuals exposed to this compound in the workplace. Although the arsenic moiety of gallium arsenide appears to be mainly responsible for its pulmonary toxicity, gallium may contribute to some of the detrimental effects in other organs. The use of older and newer gallium compounds in clinical medicine may be advanced by a better understanding of their mechanisms of action, drug resistance, pharmacology, and side-effects. This review will discuss the medical applications of gallium and its mechanisms of action, the newer gallium compounds and future directions for development, and the toxicities of gallium compounds in current use.

  1. Anti-Human Rhinoviral Activity of Polybromocatechol Compounds Isolated from the Rhodophyta, Neorhodomela aculeata

    Directory of Open Access Journals (Sweden)

    Hui-Seong Kim

    2012-10-01

    Full Text Available An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1 and five polybromocatechols (2–6 by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC50 of 2.50 μg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC50 of 7.11 μg/mL, and anti-HRV3 activity, with an IC50 of 4.69 μg/mL, without demonstrable cytotoxicity at a concentration of 20 μg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

  2. Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains.

    Science.gov (United States)

    Nourski, Kirill V; Abbas, Paul J; Miller, Charles A; Robinson, Barbara K; Jeng, Fuh-Cherng

    2005-04-01

    This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.

  3. Dihydrochalcone Compounds Isolated from Crabapple Leaves Showed Anticancer Effects on Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Qin

    2015-11-01

    Full Text Available Seven dihydrochalcone compounds were isolated from the leaves of Malus crabapples, cv. “Radiant”, and their chemical structures were elucidated by UV, IR, ESI-MS, 1H-NMR and 13C-NMR analyses. These compounds, which include trilobatin (A1, phloretin (A2, 3-hydroxyphloretin (A3, phloretin rutinoside (A4, phlorizin (A5, 6′′-O-coumaroyl-4′-O-glucopyranosylphloretin (A6, and 3′′′-methoxy-6′′-O-feruloy-4′-O-glucopyranosyl-phloretin (A7, all belong to the phloretin class and its derivatives. Compounds A6 and A7 are two new rare dihydrochalcone compounds. The results of a MTT cancer cell growth inhibition assay demonstrated that phloretin and these derivatives showed significant positive anticancer activities against several human cancer cell lines, including the A549 human lung cancer cell line, Bel 7402 liver cancer cell line, HepG2 human ileocecal cancer cell line, and HT-29 human colon cancer cell line. A7 had significant effects on all cancer cell lines, suggesting potential applications for phloretin and its derivatives. Adding a methoxyl group to phloretin dramatically increases phloretin’s anticancer activity.

  4. Concentration and distribution of dioxins and related compounds in various human organs

    Energy Technology Data Exchange (ETDEWEB)

    Iida, T.; Hirakawa, H.; Hori, T.; Tobiishi, K.; Matsueda, T. [Fukuoka Inst. of Health and Environmental Sciences, Dazaifu, Fukuoka (Japan); Todaka, T. [Japan Food Hygiene Association, Tokyo (Japan); Watanabe, S. [Tokyo Univ. of Agriculture, Tokyo (Japan); Yamada, T. [Keio Univ. School of Medicine, Tokyo (Japan)

    2004-09-15

    Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and non-ortho coplanar polychlorinated biphenyls (Non-Co-PCBs) and mono-ortho coplanar polychlorinated biphenyls (Mono-Co-PCBs) accumulate in the human body due to their highly lipophilic properties. In recent years, there has been some concern about the potential health effects of dioxins and related chemicals for the general population of humans. Although there exists an enormous amount of data on this subject, most of it is from breast milk and blood, due to ease of collection; information concerning concentrations and distribution in various human organs hardly exists. Therefore, new data concerning various human tissues is required to evaluate the pathophysiological significance of dioxins and related compounds in humans. The aim of this study was to investigate the concentration levels and distribution of dioxins and related compounds in various human organ tissues. We previously reported on the concentration levels in the human liver and adipose tissues from 28 donors. In this paper, we determined the concentrations of dioxin-like isomers in 8 organs, including blood, lungs, liver, bile, spleen, pancreas, kidney and mesentery fat from 20 donors.

  5. Human reinforcement learning subdivides structured action spaces by learning effector-specific values.

    Science.gov (United States)

    Gershman, Samuel J; Pesaran, Bijan; Daw, Nathaniel D

    2009-10-28

    Humans and animals are endowed with a large number of effectors. Although this enables great behavioral flexibility, it presents an equally formidable reinforcement learning problem of discovering which actions are most valuable because of the high dimensionality of the action space. An unresolved question is how neural systems for reinforcement learning-such as prediction error signals for action valuation associated with dopamine and the striatum-can cope with this "curse of dimensionality." We propose a reinforcement learning framework that allows for learned action valuations to be decomposed into effector-specific components when appropriate to a task, and test it by studying to what extent human behavior and blood oxygen level-dependent (BOLD) activity can exploit such a decomposition in a multieffector choice task. Subjects made simultaneous decisions with their left and right hands and received separate reward feedback for each hand movement. We found that choice behavior was better described by a learning model that decomposed the values of bimanual movements into separate values for each effector, rather than a traditional model that treated the bimanual actions as unitary with a single value. A decomposition of value into effector-specific components was also observed in value-related BOLD signaling, in the form of lateralized biases in striatal correlates of prediction error and anticipatory value correlates in the intraparietal sulcus. These results suggest that the human brain can use decomposed value representations to "divide and conquer" reinforcement learning over high-dimensional action spaces.

  6. Protein differential expression induced by endocrine disrupting compounds in a terrestrial isopod.

    NARCIS (Netherlands)

    Lemos, M.F.L.; Esteves, A.C.; Samyn, B.; Timperman, I.; van Beeumen, J.; Correia, A.D.; van Gestel, C.A.M.; Soares, A.M.V.M.

    2010-01-01

    Endocrine disrupting compounds (EDCs) have been studied due to their impact on human health and increasing awareness of their impact on wildlife species. Studies concerning the organ-specific molecular effects of EDC in invertebrates are important to understand the mechanisms of action of this class

  7. Determination of Nerve Fiber Diameter Distribution From Compound Action Potential: A Continuous Approach.

    Science.gov (United States)

    Un, M Kerem; Kaghazchi, Hamed

    2018-01-01

    When a signal is initiated in the nerve, it is transmitted along each nerve fiber via an action potential (called single fiber action potential (SFAP)) which travels with a velocity that is related with the diameter of the fiber. The additive superposition of SFAPs constitutes the compound action potential (CAP) of the nerve. The fiber diameter distribution (FDD) in the nerve can be computed from the CAP data by solving an inverse problem. This is usually achieved by dividing the fibers into a finite number of diameter groups and solve a corresponding linear system to optimize FDD. However, number of fibers in a nerve can be measured sometimes in thousands and it is possible to assume a continuous distribution for the fiber diameters which leads to a gradient optimization problem. In this paper, we have evaluated this continuous approach to the solution of the inverse problem. We have utilized an analytical function for SFAP and an assumed a polynomial form for FDD. The inverse problem involves the optimization of polynomial coefficients to obtain the best estimate for the FDD. We have observed that an eighth order polynomial for FDD can capture both unimodal and bimodal fiber distributions present in vivo, even in case of noisy CAP data. The assumed FDD distribution regularizes the ill-conditioned inverse problem and produces good results.

  8. Direct action of endocrine disrupting chemicals on human sperm

    DEFF Research Database (Denmark)

    Schiffer, Christian; Müller, Astrid; Egeberg, Dorte L

    2014-01-01

    Synthetic endocrine disrupting chemicals (EDCs), omnipresent in food, household, and personal care products, have been implicated in adverse trends in human reproduction, including infertility and increasing demand for assisted reproduction. Here, we study the action of 96 ubiquitous EDCs on huma...

  9. Action and language integration: from humans to cognitive robots.

    Science.gov (United States)

    Borghi, Anna M; Cangelosi, Angelo

    2014-07-01

    The topic is characterized by a highly interdisciplinary approach to the issue of action and language integration. Such an approach, combining computational models and cognitive robotics experiments with neuroscience, psychology, philosophy, and linguistic approaches, can be a powerful means that can help researchers disentangle ambiguous issues, provide better and clearer definitions, and formulate clearer predictions on the links between action and language. In the introduction we briefly describe the papers and discuss the challenges they pose to future research. We identify four important phenomena the papers address and discuss in light of empirical and computational evidence: (a) the role played not only by sensorimotor and emotional information but also of natural language in conceptual representation; (b) the contextual dependency and high flexibility of the interaction between action, concepts, and language; (c) the involvement of the mirror neuron system in action and language processing; (d) the way in which the integration between action and language can be addressed by developmental robotics and Human-Robot Interaction. Copyright © 2014 Cognitive Science Society, Inc.

  10. Protective Actions of 17β-Estradiol and Progesterone on Oxidative Neuronal Injury Induced by Organometallic Compounds

    Directory of Open Access Journals (Sweden)

    Yasuhiro Ishihara

    2015-01-01

    Full Text Available Steroid hormones synthesized in and secreted from peripheral endocrine glands pass through the blood-brain barrier and play a role in the central nervous system. In addition, the brain possesses an inherent endocrine system and synthesizes steroid hormones known as neurosteroids. Increasing evidence shows that neuroactive steroids protect the central nervous system from various harmful stimuli. Reports show that the neuroprotective actions of steroid hormones attenuate oxidative stress. In this review, we summarize the antioxidative effects of neuroactive steroids, especially 17β-estradiol and progesterone, on neuronal injury in the central nervous system under various pathological conditions, and then describe our recent findings concerning the neuroprotective actions of 17β-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds, tributyltin, and methylmercury.

  11. The Use of Plant Antimicrobial Compounds for Food Preservation

    Science.gov (United States)

    Hintz, Tana; Matthews, Karl K.

    2015-01-01

    Foodborne disease is a global issue with significant impact on human health. With the growing consumer demand for natural preservatives to replace chemical compounds, plant antimicrobial compounds must be thoroughly investigated for their potential to serve as biopreservatives. This review paper will focus on the plant-derived products as antimicrobial agents for use in food preservation and to control foodborne pathogens in foods. Structure, modes of action, stability, and resistance to these plant compounds will be discussed as well as their application in food industries and possible technologies by which they can be delivered. Benefits as well as challenges, such as the need for further research for implementation and governmental regulation, will be highlighted. PMID:26539472

  12. Self-Organizing Neural Integration of Pose-Motion Features for Human Action Recognition

    Directory of Open Access Journals (Sweden)

    German Ignacio Parisi

    2015-06-01

    Full Text Available The visual recognition of complex, articulated human movements is fundamental for a wide range of artificial systems oriented towards human-robot communication, action classification, and action-driven perception. These challenging tasks may generally involve the processing of a huge amount of visual information and learning-based mechanisms for generalizing a set of training actions and classifying new samples. To operate in natural environments, a crucial property is the efficient and robust recognition of actions, also under noisy conditions caused by, for instance, systematic sensor errors and temporarily occluded persons. Studies of the mammalian visual system and its outperforming ability to process biological motion information suggest separate neural pathways for the distinct processing of pose and motion features at multiple levels and the subsequent integration of these visual cues for action perception. We present a neurobiologically-motivated approach to achieve noise-tolerant action recognition in real time. Our model consists of self-organizing Growing When Required (GWR networks that obtain progressively generalized representations of sensory inputs and learn inherent spatiotemporal dependencies. During the training, the GWR networks dynamically change their topological structure to better match the input space. We first extract pose and motion features from video sequences and then cluster actions in terms of prototypical pose-motion trajectories. Multi-cue trajectories from matching action frames are subsequently combined to provide action dynamics in the joint feature space. Reported experiments show that our approach outperforms previous results on a dataset of full-body actions captured with a depth sensor, and ranks among the best 21 results for a public benchmark of domestic daily actions.

  13. Organobromine compound profiling in human adipose: Assessment of sources of bromophenol

    International Nuclear Information System (INIS)

    Gao, Shixiong; Wan, Yi; Zheng, Guomao; Luo, Kai; Kannan, Kurunthachalam; Giesy, John P.; Lam, Michael H.W.; Hu, Jianying

    2015-01-01

    Bromophenols (BRPs) have been widely detected in human tissues, however, relative proportions from natural products and/or anthropogenic flame retardants are not clear. 21 polybrominated diphenyl ethers (PBDEs), 15 MeO/OH-PBDEs, and 10 BRPs were simultaneously quantified in adipose collected from people from New York City, USA. An in vitro assay utilizing human liver microsomes was performed for detected predominant organobromine. High concentrations of 2,4,6-triBRP and PBDEs were observed, and extremely low concentrations of naturally occurring MeO/OH-PBDEs were detected. Similar biotransformatioin rates of BRPs and MeO/OH-PBDEs indicated that the relative high concentration of 2,4,6-triBRP in humans was not of natural origin. Significant correlation observed between concentrations of 2,4,6-triBRP and BDE-209 suggested that the two chemicals may share a common source. Both 2,4,6-triBRP and BDE-209 were detected in commercial ABS resins, suggesting that plastic products made from ABS resins could be potential sources of co-exposure of the two compounds for humans. - Highlights: • 2,4,6-triBRP detected with high concentrations in human was not of natural origin. • Co-exposure of 2,4,6-triBRP and BDE-209 was observed in human samples. • Products made from ABS resins were potential exposure sources of 2,4,6-triBRP. - The profile of organobromine compounds in human together with biotransformation behaviors indicate that anthropogenic sources mainly contribute to high levels of bromophenols in humans

  14. Evaluation of a Silicone Membrane as an Alternative to Human Skin for Determining Skin Permeation Parameters of Chemical Compounds.

    Science.gov (United States)

    Uchida, Takashi; Yakumaru, Masafumi; Nishioka, Keisuke; Higashi, Yoshihiro; Sano, Tomohiko; Todo, Hiroaki; Sugibayashi, Kenji

    2016-01-01

    We evaluated the effectiveness of a silicone membrane as an alternative to human skin using the skin permeation parameters of chemical compounds. An in vitro permeation study using 15 model compounds was conducted, and permeation parameters comprising permeability coefficient (P), diffusion parameter (DL(-2)), and partition parameter (KL) were calculated from each permeation profile. Significant correlations were obtained in log P, log DL(-2), and log KL values between the silicone membrane and human skin. DL(-2) values of model compounds, except flurbiprofen, in the silicone membrane were independent of the lipophilicity of the model compounds and were 100-fold higher than those in human skin. For antipyrine and caffeine, which are hydrophilic, KL values in the silicone membrane were 100-fold lower than those in human skin, and P values, calculated as the product of a DL(-2) and KL, were similar. For lipophilic compounds, such as n-butyl paraben and flurbiprofen, KL values for silicone were similar to or 10-fold higher than those in human skin, and P values for silicone were 100-fold higher than those in human skin. Furthermore, for amphiphilic compounds with log Ko/w values from 0.5 to 3.5, KL values in the silicone membrane were 10-fold lower than those in human skin, and P values for silicone were 10-fold higher than those in human skin. The silicone membrane was useful as a human skin alternative in an in vitro skin permeation study. However, depending on the lipophilicity of the model compounds, some parameters may be over- or underestimated.

  15. The Influence of Glutamate on Axonal Compound Action Potential In Vitro.

    Science.gov (United States)

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background  Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives  The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods  Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results  The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion  The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs.

  16. A novel video recommendation system based on efficient retrieval of human actions

    Science.gov (United States)

    Ramezani, Mohsen; Yaghmaee, Farzin

    2016-09-01

    In recent years, fast growth of online video sharing eventuated new issues such as helping users to find their requirements in an efficient way. Hence, Recommender Systems (RSs) are used to find the users' most favorite items. Finding these items relies on items or users similarities. Though, many factors like sparsity and cold start user impress the recommendation quality. In some systems, attached tags are used for searching items (e.g. videos) as personalized recommendation. Different views, incomplete and inaccurate tags etc. can weaken the performance of these systems. Considering the advancement of computer vision techniques can help improving RSs. To this end, content based search can be used for finding items (here, videos are considered). In such systems, a video is taken from the user to find and recommend a list of most similar videos to the query one. Due to relating most videos to humans, we present a novel low complex scalable method to recommend videos based on the model of included action. This method has recourse to human action retrieval approaches. For modeling human actions, some interest points are extracted from each action and their motion information are used to compute the action representation. Moreover, a fuzzy dissimilarity measure is presented to compare videos for ranking them. The experimental results on HMDB, UCFYT, UCF sport and KTH datasets illustrated that, in most cases, the proposed method can reach better results than most used methods.

  17. Traditional Japanese medicines inhibit compound action potentials in the frog sciatic nerve.

    Science.gov (United States)

    Matsushita, Akitomo; Fujita, Tsugumi; Ohtsubo, Sena; Kumamoto, Eiichi

    2016-02-03

    Traditional Japanese (Kampo) medicines have a variety of clinical effects including pain alleviation, but evidence for a mechanism for their pain relief has not yet been elucidated fully. Considering that Kampo medicine contains many plant-derived chemicals having an ability to inhibit nerve action potential conduction, it is possible that this medicine inhibits nerve conduction. The purpose of the present study was to know how various Kampo medicines affect nerve conduction. We examined the effects of Kampo and crude medicines on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. Daikenchuto, rikkosan, kikyoto, rikkunshito, shakuyakukanzoto and kakkonto concentration-dependently reduced the peak amplitude of the CAP. Among the Kampo medicines, daikenchuto was the most effective in inhibiting CAPs. Daikenchuto is composed of three kinds of crude medicine, Japanese pepper, processed ginger and ginseng radix. When the crude medicines were tested, Japanese pepper and processed ginger reduced CAP peak amplitudes, while ginseng radix hardly affected CAPs. Moreover, there was an interaction between the Japanese pepper and processed ginger activities in such that one medicine at low but not high concentrations increased the extent of the inhibition by the other one that was co-applied. Kampo medicines have an ability to inhibit nerve conduction. This action of daikenchuto is due to Japanese pepper and processed ginger but not ginseng radix, probably through an interaction between Japanese pepper and processed ginger in a manner dependent on their concentrations. Nerve conduction inhibition could contribute to at least a part of Kampo medicine's clinical effects such as pain alleviation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Human reinforcement learning subdivides structured action spaces by learning effector-specific values

    OpenAIRE

    Gershman, Samuel J.; Pesaran, Bijan; Daw, Nathaniel D.

    2009-01-01

    Humans and animals are endowed with a large number of effectors. Although this enables great behavioral flexibility, it presents an equally formidable reinforcement learning problem of discovering which actions are most valuable, due to the high dimensionality of the action space. An unresolved question is how neural systems for reinforcement learning – such as prediction error signals for action valuation associated with dopamine and the striatum – can cope with this “curse of dimensionality...

  19. Incorporating gender, equity, and human rights into the action planning process: moving from rhetoric to action

    Directory of Open Access Journals (Sweden)

    Sanjeev Sridharan

    2016-09-01

    Full Text Available Background: Mainstreaming of gender, equity, and human rights (GER is an important focus of the World Health Organization (WHO and other UN organizations. This paper explores the role of action plans in mainstreaming GER. This paper is informed by a theory-driven evaluation lens. Design: A theory of change framework explored the following seven dimensions of how action plans can implement mainstreaming of GER: awareness of the foundations of GER; understanding of context; planning to impact GER; implementation for GER; monitoring, evaluation, and learning; planning for sustainability; agenda setting and buy-in. The seven dimensions were used to analyze the action plans. Reviewers also explored innovations within each of the action plans for the seven dimensions. Results: GER mainstreaming is more prominent in the foundation, background, and planning components of the plan but becomes less so along the theory of change including implementation; monitoring and evaluation; sustainability; and agenda setting and buy-in. Conclusions: Our analysis demonstrates that much more can be done to incorporate GER considerations into the action planning process. Nine specific recommendations are identified for WHO and other organizations. A theory-driven approach as described in the paper is potentially helpful for developing clarity by which action plans can help with mainstreaming GER considerations.

  20. Organotin compounds cause structure-dependent induction of progesterone in human choriocarcinoma Jar cells.

    Science.gov (United States)

    Hiromori, Youhei; Yui, Hiroki; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

    2016-01-01

    Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), are typical environmental contaminants and suspected endocrine-disrupting chemicals because they cause masculinization in female mollusks. In addition, previous studies have suggested that the endocrine disruption by organotin compounds leads to activation of peroxisome proliferator-activated receptor (PPAR)γ and retinoid X receptor (RXR). However, whether organotin compounds cause crucial toxicities in human development and reproduction is unclear. We here investigated the structure-dependent effect of 12 tin compounds on mRNA transcription of 3β-hydroxysteroid dehydrogenase type I (3β-HSD I) and progesterone production in human choriocarcinoma Jar cells. TBT, TPT, dibutyltin, monophenyltin, tripropyltin, and tricyclohexyltin enhanced progesterone production in a dose-dependent fashion. Although tetraalkyltin compounds such as tetrabutyltin increased progesterone production, the concentrations necessary for activation were 30-100 times greater than those for trialkyltins. All tested active organotins increased 3β-HSD I mRNA transcription. We further investigated the correlation between the agonistic activity of organotin compounds on PPARγ and their ability to promote progesterone production. Except for DBTCl2, the active organotins significantly induced the transactivation function of PPARγ. In addition, PPARγ knockdown significantly suppressed the induction of mRNA transcription of 3β-HSD I by all active organotins except DBTCl2. These results suggest that some organotin compounds promote progesterone biosynthesis in vitro by inducing 3β-HSD I mRNA transcription via the PPARγ signaling pathway. The placenta represents a potential target organ for these compounds, whose endocrine-disrupting effects might cause local changes in progesterone concentration in pregnant women. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Bringing humanity into view: action research with Qatar's ambulance service.

    Science.gov (United States)

    Coleman, Gill; Wiggins, Liz

    2017-08-21

    Purpose The purpose of this paper is to argue for the widening of attention in healthcare improvement efforts, to include an awareness of the humanity of people who work in the sector and an appreciation of the part human connection plays in engagement around good quality work. Theoretical frameworks and research approaches which draw on action-based, interpretive and systemic thinking are proposed, as a complement to current practices. Design/methodology/approach The paper describes the early stages of an action research (AR) project, which used the appreciative inquiry "4D" framework to conduct participative inquiry in Hamad Medical Corporation's ambulance service in Qatar, in which staff became co-researchers. Findings The co-researchers were highly motivated to work with improvement goals as a result of their participation in the AR. They, and their managers, saw each other and the work in new ways and discovered that they had much to offer. Research limitations/implications This was a small-scale pilot project, from which findings must be considered tentative. The challenges of establishing good collaboration across language, culture and organisational divides are considerable. Practical implications Appreciative and action-oriented inquiry methods can serve not only to find things out, but also to highlight and give value to aspects of humanity in the workplace that are routinely left invisible in formal processes. This, in turn, can help with quality improvement. Originality/value This paper is a challenge to the orthodox way of viewing healthcare organisations, and improvement processes within them, as reliant on control rather than empowerment. An alternative is to actively include the agency, sense-making capacity and humanity of those involved.

  2. "Unwilling" versus "Unable": Capuchin Monkeys' ("Cebus Apella") Understanding of Human Intentional Action

    Science.gov (United States)

    Phillips, Webb; Barnes, Jennifer L.; Mahajan, Neha; Yamaguchi, Mariko; Santos, Laurie R.

    2009-01-01

    A sensitivity to the intentions behind human action is a crucial developmental achievement in infants. Is this intention reading ability a unique and relatively recent product of human evolution and culture, or does this capacity instead have roots in our non-human primate ancestors? Recent work by Call and colleagues (2004) lends credence to the…

  3. Evaluation of T-lymphocyte populations in humans exposed to action of beryllium compounds

    Energy Technology Data Exchange (ETDEWEB)

    Ermakova, N G

    1977-10-01

    Earlier studies in vitro on beryllosis and cellular immunity, and knowledge of the role of T-cells in development of cellular immunity suggested usefulness of a quantitative determination of T-cell populations in beryllosis. Assay was based on the test for spontaneous rosette formation in beryllosis patients and in healthy workers who come in contact with Be compounds (Jondal, modified by M. A. Stenina) and on the leucocyte migration inhibition reaction (Soborg and Bendixen). A large range of changes were revealed in population size and in adhesion qualities of T-lymphocytes in the patients and in those exposed to Be. The test for spontaneous rosette formation was found to be sufficiently indicative for use in study of beryllosis pathogenesis and to correlate with the state of activity of the disease.

  4. Post-event human decision errors: operator action tree/time reliability correlation

    International Nuclear Information System (INIS)

    Hall, R.E.; Fragola, J.; Wreathall, J.

    1982-11-01

    This report documents an interim framework for the quantification of the probability of errors of decision on the part of nuclear power plant operators after the initiation of an accident. The framework can easily be incorporated into an event tree/fault tree analysis. The method presented consists of a structure called the operator action tree and a time reliability correlation which assumes the time available for making a decision to be the dominating factor in situations requiring cognitive human response. This limited approach decreases the magnitude and complexity of the decision modeling task. Specifically, in the past, some human performance models have attempted prediction by trying to emulate sequences of human actions, or by identifying and modeling the information processing approach applicable to the task. The model developed here is directed at describing the statistical performance of a representative group of hypothetical individuals responding to generalized situations

  5. Post-event human decision errors: operator action tree/time reliability correlation

    Energy Technology Data Exchange (ETDEWEB)

    Hall, R E; Fragola, J; Wreathall, J

    1982-11-01

    This report documents an interim framework for the quantification of the probability of errors of decision on the part of nuclear power plant operators after the initiation of an accident. The framework can easily be incorporated into an event tree/fault tree analysis. The method presented consists of a structure called the operator action tree and a time reliability correlation which assumes the time available for making a decision to be the dominating factor in situations requiring cognitive human response. This limited approach decreases the magnitude and complexity of the decision modeling task. Specifically, in the past, some human performance models have attempted prediction by trying to emulate sequences of human actions, or by identifying and modeling the information processing approach applicable to the task. The model developed here is directed at describing the statistical performance of a representative group of hypothetical individuals responding to generalized situations.

  6. A Generalized Pyramid Matching Kernel for Human Action Recognition in Realistic Videos

    Directory of Open Access Journals (Sweden)

    Wenjun Zhang

    2013-10-01

    Full Text Available Human action recognition is an increasingly important research topic in the fields of video sensing, analysis and understanding. Caused by unconstrained sensing conditions, there exist large intra-class variations and inter-class ambiguities in realistic videos, which hinder the improvement of recognition performance for recent vision-based action recognition systems. In this paper, we propose a generalized pyramid matching kernel (GPMK for recognizing human actions in realistic videos, based on a multi-channel “bag of words” representation constructed from local spatial-temporal features of video clips. As an extension to the spatial-temporal pyramid matching (STPM kernel, the GPMK leverages heterogeneous visual cues in multiple feature descriptor types and spatial-temporal grid granularity levels, to build a valid similarity metric between two video clips for kernel-based classification. Instead of the predefined and fixed weights used in STPM, we present a simple, yet effective, method to compute adaptive channel weights of GPMK based on the kernel target alignment from training data. It incorporates prior knowledge and the data-driven information of different channels in a principled way. The experimental results on three challenging video datasets (i.e., Hollywood2, Youtube and HMDB51 validate the superiority of our GPMK w.r.t. the traditional STPM kernel for realistic human action recognition and outperform the state-of-the-art results in the literature.

  7. Improvement of a synthetic lure for Anopheles gambiae using compounds produced by human skin microbiota.

    Science.gov (United States)

    Verhulst, Niels O; Mbadi, Phoebe A; Kiss, Gabriella Bukovinszkiné; Mukabana, Wolfgang R; van Loon, Joop J A; Takken, Willem; Smallegange, Renate C

    2011-02-08

    Anopheles gambiae sensu stricto is considered to be highly anthropophilic and volatiles of human origin provide essential cues during its host-seeking behaviour. A synthetic blend of three human-derived volatiles, ammonia, lactic acid and tetradecanoic acid, attracts A. gambiae. In addition, volatiles produced by human skin bacteria are attractive to this mosquito species. The purpose of the current study was to test the effect of ten compounds present in the headspace of human bacteria on the host-seeking process of A. gambiae. The effect of each of the ten compounds on the attractiveness of a basic blend of ammonia, lactic and tetradecanoic acid to A. gambiae was examined. The host-seeking response of A. gambiae was evaluated in a laboratory set-up using a dual-port olfactometer and in a semi-field facility in Kenya using MM-X traps. Odorants were released from LDPE sachets and placed inside the olfactometer as well as in the MM-X traps. Carbon dioxide was added in the semi-field experiments, provided from pressurized cylinders or fermenting yeast. The olfactometer and semi-field set-up allowed for high-throughput testing of the compounds in blends and in multiple concentrations. Compounds with an attractive or inhibitory effect were identified in both bioassays. 3-Methyl-1-butanol was the best attractant in both set-ups and increased the attractiveness of the basic blend up to three times. 2-Phenylethanol reduced the attractiveness of the basic blend in both bioassays by more than 50%. Identification of volatiles released by human skin bacteria led to the discovery of compounds that have an impact on the host-seeking behaviour of A. gambiae. 3-Methyl-1-butanol may be used to increase mosquito trap catches, whereas 2-phenylethanol has potential as a spatial repellent. These two compounds could be applied in push-pull strategies to reduce mosquito numbers in malaria endemic areas.

  8. Impedance and electrically evoked compound action potential (ECAP drop within 24 hours after cochlear implantation.

    Directory of Open Access Journals (Sweden)

    Joshua Kuang-Chao Chen

    Full Text Available Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈ 2.5 cm and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001. There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes

  9. Observation and imitation of actions performed by humans, androids, and robots: an EMG study

    Science.gov (United States)

    Hofree, Galit; Urgen, Burcu A.; Winkielman, Piotr; Saygin, Ayse P.

    2015-01-01

    Understanding others’ actions is essential for functioning in the physical and social world. In the past two decades research has shown that action perception involves the motor system, supporting theories that we understand others’ behavior via embodied motor simulation. Recently, empirical approach to action perception has been facilitated by using well-controlled artificial stimuli, such as robots. One broad question this approach can address is what aspects of similarity between the observer and the observed agent facilitate motor simulation. Since humans have evolved among other humans and animals, using artificial stimuli such as robots allows us to probe whether our social perceptual systems are specifically tuned to process other biological entities. In this study, we used humanoid robots with different degrees of human-likeness in appearance and motion along with electromyography (EMG) to measure muscle activity in participants’ arms while they either observed or imitated videos of three agents produce actions with their right arm. The agents were a Human (biological appearance and motion), a Robot (mechanical appearance and motion), and an Android (biological appearance and mechanical motion). Right arm muscle activity increased when participants imitated all agents. Increased muscle activation was found also in the stationary arm both during imitation and observation. Furthermore, muscle activity was sensitive to motion dynamics: activity was significantly stronger for imitation of the human than both mechanical agents. There was also a relationship between the dynamics of the muscle activity and motion dynamics in stimuli. Overall our data indicate that motor simulation is not limited to observation and imitation of agents with a biological appearance, but is also found for robots. However we also found sensitivity to human motion in the EMG responses. Combining data from multiple methods allows us to obtain a more complete picture of action

  10. In-vitro characterization of a cochlear implant system for recording of evoked compound action potentials

    Science.gov (United States)

    2012-01-01

    Background Modern cochlear implants have integrated recording systems for measuring electrically evoked compound action potentials of the auditory nerve. The characterization of such recording systems is important for establishing a reliable basis for the interpretation of signals acquired in vivo. In this study we investigated the characteristics of the recording system integrated into the MED-EL PULSARCI100 cochlear implant, especially its linearity and resolution, in order to develop a mathematical model describing the recording system. Methods In-vitro setup: The cochlear implant, including all attached electrodes, was fixed in a tank of physiologic saline solution. Sinusoidal signals of the same frequency but with different amplitudes were delivered via a signal generator for measuring and recording on a single electrode. Computer simulations: A basic mathematical model including the main elements of the recording system, i.e. amplification and digitalization stage, was developed. For this, digital output for sinusoidal input signals of different amplitudes were calculated using in-vitro recordings as reference. Results Using an averaging of 100 measurements the recording system behaved linearly down to approximately -60 dB of the input signal range. Using the same method, a system resolution of 10 μV was determined for sinusoidal signals. The simulation results were in very good agreement with the results obtained from in-vitro experiments. Conclusions The recording system implemented in the MED-EL PULSARCI100 cochlear implant for measuring the evoked compound action potential of the auditory nerve operates reliably. The developed mathematical model provides a good approximation of the recording system. PMID:22531599

  11. Elements of a regulatory strategy for the consideration of future human actions in safety assessments

    International Nuclear Information System (INIS)

    Wilmot, R.D.; Wickham, S.M.; Galson, D.A.

    1999-09-01

    The objective of this report is to discuss issues that should be considered in the development of a regulatory strategy for assessing future human actions in any forthcoming license application for a deep repository for spent fuel in Sweden and for sites of other repositories. The report comprises an outline of key issues concerning the treatment of future human actions in safety assessment, reviews of regulatory developments, recent safety assessments and supporting studies, and international initiatives on the treatment of future human actions in safety assessment, and the principal elements of a regulatory strategy. Performance assessments (PAs) are generally accepted as providing illustrations of system performance under given sets of assumptions. The results of PAs are clearer and easier to understand if certain large uncertainties are accounted for by determining performance under several different sets of assumptions or scenarios, each of which defines a possible evolution of the disposal system. A number of assumptions can be made that would restrict the scope of an assessment without reducing the credibility of the corresponding safety case. Reducing speculation about technological development, by assuming that the techniques used in future human activities are similar to those currently in use in the region or at similar sites, will simplify the assessment. A distinction is generally made between inadvertent and intentional intrusion, with intentional activities excluded because society cannot protect future populations from their own actions if they understand the potential consequences. A division of human activities into 'recent and ongoing' and 'future' activities considers not only the timing of the activities but also the degree of control or influence that can be imposed on them. Recent and ongoing human activities are those that affect an area beyond the immediate vicinity of the disposal facility and which neither the proponent nor the regulator

  12. Deactivation in the Sensorimotor Area during Observation of a Human Agent Performing Robotic Actions

    Science.gov (United States)

    Shimada, Sotaro

    2010-01-01

    It is well established that several motor areas, called the mirror-neuron system (MNS), are activated when an individual observes other's actions. However, whether the MNS responds similarly to robotic actions compared with human actions is still controversial. The present study investigated whether and how the motor area activity is influenced by…

  13. Human-Nature for Climate Action: Nature-Based Solutions for Urban Sustainability

    Directory of Open Access Journals (Sweden)

    Helen Santiago Fink

    2016-03-01

    Full Text Available The global climate change agenda proceeds at an incremental pace while the Earth is approaching critical tipping points in its development trajectory. Climate action at this pinnacle juncture needs to be greatly accelerated and rooted in the fundamentals of the problem—human beings’ disconnection from nature. This paper underscores the valuable role nature and nature-based solutions can play in addressing climate change at the city scale and its implications for broader sustainability. Urban ecosystems (nature in cities are seen as an integral part of a proposed local climate action rubric wherein policy measures and integrated planning guide lowcarbon/impact development to create more resilient and sustainable urban environments. The use of green infrastructure is highlighted as a cost-effective means to contribute to mitigation and adaptation needs as well as to promote human wellbeing. The paper takes an exploratory view of the influence of ecosystem services, particularly cultural services, and its economics in relation to the individual and society to understand how biophilia can be nurtured to promote environmental stewardship and climate action.

  14. A survey of synthetic and natural phytotoxic compounds and phytoalexins as potential antimalarial compounds.

    Science.gov (United States)

    Bajsa, Joanna; Singh, Kshipra; Nanayakkara, Dhammika; Duke, Stephen Oscar; Rimando, Agnes Mamaril; Evidente, Antonio; Tekwani, Babu Lal

    2007-09-01

    The apicomplexan parasites pathogens such as Plasmodium spp. possess an apicoplast, a plastid organelle similar to those of plants. The apicoplast has some essential plant-like metabolic pathways and processes, making these parasites susceptible to inhibitors of these functions. The main objective of this paper is to determine if phytotoxins with plastid target sites are more likely to be good antiplasmodial compounds than are those with other modes of action. The antiplasmodial activities of some compounds with established phytotoxic action were determined in vitro on a chloroquine (CQ) sensitive (D6, Sierra Leone) strain of Plasmodium falciparum. In this study, we provide in vitro activities of almost 50 such compounds, as well as a few phytoalexins against P. falciparum. Endothall, anisomycin, and cerulenin had sufficient antiplasmodial action to be considered as new lead antimalarial structures. Some derivatives of fusicoccin possessed markedly improved antiplasmodial action than the parent compound. Our results suggest that phytotoxins with plastid targets may not necessarily be better antiplasmodials than those that act at other molecular sites. The herbicides, phytotoxins and the phytoalexins reported here with significant antiplasmodial activity may be useful probes for identification of new antimalarial drug targets and may also be used as new lead structures for new antiplasmodial drug discovery.

  15. The influence of vegetable bioactive compounds on systemic immune reactions to ionizing radiation action

    International Nuclear Information System (INIS)

    Coretchi, Liuba; Plavan, Irina; Bahnarel, Ion; Rosca, Andrei

    2015-01-01

    The paper presents the summary of the scientific results analysis of the published in the last 10 years studies of the influence of secondary metabolites essential oils and essential-oil plants extracts, on the resistance/sensitivity of the animal and human body to the action of ionizing radiation. An essential problem is the development of new nanotechnologies for mitigation the onset of side effects caused by the use of ionizing radiation therapy of patients with different types of cancer. Widespread application of phyto therapy empiric reveals the beneficial effect of essential oils and essential-oil plants extracts on the immune system. The considered substances have natural antioxidant properties and contribute to the elimination of free radicals which are formed in the body under the action of stress, including ionizing radiation. This reveals about their use in mitigation of ionizing radiation action effects, as a radio protector agent. Unlike other preparations, used to activate the immune system, essential oils at low concentrations show a long-lasting system immune stimulation action. More of that, during their administration the onset of adverse reactions have not been demonstrated. (authors)

  16. Electrophysiologic evaluation of lumbosacral single nerve roots using compound muscle action potentials.

    Science.gov (United States)

    Ogura, Taku; Shikata, Hideto; Hase, Hitoshi; Mori, Masaki; Hayashida, Taturo; Osawa, Toru; Mikami, Yasuo; Kubo, Toshikazu

    2003-10-01

    Transcutaneous electrical stimulation applied to the vertebral column produces compound muscle action potentials (CMAPs) from the leg muscles. Using this method, we evaluated the efferent pathways of the lumbosacral nerve roots. The subjects were 26 healthy volunteers and 31 patients with lumbar disc herniation (LDH). CMAP recordings were obtained from the bilateral vastus medialis, tibialis anterior, extensor digitorum brevis, and abductor hallucis muscles using low-output-impedance stimulation. In normal subjects, the CMAP latency increased linearly with the distance between the stimulating electrode and the recording electrode, with little difference in latency between the left and the right sides in each subject. The CMAP amplitude was significantly lower in the patients with LDH, and the latency was also prolonged when the stimulating electrode was placed above the lesion. This technique may thus be a useful noninvasive method for assessing lumbosacral nerve root function in patients with LDH.

  17. A study on the dependency evaluation for multiple human actions in human reliability analysis of probabilistic safety assessment

    International Nuclear Information System (INIS)

    Kang, D. I.; Yang, J. E.; Jung, W. D.; Sung, T. Y.; Park, J. H.; Lee, Y. H.; Hwang, M. J.; Kim, K. Y.; Jin, Y. H.; Kim, S. C.

    1997-02-01

    This report describes the study results on the method of the dependency evaluation and the modeling, and the limited value of human error probability (HEP) for multiple human actions in accident sequences of probabilistic safety assessment (PSA). THERP and Parry's method, which have been generally used in dependency evaluation of human reliability analysis (HRA), are introduced and their limitations are discussed. New dependency evaluation method in HRA is established to make up for the weak points of THERP and Parry's methods. The limited value of HEP is also established based on the review of several HRA related documents. This report describes the definition, the type, the evaluation method, and the evaluation example of dependency to help the reader's understanding. It is expected that this study results will give a guidance to HRA analysts in dependency evaluation of multiple human actions and enable PSA analysts to understand HRA in detail. (author). 23 refs., 3 tabs., 2 figs

  18. Prediction of Human Intestinal Absorption of Compounds Using Artificial Intelligence Techniques.

    Science.gov (United States)

    Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

    2017-01-01

    Information about Pharmacokinetics of compounds is an essential component of drug design and development. Modeling the pharmacokinetic properties require identification of the factors effecting absorption, distribution, metabolism and excretion of compounds. There have been continuous attempts in the prediction of intestinal absorption of compounds using various Artificial intelligence methods in the effort to reduce the attrition rate of drug candidates entering to preclinical and clinical trials. Currently, there are large numbers of individual predictive models available for absorption using machine learning approaches. Six Artificial intelligence methods namely, Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis were used for prediction of absorption of compounds. Prediction accuracy of Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis for prediction of intestinal absorption of compounds was found to be 91.54%, 88.33%, 84.30%, 86.51%, 79.07% and 80.08% respectively. Comparative analysis of all the six prediction models suggested that Support vector machine with Radial basis function based kernel is comparatively better for binary classification of compounds using human intestinal absorption and may be useful at preliminary stages of drug design and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Accumulation of 19 environmental phenolic and xenobiotic heterocyclic aromatic compounds in human adipose tissue.

    Science.gov (United States)

    Wang, Lei; Asimakopoulos, Alexandros G; Kannan, Kurunthachalam

    2015-05-01

    The extensive use of environmental phenols (e.g., bisphenol A) and heterocyclic aromatic compounds (e.g., benzothiazole) in consumer products as well as widespread exposure of humans to these compounds have been well documented. Biomonitoring studies have used urinary measurements to assess exposures, based on the assumption that these chemicals are metabolized and eliminated in urine. Despite the fact that some of these chemicals are moderately lipophilic, the extent of their accumulation in adipose fat tissues has not been convincingly demonstrated. In this study, human adipose fat samples (N=20) collected from New York City, USA, were analyzed for the presence of environmental phenols, including bisphenol A (BPA), benzophenone-3 (BP-3), triclosan (TCS), and parabens, as well as heterocyclic aromatic compounds, including benzotriazole (BTR), benzothiazole (BTH), and their derivatives. BPA and TCS were frequently detected in adipose tissues at concentrations (geometric mean [GM]: 3.95ng/g wet wt for BPA and 7.21ng/g wet wt for TCS) similar to or below the values reported for human urine. High concentrations of BP-3 were found in human adipose tissues (GM: 43.4; maximum: 4940ng/g wet wt) and a positive correlation between BP-3 concentrations and donor's age was observed. The metabolite of parabens, p-hydroxybenzoic acid (p-HB), also was found at elevated levels (GM: 4160; max.: 17,400ng/g wet wt) and a positive correlation between donor's age and sum concentration of parabens and p-HB were found. The GM concentrations of BTR and BTH in human adipose tissues were below 1ng/g, although the methylated forms of BTR (i.e., TTR and XTR) and the hydrated form of BTH (i.e., 2-OH-BTH) were frequently detected in adipose samples, indicating widespread exposure to these compounds. Our results suggest that adipose tissue is an important repository for BP-3 and parabens, including p-HB, in the human body. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Observation and Imitation of Actions Performed by Humans, Androids and Robots: An EMG study

    Directory of Open Access Journals (Sweden)

    Galit eHofree

    2015-06-01

    Full Text Available Understanding others’ actions is essential for functioning in the physical and social world. In the past two decades research has shown that action perception involves the motor system, supporting theories that we understand others’ behavior via embodied motor simulation. Recently, action perception has been facilitated by using well-controlled artificial stimuli, such as robots. One key question this approach enables is what aspects of similarity between the observer and the observed agent facilitate motor simulation? Since humans have evolved among other humans and animals, using artificial stimuli such as robots allows us to probe whether our social perceptual systems are tuned to process other biological entities. In this study, we used humanoid robots with different degrees of humanlikeness in appearance and motion along with electromyography (EMG to measure muscle activity in participants’ arms while they either observed or imitated videos of three agents produce actions with their right arm. The agents were a Human (biological appearance and motion, a Robot (mechanical appearance and motion and an Android (biological appearance, mechanical motion. Right arm muscle activity increased when participants imitated all agents. Increased muscle activation was found also in the stationary arm both during imitation and observation. Furthermore, muscle activity was sensitive to motion dynamics: activity was significantly stronger for imitation of the human than both mechanical agents. There was also a relationship between the dynamics of the muscle activity and motion dynamics in stimuli. Overall our data indicate that motor simulation is not limited to observation and imitation of agents with a biological appearance, but is also found for robots. However we also found sensitivity to human motion in the EMG responses. Combining data from multiple methods allows us to obtain a more complete picture of action understanding and the underlying

  1. Elements of a regulatory strategy for the consideration of future human actions in safety assessments

    Energy Technology Data Exchange (ETDEWEB)

    Wilmot, R.D.; Wickham, S.M.; Galson, D.A. [Galson Sciences Ltd, Oakham (United Kingdom)

    1999-09-01

    The objective of this report is to discuss issues that should be considered in the development of a regulatory strategy for assessing future human actions in any forthcoming license application for a deep repository for spent fuel in Sweden and for sites of other repositories. The report comprises an outline of key issues concerning the treatment of future human actions in safety assessment, reviews of regulatory developments, recent safety assessments and supporting studies, and international initiatives on the treatment of future human actions in safety assessment, and the principal elements of a regulatory strategy. Performance assessments (PAs) are generally accepted as providing illustrations of system performance under given sets of assumptions. The results of PAs are clearer and easier tounderstand if certain large uncertainties are accounted for by determining performance under several different sets of assumptions or scenarios, each of which defines a possible evolution of the disposal system. A number of assumptions can be made that would restrict the scope of an assessment without reducing the credibility of the corresponding safety case. Reducing speculation about technological development, by assuming that the techniques used in future human activities are similar to those currently in use in the region or at similar sites, will simplify the assessment. A distinction is generally made between inadvertent and intentional intrusion, with intentional activities excluded because society cannot protect future populations from their own actions if they understand the potential consequences. A division of human activities into 'recent and ongoing' and 'future' activities considers not only the timing of the activities but also the degree of control or influence that can be imposed on them. Recent and ongoing human activities are those that affect an area beyond the immediate vicinity of the disposal facility and which neither the proponent

  2. A biotechnological approach for the development of new antifungal compounds to protect the environment and the human health

    Directory of Open Access Journals (Sweden)

    Claudia Zani

    2015-11-01

    Full Text Available Background. In the Po Valley aflatoxins play a relevant role: the local food economy is heavily based on cereal cultivations for animal feed and human nutrition. Aims of this project are the identification of new compounds that inhibit Aspergillus proliferation, the development of new inhibitors of aflatoxins production, and the set-up a practical screening procedure to identify the most effective and safe compounds. Design and Methods. New compounds will be synthetized with natural origin molecules as ligands and endogenous metal ions to increase their bioavailability for the fungi as metal complexes. A biotechnological high-throughput screening will be set up to identify efficiently the most powerful substances. The newly synthesized compounds with effective antifungal activities, will be evaluated with battery of tests with different end-points to assess the toxic potential risk for environmental and human health. Expected impact of the study for public health. The fundamental step in the project will be the synthesis of new compounds and the study of their capability to inhibit aflatoxin biosynthesis. A new, simple, inexpensive and high-throughput method to screen the anti-fungine and anti-mycotoxin activity of the new synthesised compounds will be applied. The evaluation of possible risks for humans due to toxic and genotoxic activities of the molecules will be made with a new approach using different types of cells (bacteria, plants and human cells.

  3. A statistical model of future human actions

    International Nuclear Information System (INIS)

    Woo, G.

    1992-02-01

    A critical review has been carried out of models of future human actions during the long term post-closure period of a radioactive waste repository. Various Markov models have been considered as alternatives to the standard Poisson model, and the problems of parameterisation have been addressed. Where the simplistic Poisson model unduly exaggerates the intrusion risk, some form of Markov model may have to be introduced. This situation may well arise for shallow repositories, but it is less likely for deep repositories. Recommendations are made for a practical implementation of a computer based model and its associated database. (Author)

  4. Extending breath analysis to the cellular level: current thoughts on the human microbiome and the expression of organic compounds in the human exposome

    Science.gov (United States)

    Human biomarkers are comprised of compounds from cellular metabolism, oxidative stress, and the microbiome of bacteria in the gut, genitourinary, and pulmonary tracts. When we examine patterns in human biomarkers to discern human health state or diagnose specific diseases, it is...

  5. Morphological modulation of human fibrosarcoma HT-1080 cells by hydroxybenzoate compounds during apoptosis

    Directory of Open Access Journals (Sweden)

    Jassem G Mahdi

    2015-10-01

    Full Text Available Hydroxybenzoate (HB compounds have shown to modulate the morphology in human fibrosarcoma HT-1080 cells. The changes in HT-1080 cells showed marker signs of apoptosis, which included the condensation of nucleus, cell round, blebbing and the formation of apoptotic bodies. The different stages of apoptosis were assessed microscopically using different staining and immunohistochemical techniques, as well as scanning electron microscopy. In addition, HB compounds increased the expression of caspase-3, which is closely associated with the development of the modulation in HT-1080 cells that are undergoing the programmed cell death. Both acetyl salicylic acid (ASA and HBZn compounds were dose and treatment duration dependent.

  6. Decoding natural reach-and-grasp actions from human EEG

    Science.gov (United States)

    Schwarz, Andreas; Ofner, Patrick; Pereira, Joana; Ioana Sburlea, Andreea; Müller-Putz, Gernot R.

    2018-02-01

    Objective. Despite the high number of degrees of freedom of the human hand, most actions of daily life can be executed incorporating only palmar, pincer and lateral grasp. In this study we attempt to discriminate these three different executed reach-and-grasp actions utilizing their EEG neural correlates. Approach. In a cue-guided experiment, 15 healthy individuals were asked to perform these actions using daily life objects. We recorded 72 trials for each reach-and-grasp condition and from a no-movement condition. Main results. Using low-frequency time domain features from 0.3 to 3 Hz, we achieved binary classification accuracies of 72.4%, STD  ±  5.8% between grasp types, for grasps versus no-movement condition peak performances of 93.5%, STD  ±  4.6% could be reached. In an offline multiclass classification scenario which incorporated not only all reach-and-grasp actions but also the no-movement condition, the highest performance could be reached using a window of 1000 ms for feature extraction. Classification performance peaked at 65.9%, STD  ±  8.1%. Underlying neural correlates of the reach-and-grasp actions, investigated over the primary motor cortex, showed significant differences starting from approximately 800 ms to 1200 ms after the movement onset which is also the same time frame where classification performance reached its maximum. Significance. We could show that it is possible to discriminate three executed reach-and-grasp actions prominent in people’s everyday use from non-invasive EEG. Underlying neural correlates showed significant differences between all tested conditions. These findings will eventually contribute to our attempt of controlling a neuroprosthesis in a natural and intuitive way, which could ultimately benefit motor impaired end users in their daily life actions.

  7. Improved Collaborative Representation Classifier Based on l2-Regularized for Human Action Recognition

    Directory of Open Access Journals (Sweden)

    Shirui Huo

    2017-01-01

    Full Text Available Human action recognition is an important recent challenging task. Projecting depth images onto three depth motion maps (DMMs and extracting deep convolutional neural network (DCNN features are discriminant descriptor features to characterize the spatiotemporal information of a specific action from a sequence of depth images. In this paper, a unified improved collaborative representation framework is proposed in which the probability that a test sample belongs to the collaborative subspace of all classes can be well defined and calculated. The improved collaborative representation classifier (ICRC based on l2-regularized for human action recognition is presented to maximize the likelihood that a test sample belongs to each class, then theoretical investigation into ICRC shows that it obtains a final classification by computing the likelihood for each class. Coupled with the DMMs and DCNN features, experiments on depth image-based action recognition, including MSRAction3D and MSRGesture3D datasets, demonstrate that the proposed approach successfully using a distance-based representation classifier achieves superior performance over the state-of-the-art methods, including SRC, CRC, and SVM.

  8. The action characterization matrix: A link between HERA (Human Events Reference for ATHEANA) and ATHEANA (a technique for human error analysis)

    International Nuclear Information System (INIS)

    Hahn, H.A.

    1997-01-01

    The Technique for Human Error Analysis (ATHEANA) is a newly developed human reliability analysis (HRA) methodology that aims to facilitate better representation and integration of human performance into probabilistic risk assessment (PRA) modeling and quantification by analyzing risk-significant operating experience in the context of existing behavior science models. The fundamental premise of ATHEANA is that error-forcing contexts (EFCs), which refer to combinations of equipment/material conditions and performance shaping factors (PSFs), set up or create the conditions under which unsafe actions (UAs) can occur. ATHEANA is being developed in the context of nuclear power plant (NPP) PRAs, and much of the language used to describe the method and provide examples of its application are specific to that industry. Because ATHEANA relies heavily on the analysis of operational events that have already occurred as a mechanism for generating creative thinking about possible EFCs, a database, called the Human Events Reference for ATHEANA (HERA), has been developed to support the methodology. Los Alamos National Laboratory's (LANL) Human Factors Group has recently joined the ATHEANA project team; LANL is responsible for further developing the database structure and for analyzing additional exemplar operational events for entry into the database. The Action Characterization Matrix (ACM) is conceived as a bridge between the HERA database structure and ATHEANA. Specifically, the ACM allows each unsafe action or human failure event to be characterized according to its representation along each of six different dimensions: system status, initiator status, unsafe action mechanism, information processing stage, equipment/material conditions, and performance shaping factors. This report describes the development of the ACM and provides details on the structure and content of its dimensions

  9. The effects of compound danshen dripping pills and human umbilical cord blood mononuclear cell transplant after acute myocardial infarction.

    Science.gov (United States)

    Jun, Yi; Chunju, Yuan; Qi, Ai; Liuxia, Deng; Guolong, Yu

    2014-04-01

    The low frequency of survival of stem cells implanted in the myocardium after acute myocardial infarction may be caused by inflammation and oxidative stress in the myocardial microenvironment. We evaluated the effects of a traditional Chinese medicine, Compound Danshen Dripping Pills, on the cardiac microenvironment and cardiac function when used alone or in combination with human umbilical cord blood mononuclear cell transplant after acute myocardial infarction. After surgically induced acute myocardial infarction, rabbits were treated with Compound Danshen Dripping Pills alone or in combination with human umbilical cord blood mononuclear cell transplant. Evaluation included histology, measurement of left ventricular ejection fraction and fractional shortening, leukocyte count, count of green fluorescent protein positive cells, superoxide dismutase activity, and malondialdehyde content. Combination treatment with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cell transplant significantly increased the survival of implanted cells, inhibited cardiac cell apoptosis, decreased oxidative stress, decreased the inflammatory response, and improved cardiac function. Rabbits treated with either Compound Danshen Dripping Pills or human umbilical cord blood mononuclear cells alone had improvement in these effects compared with untreated control rabbits. Combination therapy with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cells may improve cardiac function and morphology after acute myocardial infarction.

  10. Human fMRI reveals that delayed action re-recruits visual perception.

    Science.gov (United States)

    Singhal, Anthony; Monaco, Simona; Kaufman, Liam D; Culham, Jody C

    2013-01-01

    Behavioral and neuropsychological research suggests that delayed actions rely on different neural substrates than immediate actions; however, the specific brain areas implicated in the two types of actions remain unknown. We used functional magnetic resonance imaging (fMRI) to measure human brain activation during delayed grasping and reaching. Specifically, we examined activation during visual stimulation and action execution separated by a 18-s delay interval in which subjects had to remember an intended action toward the remembered object. The long delay interval enabled us to unambiguously distinguish visual, memory-related, and action responses. Most strikingly, we observed reactivation of the lateral occipital complex (LOC), a ventral-stream area implicated in visual object recognition, and early visual cortex (EVC) at the time of action. Importantly this reactivation was observed even though participants remained in complete darkness with no visual stimulation at the time of the action. Moreover, within EVC, higher activation was observed for grasping than reaching during both vision and action execution. Areas in the dorsal visual stream were activated during action execution as expected and, for some, also during vision. Several areas, including the anterior intraparietal sulcus (aIPS), dorsal premotor cortex (PMd), primary motor cortex (M1) and the supplementary motor area (SMA), showed sustained activation during the delay phase. We propose that during delayed actions, dorsal-stream areas plan and maintain coarse action goals; however, at the time of execution, motor programming requires re-recruitment of detailed visual information about the object through reactivation of (1) ventral-stream areas involved in object perception and (2) early visual areas that contain richly detailed visual representations, particularly for grasping.

  11. Human fMRI reveals that delayed action re-recruits visual perception.

    Directory of Open Access Journals (Sweden)

    Anthony Singhal

    Full Text Available Behavioral and neuropsychological research suggests that delayed actions rely on different neural substrates than immediate actions; however, the specific brain areas implicated in the two types of actions remain unknown. We used functional magnetic resonance imaging (fMRI to measure human brain activation during delayed grasping and reaching. Specifically, we examined activation during visual stimulation and action execution separated by a 18-s delay interval in which subjects had to remember an intended action toward the remembered object. The long delay interval enabled us to unambiguously distinguish visual, memory-related, and action responses. Most strikingly, we observed reactivation of the lateral occipital complex (LOC, a ventral-stream area implicated in visual object recognition, and early visual cortex (EVC at the time of action. Importantly this reactivation was observed even though participants remained in complete darkness with no visual stimulation at the time of the action. Moreover, within EVC, higher activation was observed for grasping than reaching during both vision and action execution. Areas in the dorsal visual stream were activated during action execution as expected and, for some, also during vision. Several areas, including the anterior intraparietal sulcus (aIPS, dorsal premotor cortex (PMd, primary motor cortex (M1 and the supplementary motor area (SMA, showed sustained activation during the delay phase. We propose that during delayed actions, dorsal-stream areas plan and maintain coarse action goals; however, at the time of execution, motor programming requires re-recruitment of detailed visual information about the object through reactivation of (1 ventral-stream areas involved in object perception and (2 early visual areas that contain richly detailed visual representations, particularly for grasping.

  12. Strawberry Achenes Are an Important Source of Bioactive Compounds for Human Health

    Directory of Open Access Journals (Sweden)

    María Teresa Ariza

    2016-07-01

    Full Text Available Strawberries are highly appreciated for their taste, nutritional value and antioxidant compounds, mainly phenolics. Fruit antioxidants derive from achenes and flesh, but achene contribution to the total fruit antioxidant capacity and to the bioaccessibility after intake is still unknown. In this work, the content of total phenolic compounds, flavonoids, anthocyanins and antioxidant capacity (TEAC, FRAP and DPPH of achenes and flesh were compared in non-digested as well as in gastric and intestinal extracts after in vitro digestion. Results showed that, despite strawberry achenes represent a small fraction of the fruit, their contribution to total fruit antioxidant content was more than 41% and accounted for 81% of antioxidant capacity (TEAC. Achenes have higher quantity and different quality of antioxidants in non-digested and digested extracts. Antioxidant release was higher in the in vitro gastric digested extracts, but digestion conditions did not only affect quantity but quality, resulting in differences in antioxidant capacity and highlighting the importance of simulating physiological-like extraction conditions for assessing fruit antioxidant properties on human health. These results give new insights into the use of strawberry achenes as a source of bioactive compounds to be considered in strawberry breeding programs for improving human health.

  13. Strawberry Achenes Are an Important Source of Bioactive Compounds for Human Health

    Science.gov (United States)

    Ariza, María Teresa; Reboredo-Rodríguez, Patricia; Mazzoni, Luca; Forbes-Hernández, Tamara Yuliett; Giampieri, Francesca; Afrin, Sadia; Gasparrini, Massimiliano; Soria, Carmen; Martínez-Ferri, Elsa; Battino, Maurizio; Mezzetti, Bruno

    2016-01-01

    Strawberries are highly appreciated for their taste, nutritional value and antioxidant compounds, mainly phenolics. Fruit antioxidants derive from achenes and flesh, but achene contribution to the total fruit antioxidant capacity and to the bioaccessibility after intake is still unknown. In this work, the content of total phenolic compounds, flavonoids, anthocyanins and antioxidant capacity (TEAC, FRAP and DPPH) of achenes and flesh were compared in non-digested as well as in gastric and intestinal extracts after in vitro digestion. Results showed that, despite strawberry achenes represent a small fraction of the fruit, their contribution to total fruit antioxidant content was more than 41% and accounted for 81% of antioxidant capacity (TEAC). Achenes have higher quantity and different quality of antioxidants in non-digested and digested extracts. Antioxidant release was higher in the in vitro gastric digested extracts, but digestion conditions did not only affect quantity but quality, resulting in differences in antioxidant capacity and highlighting the importance of simulating physiological-like extraction conditions for assessing fruit antioxidant properties on human health. These results give new insights into the use of strawberry achenes as a source of bioactive compounds to be considered in strawberry breeding programs for improving human health. PMID:27409612

  14. Human dorsal striatum encodes prediction errors during observational learning of instrumental actions.

    Science.gov (United States)

    Cooper, Jeffrey C; Dunne, Simon; Furey, Teresa; O'Doherty, John P

    2012-01-01

    The dorsal striatum plays a key role in the learning and expression of instrumental reward associations that are acquired through direct experience. However, not all learning about instrumental actions require direct experience. Instead, humans and other animals are also capable of acquiring instrumental actions by observing the experiences of others. In this study, we investigated the extent to which human dorsal striatum is involved in observational as well as experiential instrumental reward learning. Human participants were scanned with fMRI while they observed a confederate over a live video performing an instrumental conditioning task to obtain liquid juice rewards. Participants also performed a similar instrumental task for their own rewards. Using a computational model-based analysis, we found reward prediction errors in the dorsal striatum not only during the experiential learning condition but also during observational learning. These results suggest a key role for the dorsal striatum in learning instrumental associations, even when those associations are acquired purely by observing others.

  15. Compound K induced apoptosis via endoplasmic reticulum Ca2+ release through ryanodine receptor in human lung cancer cells

    Directory of Open Access Journals (Sweden)

    Dong-Hyun Shin

    2018-04-01

    Full Text Available Background: Extended endoplasmic reticulum (ER stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. Methods: The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. Results: Compound K-induced ER stress was confirmed through increased phosphorylation of eIF2α and protein levels of GRP78/BiP, XBP-1S, and IRE1α in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular Ca2+ chelator or dantrolene (an RyR channel antagonist. These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12 partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor dramatically improved the compound K-induced apoptosis. Conclusion: Cell survival and intracellular Ca2+ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway. Keywords: apoptosis, calcium, compound K, ER stress, lung cancer cells

  16. Normative findings of electrically evoked compound action potential measurements using the neural response telemetry of the Nucleus CI24M cochlear implant system.

    NARCIS (Netherlands)

    Cafarelli-Dees, D.; Dillier, N.; Lai, W.K.; Wallenberg, E. von; Dijk, B. van; Akdas, F.; Aksit, M.; Batman, C.; Beynon, A.J.; Burdo, S.; Chanal, J.M.; Collet, L.; Conway, M.; Coudert, C.; Craddock, L.; Cullington, H.; Deggouj, N.; Fraysse, B.; Grabel, S.; Kiefer, J.; Kiss, J.G.; Lenarz, T.; Mair, A.; Maune, S.; Muller-Deile, J.; Piron, J.P.; Razza, S.; Tasche, C.; Thai-Van, H.; Toth, F.; Truy, E.; Uziel, A.; Smoorenburg, G.F.

    2005-01-01

    One hundred and forty-seven adult recipients of the Nucleus 24 cochlear implant system, from 13 different European countries, were tested using neural response telemetry to measure the electrically evoked compound action potential (ECAP), according to a standardised postoperative measurement

  17. Efficient Human Action and Gait Analysis Using Multiresolution Motion Energy Histogram

    Directory of Open Access Journals (Sweden)

    Kuo-Chin Fan

    2010-01-01

    Full Text Available Average Motion Energy (AME image is a good way to describe human motions. However, it has to face the computation efficiency problem with the increasing number of database templates. In this paper, we propose a histogram-based approach to improve the computation efficiency. We convert the human action/gait recognition problem to a histogram matching problem. In order to speed up the recognition process, we adopt a multiresolution structure on the Motion Energy Histogram (MEH. To utilize the multiresolution structure more efficiently, we propose an automated uneven partitioning method which is achieved by utilizing the quadtree decomposition results of MEH. In that case, the computation time is only relevant to the number of partitioned histogram bins, which is much less than the AME method. Two applications, action recognition and gait classification, are conducted in the experiments to demonstrate the feasibility and validity of the proposed approach.

  18. Structure Properties and Mechanisms of Action of Naturally Originated Phenolic Acids and Their Derivatives against Human Viral Infections.

    Science.gov (United States)

    Wu, Yi-Hang; Zhang, Bing-Yi; Qiu, Li-Peng; Guan, Rong-Fa; Ye, Zi-Hong; Yu, Xiao-Ping

    2017-01-01

    A great effort has been made to develop efficacious antiviral drugs, but many viral infections are still lack of efficient antiviral therapies so far. The related exploration of natural products to fight viruses has been raised in recent years. Natural compounds with structural diversity and complexity offer a great chance to find new antiviral agents. Particularly, phenolic acids have attracted considerable attention owing to their potent antiviral abilities and unique mechanisms. The aim of this review is to report new discoveries and updates pertaining to antiviral phenolic acids. The relevant references on natural phenolic acids were searched. The antiviral phenolic acids were classified according to their structural properties and antiviral types. Meanwhile, the antiviral characteristics and structure-activity relationships of phenolic acids and their derivatives were summarized. The review finds that natural phenolic acids and their derivatives possessed potent inhibitory effects on multiple virus in humans such as human immunodeficiency virus, hepatitis C virus, hepatitis B virus, herpes simplex virus, influenza virus and respiratory syncytial virus. In particular, caffeic acid/gallic acid and their derivatives exhibited outstanding antiviral properties by a variety of modes of action. Naturally derived phenolic acids especially caffeic acid/gallic acid and their derivatives may be regarded as novel promising antiviral leads or candidates. Additionally, scarcely any of these compounds has been used as antiviral treatment in clinical practice. Therefore, these phenolic acids with diverse skeletons and mechanisms provide us an excellent resource for finding novel antiviral drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Perfluorinated compounds in human serum and seminal plasma from an urban and rural population in Sri Lanka

    Energy Technology Data Exchange (ETDEWEB)

    Guruge, Keerthi; Miyazaki, Shigeru; Yamanaka, Noriko [National Institute of Animal Health, Tsukuba (Japan); Taniyasu, Sacgu; Yamashita, Nobuyoshi [National Institute of Advance Industrial and Technology, Tsukuba (Japan); Wijeratna, S.; Seneviratne, H. [Colombo Univ. (Sri Lanka)

    2004-09-15

    Fluorinated organic compounds (FOCs) have been used for variety of industrial applications such as surfactants, adhesives, insecticides, and their global production increase since 1970s. These compounds repel both water and oil. The high-energy carbon-fluorine covalent bonds in FOCs are strong enough to have high persistency in the environment. These compounds emerged as priory environmental pollutants since they are found in various biota throughout the world. Human contamination of some FOCs was reported mostly in developed countries such as USA, Japan and from Europe. In the present study, we report 10 FOCs in human serum including seminal plasma for the first time, collected from volunteers from Sri Lanka.

  20. HiRITER - An evaluation tool to reduce the adverse effect of inappropriate human actions in nuclear power plants

    International Nuclear Information System (INIS)

    Park, J.; Jung, W.; Kim, J.; Kim, S.; Heo, G.

    2012-01-01

    From end-users to regulatory bodies, it is widely recognized that human-induced events including inappropriate human actions are one of the most crucial sources degrading the overall safety of nuclear power plants (NPPs). This means that a systematic framework through which inappropriate human actions can be effectively identified is necessary to enhance the safety of NPPs. For this reason, HiRITER (High Risk Inducible Task Evaluator) has been developed, which is able to evaluate the effect of inappropriate human actions on risk as well as performance. To this end, HiRITER integrates three modules that have distinctive roles: human error prediction module that is able to determine the types of failure modes resulting from inappropriate human actions with the associated daily task, performance evaluation module that computes the loss of electric power due to the change of component configurations caused by human error and risk evaluation module that clarifies whether or not the propagation of human error can trigger an unexpected shutdown of NPPs. In addition, a couple of real events that had occurred in domestic NPPs are simulated in order to validate the feasibility of HiRITER. As a result, it is observed that the results of HiRITER are largely congruent with those of real events. Therefore, although a huge amount of additional effort is indispensable to enhance the overall accuracy of estimated results, it is expected that HiRITER could be a good starting point to reduce the adverse effect of inappropriate human actions in NPPs

  1. Human rights literacy: Moving towards rights-based education and transformative action through understandings of dignity, equality and freedom

    Directory of Open Access Journals (Sweden)

    Anne Becker

    2015-05-01

    Full Text Available The twentieth century has been characterised by the proliferation of human rights in the discursive practices of the United Nations (Baxi, 1997. In this article, we explore the continual process of rights-based education towards transformative action, and an open and democratic society, as dependent upon the facilitation of human rights literacy in teacher training. Our theoretical framework examines the continual process of moving towards an open and democratic society through the facilitation of human rights literacy, rights-based education and transformative action. We focus specifically on understandings of dignity, equality and freedom, as both rights (legal claims and values (moral action across horizontal and vertical applications, considering the internalisation and implementation of dignity, equality and freedom towards transformative action. Our analysis of data stemming from a project funded by the National Research Foundation (NRF entitled 'Human Rights Literacy: A quest for meaning', brought student-teachers' understandings into conversation with the proposed theoretical framework. In terms of understandings related to dignity, equality and freedom, participants seemingly understand human rights either as legal interests, or alternatively, as they pertain to values such as caring, ubuntu, respect, human dignity and equality. Legal understandings primarily focus on the vertical application of the Bill of Rights (RSA, 1996a and the role of government in this regard, whereas understandings related to the realisation of values tended to focus on the horizontal applications of particularly dignity and equality as the product of the relation between self and other. We conclude the article by linking the analysis and the theoretical framework to education as a humanising practice within human rights as a common language of humanity. In so doing, we argue that human rights literacy and rights-based education transcend knowledge about human

  2. Two Equals One: Two Human Actions During Social Interaction Are Grouped as One Unit in Working Memory.

    Science.gov (United States)

    Ding, Xiaowei; Gao, Zaifeng; Shen, Mowei

    2017-09-01

    Every day, people perceive other people performing interactive actions. Retaining these actions of human agents in working memory (WM) plays a pivotal role in a normal social life. However, whether the semantic knowledge embedded in the interactive actions has a pervasive impact on the storage of the actions in WM remains unknown. In the current study, we investigated two opposing hypotheses: (a) that WM stores the interactions individually (the individual-storage hypothesis) and (b) that WM stores the interactions as chunks (the chunk-storage hypothesis). We required participants to memorize a set of individual actions while ignoring the underlying social interactions. We found that although the social-interaction aspect was task irrelevant, the interactive actions were stored in WM as chunks that were not affected by memory load (Experiments 1 and 2); however, inverting the human actions vertically abolished this chunking effect (Experiment 3). These results suggest that WM automatically and efficiently used semantic knowledge about interactive actions to store them and support the chunk-storage hypothesis.

  3. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    International Nuclear Information System (INIS)

    Fischer, L.; Deppert, W.R.; Pfeifer, D.; Stanzel, S.; Weimer, M.; Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P.; Schaefer, W.R.

    2012-01-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  4. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  5. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    Science.gov (United States)

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  6. Adjuvants and Their Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Masoumeh Foumani

    2012-09-01

    Full Text Available Adjuvants are chemicals, microbial components, or mammalian proteins that enhance the immune response to vaccine antigens. Reducing vaccine-related adverse effects and inducing specific types of immunity has led to the development of numerous new adjuvants. Adjuvants in experimental and commercial vaccines include aluminum salts (alum, oil emulsions, saponins, immune-stimulating complexes (ISCOMs, liposomes, microparticles, nonionic block copolymers, derivatized polysaccharides, cytokines, and a wide variety of bacterial derivatives. The mechanisms of action of these diverse compounds are different. Factors influencing the selection of an adjuvant include animal species, specific pathogen, vaccine antigen, route of immunization, and type of immunity needed. In this paper we review the current adjuvant types, structure and mechanism of action and their application in the design and production of animal and human vaccines to provide a source for students and researchers in related fields .

  7. How to support action prediction: Evidence from human coordination tasks

    DEFF Research Database (Denmark)

    Vesper, Cordula

    2014-01-01

    When two or more people perform actions together such as shaking hands, playing ensemble music or carrying an object together, they often naturally adjust the spatial and temporal parameters of their movements to facilitate smooth task performance. This paper reviews recent findings from experime......When two or more people perform actions together such as shaking hands, playing ensemble music or carrying an object together, they often naturally adjust the spatial and temporal parameters of their movements to facilitate smooth task performance. This paper reviews recent findings from......”) might be a useful approach also for robotic systems to assist human users, thereby reducing cognitive load and flexibly supporting the acquisition of new skills....

  8. Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    Science.gov (United States)

    Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

    2017-04-01

    Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

  9. Inhibition of ultraviolet irradiation response of human skin by topical phlogostatic compounds

    International Nuclear Information System (INIS)

    Weirich, E.G.; Lutz, U.C.

    1977-01-01

    By adaption of the model of UV dermatitis in human skin a test procedure has been developed which facilitates realistic assessment of topical contra-inflammatory activity of steroidal as well as non-steroidal compounds. Sixt typical skin drug agents were tested according to their reaction inhibition effect. (orig./MG) [de

  10. Developing Library GIS Services for Humanities and Social Science: An Action Research Approach

    Science.gov (United States)

    Kong, Ningning; Fosmire, Michael; Branch, Benjamin Dewayne

    2017-01-01

    In the academic libraries' efforts to support digital humanities and social science, GIS service plays an important role. However, there is no general service model existing about how libraries can develop GIS services to best engage with digital humanities and social science. In this study, we adopted the action research method to develop and…

  11. Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia.

    Science.gov (United States)

    Bouhenna, Mustapha M; Orlikova, Barbora; Talhi, Oualid; Schram, Ben; Pinto, Diana C G A; Taibi, Nadia; Bachari, Khaldoun; Diederich, Marc; Silva, Artur M S; Mameri, Nabil

    2017-09-01

    NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Mesoionic Compounds

    Indian Academy of Sciences (India)

    Organic Chemistry. Kamatak University,. Dharwad. Her research interests are synthesis, reactions and synthetic utility of sydnones. She is currently working on electrochemical and insecticidal/antifungal activities for some of these compounds. Keywords. Aromaticity, mesoionic hetero- cycles, sydnones, tandem re- actions.

  13. Catalytic properties of niobium compounds

    International Nuclear Information System (INIS)

    Tanabe, K.; Iizuka, T.

    1983-04-01

    The catalytic activity and selectivity of niobium compounds including oxides, salts, organometallic compounds and others are outlined. The application of these compounds as catalysts to diversified reactions is reported. The nature and action of niobium catalysts are characteristic and sometimes anomalous, suggesting the necessity of basic research and the potential use as catalysts for important processes in the chemical industry. (Author) [pt

  14. Simultaneous quantitative analysis of nine vitamin D compounds in human blood using LC-MS/MS.

    Science.gov (United States)

    Abu Kassim, Nur Sofiah; Gomes, Fabio P; Shaw, Paul Nicholas; Hewavitharana, Amitha K

    2016-01-01

    It has been suggested that each member of the family of vitamin D compounds may have different function(s). Therefore, selective quantification of each compound is important in clinical research. Development and validation attempts of a simultaneous determination method of 12 vitamin D compounds in human blood using precolumn derivatization followed by LC-MS/MS is described. Internal standard calibration with 12 stable isotope labeled analogs was used to correct for matrix effects in MS detector. Nine vitamin D compounds were quantifiable in blood samples with detection limits within femtomole levels. Serum (compared with plasma) was found to be a more suitable sample type, and protein precipitation (compared with saponification) a more effective extraction method for vitamin D assay.

  15. Pro-oxidative and pro-apoptotic action of defatted seeds of Oenothera paradoxa on human skin melanoma cells.

    Science.gov (United States)

    Jaszewska, Edyta; Kośmider, Anita; Kiss, Anna K; Naruszewicz, Marek

    2009-09-23

    Three extracts of defatted seeds of Oenothera paradoxa Hudziok, aqueous extract, 60% ethanolic extract, and 30% isopropanolic extract, differing by their total content of phenolic compounds and by their contents of individual polyphenols, were investigated in this study. The extracts exerted cytotoxic action on HTB-140 human skin melanoma cells. After 24 h of incubation, IC(50) values of 169.7 +/- 5.9 micog/mL, 72.4 +/- 3.8 microg/mL, and 155.3 +/- 6.3 microg/mL were obtained for HTB-140 cells with the aqueous extract, 60% ethanolic extract, and 30% isopropanolic extract at the tested concentrations (5-200 microg/mL), respectively, while IC(50) for normal fibroblast cells NHDFs was not attained. Moreover, for HTB-140 cells, LD(50) (concentration at which 50% of cells were dead) of 89.2 +/- 4.3 microg/mL and 181.4 +/- 6.5 microg/mL were obtained with 60% ethanolic extract and 30% isopropanolic extract, respectively. In melanoma cells, all three extracts caused a concentration-dependent increase of ROS production, GSH, and ATP lowering, and appearance of phosphatidylserine on the external surface of cellular membranes where it was bound to annexin V-FITC; furthermore, apoptosis without activation of caspase-3 took place. The most effective was 60% ethanolic extract, which had the greatest total content of phenolic compounds and the greatest content of pentagalloyloglucose (PGG).

  16. Mode of action of alginic acid compound in the reduction of gastroesophageal reflux

    International Nuclear Information System (INIS)

    Malmud, L.S.; Charkes, N.D.; Littlefield, J.; Reilley, J.; Stern, H.; Rosenberg, R.; Fisher, R.S.

    1979-01-01

    This study was designed to evaluate quantitatively the mode of action of alginic acid compound (AAC) in the treatment of patients with symptomatic gastroesophageal reflux. Gastroesophageal scintigraphy using an orally administered Tc-99m sulfur colloid solution was used to demonstrate that AAC decreased significantly the gastroesophageal reflux index from (9.9 +- 1.3)% to (6.5 +- 0.8)% (p < 0.05). No alteration of lower esophageal sphincter pressure was observed. After AAC was suitably labeled with Sr-87m, a dual-nuclide scintigraphic technique was used to show that most (< 75%) of the AAC was located in the upper half of the stomach in both normal subjects and patients with gastroesophageal reflux. In those subjects in whom reflux did occur after treatment with AAC, the Sr-87m-AAC refluxed into the esophagus preferentially compared with the liquid containing Tc-99m sulfur colloid. These findings suggest that AAC diminishes gastroesophageal reflux by means of its foaming, floating, and viscous properties

  17. Human action contribution to ET-RR-II reactor systems unstems unavailability

    International Nuclear Information System (INIS)

    Sabek, M.G.

    2001-01-01

    This paper gives a study on the human action contribution to the systems unavailability of ET-RR-II reactor as a result of the test and maintenance procedures. The human contribution is expressed in terms of Fussel-Vesely importance which is defined by the probability that event is contributing to system failure (unavailability). The human error basic events contribution was analyzed for all initiating events and systems fault trees. The calculations result shows a high contribution value (61%) for the human error to systems unavailability. This means that the operator and the maintenance people should be highly qualified trained. Moreover, there should be programs for continuous training. Also, the procedures of tests and maintenance should be in a simple way and clear in order to minimize the contribution of the human errors. The calculations were done using the IRRAS cods

  18. Dioxin-like activity of environmental compounds in human blood and environmental samples

    DEFF Research Database (Denmark)

    Long, Manhai; Bonefeld-Jørgensen, Eva Cecilie

    2012-01-01

    and humans. We found that some pesticides, plasticizers and phytoestrogens can activate the AhR, and the combined effect of compounds with no or weak AhR potency cannot be ignored. The significant DL-activity in the wastewater effluent indicates the treatment is not sufficient to prevent contamination...... of surface waters with dioxins. Our results from human studies suggest that the serum DL-activity reflect the complex mixture of persistent organic pollutants (POPs). Greenlandic Inuit had lower serum DL-activity level compared to Europeans, probably due to long distance from the dioxin sources and UV...

  19. Human Intestinal Fluid Layer Separation: The Effect On Colloidal Structures & Solubility Of Lipophilic Compounds.

    Science.gov (United States)

    Danny, Riethorst; Amitava, Mitra; Filippos, Kesisoglou; Wei, Xu; Jan, Tack; Joachim, Brouwers; Patrick, Augustijns

    2018-05-23

    In addition to individual intestinal fluid components, colloidal structures are responsible for enhancing the solubility of lipophilic compounds. The present study investigated the link between as well as the variability in the ultrastructure of fed state human intestinal fluids (FeHIF) and their solubilizing capacity for lipophilic compounds. For this purpose, FeHIF samples from 10 healthy volunteers with known composition and ultrastructure were used to determine the solubility of four lipophilic compounds. In light of the focus on solubility and ultrastructure, the study carefully considered the methodology of solubility determination in relation to colloid composition and solubilizing capacity of FeHIF. To determine the solubilizing capacity of human and simulated intestinal fluids, the samples were saturated with the compound of interest, shaken for 24 h, and centrifuged. When using FeHIF, solubilities were determined in the micellar layer of FeHIF, i.e. after removing the upper (lipid) layer (standard procedure), as well as in 'full' FeHIF (without removal of the upper layer). Compound concentrations were determined using HPLC-UV/fluorescence. To link the solubilizing capacity with the ultrastructure, all human and simulated fluids were imaged using transmission electron microscopy (TEM) before and after centrifugation and top layer (lipid) removal. Comparing the ultrastructure and solubilizing capacity of individual FeHIF samples demonstrated a high intersubject variability in postprandial intestinal conditions. Imaging of FeHIF after removal of the upper layer clearly showed that only micellar structures remain in the lower layer. This observation suggests that larger colloids such as vesicles and lipid droplets are contained in the upper, lipid layer. The solubilizing capacity of most FeHIF samples substantially increased with inclusion of this lipid layer. The relative increase in solubilizing capacity upon inclusion of the lipid layer was most pronounced

  20. Researcher liability for negligence in human subject research: informed consent and researcher malpractice actions.

    Science.gov (United States)

    Jansson, Roger L

    2003-02-01

    Two sets of federal regulations, the "Common Rule" and Food and Drug Administration (FDA) regulations, govern human subject research that is either federally-funded or involves FDA regulated products. These regulations require, inter alia, that: (1) researchers obtain informed consent from human subjects, and (2) that an Institutional Review Board (IRB) independently review and approve the research protocol. Although the federal regulations do not provide an express cause of action against researchers, research subjects should be able to bring informed consent and malpractice actions against researchers by establishing a duty of care and standard of care. Researchers owe human subjects a duty of care analogous to the special relationship between physicians and patients. The federal regulations should provide the minimum standard of care for informed consent in human subject research, and complying with them should be a partial defense. In contrast, expert testimony should establish the standard of care for researcher malpractice, and IRB approval should be a partial defense.

  1. Is Insulin Action in the Brain Relevant in Regulating Blood Glucose in Humans?

    Science.gov (United States)

    Dash, Satya; Xiao, Changting; Morgantini, Cecilia; Koulajian, Khajag; Lewis, Gary F

    2015-07-01

    In addition to its direct action on the liver to lower hepatic glucose production, insulin action in the central nervous system (CNS) also lowers hepatic glucose production in rodents after 4 hours. Although CNS insulin action (CNSIA) modulates hepatic glycogen synthesis in dogs, it has no net effect on hepatic glucose output over a 4-hour period. The role of CNSIA in regulating plasma glucose has recently been examined in humans and is the focus of this review. Intransal insulin (INI) administration increases CNS insulin concentration. Hence, INI can address whether CNSIA regulates plasma glucose concentration in humans. We and three other groups have sought to answer this question, with differing conclusions. Here we will review the critical aspects of each study, including its design, which may explain these discordant conclusions. The early glucose-lowering effect of INI is likely due to spillover of insulin into the systemic circulation. In the presence of simultaneous portal and CNS hyperinsulinemia, portal insulin action is dominant. INI administration does lower plasma glucose independent of peripheral insulin concentration (between ∼3 and 6 h after administration), suggesting that CNSIA may play a role in glucose homeostasis in the late postprandial period when its action is likely greatest and portal insulin concentration is at baseline. The potential physiological role and purpose of this pathway are discussed in this review. Because the effects of INI are attenuated in patients with type 2 diabetes and obesity, this is unlikely to be of therapeutic utility.

  2. Coumarin Antifungal Lead Compounds from Millettia thonningii and Their Predicted Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Daniel M. Ayine-Tora

    2016-10-01

    Full Text Available Fungal pathogens continue to pose challenges to humans and plants despite efforts to control them. Two coumarins, robustic acid and thonningine-C isolated from Millettia thonningii, show promising activity against the fungus Candida albicans with minimum fungicidal concentration of 1.0 and 0.5 mg/mL, respectively. Molecular modelling against the putative bio-molecular target, lanosterol 14α-demethylase (CYP51, revealed a plausible binding mode for the active compounds, in which the hydroxyl group binds with a methionine backbone carboxylic group blocking access to the iron catalytic site. This binding disrupts the synthesis of several important sterols for the survival of fungi.

  3. Exposure to perfluorinated compounds and human semen quality in arctic and European populations

    NARCIS (Netherlands)

    Toft, G.; Jönsson, B.A.G.; Lindh, C.H.; Giwercman, A.; Spano, M.; Heederik, D.J.J.; Lenters, V.C.; Vermeulen, R.C.H.; Rylander, L.; Pedersen, H.S.; Ludwicki, J.K.; Zviezdai, V.; Bonde, J.P.

    2012-01-01

    BACKGROUND Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality. METHODS PFCs were measured in serum from 588 partners of pregnant women from Greenland,

  4. GestuRe and ACtion Exemplar (GRACE) video database: stimuli for research on manners of human locomotion and iconic gestures.

    Science.gov (United States)

    Aussems, Suzanne; Kwok, Natasha; Kita, Sotaro

    2018-06-01

    Human locomotion is a fundamental class of events, and manners of locomotion (e.g., how the limbs are used to achieve a change of location) are commonly encoded in language and gesture. To our knowledge, there is no openly accessible database containing normed human locomotion stimuli. Therefore, we introduce the GestuRe and ACtion Exemplar (GRACE) video database, which contains 676 videos of actors performing novel manners of human locomotion (i.e., moving from one location to another in an unusual manner) and videos of a female actor producing iconic gestures that represent these actions. The usefulness of the database was demonstrated across four norming experiments. First, our database contains clear matches and mismatches between iconic gesture videos and action videos. Second, the male actors and female actors whose action videos matched the gestures in the best possible way, perform the same actions in very similar manners and different actions in highly distinct manners. Third, all the actions in the database are distinct from each other. Fourth, adult native English speakers were unable to describe the 26 different actions concisely, indicating that the actions are unusual. This normed stimuli set is useful for experimental psychologists working in the language, gesture, visual perception, categorization, memory, and other related domains.

  5. Effect of lipopolysaccharide on inflammation and insulin action in human muscle.

    Science.gov (United States)

    Liang, Hanyu; Hussey, Sophie E; Sanchez-Avila, Alicia; Tantiwong, Puntip; Musi, Nicolas

    2013-01-01

    Accumulating evidence from animal studies suggest that chronic elevation of circulating intestinal-generated lipopolysaccharide (LPS) (i.e., metabolic endotoxemia) could play a role in the pathogenesis of insulin resistance. However, the effect of LPS in human muscle is unclear. Moreover, it is unknown whether blockade/down regulation of toll-like receptor (TLR)4 can prevent the effect of LPS on insulin action and glucose metabolism in human muscle cells. In the present study we compared plasma LPS concentration in insulin resistant [obese non-diabetic and obese type 2 diabetic (T2DM)] subjects versus lean individuals. In addition, we employed a primary human skeletal muscle cell culture system to investigate the effect of LPS on glucose metabolism and whether these effects are mediated via TLR4. Obese non-diabetic and T2DM subjects had significantly elevated plasma LPS and LPS binding protein (LBP) concentrations. Plasma LPS (r = -0.46, P = 0.005) and LBP (r = -0.49, P = 0.005) concentrations negatively correlated with muscle insulin sensitivity (M). In human myotubes, LPS increased JNK phosphorylation and MCP-1 and IL-6 gene expression. This inflammatory response led to reduced insulin-stimulated IRS-1, Akt and AS160 phosphorylation and impaired glucose transport. Both pharmacologic blockade of TLR4 with TAK-242, and TLR4 gene silencing, suppressed the inflammatory response and insulin resistance caused by LPS in human muscle cells. Taken together, these findings suggest that elevations in plasma LPS concentration found in obese and T2DM subjects could play a role in the pathogenesis of insulin resistance and that antagonists of TLR4 may improve insulin action in these individuals.

  6. Analytical method for biomonitoring of endocrine-disrupting compounds (bisphenol A, parabens, perfluoroalkyl compounds and a brominated flame retardant) in human hair by liquid chromatography-tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Martín, Julia; Santos, Juan Luis; Aparicio, Irene, E-mail: iaparicio@us.es; Alonso, Esteban

    2016-11-16

    In this paper, a method for the determination of four groups of endocrine-disrupting compounds in human hair is proposed. Target compounds were a plastic monomer (bisphenol A), three parabens commonly used as preservatives (methylparaben, ethylparaben and propylparaben), six perfluoroalkyl compounds commonly used as water, oil and dirt repellents (perfluorooctane sulfonic acid and five perfluoroalkyl carboxylic acids, with alkyl chains from four to eight carbon atoms) and a brominated flame retardant (hexabromocyclododecane). All of them are of especial concern to human health because they are utilized in many everyday products. The method is based on hair incubation with methanol/acetic acid solution (85:15, v/v), extraction with acetone for 15 min in an ultrasonic bath and analysis by liquid chromatography-electrospray-tandem mass spectrometry in negative ionization mode. Limits of quantification in hair samples ranged from 0.6 ng g{sup −1} to 6.1 ng g{sup −1}, except for hexabromocyclododecane (36 ng g{sup −1}). Recoveries were higher than 69%. Intra-day and inter-day precision, expressed as relative standard deviation, were lower than 15% and 10%, respectively. The applicability of the method was proven by analyzing the target compounds in hair samples from six volunteers. High frequencies of detection and concentrations were obtained for bisphenol A (83% of samples; concentrations up to 158 ng g{sup −1}) and parabens (100% of samples; concentrations up to 624 ng g{sup −1}). Lower concentrations were detected for the perfluoroalkyl compounds (up to 13 ng g{sup −1}). Hexabromocyclododecane was not detected. - Highlights: • Method for biomonitoring of endocrine-disrupting compounds in human hair. • Target compounds are commonly present in everyday products. • Method based on hair digestion and liquid chromatography-tandem mass spectrometry. • Good sensitivity, recoveries and precision and low matrix effect were obtained.

  7. Analytical method for biomonitoring of endocrine-disrupting compounds (bisphenol A, parabens, perfluoroalkyl compounds and a brominated flame retardant) in human hair by liquid chromatography-tandem mass spectrometry

    International Nuclear Information System (INIS)

    Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

    2016-01-01

    In this paper, a method for the determination of four groups of endocrine-disrupting compounds in human hair is proposed. Target compounds were a plastic monomer (bisphenol A), three parabens commonly used as preservatives (methylparaben, ethylparaben and propylparaben), six perfluoroalkyl compounds commonly used as water, oil and dirt repellents (perfluorooctane sulfonic acid and five perfluoroalkyl carboxylic acids, with alkyl chains from four to eight carbon atoms) and a brominated flame retardant (hexabromocyclododecane). All of them are of especial concern to human health because they are utilized in many everyday products. The method is based on hair incubation with methanol/acetic acid solution (85:15, v/v), extraction with acetone for 15 min in an ultrasonic bath and analysis by liquid chromatography-electrospray-tandem mass spectrometry in negative ionization mode. Limits of quantification in hair samples ranged from 0.6 ng g"−"1 to 6.1 ng g"−"1, except for hexabromocyclododecane (36 ng g"−"1). Recoveries were higher than 69%. Intra-day and inter-day precision, expressed as relative standard deviation, were lower than 15% and 10%, respectively. The applicability of the method was proven by analyzing the target compounds in hair samples from six volunteers. High frequencies of detection and concentrations were obtained for bisphenol A (83% of samples; concentrations up to 158 ng g"−"1) and parabens (100% of samples; concentrations up to 624 ng g"−"1). Lower concentrations were detected for the perfluoroalkyl compounds (up to 13 ng g"−"1). Hexabromocyclododecane was not detected. - Highlights: • Method for biomonitoring of endocrine-disrupting compounds in human hair. • Target compounds are commonly present in everyday products. • Method based on hair digestion and liquid chromatography-tandem mass spectrometry. • Good sensitivity, recoveries and precision and low matrix effect were obtained. • Method was successfully

  8. Comparing sequencing assays and human-machine analyses in actionable genomics for glioblastoma.

    Science.gov (United States)

    Wrzeszczynski, Kazimierz O; Frank, Mayu O; Koyama, Takahiko; Rhrissorrakrai, Kahn; Robine, Nicolas; Utro, Filippo; Emde, Anne-Katrin; Chen, Bo-Juen; Arora, Kanika; Shah, Minita; Vacic, Vladimir; Norel, Raquel; Bilal, Erhan; Bergmann, Ewa A; Moore Vogel, Julia L; Bruce, Jeffrey N; Lassman, Andrew B; Canoll, Peter; Grommes, Christian; Harvey, Steve; Parida, Laxmi; Michelini, Vanessa V; Zody, Michael C; Jobanputra, Vaidehi; Royyuru, Ajay K; Darnell, Robert B

    2017-08-01

    To analyze a glioblastoma tumor specimen with 3 different platforms and compare potentially actionable calls from each. Tumor DNA was analyzed by a commercial targeted panel. In addition, tumor-normal DNA was analyzed by whole-genome sequencing (WGS) and tumor RNA was analyzed by RNA sequencing (RNA-seq). The WGS and RNA-seq data were analyzed by a team of bioinformaticians and cancer oncologists, and separately by IBM Watson Genomic Analytics (WGA), an automated system for prioritizing somatic variants and identifying drugs. More variants were identified by WGS/RNA analysis than by targeted panels. WGA completed a comparable analysis in a fraction of the time required by the human analysts. The development of an effective human-machine interface in the analysis of deep cancer genomic datasets may provide potentially clinically actionable calls for individual patients in a more timely and efficient manner than currently possible. NCT02725684.

  9. Action of fluor and its compounds on plants

    Energy Technology Data Exchange (ETDEWEB)

    Kluczynski, B

    1976-01-01

    This paper contains a brief synthesis of data available from the literature and experimental studies on the influence of fluor and its compounds on plants. The basic part of the paper consists of a list of 301 plants (separately for trees and shrubs and separately for other plants) the resistance of which to fluor compounds has been estimated. The information on resistance has been collected either from field observations or from cabin studies (artificial gassing of plants). The plants have been assigned to three classes: resistant, medium resistant and susceptible. When the resistance has been reported on a more detailed scale than a 3 point one, the data was compressed with some approximation to these three classes. In the list only plants are included with a definite specific or varietal name.

  10. Stimulated human mast cells secrete mitochondrial components that have autocrine and paracrine inflammatory actions.

    Directory of Open Access Journals (Sweden)

    Bodi Zhang

    Full Text Available Mast cells are hematopoietically-derived tissue immune cells that participate in acquired and innate immunity, as well as in inflammation through release of many chemokines and cytokines, especially in response to the pro-inflammatory peptide substance P (SP. Inflammation is critical in the pathogenesis of many diseases, but the trigger(s is often unknown. We investigated if mast cell stimulation leads to secretion of mitochondrial components and whether these could elicit autocrine and/or paracrine inflammatory effects. Here we show that human LAD2 mast cells stimulated by IgE/anti-IgE or by the SP led to secretion of mitochondrial particles, mitochondrial (mt mtDNA and ATP without cell death. Mitochondria purified from LAD2 cells and, when mitochondria added to mast cells trigger degranulation and release of histamine, PGD(2, IL-8, TNF, and IL-1β. This stimulatory effect is partially inhibited by an ATP receptor antagonist and by DNAse. These results suggest that the mitochondrial protein fraction may also contribute. Purified mitochondria also stimulate IL-8 and vascular endothelial growth factor (VEGF release from cultured human keratinocytes, and VEGF release from primary human microvascular endothelial cells. In order to investigate if mitochondrial components could be secreted in vivo, we injected rats intraperiotoneally (ip with compound 48/80, which mimicks the action of SP. Peritoneal mast cells degranulated and mitochondrial particles were documented by transimission electron microscopy outside the cells. We also wished to investigate if mitochondrial components secreted locally could reach the systemic circulation. Administration ip of mtDNA isolated from LAD2 cells in rats was detected in their serum within 4 hr, indicating that extravascular mtDNA could enter the systemic circulation. Secretion of mitochondrial components from stimulated live mast cells may act as "autopathogens" contributing to the pathogenesis of inflammatory

  11. The human-animal relationship: a new field of socio-educational action

    Directory of Open Access Journals (Sweden)

    Joan-María Senent

    2014-07-01

    Full Text Available This article analyses the educational approaches towards the animal-human relationship which have been developed during the last 20 years. The article establishes a chain of states in that relationship and presents the reasons why those states are consecutive or, occasionally, simultaneous. Next, the different European profiles of social educators are reviewed to see which of these are more open towards educational action with animals, something which could be considered a new field for educators if they have adequate professional training. A series of European (and some American websites are analysed in order to determine their approach towards the human-animal relationship. Although most of them are related to animal-assisted therapy, some francophone and Italian websites show approaches that go beyond that. That could imply an extension of the social educators’ field of action. Indeed, French and Southern-European models are closer to that point than the rest of the profiles analysed, in terms of the openness and flexibility they show towards new fields.

  12. How to support action prediction: Evidence from human coordination tasks

    DEFF Research Database (Denmark)

    Vesper, Cordula

    2014-01-01

    When two or more people perform actions together such as shaking hands, playing ensemble music or carrying an object together, they often naturally adjust the spatial and temporal parameters of their movements to facilitate smooth task performance. This paper reviews recent findings from experime......”) might be a useful approach also for robotic systems to assist human users, thereby reducing cognitive load and flexibly supporting the acquisition of new skills....

  13. Inferring Action Structure and Causal Relationships in Continuous Sequences of Human Action

    Science.gov (United States)

    2014-01-01

    and MySQL . However, all participants participated from in-lab computers. Results Figure 6 shows the distribution of participants’ raw key presses... Java program to present video of action sequences and collect ratings. The program presented all 12 actions, non-actions, and part-actions

  14. Automated grouping of action potentials of human embryonic stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Gorospe, Giann; Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie; Vidal, Rene

    2014-09-01

    Methods for obtaining cardiomyocytes from human embryonic stem cells (hESCs) are improving at a significant rate. However, the characterization of these cardiomyocytes (CMs) is evolving at a relatively slower rate. In particular, there is still uncertainty in classifying the phenotype (ventricular-like, atrial-like, nodal-like, etc.) of an hESC-derived cardiomyocyte (hESC-CM). While previous studies identified the phenotype of a CM based on electrophysiological features of its action potential, the criteria for classification were typically subjective and differed across studies. In this paper, we use techniques from signal processing and machine learning to develop an automated approach to discriminate the electrophysiological differences between hESC-CMs. Specifically, we propose a spectral grouping-based algorithm to separate a population of CMs into distinct groups based on the similarity of their action potential shapes. We applied this method to a dataset of optical maps of cardiac cell clusters dissected from human embryoid bodies. While some of the nine cell clusters in the dataset are presented with just one phenotype, the majority of the cell clusters are presented with multiple phenotypes. The proposed algorithm is generally applicable to other action potential datasets and could prove useful in investigating the purification of specific types of CMs from an electrophysiological perspective.

  15. President's Committee on the Arts and the Humanities 2009-2016: A Legacy of Action

    Science.gov (United States)

    President's Committee on the Arts and the Humanities, 2016

    2016-01-01

    The "President's Committee on the Arts and the Humanities 2009-2016: A Legacy of Action" highlights the results of the synergy of collaboration the President's Committee on the Arts and the Humanities (PCAH) forged with the private sector and each of the cultural agencies--National Endowment for the Arts, National Endowment for the…

  16. Erythropoietin enhances hippocampal response during memory retrieval in humans

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla; O'Sullivan, Ursula; Harmer, Catherine J

    2007-01-01

    Although erythropoietin (Epo) is best known for its effects on erythropoiesis, recent evidence suggests that it also has neurotrophic and neuroprotective properties in animal models of hippocampal function. Such an action in humans would make it an intriguing novel compound for the treatment....... This is consistent with upregulation of hippocampal BDNF and neurotrophic actions found in animals and highlights Epo as a promising candidate for treatment of psychiatric disorders....

  17. Modes of Action of Microbially-Produced Phytotoxins

    Science.gov (United States)

    Duke, Stephen O.; Dayan, Franck E.

    2011-01-01

    Some of the most potent phytotoxins are synthesized by microbes. A few of these share molecular target sites with some synthetic herbicides, but many microbial toxins have unique target sites with potential for exploitation by the herbicide industry. Compounds from both non-pathogenic and pathogenic microbes are discussed. Microbial phytotoxins with modes of action the same as those of commercial herbicides and those with novel modes of action of action are covered. Examples of the compounds discussed are tentoxin, AAL-toxin, auscaulitoxin aglycone, hydantocidin, thaxtomin, and tabtoxin. PMID:22069756

  18. Anxiolytic-Like Actions of Fatty Acids Identified in Human Amniotic Fluid

    Directory of Open Access Journals (Sweden)

    Rosa Isela García-Ríos

    2013-01-01

    Full Text Available Eight fatty acids (C12–C18 were previously identified in human amniotic fluid, colostrum, and milk in similar proportions but different amounts. Amniotic fluid is well known to be the natural environment for development in mammals. Interestingly, amniotic fluid and an artificial mixture of fatty acids contained in amniotic fluid produce similar anxiolytic-like actions in Wistar rats. We explored whether the lowest amount of fatty acids contained in amniotic fluid with respect to colostrum and milk produces such anxiolytic-like effects. Although a trend toward a dose-response effect was observed, only an amount of fatty acids that was similar to amniotic fluid fully mimicked the effect of diazepam (2 mg/kg, i.p. in the defensive burying test, an action devoid of effects on locomotor activity and motor coordination. Our results confirm that the amount of fatty acids contained in amniotic fluid is sufficient to produce anxiolytic-like effects, suggesting similar actions during intrauterine development.

  19. By the sound of it. An ERP investigation of human action sound processing in 7-month-old infants

    Directory of Open Access Journals (Sweden)

    Elena Geangu

    2015-04-01

    Full Text Available Recent evidence suggests that human adults perceive human action sounds as a distinct category from human vocalizations, environmental, and mechanical sounds, activating different neural networks (Engel et al., 2009; Lewis et al., 2011. Yet, little is known about the development of such specialization. Using event-related potentials (ERP, this study investigated neural correlates of 7-month-olds’ processing of human action (HA sounds in comparison to human vocalizations (HV, environmental (ENV, and mechanical (MEC sounds. Relative to the other categories, HA sounds led to increased positive amplitudes between 470 and 570 ms post-stimulus onset at left anterior temporal locations, while HV led to increased negative amplitudes at the more posterior temporal locations in both hemispheres. Collectively, human produced sounds (HA + HV led to significantly different response profiles compared to non-living sound sources (ENV + MEC at parietal and frontal locations in both hemispheres. Overall, by 7 months of age human action sounds are being differentially processed in the brain, consistent with a dichotomy for processing living versus non-living things. This provides novel evidence regarding the typical categorical processing of socially relevant sounds.

  20. MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Maywan Hariono

    2016-05-01

    Full Text Available A study on molecular docking-based virtual screening has been conducted to select virtual hit of compounds, reported its existence in fungal endophytes of Chaetomium sp. as cytotoxic agent of breast cancer. The ligands were docked into Human Estrogen Receptor alpha (HERa as the protein which regulates the breast cancer growth via estradiol-estrogen receptor binding intervention. The results showed that two compounds bearing xanthone and two compounds bearing benzonaphtyridinedione scaffolds were selected as virtual hit ligands for HERa leading to the conclusion that these compounds were good to be developed as anti breast cancer.

  1. Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum

    Science.gov (United States)

    Vaidya, Akhil B.; Morrisey, Joanne M.; Zhang, Zhongsheng; Das, Sudipta; Daly, Thomas M.; Otto, Thomas D.; Spillman, Natalie J.; Wyvratt, Matthew; Siegl, Peter; Marfurt, Jutta; Wirjanata, Grennady; Sebayang, Boni F.; Price, Ric N.; Chatterjee, Arnab; Nagle, Advait; Stasiak, Marcin; Charman, Susan A.; Angulo-Barturen, Iñigo; Ferrer, Santiago; Belén Jiménez-Díaz, María; Martínez, María Santos; Gamo, Francisco Javier; Avery, Vicky M.; Ruecker, Andrea; Delves, Michael; Kirk, Kiaran; Berriman, Matthew; Kortagere, Sandhya; Burrows, Jeremy; Fan, Erkang; Bergman, Lawrence W.

    2014-01-01

    The quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na+ regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na+ homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na+ homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes. PMID:25422853

  2. Non-occlusive topical exposure of human skin in vitro as model for cytotoxicity testing of irritant compounds.

    Science.gov (United States)

    Lönnqvist, Susanna; Briheim, Kristina; Kratz, Gunnar

    2016-02-01

    Testing of irritant compounds has traditionally been performed on animals and human volunteers. Animal testing should always be restricted and for skin irritancy mice and rabbits hold poor predictive value for irritant potential in humans. Irritant testing on human volunteers is restricted by the duration subjects can be exposed, and by the subjectivity of interpreting the visual signs of skin irritation. We propose an irritant testing system using viable human full thickness skin with the loss of cell viability in the exposed skin area as end point measurement. Skin was exposed to sodium dodecyl sulfate (SDS) at 20% concentration by non-occluded topical exposure to establish a positive control response and subsequent test compounds were statistically compared with the 20% SDS response. Cell viability and metabolism were measured with 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The model presents correlation between increased concentration of SDS and decreased viability of cells in the exposed skin area (R(2) = 0.76). We propose the model to be used for cytotoxicity testing of irritant compounds. With fully intact barrier function, the model comprises all cells present in the skin with quantifiable end point measurement.

  3. Microencapsulated bitter compounds (from Gentiana lutea) reduce daily energy intakes in humans.

    Science.gov (United States)

    Mennella, Ilario; Fogliano, Vincenzo; Ferracane, Rosalia; Arlorio, Marco; Pattarino, Franco; Vitaglione, Paola

    2016-11-10

    Mounting evidence showed that bitter-tasting compounds modulate eating behaviour through bitter taste receptors in the gastrointestinal tract. This study aimed at evaluating the influence of microencapsulated bitter compounds on human appetite and energy intakes. A microencapsulated bitter ingredient (EBI) with a core of bitter Gentiana lutea root extract and a coating of ethylcellulose-stearate was developed and included in a vanilla microencapsulated bitter ingredient-enriched pudding (EBIP). The coating masked bitterness in the mouth, allowing the release of bitter secoiridoids in the gastrointestinal tract. A cross-over randomised study was performed: twenty healthy subjects consumed at breakfast EBIP (providing 100 mg of secoiridoids) or the control pudding (CP) on two different occasions. Blood samples, glycaemia and appetite ratings were collected at baseline and 30, 60, 120 and 180 min after breakfast. Gastrointestinal peptides, endocannabinoids (EC) and N-acylethanolamines (NAE) were measured in plasma samples. Energy intakes were measured at an ad libitum lunch 3 h after breakfast and over the rest of the day (post lunch) through food diaries. No significant difference in postprandial plasma responses of gastrointestinal hormones, glucose, EC and NAE and of appetite between EBIP and CP was found. However, a trend for a higher response of glucagon-like peptide-1 after EBIP than after CP was observed. EBIP determined a significant 30 % lower energy intake over the post-lunch period compared with CP. These findings were consistent with the tailored release of bitter-tasting compounds from EBIP along the gastrointestinal tract. This study demonstrated that microencapsulated bitter secoiridoids were effective in reducing daily energy intake in humans.

  4. Determination of the levels of dioxin and dioxin-like compounds in the Australian population by analysis of pooled human breast milk

    Energy Technology Data Exchange (ETDEWEB)

    Harden, F.; Mueller, J.F.; Toms, L.M.L.; Moore, M. [National Research Centre for Environmental Toxicology, The Univ. of Queensland, Brisbane (Australia); Burniston, D.; Symons, R. [AGAL, Sydney (Australia); Ahokas, J. [RMIT, Melbourne (Australia); Fuerst, P. [State Lab. of NRW, Muenster (Germany); Paepke, O. [ERGO Forschungsgesellschaft, Hamburg (Germany)

    2004-09-15

    Dioxin-like compounds are ubiquitously distributed and humans are exposed to them via various sources but primarily through food. They can be detected in air, water, soil, sediment and biota. These compounds are lipid soluble, poorly eliminated and thus can accumulate in human adipose tissue. They can cross the placenta and are also transferred to breast milk during the lactation process. Therefore infants are exposed ante and postnatally. Since PCDD/PCDF concentration in blood and human milk are very similar when concentrations are expressed on a lipid basis, human milk provides a good monitoring tool of exposure for a given population in a given area. Previously the WHO has co-ordinated international studies on dioxin-like compounds in breast milk. These were conducted in 1987/88, 1992/93 and 2001. In summary, these studies demonstrated that levels of dioxins in breast milk are relatively high in industrialised countries when compared to non-industrialised countries that PCDD/PCDFs were higher in human milk from mothers with their first child and that the levels decrease over a given lactation period. The present study aims to examine the levels of these compounds in primiparae women throughout Australia.

  5. Chemopreventive effect of natural dietary compounds on xenobiotic-induced toxicity

    Directory of Open Access Journals (Sweden)

    Jia-Ching Wu

    2017-01-01

    Full Text Available Contaminants (or pollutants that affect human health have become an important issue, spawning a myriad of studies on how to prevent harmful contaminant-induced effects. Recently, a variety of biological functions of natural dietary compounds derived from consumed foods and plants have been demonstrated in a number of studies. Natural dietary compounds exhibited several beneficial effects for the prevention of disease and the inhibition of chemically-induced carcinogenesis. Contaminant-induced toxicity and carcinogenesis are mostly attributed to the mutagenic activity of reactive metabolites and the disruption of normal biological functions. Therefore, the metabolic regulation of hazardous chemicals is key to reducing contaminant-induced adverse health effects. Moreover, promoting contaminant excretion from the body through Phase I and II metabolizing enzymes is also a useful strategy for reducing contaminant-induced toxicity. This review focuses on summarizing the natural dietary compounds derived from common dietary foods and plants and their possible mechanisms of action in the prevention/suppression of contaminant-induced toxicity.

  6. Effect of exercise on insulin action in human skeletal muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Mikines, K J; Galbo, Henrik

    1989-01-01

    The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization...... was performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

  7. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

    OpenAIRE

    Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Na?ra; Rau, Fr?d?rique; Jollet, Arnaud; Edom-Vovard, Fr?d?rique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois

    2017-01-01

    International audience; Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded rep...

  8. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action

    International Nuclear Information System (INIS)

    Kampa, Marilena; Boskou, Dimitrios; Gravanis, Achille; Castanas, Elias; Alexaki, Vassilia-Ismini; Notas, George; Nifli, Artemissia-Phoebe; Nistikaki, Anastassia; Hatzoglou, Anastassia; Bakogeorgou, Efstathia; Kouimtzoglou, Elena; Blekas, George

    2004-01-01

    The oncoprotective role of food-derived polyphenol antioxidants has been described but the implicated mechanisms are not yet clear. In addition to polyphenols, phenolic acids, found at high concentrations in a number of plants, possess antioxidant action. The main phenolic acids found in foods are derivatives of 4-hydroxybenzoic acid and 4-hydroxycinnamic acid. This work concentrates on the antiproliferative action of caffeic acid, syringic acid, sinapic acid, protocatechuic acid, ferulic acid and 3,4-dihydroxy-phenylacetic acid (PAA) on T47D human breast cancer cells, testing their antioxidant activity and a number of possible mechanisms involved (interaction with membrane and intracellular receptors, nitric oxide production). The tested compounds showed a time-dependent and dose-dependent inhibitory effect on cell growth with the following potency: caffeic acid > ferulic acid = protocatechuic acid = PAA > sinapic acid = syringic acid. Caffeic acid and PAA were chosen for further analysis. The antioxidative activity of these phenolic acids in T47D cells does not coincide with their inhibitory effect on tumoral proliferation. No interaction was found with steroid and adrenergic receptors. PAA induced an inhibition of nitric oxide synthase, while caffeic acid competes for binding and results in an inhibition of aryl hydrocarbon receptor-induced CYP1A1 enzyme. Both agents induce apoptosis via the Fas/FasL system. Phenolic acids exert a direct antiproliferative action, evident at low concentrations, comparable with those found in biological fluids after ingestion of foods rich in phenolic acids. Furthermore, the direct interaction with the aryl hydrocarbon receptor, the nitric oxide synthase inhibition and their pro-apoptotic effect provide some insights into their biological mode of action

  9. Bioavailability of dietary phenolic compounds: Review

    Directory of Open Access Journals (Sweden)

    Erick Gutiérrez-Grijalva Paul Gutiérrez-Grijalva

    2015-12-01

    Full Text Available Phenolic compounds are ubiquitous in plant-based foods. High dietary intake of fruits, vegetables and cereals is related to a decreased rate in chronic diseases. Phenolic compounds are thought to be responsible, at least in part, for those health effects. Nonetheless, phenolic compounds bioaccessibility and biotransformation is often not considered in these studies; thus, a precise mechanism of action of phenolic compounds is not known. In this review we aim to present a comprehensive knowledge of the metabolic processes through which phenolic compounds go after intake.

  10. Properties of tritium and its compounds

    International Nuclear Information System (INIS)

    Belovodskij, L.F.; Gaevoj, V.K.; Grishmanovskij, V.I.

    1985-01-01

    Ways of tritium preparation and different aspects of its application are considered. Physicochemical properties of this isotope and some compounds of it - tritium oxides, lithium, titanium, zirconium, uranium tritides, tritium organic compounds - are discussed. In particular, diffusion of tritium and its oxide through different materials, tritium oxidation processes, decomposition of tritium-containing compounds under the action of self-radiation are considered. Main radiobiological tritium properties are described

  11. Cinnamic Acid Is Partially Involved in Propolis Immunomodulatory Action on Human Monocytes

    Directory of Open Access Journals (Sweden)

    Bruno José Conti

    2013-01-01

    Full Text Available Propolis is a beehive product used in traditional medicine due to its biological properties. It shows a complex chemical composition including phenolics, such as cinnamic acid (Ci. The mechanisms of action of propolis have been the subject of research recently; however, the involvement of Ci on propolis activity was not investigated on immune cells. Ci effects were evaluated on human monocytes, assessing the expression of Toll-like receptors (TLRs, HLA-DR, and CD80. Cytokine production (TNF-α and IL-10 and the fungicidal activity of monocytes were evaluated as well. Data showed that Ci downregulated TLR-2, HLA-DR, and CD80 and upregulated TLR-4 expression by human monocytes. High concentrations of Ci inhibited both TNF-α and IL-10 production, whereas the same concentrations induced a higher fungicidal activity against Candida albicans. TNF-α and IL-10 production was decreased by blocking TLR-4, while the fungicidal activity of monocytes was not affected by blocking TLRs. These results suggest that Ci modulated antigen receptors, cytokine production, and the fungicidal activity of human monocytes depending on concentration, and TLR-4 may be involved in its mechanism of action. Ci seemed to be partially involved in propolis activities.

  12. Human Elimination of Phthalate Compounds: Blood, Urine, and Sweat (BUS) Study

    Science.gov (United States)

    Genuis, Stephen J.; Beesoon, Sanjay; Lobo, Rebecca A.; Birkholz, Detlef

    2012-01-01

    Background. Individual members of the phthalate family of chemical compounds are components of innumerable everyday consumer products, resulting in a high exposure scenario for some individuals and population groups. Multiple epidemiological studies have demonstrated statistically significant exposure-disease relationships involving phthalates and toxicological studies have shown estrogenic effects in vitro. Data is lacking in the medical literature, however, on effective means to facilitate phthalate excretion. Methods. Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for parent phthalate compounds as well as phthalate metabolites using high performance liquid chromatography-tandem mass spectrometry. Results. Some parent phthalates as well as their metabolites were excreted into sweat. All patients had MEHP (mono(2-ethylhexyl) phthalate) in their blood, sweat, and urine samples, suggesting widespread phthalate exposure. In several individuals, DEHP (di (2-ethylhexl) phthalate) was found in sweat but not in serum, suggesting the possibility of phthalate retention and bioaccumulation. On average, MEHP concentration in sweat was more than twice as high as urine levels. Conclusions. Induced perspiration may be useful to facilitate elimination of some potentially toxic phthalate compounds including DEHP and MEHP. Sweat analysis may be helpful in establishing the existence of accrued DEHP in the human body. PMID:23213291

  13. Unsupervised Learning of Action Primitives

    DEFF Research Database (Denmark)

    Baby, Sanmohan; Krüger, Volker; Kragic, Danica

    2010-01-01

    and scale, the use of the object can provide a strong invariant for the detection of motion primitives. In this paper we propose an unsupervised learning approach for action primitives that makes use of the human movements as well as the object state changes. We group actions according to the changes......Action representation is a key issue in imitation learning for humanoids. With the recent finding of mirror neurons there has been a growing interest in expressing actions as a combination meaningful subparts called primitives. Primitives could be thought of as an alphabet for the human actions....... In this paper we observe that human actions and objects can be seen as being intertwined: we can interpret actions from the way the body parts are moving, but as well from how their effect on the involved object. While human movements can look vastly different even under minor changes in location, orientation...

  14. Lifelong learning of human actions with deep neural network self-organization.

    Science.gov (United States)

    Parisi, German I; Tani, Jun; Weber, Cornelius; Wermter, Stefan

    2017-12-01

    Lifelong learning is fundamental in autonomous robotics for the acquisition and fine-tuning of knowledge through experience. However, conventional deep neural models for action recognition from videos do not account for lifelong learning but rather learn a batch of training data with a predefined number of action classes and samples. Thus, there is the need to develop learning systems with the ability to incrementally process available perceptual cues and to adapt their responses over time. We propose a self-organizing neural architecture for incrementally learning to classify human actions from video sequences. The architecture comprises growing self-organizing networks equipped with recurrent neurons for processing time-varying patterns. We use a set of hierarchically arranged recurrent networks for the unsupervised learning of action representations with increasingly large spatiotemporal receptive fields. Lifelong learning is achieved in terms of prediction-driven neural dynamics in which the growth and the adaptation of the recurrent networks are driven by their capability to reconstruct temporally ordered input sequences. Experimental results on a classification task using two action benchmark datasets show that our model is competitive with state-of-the-art methods for batch learning also when a significant number of sample labels are missing or corrupted during training sessions. Additional experiments show the ability of our model to adapt to non-stationary input avoiding catastrophic interference. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  15. Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro.

    Science.gov (United States)

    Portelli, J; Gordon, A; May, J T

    1998-11-01

    The effect of some antibacterial compounds present in human milk were tested for antiviral activity against respiratory syncytial virus, Semliki Forest virus and cytomegalovirus. These included the gangliosides GM1, GM2 and GM3, sialyl-lactose, lactoferrin and chondroitin sulphate A, B and C, which were all tested for their ability to inhibit the viruses in cell culture. Of the compounds tested, only the ganglioside GM2, chondroitin sulphate B and lactoferrin inhibited the absorption and growth of respiratory syncytial virus in cell culture, and none inhibited the growth of Semliki Forest virus, indicating that lipid antiviral activity was not associated with any of the gangliosides. While the concentrations of these two compounds required to inhibit respiratory syncytial virus were in excess of those present in human milk, sialyl-lactose concentrations similar to those present in human milk increased the growth of cytomegalovirus. Lactoferrin was confirmed as inhibiting both respiratory syncytial virus and cytomegalovirus growth in culture even when used at lower concentrations than those present in human milk. The antiviral activities of GM2, chondroitin sulphate B and lactoferrin were tested when added to an infant formula. Lactoferrin continued to have antiviral activity against cytomegalovirus, but a lower activity against respiratory syncytial virus; ganglioside GM2 and chondroitin sulphate B still maintained antiviral activity against respiratory syncytial virus.

  16. Development of an Intracellular Screen for New Compounds Able To Inhibit Mycobacterium tuberculosis Growth in Human Macrophages.

    Science.gov (United States)

    Sorrentino, Flavia; Gonzalez del Rio, Ruben; Zheng, Xingji; Presa Matilla, Jesus; Torres Gomez, Pedro; Martinez Hoyos, Maria; Perez Herran, Maria Esther; Mendoza Losana, Alfonso; Av-Gay, Yossef

    2016-01-01

    Here we describe the development and validation of an intracellular high-throughput screening assay for finding new antituberculosis compounds active in human macrophages. The assay consists of a luciferase-based primary identification assay, followed by a green fluorescent protein-based secondary profiling assay. Standard tuberculosis drugs and 158 previously recognized active antimycobacterial compounds were used to evaluate assay robustness. Data show that the assay developed is a short and valuable tool for the discovery of new antimycobacterial compounds. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. The human dorsal action control system develops in the absence of vision.

    Science.gov (United States)

    Fiehler, Katja; Burke, Michael; Bien, Siegfried; Röder, Brigitte; Rösler, Frank

    2009-01-01

    The primate dorsal pathway has been proposed to compute vision for action. Although recent findings suggest that dorsal pathway structures contribute to somatosensory action control as well, it is yet not clear whether or not the development of dorsal pathway functions depends on early visual experience. Using functional magnetic resonance imaging, we investigated the pattern of cortical activation in congenitally blind and matched blindfolded sighted adults while performing kinesthetically guided hand movements. Congenitally blind adults activated similar dorsal pathway structures as sighted controls. Group-specific activations were found in the extrastriate cortex and the auditory cortex for congenitally blind humans and in the precuneus and the presupplementary motor area for sighted humans. Dorsal pathway activity was in addition observed for working memory maintenance of kinesthetic movement information in both groups. Thus, the results suggest that dorsal pathway functions develop in the absence of vision. This favors the idea of a general mechanism of movement control that operates regardless of the sensory input modality. Group differences in cortical activation patterns imply different movement control strategies as a function of visual experience.

  18. 78 FR 72899 - Draft Guidance for Industry on Registration for Human Drug Compounding Outsourcing Facilities...

    Science.gov (United States)

    2013-12-04

    ... information technology. Under the draft guidance, outsourcing facilities that elect to register should submit... guidance provides information on how an outsourcing facility should submit facility registration...] Draft Guidance for Industry on Registration for Human Drug Compounding Outsourcing Facilities Under...

  19. Mechanism of action of a pestivirus antiviral compound

    Science.gov (United States)

    Baginski, Scott G.; Pevear, Daniel C.; Seipel, Marty; Sun, Siu Chi Chang; Benetatos, Christopher A.; Chunduru, Srinivas K.; Rice, Charles M.; Collett, Marc S.

    2000-01-01

    We report here the discovery of a small molecule inhibitor of pestivirus replication. The compound, designated VP32947, inhibits the replication of bovine viral diarrhea virus (BVDV) in cell culture at a 50% inhibitory concentration of approximately 20 nM. VP32947 inhibits both cytopathic and noncytopathic pestiviruses, including isolates of BVDV-1, BVDV-2, border disease virus, and classical swine fever virus. However, the compound shows no activity against viruses from unrelated virus groups. Time of drug addition studies indicated that VP32947 acts after virus adsorption and penetration and before virus assembly and release. Analysis of viral macromolecular synthesis showed VP32947 had no effect on viral protein synthesis or polyprotein processing but did inhibit viral RNA synthesis. To identify the molecular target of VP32947, we isolated drug-resistant (DR) variants of BVDV-1 in cell culture. Sequence analysis of the complete genomic RNA of two DR variants revealed a single common amino acid change located within the coding region of the NS5B protein, the viral RNA-dependent RNA polymerase. When this single amino acid change was introduced into an infectious clone of drug-sensitive wild-type (WT) BVDV-1, replication of the resulting virus was resistant to VP32947. The RNA-dependent RNA polymerase activity of the NS5B proteins derived from WT and DR viruses expressed and purified from recombinant baculovirus-infected insect cells confirmed the drug sensitivity of the WT enzyme and the drug resistance of the DR enzyme. This work formally validates NS5B as a target for antiviral drug discovery and development. The utility of VP32947 and similar compounds for the control of pestivirus diseases, and for hepatitis C virus drug discovery efforts, is discussed. PMID:10869440

  20. Efficient Temporal Action Localization in Videos

    KAUST Repository

    Alwassel, Humam

    2018-04-17

    State-of-the-art temporal action detectors inefficiently search the entire video for specific actions. Despite the encouraging progress these methods achieve, it is crucial to design automated approaches that only explore parts of the video which are the most relevant to the actions being searched. To address this need, we propose the new problem of action spotting in videos, which we define as finding a specific action in a video while observing a small portion of that video. Inspired by the observation that humans are extremely efficient and accurate in spotting and finding action instances in a video, we propose Action Search, a novel Recurrent Neural Network approach that mimics the way humans spot actions. Moreover, to address the absence of data recording the behavior of human annotators, we put forward the Human Searches dataset, which compiles the search sequences employed by human annotators spotting actions in the AVA and THUMOS14 datasets. We consider temporal action localization as an application of the action spotting problem. Experiments on the THUMOS14 dataset reveal that our model is not only able to explore the video efficiently (observing on average 17.3% of the video) but it also accurately finds human activities with 30.8% mAP (0.5 tIoU), outperforming state-of-the-art methods

  1. SEURAT-1 liver gold reference compounds: a mechanism-based review.

    Science.gov (United States)

    Jennings, Paul; Schwarz, Michael; Landesmann, Brigitte; Maggioni, Silvia; Goumenou, Marina; Bower, David; Leonard, Martin O; Wiseman, Jeffrey S

    2014-12-01

    There is an urgent need for the development of alternative methods to replace animal testing for the prediction of repeat dose chemical toxicity. To address this need, the European Commission and Cosmetics Europe have jointly funded a research program for 'Safety Evaluation Ultimately Replacing Animal Testing.' The goal of this program was the development of in vitro cellular systems and associated computational capabilities for the prediction of hepatic, cardiac, renal, neuronal, muscle, and skin toxicities. An essential component of this effort is the choice of appropriate reference compounds that can be used in the development and validation of assays. In this review, we focus on the selection of reference compounds for liver pathologies in the broad categories of cytotoxicity and lipid disorders. Mitochondrial impairment, oxidative stress, and apoptosis are considered under the category of cytotoxicity, while steatosis, cholestasis, and phospholipidosis are considered under the category of lipid dysregulation. We focused on four compound classes capable of initiating such events, i.e., chemically reactive compounds, compounds with specific cellular targets, compounds that modulate lipid regulatory networks, and compounds that disrupt the plasma membrane. We describe the molecular mechanisms of these compounds and the cellular response networks which they elicit. This information will be helpful to both improve our understanding of mode of action and help in the selection of appropriate mechanistic biomarkers, allowing us to progress the development of animal-free models with improved predictivity to the human situation.

  2. Organohalogen compounds in human breast milk from Republic of Buryatia, Russia

    International Nuclear Information System (INIS)

    Tsydenova, Oyuna V.; Sudaryanto, Agus; Kajiwara, Natsuko; Kunisue, Tatsuya; Batoev, Valeriy B.; Tanabe, Shinsuke

    2007-01-01

    Human breast milk samples collected during 2003/04 in Buryatia, a Russian autonomous republic, were analyzed in order to assess human exposure to organohalogen compounds including organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). When compared with available worldwide data, levels of HCB (23-880 ng/g lipid wt.), PCBs (69-680 ng/g lipid wt.), and HCHs (100-3700 ng/g lipid wt.) were relatively high, indicating elevated human exposure to these organochlorines (OCs) in Buryatia. In contrast to OCs, PBDE concentrations were low (0.46-1.7 ng/g lipid wt.). Out of 14 BDE congeners analyzed, BDE-28, BDE-47, BDE-100, BDE-153, BDE-197, and BDE-207 were detected. Estimated daily intakes (EDIs) of HCHs, HCB, CHLs, and PCBs by infants solely from human milk for 100%, 43%, 34%, and 17% of the samples, respectively, exceeded guideline thresholds. Although high EDIs raise concern for possible toxic effects of OCs, women in Buryatia are recommended to breastfeed due to numerous advantages of breastfeeding for mother and child. - People in the Republic of Buryatia, Russia are exposed to relatively high levels of HCHs, HCB and PCBs

  3. Organohalogen compounds in human breast milk from Republic of Buryatia, Russia

    Energy Technology Data Exchange (ETDEWEB)

    Tsydenova, Oyuna V. [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Sudaryanto, Agus [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Kajiwara, Natsuko [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Kunisue, Tatsuya [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Batoev, Valeriy B. [Baikal Institute of Nature Management, Siberian Branch of Russian Academy of Sciences, Sakhyanova st. 6, Ulan-Ude 670047 (Russian Federation); Tanabe, Shinsuke [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan)]. E-mail: shinsuke@agr.ehime-u.ac.jp

    2007-03-15

    Human breast milk samples collected during 2003/04 in Buryatia, a Russian autonomous republic, were analyzed in order to assess human exposure to organohalogen compounds including organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). When compared with available worldwide data, levels of HCB (23-880 ng/g lipid wt.), PCBs (69-680 ng/g lipid wt.), and HCHs (100-3700 ng/g lipid wt.) were relatively high, indicating elevated human exposure to these organochlorines (OCs) in Buryatia. In contrast to OCs, PBDE concentrations were low (0.46-1.7 ng/g lipid wt.). Out of 14 BDE congeners analyzed, BDE-28, BDE-47, BDE-100, BDE-153, BDE-197, and BDE-207 were detected. Estimated daily intakes (EDIs) of HCHs, HCB, CHLs, and PCBs by infants solely from human milk for 100%, 43%, 34%, and 17% of the samples, respectively, exceeded guideline thresholds. Although high EDIs raise concern for possible toxic effects of OCs, women in Buryatia are recommended to breastfeed due to numerous advantages of breastfeeding for mother and child. - People in the Republic of Buryatia, Russia are exposed to relatively high levels of HCHs, HCB and PCBs.

  4. Bioactive compounds in different cocoa (Theobroma cacao, L cultivars during fermentation

    Directory of Open Access Journals (Sweden)

    Jaqueline Fontes Moreau Cruz

    2015-06-01

    Full Text Available One component that contribute to the flavor and aroma of chocolate are the polyphenols, which have received much attention due to their beneficial implications to human health. Besides bioactive action, polyphenols and methylxantines are responsible for astringency and bitterness in cocoa beans. Another important point is its drastic reduction during cocoa processing for chocolate production and the difference between cultivars. Thus, the present study aimed to evaluate the modifications in monomeric phenolic compounds and methylxanthines during fermentation of three cocoa cultivars grown in southern Bahia. Cocoa beans from three cultivars were fermented and sun dried and monomeric phenolic compounds and methylxantines were determinated. The results showed that each cultivar have different amounts of phenolic compounds and the behaviour of them is different during fermentation. The amount of methylxantines varied but there was not a pattern for methylxantines behavior during process. In addition a huge reduction in phenolic compounds could be observed after drying. Differently of phenolic compounds, methylxantines did not have great modification after sun drying. So, the differences observed in this study between cultivars, take to the conclusion that the compounds studied in those cocoa cultivars have different behavior during fermentation and drying, which consequently, give to these cultivars differences in sensory characteristics.

  5. Action of certain chemical compounds on radiation haemolysis of erythrocytes

    International Nuclear Information System (INIS)

    Kolesnikov, Yu.A.; Shulgina, M.A.; Yartsev, E.I.; Novoseltseva, S.D.; Bogatyrev, G.P.

    1975-01-01

    A radioprotective action of a number of protective chemicals on radiation haemolysis of erythrocytes has been studied. S-bearing radioprotectors, serotonin and arginine possess the highest radioprotective activity. The same radioprotectors delivered to the medium after irradiation do not influence the development of the post-irradiation haemolysis. Certain amino acids, namely proline, serine and taurine have a pronounced radio-protective action when given to the medium after irradiation, taurine producing the strongest effect on the development of radiation haemolysis. The mechanism of action of these substances is unrelated to the increased osmotic pressure of the medium and might be explained by normalization of the functional state of cytomembranes and processes of cell metabolism

  6. An ergonomics action research demonstration: integrating human factors into assembly design processes.

    Science.gov (United States)

    Village, J; Greig, M; Salustri, F; Zolfaghari, S; Neumann, W P

    2014-01-01

    In action research (AR), the researcher participates 'in' the actions in an organisation, while simultaneously reflecting 'on' the actions to promote learning for both the organisation and the researchers. This paper demonstrates a longitudinal AR collaboration with an electronics manufacturing firm where the goal was to improve the organisation's ability to integrate human factors (HF) proactively into their design processes. During the three-year collaboration, all meetings, workshops, interviews and reflections were digitally recorded and qualitatively analysed to inform new 'actions'. By the end of the collaboration, HF tools with targets and sign-off by the HF specialist were integrated into several stages of the design process, and engineers were held accountable for meeting the HF targets. We conclude that the AR approach combined with targeting multiple initiatives at different stages of the design process helped the organisation find ways to integrate HF into their processes in a sustainable way. Researchers acted as a catalyst to help integrate HF into the engineering design process in a sustainable way. This paper demonstrates how an AR approach can help achieve HF integration, the benefits of using a reflective stance and one method for reporting an AR study.

  7. Skeleton-Based Human Action Recognition With Global Context-Aware Attention LSTM Networks

    Science.gov (United States)

    Liu, Jun; Wang, Gang; Duan, Ling-Yu; Abdiyeva, Kamila; Kot, Alex C.

    2018-04-01

    Human action recognition in 3D skeleton sequences has attracted a lot of research attention. Recently, Long Short-Term Memory (LSTM) networks have shown promising performance in this task due to their strengths in modeling the dependencies and dynamics in sequential data. As not all skeletal joints are informative for action recognition, and the irrelevant joints often bring noise which can degrade the performance, we need to pay more attention to the informative ones. However, the original LSTM network does not have explicit attention ability. In this paper, we propose a new class of LSTM network, Global Context-Aware Attention LSTM (GCA-LSTM), for skeleton based action recognition. This network is capable of selectively focusing on the informative joints in each frame of each skeleton sequence by using a global context memory cell. To further improve the attention capability of our network, we also introduce a recurrent attention mechanism, with which the attention performance of the network can be enhanced progressively. Moreover, we propose a stepwise training scheme in order to train our network effectively. Our approach achieves state-of-the-art performance on five challenging benchmark datasets for skeleton based action recognition.

  8. Involvement of transient receptor potential A1 channel in algesic and analgesic actions of the organic compound limonene.

    Science.gov (United States)

    Kaimoto, T; Hatakeyama, Y; Takahashi, K; Imagawa, T; Tominaga, M; Ohta, T

    2016-08-01

    TRPA1 is a Ca-permeable nonselective cation channel expressed in sensory neurons and acts as a nocisensor. Recent reports show that some monoterpenes, a group of naturally occurring organic compounds, modulate TRP channel activity. Here, we report that limonene, being contained in citrus fruits and mushrooms, shows a unique bimodal action on TRPA1 channel. We examine the effects of limonene on sensory neurons from wild-type, TRPV1- and TRPA1-gene-deficient mice and on heterologously expressed channels in vitro. Molecular determinants were identified with using mutated channels. Cellular excitability is monitored with ratiometric Ca imaging. Nociceptive and analgesic actions of limonene are also examined in vivo. In wild-type mouse sensory neurons, limonene increased the intracellular Ca(2+) concentration ([Ca(2+) ]i ), which was inhibited by selective inhibitors of TRPA1 but not TRPV1. Limonene-responsive neurons highly corresponded to TRPA1 agonist-sensitive ones. Limonene failed to stimulate sensory neurons from the TRPA1 (-/-) mouse. Heterologously expressed mouse TRPA1 was activated by limonene. Intraplantar injection of limonene elicited acute pain, which was significantly less in TRPA1 (-/-) mice. Systemic administration of limonene reduced nociceptive behaviours evoked by H2 O2 . In both heterologously and endogenously expressed TRPA1, a low concentration of limonene significantly inhibited H2 O2 -induced TRPA1 activation. TRPA1 activation by limonene was abolished in H2 O2 -insensitive cysteine-mutated channels. Topically applied limonene stimulates TRPA1, resulting in elicitation of acute pain, but its systemic application inhibits nociception induced by oxidative stress. Because limonene is a safe compound, it may be utilized for pain control due to its inhibition of TRPA1 channels. What does this study add: Limonene, a monoterpene in essential oils of various plants, has been known for its antitumor and anti-inflammatory properties. However, molecular

  9. Effects of terpineol on the compound action potential of the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    M.R. Moreira

    2001-10-01

    Full Text Available Terpineol, a volatile terpenoid alcohol of low toxicity, is widely used in the perfumery industry. It is an important chemical constituent of the essential oil of many plants with widespread applications in folk medicine and in aromatherapy. The effects of terpineol on the compound action potential (CAP of rat sciatic nerve were studied. Terpineol induced a dose-dependent blockade of the CAP. At 100 µM, terpineol had no demonstrable effect. At 300 µM terpineol, peak-to-peak amplitude and conduction velocity of CAP were significantly reduced at the end of 180-min exposure of the nerve to the drug, from 3.28 ± 0.22 mV and 33.5 ± 7.05 m/s, respectively, to 1.91 ± 0.51 mV and 26.2 ± 4.55 m/s. At 600 µM, terpineol significantly reduced peak-to-peak amplitude and conduction velocity from 2.97 ± 0.55 mV and 32.8 ± 3.91 m/s to 0.24 ± 0.23 mV and 2.72 ± 2.72 m/s, respectively (N = 5. All these effects developed slowly and were reversible upon 180-min washout.

  10. Contents of a regulatory strategy for assessing future human actions in the safety evaluation of a repository for spent fuels

    International Nuclear Information System (INIS)

    Wilmot, R.D.; Wickham, S.M.; Galson, D.A.

    2001-08-01

    The objective of this report is to discuss issues that should be considered in the development of a regulatory strategy for assessing future human actions in any forthcoming license application for a deep repository for spent fuel in Sweden and for sites of other repositories. The report comprises an outline of key issues concerning the treatment of future human actions in safety assessment, reviews of regulatory developments, recent safety assessments and supporting studies, and international initiatives on the treatment of future human actions in safety assessment, and the principal elements of a regulatory strategy. Performance assessments (PAs) are generally accepted as providing illustrations of system performance under given sets of assumptions. The results of PAs are clearer and easier to understand if certain large uncertainties are accounted for by determining performance under several different sets of assumptions or scenarios, each of which defines a possible evolution of the disposal system. A number of assumptions can be made that would restrict the scope of an assessment without reducing the credibility of the corresponding safety case. Reducing speculation about technological development, by assuming that the techniques used in future human activities are similar to those currently in use in the region or at similar sites, will simplify the assessment. A distinction is generally made between inadvertent and intentional intrusion, with intentional activities excluded because society cannot protect future populations from their own actions if they understand the potential consequences. A division of human activities into 'recent and ongoing' and 'future' activities considers not only the timing of the activities but also the degree of control or influence that can be imposed on them. Recent and ongoing human activities are those that affect an area beyond the immediate vicinity of the disposal facility and which neither the proponent nor the regulator

  11. Quantification of volatile organic compounds in exhaled human breath. Acetonitrile as biomarker for passive smoking. Model for isoprene in human breath

    International Nuclear Information System (INIS)

    Prazeller, P.

    2000-03-01

    The topic of this thesis is the quantification of volatile organic compounds in human breath under various circumstances. The composition of exhaled breath reflects metabolic processes in the human body. Breath analysis is a non invasive technique which makes it most interesting especially for medical or toxicological applications. Measurements were done with Proton-Transfer-Reaction Mass-Spectrometry (PTR-MS). This technique combines the advantage of small fragmentation of chemical ionization with highly time resolved mass spectrometry. A big part of this work is about investigations of exposition due to tobacco smoke. After smoking cigarettes the initial increase and time dependence of some compounds in the human breath are monitored . The calculated decrease resulting only from breathing out the compounds is presented and compared to the measured decline in the breath. This allows the distinction whether breathing is the dominant loss of a compound or a different metabolic process remover it more efficiently. Acetonitrile measured in human breath is presented as a biomarker for exposition to tobacco smoke. Especially its use for quantification of passive smoking, the exposition to environmental tobacco smoke (ETS) is shown. The reached accuracy and the fast way of measuring of acetonitrile in human breath using PTR-MS offer a good alternative to common used biomarkers. Numerous publications have described measurements of breath isoprene in humans, and there has been a hope that breath isoprene analyses could be a non-invasive diagnostic tool to assess serum cholesterol levels or cholesterol synthesis rate. However, significant analytical problems in breath isoprene analysis and variability in isoprene levels with age, exercise, diet, etc. have limited the usefulness of these measurements. Here, we have applied proton-transfer-reaction mass spectrometry (PTR-MS) to this problem, allowing on-line detection of breath isoprene. We show that breath isoprene

  12. Human actions in the pre-operational probabilistic safety analysis of Juragua Nuclear Power Plant

    International Nuclear Information System (INIS)

    Ferro, R.

    1995-01-01

    Human error is one of the main contributors to the biggest industrial disasters that the world has suffered in the last years. Safety probabilistic analysis techniques allow to consider, in the some study, the contribution of a facility's mechanical and human components safety, this guaranteeing a move integral assessment of these two factors although the PSA study of Juragua Nuclear Power Plant is carried out at a preoperational stage which causes important information limitations fos assessment of human reliability some considerations and suppositions in order to conduct treatment of human actions this stage were adopted. The present work describes the projected targets, approach applied and results obtained from the lakes of human reliability of this study

  13. Natural compounds with herbicidal activity

    Directory of Open Access Journals (Sweden)

    Mariano Fracchiolla

    2007-12-01

    Full Text Available Research about phytotoxic activity of natural compounds could lead both to find new herbicidal active ingredients and to plan environmental friendly weed control strategies. Particularly, living organisms could be a source of compounds that are impossible, for their complexity, to synthesize artificially. More over, they could have alternative sites of action respect to the known chemical herbicides and, due to their origin, they should be more environmental safe. Many living organism, such as bacteria, fungi, insects, lichens and plants, are able to produce bioactive compounds. They generally are secondary metabolites or simply waste molecules. In this paper we make a review about these compounds, highlighting potential and constraints.

  14. Natural compounds with herbicidal activity

    Directory of Open Access Journals (Sweden)

    Pasquale Montemurro

    2011-02-01

    Full Text Available Research about phytotoxic activity of natural compounds could lead both to find new herbicidal active ingredients and to plan environmental friendly weed control strategies. Particularly, living organisms could be a source of compounds that are impossible, for their complexity, to synthesize artificially. More over, they could have alternative sites of action respect to the known chemical herbicides and, due to their origin, they should be more environmental safe. Many living organism, such as bacteria, fungi, insects, lichens and plants, are able to produce bioactive compounds. They generally are secondary metabolites or simply waste molecules. In this paper we make a review about these compounds, highlighting potential and constraints.

  15. Enabling robots to make use of the structure of human actions - a user study employing Acoustic Packaging

    NARCIS (Netherlands)

    Lohse, M.; Wrede, Britta; Schillingmann, Lars

    2013-01-01

    Human learning strongly depends on the ability to structure the actions of teachers in order to identify relevant parts. We propose that this is also true for learning in robots. Therefore, we apply a method for multimodal action segmentation called Acoustic Packaging to a corpus of pairs of users

  16. Molecular mechanism of action of oxazolinoanthracyclines in cells derived from human solid tumors. Part 2.

    Science.gov (United States)

    Denel-Bobrowska, Marta; Łukawska, Małgorzata; Bukowska, Barbara; Gajek, Arkadiusz; Oszczapowicz, Irena; Marczak, Agnieszka

    2018-02-01

    Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are derivatives of anthracyclines (DOX and DAU) with a modified daunosamine moiety. We aimed to clarify their mechanisms of action by investigating intracellular accumulation and effects on the cell cycle, phosphatidylserine externalization, and proteasome 20S activity. Experimental model consisted of SKOV-3, A549 and HepG2 cells. Compounds were used at the concentration of 80nM. Intracellular accumulation, drug uptake, and proteasome 20S activity were evaluated by fluorimetric methods. The effects on the cell cycle and phosphatidylserine externalization were measured by flow cytometry. O-DOX was equivalent to DOX in terms of inducing G2/M arrest, but O-DAU was less potent in SKOV-3, HepG2, and A549 cells. O-DOX had the greatest effect on initiating apoptosis in all tested cells. Externalization of phosphatidylserine was significantly higher following O-DOX treatment compared with control cells and cells incubated with DOX. The intracellular accumulation and uptake of the derivatives were similar to those of the reference drugs. Tested compounds are able to activate proteasome 20S activity. Our results extended the understanding of the toxicity, mechanism of action, and biochemical properties of oxazoline derivatives of doxorubicin and daunorubicin, including their effects on cell cycle, apoptosis and DNA degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. 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.

  18. Valenced action/inhibition learning in humans is modulated by a genetic variant linked to dopamine D2 receptor expression

    Directory of Open Access Journals (Sweden)

    Anni eRichter

    2014-08-01

    Full Text Available Motivational salience plays an important role in shaping human behavior, but recent studies demonstrate that human performance is not uniformly improved by motivation. Instead, action has been shown to dominate valence in motivated tasks, and it is particularly difficult for humans to learn the inhibition of an action to obtain a reward, but the neural mechanism behind this behavioral specificity is yet unclear. In all mammals, including humans, the monoamine neurotransmitter dopamine is particularly important in the neural manifestation of appetitively motivated behavior, and the human dopamine system is subject to considerable genetic variability. The well-studied TaqIA restriction fragment length polymorphism (rs1800497 has previously been shown to affect striatal dopamine metabolism. In this study we investigated a potential effect of this genetic variation on motivated action/inhibition learning. Two independent cohorts consisting of 87 and 95 healthy participants, respectively, were tested using the previously described valenced go/no-go learning paradigm in which participants learned the reward-associated no-go condition significantly worse than all other conditions. This effect was modulated by the TaqIA polymorphism, with carriers of the A1 allele showing a diminished learning-related performance enhancement in the rewarded no-go condition compared to the A2 homozygotes. This result highlights a modulatory role for genetic variability of the dopaminergic system in individual learning differences of action-valence interaction.

  19. Assessment of chimeric mice with humanized livers in new drug development: generation of pharmacokinetics, metabolism and toxicity data for selecting the final candidate compound.

    Science.gov (United States)

    Kamimura, Hidetaka; Ito, Satoshi

    2016-01-01

    1. Chimeric mice with humanized livers are expected to be a novel tool for new drug development. This review discusses four applications where these animals can be used efficiently to collect supportive data for selecting the best compound in the final stage of drug discovery. 2. The first application is selection of the final compound based on estimated pharmacokinetic parameters in humans. Since chimeric mouse livers are highly repopulated with human hepatocytes, hepatic clearance values in vivo could be used preferentially to estimate pharmacokinetic profiles for humans. 3. The second is prediction of human-specific or disproportionate metabolites. Chimeric mice reproduce human-specific metabolites of drugs under development to conform to ICH guidance M3(R2), except for compounds that were extensively eliminated by co-existing mouse hepatocytes. 4. The third is identifying metabolites with distinct pharmacokinetic profiles in humans. Slow metabolite elimination specifically in humans increases its exposure level, but if its elimination is faster in laboratory animals, the animal exposure level might not satisfy ICH guidance M3(R2). 5. Finally, two examples of reproducing acute liver toxicity in chimeric mice are introduced. Integrated pharmacokinetics, metabolism and toxicity information are expected to assist pharmaceutical scientists in selecting the best candidate compound in new drug development.

  20. Handling of future human actions in the safety assessment SR-Site

    International Nuclear Information System (INIS)

    2010-12-01

    This report documents the future human actions, FHA, considered in the long-term safety analysis of a KBS-3 repository. The report is one of the supporting documents to the safety assessment SR-Site (see further the Main report /SKB 2011/). The purpose of this report is to provide an account of general considerations concerning FHA, the methodology applied in SR-Site to assess FHA, the aspects of FHA needed to be considered in the evaluation of their impact on a deep geological repository and to select and analyse representative scenarios for illustrative consequence analysis. The main focus of this report is a time period when institutional control has ceased to be effective, thereby permitting inadvertent intrusion. However, a brief discussion of the earlier period when the repository has been closed, sealed and continuously kept under institutional control is also provided. General The potential exposure to large quantities of radiotoxic material is an inescapable consequence of the deposition of spent nuclear fuel in a final repository, and consequently intrusion into the repository needs to be considered in repository design and safety assessment. In accordance with ICRP recommendations /ICRP 2000/, intrusion in the post-closure phase of institutional control and beyond is primarily prevented through the design of the repository. In addition to that there will presumably continue to be safeguards measures, preservation of information (record keeping) and possibly some sort of markers placed at the site. During the institutional control period, activities at the site have to be restricted or directed if they have the potential to interfere with or hinder surveillance of the site, but this does not necessarily rule out all forms of access to the area. Also the fact that the repository contains fissile materials is an important aspect. Control of safeguards measures will most likely be upheld by national as well as international agencies. Furthermore, the

  1. Handling of future human actions in the safety assessment SR-Site

    Energy Technology Data Exchange (ETDEWEB)

    2010-12-15

    This report documents the future human actions, FHA, considered in the long-term safety analysis of a KBS-3 repository. The report is one of the supporting documents to the safety assessment SR-Site (see further the Main report /SKB 2011/). The purpose of this report is to provide an account of general considerations concerning FHA, the methodology applied in SR-Site to assess FHA, the aspects of FHA needed to be considered in the evaluation of their impact on a deep geological repository and to select and analyse representative scenarios for illustrative consequence analysis. The main focus of this report is a time period when institutional control has ceased to be effective, thereby permitting inadvertent intrusion. However, a brief discussion of the earlier period when the repository has been closed, sealed and continuously kept under institutional control is also provided. General The potential exposure to large quantities of radiotoxic material is an inescapable consequence of the deposition of spent nuclear fuel in a final repository, and consequently intrusion into the repository needs to be considered in repository design and safety assessment. In accordance with ICRP recommendations /ICRP 2000/, intrusion in the post-closure phase of institutional control and beyond is primarily prevented through the design of the repository. In addition to that there will presumably continue to be safeguards measures, preservation of information (record keeping) and possibly some sort of markers placed at the site. During the institutional control period, activities at the site have to be restricted or directed if they have the potential to interfere with or hinder surveillance of the site, but this does not necessarily rule out all forms of access to the area. Also the fact that the repository contains fissile materials is an important aspect. Control of safeguards measures will most likely be upheld by national as well as international agencies. Furthermore, the

  2. Corrective Action Investigation Plan for Corrective Action Unit 410: Waste Disposal Trenches, Tonopah Test Range, Nevada, Revision No.:0

    International Nuclear Information System (INIS)

    2002-01-01

    This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 410 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 410 is located on the Tonopah Test Range (TTR), which is included in the Nevada Test and Training Range (formerly the Nellis Air Force Range) approximately 140 miles northwest of Las Vegas, Nevada. This CAU is comprised of five Corrective Action Sites (CASs): TA-19-002-TAB2, Debris Mound; TA-21-003-TANL, Disposal Trench; TA-21-002-TAAL, Disposal Trench; 09-21-001-TA09, Disposal Trenches; 03-19-001, Waste Disposal Site. This CAU is being investigated because contaminants may be present in concentrations that could potentially pose a threat to human health and/or the environment, and waste may have been disposed of with out appropriate controls. Four out of five of these CASs are the result of weapons testing and disposal activities at the TTR, and they are grouped together for site closure based on the similarity of the sites (waste disposal sites and trenches). The fifth CAS, CAS 03-19-001, is a hydrocarbon spill related to activities in the area. This site is grouped with this CAU because of the location (TTR). Based on historical documentation and process know-ledge, vertical and lateral migration routes are possible for all CASs. Migration of contaminants may have occurred through transport by infiltration of precipitation through surface soil which serves as a driving force for downward migration of contaminants. Land-use scenarios limit future use of these CASs to industrial activities. The suspected contaminants of potential concern which have been identified are volatile organic compounds; semivolatile organic compounds; high explosives; radiological constituents including depleted uranium

  3. [Development of human resources and the Plan of Action].

    Science.gov (United States)

    Vidal, C

    1984-01-01

    This article (whose first part was published in the previous issue of Educación Médica y Salud) concludes an exhaustive review of manpower development in the Americas. This part considers the specific measures in this field enunciated in the Plan of Action; these measures pertain to four main areas: planning and programming of human resources, training in priority areas, utilization of human resources, and educational technology. The author discusses the present and future possibilities and obstacles of each of these activities and the steps to be taken to bring needs into line with real situations. It is of paramount importance that the national health authorities clearly spell out their policies for the development of human resources in the health field within the framework of general development policies. Another point to be insisted upon is the multiprofessional and multidisciplinary training of the health team and the importance of the education-service-supervision function, which usually results in permanent and continuing education, which in turn optimizes the utilization of personnel. However, none of this will be possible without an appropriate education technology with which to innovate, analyze and refine the entire education process and so meet the needs of both society and the health services.

  4. p53-independent structure-activity relationships of 3-ring mesogenic compounds' activity as cytotoxic effects against human non-small cell lung cancer lines.

    Science.gov (United States)

    Fukushi, Saori; Yoshino, Hironori; Yoshizawa, Atsushi; Kashiwakura, Ikuo

    2016-07-25

    We recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as "mesogenic compounds") in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. To develop more effective and cancer-specific agents, in this study, we investigated the structure-activity relationships of mesogenic compounds with cytotoxic effects against multiple NSCLC cells. The pharmacological effects of mesogenic compounds were examined in human NSCLC cells (A549, LU99, EBC-1, and H1299) and normal WI-38 human fibroblast. Analyses of the cell cycle, cell-death induction, and capsases expression were performed. The 3-ring compounds possessing terminal alkyl and hydroxyl groups (compounds C1-C5) showed cytotoxicity in NSCLC cells regardless of the p53 status. The compounds C1 and C3, which possess a pyrimidine at the center of the core, induced G2/M arrest, while the compounds without a pyrimidine (C2, C4, and C5) caused G1 arrest; all compounds produced caspase-mediated cell death. These events occurred in a p53-independent manner. Furthermore, it was suggested that compounds induced cell death through p53-independent DNA damage-signaling pathway. Compounds C2, C4, and C5 did not show strong cytotoxicity in WI-38 cells, whereas C1 and C3 did. However, the cytotoxicity of compound C1 against WI-38 cells was improved by modulating the terminal alkyl chain lengths of the compound. We showed the p53-indepdent structure-activity relationships of mesogenic compounds related to the cytotoxic effects. These structure-activity relationships will be helpful in the development of more effective and cancer-specific agents.

  5. Human-health pharmaceutical compounds in Lake Mead, Nevada and Arizona, and Las Vegas Wash, Nevada, October 2000-August 2001

    Science.gov (United States)

    Boyd, Robert A.; Furlong, Edward T.

    2002-01-01

    The U.S. Geological Survey and the National Park Service conducted a reconnaissance study to investigate the occurrence of selected human-health pharmaceutical compounds in water samples collected from Lake Mead on the Colorado River and Las Vegas Wash, a waterway used to transport treated wastewater from the Las Vegas metropolitan area to Lake Mead. Current research indicates many of these compounds can bioaccumulate and may adversely affect aquatic organisms by disrupting physiological processes, impairing reproductive functions, increasing cancer rates, contributing to the development of antibiotic-resistant strains of bacteria, and acting in undesirable ways when mixed with other substances. These compounds may be present in effluent because a high percentage of prescription and non-prescription drugs used for human-health purposes are excreted from the body as a mixture of parent compounds and degraded metabolite compounds; also, they can be released to the environment when unused products are discarded by way of toilets, sinks, and trash in landfills. Thirteen of 33 targeted compounds were detected in at least one water sample collected between October 2000 and August 2001. All concentrations were less than or equal to 0.20 micrograms per liter. The most frequently detected compounds in samples from Las Vegas Wash were caffeine, carbamazepine (used to treat epilepsy), cotinine (a metabolite of nicotine), and dehydronifedipine (a metabolite of the antianginal Procardia). Less frequently detected compounds in samples collected from Las Vegas Wash were antibiotics (clarithromycin, erythromycin, sulfamethoxazole, and trimethoprim), acetaminophen (an analgesic and anti-inflammatory), cimetidine (used to treat ulcers), codeine (a narcotic and analgesic), diltiazem (an antihypertensive), and 1,7-dimethylxanthine (a metabolite of caffeine). Fewer compounds were detected in samples collected from Lake Mead than from Las Vegas Wash. Caffeine was detected in all samples

  6. Lethal action of ultraviolet and visible (blue violet) radiations at defined wavelengths on human lymphoblastoid cells; action spectra and interaction sites

    Energy Technology Data Exchange (ETDEWEB)

    Tyrrell, R.M.; Werfelli, P.; Moraes, E.C. (Institut Suisse de Recherches Experimentales sur le Cancer, Lausanne)

    1984-02-01

    The repair proficient human lymphoblastoid line (TK6) has been employed to construct an action spectrum for the lethal action of ultraviolet (UV) radiation in the range 254 to 434 nm and to examine possible interactions between longer (334, 365 and 405 nm) and shorter wavelength (254 and 313 nm) radiations. The action spectrum follows a DNA absorption spectrum fairly closely out to 360 nm. As in previously determined lethal action spectra for procaryotic and eucaryotic cell populations, there is a broad shoulder in the 334 to 405 nm region which could reflect the existence of either (a) a non-DNA chromophore or (b) a unique photochemical reaction in the DNA over this region. Pre-treatment with radiation at 334 or 365 nm causes either a slight sensitivity to (low fluences) or protection from (higher fluences) subsequent exposure to radiation at a shorter wavelength (254 or 313 nm). Pre-irradiation at a visible wavelength (405 nm) at all fluence levels employed sensitizes the populations to treatment with 254 or 313 nm radiations. These interactions will influence the lethal outcome of cellular exposure to broad-band radiation sources.

  7. Lethal action of ultraviolet and visible (blue violet) radiations at defined wavelengths on human lymphoblastoid cells; action spectra and interaction sites

    International Nuclear Information System (INIS)

    Tyrrell, R.M.; Werfelli, P.; Moraes, E.C.

    1984-01-01

    The repair proficient human lymphoblastoid line (TK6) has been employed to construct an action spectrum for the lethal action of ultraviolet (UV) radiation in the range 254 to 434 nm and to examine possible interactions between longer (334, 365 and 405 nm) and shorter wavelength (254 and 313 nm) radiations. The action spectrum follows a DNA absorption spectrum fairly closely out to 360 nm. As in previously determined lethal action spectra for procaryotic and eucaryotic cell populations, there is a broad shoulder in the 334 to 405 nm region which could reflect the existence of either (a) a non-DNA chromophore or (b) a unique photochemical reaction in the DNA over this region. Pre-treatment with radiation at 334 or 365 nm causes either a slight sensitivity to (low fluences) or protection from (higher fluences) subsequent exposure to radiation at a shorter wavelength (254 or 313 nm). Pre-irradiation at a visible wavelength (405 nm) at all fluence levels employed sensitizes the populations to treatment with 254 or 313 nm radiations. These interactions will influence the lethal outcome of cellular exposure to broad-band radiation sources. (author)

  8. The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva.

    Science.gov (United States)

    Amann, Anton; Costello, Ben de Lacy; Miekisch, Wolfram; Schubert, Jochen; Buszewski, Bogusław; Pleil, Joachim; Ratcliffe, Norman; Risby, Terence

    2014-09-01

    Breath analysis is a young field of research with its roots in antiquity. Antoine Lavoisier discovered carbon dioxide in exhaled breath during the period 1777-1783, Wilhelm (Vilém) Petters discovered acetone in breath in 1857 and Johannes Müller reported the first quantitative measurements of acetone in 1898. A recent review reported 1765 volatile compounds appearing in exhaled breath, skin emanations, urine, saliva, human breast milk, blood and feces. For a large number of compounds, real-time analysis of exhaled breath or skin emanations has been performed, e.g., during exertion of effort on a stationary bicycle or during sleep. Volatile compounds in exhaled breath, which record historical exposure, are called the 'exposome'. Changes in biogenic volatile organic compound concentrations can be used to mirror metabolic or (patho)physiological processes in the whole body or blood concentrations of drugs (e.g. propofol) in clinical settings-even during artificial ventilation or during surgery. Also compounds released by bacterial strains like Pseudomonas aeruginosa or Streptococcus pneumonia could be very interesting. Methyl methacrylate (CAS 80-62-6), for example, was observed in the headspace of Streptococcus pneumonia in concentrations up to 1420 ppb. Fecal volatiles have been implicated in differentiating certain infectious bowel diseases such as Clostridium difficile, Campylobacter, Salmonella and Cholera. They have also been used to differentiate other non-infectious conditions such as irritable bowel syndrome and inflammatory bowel disease. In addition, alterations in urine volatiles have been used to detect urinary tract infections, bladder, prostate and other cancers. Peroxidation of lipids and other biomolecules by reactive oxygen species produce volatile compounds like ethane and 1-pentane. Noninvasive detection and therapeutic monitoring of oxidative stress would be highly desirable in autoimmunological, neurological, inflammatory diseases and cancer

  9. Conduction velocity of action potentials measured from unidimensional latency-topography in human and frog skeletal muscle fibers.

    Science.gov (United States)

    Homma, S; Nakajima, Y; Hayashi, K; Toma, S

    1986-01-01

    Conduction of an action potential along skeletal muscle fibers was graphically displayed by unidimensional latency-topography, UDLT. Since the slopes of the equipotential line were linear and the width of the line was constant, it was possible to calculate conduction velocity from the slope. To determine conduction direction of the muscle action potential elicited by electric stimulation applied directly to the muscle, surface recording electrodes were placed on a two-dimensional plane over a human muscle. Thus a bi-dimensional topography was obtained. Then, twelve or sixteen surface electrodes were placed linearly along the longitudinal direction of the action potential conduction which was disclosed by the bi-dimensional topography. Thus conduction velocity of muscle action potential in man, calculated from the slope, was for m. brachioradialis, 3.9 +/- 0.4 m/s; for m. biceps brachii, 3.6 +/- 0.2 m/s; for m. sternocleidomastoideus, 3.6 +/- 0.4 m/s. By using a tungsten microelectrode to stimulate the motor axons, a convex-like equipotential line of an action potential in UDLT was obtained from human muscle fibers. Since a similar pattern of UDLT was obtained from experiments on isolated frog muscles, in which the muscle action potential was elicited by stimulating the motor axon, it was assumed that the maximum of the curve corresponds to the end-plate region, and that the slopes on both sides indicate bi-directional conduction of the action potential.

  10. Short latency compound action potentials from mammalian gravity receptor organs

    Science.gov (United States)

    Jones, T. A.; Jones, S. M.

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  11. The minimalist grammar of action

    Science.gov (United States)

    Pastra, Katerina; Aloimonos, Yiannis

    2012-01-01

    Language and action have been found to share a common neural basis and in particular a common ‘syntax’, an analogous hierarchical and compositional organization. While language structure analysis has led to the formulation of different grammatical formalisms and associated discriminative or generative computational models, the structure of action is still elusive and so are the related computational models. However, structuring action has important implications on action learning and generalization, in both human cognition research and computation. In this study, we present a biologically inspired generative grammar of action, which employs the structure-building operations and principles of Chomsky's Minimalist Programme as a reference model. In this grammar, action terminals combine hierarchically into temporal sequences of actions of increasing complexity; the actions are bound with the involved tools and affected objects and are governed by certain goals. We show, how the tool role and the affected-object role of an entity within an action drives the derivation of the action syntax in this grammar and controls recursion, merge and move, the latter being mechanisms that manifest themselves not only in human language, but in human action too. PMID:22106430

  12. Human action pattern monitor for telecare system utilizing magnetic thin film infrared sensor

    International Nuclear Information System (INIS)

    Osada, H.; Chiba, S.; Oka, H.; Seki, K.

    2002-01-01

    The magnetic thin film infrared sensor (MFI) is an infrared sensing device utilizing a temperature-sensitive magnetic thin film with marked temperature dependence in the room temperature range. We propose a human action pattern monitor (HPM) constructed with the MFI, without a monitor camera to save the clients' privacy, as a telecare system

  13. mechanism of action

    African Journals Online (AJOL)

    known as azidothymidine) in 1987. Fourteen agents are available for general use in South Africa. Several newer compounds are in preclinical development or have ... Site of action penetration. AlJ. Thymidine. Zidovudine. Retrovir. Intracellularly;. Good activated Tcells. d4T. Thymidine. Stavudine. Zerit. Intracellularly;. Good.

  14. Hearing sounds, understanding actions: action representation in mirror neurons.

    Science.gov (United States)

    Kohler, Evelyne; Keysers, Christian; Umiltà, M Alessandra; Fogassi, Leonardo; Gallese, Vittorio; Rizzolatti, Giacomo

    2002-08-02

    Many object-related actions can be recognized by their sound. We found neurons in monkey premotor cortex that discharge when the animal performs a specific action and when it hears the related sound. Most of the neurons also discharge when the monkey observes the same action. These audiovisual mirror neurons code actions independently of whether these actions are performed, heard, or seen. This discovery in the monkey homolog of Broca's area might shed light on the origin of language: audiovisual mirror neurons code abstract contents-the meaning of actions-and have the auditory access typical of human language to these contents.

  15. Impact of Saccharomyces cerevisiae Strains on Health-Promoting Compounds in Wine

    Directory of Open Access Journals (Sweden)

    Simona Guerrini

    2018-04-01

    Full Text Available Moderate wine consumption is associated with human health benefits (reduction of cardiovascular risk and neurodegenerative diseases, decrease of onset of certain cancers attributed to a series of bioactive compounds, mainly polyphenols, with antioxidant power capable of counteracting the negative action of free radicals. Polyphenols are naturally present in the grapes, but an additional amount originates during winemaking. The aim of this work was to assess the ability of four commercial and two indigenous Saccharomyces cerevisiae strains to produce bioactive compounds (tyrosol, hydroxytyrosol, tryptophol, melatonin and glutathione during alcoholic fermentation. In order to exclude the fraction of antioxidant compounds naturally occurring in grapes, the strains were inoculated in a synthetic must. At the end of fermentation the bioactive compounds were analysed by High-Performance Liquid Chromatography, while antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay. Moreover, freeze-dried samples, originating from the experimental wines, were used to perform ex-vivo assays on cultured cells (RAW 264.7 murine macrophages with the aim to evaluate their antioxidant and anti-inflammatory activities. The results indicated that the production of the considered bioactive compounds is a strain-specific property; therefore, the different yeast strains utilized during fermentation have different capabilities to modify the antioxidant and anti-inflammatory properties of the wine.

  16. Precursor processes of human self-initiated action.

    Science.gov (United States)

    Khalighinejad, Nima; Schurger, Aaron; Desantis, Andrea; Zmigrod, Leor; Haggard, Patrick

    2018-01-15

    A gradual buildup of electrical potential over motor areas precedes self-initiated movements. Recently, such "readiness potentials" (RPs) were attributed to stochastic fluctuations in neural activity. We developed a new experimental paradigm that operationalized self-initiated actions as endogenous 'skip' responses while waiting for target stimuli in a perceptual decision task. We compared these to a block of trials where participants could not choose when to skip, but were instead instructed to skip. Frequency and timing of motor action were therefore balanced across blocks, so that conditions differed only in how the timing of skip decisions was generated. We reasoned that across-trial variability of EEG could carry as much information about the source of skip decisions as the mean RP. EEG variability decreased more markedly prior to self-initiated compared to externally-triggered skip actions. This convergence suggests a consistent preparatory process prior to self-initiated action. A leaky stochastic accumulator model could reproduce this convergence given the additional assumption of a systematic decrease in input noise prior to self-initiated actions. Our results may provide a novel neurophysiological perspective on the topical debate regarding whether self-initiated actions arise from a deterministic neurocognitive process, or from neural stochasticity. We suggest that the key precursor of self-initiated action may manifest as a reduction in neural noise. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Documents for Recommended Toxicity Equivalency Factors for Human Health Risk Assessments of Dioxin and Dioxin-Like Compounds

    Science.gov (United States)

    This document describes the U.S. Environmental Protection Agency’s (U.S. EPA’s) updated approach for evaluating the human health risks from exposures to environmental media containing dioxin-like compounds (DLCs).

  18. Effect of the human follicle-stimulating hormone-binding inhibitor ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    a fragment of FSHBI, and the native protein have similar activity in vitro and both compounds alter FSH action at the receptor level ... of the rest of the cohort and meiotic arrest of oocytes until ... et al 1989) and preliminary studies performed using the partially .... that human ovarian follicular fluid contains a low molecular-.

  19. Molecular Properties of Red Wine Compounds and Cardiometabolic Benefits.

    Science.gov (United States)

    Markoski, Melissa M; Garavaglia, Juliano; Oliveira, Aline; Olivaes, Jessica; Marcadenti, Aline

    2016-01-01

    Wine has been used since the dawn of human civilization. Despite many health benefits, there is still a lot of discussion about the real properties of its components and its actions on cells and molecular interactions. A large part of these issues permeate the fine line between the amount of alcohol that causes problems to organic systems and the amount that could be beneficial for the health. However, even after the process of fermentation, wine conserves different organic compounds from grapes, such as polysaccharides, acids, and phenolic compounds, such as flavonoids and nonflavonoids. These substances have known anti-inflammatory and antioxidant capacities, and are considered as regulatory agents in cardiometabolic process. In this study, the main chemical components present in the wine, its interaction with molecules and biological mechanisms, and their interference with intra- and extracellular signaling are reviewed. Finally, the properties of wine that may benefit cardiovascular system are also revised.

  20. Molecular Properties of Red Wine Compounds and Cardiometabolic Benefits

    Science.gov (United States)

    Markoski, Melissa M.; Garavaglia, Juliano; Oliveira, Aline; Olivaes, Jessica; Marcadenti, Aline

    2016-01-01

    Wine has been used since the dawn of human civilization. Despite many health benefits, there is still a lot of discussion about the real properties of its components and its actions on cells and molecular interactions. A large part of these issues permeate the fine line between the amount of alcohol that causes problems to organic systems and the amount that could be beneficial for the health. However, even after the process of fermentation, wine conserves different organic compounds from grapes, such as polysaccharides, acids, and phenolic compounds, such as flavonoids and nonflavonoids. These substances have known anti-inflammatory and antioxidant capacities, and are considered as regulatory agents in cardiometabolic process. In this study, the main chemical components present in the wine, its interaction with molecules and biological mechanisms, and their interference with intra- and extracellular signaling are reviewed. Finally, the properties of wine that may benefit cardiovascular system are also revised. PMID:27512338

  1. Molecular Properties of Red Wine Compounds and Cardiometabolic Benefits

    Directory of Open Access Journals (Sweden)

    Melissa M. Markoski

    2016-01-01

    Full Text Available Wine has been used since the dawn of human civilization. Despite many health benefits, there is still a lot of discussion about the real properties of its components and its actions on cells and molecular interactions. A large part of these issues permeate the fine line between the amount of alcohol that causes problems to organic systems and the amount that could be beneficial for the health. However, even after the process of fermentation, wine conserves different organic compounds from grapes, such as polysaccharides, acids, and phenolic compounds, such as flavonoids and nonflavonoids. These substances have known anti-inflammatory and antioxidant capacities, and are considered as regulatory agents in cardiometabolic process. In this study, the main chemical components present in the wine, its interaction with molecules and biological mechanisms, and their interference with intra- and extracellular signaling are reviewed. Finally, the properties of wine that may benefit cardiovascular system are also revised.

  2. Comparison of the neurotoxicities between volatile organic compounds and fragrant organic compounds on human neuroblastoma SK-N-SH cells and primary cultured rat neurons

    Directory of Open Access Journals (Sweden)

    Yasue Yamada

    2015-01-01

    Full Text Available These are many volatile organic compounds (VOCs that are synthesized, produced from petroleum or derived from natural compounds, mostly plants. Fragrant and volatile organic compounds from plants have been used as food additives, medicines and aromatherapy. Several clinical and pathological studies have shown that chronic abuse of VOCs, mainly toluene, causes several neuropsychiatric disorders. Little is known about the mechanisms of neurotoxicity of the solvents. n-Octanal, nonanal, and 2-ethyl-1-hexanol, which are used catalyzers or intermediates of chemical reactions, are released into the environment. Essential oils have the functions of self-defense, sterilization, and antibiosis in plants. When volatile organic compounds enter the body, there is the possibility that they will pass through the blood–brain barrier (BBB and affect the central nervous system (CNS. However, the direct effects of volatile organic compounds on neural function and their toxicities are still unclear. We compared the toxicities of n-octanal, nonanal and 2-ethyl-1-hexanol with those of five naturally derived fragrant organic compounds (FOCs, linalool, cis-3-hexen-1-ol, isoamyl alcohol, n-propyl alcohol and n-phenethyl alcohol. MTT assay of human neuroblastoma SK-N-SH cells showed that the IC50 values of linalool, cis-3-hexen-1-ol, isoamyl alcohol, n-propyl alcohol and phenethyl alcohol were 1.33, 2.3, >5, >5, and 2.39 mM, respectively, and the IC50 values of toluene, n-octanal, nonanal and 2-ethyl-1-hexanol were 850, 37.2, 8.31 and 15.1 μM, respectively. FOCs showed lower toxicities than those of VOCs. These results indicate that FOCs are safer than other compounds.

  3. Acacetin and Chrysin, Two Polyphenolic Compounds, Alleviate Telomeric Position Effect in Human Cells

    Directory of Open Access Journals (Sweden)

    Amina Boussouar

    2013-01-01

    Full Text Available We took advantage of the ability of human telomeres to silence neighboring genes (telomere position effect or TPE to design a high-throughput screening assay for drugs altering telomeres. We identified, for the first time, that two dietary flavones, acacetin and chrysin, are able to specifically alleviate TPE in human cells. We further investigated their influence on telomere integrity and showed that both drugs drastically deprotect telomeres against DNA damage response. However, telomere deprotection triggered by shelterin dysfunction does not affect TPE, indicating that acacetin and chrysin target several functions of telomeres. These results show that TPE-based screening assays represent valuable methods to discover new compounds targeting telomeres.

  4. Endocrine disrupting compounds in drinking water supply system and human health risk implication.

    Science.gov (United States)

    Wee, Sze Yee; Aris, Ahmad Zaharin

    2017-09-01

    To date, experimental and epidemiological evidence of endocrine disrupting compounds (EDCs) adversely affecting human and animal populations has been widely debated. Notably, human health risk assessment is required for risk mitigation. The lack of human health risk assessment and management may thus unreliably regulate the quality of water resources and efficiency of treatment processes. Therefore, drinking water supply systems (DWSSs) may be still unwarranted in assuring safe access to potable drinking water. Drinking water supply, such as tap water, is an additional and crucial route of human exposure to the health risks associated with EDCs. A holistic system, incorporating continuous research in DWSS monitoring and management using multi-barrier approach, is proposed as a preventive measure to reduce human exposure to the risks associated with EDCs through drinking water consumption. The occurrence of EDCs in DWSSs and corresponding human health risk implications are analyzed using the Needs, Approaches, Benefits, and Challenges (NABC) method. Therefore, this review may act as a supportive tool in protecting human health and environmental quality from EDCs, which is essential for decision-making regarding environmental monitoring and management purposes. Subsequently, the public could have sustainable access to safer and more reliable drinking water. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. High-content screening of small compounds on human embryonic stem cells.

    Science.gov (United States)

    Barbaric, Ivana; Gokhale, Paul J; Andrews, Peter W

    2010-08-01

    Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.

  6. Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds

    International Nuclear Information System (INIS)

    Josse, Rozenn; Dumont, Julie; Fautrel, Alain; Robin, Marie-Anne; Guillouzo, André

    2012-01-01

    Gene expression profiling has recently emerged as a promising approach to identify early target genes and discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens. However, early gene changes induced by genotoxic compounds in human liver remain largely unknown. Primary human hepatocytes and differentiated HepaRG cells were exposed to aflatoxin B1 (AFB1) that induces DNA damage following enzyme-mediated bioactivation. Gene expression profile changes induced by a 24 h exposure of these hepatocyte models to 0.05 and 0.25 μM AFB1 were analyzed by using oligonucleotide pangenomic microarrays. The main altered signaling pathway was the p53 pathway and related functions such as cell cycle, apoptosis and DNA repair. Direct involvement of the p53 protein in response to AFB1 was verified by using siRNA directed against p53. Among the 83 well-annotated genes commonly modulated in two pools of three human hepatocyte populations and HepaRG cells, several genes were identified as altered by AFB1 for the first time. In addition, a subset of 10 AFB1-altered genes, selected upon basis of their function or tumor suppressor role, was tested in four human hepatocyte populations and in response to other chemicals. Although they exhibited large variable inter-donor fold-changes, several of these genes, particularly FHIT, BCAS3 and SMYD3, were found to be altered by various direct and other indirect genotoxic compounds and unaffected by non-genotoxic compounds. Overall, this comprehensive analysis of early gene expression changes induced by AFB1 in human hepatocytes identified a gene subset that included several genes representing potential biomarkers of genotoxic compounds. -- Highlights: ► Gene expression profile changes induced by aflatoxin B1 in human hepatocytes. ► AFB1 modulates various genes including tumor suppressor genes and proto-oncogenes. ► Important inter-individual variations in the response to AFB1. ► Some genes also altered by other

  7. Fast Temporal Activity Proposals for Efficient Detection of Human Actions in Untrimmed Videos

    KAUST Repository

    Heilbron, Fabian Caba; Niebles, Juan Carlos; Ghanem, Bernard

    2016-01-01

    In many large-scale video analysis scenarios, one is interested in localizing and recognizing human activities that occur in short temporal intervals within long untrimmed videos. Current approaches for activity detection still struggle to handle large-scale video collections and the task remains relatively unexplored. This is in part due to the computational complexity of current action recognition approaches and the lack of a method that proposes fewer intervals in the video, where activity processing can be focused. In this paper, we introduce a proposal method that aims to recover temporal segments containing actions in untrimmed videos. Building on techniques for learning sparse dictionaries, we introduce a learning framework to represent and retrieve activity proposals. We demonstrate the capabilities of our method in not only producing high quality proposals but also in its efficiency. Finally, we show the positive impact our method has on recognition performance when it is used for action detection, while running at 10FPS.

  8. Fast Temporal Activity Proposals for Efficient Detection of Human Actions in Untrimmed Videos

    KAUST Repository

    Heilbron, Fabian Caba

    2016-12-13

    In many large-scale video analysis scenarios, one is interested in localizing and recognizing human activities that occur in short temporal intervals within long untrimmed videos. Current approaches for activity detection still struggle to handle large-scale video collections and the task remains relatively unexplored. This is in part due to the computational complexity of current action recognition approaches and the lack of a method that proposes fewer intervals in the video, where activity processing can be focused. In this paper, we introduce a proposal method that aims to recover temporal segments containing actions in untrimmed videos. Building on techniques for learning sparse dictionaries, we introduce a learning framework to represent and retrieve activity proposals. We demonstrate the capabilities of our method in not only producing high quality proposals but also in its efficiency. Finally, we show the positive impact our method has on recognition performance when it is used for action detection, while running at 10FPS.

  9. Endogenous glutathione protects human skin fibroblasts against the cytotoxic action of UVB, UVA and near-visible radiations

    International Nuclear Information System (INIS)

    Tyrell, R.M.; Pidoux, Mireille

    1986-01-01

    Both the UVB (290-320 nm) and UVA (320-380 nm) regions of sunlight damage human skin cells but, particularly at the longer wavelengths, information is scant concerning the mechanism(s) of damage induction and the roles of cellular defense mechanisms. Following extensive glutathione depletion of cultured human skin fibroblasts, the cells become strongly sensitized to the cytotoxic action of near-visible (405 nm), UVA (334 nm, 365 nm) and UVB (313 nm) but not UVC (254 nm) radiations. In the critical UVB region, the magnitude of the protection afforded by endogenous glutathione approaches that of the protection provided by excision repair. The results suggest that a significant fraction of even UVB damage can be mediated by free radical attack and that a major role of glutathione in human skin cells is to protect them from the cytotoxic action of sunlight. (author)

  10. Promising Potential of Dietary (Poly)Phenolic Compounds in the Prevention and Treatment of Diabetes Mellitus.

    Science.gov (United States)

    Dias, Tania R; Alves, Marco G; Casal, Susana; Oliveira, Pedro F; Silva, Branca M

    2017-01-01

    The incidence of diabetes mellitus (DM) is reaching alarming proportions worldwide, particularly because it is increasingly affecting younger people. This reflects the sedentary lifestyle and inappropriate dietary habits, especially due to the advent of processed foods in modern societies. Thus, unsurprisingly, the first medical recommendation to patients with clinically evident DM is the alteration in their eating behaviour, particularly regarding carbohydrates and total energy intake. Despite individual and cultural preferences, human diet makes available a large amount of phytochemicals with therapeutic potential. Phenolic compounds are the most abundant class of phytochemicals in edible plants, fruits and beverages. These compounds have strong antioxidant and anti-inflammatory activities that have been associated with specific features of their chemical structure. Among others, such properties make them promising antidiabetic agents and several mechanisms of action have already been proposed. Herein, we discuss the recent findings on the potential of dietary phenolic compounds for the prevention and/or treatment of (pre)diabetes, and associated complications. A broad range of studies supports the innate potential of phenolic compounds to protect against DM-associated deleterious effects. Their antidiabetic activity has been demonstrated by: i) regulation of carbohydrate metabolism; ii) improvement of glucose uptake; iii) protection of pancreatic β-cells; iv) enhancement of insulin action and v) regulation of crucial signalling pathways to cell homeostasis. Dietary phenolic compounds constitute an easy, safe and cost-effective way to combat the worrying scenario of DM. The interesting particularities of phenolic compounds reinforce the implementation of a (poly)phenolic-rich nutritional regime, not only for (pre)diabetic patients, but also for non-diabetic people. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. PHARMACOLOGICAL AND MEDICINAL CHEMISTRY ASPECTS OF CANNABIS COMPOUNDS

    Directory of Open Access Journals (Sweden)

    T. Cotelea

    2011-12-01

    Full Text Available The current communication includes a general overview of the scientific interest and medicianl chemistry aspects of Cannabis compounds. It relates to metabolism, pharmacological action and phisico-chemical analysis of these compounds, as well as of some isomers differing in spatial arrangement of functional groups.

  12. Coffee contains cholinomimetic compound distinct from caffeine. I: Purification and chromatographic analysis.

    Science.gov (United States)

    Tse, S Y

    1991-07-01

    Both regular and decaffeinated coffees were found to have cholinomimetic actions when tested in urethane-anesthetized rats. These actions were distinct from those of caffeine and reversible by atropine. The bioactive fraction was purified from alcoholic extracts of instant decaffeinated coffee by liquid column chromatography and preparative TLC. The purified compound showed similar pharmacological actions as the starting material. Chromatographic behavior was further characterized by analytical TLC and HPLC. Chromatographic analyses of extracts of green coffee beans and roasted ground coffees showed that the cardioactive compound was only present in roasted coffees. Similar analyses of other commonly consumed beverages, including teas and cocoa, showed that this compound was not present in beverages besides coffee.

  13. Chloric organic compound

    International Nuclear Information System (INIS)

    Moalem, F.

    2000-01-01

    Since many years ago, hazardous and toxic refuses which are results of human activities has been carelessly without any Biological and Engineering facts and knowledge discharged into our land and water. The effects of discharging those materials in environment are different. Some of refuse materials shows short and other has long-time adverse effects in our environment, Among hazardous organic chemical materials, chlorine, consider, to be the main element. Organic materials with chlorine is called chlorine hydrocarbon as a hazardous compound. This paper discuss the hazardous materials especially chloric organic compound and their misuse effects in environment and human being

  14. An Overview of Plant Phenolic Compounds and Their Importance in Human Nutrition and Management of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Derong Lin

    2016-10-01

    Full Text Available In this paper, the biosynthesis process of phenolic compounds in plants is summarized, which includes the shikimate, pentose phosphate and phenylpropanoid pathways. Plant phenolic compounds can act as antioxidants, structural polymers (lignin, attractants (flavonoids and carotenoids, UV screens (flavonoids, signal compounds (salicylic acid and flavonoids and defense response chemicals (tannins and phytoalexins. From a human physiological standpoint, phenolic compounds are vital in defense responses, such as anti-aging, anti-inflammatory, antioxidant and anti-proliferative activities. Therefore, it is beneficial to eat such plant foods that have a high antioxidant compound content, which will cut down the incidence of certain chronic diseases, for instance diabetes, cancers and cardiovascular diseases, through the management of oxidative stress. Furthermore, berries and other fruits with low-amylase and high-glucosidase inhibitory activities could be regarded as candidate food items in the control of the early stages of hyperglycemia associated with type 2 diabetes.

  15. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

    Science.gov (United States)

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies.

  16. Quinoxaline 1, 4-di-N-oxides: Biological activities and mechanisms of actions

    Directory of Open Access Journals (Sweden)

    Guyue eCheng

    2016-03-01

    Full Text Available Quinoxaline 1, 4-di-N-oxides (QdNOs have manifold biological properties, including antimicrobial, antitumoral, antitrypanosomal and antiinflammatory/antioxidant activities. These diverse activities endow them broad applications and prospects in human and veterinary medicines. As QdNOs arouse widespread interest, the evaluation of their medicinal chemistry is still in progress. In the meantime, adverse effects have been reported in some of the QdNO derivatives. For example, genotoxicity and bacterial resistance have been found in QdNO antibacterial growth promoters, conferring urgent need for discovery of new QdNO drugs. However, the modes of actions of QdNOs are not fully understood, hindering the development and innovation of these promising compounds. Here, QdNOs are categorized based on the activities and usages, among which the antimicrobial activities are consist of antibacterial, antimycobacterial and anticandida activities, and the antiprotozoal activities include antitrypanosomal, antimalarial, antitrichomonas and antiamoebic activities. The structure-activity relationship and the mode of actions of each type of activity of QdNOs are summarized, and the toxicity and the underlying mechanisms are also discussed, providing insight for the future research and development of these fascinating compounds.

  17. Handling of future human actions in the safety assessment SR-Can

    International Nuclear Information System (INIS)

    Moren, Lena

    2006-10-01

    This report documents the future human actions (FHA) considered in the long-term safety analysis of a KBS-3 repository. The report is one of the supporting documents to the safety assessment SR-Can. The purpose of this report is to provide an account of: General considerations concerning FHA; The methodology applied in SR-Can to assess FHA; The aspects of FHA that need to be considered in the evaluation of their impact on a deep geological repository; and The selection of representative scenarios for illustrative consequence analysis

  18. Handling of future human actions in the safety assessment SR-Can

    Energy Technology Data Exchange (ETDEWEB)

    Moren, Lena

    2006-10-15

    This report documents the future human actions (FHA) considered in the long-term safety analysis of a KBS-3 repository. The report is one of the supporting documents to the safety assessment SR-Can. The purpose of this report is to provide an account of: General considerations concerning FHA; The methodology applied in SR-Can to assess FHA; The aspects of FHA that need to be considered in the evaluation of their impact on a deep geological repository; and The selection of representative scenarios for illustrative consequence analysis.

  19. Gene expression profiling in Ishikawa cells: A fingerprint for estrogen active compounds

    International Nuclear Information System (INIS)

    Boehme, Kathleen; Simon, Stephanie; Mueller, Stefan O.

    2009-01-01

    Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (Diethylstilbestrol, Genistein, Zearalenone, Resveratrol, Bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused by these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, Bisphenol A, o,p'-DDT, Zearalenone, Genistein and Resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of Resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals Bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects

  20. Invariant recognition drives neural representations of action sequences.

    Directory of Open Access Journals (Sweden)

    Andrea Tacchetti

    2017-12-01

    Full Text Available Recognizing the actions of others from visual stimuli is a crucial aspect of human perception that allows individuals to respond to social cues. Humans are able to discriminate between similar actions despite transformations, like changes in viewpoint or actor, that substantially alter the visual appearance of a scene. This ability to generalize across complex transformations is a hallmark of human visual intelligence. Advances in understanding action recognition at the neural level have not always translated into precise accounts of the computational principles underlying what representations of action sequences are constructed by human visual cortex. Here we test the hypothesis that invariant action discrimination might fill this gap. Recently, the study of artificial systems for static object perception has produced models, Convolutional Neural Networks (CNNs, that achieve human level performance in complex discriminative tasks. Within this class, architectures that better support invariant object recognition also produce image representations that better match those implied by human and primate neural data. However, whether these models produce representations of action sequences that support recognition across complex transformations and closely follow neural representations of actions remains unknown. Here we show that spatiotemporal CNNs accurately categorize video stimuli into action classes, and that deliberate model modifications that improve performance on an invariant action recognition task lead to data representations that better match human neural recordings. Our results support our hypothesis that performance on invariant discrimination dictates the neural representations of actions computed in the brain. These results broaden the scope of the invariant recognition framework for understanding visual intelligence from perception of inanimate objects and faces in static images to the study of human perception of action sequences.

  1. Polyphenol Compound as a Transcription Factor Inhibitor

    Directory of Open Access Journals (Sweden)

    Seyeon Park

    2015-10-01

    Full Text Available A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor–DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein–protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1, c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and β-catenin/T cell factor (Tcf.

  2. Polyphenol Compound as a Transcription Factor Inhibitor.

    Science.gov (United States)

    Park, Seyeon

    2015-10-30

    A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor-DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein-protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1), c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and β-catenin/T cell factor (Tcf)).

  3. Ontogeny of vestibular compound action potentials in the domestic chicken

    Science.gov (United States)

    Jones, S. M.; Jones, T. A.

    2000-01-01

    Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

  4. Grape Seed Oil Compounds: Biological and Chemical Actions for Health

    Directory of Open Access Journals (Sweden)

    Juliano Garavaglia

    2016-01-01

    Full Text Available Grape seed oil is rich in phenolic compounds, fatty acids, and vitamins, with economic importance to pharmaceutical, cosmetic, and food industry. Its use as an edible oil has also been suggested, especially due to its pleasant sensory characteristics. Grape seed oil has beneficial properties for health that are mainly detected by in vitro studies, such as anti-inflammatory, cardioprotective, antimicrobial, and anticancer properties, and may interact with cellular and molecular pathways. These effects have been related to grape seed oil constituents, mainly tocopherol, linolenic acid, resveratrol, quercetin, procyanidins, carotenoids, and phytosterols. The aim of this article was to briefly review the composition and nutritional aspects of grape seed oil, the interactions of its compounds with molecular and cellular pathways, and its possible beneficial effects on health.

  5. Grape Seed Oil Compounds: Biological and Chemical Actions for Health

    Science.gov (United States)

    Garavaglia, Juliano; Markoski, Melissa M.; Oliveira, Aline; Marcadenti, Aline

    2016-01-01

    Grape seed oil is rich in phenolic compounds, fatty acids, and vitamins, with economic importance to pharmaceutical, cosmetic, and food industry. Its use as an edible oil has also been suggested, especially due to its pleasant sensory characteristics. Grape seed oil has beneficial properties for health that are mainly detected by in vitro studies, such as anti-inflammatory, cardioprotective, antimicrobial, and anticancer properties, and may interact with cellular and molecular pathways. These effects have been related to grape seed oil constituents, mainly tocopherol, linolenic acid, resveratrol, quercetin, procyanidins, carotenoids, and phytosterols. The aim of this article was to briefly review the composition and nutritional aspects of grape seed oil, the interactions of its compounds with molecular and cellular pathways, and its possible beneficial effects on health. PMID:27559299

  6. Action spectrum for photobleaching of human lenses by short wavelength visible irradiation

    DEFF Research Database (Denmark)

    Kessel, Line; Larsen, Michael

    2015-01-01

    transmission with increasing laser irradiation. CONCLUSIONS: For a 75 year old lens an effect corresponding to elimination of 15 years or more of optical ageing was obtained. This study of the spectral characteristics and intensity needed to bleach the human lens with single-photon laser effects found...... an action-spectrum peak at 420 nm tailing gradually off toward longer wavelengths and more steeply toward shorter wavelengths. The results may be used to guide experiments with two-photon bleaching....

  7. Coriandrum sativum L. (Coriander essential oil: antifungal activity and mode of action on Candida spp., and molecular targets affected in human whole-genome expression.

    Directory of Open Access Journals (Sweden)

    Irlan de Almeida Freires

    Full Text Available Oral candidiasis is an opportunistic fungal infection of the oral cavity with increasingly worldwide prevalence and incidence rates. Novel specifically-targeted strategies to manage this ailment have been proposed using essential oils (EO known to have antifungal properties. In this study, we aim to investigate the antifungal activity and mode of action of the EO from Coriandrum sativum L. (coriander leaves on Candida spp. In addition, we detected the molecular targets affected in whole-genome expression in human cells. The EO phytochemical profile indicates monoterpenes and sesquiterpenes as major components, which are likely to negatively impact the viability of yeast cells. There seems to be a synergistic activity of the EO chemical compounds as their isolation into fractions led to a decreased antimicrobial effect. C. sativum EO may bind to membrane ergosterol, increasing ionic permeability and causing membrane damage leading to cell death, but it does not act on cell wall biosynthesis-related pathways. This mode of action is illustrated by photomicrographs showing disruption in biofilm integrity caused by the EO at varied concentrations. The EO also inhibited Candida biofilm adherence to a polystyrene substrate at low concentrations, and decreased the proteolytic activity of Candida albicans at minimum inhibitory concentration. Finally, the EO and its selected active fraction had low cytotoxicity on human cells, with putative mechanisms affecting gene expression in pathways involving chemokines and MAP-kinase (proliferation/apoptosis, as well as adhesion proteins. These findings highlight the potential antifungal activity of the EO from C. sativum leaves and suggest avenues for future translational toxicological research.

  8. Cytogenetic analysis of the combined action of pesticides and radiation on human lymphocytes

    International Nuclear Information System (INIS)

    Ryabchenko, N.I.; Fesenko, Eh.V.; Antoshchina, M.M.

    1995-01-01

    The efficiency of the combined action of pesticides and irradiation at the G 0 stage was studied in cultured human lymphocytes. Carbophos (malathion) increased the yield of chromosome and chromatid fragments in irradiated lymphocytes. Herbicide 2,4-D (dichlorophenoxyacetic acid) raised lymphocyte radiosensitivity by increasing the yield of chromosome type aberrations, the radiosensitizing effect of the herbicide decreased as its concentration increased. 4 refs

  9. Exposure to perfluorononanoic acid combined with a low-dose mixture of 14 human-relevant compounds disturbs energy/lipid homeostasis in rats

    DEFF Research Database (Denmark)

    Skov, Kasper; Kongsbak, Kristine Grønning; Hadrup, Niels

    2015-01-01

    , whereas effects on lipid metabolism in the liver were mainly driven by PFNA. This study verifies that a chemical mixture given at high-end human exposure levels can affect lipid homeostasis and that the combined use of metabolomics and transcriptomics can provide complimentary information allowing......Humans are constantly exposed to a significant number of compounds and many are readily detected in human body fluids. Worryingly, several of these compounds are either suspected to be, or have already been shown to be harmful to humans either individually or in combination. However, the potential...... consequences of low-dose exposure to complex mixtures remain poorly understood. We have profiled the effects on rat blood plasma and liver homeostasis using metabolomics and transcriptomics following 2-week exposure to either a mixture of 14 common chemicals (Mix), perfluorononanoic acid (PFNA) at low (0...

  10. Antibacterial compounds of Canadian honeys target bacterial cell wall inducing phenotype changes, growth inhibition and cell lysis that resemble action of β-lactam antibiotics.

    Directory of Open Access Journals (Sweden)

    Katrina Brudzynski

    Full Text Available Honeys show a desirable broad spectrum activity against Gram-positive and negative bacteria making antibacterial activity an intrinsic property of honey and a desirable source for new drug development. The cellular targets and underlying mechanism of action of honey antibacterial compounds remain largely unknown. To facilitate the target discovery, we employed a method of phenotypic profiling by directly comparing morphological changes in Escherichia coli induced by honeys to that of ampicillin, the cell wall-active β-lactam of known mechanism of action. Firstly, we demonstrated the purity of tested honeys from potential β-lactam contaminations using quantitative LC-ESI-MS. Exposure of log-phase E. coli to honey or ampicillin resulted in time- and concentration-dependent changes in bacterial cell shape with the appearance of filamentous phenotypes at sub-inhibitory concentrations and spheroplasts at the MBC. Cell wall destruction by both agents, clearly visible on microscopic micrographs, was accompanied by increased permeability of the lipopolysaccharide outer membrane as indicated by fluorescence-activated cell sorting (FACS. More than 90% E. coli exposed to honey or ampicillin became permeable to propidium iodide. Consistently with the FACS results, both honey-treated and ampicillin-treated E. coli cells released lipopolysaccharide endotoxins at comparable levels, which were significantly higher than controls (p<0.0001. E. coli cells transformed with the ampicillin-resistance gene (β-lactamase remained sensitive to honey, displayed the same level of cytotoxicity, cell shape changes and endotoxin release as ampicillin-sensitive cells. As expected, β-lactamase protected the host cell from antibacterial action of ampicillin. Thus, both honey and ampicillin induced similar structural changes to the cell wall and LPS and that this ability underlies antibacterial activities of both agents. Since the cell wall is critical for cell growth and

  11. Thyrotropic action of human chorionic gonadotropin.

    Science.gov (United States)

    Yoshimura, M; Hershman, J M

    1995-10-01

    Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors. In these cases, greatly increased human chorionic gonadotropin (hCG) levels and suppressed TSH levels suggest that hCG has thyrotropic activity. Recent investigations have clarified the structural homology not only in the hCG and TSH molecules but also in their receptors, and this homology suggests the basis for the reactivity of hCG with the TSH receptor. The clinical significance of the thyrotropic action of hCG is now also recognized in normal pregnancy and hyperemesis gravidarum. Highly purified hLH binds to recombinant hTSH receptor and is about 10 times as potent as purified hCG in increasing cAMP. The beta-subunits of hCG and hLH share 85% sequence identity in their first 114 amino acids but differ in the carboxy-terminal peptide because hCG beta contains a 31-amino acid extension (beta-CTP). A recombinant mutant hCG that lacks beta-CTP showed almost identical potency to LH on stimulation of recombinant hTSH receptor. If intact hCG were as potent as hLH in regard to its thyrotropic activity, most pregnant women would become thyrotoxic. One of the roles of the beta-CTP may be to prevent overt hyperthyroidism in the first trimester of pregnancy when a large amount of hCG is produced by the placenta. Nicked hCG preparations, obtained from patients with trophoblastic disease or by enzymatic digestion of intact hCG, showed approximately 1.5- to 2-fold stimulation of recombinant hTSH receptor compared with intact hCG. This suggests that the thyrotropic activity of hCG may be influenced by the metabolism of the hCG molecule itself. Deglycosylation and/or desialylation of hCG enhances its thyrotropic potency. Basic hCG isoforms with lower sialic acid content extracted from hydatidiform moles were more potent in activating adenylate cyclase, and showed high bioactivity/immunoactivity (B/I) ratio in CHO cells expressing human TSH receptors. This is consistent

  12. Verification of human actions in SBO sequences with LOCA stamps in Westinghouse PWRs

    International Nuclear Information System (INIS)

    Queral, C.; Mena Rosell, L.; Jimenez Varas, G.

    2013-01-01

    The Fukushima accident has shown the need for tools and methodologies able to analyze human activities and / or capabilities of portable systems that has given the Spanish plants as a result of the stress tests . In this work we have applied the methodology of integrated safety analysis developed by the CSN , to SBO sequences with LOCA stamp. The aim is to show a methodology for testing the performances of the Emergency Operating Procedures and Guides Severe Accident Management. The simulations were performed with the tool SCAIS coupled to MAAP . The results show that there are human activities that may be beneficial in certain sequences but harmful in others. This type of problem is already known and referred to in the GGAS . However, FSR shows a practical way to check human actions cannot be obtained with other methods.

  13. Troubling practices of control: re-visiting Hannah Arendt's ideas of human action as praxis of the unpredictable.

    Science.gov (United States)

    Kohlen, Helen

    2015-07-01

    In this article, Hannah Arendt's concept of action will be used to problematize current transformations of the health care sector and examine some responses by ethicists in light of those transformations. The sphere of human interaction that should typify health care work is identified as an action of unpredictable praxis in contrast to controllable procedures and techniques which increasingly take place in the health care sector. © 2015 John Wiley & Sons Ltd.

  14. Action simulation plays a critical role in deceptive action recognition.

    Science.gov (United States)

    Tidoni, Emmanuele; Borgomaneri, Sara; di Pellegrino, Giuseppe; Avenanti, Alessio

    2013-01-09

    The ability to infer deceptive intents from nonverbal behavior is critical for social interactions. By combining single-pulse and repetitive transcranial magnetic stimulation (TMS) in healthy humans, we provide both correlational and causative evidence that action simulation is actively involved in the ability to recognize deceptive body movements. We recorded motor-evoked potentials during a faked-action discrimination (FAD) task: participants watched videos of actors lifting a cube and judged whether the actors were trying to deceive them concerning the real weight of the cube. Seeing faked actions facilitated the observers' motor system more than truthful actions in a body-part-specific manner, suggesting that motor resonance was sensitive to deceptive movements. Furthermore, we found that TMS virtual lesion to the anterior node of the action observation network, namely the left inferior frontal cortex (IFC), reduced perceptual sensitivity in the FAD task. In contrast, no change in FAD task performance was found after virtual lesions to the left temporoparietal junction (control site). Moreover, virtual lesion to the IFC failed to affect performance in a difficulty-matched spatial-control task that did not require processing of spatiotemporal (acceleration) and configurational (limb displacement) features of seen actions, which are critical to detecting deceptive intent in the actions of others. These findings indicate that the human IFC is critical for recognizing deceptive body movements and suggest that FAD relies on the simulation of subtle changes in action kinematics within the motor system.

  15. Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.

    Science.gov (United States)

    Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca

    2017-10-01

    Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Human-Health Pharmaceutical Compounds in Lake Mead, Nevada and Arizona, and Las Vegas Wash, Nevada, October 2000-August 2001

    National Research Council Canada - National Science Library

    Boyd, Robert A; Furlong, Edward T

    2002-01-01

    The U.S. Geological Survey and the National Park Service conducted a reconnaissance study to investigate the occurrence of selected human-health pharmaceutical compounds in water samples collected from Lake...

  17. Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism.

    Science.gov (United States)

    Harrison, Neil A; Doeller, Christian F; Voon, Valerie; Burgess, Neil; Critchley, Hugo D

    2014-10-01

    Inflammation impairs cognitive performance and is implicated in the progression of neurodegenerative disorders. Rodent studies demonstrated key roles for inflammatory mediators in many processes critical to memory, including long-term potentiation, synaptic plasticity, and neurogenesis. They also demonstrated functional impairment of medial temporal lobe (MTL) structures by systemic inflammation. However, human data to support this position are limited. Sequential fluorodeoxyglucose positron emission tomography together with experimentally induced inflammation was used to investigate effects of a systemic inflammatory challenge on human MTL function. Fluorodeoxyglucose positron emission tomography scanning was performed in 20 healthy participants before and after typhoid vaccination and saline control injection. After each scanning session, participants performed a virtual reality spatial memory task analogous to the Morris water maze and a mirror-tracing procedural memory control task. Fluorodeoxyglucose positron emission tomography data demonstrated an acute reduction in human MTL glucose metabolism after inflammation. The inflammatory challenge also selectively compromised human spatial, but not procedural, memory; this effect that was independent of actions on motivation or psychomotor response. Effects of inflammation on parahippocampal and rhinal glucose metabolism directly mediated actions of inflammation on spatial memory. These data demonstrate acute sensitivity of human MTL to mild peripheral inflammation, giving rise to associated functional impairment in the form of reduced spatial memory performance. Our findings suggest a mechanism for the observed epidemiologic link between inflammation and risk of age-related cognitive decline and progression of neurodegenerative disorders including Alzheimer's disease. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Candidacidal Action of CF66I, an Antifungal Compound Produced ...

    African Journals Online (AJOL)

    Erah

    terms of efficacy and/or safety is needed. During the search for .... and the formation of interconnected cells. Cell surfaces were wrinkled, and ... roughening and disruption (Fig 3b, 3c and. 3d). In addition, this compound caused the clusters of ...

  19. Human Rights Literacy: Moving towards Rights-Based Education and Transformative Action through Understandings of Dignity, Equality and Freedom

    Science.gov (United States)

    Becker, Anne; de Wet, Annamagriet; van Vollenhoven, Willie

    2015-01-01

    The twentieth century has been characterised by the proliferation of human rights in the discursive practices of the United Nations (Baxi, 1997). In this article, we explore the continual process of rights-based education towards transformative action, and an open and democratic society, as dependent upon the facilitation of human rights literacy…

  20. Evidence of the protein content of bovine and human dental pulps by the action of endodontic irrigation solutions through electrophoretic patterns

    Directory of Open Access Journals (Sweden)

    María E López

    2013-01-01

    Full Text Available Background: Sodium dodecyl sulfate polyacrylamide gel electrophoresis let to show the protein content of different tissues. Dental pulp contains connective tissue which is removed during the endodontic treatment. Many studies consider bovine rather than human pulp tissue because of its size. Aim: To evidence the protein content of bovine and human dental pulps and the action of endodontic irrigation solutions through electrophoretic patterns. Materials and Methods: Extracts of human and bovine dental pulps were prepared. Sodium hypochlorite, calcium hydroxide, chlorhexidine and ethylenediamine tetraacetic acid were used as irrigating solutions. Results: Bovine and human pulps have a small difference in two bands of proteins present between 74 kDa and 80 kDa. The denaturizing capacity of sodium hypochlorite and the washing action of calcium hydroxide and chlorhexidine were evidenced. Ethylenediamine tetraacetic acid solution was shown to contain proteins continuously during the endodontic root canal washing. Conclusions: Differences in pulp tissues and the action of irrigating solutions on their protein content would help on the understanding of the biological process of the endodontic treatment.

  1. Corrective Action Investigation Plan for Corrective Action Unit 232: Area 25 Sewage Lagoons, Nevada Test Site, Nevada, Revision 0

    International Nuclear Information System (INIS)

    1999-01-01

    The Corrective Action Investigation Plan for Corrective Action Unit 232, Area 25 Sewage Lagoons, has been developed in accordance with the Federal Facility Agreement and Consent Order that was agreed to by the U.S. Department of Energy, Nevada Operations Office; the State of Nevada Division of Environmental Protection; and the U. S. Department of Defense. Corrective Action Unit 232 consists of Corrective Action Site 25-03-01, Sewage Lagoon. Corrective Action Unit 232, Area 25 Sewage Lagoons, received sanitary effluent from four buildings within the Test Cell ''C'' Facility from the mid-1960s through approximately 1996. The Test Cell ''C'' Facility was used to develop nuclear propulsion technology by conducting nuclear test reactor studies. Based on the site history collected to support the Data Quality Objectives process, contaminants of potential concern include volatile organic compounds, semivolatile organic compounds, Resource Conservation and Recovery Act metals, petroleum hydrocarbons, polychlorinated biphenyls, pesticides, herbicides, gamma emitting radionuclides, isotopic plutonium, isotopic uranium, and strontium-90. A detailed conceptual site model is presented in Section 3.0 and Appendix A of this Corrective Action Investigation Plan. The conceptual model serves as the basis for the sampling strategy. Under the Federal Facility Agreement and Consent Order, the Corrective Action Investigation Plan will be submitted to the Nevada Division of Environmental Protection for approval. Field work will be conducted following approval of the plan. The results of the field investigation will support a defensible evaluation of corrective action alternatives in the Corrective Action Decision Document

  2. Corrective Action Investigation Plan for Corrective Action Unit 232: Area 25 Sewage Lagoons, Nevada Test Site, Nevada, Revision 0

    Energy Technology Data Exchange (ETDEWEB)

    USDOE/NV

    1999-05-01

    The Corrective Action Investigation Plan for Corrective Action Unit 232, Area 25 Sewage Lagoons, has been developed in accordance with the Federal Facility Agreement and Consent Order that was agreed to by the U.S. Department of Energy, Nevada Operations Office; the State of Nevada Division of Environmental Protection; and the U. S. Department of Defense. Corrective Action Unit 232 consists of Corrective Action Site 25-03-01, Sewage Lagoon. Corrective Action Unit 232, Area 25 Sewage Lagoons, received sanitary effluent from four buildings within the Test Cell ''C'' Facility from the mid-1960s through approximately 1996. The Test Cell ''C'' Facility was used to develop nuclear propulsion technology by conducting nuclear test reactor studies. Based on the site history collected to support the Data Quality Objectives process, contaminants of potential concern include volatile organic compounds, semivolatile organic compounds, Resource Conservation and Recovery Act metals, petroleum hydrocarbons, polychlorinated biphenyls, pesticides, herbicides, gamma emitting radionuclides, isotopic plutonium, isotopic uranium, and strontium-90. A detailed conceptual site model is presented in Section 3.0 and Appendix A of this Corrective Action Investigation Plan. The conceptual model serves as the basis for the sampling strategy. Under the Federal Facility Agreement and Consent Order, the Corrective Action Investigation Plan will be submitted to the Nevada Division of Environmental Protection for approval. Field work will be conducted following approval of the plan. The results of the field investigation will support a defensible evaluation of corrective action alternatives in the Corrective Action Decision Document.

  3. Corrective Action Investigation Plan for Corrective Action Unit 410: Waste Disposal Trenches, Tonopah Test Range, Nevada, Revision 0 (includes ROTCs 1, 2, and 3)

    Energy Technology Data Exchange (ETDEWEB)

    NNSA/NV

    2002-07-16

    This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 410 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 410 is located on the Tonopah Test Range (TTR), which is included in the Nevada Test and Training Range (formerly the Nellis Air Force Range) approximately 140 miles northwest of Las Vegas, Nevada. This CAU is comprised of five Corrective Action Sites (CASs): TA-19-002-TAB2, Debris Mound; TA-21-003-TANL, Disposal Trench; TA-21-002-TAAL, Disposal Trench; 09-21-001-TA09, Disposal Trenches; 03-19-001, Waste Disposal Site. This CAU is being investigated because contaminants may be present in concentrations that could potentially pose a threat to human health and/or the environment, and waste may have been disposed of with out appropriate controls. Four out of five of these CASs are the result of weapons testing and disposal activities at the TTR, and they are grouped together for site closure based on the similarity of the sites (waste disposal sites and trenches). The fifth CAS, CAS 03-19-001, is a hydrocarbon spill related to activities in the area. This site is grouped with this CAU because of the location (TTR). Based on historical documentation and process know-ledge, vertical and lateral migration routes are possible for all CASs. Migration of contaminants may have occurred through transport by infiltration of precipitation through surface soil which serves as a driving force for downward migration of contaminants. Land-use scenarios limit future use of these CASs to industrial activities. The suspected contaminants of potential concern which have been identified are volatile organic compounds; semivolatile organic compounds; high explosives; radiological constituents including depleted

  4. Rhythm Patterns Interaction - Synchronization Behavior for Human-Robot Joint Action

    Science.gov (United States)

    Mörtl, Alexander; Lorenz, Tamara; Hirche, Sandra

    2014-01-01

    Interactive behavior among humans is governed by the dynamics of movement synchronization in a variety of repetitive tasks. This requires the interaction partners to perform for example rhythmic limb swinging or even goal-directed arm movements. Inspired by that essential feature of human interaction, we present a novel concept and design methodology to synthesize goal-directed synchronization behavior for robotic agents in repetitive joint action tasks. The agents’ tasks are described by closed movement trajectories and interpreted as limit cycles, for which instantaneous phase variables are derived based on oscillator theory. Events segmenting the trajectories into multiple primitives are introduced as anchoring points for enhanced synchronization modes. Utilizing both continuous phases and discrete events in a unifying view, we design a continuous dynamical process synchronizing the derived modes. Inverse to the derivation of phases, we also address the generation of goal-directed movements from the behavioral dynamics. The developed concept is implemented to an anthropomorphic robot. For evaluation of the concept an experiment is designed and conducted in which the robot performs a prototypical pick-and-place task jointly with human partners. The effectiveness of the designed behavior is successfully evidenced by objective measures of phase and event synchronization. Feedback gathered from the participants of our exploratory study suggests a subjectively pleasant sense of interaction created by the interactive behavior. The results highlight potential applications of the synchronization concept both in motor coordination among robotic agents and in enhanced social interaction between humanoid agents and humans. PMID:24752212

  5. Planning Ahead: Object-Directed Sequential Actions Decoded from Human Frontoparietal and Occipitotemporal Networks

    Science.gov (United States)

    Gallivan, Jason P.; Johnsrude, Ingrid S.; Randall Flanagan, J.

    2016-01-01

    Object-manipulation tasks (e.g., drinking from a cup) typically involve sequencing together a series of distinct motor acts (e.g., reaching toward, grasping, lifting, and transporting the cup) in order to accomplish some overarching goal (e.g., quenching thirst). Although several studies in humans have investigated the neural mechanisms supporting the planning of visually guided movements directed toward objects (such as reaching or pointing), only a handful have examined how manipulatory sequences of actions—those that occur after an object has been grasped—are planned and represented in the brain. Here, using event-related functional MRI and pattern decoding methods, we investigated the neural basis of real-object manipulation using a delayed-movement task in which participants first prepared and then executed different object-directed action sequences that varied either in their complexity or final spatial goals. Consistent with previous reports of preparatory brain activity in non-human primates, we found that activity patterns in several frontoparietal areas reliably predicted entire action sequences in advance of movement. Notably, we found that similar sequence-related information could also be decoded from pre-movement signals in object- and body-selective occipitotemporal cortex (OTC). These findings suggest that both frontoparietal and occipitotemporal circuits are engaged in transforming object-related information into complex, goal-directed movements. PMID:25576538

  6. Testing antidepressant compounds in a neuropsychological model of drug action

    NARCIS (Netherlands)

    Cerit, Hilal

    2015-01-01

    Although much research effort has been put into the development of new antidepressant drugs, the process of developing a drug often fails at the stage of large randomized controlled trials (RCTs) in which an initially promising compound appears to lack efficacy after all. Several experimental

  7. Human action in a Genomic Era: debates on human nature Ação humana na Era do Genoma: debates sobre a natureza humana

    Directory of Open Access Journals (Sweden)

    Tatiana Gomes Rotondaro

    2009-03-01

    Full Text Available The supposed properties of 'genes' have led natural scientists to claim authority to explain the reasons of human action, behavior, and even human nature, which has traditionally been the object of study of the humanities. The aim of this paper is to discuss the possibilities of sociological theory dealing with the biological reductionism that establishes the strict articulation between 'human nature' and 'human action', presented in several speeches and papers by scientists and journalists and supported by features of 'genes'. I intend to argue that sociological theories may broaden their scope of analysis by encompassing biological dimensions, which does not necessarily mean adopting a biological reductionist approach.As supostas propriedades dos 'genes' levam os cientistas naturais a reivindicar autoridade para explicar as razões de atos, comportamentos e até a natureza humana, tradicional objeto de estudo das ciências humanas. O objetivo deste artigo é discutir as possibilidades de a teoria sociológica lidar com o reducionismo biológico, que estabelece uma articulação exata entre 'natureza humana' e 'ação humana'. Tal reducionismo está presente em discursos e artigos de cientistas e jornalistas, e é embasado por características dos 'genes'. Argumento que as teorias sociológicas podem ampliar suas possibilidades de análise se incorporarem dimensões biológicas, o que não implica necessariamente adotar uma abordagem reducionista.

  8. Novel Platinum (Pt)-Vandetanib Hybrid Compounds: Design, Synthesis and Investigation of Anti-cancer Activity and Mechanism of Action

    Science.gov (United States)

    Fei, Rong

    of them formed mono-dentate adducts. Moreover, hybrid compounds exhibited low toxicity in human normal kidney cells. Compounds maintained the inhibition selectivity towards EGFR from the results of kinase inhibition profiling and cell-free kinase inhibition assay. Hybrids formed strong H-bond at D800 on EGFR. Pt-vandetanib hybrids were highly effective against HCC827 cells harboring sensitizing EGFR mutation. Importantly, relative resistant rate of hybrids were much smaller than vandetanib in H1975 cells. Western blot analysis results revealed that the hybrid compounds could efficiently inhibit EGFR phosphorylation in a dose dependent manner in HCC827. While, inhibition of p-EGFR was not as good as the original TKI in H1975 cells. However, the hybrid compounds induced DNA damage and caused apoptosis of the NSCLC cells. Both of the two pathways were contributed to cancer cell death and overcome vandetanib resistance. Pt-vandetanib hybrids showed little resistance in cisplatin resistant cell line KB-CP20. Drug accumulation evaluation revealed that cisplatin accumulation in CP20 cells decreased to one eighth of that in the parental KB3.1 cells. While hybrids maintained similar drug accumulation extent in both cells lines. Mechanistic study showed that hybrid compounds could induce DNA damage and cause apoptosis, whereas cisplatin failed to cause DNA damage in KB-CP20 cells. Oncoprotein CIP2A was overexpressed in CP20 cell and was ascribed to CDDP resistance. The hybrids inhibited CIP2A expression and downstream AKT phosphorylation. It was hypothesized that downregulation of CIP2A contributed to circumvention platinum resistance. Conclusion: Novel Pt-vandetanib hybrid compounds were able to overcome vandetanib resistance in H1975 cells by maintaining inhibition to the EGFR and inducing DNA damage and apoptosis. Moreover, Pt-vandetanib hybrid compounds behaved low toxicity and overcome cisplatin resistance by being "non-substrate" to efflux transporter and successfully

  9. Learning Human Actions by Combining Global Dynamics and Local Appearance.

    Science.gov (United States)

    Luo, Guan; Yang, Shuang; Tian, Guodong; Yuan, Chunfeng; Hu, Weiming; Maybank, Stephen J

    2014-12-01

    In this paper, we address the problem of human action recognition through combining global temporal dynamics and local visual spatio-temporal appearance features. For this purpose, in the global temporal dimension, we propose to model the motion dynamics with robust linear dynamical systems (LDSs) and use the model parameters as motion descriptors. Since LDSs live in a non-Euclidean space and the descriptors are in non-vector form, we propose a shift invariant subspace angles based distance to measure the similarity between LDSs. In the local visual dimension, we construct curved spatio-temporal cuboids along the trajectories of densely sampled feature points and describe them using histograms of oriented gradients (HOG). The distance between motion sequences is computed with the Chi-Squared histogram distance in the bag-of-words framework. Finally we perform classification using the maximum margin distance learning method by combining the global dynamic distances and the local visual distances. We evaluate our approach for action recognition on five short clips data sets, namely Weizmann, KTH, UCF sports, Hollywood2 and UCF50, as well as three long continuous data sets, namely VIRAT, ADL and CRIM13. We show competitive results as compared with current state-of-the-art methods.

  10. Basic Characteristics of Human Erroneous Actions during Test and Maintenance Activities Leading to Unplanned Reactor Trips

    International Nuclear Information System (INIS)

    Kim, Jae Whan; Park, Jin Kyun

    2010-01-01

    Test and maintenance (T and M) activities of nuclear power plants are essential for sustaining the safety of a power plant and maintaining the reliability of plant systems and components. However, the potential of human errors during T and M activities has also the potential to induce unplanned reactor trips or power derate or making safety-related systems unavailable. According to the major incident/accident reports of nuclear power plants in Korea, contribution of human errors takes up about 20% of the total events. The previous study presents that most of human-related unplanned reactor trip events during normal power operation are associated with T and M activities (63%), which are comprised of plant maintenance activities such as a 'periodic preventive maintenance (PPM)', a 'planned maintenance (PM)' and a 'corrective maintenance (CM)'. This means that T and M activities should be a major subject for reducing the frequency of human-related unplanned reactor trips. This paper aims to introduce basic characteristics of human erroneous actions involved in the test and maintenance-induced unplanned reactor trip events that have occurred between 1986 and 2006 in Korean nuclear power plants. The basic characteristics are described by dividing human erroneous actions into planning-based errors and execution-based errors. For the events associated with planning failures, they are, firstly, classified according to existence of the work procedure and then described for what aspects of the procedure or work plan have deficiency or problem. On the other hand, for the events associated with execution failures, they are described from the aspect of external error modes

  11. Corrective Action Decision Document/Closure Report for Corrective Action Unit 232: Area 25 Sewage Lagoons, Nevada Test Site, Nevada

    International Nuclear Information System (INIS)

    US Department of Energy Nevada Operations Office

    1999-01-01

    This Corrective Action Decision Document/Closure Report (CADD/CR) has been prepared for Corrective Action Unit (CAU) 232, Area 25 Sewage Lagoons, in accordance with the Federal Facility Agreement and Consent Order. Located at the Nevada Test Site in Nevada, approximately 65 miles northwest of Las Vegas, CAU 232 is comprised of Corrective Action Site 25-03-01, Sewage Lagoon. This CADD/CR identifies and rationalizes the U.S. Department of Energy, Nevada Operations Office's (DOE/NV's) recommendation that no corrective action is deemed necessary for CAU 232. The Corrective Action Decision Document and Closure Report have been combined into one report because sample data collected during the July 1999 corrective action investigation (CAI) activities disclosed no evidence of contamination at the site. Contaminants of potential concern (COPCs) addressed during the CAI included total volatile organic compounds, total semivolatile organic compounds, total Resource Conservation and Recovery Act metals, total pesticides, total herbicides, total petroleum hydrocarbons (gasoline and diesel/oil range), polychlorinated biphenyls, isotopic uranium, isotopic plutonium, strontium-90, and gamma-emitting radionuclides. The data confirmed that none of the COPCs identified exceeded preliminary action levels outlined in the CAIP; therefore, no corrective actions were necessary for CAU 232. After the CAI, best management practice activities were completed and included installation of a fence and signs to limit access to the lagoons, cementing Manhole No. 2 and the diverter box, and closing off influent and effluent ends of the sewage lagoon piping. As a result of the CAI, the DOE/NV recommended that: (1) no further actions were required; (2) no Corrective Action Plan would be required; and (3) no use restrictions were required to be placed on the CAU

  12. Globalisation and health inequalities: can a human rights paradigm create space for civil society action?

    Science.gov (United States)

    London, Leslie; Schneider, Helen

    2012-01-01

    While neoliberal globalisation is associated with increasing inequalities, global integration has simultaneously strengthened the dissemination of human rights discourse across the world. This paper explores the seeming contradiction that globalisation is conceived as disempowering nations states' ability to act in their population's interests, yet implementation of human rights obligations requires effective states to deliver socio-economic entitlements, such as health. Central to the actions required of the state to build a health system based on a human rights approach is the notion of accountability. Two case studies are used to explore the constraints on states meeting their human rights obligations regarding health, the first drawing on data from interviews with parliamentarians responsible for health in East and Southern Africa, and the second reflecting on the response to the HIV/AIDS epidemic in South Africa. The case studies illustrate the importance of a human rights paradigm in strengthening parliamentary oversight over the executive in ways that prioritise pro-poor protections and in increasing leverage for resources for the health sector within parliamentary processes. Further, a rights framework creates the space for civil society action to engage with the legislature to hold public officials accountable and confirms the importance of rights as enabling civil society mobilization, reinforcing community agency to advance health rights for poor communities. In this context, critical assessment of state incapacity to meet claims to health rights raises questions as to the diffusion of accountability rife under modern international aid systems. Such diffusion of accountability opens the door to 'cunning' states to deflect rights claims of their populations. We argue that human rights, as both a normative framework for legal challenges and as a means to create room for active civil society engagement provide a means to contest both the real and the

  13. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

    Science.gov (United States)

    Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F.

    2017-01-01

    ABSTRACT Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. PMID:28188264

  14. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

    Directory of Open Access Journals (Sweden)

    Ludovic Arandel

    2017-04-01

    Full Text Available Myotonic dystrophy type 1 (DM1 and type 2 (DM2 are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations.

  15. Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds.

    Science.gov (United States)

    Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F; Furling, Denis

    2017-04-01

    Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. © 2017. Published by The Company of Biologists Ltd.

  16. Chlorinated volatile organic compounds (Cl-VOCs) in environment - sources, potential human health impacts, and current remediation technologies.

    Science.gov (United States)

    Huang, Binbin; Lei, Chao; Wei, Chaohai; Zeng, Guangming

    2014-10-01

    Chlorinated volatile organic compounds (Cl-VOCs), including polychloromethanes, polychloroethanes and polychloroethylenes, are widely used as solvents, degreasing agents and a variety of commercial products. These compounds belong to a group of ubiquitous contaminants that can be found in contaminated soil, air and any kind of fluvial mediums such as groundwater, rivers and lakes. This review presents a summary of the research concerning the production levels and sources of Cl-VOCs, their potential impacts on human health as well as state-of-the-art remediation technologies. Important sources of Cl-VOCs principally include the emissions from industrial processes, the consumption of Cl-VOC-containing products, the disinfection process, as well as improper storage and disposal methods. Human exposure to Cl-VOCs can occur through different routes, including ingestion, inhalation and dermal contact. The toxicological impacts of these compounds have been carefully assessed, and the results demonstrate the potential associations of cancer incidence with exposure to Cl-VOCs. Most Cl-VOCs thus have been listed as priority pollutants by the Ministry of Environmental Protection (MEP) of China, Environmental Protection Agency of the U.S. (U.S. EPA) and European Commission (EC), and are under close monitor and strict control. Yet, more efforts will be put into the epidemiological studies for the risk of human exposure to Cl-VOCs and the exposure level measurements in contaminated sites in the future. State-of-the-art remediation technologies for Cl-VOCs employ non-destructive methods and destructive methods (e.g. thermal incineration, phytoremediation, biodegradation, advanced oxidation processes (AOPs) and reductive dechlorination), whose advantages, drawbacks and future developments are thoroughly discussed in the later sections. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Guess Where? Actor-Supervision for Spatiotemporal Action Localization

    KAUST Repository

    Escorcia, Victor

    2018-04-05

    This paper addresses the problem of spatiotemporal localization of actions in videos. Compared to leading approaches, which all learn to localize based on carefully annotated boxes on training video frames, we adhere to a weakly-supervised solution that only requires a video class label. We introduce an actor-supervised architecture that exploits the inherent compositionality of actions in terms of actor transformations, to localize actions. We make two contributions. First, we propose actor proposals derived from a detector for human and non-human actors intended for images, which is linked over time by Siamese similarity matching to account for actor deformations. Second, we propose an actor-based attention mechanism that enables the localization of the actions from action class labels and actor proposals and is end-to-end trainable. Experiments on three human and non-human action datasets show actor supervision is state-of-the-art for weakly-supervised action localization and is even competitive to some fully-supervised alternatives.

  18. Guess Where? Actor-Supervision for Spatiotemporal Action Localization

    KAUST Repository

    Escorcia, Victor; Dao, Cuong D.; Jain, Mihir; Ghanem, Bernard; Snoek, Cees

    2018-01-01

    This paper addresses the problem of spatiotemporal localization of actions in videos. Compared to leading approaches, which all learn to localize based on carefully annotated boxes on training video frames, we adhere to a weakly-supervised solution that only requires a video class label. We introduce an actor-supervised architecture that exploits the inherent compositionality of actions in terms of actor transformations, to localize actions. We make two contributions. First, we propose actor proposals derived from a detector for human and non-human actors intended for images, which is linked over time by Siamese similarity matching to account for actor deformations. Second, we propose an actor-based attention mechanism that enables the localization of the actions from action class labels and actor proposals and is end-to-end trainable. Experiments on three human and non-human action datasets show actor supervision is state-of-the-art for weakly-supervised action localization and is even competitive to some fully-supervised alternatives.

  19. In Vitro Wound Healing Potential and Identification of Bioactive Compounds from Moringa oleifera Lam

    Directory of Open Access Journals (Sweden)

    Abubakar Amali Muhammad

    2013-01-01

    Full Text Available Moringa oleifera Lam. (M. oleifera from the monogeneric family Moringaceae is found in tropical and subtropical countries. The present study was aimed at exploring the in vitro wound healing potential of M. oleifera and identification of active compounds that may be responsible for its wound healing action. The study included cell viability, proliferation, and wound scratch test assays. Different solvent crude extracts were screened, and the most active crude extract was further subjected to differential bioguided fractionation. Fractions were also screened and most active aqueous fraction was finally obtained for further investigation. HPLC and LC-MS/MS analysis were used for identification and confirmation of bioactive compounds. The results of our study demonstrated that aqueous fraction of M. oleifera significantly enhanced proliferation and viability as well as migration of human dermal fibroblast (HDF cells compared to the untreated control and other fractions. The HPLC and LC-MS/MS studies revealed kaempferol and quercetin compounds in the crude methanolic extract and a major bioactive compound Vicenin-2 was identified in the bioactive aqueous fraction which was confirmed with standard Vicenin-2 using HPLC and UV spectroscopic methods. These findings suggest that bioactive fraction of M. oleifera containing Vicenin-2 compound may enhance faster wound healing in vitro.

  20. Multipurpose Compound

    Science.gov (United States)

    1983-01-01

    Specially formulated derivatives of an unusual basic compound known as Alcide may be the answer to effective treatment and prevention of the disease bovine mastitis, a bacterial inflammation of a cow's mammary gland that results in loss of milk production and in extreme cases, death. Manufactured by Alcide Corporation the Alcide compound has killed all tested bacteria, virus and fungi, shortly after contact, with minimal toxic effects on humans or animals. Alcide Corporation credits the existence of the mastitis treatment/prevention products to assistance provided the company by NERAC, Inc.

  1. Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Alejandro M. S. Mayer

    2017-08-01

    Full Text Available The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012–2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories.

  2. A Praxeological Approach to Intentional Action

    Directory of Open Access Journals (Sweden)

    Futerman Alan G.

    2017-10-01

    Full Text Available The concept of Intentional Action is at the core of Praxeology, as developed by the Austrian economist Ludwig von Mises. Under this unique approach, defined as the science of human action and designed to study the field of the social sciences, Mises create “action axiom”: the contention that every acting man more satisfactory state of affairs for a Austrian scholar is able to derive the fundament human action; such as value, scale of value, scarcity, abundance, profit, loss, uncertainty and causality, among others. This paper intends to present the praxeological perspective on intentional action and its epistemologic implications; it also attempts to answer objections to this thesis.

  3. The Influence of Estrogens on the Biological and Therapeutic Actions of Growth Hormone in the Liver

    Directory of Open Access Journals (Sweden)

    Leandro Fernández-Pérez

    2012-07-01

    Full Text Available GH is main regulator of body growth and composition, somatic development, intermediate metabolism and gender-dependent dimorphism in mammals. The liver is a direct target of estrogens because it expresses estrogen receptors which are connected with development, lipid metabolism and insulin sensitivity, hepatic carcinogenesis, protection from drug-induced toxicity and fertility. In addition, estrogens can modulate GH actions in liver by acting centrally, regulating pituitary GH secretion, and, peripherally, by modulating GHR-JAK2-STAT5 signalling pathway. Therefore, the interactions of estrogens with GH actions in liver are biologically and clinically relevant because disruption of GH signaling may cause alterations of its endocrine, metabolic, and gender differentiated functions and it could be linked to dramatic impact in liver physiology during development as well as in adulthood. Finally, the interplay of estrogens with GH is relevant because physiological roles these hormones have in human, and the widespread exposition of estrogen or estrogen-related compounds in human. This review highlights the importance of these hormones in liver physiology as well as how estrogens modulate GH actions in liver which will help to improve the clinical use of these hormones.

  4. Modulation of Telomerase Activity in Cancer Cells by Dietary Compounds: A Review

    Directory of Open Access Journals (Sweden)

    Takahiro Eitsuka

    2018-02-01

    Full Text Available Telomerase is expressed in ~90% of human cancer cell lines and tumor specimens, whereas its enzymatic activity is not detectable in most human somatic cells, suggesting that telomerase represents a highly attractive target for selective cancer treatment. Accordingly, various classes of telomerase inhibitors have been screened and developed in recent years. We and other researchers have successfully found that some dietary compounds can modulate telomerase activity in cancer cells. Telomerase inhibitors derived from food are subdivided into two groups: one group directly blocks the enzymatic activity of telomerase (e.g., catechin and sulfoquinovosyldiacylglycerol, and the other downregulates the expression of human telomerase reverse transcriptase (hTERT, the catalytic subunit of human telomerase, via signal transduction pathways (e.g., retinoic acid and tocotrienol. In contrast, a few dietary components, including genistein and glycated lipid, induce cellular telomerase activity in several types of cancer cells, suggesting that they may be involved in tumor progression. This review summarizes the current knowledge about the effects of dietary factors on telomerase regulation in cancer cells and discusses their molecular mechanisms of action.

  5. Corrective Action Investigation Plan for Corrective Action Unit 428: Area 3 Septic Waste Systems 1 and 5, Tonopah Test Range, Nevada

    International Nuclear Information System (INIS)

    ITLV

    1999-01-01

    and Recovery Act characteristic volatile organic compounds, semivolatile organic compounds, and metals. A limited number of samples will be analyzed for gamma- emitting radionuclides and isotopic uranium from four of the septic tanks and if radiological field screening levels are exceeded. Additional samples will be analyzed for geotechnical and hydrological properties and a bioassessment may be performed. The technical approach for investigating this Corrective Action Unit consists of the following activities: Perform video surveys of the discharge and outfall lines. Collect samples of material in the septic tanks. Conduct exploratory trenching to locate and inspect subsurface components. Collect subsurface soil samples in areas of the collection system including the septic tanks and outfall end of distribution boxes. Collect subsurface soil samples underlying the leachfield distribution pipes via trenching. Collect surface and near- surface samples near potential locations of the Acid Sewer Outfall if Septic Waste System 5 Leachfield cannot be located. Field screen samples for volatile organic compounds, total petroleum hydrocarbons, and radiological activity. Drill boreholes and collect subsurface soil samples if required. Analyze samples for total volatile organic compounds, total semivolatile organic compounds, total Resource Conservation and Recovery Act metals, and total petroleum hydrocarbons (oil/ diesel range organics). Limited number of samples will be analyzed for gamma- emitting radionuclides and isotopic uranium from particular septic tanks and if radiological field screening levels are exceeded. Collect samples from native soils beneath the distribution system and analyze for geotechnical/ hydrologic parameters. Collect and analyze bioassessment samples at the discretion of the Site Supervisor if total petroleum hydrocarbons exceed field- screening levels

  6. Impact of estrogenic compounds on DNA integrity in human spermatozoa: Evidence for cross-linking and redox cycling activities

    International Nuclear Information System (INIS)

    Bennetts, L.E.; De Iuliis, G.N.; Nixon, B.; Kime, M.; Zelski, K.; McVicar, C.M.; Lewis, S.E.; Aitken, R.J.

    2008-01-01

    A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the factors responsible for creating this stress have not been elucidated. One group of compounds that are thought to be active in this context are the estrogens, either generated as a result of the endogenous metabolism of androgens within the male reproductive tract or gaining access to the latter as a consequence of environmental exposure. In this study, a wide variety of estrogenic compounds were assessed for their direct effects on human spermatozoa in vitro. DNA integrity was assessed using the Comet and TUNEL assays, lesion frequencies were quantified by QPCR using targets within the mitochondrial and nuclear (β-globin) genomes, DNA adducts were characterized by mass spectrometry and redox activity was monitored using dihydroethidium (DHE) as the probe. Of the estrogenic and estrogen analogue compounds evaluated, catechol estrogens, quercetin, diethylstilbestrol and pyrocatechol stimulated intense redox activity while genistein was only active at the highest doses tested. Other estrogens and estrogen analogues, such as 17β-estradiol, nonylphenol, bisphenol A and 2,3-dihydroxynaphthalene were inactive. Estrogen-induced redox activity was associated with a dramatic loss of motility and, in the case of 2-hydroxyestradiol, the induction of significant DNA fragmentation. Mass spectrometry also indicated that catechol estrogens were capable of forming dimers that can cross-link the densely packed DNA strands in sperm chromatin, impairing nuclear decondensation. These results highlight the potential importance of estrogenic compounds in creating oxidative stress and DNA damage in the male germ line and suggest that further exploration of these compounds in the aetiology of male

  7. Impact of estrogenic compounds on DNA integrity in human spermatozoa: Evidence for cross-linking and redox cycling activities

    Energy Technology Data Exchange (ETDEWEB)

    Bennetts, L.E.; De Iuliis, G.N.; Nixon, B.; Kime, M.; Zelski, K. [ARC Centre of Excellence in Biotechnology and Development and Discipline of Biological Sciences, University of Newcastle, NSW (Australia); McVicar, C.M.; Lewis, S.E. [Obstetrics and Gynaecology, Queen' s University, Belfast (United Kingdom); Aitken, R.J. [ARC Centre of Excellence in Biotechnology and Development and Discipline of Biological Sciences, University of Newcastle, NSW (Australia)], E-mail: jaitken@mail.newcastle.edu.au

    2008-05-10

    A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the factors responsible for creating this stress have not been elucidated. One group of compounds that are thought to be active in this context are the estrogens, either generated as a result of the endogenous metabolism of androgens within the male reproductive tract or gaining access to the latter as a consequence of environmental exposure. In this study, a wide variety of estrogenic compounds were assessed for their direct effects on human spermatozoa in vitro. DNA integrity was assessed using the Comet and TUNEL assays, lesion frequencies were quantified by QPCR using targets within the mitochondrial and nuclear ({beta}-globin) genomes, DNA adducts were characterized by mass spectrometry and redox activity was monitored using dihydroethidium (DHE) as the probe. Of the estrogenic and estrogen analogue compounds evaluated, catechol estrogens, quercetin, diethylstilbestrol and pyrocatechol stimulated intense redox activity while genistein was only active at the highest doses tested. Other estrogens and estrogen analogues, such as 17{beta}-estradiol, nonylphenol, bisphenol A and 2,3-dihydroxynaphthalene were inactive. Estrogen-induced redox activity was associated with a dramatic loss of motility and, in the case of 2-hydroxyestradiol, the induction of significant DNA fragmentation. Mass spectrometry also indicated that catechol estrogens were capable of forming dimers that can cross-link the densely packed DNA strands in sperm chromatin, impairing nuclear decondensation. These results highlight the potential importance of estrogenic compounds in creating oxidative stress and DNA damage in the male germ line and suggest that further exploration of these compounds in the aetiology of

  8. Corrective Action Decision Document for Corrective Action Unit 254: Area 25 R-MAD Decontamination Facility, Nevada Test Site, Nevada

    International Nuclear Information System (INIS)

    2000-01-01

    This Corrective Action Decision Document identifies and rationalizes the US Department of Energy, Nevada Operations Office's selection of a recommended corrective action alternative (CAA) appropriate to facilitate the closure of Corrective Action Unit (CAU) 254, R-MAD Decontamination Facility, under the Federal Facility Agreement and Consent Order. Located in Area 25 at the Nevada Test Site in Nevada, CAU 254 is comprised of Corrective Action Site (CAS) 25-23-06, Decontamination Facility. A corrective action investigation for this CAS as conducted in January 2000 as set forth in the related Corrective Action Investigation Plan. Samples were collected from various media throughout the CAS and sent to an off-site laboratory for analysis. The laboratory results indicated the following: radiation dose rates inside the Decontamination Facility, Building 3126, and in the storage yard exceeded the average general dose rate; scanning and static total surface contamination surveys indicated that portions of the locker and shower room floor, decontamination bay floor, loft floor, east and west decon pads, north and south decontamination bay interior walls, exterior west and south walls, and loft walls were above preliminary action levels (PALs). The investigation-derived contaminants of concern (COCs) included: polychlorinated biphenyls, radionuclides (strontium-90, niobium-94, cesium-137, uranium-234 and -235), total volatile and semivolatile organic compounds, total petroleum hydrocarbons, and total Resource Conservation and Recovery Act (Metals). During the investigation, two corrective action objectives (CAOs) were identified to prevent or mitigate human exposure to COCs. Based on these CAOs, a review of existing data, future use, and current operations at the Nevada Test Site, three CAAs were developed for consideration: Alternative 1 - No Further Action; Alternative 2 - Unrestricted Release Decontamination and Verification Survey; and Alternative 3 - Unrestricted

  9. Factors for assessment of human health risk associated with remedial action at hazardous waste sites

    International Nuclear Information System (INIS)

    Stephenson, D.E.; King, C.M.; Looney, B.B.; Holmes, W.G.; Gordon, D.E.

    1985-01-01

    A risk assessment strategy that is cost effective and minimized human health risks was developed for closure of hazardous waste sites at the Savannah River Plant. The strategy consists of (1) site characterization, (2) contaminant transport modeling, and (3) determination of relative merits of alternative remedial actions according to the degree of health protection they provide

  10. Prediction of Thorough QT study results using action potential simulations based on ion channel screens.

    Science.gov (United States)

    Mirams, Gary R; Davies, Mark R; Brough, Stephen J; Bridgland-Taylor, Matthew H; Cui, Yi; Gavaghan, David J; Abi-Gerges, Najah

    2014-01-01

    Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development. Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration-effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1Hz and running to steady state, for a range of concentrations. We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of ≥5ms was predicted with up to 79% sensitivity and 100% specificity. This study provides a proof-of-principle for the prediction of human TQT study results using data available early in drug development. We highlight a number of areas that need refinement to improve the method's predictive power, but the results suggest that such approaches will provide a useful tool in cardiac safety

  11. Action understanding as inverse planning.

    Science.gov (United States)

    Baker, Chris L; Saxe, Rebecca; Tenenbaum, Joshua B

    2009-12-01

    Humans are adept at inferring the mental states underlying other agents' actions, such as goals, beliefs, desires, emotions and other thoughts. We propose a computational framework based on Bayesian inverse planning for modeling human action understanding. The framework represents an intuitive theory of intentional agents' behavior based on the principle of rationality: the expectation that agents will plan approximately rationally to achieve their goals, given their beliefs about the world. The mental states that caused an agent's behavior are inferred by inverting this model of rational planning using Bayesian inference, integrating the likelihood of the observed actions with the prior over mental states. This approach formalizes in precise probabilistic terms the essence of previous qualitative approaches to action understanding based on an "intentional stance" [Dennett, D. C. (1987). The intentional stance. Cambridge, MA: MIT Press] or a "teleological stance" [Gergely, G., Nádasdy, Z., Csibra, G., & Biró, S. (1995). Taking the intentional stance at 12 months of age. Cognition, 56, 165-193]. In three psychophysical experiments using animated stimuli of agents moving in simple mazes, we assess how well different inverse planning models based on different goal priors can predict human goal inferences. The results provide quantitative evidence for an approximately rational inference mechanism in human goal inference within our simplified stimulus paradigm, and for the flexible nature of goal representations that human observers can adopt. We discuss the implications of our experimental results for human action understanding in real-world contexts, and suggest how our framework might be extended to capture other kinds of mental state inferences, such as inferences about beliefs, or inferring whether an entity is an intentional agent.

  12. Transformations of Phenolic Compounds in an in vitro Model Simulating the Human Alimentary Tract

    Directory of Open Access Journals (Sweden)

    Aleksandra Duda-Chodak

    2009-01-01

    Full Text Available The aim of this work is to establish the antioxidant properties of polyphenolic compounds of selected fruits before and after their transformations during digestion. The experiment was conducted in in vitro conditions on a set of dialysis membranes which simulated the human digestive tract. Apples of the Šampion, Malinowka and Golden Delicious cultivars, black chokeberry, banana, Wegierka zwykla blue plum, melon and Lukasowka pear were chosen for examination. It was found that compounds obtained after simulated digestion of chokeberries, pears and bananas showed lower antioxidant potential than fresh fruits, while the opposite results were obtained for apples and plums. All dialysates obtained after digestion were characterized by lower content of total polyphenols in comparison with raw material (fresh fruits. It was found that the polyphenols were hydrolyzed, especially glycosides of quercetin and cyanidin. Phenolic acids and cyanidin were characterized by low availability for absorption, whereas catechin and quercetin had a very high level of accessibility in the model small intestine.

  13. Screening of Compounds Toxicity against Human Monocytic cell line-THP-1 by Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Pick Neora

    2004-01-01

    Full Text Available The worldwide rapid increase in bacterial resistance to numerous antibiotics requires on-going development of new drugs to enter the market. As the development of new antibiotics is lengthy and costly, early monitoring of compound's toxicity is essential in the development of novel agents. Our interest is in a rapid, simple, high throughput screening method to assess cytotoxicity induced by potential agents. Some intracellular pathogens, such as Mycobacterium tuberculosis primary site of infection is human alveolar macrophages. Thus, evaluation of candidate drugs for macrophage toxicity is crucial. Protocols for high throughput drug toxicity screening of macrophages using flow cytometry are lacking in the literature. For this application we modified a preexisting technique, propidium iodide (PI exclusion staining and utilized it for rapid toxicity tests. Samples were prepared in 96 well plates and analyzed by flow cytometry, which allowed for rapid, inexpensive and precise assessment of compound's toxicity associated with cell death.

  14. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

    Science.gov (United States)

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected.

  15. Human health effects of air pollution

    International Nuclear Information System (INIS)

    Kampa, Marilena; Castanas, Elias

    2008-01-01

    Hazardous chemicals escape to the environment by a number of natural and/or anthropogenic activities and may cause adverse effects on human health and the environment. Increased combustion of fossil fuels in the last century is responsible for the progressive change in the atmospheric composition. Air pollutants, such as carbon monoxide (CO), sulfur dioxide (SO 2 ), nitrogen oxides (NOx), volatile organic compounds (VOCs), ozone (O 3 ), heavy metals, and respirable particulate matter (PM2.5 and PM10), differ in their chemical composition, reaction properties, emission, time of disintegration and ability to diffuse in long or short distances. Air pollution has both acute and chronic effects on human health, affecting a number of different systems and organs. It ranges from minor upper respiratory irritation to chronic respiratory and heart disease, lung cancer, acute respiratory infections in children and chronic bronchitis in adults, aggravating pre-existing heart and lung disease, or asthmatic attacks. In addition, short- and long-term exposures have also been linked with premature mortality and reduced life expectancy. These effects of air pollutants on human health and their mechanism of action are briefly discussed. - The effect of air pollutants on human health and underlying mechanisms of cellular action are discussed

  16. Adjuvant effects and antiserum action potentiation by a (herbal) compound 2-hydroxy-4-methoxy benzoic acid isolated from the root extract of the Indian medicinal plant 'sarsaparilla' (Hemidesmus indicus R. Br.).

    Science.gov (United States)

    Alam, M I; Gomes, A

    1998-10-01

    The adjuvant effect and antiserum potentiation of a compound 2-hydroxy-4-methoxy benzoic acid were explored in the present investigation. This compound, isolated and purified from the Indian medicinal plant Hemidesmus indicus R. Br, possessed antisnake venom activity. Rabbits immunized with Vipera russellii venom in the presence and absence of the compound along with Freund's complete adjuvant, produced a precipitating band in immunogel diffusion and immunogel electrophoresis. The venom neutralizing capacity of this antiserum showed positive adjuvant effects as evident by the higher neutralization capacity (lethal and hemorrhage) when compared with the antiserum raised with venom alone. The pure compound potentiated the lethal action neutralization of venom by commercial equine polyvalent snake venom antiserum in experimental models. These observations raised the possibility of the use of chemical antagonists (from herbs) against snake bite, which may provide a better protection in presence of antiserum, especially in the rural parts of India.

  17. Phytosterols: natural compounds with established and emerging health benefits

    Directory of Open Access Journals (Sweden)

    Trautwein Elke A.

    2007-09-01

    Full Text Available Phytosterols (plant sterols and stanols are naturally occurring compounds which are found in all foods of plant origin. The term phytosterols refers to more than 200 different compounds. The most abundant ones in the human diet are sitosterol and campesterol. Their saturated counterparts, sitostanol and campestanol, are found in much lower amounts. Good food sources of phytosterols include vegetable oils, cereal grains, nuts, legumes, and fruits and vegetables. Phytosterols are structurally similar to cholesterol. Despite this structural similarity, they are not absorbed in significant quantities. Absorption is less than 2% for phytosterols, while it is 30-60% for cholesterol. Phytosterols are known to have various bioactive properties, which may have an impact on human health, and as such boosted interest in phytosterols in the past decade. The most important benefit is their blood cholesterol-lowering effect via partial inhibition of intestinal cholesterol absorption. The recommended daily intake of 2 g of phytosterols reduces cholesterol absorption by 30-40% and LDL-cholesterol by 10% on average. Other claimed benefits of phytosterols are possible anti-atherogenic effects as well as, particularly for beta-sitosterol, immune stimulating and anti-inflammatory activities. Furthermore, there is emerging evidence suggesting that particularly plant sterols may have beneficial effects against the development of different types of cancers, like colorectal, breast and prostate cancers. It is not clear whether mechanisms other than the established cholesterol-lowering action of phytosterols as such also contribute to these potential health benefits.

  18. Degradation of organic compounds by the combined action of light and microorganisms

    International Nuclear Information System (INIS)

    Amador, J.A.

    1990-01-01

    The degradation of organic compounds bound to soil humic acid and of pyridinedicarboxylic acids by the combined action of light and microorganisms was studied. The rate and extent of microbial mineralization of [2 14 C]glycine/humic acid complexes in the dark increased inversely with molecular weight of the molecules. Sunlight irradiation of [ 14 C] glycine/humic acid complexes resulted in loss of UV-light absorbance and an increase in the yield of 14 C-labeled low-molecular weight products. The rate and extent of microbial mineralization were also enhanced by the initial photolysis of the complexes. Greater than half of the radioactivity in the low-molecular-weight photoproducts appeared to be associated with carboxylic acids. Microbial mineralization of the organic carbon increased with integrated solar flux and with the loss of absorbance at 330 nm. Mineralization increased with the percentage of the original complex that was converted to low-molecular weight photoproducts. Only light at wavelengths below 380 nm had an effect on the molecular-weight distribution of the products formed from the glycine/humic acid complexes and on the subsequent microbial mineralization. Irradiation of [U 14 C]aniline/humic acid and of [U- 14 C]phenol/humic acid complexes in sunlight resulted in a loss of UV-light absorbance and an increase in the yield of C-labeled low molecular-weight products. Sunlight irradiation of the [ 14 C]aniline/humic acid complexes had no effect on their subsequent mineralization, but sunlight irradiation enhanced the rate and extent of mineralization of the [ 14 C]phenol/humic acid complexes. The mineralization of phenol/humic acid complexes increased with integrated solar flux and was proportional to the percentage of the original complex that was converted to low-molecular-weight photoproducts

  19. Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant compound.

    Science.gov (United States)

    Biemel, Klaus M; Friedl, D Alexander; Lederer, Markus O

    2002-07-12

    Glycation reactions leading to protein modifications (advanced glycation end products) contribute to various pathologies associated with the general aging process and long term complications of diabetes. However, only few relevant compounds have so far been detected in vivo. We now report on the first unequivocal identification of the lysine-arginine cross-links glucosepane 5, DOGDIC 6, MODIC 7, and GODIC 8 in human material. For their accurate quantification by coupled liquid chromatography-electrospray ionization mass spectrometry, (13)C-labeled reference compounds were synthesized independently. Compounds 5-8 are formed via the alpha-dicarbonyl compounds N(6)-(2,3-dihydroxy-5,6-dioxohexyl)-l-lysinate (1a,b), 3-deoxyglucosone (), methylglyoxal (), and glyoxal (), respectively. The protein-bound dideoxyosone 1a,b seems to be of prime significance for cross-linking because it presumably is not detoxified by mammalian enzymes as readily as 2-4. Hence, the follow-up product glucosepane 5 was found to be the dominant compound. Up to 42.3 pmol of 5/mg of protein was identified in human serum albumin of diabetics; the level of 5 correlates markedly with the glycated hemoglobin HbA(1c). In the water-insoluble fraction of lens proteins from normoglycemics, concentration of 5 ranges between 132.3 and 241.7 pmol/mg. The advanced glycoxidation end product GODIC 8 is elevated significantly in brunescent lenses, indicating enhanced oxidative stress in this material. Compounds 5-8 thus appear predestined as markers for pathophysiological processes.

  20. A new method to consider human actions in the framework of a dynamic PSA

    International Nuclear Information System (INIS)

    Kloos, M.; Peschke, J.

    2006-01-01

    The variety of accident sequences to be considered in the framework of a PSA derives from mutual dependencies between the physical process, the behaviour of the technical system, human actions and stochastic influences along the time axis. Because the conventional PSA approach is not able to adequately account for these interactions, so-called probabilistic dynamics methods have been developed. They generally achieve a more realistic modelling of accident scenarios and a more realistic safety assessment. At GRS, the method MCDET - a combination of Monte Carlo Simulation und the Discrete Dynamic Event Tree method - was developed. The implementation of MCDET was supplemented by a so called Crew-Module which allows - together with a deterministic dynamics code - to simulate human actions as a dynamic process evolving over time in interaction with the system and process dynamics. The Crew-Module accounts for communications between crew members and for performance shaping factors like stress, knowledge or ergonomics. This paper presents the Crew- Module and gives an overview of the results which may be obtained from its combination with MCDET and a deterministic dynamics code. The emergency operating procedure 'Secondary Side Bleed and Feed' in a German PWR is selected as an illustrative application. (authors)

  1. Action video games and improved attentional control: Disentangling selection- and response-based processes.

    Science.gov (United States)

    Chisholm, Joseph D; Kingstone, Alan

    2015-10-01

    Research has demonstrated that experience with action video games is associated with improvements in a host of cognitive tasks. Evidence from paradigms that assess aspects of attention has suggested that action video game players (AVGPs) possess greater control over the allocation of attentional resources than do non-video-game players (NVGPs). Using a compound search task that teased apart selection- and response-based processes (Duncan, 1985), we required participants to perform an oculomotor capture task in which they made saccades to a uniquely colored target (selection-based process) and then produced a manual directional response based on information within the target (response-based process). We replicated the finding that AVGPs are less susceptible to attentional distraction and, critically, revealed that AVGPs outperform NVGPs on both selection-based and response-based processes. These results not only are consistent with the improved-attentional-control account of AVGP benefits, but they suggest that the benefit of action video game playing extends across the full breadth of attention-mediated stimulus-response processes that impact human performance.

  2. Detrended fluctuation analysis of compound action potentials re-corded in the cutaneous nerves of diabetic rats

    International Nuclear Information System (INIS)

    Quiroz-González, Salvador; Rodríguez-Torres, Erika Elizabeth; Segura-Alegría, Bertha; Pereira-Venegas, Javier; Lopez-Gomez, Rosa Estela; Jiménez-Estrada, Ismael

    2016-01-01

    Highlights: • Fractal analysis of compound action potentials (CAP) evoked in diabetic nerves. • Diabetic rats showed an increment in the chaotic behavior of CAP responses. • Diabetes provokes impaired transmission of sensory information in rats. - Abstract: The electrophysiological alterations in nerves due to diabetes are classically studied in relation to their instantaneous frequency, conduction velocity and amplitude. However, analysis of amplitude variability may reflect the occurrence of feedback loop mechanisms that adjust the output as a function of its previous activity could indicate fractal dynamics. We assume that a peripheral neuropathy, such as that evoked by diabetes, the inability to maintain a steady flow of sensory information is reflected as a breakdown of the long range power-law correlation of CAP area fluctuation from cutaneous nerves. To test this, we first explored in normal rats whether fluctuations in the trial-to-trial CAP area showed a self-similar behavior or fractal structure by means of detrended fluctuations analysis (DFA), and Poincare plots. In addition, we determine whether such CAP fluctuations varied by diabetes induction. Results showed that CAP area fluctuation of SU nerves evoked in normal rats present a long term correlation and self-similar organization (fractal behavior) from trial to trial stimulation as evidenced by DFA of CAP areas. However, CAPs recorded in diabetic nerves exhibited significant reductions in area, larger duration and increased area variability and different Poincare plots than control nerves. The Hurst exponent value determined with the DFA method from a series of 2000 CAPs evoked in diabetic SU nerves was smaller than in control nerves. It is proposed that in cutaneous nerves of normal rats variability of the CAP area present a long term correlation and self-similar organization (fractal behavior), and reflect the ability to maintain a steady flow of sensory information through cutaneous nerves

  3. A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Josinete B. Vieira

    2014-07-01

    Full Text Available The Density Functional Theory (DFT method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA and hierarchical cluster analysis (HCA were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS and principal component regression (PCR models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R2 = ±0.0106, R2ajust = ±0.0125, s = ±0.0234, F(4,11 = ±12.7802, Q2 = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and SPRESS = ±0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA, cellular permeability (PCaCO2, cell permeability Maden Darby Canine Kidney (PMDCK, skin permeability (PSkin, plasma protein binding (PPB and penetration of the blood-brain barrier (CBrain/Blood, and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.

  4. Dietary Phenolic Compounds Interfere with the Fate of Hydrogen Peroxide in Human Adipose Tissue but Do Not Directly Inhibit Primary Amine Oxidase Activity

    Directory of Open Access Journals (Sweden)

    Christian Carpéné

    2016-01-01

    Full Text Available Resveratrol has been reported to inhibit monoamine oxidases (MAO. Many substrates or inhibitors of neuronal MAO interact also with other amine oxidases (AO in peripheral organs, such as semicarbazide-sensitive AO (SSAO, known as primary amine oxidase, absent in neurones, but abundant in adipocytes. We asked whether phenolic compounds (resveratrol, pterostilbene, quercetin, and caffeic acid behave as MAO and SSAO inhibitors. AO activity was determined in human adipose tissue. Computational docking and glucose uptake assays were performed in 3D models of human AO proteins and in adipocytes, respectively. Phenolic compounds fully inhibited the fluorescent detection of H2O2 generated during MAO and SSAO activation by tyramine and benzylamine. They also quenched H2O2-induced fluorescence in absence of biological material and were unable to abolish the oxidation of radiolabelled tyramine and benzylamine. Thus, phenolic compounds hampered H2O2 detection but did not block AO activity. Only resveratrol and quercetin partially impaired MAO-dependent [14C]-tyramine oxidation and behaved as MAO inhibitors. Phenolic compounds counteracted the H2O2-dependent benzylamine-stimulated glucose transport. This indicates that various phenolic compounds block downstream effects of H2O2 produced by biogenic or exogenous amine oxidation without directly inhibiting AO. Phenolic compounds remain of interest regarding their capacity to limit oxidative stress rather than inhibiting AO.

  5. Two new acetylenic compounds from Asparagus officinalis.

    Science.gov (United States)

    Li, Xue-Mei; Cai, Jin-Long; Wang, Wen-Xiang; Ai, Hong-Lian; Mao, Zi-Chao

    2016-01-01

    Two new acetylenic compounds, asparoffins A (1) and B (2), together with two known compounds, nyasol (3) and 3″-methoxynyasol (4), were isolated from stems of Asparagus officinalis. The structures of two new compounds were elucidated on the basis of detailed spectroscopic analyses (UV, IR, MS, 1D, and 2D NMR). All compounds were evaluated for their cytotoxicities against three human cancer cell lines.

  6. Curcumin as a potential protective compound against cardiac diseases.

    Science.gov (United States)

    Jiang, Shuai; Han, Jing; Li, Tian; Xin, Zhenlong; Ma, Zhiqiang; Di, Wencheng; Hu, Wei; Gong, Bing; Di, Shouyin; Wang, Dongjin; Yang, Yang

    2017-05-01

    Curcumin, which was first used 3000 years ago as an anti-inflammatory agent, is a well-known bioactive compound derived from the active ingredient of turmeric (Curcuma longa). Previous research has demonstrated that curcumin has immense therapeutic potential in a variety of diseases via anti-oxidative, anti-apoptotic, and anti-inflammatory pathways. Cardiac diseases are the leading cause of mortality worldwide and cause considerable harm to human beings. Numerous studies have suggested that curcumin exerts a protective role in the human body whereas its actions in cardiac diseases remain elusive and poorly understood. On the basis of the current evidence, we first give a brief introduction of cardiac diseases and curcumin, especially regarding the effects of curcumin in embryonic heart development. Secondly, we analyze the basic roles of curcumin in pathways that are dysregulated in cardiac diseases, including oxidative stress, apoptosis, and inflammation. Thirdly, actions of curcumin in different cardiac diseases will be discussed, as will relevant clinical trials. Eventually, we would like to discuss the existing controversial opinions and provide a detailed analysis followed by the remaining obstacles, advancement, and further prospects of the clinical application of curcumin. The information compiled here may serve as a comprehensive reference of the protective effects of curcumin in the heart, which is significant to the further research and design of curcumin analogs as therapeutic options for cardiac diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. A herbicide structure-activity analysis of the antimalarial lead compound MMV007978 against Arabidopsis thaliana.

    Science.gov (United States)

    Corral, Maxime G; Leroux, Julie; Tresch, Stefan; Newton, Trevor; Stubbs, Keith A; Mylne, Joshua S

    2018-07-01

    To fight herbicide-resistant weeds, new herbicides are needed; particularly ones with new modes of action. Building on the revelation that many antimalarial drugs are herbicidal, here we focus on the Medicines for Malaria Venture antimalarial lead compound MMV007978 that has herbicidal activity against the model plant Arabidopsis thaliana. Twenty-two variations of the lead compound thiophenyl motif revealed that change was tolerated provided ring size and charge were retained. MMV007978 was active against select monocot and dicot weeds, and physiological profiling indicated that its mode of action is related to germination and cell division. Of interest is the fact that the compound has a profile that is currently not found among known herbicides. We demonstrate that the antimalarial compound MMV007978 is also herbicidal and that exploiting lead compounds that are often understudied could lead to the identification of interesting herbicidal scaffolds. Further structural investigation of MMV007978 could provide improved herbicidal chemistries with a potential new mode of action. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  8. Radiation method of sulfide compound transformation in petroleum products

    International Nuclear Information System (INIS)

    Nadirov, N.K.; Zajkina, R.F.; Zajkin, Yu.A.; Mamonova, T.B.; Bakirova, S.F.

    1997-01-01

    Processes of sulphuric compounds transformation for petroleum and heavy residuals under radiation and thermal treatment action are studied. It is shown that sulphuric compounds are concentrated in heavy fractions as a result of radiation processing. Heavy petroleum products irradiation provokes considerable decrease in the content of mercaptans, disulphides and sulphides, which transfer to sulphoxides and sulphones appearing during radiation-induced oxidation process. (author)

  9. Cyanotoxins: producing organisms, occurrence, toxicity, mechanism of action and human health toxicological risk evaluation.

    Science.gov (United States)

    Buratti, Franca M; Manganelli, Maura; Vichi, Susanna; Stefanelli, Mara; Scardala, Simona; Testai, Emanuela; Funari, Enzo

    2017-03-01

    Cyanobacteria were present on the earth 3.5 billion years ago; since then they have colonized almost all terrestrial and aquatic ecosystems. They produce a high number of bioactive molecules, among which some are cyanotoxins. Cyanobacterial growth at high densities, forming blooms, is increasing in extension and frequency, following anthropogenic activities and climate changes, giving rise to some concern for human health and animal life exposed to cyanotoxins. Numerous cases of lethal poisonings have been associated with cyanotoxins ingestion in wild animal and livestock. In humans few episodes of lethal or severe human poisonings have been recorded after acute or short-term exposure, but the repeated/chronic exposure to low cyanotoxin levels remains a critical issue. The properties of the most frequently detected cyanotoxins (namely, microcystins, nodularins, cylindrospermopsin and neurotoxins) are here critically reviewed, describing for each toxin the available information on producing organisms, biosynthesis/genetic and occurrence, with a focus on the toxicological profile (including kinetics, acute systemic toxicity, mechanism and mode of action, local effects, repeated toxicity, genotoxicity, carcinogenicity, reproductive toxicity; human health effects and epidemiological studies; animal poisoning) with the derivation of health-based values and considerations on the risks for human health.

  10. Action observation and robotic agents: learning and anthropomorphism.

    Science.gov (United States)

    Press, Clare

    2011-05-01

    The 'action observation network' (AON), which is thought to translate observed actions into motor codes required for their execution, is biologically tuned: it responds more to observation of human, than non-human, movement. This biological specificity has been taken to support the hypothesis that the AON underlies various social functions, such as theory of mind and action understanding, and that, when it is active during observation of non-human agents like humanoid robots, it is a sign of ascription of human mental states to these agents. This review will outline evidence for biological tuning in the AON, examining the features which generate it, and concluding that there is evidence for tuning to both the form and kinematic profile of observed movements, and little evidence for tuning to belief about stimulus identity. It will propose that a likely reason for biological tuning is that human actions, relative to non-biological movements, have been observed more frequently while executing corresponding actions. If the associative hypothesis of the AON is correct, and the network indeed supports social functioning, sensorimotor experience with non-human agents may help us to predict, and therefore interpret, their movements. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Interaction of Human Enteric Viruses with Microbial Compounds: Implication for Virus Persistence and Disinfection Treatments.

    Science.gov (United States)

    Waldman, Prunelle; Meseguer, Alba; Lucas, Françoise; Moulin, Laurent; Wurtzer, Sébastien

    2017-12-05

    Although the interaction between phages and bacteria has already been well described, it only recently emerged that human viruses also interact with bacteria in the mammalian gut. We studied whether this interaction could occur in tap water and thus confer enteric viruses protection against temperature and the classical disinfection treatments used in drinking water production. We demonstrated that the addition of lipopolysaccharide or peptidoglycan of bacterial origin to enterovirus provides thermal protection through stabilization of the viral capsid. This interaction plays a role when viruses are exposed to disinfection that targets the capsid, but less so when the virus genome is directly targeted. The interaction seems to be serotype-specific, suggesting that the capsid protein sequence could be important. The protection is linked to a direct association between viral particles and bacterial compounds as observed by microscopy. These results show that bacterial compounds present in the environment can affect virus inactivation.

  12. Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones.

    Science.gov (United States)

    Colletti, Vittorio; Mandalà, Marco; Manganotti, Paolo; Ramat, Stefano; Sacchetto, Luca; Colletti, Liliana

    2011-07-01

    The rapid spread of devices generating electromagnetic fields (EMF) has raised concerns as to the possible effects of this technology on humans. The auditory system is the neural organ most frequently and directly exposed to electromagnetic activity owing to the daily use of mobile phones. In recent publications, a possible correlation between mobile phone usage and central nervous system tumours has been detected. Very recently a deterioration in otoacoustic emissions and in the auditory middle latency responses after intensive and long-term magnetic field exposure in humans has been demonstrated. To determine with objective observations if exposure to mobile phone EMF affects acoustically evoked cochlear nerve compound action potentials, seven patients suffering from Ménière's disease and undergoing retrosigmoid vestibular neurectomy were exposed to the effects of mobile phone placed over the craniotomy for 5 min. All patients showed a substantial decrease in amplitude and a significant increase in latency of cochlear nerve compound action potentials during the 5 min of exposure to EMF. These changes lasted for a period of around 5 min after exposure. The possibility that EMF can produce relatively long-lasting effects on cochlear nerve conduction is discussed and analysed in light of contrasting previous literature obtained under non-surgical conditions. Limitations of this novel approach, including the effects of the anaesthetics, craniotomy and surgical procedure, are presented in detail.

  13. Antibacterial Compounds from Red Seaweeds (Rhodophyta)

    OpenAIRE

    Noer Kasanah; Triyanto Triyanto; Drajad Sarwo Seto; Windi Amelia; Alim Isnansetyo

    2015-01-01

    Seaweeds produce great variety of metabolites benefit for human. Red seaweeds (Rhodophyta) are well known as producer of phycocolloids such agar, agarose, carragenan and great variety of secondary metabolites. This review discusses the red algal secondary metabolites with antibacterial activity. The chemical constituents of red algae are steroid, terpenoid, acetogenin and dominated by halogenated compounds mainly brominated compounds. Novel compounds with intriguing skeleton are also reported...

  14. Antispasmodic action of 5-methyl benzoxazoline-2-one: A preliminary study

    Digital Repository Service at National Institute of Oceanography (India)

    DeSouza, R.D.; Bhandare, P.N.; Fernandes, N.; Wahidullah, S.; DeSouza, L.

    In the present study, compound (1) depressed both phases of the dose-response curve. The marked effect on 5-HT response cannot be attributed solely to an antimuscarinic action of the compound which was much less (66%) as compared to (88...

  15. How can the study of action kinematics inform our understanding of human social interaction?

    Science.gov (United States)

    Krishnan-Barman, Sujatha; Forbes, Paul A G; Hamilton, Antonia F de C

    2017-10-01

    The kinematics of human actions are influenced by the social context in which they are performed. Motion-capture technology has allowed researchers to build up a detailed and complex picture of how action kinematics vary across different social contexts. Here we review three task domains-point-to-point imitation tasks, motor interference tasks and reach-to-grasp tasks-to critically evaluate how these tasks can inform our understanding of social interactions. First, we consider how actions within these task domains are performed in a non-social context, before highlighting how a plethora of social cues can perturb the baseline kinematics. We show that there is considerable overlap in the findings from these different tasks domains but also highlight the inconsistencies in the literature and the possible reasons for this. Specifically, we draw attention to the pitfalls of dealing with rich, kinematic data. As a way to avoid these pitfalls, we call for greater standardisation and clarity in the reporting of kinematic measures and suggest the field would benefit from a move towards more naturalistic tasks. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Across-site patterns of electrically evoked compound action potential amplitude-growth functions in multichannel cochlear implant recipients and the effects of the interphase gap.

    Science.gov (United States)

    Schvartz-Leyzac, Kara C; Pfingst, Bryan E

    2016-11-01

    Electrically evoked compound action potential (ECAP) measures of peak amplitude, and amplitude-growth function (AGF) slope have been shown to reflect characteristics of cochlear health (primarily spiral ganglion density) in anesthetized cochlear-implanted guinea pigs. Likewise, the effect of increasing the interphase gap (IPG) in each of these measures also reflects SGN density in the implanted guinea pig. Based on these findings, we hypothesize that suprathreshold ECAP measures, and also how they change as the IPG is increased, have the potential to be clinically applicable in human subjects. However, further work is first needed in order to determine the characteristics of these measures in humans who use cochlear implants. The current study examined across-site patterns of suprathreshold ECAP measures in 10 bilaterally-implanted, adult cochlear implant users. Results showed that both peak amplitude and slope of the AGF varied significantly from electrode to electrode in ear-specific patterns across the subjects' electrode arrays. As expected, increasing the IPG on average increased the peak amplitude and slope. Across ears, there was a significant, negative correlation between the slope of the ECAP AGF and the duration of hearing loss. Across-site patterns of ECAP peak amplitude and AGF slopes were also compared with common ground impedance values and significant correlations were observed in some cases, depending on the subject and condition. The results of this study, coupled with previous studies in animals, suggest that it is feasible to measure the change in suprathreshold ECAP measures as the IPG increases on most electrodes. Further work is needed to investigate the relationship between these measures and cochlear implant outcomes, and determine how these measures might be used when programming a cochlear-implant processor. Published by Elsevier B.V.

  17. The underlying mechanism of action for various medicinal properties of Piper betle (betel).

    Science.gov (United States)

    Haslan, H; Suhaimi, F H; Thent, Zar Chi; Das, S

    2015-01-01

    Piper betle (betel) plant belongs to the Piperaceae family. Piper. betle is widely known for its potent medicinal properties. Various active compounds are present in Piper. betle such as allylpyrocatechol, hydroxychavicol, piperbetol, ethylpiperbetol, piperol A, piperol B, chavibetol, and alkaloids which account for these beneficial medicinal properties. In the present narrative review, we looked into the various active compounds present in the Piper betle and attempted to understand their underlying mechanism of action. Proper understanding of the molecular biology involving the mechanism of action may help in better drug formulation and provide better therapeutic actions in the field of alternative and complementary medicine.

  18. On the radioprotective properties of heterocyclic nitrogenous compounds

    International Nuclear Information System (INIS)

    Rinaldi, R.; Bernard, Y.

    1964-01-01

    Continuing their study of the possible radioprotective properties of heterocyclic nitrogenous compounds, the authors study certain derivatives of imidazole and other compounds of similar structure. The results obtained showed: 1 - that the derivatives resulting from the presence in the imidazole ring of the mercapto, methyl, carbonyl, or benzyl groups are inactive: these substitutions appear to destroy the significant radioprotective activity of the imidazole, 2 - that benzimidazole, on the contrary, seems to possess highly interesting properties. The percentage of survivals obtained with mice treated with benzimidazole and exposed to lethal irradiation has encouraged the authors to undertake careful study of this substance, with a view to define optimum activity conditions, and to determine the mechanism responsible for its radioprotective action. Further on and so as to of clarify certain points that might give useful data concerning the mechanisms of action of radioprotective chemicals, in respect of each of the products the authors have studied: a - the action of these bodies on the internal temperature of mice, b - their radioprotective activity in vitro, in a solution of irradiated hemin. (authors) [fr

  19. Corrective Action Investigation Plan for Corrective Action Unit 230: Area 22 Sewage Lagoons and Corrective Action Unit 320: Area 22 Desert Rock Airport Strainer Box, Nevada Test Site, Nevada

    International Nuclear Information System (INIS)

    1999-01-01

    This Corrective Action Investigation Plan contains the U.S. Department of Energy, Nevada Operation Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 230/320 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 230 consists of Corrective Action Site (CAS) 22-03-01, Sewage Lagoon; while CAU 320 consists of CAS 22-99-01, Strainer Box. These CAUs are referred to as CAU 230/320 or the Sewage Lagoons Site. The Sewage Lagoons Site also includes an Imhoff tank, sludge bed, and associated buried sewer piping. Located in Area 22, the site was used between 1951 to 1958 for disposal of sanitary sewage effluent from the historic Camp Desert Rock Facility at the Nevada Test Site in Nevada. Based on site history, the contaminants of potential concern include volatile organic compounds (VOCs), semivolatile organic compounds, total petroleum hydrocarbons (TPH), and radionuclides. Vertical migration is estimated to be less than 12 feet below ground surface, and lateral migration is limited to the soil immediately adjacent to or within areas of concern. The proposed investigation will involve a combination of field screening for VOCs and TPH using the direct-push method and excavation using a backhoe to gather soil samples for analysis. Gamma spectroscopy will also be conducted for waste management purposes. Sampling locations will be biased to suspected worst-case areas including the nearby sludge bed, sewage lagoon inlet(s) and outlet(s), disturbed soil surrounding the lagoons, surface drainage channel south of the lagoons, and the area near the Imhoff tank. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document

  20. HIV-1 pseudovirus neutralisation by a natural compound: a potential microbicide

    CSIR Research Space (South Africa)

    Van den Berg, N

    2011-02-01

    Full Text Available . The mode of action of the compound is, however, yet to be determined. The aim is to develop a microbicide based on an indigenous plant for people infected with HIV-1. The compound will also be screened against other HIV-1 subtypes to test the neutralisation...

  1. A network approach to response inhibition: dissociating functional connectivity of neural components involved in action restraint and action cancellation

    NARCIS (Netherlands)

    Dambacher, F.; Sack, A.T.; Lobbestael, J.; Arntz, A.; Brugman, S.; Schuhmann, T.

    2014-01-01

    The ability to inhibit action tendencies is vital for adaptive human behaviour. Various paradigms are supposed to assess action inhibition and are often used interchangeably. However, these paradigms are based on different conceptualizations (action restraint vs. action cancellation) and the

  2. Corrective Action Investigation Plan for Corrective Action Unit 543: Liquid Disposal Units, Nevada Test Site, Nevada: Revision 0

    Energy Technology Data Exchange (ETDEWEB)

    U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office

    2004-05-03

    The general purpose of this Corrective Action Investigation Plan is to ensure that adequate data are collected to provide sufficient and reliable information to identify, evaluate, and select technically viable corrective action alternatives (CAAs) for Corrective Action Unit (CAU) 543: Liquid Disposal Units, Nevada Test Site (NTS), Nevada. Located in Areas 6 and 15 on the NTS, CAU 543 is comprised of a total of seven corrective action sites (CASs), one in Area 6 and six in Area 15. The CAS in Area 6 consists of a Decontamination Facility and its components which are associated with decontamination of equipment, vehicles, and materials related to nuclear testing. The six CASs in Area 15 are located at the U.S. Environmental Protection Agency Farm and are related to waste disposal activities at the farm. Sources of possible contamination at Area 6 include potentially contaminated process waste effluent discharged through a process waste system, a sanitary waste stream generated within buildings of the Decon Facility, and radiologically contaminated materials stored within a portion of the facility yard. At Area 15, sources of potential contamination are associated with the dairy operations and the animal tests and experiments involving radionuclide uptake. Identified contaminants of potential concern include volatile organic compounds, semivolatile organic compounds, petroleum hydrocarbons, pesticides, herbicides, polychlorinated biphenyls, metals, and radionuclides. Three corrective action closure alternatives - No Further Action, Close in Place, or Clean Closure - will be recommended for CAU 543 based on an evaluation of all the data quality objective-related data. Field work will be conducted following approval of the plan. The results of the field investigation will support a defensible evaluation of CAAs that will be presented in the Corrective Action Decision Document.

  3. Effect of tritiated compounds on sister-chromatid exchanges (SCE) in human lymphocytes in vitro

    International Nuclear Information System (INIS)

    Gong Manli; Rao Yongqing; Chen Guanying; Wu Weiwei; Zhao Zilan; Shen Lei

    1990-01-01

    Human lymphocytes treated in vitro with various activities of 3 H-TdR and 3 H-UdR were cultured to understand the effects of tritium on the cell cycle and the frequency of SCE. The results of these experiments indicated that both tritiated compounds make the frequency of SCE increase and the cell cycle delay. The frequency of SCE increased markedly with activity of 3 H. With respect to delaying cell cycle, 3 H-UdR was more effective than 3 H-TdR. The average frequencies of SCE for 3 H-UdR were higher than those for 3 H-TdR. With the exception of 3.7 x 10 3 Bq/mL group and differences between other 3 H-UdR groups and corresponding 3 H-TdR group were significant (t test, p < 0.01). These results suggest that tritiated compounds may have the effect on the cell proliferating rate. The cell proliferating rate index (PRI) seems to be related with the frequency of SCE: the higher the frequency of SCE, the lower the PRI is

  4. Electrically evoked compound action potentials artefact rejection by independent component analysis: procedure automation.

    Science.gov (United States)

    Akhoun, Idrick; McKay, Colette; El-Deredy, Wael

    2015-01-15

    Independent-components-analysis (ICA) successfully separated electrically-evoked compound action potentials (ECAPs) from the stimulation artefact and noise (ECAP-ICA, Akhoun et al., 2013). This paper shows how to automate the ECAP-ICA artefact cancellation process. Raw-ECAPs without artefact rejection were consecutively recorded for each stimulation condition from at least 8 intra-cochlear electrodes. Firstly, amplifier-saturated recordings were discarded, and the data from different stimulus conditions (different current-levels) were concatenated temporally. The key aspect of the automation procedure was the sequential deductive source categorisation after ICA was applied with a restriction to 4 sources. The stereotypical aspect of the 4 sources enables their automatic classification as two artefact components, a noise and the sought ECAP based on theoretical and empirical considerations. The automatic procedure was tested using 8 cochlear implant (CI) users and one to four stimulus electrodes. The artefact and noise sources were successively identified and discarded, leaving the ECAP as the remaining source. The automated ECAP-ICA procedure successfully extracted the correct ECAPs compared to standard clinical forward masking paradigm in 22 out of 26 cases. ECAP-ICA does not require extracting the ECAP from a combination of distinct buffers as it is the case with regular methods. It is an alternative that does not have the possible bias of traditional artefact rejections such as alternate-polarity or forward-masking paradigms. The ECAP-ICA procedure bears clinical relevance, for example as the artefact rejection sub-module of automated ECAP-threshold detection techniques, which are common features of CI clinical fitting software. Copyright © 2014. Published by Elsevier B.V.

  5. Coordinated action of histone modification and microRNA regulations in human genome.

    Science.gov (United States)

    Wang, Xuan; Zheng, Guantao; Dong, Dong

    2015-10-10

    Both histone modifications and microRNAs (miRNAs) play pivotal role in gene expression regulation. Although numerous studies have been devoted to explore the gene regulation by miRNA and epigenetic regulations, their coordinated actions have not been comprehensively examined. In this work, we systematically investigated the combinatorial relationship between miRNA and epigenetic regulation by taking advantage of recently published whole genome-wide histone modification data and high quality miRNA targeting data. The results showed that miRNA targets have distinct histone modification patterns compared with non-targets in their promoter regions. Based on this finding, we proposed a machine learning approach to fit predictive models on the task to discern whether a gene is targeted by a specific miRNA. We found a considerable advantage in both sensitivity and specificity in diverse human cell lines. Finally, we found that our predicted miRNA targets are consistently annotated with Gene Ontology terms. Our work is the first genome-wide investigation of the coordinated action of miRNA and histone modification regulations, which provide a guide to deeply understand the complexity of transcriptional regulation. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Review of Natural Compounds for Potential Skin Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tawona N. Chinembiri

    2014-08-01

    Full Text Available Most anti-cancer drugs are derived from natural resources such as marine, microbial and botanical sources. Cutaneous malignant melanoma is the most aggressive form of skin cancer, with a high mortality rate. Various treatments for malignant melanoma are available, but due to the development of multi-drug resistance, current or emerging chemotherapies have a relatively low success rates. This emphasizes the importance of discovering new compounds that are both safe and effective against melanoma. In vitro testing of melanoma cell lines and murine melanoma models offers the opportunity for identifying mechanisms of action of plant derived compounds and extracts. Common anti-melanoma effects of natural compounds include potentiating apoptosis, inhibiting cell proliferation and inhibiting metastasis. There are different mechanisms and pathways responsible for anti-melanoma actions of medicinal compounds such as promotion of caspase activity, inhibition of angiogenesis and inhibition of the effects of tumor promoting proteins such as PI3-K, Bcl-2, STAT3 and MMPs. This review thus aims at providing an overview of anti-cancer compounds, derived from natural sources, that are currently used in cancer chemotherapies, or that have been reported to show anti-melanoma, or anti-skin cancer activities. Phytochemicals that are discussed in this review include flavonoids, carotenoids, terpenoids, vitamins, sulforaphane, some polyphenols and crude plant extracts.

  7. Sensory and Physiological Effects on Humans of Combined Exposures to Air Temperatures and Volatile Organic Compounds

    DEFF Research Database (Denmark)

    Mølhave, Lars; Liu, Zunyong; Jørgensen, Anne Hempel

    1993-01-01

    Ten healthy humans were exposed to combinations of volatile organic compounds (VOCs) and air temperature (0 mg/m3 and 10 mg/m3 of a mixture of 22 volatile organic compounds and 18, 22 and 26° C). Previously demonstrated effects of VOCs and thermal exposures were replicated. For the first time nasal...... cross-sectional areas and nasal volumes, as measured by acoustic rhinometry, were shown to decrease with decreasing temperature and increasing VOC exposure. Temperature and pollutant exposures affected air quality, the need for more ventilation, skin humidity on the forehead, sweating, acute sensory...... irritation and possibly watering eyes in an additive way. Interactions were found for odor intensity (p = 0.1), perceived facial skin temperature and dryness, general well-being, tear film stability, and nasal cavity dimension. The presence of interactions implies that in the future guidelines for acceptable...

  8. The mast cell degranulator compound 48/80 directly activates neurons.

    Directory of Open Access Journals (Sweden)

    Michael Schemann

    Full Text Available BACKGROUND: Compound 48/80 is widely used in animal and tissue models as a "selective" mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents. METHODOLOGY/PRINCIPAL FINDINGS: We used in vivo recordings from extrinsic intestinal afferents together with Ca(++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca(++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca(++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H(1 and H(2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca(++ transients in mast cell-free enteric neuron cultures. CONCLUSIONS/SIGNIFICANCE: The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn.

  9. Integrating women's human rights into global health research: an action framework.

    Science.gov (United States)

    Baptiste, Donna; Kapungu, Chisina; Khare, Manorama H; Lewis, Yvonne; Barlow-Mosha, Linda

    2010-11-01

    This article uses Scale of Change theory as a framework to guide global health researchers to synergistically target women's health outcomes in the context of improving their right to freedom, equity, and equality of opportunities. We hypothesize that health researchers can do so through six action strategies. These strategies include (1) becoming fully informed of women's human rights directives to integrate them into research, (2) mainstreaming gender in the research, (3) using the expertise of grass roots women's organizations in the setting, (4) showcasing women's equity and equality in the organizational infrastructure, (5) disseminating research findings to policymakers in the study locale to influence health priorities, and (6) publicizing the social conditions that are linked to women's diseases. We explore conceptual and logistical dilemmas in transforming a study using these principles and also provide a case study of obstetric fistula reduction in Nigeria to illustrate how these strategies can be operationalized. Our intent is to offer a feasible approach to health researchers who, conceptually, may link women's health to social and cultural conditions but are looking for practical implementation strategies to examine a women's health issue through the lens of their human rights.

  10. In Vitro and Ex Vivo Chemopreventive Action of Mauritia flexuosa Products

    Directory of Open Access Journals (Sweden)

    Joilane Alves Pereira-Freire

    2018-01-01

    Full Text Available Mauritia flexuosa (Arecaceae, known as “Buriti,” is a Brazilian palm tree with high economic potential for local communities. Herein, we investigated the phytochemistry profile and antioxidant potential of M. flexuosa fruits and determined the bioaccessibility of phenolic compounds. Peels revealed upper values for phenols, flavonoids, carotenoids, tannins, and ascorbic acid when compared to the pulps and endocarps. All samples showed capacity to scavenger free radicals (0.5, 1.0, 2.0, 4.0, and 8.0 mg/mL but peels presented higher scavenger action in all methods explored. Phenolic compounds identified by HPLC displayed reduced bioaccessibility after in vitro simulated gastrointestinal digestion for pulp (38.7%, peel (18.7%, and endocarp (22.3% extracts (P<0.05. Buriti fruits also protected rat blood cells against lysis induced by peroxyl radicals. We demonstrated the promising chemopreventive potentialities of M. flexuosa fruits and their by-products and peels with higher quantities of bioactive compounds and phenolic substances before and after in vitro bioaccessibility investigation. In Brazil, these parts are discarded or underused, mainly as feed for ruminant animals. Consequently, it is extremely important to explore nutritional characteristics of these by-products for human/livestock foods and to install biofriendly techniques and sustainable biotechnology handling of natural resources.

  11. COST action TD1407: network on technology-critical elements (NOTICE)--from environmental processes to human health threats.

    Science.gov (United States)

    Cobelo-García, A; Filella, M; Croot, P; Frazzoli, C; Du Laing, G; Ospina-Alvarez, N; Rauch, S; Salaun, P; Schäfer, J; Zimmermann, S

    2015-10-01

    The current socio-economic, environmental and public health challenges that countries are facing clearly need common-defined strategies to inform and support our transition to a sustainable economy. Here, the technology-critical elements (which includes Ga, Ge, In, Te, Nb, Ta, Tl, the Platinum Group Elements and most of the rare-earth elements) are of great relevance in the development of emerging key technologies-including renewable energy, energy efficiency, electronics or the aerospace industry. In this context, the increasing use of technology-critical elements (TCEs) and associated environmental impacts (from mining to end-of-life waste products) is not restricted to a national level but covers most likely a global scale. Accordingly, the European COST Action TD1407: Network on Technology-Critical Elements (NOTICE)-from environmental processes to human health threats, has an overall objective for creating a network of scientists and practitioners interested in TCEs, from the evaluation of their environmental processes to understanding potential human health threats, with the aim of defining the current state of knowledge and gaps, proposing priority research lines/activities and acting as a platform for new collaborations and joint research projects. The Action is focused on three major scientific areas: (i) analytical chemistry, (ii) environmental biogeochemistry and (iii) human exposure and (eco)-toxicology.

  12. Distributions of polyhalogenated compounds in Hudson River (New York, USA) fish in relation to human uses along the river

    International Nuclear Information System (INIS)

    Skinner, Lawrence C.

    2011-01-01

    PCBs (as Aroclor concentrations) have been extensively examined in fish along the Hudson River, but other xenobiotic chemicals in fish have had limited assessment. This study determined concentrations and congener distributions of polybrominated diphenyl ethers (PBDEs), polybrominated and polychlorinated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs and PCDD/Fs), and polychlorinated biphenyls (PCBs) in smallmouth bass and striped bass taken from a 385 km reach of the Hudson River. Concentrations of PBDEs and PCBs in smallmouth bass, and PCBs in striped bass, were positively related to human uses of the compounds in the basin. Generally low levels of PCDD/Fs were found. One striped bass, however, contained elevated 2,3,7,8-TCDD, indicating exposure to a known source in the adjacent Newark Bay-Passaic River basin. PBDDs were generally below detection. PBDFs were present in four of 18 smallmouth bass, but were not detected in striped bass. Dioxin-like PCBs contribute most to 2,3,7,8-TCDD toxic equivalents in 29 of 30 samples. - Highlights: → In the Hudson River, → PBDEs in smallmouth bass follow human population patterns, but do not for striped bass. → Proximity to known PCB sources govern PCB levels and patterns in fish. → PBDFs were in smallmouth bass but not striped bass. PBDDs were present in one fish. → PCDD/Fs were low in 29 of 30 fish. A 2,3,7,8-TCDD source affected one striped bass. → PCBs contribute most to 2,3,7,8-TCDD toxic equivalents in 29 of 30 samples. - Residues of polyhalogenated compounds in resident and migratory fish from the Hudson River are compared with human uses of the compounds in the river basin.

  13. Distributions of polyhalogenated compounds in Hudson River (New York, USA) fish in relation to human uses along the river

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, Lawrence C., E-mail: lxskinne@gw.dec.state.ny.us [New York State Department of Environmental Conservation, 625 Broadway, Albany, NY 12233 (United States)

    2011-10-15

    PCBs (as Aroclor concentrations) have been extensively examined in fish along the Hudson River, but other xenobiotic chemicals in fish have had limited assessment. This study determined concentrations and congener distributions of polybrominated diphenyl ethers (PBDEs), polybrominated and polychlorinated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs and PCDD/Fs), and polychlorinated biphenyls (PCBs) in smallmouth bass and striped bass taken from a 385 km reach of the Hudson River. Concentrations of PBDEs and PCBs in smallmouth bass, and PCBs in striped bass, were positively related to human uses of the compounds in the basin. Generally low levels of PCDD/Fs were found. One striped bass, however, contained elevated 2,3,7,8-TCDD, indicating exposure to a known source in the adjacent Newark Bay-Passaic River basin. PBDDs were generally below detection. PBDFs were present in four of 18 smallmouth bass, but were not detected in striped bass. Dioxin-like PCBs contribute most to 2,3,7,8-TCDD toxic equivalents in 29 of 30 samples. - Highlights: > In the Hudson River, > PBDEs in smallmouth bass follow human population patterns, but do not for striped bass. > Proximity to known PCB sources govern PCB levels and patterns in fish. > PBDFs were in smallmouth bass but not striped bass. PBDDs were present in one fish. > PCDD/Fs were low in 29 of 30 fish. A 2,3,7,8-TCDD source affected one striped bass. > PCBs contribute most to 2,3,7,8-TCDD toxic equivalents in 29 of 30 samples. - Residues of polyhalogenated compounds in resident and migratory fish from the Hudson River are compared with human uses of the compounds in the river basin.

  14. Adaptive control of human action: The role of outcome representations and reward signals

    Directory of Open Access Journals (Sweden)

    Hans eMarien

    2013-09-01

    Full Text Available The present paper aims to advance the understanding of the control of human behavior by integrating two lines of literature that so far have led separate lives. First, one line of literature is concerned with the ideomotor principle of human behavior, according to which actions are represented in terms of their outcomes. The second line of literature mainly considers the role of reward signals in adaptive control. Here, we offer a combined perspective on how outcome representations and reward signals work together to modulate adaptive control processes. We propose that reward signals signify the value of outcome representations and facilitate the recruitment of control resources in situations where behavior needs to be maintained or adapted to attain the represented outcome. We discuss recent research demonstrating how adaptive control of goal-directed behavior may emerge when outcome representations are co-activated with positive reward signals.

  15. Antiviral agents: structural basis of action and rational design.

    Science.gov (United States)

    Menéndez-Arias, Luis; Gago, Federico

    2013-01-01

    During the last 30 years, significant progress has been made in the development of novel antiviral drugs, mainly crystallizing in the establishment of potent antiretroviral therapies and the approval of drugs inhibiting hepatitis C virus replication. Although major targets of antiviral intervention involve intracellular processes required for the synthesis of viral proteins and nucleic acids, a number of inhibitors blocking virus assembly, budding, maturation, entry or uncoating act on virions or viral capsids. In this review, we focus on the drug discovery process while presenting the currently used methodologies to identify novel antiviral drugs by using a computer-based approach. We provide examples illustrating structure-based antiviral drug development, specifically neuraminidase inhibitors against influenza virus (e.g. oseltamivir and zanamivir) and human immunodeficiency virus type 1 protease inhibitors (i.e. the development of darunavir from early peptidomimetic compounds such as saquinavir). A number of drugs in preclinical development acting against picornaviruses, hepatitis B virus and human immunodeficiency virus and their mechanism of action are presented to show how viral capsids can be exploited as targets of antiviral therapy.

  16. Physicochemical Mechanisms of Synergistic Biological Action of Combinations of Aromatic Heterocyclic Compounds

    OpenAIRE

    Evstigneev, Maxim P.

    2013-01-01

    The mechanisms of synergistic biological effects observed in the simultaneous use of aromatic heterocyclic compounds in combination are reviewed, and the specific biological role of heteroassociation of aromatic molecules is discussed.

  17. What did domestication do to dogs? A new account of dogs' sensitivity to human actions.

    Science.gov (United States)

    Udell, Monique A R; Dorey, Nicole R; Wynne, Clive D L

    2010-05-01

    Over the last two decades increasing evidence for an acute sensitivity to human gestures and attentional states in domestic dogs has led to a burgeoning of research into the social cognition of this highly familiar yet previously under-studied animal. Dogs (Canis lupus familiaris) have been shown to be more successful than their closest relative (and wild progenitor) the wolf, and than man's closest relative, the chimpanzee, on tests of sensitivity to human social cues, such as following points to a container holding hidden food. The "Domestication Hypothesis" asserts that during domestication dogs evolved an inherent sensitivity to human gestures that their non-domesticated counterparts do not share. According to this view, sensitivity to human cues is present in dogs at an early age and shows little evidence of acquisition during ontogeny. A closer look at the findings of research on canine domestication, socialization, and conditioning, brings the assumptions of this hypothesis into question. We propose the Two Stage Hypothesis, according to which the sensitivity of an individual animal to human actions depends on acceptance of humans as social companions, and conditioning to follow human limbs. This offers a more parsimonious explanation for the domestic dog's sensitivity to human gestures, without requiring the use of additional mechanisms. We outline how tests of this new hypothesis open directions for future study that offer promise of a deeper understanding of mankind's oldest companion.

  18. Action-based effects on music perception.

    Science.gov (United States)

    Maes, Pieter-Jan; Leman, Marc; Palmer, Caroline; Wanderley, Marcelo M

    2014-01-03

    The classical, disembodied approach to music cognition conceptualizes action and perception as separate, peripheral processes. In contrast, embodied accounts of music cognition emphasize the central role of the close coupling of action and perception. It is a commonly established fact that perception spurs action tendencies. We present a theoretical framework that captures the ways in which the human motor system and its actions can reciprocally influence the perception of music. The cornerstone of this framework is the common coding theory, postulating a representational overlap in the brain between the planning, the execution, and the perception of movement. The integration of action and perception in so-called internal models is explained as a result of associative learning processes. Characteristic of internal models is that they allow intended or perceived sensory states to be transferred into corresponding motor commands (inverse modeling), and vice versa, to predict the sensory outcomes of planned actions (forward modeling). Embodied accounts typically refer to inverse modeling to explain action effects on music perception (Leman, 2007). We extend this account by pinpointing forward modeling as an alternative mechanism by which action can modulate perception. We provide an extensive overview of recent empirical evidence in support of this idea. Additionally, we demonstrate that motor dysfunctions can cause perceptual disabilities, supporting the main idea of the paper that the human motor system plays a functional role in auditory perception. The finding that music perception is shaped by the human motor system and its actions suggests that the musical mind is highly embodied. However, we advocate for a more radical approach to embodied (music) cognition in the sense that it needs to be considered as a dynamical process, in which aspects of action, perception, introspection, and social interaction are of crucial importance.

  19. Action-based effects on music perception

    Science.gov (United States)

    Maes, Pieter-Jan; Leman, Marc; Palmer, Caroline; Wanderley, Marcelo M.

    2013-01-01

    The classical, disembodied approach to music cognition conceptualizes action and perception as separate, peripheral processes. In contrast, embodied accounts of music cognition emphasize the central role of the close coupling of action and perception. It is a commonly established fact that perception spurs action tendencies. We present a theoretical framework that captures the ways in which the human motor system and its actions can reciprocally influence the perception of music. The cornerstone of this framework is the common coding theory, postulating a representational overlap in the brain between the planning, the execution, and the perception of movement. The integration of action and perception in so-called internal models is explained as a result of associative learning processes. Characteristic of internal models is that they allow intended or perceived sensory states to be transferred into corresponding motor commands (inverse modeling), and vice versa, to predict the sensory outcomes of planned actions (forward modeling). Embodied accounts typically refer to inverse modeling to explain action effects on music perception (Leman, 2007). We extend this account by pinpointing forward modeling as an alternative mechanism by which action can modulate perception. We provide an extensive overview of recent empirical evidence in support of this idea. Additionally, we demonstrate that motor dysfunctions can cause perceptual disabilities, supporting the main idea of the paper that the human motor system plays a functional role in auditory perception. The finding that music perception is shaped by the human motor system and its actions suggests that the musical mind is highly embodied. However, we advocate for a more radical approach to embodied (music) cognition in the sense that it needs to be considered as a dynamical process, in which aspects of action, perception, introspection, and social interaction are of crucial importance. PMID:24454299

  20. Action-based effects on music perception

    Directory of Open Access Journals (Sweden)

    Pieter-Jan eMaes

    2014-01-01

    Full Text Available The classical, disembodied approach to music cognition conceptualizes action and perception as separate, peripheral phenomena. In contrast, embodied accounts to music cognition emphasize the central role of the close coupling of action and perception. It is a commonly established fact that perception spurs action tendencies. We present a theoretical framework capturing the ways that the human motor system, and the actions it produces, can reciprocally influence the perception of music. The cornerstone of this framework is the common coding theory postulating a representational overlap in the brain between the planning, the execution, and the perception of movement. The integration of action and perception in so-called internal models is explained as a result of associative learning processes. Characteristic of internal models is that they allow intended or perceived sensory states to be transferred into corresponding motor commands (inverse modelling, and vice versa, to predict the sensory outcomes of planned actions (forward modelling. Embodied accounts typically adhere to inverse modelling to explain action effects on music perception (Leman, 2007. We extent this account by pinpointing forward modelling as an alternative mechanism by which action can modulate perception. We provide an extensive overview of recent empirical evidence in support of this idea. Additionally, we demonstrate that motor dysfunctions can cause perceptual disabilities, supporting the main idea of the paper that the human motor system plays a functional role in auditory perception. The finding that music perception is shaped by the human motor system, and the action it produces, suggests that the musical mind is highly embodied. However, we advocate for a more radical approach to embodied (music cognition in the sense that it needs to be considered as a dynamic process, in which aspects of action, perception, introspection, and social interaction are of crucial

  1. Perfluorinated Compounds: Emerging POPs with Potential Immunotoxicity

    Science.gov (United States)

    Perfluorinated compounds (PFCs) have been recognized as an important class of environmental contaminants commonly detected in blood samples of both wildlife and humans. These compounds have been in use for more than 60 years as surface treatment chemicals, polymerization aids, an...

  2. Speciation analysis of organotin compounds in human urine by headspace solid-phase micro-extraction and gas chromatography with pulsed flame photometric detection.

    Science.gov (United States)

    Valenzuela, Aníbal; Lespes, Gaëtane; Quiroz, Waldo; Aguilar, Luis F; Bravo, Manuel A

    2014-07-01

    A new headspace solid-phase micro-extraction (HS-SPME) method followed by gas chromatography with pulsed flame photometric detection (GC-PFPD) analysis has been developed for the simultaneous determination of 11 organotin compounds, including methyl-, butyl-, phenyl- and octyltin derivates, in human urine. The methodology has been validated by the analysis of urine samples fortified with all analytes at different concentration levels, and recovery rates above 87% and relative precisions between 2% and 7% were obtained. Additionally, an experimental-design approach has been used to model the storage stability of organotin compounds in human urine, demonstrating that organotins are highly degraded in this medium, although their stability is satisfactory during the first 4 days of storage at 4 °C and pH=4. Finally, this methodology was applied to urine samples collected from harbor workers exposed to antifouling paints; methyl- and butyltins were detected, confirming human exposure in this type of work environment. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. IRIS Toxicological Review of Thallium and Compounds ...

    Science.gov (United States)

    Thallium compounds are used in the semiconductor industry, the manufacture of optic lenses and low-melting glass, low-temperature thermometers, alloys, electronic devices, mercury lamps, fireworks, and imitation germs, and clinically as an imaging agent in the diagnosis of certain tumors. EPA's assessment of noncancer health effects and carcinogenic potential of thallium compounds was last prepared and added to the IRIS database between 1988 and 1990. The IRIS program is preparing an assessment that will incorporate current health effects information available for thallium and compounds, and current risk assessment methods. The IRIS assessment for thallium compounds will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physiochemical and toxicokinetic properties of a chemical, and its toxicity in humans and experimental systems. The assessment will present reference values for the noncancer effects of thallium compounds (RfD and Rfc), and a cancer assessment. The Toxicological Review and IRIS Summary have been subject to Agency review, Interagency review, and external scientific peer review. The final product will reflect the Agency opinion on the overall toxicity of thallium and compounds. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for thallium and compounds. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effec

  4. Translating visual information into action predictions: Statistical learning in action and nonaction contexts.

    Science.gov (United States)

    Monroy, Claire D; Gerson, Sarah A; Hunnius, Sabine

    2018-05-01

    Humans are sensitive to the statistical regularities in action sequences carried out by others. In the present eyetracking study, we investigated whether this sensitivity can support the prediction of upcoming actions when observing unfamiliar action sequences. In two between-subjects conditions, we examined whether observers would be more sensitive to statistical regularities in sequences performed by a human agent versus self-propelled 'ghost' events. Secondly, we investigated whether regularities are learned better when they are associated with contingent effects. Both implicit and explicit measures of learning were compared between agent and ghost conditions. Implicit learning was measured via predictive eye movements to upcoming actions or events, and explicit learning was measured via both uninstructed reproduction of the action sequences and verbal reports of the regularities. The findings revealed that participants, regardless of condition, readily learned the regularities and made correct predictive eye movements to upcoming events during online observation. However, different patterns of explicit-learning outcomes emerged following observation: Participants were most likely to re-create the sequence regularities and to verbally report them when they had observed an actor create a contingent effect. These results suggest that the shift from implicit predictions to explicit knowledge of what has been learned is facilitated when observers perceive another agent's actions and when these actions cause effects. These findings are discussed with respect to the potential role of the motor system in modulating how statistical regularities are learned and used to modify behavior.

  5. Time Based Workload Analysis Method for Safety-Related Operator Actions in Safety Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yun Goo; Oh, Eung Se [Korea Hydro and Nuclear Power Co., Daejeon (Korea, Republic of)

    2016-05-15

    During the design basis event, the safety system performs safety functions to mitigate the event. The most of safety system is actuated by automatic system however, there are operator manual actions that are needed for the plant safety. These operator actions are classified as important human actions in human factors engineering design. The human factors engineering analysis and evaluation is needed for these important human actions to assure that operator successfully perform their tasks for plant safety and operational goals. The work load analysis is one of the required analysis for the important human actions.

  6. Time Based Workload Analysis Method for Safety-Related Operator Actions in Safety Analysis

    International Nuclear Information System (INIS)

    Kim, Yun Goo; Oh, Eung Se

    2016-01-01

    During the design basis event, the safety system performs safety functions to mitigate the event. The most of safety system is actuated by automatic system however, there are operator manual actions that are needed for the plant safety. These operator actions are classified as important human actions in human factors engineering design. The human factors engineering analysis and evaluation is needed for these important human actions to assure that operator successfully perform their tasks for plant safety and operational goals. The work load analysis is one of the required analysis for the important human actions.

  7. Apoptosis induction in human lymphocytes after in vitro exposure to cobalt/hard metal compounds

    International Nuclear Information System (INIS)

    Boeck, M. de; Decordier, I.; Lombaert, N.; Cundari, E.; Kirsch-Volders, M.; Lison, D.

    2001-01-01

    Full text: An increased risk of lung cancer is associated with occupational exposure to mixtures of cobalt metal (Co) and tungsten carbide (WC) particles, but apparently not when exposure is to cobalt alone. The mechanism for this increased cancer risk is not fully understood. The evaluation of the in vitro genotoxic effects in lymphocytes exposed to varying cobalt species demonstrated that the WC-Co hard metal mixture is more genotoxic (DNA damage, chromosome/genome mutations) than metallic Co alone. WC alone was not genotoxic. Thus, WC-Co represents a specific (geno)toxic entity. In order to assess the survival of human lymphocytes after in vitro exposure to metallic Co, CoCl 2 , WC and the WC-Co mixture, two apoptosis/necrosis detection methods were applied (annexin V staining and flow cytometry). Annexin-V staining of early apoptotic cells demonstrated a dose- and time dependent induction of apoptosis by metallic Co, CoCl 2 , WC and the WC-Co mixture. The time course of the process varied according to the metal species tested. Metallic Co and CoCl 2 caused a gradually increasing frequency of apoptotic cells with time (up to 24 h). WC-induced apoptosis displayed a typical 6 hour peak, which was not the case for the WC-Co mixture or for Co. Apoptosis induction by the WC-Co mixture was intermediate between that induced by Co and WC separately. Analysis of propidium iodide stained cells by flow cytometry was performed as a later marker for apoptosis induction. Preliminary data indicate similar tendencies of apoptosis induction as those detected by annexin-V. Identification of the apoptotic pathway triggered by the metal compounds was studied by inhibition of the ceramide-apoptosis pathway by fumonisin causing reduction of apoptosis induction for all compounds, but strongest after 6 hour exposure to WC. The use of specific caspase inhibitors will allow to further elucidate the different pathways involved. The current data demonstrating in vitro the apoptosis

  8. Apoptosis induction in human lymphocytes after in vitro exposure to cobalt/hard metal compounds

    Energy Technology Data Exchange (ETDEWEB)

    Boeck, M de; Decordier, I; Lombaert, N; Cundari, E; Kirsch-Volders, M [Vrije Universiteit Brussel, Laboratorium voor Cellulaire Genetica, Brussel (Belgium); Lison, D [Universite catholique de Louvain, Unite de Toxicologie industrielle et Medecine du Travail, Bruxelles (Belgium)

    2001-07-01

    Full text: An increased risk of lung cancer is associated with occupational exposure to mixtures of cobalt metal (Co) and tungsten carbide (WC) particles, but apparently not when exposure is to cobalt alone. The mechanism for this increased cancer risk is not fully understood. The evaluation of the in vitro genotoxic effects in lymphocytes exposed to varying cobalt species demonstrated that the WC-Co hard metal mixture is more genotoxic (DNA damage, chromosome/genome mutations) than metallic Co alone. WC alone was not genotoxic. Thus, WC-Co represents a specific (geno)toxic entity. In order to assess the survival of human lymphocytes after in vitro exposure to metallic Co, CoCl{sub 2}, WC and the WC-Co mixture, two apoptosis/necrosis detection methods were applied (annexin V staining and flow cytometry). Annexin-V staining of early apoptotic cells demonstrated a dose- and time dependent induction of apoptosis by metallic Co, CoCl{sub 2}, WC and the WC-Co mixture. The time course of the process varied according to the metal species tested. Metallic Co and CoCl{sub 2} caused a gradually increasing frequency of apoptotic cells with time (up to 24 h). WC-induced apoptosis displayed a typical 6 hour peak, which was not the case for the WC-Co mixture or for Co. Apoptosis induction by the WC-Co mixture was intermediate between that induced by Co and WC separately. Analysis of propidium iodide stained cells by flow cytometry was performed as a later marker for apoptosis induction. Preliminary data indicate similar tendencies of apoptosis induction as those detected by annexin-V. Identification of the apoptotic pathway triggered by the metal compounds was studied by inhibition of the ceramide-apoptosis pathway by fumonisin causing reduction of apoptosis induction for all compounds, but strongest after 6 hour exposure to WC. The use of specific caspase inhibitors will allow to further elucidate the different pathways involved. The current data demonstrating in vitro the

  9. Molecular action mechanisms of solar infrared radiation and heat on human skin.

    Science.gov (United States)

    Akhalaya, M Ya; Maksimov, G V; Rubin, A B; Lademann, J; Darvin, M E

    2014-07-01

    The generation of ROS underlies all solar infrared-affected therapeutic and pathological cutaneous effects. The signaling pathway NF-kB is responsible for the induced therapeutic effects, while the AP-1 for the pathological effects. The different signaling pathways of infrared-induced ROS and infrared-induced heat shock ROS were shown to act independently multiplying the influence on each other by increasing the doses of irradiation and/or increasing the temperature. The molecular action mechanisms of solar infrared radiation and heat on human skin are summarized and discussed in detail in the present paper. The critical doses are determined. Protection strategies against infrared-induced skin damage are proposed. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. A Suspicious Action Detection System Considering Time Series

    Science.gov (United States)

    Kozuka, Noriaki; Kimura, Koji; Hagiwara, Masafumi

    The paper proposes a new system that can detect suspicious actions such as a car break-in and surroundings in an open space parking, based on image processing. The proposed system focuses on three points of “order”, “time”, and “location” of human actions. The proposed system has the following features: it 1) deals time series data flow, 2) estimates human actions and the location, 3) extracts suspicious action detection rules automatically, 4) detects suspicious actions using the suspicious score. We carried out experiments using real image sequences. As a result, we obtained about 7.8% higher estimation rate than the conventional system.

  11. Possible additional exposure to dioxin and dioxin-like compounds from waste incineration. Biomonitoring using human milk and animal samples

    Energy Technology Data Exchange (ETDEWEB)

    Sampaio, C.; M. Fatima Reis; J. Pereira Miguel [Inst. of Preventive Medicine, Univ. of Lisbon (Portugal); Murk, A. [Wageningen Univ., Dept. of Toxicology (Netherlands)

    2004-09-15

    In the ambit of an Environmental Health Survey Program relative to a MSW facility, which has been operating near to Lisbon since 1999 a biomonitoring study using human breast milk has been performed. Specific aims of this study were: (1) determine whether living in the vicinity of the incinerator increases dioxin maternal body burden and accordingly perinatal (intra-uterus and lactacional) exposure; (2) to investigate the possibility of increased human exposure to dioxins and dioxin-like compounds via locally produced food items from animal origin. Therefore, levels of dioxins and dioxin-like compounds have been determined in human milk samples collected in the vicinity of the incinerator and in a control area, for comparison. From the same areas, cow and sheep milk and eggs from free-range chickens have also been collected to get an indication of possible local additional exposure to air-borne dioxins via the food chain. Analyses of TCDD-equivalents (TEQs) were mainly performed with a reporter gene assay for dioxin-like activity, the DR-CALUX bioassay (Dioxin Responsive Chemical Activated LUciferase gene eXpression).To determine congeners profile, some human milk samples have also been analysed for PCDD/Fs and relevant dioxin-like PCBs, by using high-resolution gas chromatography and high-resolution mass spectrometry (HRGC/HRMS). Both the Ethics Committees of the Faculty of Medicine, University of Lisbon, and of the Maternity Dr. Alfredo da Costa have approved the study protocol.

  12. Robotic movement preferentially engages the action observation network

    NARCIS (Netherlands)

    Cross, E.S.; Liepelt, R.; Hamilton, A.F.D.C.; Parkinson, J.; Ramsey, R.; Stadler, W.; Prinz, W.G.

    2012-01-01

    As humans, we gather a wide range of information about other people from watching them move. A network of parietal, premotor, and occipitotemporal regions within the human brain, termed the action observation network (AON), has been implicated in understanding others' actions by means of an

  13. Effects of estragole on the compound action potential of the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    J.H. Leal-Cardoso

    2004-08-01

    Full Text Available Estragole, a relatively nontoxic terpenoid ether, is an important constituent of many essential oils with widespread applications in folk medicine and aromatherapy and known to have potent local anesthetic activity. We investigated the effects of estragole on the compound action potential (CAP of the rat sciatic nerve. The experiments were carried out on sciatic nerves dissected from Wistar rats. Nerves, mounted in a moist chamber, were stimulated at a frequency of 0.2 Hz, with electric pulses of 50-100-µs duration at 10-20 V, and evoked CAP were monitored on an oscilloscope and recorded on a computer. CAP control parameters were: peak-to-peak amplitude (PPA, 9.9 ± 0.55 mV (N = 15, conduction velocity, 92.2 ± 4.36 m/s (N = 15, chronaxy, 45.6 ± 3.74 µs (N = 5, and rheobase, 3.9 ± 0.78 V (N = 5. Estragole induced a dose-dependent blockade of the CAP. At 0.6 mM, estragole had no demonstrable effect. At 2.0 and 6.0 mM estragole, PPA was significantly reduced at the end of 180-min exposure of the nerve to the drug to 85.6 ± 3.96 and 13.04 ± 1.80% of control, respectively. At 4.0 mM, estragole significantly altered PPA, conduction velocity, chronaxy, and rheobase (P <= 0.05, ANOVA; N = 5 to 49.3 ± 6.21 and 77.7 ± 3.84, 125.9 ± 10.43 and 116.7 ± 4.59%, of control, respectively. All of these effects developed slowly and were reversible upon a 300-min wash-out. The data show that estragole dose-dependently blocks nerve excitability.

  14. Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling.

    Science.gov (United States)

    Le Bihan, Amélie; de Kanter, Ruben; Angulo-Barturen, Iñigo; Binkert, Christoph; Boss, Christoph; Brun, Reto; Brunner, Ralf; Buchmann, Stephan; Burrows, Jeremy; Dechering, Koen J; Delves, Michael; Ewerling, Sonja; Ferrer, Santiago; Fischli, Christoph; Gamo-Benito, Francisco Javier; Gnädig, Nina F; Heidmann, Bibia; Jiménez-Díaz, María Belén; Leroy, Didier; Martínez, Maria Santos; Meyer, Solange; Moehrle, Joerg J; Ng, Caroline L; Noviyanti, Rintis; Ruecker, Andrea; Sanz, Laura María; Sauerwein, Robert W; Scheurer, Christian; Schleiferboeck, Sarah; Sinden, Robert; Snyder, Christopher; Straimer, Judith; Wirjanata, Grennady; Marfurt, Jutta; Price, Ric N; Weller, Thomas; Fischli, Walter; Fidock, David A; Clozel, Martine; Wittlin, Sergio

    2016-10-01

    Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented. The properties of ACT-451840 are described, including its spectrum of activities against multiple life cycle stages of the human malaria parasite Plasmodium falciparum (asexual and sexual) and Plasmodium vivax (asexual) as well as oral in vivo efficacies in two murine malaria models that permit infection with the human and the rodent parasites P. falciparum and Plasmodium berghei, respectively. In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. The 90% effective doses in the in vivo efficacy models were 3.7 mg/kg against P. falciparum (95% confidence interval: 3.3-4.9 mg/kg) and 13 mg/kg against P. berghei (95% confidence interval: 11-16 mg/kg). ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23-39). The compound's preclinical safety profile is presented and is in line with the published results of the first-in-man study in healthy male participants, in whom ACT-451840 was well tolerated. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was applied using efficacy in the murine models (defined either as antimalarial activity or as survival) in relation to area under

  15. Corrective Action Decision Document/Closure Report for Corrective Action Unit 500: Test Cell A Septic System, Nevada Test Site, Nevada, Rev. 0

    International Nuclear Information System (INIS)

    2000-01-01

    This Corrective Action Decision Document/Closure Report (CADD/CR) has been prepared for Corrective Action Unit (CAU) 500: Test Cell A Septic System, in accordance with the Federal Facility Agreement and Consent Order. Located in Area 25 at the Nevada Test Site in Nevada, CAU 500 is comprised of one Corrective Action Site, CAS 25-04-05. This CADD/CR identifies and rationalizes the U.S. Department of Energy, Nevada Operations Office's (DOE/NV's) recommendation that no corrective action is deemed necessary for CAU 500. The Corrective Action Decision Document and Closure Report have been combined into one report based on sample data collected during the field investigation performed between February and May 1999, which showed no evidence of soil contamination at this site. The clean closure justification for CAU 500 is based on these results. Analytes detected were evaluated against preliminary action levels (PALs) to determine contaminants of concern (COCs) for CAU 500, and it was determined that the PALs were not exceeded for total volatile organic compounds, total semivolatile organic compounds, total petroleum hydrocarbons, polychlorinated biphenyls, total Resource Conservation and Recovery Act metals, gamma-emitting radionuclides, isotopic uranium, and strontium-90 for any of the soil samples collected. COCs were identified only within the septic tank and distribution box at the CAU. No COCs were identified outside these two areas; therefore, no corrective action was necessary for the soil. Closure activities were performed to address the COCs identified within the septic tank and distribution box. The DOE/NV recommended that neither corrective action nor a corrective action plan was required at CAU 500. Further, no use restrictions were required to be placed on CAU 500, and the septic tank and distribution box have been closed in accordance with all applicable state and federal regulations for closure of the site

  16. Assessing in Vitro Acaricidal Effect and Joint Action of a Binary Mixture Between Essential Oil Compounds (Thymol, Phellandrene, Eucalyptol, Cinnamaldehyde, Myrcene, Carvacrol Over Ectoparasitic Mite Varroa Destructor (Acari: Varroidae

    Directory of Open Access Journals (Sweden)

    Brasesco Constanza

    2017-12-01

    Full Text Available Varroa destructor (Anderson & Trueman, 2000 causes the most important parasitosis of beekeeping in the world. For this reason, prevention is needed to avoid colony death. The most typical treatments involve synthetic acaricides. However, the use of these acaricides results in the emergence of resistant populations of mites to these products and in the appearances of drug residues in products of the hives. Compounds of essential oils have emerged as an alternative to traditional acaricides; however the toxicity produced by these mixtures is currently poorly explored. The aim of this work was to assess, by means of in vitro tests with adult bees, how acaricidal action and toxic interactions in a binary mixture of essential oil compounds (Thymol, Phellandrene, Eucalyptol, Cinnamaldehyde, Myrcene, and Carvacrol affect V. destructor. Calculations of LC50 ’s of the individual compounds on A. mellifera and V. destructor made clear that the toxic effect of each compound is different for both species. Thymol and Phellandrene turned out to be lethal for mites at lower concentrations than for bees. The binary mixture of these two substances presented a different toxicity than one produced by each pure compound, as it was highly selective for mites in bioassays at 24 hours through complete exposure to both A. mellifera and V. destructor. These results make such formulations optimal substances to be considered as alternative controls for the parasitosis.

  17. Isolation and identification of compounds from Kalanchoe pinnata having human alphaherpesvirus and vaccinia virus antiviral activity.

    Science.gov (United States)

    Cryer, Matthew; Lane, Kyle; Greer, Mary; Cates, Rex; Burt, Scott; Andrus, Merritt; Zou, Jiping; Rogers, Paul; Hansen, Marc D H; Burgado, Jillybeth; Panayampalli, Subbian Satheshkumar; Day, Craig W; Smee, Donald F; Johnson, Brent F

    2017-12-01

    Kalanchoe pinnata (Lam.) Pers. (Crassulaceae) is a succulent plant that is known for its traditional antivirus and antibacterial usage. This work examines two compounds identified from the K. pinnata plant for their antivirus activity against human alphaherpesvirus (HHV) 1 and 2 and vaccinia virus (VACV). Compounds KPB-100 and KPB-200 were isolated using HPLC and were identified using NMR and MS. Both compounds were tested in plaque reduction assay of HHV-2 wild type (WT) and VACV. Both compounds were then tested in virus spread inhibition and virus yield reduction (VYR) assays of VACV. KPB-100 was further tested in viral cytopathic effect (CPE) inhibition assay of HHV-2 TK-mutant and VYR assay of HHV-1 WT. KPB-100 and KPB-200 inhibited HHV-2 at IC 50 values of 2.5 and 2.9 μg/mL, respectively, and VACV at IC 50 values of 3.1 and 7.4 μg/mL, respectively, in plaque reduction assays. In virus spread inhibition assay of VACV KPB-100 and KPB-200 yielded IC 50 values of 1.63 and 13.2 μg/mL, respectively, and KPB-100 showed a nearly 2-log reduction in virus in VYR assay of VACV at 20 μg/mL. Finally, KPB-100 inhibited HHV-2 TK- at an IC 50 value of 4.5 μg/mL in CPE inhibition assay and HHV-1 at an IC 90 of 3.0 μg/mL in VYR assay. Both compounds are promising targets for synthetic optimization and in vivo study. KPB-100 in particular showed strong inhibition of all viruses tested.

  18. "The Human Condition" as social ontology: Hannah Arendt on society, action and knowledge.

    Science.gov (United States)

    Walsh, Philip

    2011-01-01

    Hannah Arendt is widely regarded as a political theorist who sought to rescue politics from "society," and political theory from the social sciences. This conventional view has had the effect of distracting attention from many of Arendt's most important insights concerning the constitution of "society" and the significance of the social sciences. In this article, I argue that Hannah Arendt's distinctions between labor, work, and action, as these are discussed in "The Human Condition" and elsewhere, are best understood as a set of claims about the fundamental structures of human societies. Understanding Arendt in this way introduces interesting parallels between Arendt's work and both classical and contemporary sociology. From this I draw a number of conclusions concerning Arendt's conception of "society," and extend these insights into two contemporary debates within contemporary theoretical sociology: the need for a differentiated ontology of the social world, and the changing role that novel forms of knowledge play in contemporary society as major sources of social change and order.

  19. Assembled microneedle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatomed skin

    NARCIS (Netherlands)

    Verbaan, F.J.; Bal, S.M.; van den Berg, D.J.; Groenink, W.H.H.; Verpoorten, H.; Lüttge, Regina; Bouwstra, J.A.

    2007-01-01

    In this study, we demonstrate the feasibility to use microneedle arrays manufactured from commercially available 30G hypodermal needles to enhance the transport of compounds up to a molecular weight of 72 kDa. Piercing of human dermatomed skin with microneedle arrays was studied by Trypan Blue

  20. 75 FR 57390 - Approval and Promulgation of Implementation Plans; Alabama: Volatile Organic Compounds

    Science.gov (United States)

    2010-09-21

    ... Environmental Management (ADEM) on March 3, 2010. The revision modifies the definition of ``volatile organic... the VOC definition on the basis that these compounds make a negligible contribution to tropospheric..., 2009, which excludes these compounds from the regulatory VOC definition. This action is being taken...

  1. Anti-Inflammatory Activity of Compounds Isolated from Plants

    Directory of Open Access Journals (Sweden)

    R.M. Perez G.

    2001-01-01

    Full Text Available This review shows over 300 compounds isolated and identified from plants that previously demonstrated anti-inflammatory activity. They have been classified in appropriate chemical groups and data are reported on their pharmacological effects, mechanisms of action, and other properties.

  2. Endocrine-disrupting chemicals-Mechanisms of action on male reproductive system.

    Science.gov (United States)

    Sidorkiewicz, Iwona; Zaręba, Kamil; Wołczyński, Sławomir; Czerniecki, Jan

    2017-07-01

    Endocrine-disrupting chemicals (EDCs) are exogenous compounds that can cause disturbances in the endocrine system and have multiple harmful effects on health by targeting different organs and systems in the human body. Mass industrial production and widespread use of EDCs have resulted in worldwide contamination. Accumulating evidence suggest that human exposure to EDCs is related to the impairment of male reproductive function and can interrupt other hormonally regulated metabolic processes, particularly if exposure occurs during early development. Investigation of studies absent in previous reviews and meta-analysis of adverse effects of EDCs on functioning of the male reproductive system is the core of this work. Four main modes of action of EDCs on male fertility have been summarized in this review. First, studies describing estrogen- pathway disturbing chemicals are investigated. Second, androgen-signaling pathway alterations and influence on androgen sensitive tissues are examined. Third, evaluation of steroidogenesis dysfunction is discussed by focusing on the steroid hormone biosynthesis pathway, which is targeted by EDCs. Last, the reportedly destructive role of reactive oxygen species (ROS) on sperm function is discussed. Spermatogenesis is a remarkably complex process, hence multiple studies point out various dysfunctions depending on the development state at which the exposure occurred. Collected data show the need to account for critical windows of exposure such as fetal, perinatal and pubertal periods as well as effects of mixtures of several compounds in future research.

  3. Animated pose templates for modeling and detecting human actions.

    Science.gov (United States)

    Yao, Benjamin Z; Nie, Bruce X; Liu, Zicheng; Zhu, Song-Chun

    2014-03-01

    This paper presents animated pose templates (APTs) for detecting short-term, long-term, and contextual actions from cluttered scenes in videos. Each pose template consists of two components: 1) a shape template with deformable parts represented in an And-node whose appearances are represented by the Histogram of Oriented Gradient (HOG) features, and 2) a motion template specifying the motion of the parts by the Histogram of Optical-Flows (HOF) features. A shape template may have more than one motion template represented by an Or-node. Therefore, each action is defined as a mixture (Or-node) of pose templates in an And-Or tree structure. While this pose template is suitable for detecting short-term action snippets in two to five frames, we extend it in two ways: 1) For long-term actions, we animate the pose templates by adding temporal constraints in a Hidden Markov Model (HMM), and 2) for contextual actions, we treat contextual objects as additional parts of the pose templates and add constraints that encode spatial correlations between parts. To train the model, we manually annotate part locations on several keyframes of each video and cluster them into pose templates using EM. This leaves the unknown parameters for our learning algorithm in two groups: 1) latent variables for the unannotated frames including pose-IDs and part locations, 2) model parameters shared by all training samples such as weights for HOG and HOF features, canonical part locations of each pose, coefficients penalizing pose-transition and part-deformation. To learn these parameters, we introduce a semi-supervised structural SVM algorithm that iterates between two steps: 1) learning (updating) model parameters using labeled data by solving a structural SVM optimization, and 2) imputing missing variables (i.e., detecting actions on unlabeled frames) with parameters learned from the previous step and progressively accepting high-score frames as newly labeled examples. This algorithm belongs to a

  4. Corrective Action Investigation Plan for Corrective Action Unit 409: Other Waste Sites, Tonopah Test Range, Nevada (Rev. 0)

    International Nuclear Information System (INIS)

    2000-01-01

    This Corrective Action Investigation Plan contains the U.S. Department of Energy, Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 409 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 409 consists of three Corrective Action Sites (CASs): TA-53-001-TAB2, Septic Sludge Disposal Pit No.1; TA-53-002-TAB2, Septic Sludge Disposal Pit No.2; and RG-24-001-RGCR, Battery Dump Site. The Septic Sludge Disposal Pits are located near Bunker Two, close to Area 3, on the Tonopah Test Range. The Battery Dump Site is located at the abandoned Cactus Repeater Station on Cactus Peak. The Cactus Repeater Station was a remote, battery-powered, signal repeater station. The two Septic Sludge Disposal Pits were suspected to be used through the late 1980s as disposal sites for sludge from septic tanks located in Area 3. Based on site history collected to support the Data Quality Objectives process, contaminants of potential concern are the same for the disposal pits and include: volatile organic compounds (VOCs), semivolatile organic compounds, total petroleum hydrocarbons (TPHs) as gasoline- and diesel-range organics, polychlorinated biphenyls, Resource Conservation and Recovery Act metals, and radionuclides (including plutonium and depleted uranium). The Battery Dump Site consists of discarded lead-acid batteries and associated construction debris, placing the site in a Housekeeping Category and, consequently, no contaminants are expected to be encountered during the cleanup process. The corrective action the at this CAU will include collection of discarded batteries and construction debris at the Battery Dump Site for proper disposal and recycling, along with photographic documentation as the process progresses. The corrective action for the remaining CASs involves the collection of background radiological data through borings drilled at

  5. The Non-Genomic Actions of Vitamin D

    Directory of Open Access Journals (Sweden)

    Charles S Hii

    2016-03-01

    Full Text Available Since its discovery in 1920, a great deal of effort has gone into investigating the physiological actions of vitamin D and the impact its deficiency has on human health. Despite this intense interest, there is still disagreement on what constitutes the lower boundary of adequacy and on the Recommended Dietary Allowance. There has also been a major push to elucidate the biochemistry of vitamin D, its metabolic pathways and the mechanisms that mediate its action. Originally thought to act by altering the expression of target genes, it was realized in the mid-1980s that some of the actions of vitamin D were too rapid to be accounted for by changes at the genomic level. These rapid non-genomic actions have attracted as much interest as the genomic actions and they have spawned additional questions in an already busy field. This mini-review attempts to summarise the in vitro and in vivo work that has been conducted to characterise the rapid non-genomic actions, the mechanisms that give rise to these properties and the roles that these play in the overall action of vitamin D at the cellular level. Understanding the effects of vitamin D at the cellular level should enable the design of elegant human studies to extract the full potential of vitamin D to benefit human health.

  6. Recognizing human actions by learning and matching shape-motion prototype trees.

    Science.gov (United States)

    Jiang, Zhuolin; Lin, Zhe; Davis, Larry S

    2012-03-01

    A shape-motion prototype-based approach is introduced for action recognition. The approach represents an action as a sequence of prototypes for efficient and flexible action matching in long video sequences. During training, an action prototype tree is learned in a joint shape and motion space via hierarchical K-means clustering and each training sequence is represented as a labeled prototype sequence; then a look-up table of prototype-to-prototype distances is generated. During testing, based on a joint probability model of the actor location and action prototype, the actor is tracked while a frame-to-prototype correspondence is established by maximizing the joint probability, which is efficiently performed by searching the learned prototype tree; then actions are recognized using dynamic prototype sequence matching. Distance measures used for sequence matching are rapidly obtained by look-up table indexing, which is an order of magnitude faster than brute-force computation of frame-to-frame distances. Our approach enables robust action matching in challenging situations (such as moving cameras, dynamic backgrounds) and allows automatic alignment of action sequences. Experimental results demonstrate that our approach achieves recognition rates of 92.86 percent on a large gesture data set (with dynamic backgrounds), 100 percent on the Weizmann action data set, 95.77 percent on the KTH action data set, 88 percent on the UCF sports data set, and 87.27 percent on the CMU action data set.

  7. Building public trust: Actions to respond to the report of the Advisory Committee on human radiation experiments

    International Nuclear Information System (INIS)

    1997-03-01

    Democratic government requires trust: people need to know and believe that the government is telling the truth. Without information about what the government is doing and why, citizens cannot exercise democratic control over government institutions. During his first year in office, President Clinton became concerned about reports that the government had conducted unethical secret human radiation experiments during the Cold War. To address this issue, in January 1994, President Clinton established the Advisory Committee on Human Radiation Experiments (ACHRE), chaired by bioethicist Dr. Ruth Faden of Johns Hopkins University. The President also directed all Federal agencies to search for records related to human subjects radiation research and provide them to the Advisory Committee. This report presents the Administration's actions to respond to the ACHRE's findings and recommendations

  8. Bioactive Compound Content and Cytotoxic Effect on Human Cancer Cells of Fresh and Processed Yellow Tomatoes

    Directory of Open Access Journals (Sweden)

    Assunta Raiola

    2015-12-01

    Full Text Available Tomato, as a fresh or processed product, has a high nutritional value due to its content of bioactive components such as phenolic compounds. Few studies describe the effect of processing on antioxidant content and the cancer cell growth inhibition activity. In this study we determined the phenolic and ascorbic acid content of three yellow tomato varieties, before and after thermal processing. Moreover, we determined the antioxidative power and tested the effects of tomato extracts on three human cancer cell lines. We found that the amount of phenolic acids (chlorogenic acid and caffeic acid decreased in all the samples after processing, whereas the flavonoid content increased after the heat treatment in two samples. A cytotoxic effect of tomato extracts was observed only after processing. This result well correlates with the flavonoid content after processing and clearly indicates that processed yellow tomatoes have a high content of bioactive compounds endowed with cytotoxicity towards cancer cells, thus opening the way to obtain tomato-based functional foods.

  9. Actions of piperidine alkaloid teratogens at fetal nicotinic acetylcholine receptors.

    Science.gov (United States)

    Green, Benedict T; Lee, Stephen T; Panter, Kip E; Welch, Kevin D; Cook, Daniel; Pfister, James A; Kem, William R

    2010-01-01

    Teratogenic alkaloids are found in many species of plants including Conium maculatum L., Nicotiana glauca, Nicotiana tabaccum, and multiple Lupinus spp. Fetal musculoskeletal defects produced by alkaloids from these plants include arthrogyropisis, scoliosis, torticollis, kyposis, lordosis, and cleft palate. A pharmacodynamic comparison of the alkaloids ammodendrine, anabasine, anabaseine, anagyrine, and coniine in SH-SY5Y cells and TE-671 cells was made. These alkaloids and their enantiomers were more effective in depolarizing TE-671 cells which express the human fetal-muscle type nicotinic acetylcholine receptor (nAChR) relative to SH-SY5Y cells which predominately express autonomic nAChRs. The rank order of potency in TE-671 cells was: anabaseine>(+)-anabasine>(-)-anabasine > (+/-)-anabasine>anagyrine>(-)-coniine > (+/-)-coniine>(+)-coniine>(+/-)-ammodendrine>(+)-ammodendrine. The rank order potency in SH-SY5Y cells was: anabaseine>(+)-anabasine>(-)-coniine>(+)-coniine>(+)-ammodendrine>anagyrine>(-)-anabasine>(+/-)-coniine>(+/-)-anabasine>(-)-ammodendrine. The actions of these alkaloids at nAChRs in both cell lines could be distinguished by their maximum effects in depolarizing cell membrane potential. The teratogenic action of these compounds may be related to their ability to activate and subsequently desensitize nAChRs.

  10. An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors.

    Science.gov (United States)

    Pagano, Nicholas; Teriete, Peter; Mattmann, Margrith E; Yang, Li; Snyder, Beth A; Cai, Zhaohui; Heil, Marintha L; Cosford, Nicholas D P

    2017-12-01

    Continuous flow (microfluidic) chemistry was employed to prepare a small focused library of dihydropyrimidinone (DHPM) derivatives. Compounds in this class have been reported to exhibit activity against the human immunodeficiency virus (HIV), but their molecular target had not been identified. We tested the initial set of DHPMs in phenotypic assays providing a hit (1i) that inhibited the replication of the human immunodeficiency virus HIV in cells. Flow chemistry-driven optimization of 1i led to the identification of HIV replication inhibitors such as 1l with cellular potency comparable with the clinical drug nevirapine (NVP). Mechanism of action (MOA) studies using cellular and biochemical assays coupled with 3D fingerprinting and in silico modeling demonstrated that these drug-like probe compounds exert their effects by inhibiting the viral reverse transcriptase polymerase (RT). This led to the design and synthesis of the novel DHPM 1at that inhibits the replication of drug resistant strains of HIV. Our work demonstrates that combining flow chemistry-driven analogue refinement with phenotypic assays, in silico modeling and MOA studies is a highly effective strategy for hit-to-lead optimization applicable to the discovery of future therapeutic agents. Copyright © 2017. Published by Elsevier Ltd.

  11. RCRA corrective action determination of no further action

    International Nuclear Information System (INIS)

    1996-06-01

    On July 27, 1990, the U.S. Environmental Protection Agency (EPA) proposed a regulatory framework (55 FR 30798) for responding to releases of hazardous waste and hazardous constituents from solid waste management units (SWMUs) at facilities seeking permits or permitted under the Resource Conservation and Recovery Act (RCRA). The proposed rule, 'Corrective Action for Solid Waste Management Units at Hazardous Waste Facilities', would create a new Subpart S under the 40 CFR 264 regulations, and outlines requirements for conducting RCRA Facility Investigations, evaluating potential remedies, and selecting and implementing remedies (i.e., corrective measures) at RCRA facilities. EPA anticipates instances where releases or suspected releases of hazardous wastes or constituents from SWMUs identified in a RCRA Facility Assessment, and subsequently addressed as part of required RCRA Facility Investigations, will be found to be non-existent or non-threatening to human health or the environment. Such releases may require no further action. For such situations, EPA proposed a mechanism for making a determination that no further corrective action is needed. This mechanism is known as a Determination of No Further Action (DNFA) (55 FR 30875). This information Brief describes what a DNFA is and discusses the mechanism for making a DNFA. This is one of a series of Information Briefs on RCRA corrective action

  12. Clean Slate 1 corrective action decision document, Corrective Action Unit No. 412. Revision 1

    International Nuclear Information System (INIS)

    1997-04-01

    A Corrective Action Investigation has been completed at the Clean Slate 1 (CS-1) Site, located in the central portion of the Tonopah Test Range. The purpose of this CADD is to identify and evaluate potential correct action alternatives at the CS-1 Site and to evaluate these alternatives with respect to their technical, human health, and environmental benefits and to their cost. Base on this evaluation a corrective action will be recommended for implementation at the CS-1 Site

  13. Action Simulation Plays a Critical Role in Deceptive Action Recognition

    NARCIS (Netherlands)

    Tidoni, Emmanuele; Borgomaneri, Sara; Di Pellegrino, Giuseppe; Avenanti, Alessio

    2013-01-01

    The ability to infer deceptive intents from nonverbal behavior is critical for social interactions. By combining single-pulse and repetitive transcranial magnetic stimulation (TMS) in healthy humans, we provide both correlational and causative evidence that action simulation is actively involved in

  14. Fronto-parietal coding of goal-directed actions performed by artificial agents.

    Science.gov (United States)

    Kupferberg, Aleksandra; Iacoboni, Marco; Flanagin, Virginia; Huber, Markus; Kasparbauer, Anna; Baumgartner, Thomas; Hasler, Gregor; Schmidt, Florian; Borst, Christoph; Glasauer, Stefan

    2018-03-01

    With advances in technology, artificial agents such as humanoid robots will soon become a part of our daily lives. For safe and intuitive collaboration, it is important to understand the goals behind their motor actions. In humans, this process is mediated by changes in activity in fronto-parietal brain areas. The extent to which these areas are activated when observing artificial agents indicates the naturalness and easiness of interaction. Previous studies indicated that fronto-parietal activity does not depend on whether the agent is human or artificial. However, it is unknown whether this activity is modulated by observing grasping (self-related action) and pointing actions (other-related action) performed by an artificial agent depending on the action goal. Therefore, we designed an experiment in which subjects observed human and artificial agents perform pointing and grasping actions aimed at two different object categories suggesting different goals. We found a signal increase in the bilateral inferior parietal lobule and the premotor cortex when tool versus food items were pointed to or grasped by both agents, probably reflecting the association of hand actions with the functional use of tools. Our results show that goal attribution engages the fronto-parietal network not only for observing a human but also a robotic agent for both self-related and social actions. The debriefing after the experiment has shown that actions of human-like artificial agents can be perceived as being goal-directed. Therefore, humans will be able to interact with service robots intuitively in various domains such as education, healthcare, public service, and entertainment. © 2017 Wiley Periodicals, Inc.

  15. Antibacterial Compounds from Red Seaweeds (Rhodophyta

    Directory of Open Access Journals (Sweden)

    Noer Kasanah

    2015-07-01

    Full Text Available Seaweeds produce great variety of metabolites benefit for human. Red seaweeds (Rhodophyta are well known as producer of phycocolloids such agar, agarose, carragenan and great variety of secondary metabolites. This review discusses the red algal secondary metabolites with antibacterial activity. The chemical constituents of red algae are steroid, terpenoid, acetogenin and dominated by halogenated compounds mainly brominated compounds. Novel compounds with intriguing skeleton are also reported such as bromophycolides and neurymenolides. In summary, red seaweeds are potential sources for antibacterial agents and can serve as lead in synthesis of new natural medicines.

  16. Communicative Elements of Action Research

    Science.gov (United States)

    Ryan, Thomas G.

    2013-01-01

    This review considers human communications as utilized within a research design; in this case collaborative action research (CAR), a derivative of action research (AR), to achieve outcomes that change, and move participants forward. The association between AR and CAR is a deliberate attempt by the author to draw attention to communicative actions…

  17. Building public trust: Actions to respond to the report of the Advisory Committee on human radiation experiments

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    Democratic government requires trust: people need to know and believe that the government is telling the truth. Without information about what the government is doing and why, citizens cannot exercise democratic control over government institutions. During his first year in office, President Clinton became concerned about reports that the government had conducted unethical secret human radiation experiments during the Cold War. To address this issue, in January 1994, President Clinton established the Advisory Committee on Human Radiation Experiments (ACHRE), chaired by bioethicist Dr. Ruth Faden of Johns Hopkins University. The President also directed all Federal agencies to search for records related to human subjects radiation research and provide them to the Advisory Committee. This report presents the Administration`s actions to respond to the ACHRE`s findings and recommendations.

  18. Where one hand meets the other: limb-specific and action-dependent movement plans decoded from preparatory signals in single human frontoparietal brain areas.

    Science.gov (United States)

    Gallivan, Jason P; McLean, D Adam; Flanagan, J Randall; Culham, Jody C

    2013-01-30

    Planning object-directed hand actions requires successful integration of the movement goal with the acting limb. Exactly where and how this sensorimotor integration occurs in the brain has been studied extensively with neurophysiological recordings in nonhuman primates, yet to date, because of limitations of non-invasive methodologies, the ability to examine the same types of planning-related signals in humans has been challenging. Here we show, using a multivoxel pattern analysis of functional MRI (fMRI) data, that the preparatory activity patterns in several frontoparietal brain regions can be used to predict both the limb used and hand action performed in an upcoming movement. Participants performed an event-related delayed movement task whereby they planned and executed grasp or reach actions with either their left or right hand toward a single target object. We found that, although the majority of frontoparietal areas represented hand actions (grasping vs reaching) for the contralateral limb, several areas additionally coded hand actions for the ipsilateral limb. Notable among these were subregions within the posterior parietal cortex (PPC), dorsal premotor cortex (PMd), ventral premotor cortex, dorsolateral prefrontal cortex, presupplementary motor area, and motor cortex, a region more traditionally implicated in contralateral movement generation. Additional analyses suggest that hand actions are represented independently of the intended limb in PPC and PMd. In addition to providing a unique mapping of limb-specific and action-dependent intention-related signals across the human cortical motor system, these findings uncover a much stronger representation of the ipsilateral limb than expected from previous fMRI findings.

  19. Predictive Mechanisms Are Not Involved the Same Way during Human-Human vs. Human-Machine Interactions: A Review

    Directory of Open Access Journals (Sweden)

    Aïsha Sahaï

    2017-10-01

    Full Text Available Nowadays, interactions with others do not only involve human peers but also automated systems. Many studies suggest that the motor predictive systems that are engaged during action execution are also involved during joint actions with peers and during other human generated action observation. Indeed, the comparator model hypothesis suggests that the comparison between a predicted state and an estimated real state enables motor control, and by a similar functioning, understanding and anticipating observed actions. Such a mechanism allows making predictions about an ongoing action, and is essential to action regulation, especially during joint actions with peers. Interestingly, the same comparison process has been shown to be involved in the construction of an individual's sense of agency, both for self-generated and observed other human generated actions. However, the implication of such predictive mechanisms during interactions with machines is not consensual, probably due to the high heterogeneousness of the automata used in the experimentations, from very simplistic devices to full humanoid robots. The discrepancies that are observed during human/machine interactions could arise from the absence of action/observation matching abilities when interacting with traditional low-level automata. Consistently, the difficulties to build a joint agency with this kind of machines could stem from the same problem. In this context, we aim to review the studies investigating predictive mechanisms during social interactions with humans and with automated artificial systems. We will start by presenting human data that show the involvement of predictions in action control and in the sense of agency during social interactions. Thereafter, we will confront this literature with data from the robotic field. Finally, we will address the upcoming issues in the field of robotics related to automated systems aimed at acting as collaborative agents.

  20. The Dual Antioxidant/Prooxidant Effect of Eugenol and Its Action in Cancer Development and Treatment

    Directory of Open Access Journals (Sweden)

    Daniel Pereira Bezerra

    2017-12-01

    Full Text Available The formation of reactive oxygen species (ROS during metabolism is a normal process usually compensated for by the antioxidant defense system of an organism. However, ROS can cause oxidative damage and have been proposed to be the main cause of age-related clinical complications and diseases such as cancer. In recent decades, the relationship between diet and cancer has been more studied, especially with foods containing antioxidant compounds. Eugenol is a natural compound widely found in many aromatic plant species, spices and foods and is used in cosmetics and pharmaceutical products. Eugenol has a dual effect on oxidative stress, which can action as an antioxidant or prooxidant agent. In addition, it has anti-carcinogenic, cytotoxic and antitumor properties. Considering the importance of eugenol in the area of food and human health, in this review, we discuss the role of eugenol on redox status and its potential use in the treatment and prevention of cancer.

  1. Ubuntu and Capabilities Approach: Basic Doctrines for Calibrating Humanitarian Action

    Directory of Open Access Journals (Sweden)

    Rapatsa Mashele

    2016-06-01

    Full Text Available This article explores prospects of using Ubuntu and Capabilities Approach to expand the scope of humanitarian action, to design one which serves humanity better even in the absence of disaster to essentially fulfil human development needs. It is considerate of the fact that humanitarian works contributes immensely in determining the extent to which humanity thrives. The traditional view on humanitarianism presupposes action-driven initiatives geared towards devising interventions to restore or reinforce human social order, improve livelihoods and quality of life. In sociological terms, human development is dependent on realizing and safeguarding, amongst others, human well-being, civil liberties and social security. The article utilizes core values enshrined in Ubuntu, Africa’s historic philosophy of life, and Amartya Sen’s Capabilities Approach as tools of analysis, with the view to expressing how to operationalize what should be considered stable humanitarian conditions and human well-being. Owing to persistent socio-economic challenges, especially the poverty problem, it is asserted that humanitarian action ought to depart from being a post-disaster intervention strategy, to being a pro-active and preventative pre-disaster orientated action, intended to nurture well-being and resultantly enable human development.

  2. Determination of total and methylmercury compounds in the IAEA human hair intercomparison samples - Experience of the IAEA-MEL

    International Nuclear Information System (INIS)

    Horvat, M.; Liang, L.; Mandic, V.

    1995-01-01

    The programme of this CRP is focused on the analyses of human hair samples. There are only two human hair samples certified for total mercury, and no RMs for methylmercury compounds is available. One of the main objectives of this CRP is to produce, through the IAEA AQCS Programme, a human hair intercomparison material for quality assurance requirements in population monitoring programmes for total and methylmercury exposure. Through the reporting period, MESL has introduced a new method for simultaneous determination of total and methylmercury in biological samples. As the laboratory has close collaboration with the CRP's Reference Laboratory in Ljubljana, Slovenia, it has also been actively involved in the quality assurance component of this CRP. This report represents a summary on the results for total and methylmercury in two intercomparison samples, IAEA-085 and IAEA-086 using newly developed method

  3. Corrective Action Investigation Plan for Corrective Action Unit 165: Areas 25 and 26 Dry Well and Washdown Areas, Nevada Test Site, Nevada (including Record of Technical Change Nos. 1, 2, and 3) (January 2002, Rev. 0)

    Energy Technology Data Exchange (ETDEWEB)

    U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office (NNSA/NV)

    2002-01-09

    This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 165 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 165 consists of eight Corrective Action Sites (CASs): CAS 25-20-01, Lab Drain Dry Well; CAS 25-51-02, Dry Well; CAS 25-59-01, Septic System; CAS 26-59-01, Septic System; CAS 25-07-06, Train Decontamination Area; CAS 25-07-07, Vehicle Washdown; CAS 26-07-01, Vehicle Washdown Station; and CAS 25-47-01, Reservoir and French Drain. All eight CASs are located in the Nevada Test Site, Nevada. Six of these CASs are located in Area 25 facilities and two CASs are located in Area 26 facilities. The eight CASs at CAU 165 consist of dry wells, septic systems, decontamination pads, and a reservoir. The six CASs in Area 25 are associated with the Nuclear Rocket Development Station that operated from 1958 to 1973. The two CASs in Area 26 are associated with facilities constructed for Project Pluto, a series of nuclear reactor tests conducted between 1961 to 1964 to develop a nuclear-powered ramjet engine. Based on site history, the scope of this plan will be a two-phased approach to investigate the possible presence of hazardous and/or radioactive constituents at concentrations that could potentially pose a threat to human health and the environment. The Phase I analytical program for most CASs will include volatile organic compounds, semivolatile organic compounds, Resource Conservation and Recovery Act metals, total petroleum hydrocarbons, polychlorinated biphenyls, and radionuclides. If laboratory data obtained from the Phase I investigation indicates the presence of contaminants of concern, the process will continue with a Phase II investigation to define the extent of contamination. Based on the

  4. Artemisinin inhibits chloroplast electron transport activity: mode of action.

    Directory of Open Access Journals (Sweden)

    Adyasha Bharati

    Full Text Available Artemisinin, a secondary metabolite produced in Artemisia plant species, besides having antimalarial properties is also phytotoxic. Although, the phytotoxic activity of the compound has been long recognized, no information is available on the mechanism of action of the compound on photosynthetic activity of the plant. In this report, we have evaluated the effect of artemisinin on photoelectron transport activity of chloroplast thylakoid membrane. The inhibitory effect of the compound, under in vitro condition, was pronounced in loosely and fully coupled thylakoids; being strong in the former. The extent of inhibition was drastically reduced in the presence of uncouplers like ammonium chloride or gramicidin; a characteristic feature described for energy transfer inhibitors. The compound, on the other hand, when applied to plants (in vivo, behaved as a potent inhibitor of photosynthetic electron transport. The major site of its action was identified to be the Q(B; the secondary quinone moiety of photosystemII complex. Analysis of photoreduction kinetics of para-benzoquinone and duroquinone suggest that the inhibition leads to formation of low pool of plastoquinol, which becomes limiting for electron flow through photosystemI. Further it was ascertained that the in vivo inhibitory effect appeared as a consequence of the formation of an unidentified artemisinin-metabolite rather than by the interaction of the compound per se. The putative metabolite of artemisinin is highly reactive in instituting the inhibition of photosynthetic electron flow eventually reducing the plant growth.

  5. Compound mitochondrial DNA mutations in a neurological patient ...

    Indian Academy of Sciences (India)

    and wrist, while recording compound muscle action poten- tials (CMAPs) over the abductor ... Terminator Cycle Sequencing Ready Reaction Kit (Life. Technology). ... The patient (57-year-old man) was initially admitted to Ewha. Womans ... enced jerking of his arms when engaged in purposeful move- ments. At 56 years, he ...

  6. A minimal architecture for joint action

    DEFF Research Database (Denmark)

    Vesper, Cordula; Butterfill, Stephen; Knoblich, Günther

    2010-01-01

    What kinds of processes and representations make joint action possible? In this paper we suggest a minimal architecture for joint action that focuses on representations, action monitoring and action prediction processes, as well as ways of simplifying coordination. The architecture spells out...... minimal requirements for an individual agent to engage in a joint action. We discuss existing evidence in support of the architecture as well as open questions that remain to be empirically addressed. In addition, we suggest possible interfaces between the minimal architecture and other approaches...... to joint action. The minimal architecture has implications for theorizing about the emergence of joint action, for human-machine interaction, and for understanding how coordination can be facilitated by exploiting relations between multiple agents’ actions and between actions and the environment....

  7. Partial purification of endogenous digitalis-like compound(s) in cord blood

    Energy Technology Data Exchange (ETDEWEB)

    Balzan, S.; Ghione, S.; Biver, P.; Gazzetti, P.; Montali, U. (C.N.R. Institute of Clinical Physiology, Pisa (Italy))

    1991-02-01

    Increasing evidence indicates the presence of endogenous digitalis-like compound(s) in human body fluids. In this preliminary report, we describe a study of the partial purification by HPLC of these compounds in the plasma of neonates (who have particularly high concentrations of this substance) and adults. Plasma samples from neonates (cord blood) and adults, lyophilized and extracted with methanol, were applied on a 300 x 3.9 mm C18 Nova Pak column and eluted with a mobile phase of acetonitrile/methanol/water (17/17/66 or 14/14/72 by vol) and, after 30 min, with 100% methanol. We assayed eluted fractions for inhibitory activity of 86Rb uptake and for digoxin-like immunoreactivity. The elution profile revealed a first peak of inhibitory activity of 86Rb uptake at the beginning of the chromatography; another peak was eluted with the 100% methanol. The two peaks also cross-reacted with antidigoxin antibodies. Because the second peak could possibly reflect the nonspecific interference of various lipophilic compounds, we focused our attention on the first peak. For these fractions dose-response curves for 86Rb uptake and for displacement of digoxin were parallel, respectively, to those of ouabain and digoxin, suggesting similarities of digoxin-like immunoreactive substance to cardiac glycosides. Similar chromatographic profiles were also obtained for plasma from adults, suggesting that the endogenous glycoside-like compound(s) in the neonate may be the same as those in the adult.

  8. The chemokine CXCL12 mediates the anti-amyloidogenic action of painless human nerve growth factor.

    Science.gov (United States)

    Capsoni, Simona; Malerba, Francesca; Carucci, Nicola Maria; Rizzi, Caterina; Criscuolo, Chiara; Origlia, Nicola; Calvello, Mariantonietta; Viegi, Alessandro; Meli, Giovanni; Cattaneo, Antonino

    2017-01-01

    Nerve growth factor is a therapeutic candidate for Alzheimer's disease. Due to its pain-inducing activity, in current clinical trials nerve growth factor is delivered locally into the brain by neurosurgery, but data on the efficacy of local nerve growth factor delivery in decreasing amyloid-β deposition are not available. To reduce the nerve growth factor pain-inducing side effects, thus avoiding the need for local brain injection, we developed human painless nerve growth factor (hNGFp), inspired by the human genetic disease hereditary sensory and autonomic neuropathy type V. hNGFp has identical neurotrophic potency as wild-type human nerve growth factor, but a 10-fold lower pain sensitizing activity. In this study we first mimicked, in the 5xFAD mouse model, the intraparenchymal delivery of hNGFp used in clinical trials and found it to be ineffective in decreasing amyloid-β plaque load. On the contrary, the same dose of hNGFp delivered intranasally, which was widely biodistributed in the brain and did not induce pain, showed a potent anti-amyloidogenic action and rescued synaptic plasticity and memory deficits. We found that hNGFp acts on glial cells, modulating inflammatory proteins such as the soluble TNFα receptor II and the chemokine CXCL12. We further established that the rescuing effect by hNGFp is mediated by CXCL12, as pharmacological inhibition of CXCL12 receptor CXCR4 occludes most of hNGFp effects. These findings have significant therapeutic implications: (i) we established that a widespread exposure of the brain is required for nerve growth factor to fully exert its neuroprotective actions; and (ii) we have identified a new anti-neurodegenerative pathway as a broad target for new therapeutic opportunities for neurodegenerative diseases. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  9. Joint action without and beyond planning

    DEFF Research Database (Denmark)

    Blomberg, Olle

    2013-01-01

    ” that one must have in order to be a party to a shared intention (consider, for example, the social play of young children or the cooperative hunting of non-human primates or social carnivores). The second lacuna concerns how participants (including adult human agents) are able to coordinate their actions......, to make sense of the idea that joint activities are non-accidentally coordinated. In chapter 3, I offer an account of a kind of joint activity in which agents such as young children and some non-human primates could participate, given what we know about their socio-cognitive capacities. In chapter 4, I...... to perform “our” joint action. I reject this constraint and argue that some joint actions (such as a joint manoeuvre performed by two figure skaters) are joint in virtue of each participant having what I call ‘socially extended intention-in-action’ that overlap. In chapter 5, I review empirical work...

  10. Induction of apoptosis in human cervical carcinoma HeLa cells by active compounds from Hypericum ascyron L.

    Science.gov (United States)

    Li, Xiu-Mei; Luo, Xue-Gang; He, Jun-Fang; Wang, Nan; Zhou, Hao; Yang, Pei-Long; Zhang, Tong-Cun

    2018-03-01

    Hypericum ascyron L. (Great St. Johnswort), which belongs to the Hypericaceae family, has been used for the treatment of hematemesis, metrorrhagia, rheumatism, swelling, stomach ache, abscesses, dysentery and irregular menstruation for >2,000 years in China. The aim of the present study was to clarify the anticancer activity compounds from H. ascyron L. and the underlying molecular mechanism. Anticancer activity of H. ascyron L. extract was evaluated using an MTT assay. To confirm the anticancer mechanism of activity compounds, Hoechst 33258, Annexin V-fluorescein isothiocyanate/propidium iodide, 2',7'-dichlorodihydrofluorescein diacetate, rhodamine 123 staining and caspase-3 activity analysis were performed. The results demonstrated that the anti-proliferative action of the mixture of kaempferol 3-O-β-(2″-acetyl) galactopyranoside (K) and quercetin (Q) (molar ratio, 1:1) was significantly increased compared with either of these two compounds separately, and the active fraction of the H. ascyron L. extract |(HALE). HALE, indicating that the anti-proliferative function of H. ascyron L. may be a synergic effect of K and Q. Furthermore, the inhibitory effect of KQ on the growth of HeLa cells was mediated by the induction of apoptosis. To the best of our knowledge, the present study is the first to identify that KQ exhibits significant anti-proliferation activity on HeLa cells via the apoptotic pathway, and is also the first to evaluate the anticancer potential of H. ascyron L. The results of the present study may provide a rational base for the use of H. ascyron L. in the clinic, and shed light on the development of novel anticancer drugs.

  11. Mining Key Skeleton Poses with Latent SVM for Action Recognition

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Li

    2017-01-01

    Full Text Available Human action recognition based on 3D skeleton has become an active research field in recent years with the recently developed commodity depth sensors. Most published methods analyze an entire 3D depth data, construct mid-level part representations, or use trajectory descriptor of spatial-temporal interest point for recognizing human activities. Unlike previous work, a novel and simple action representation is proposed in this paper which models the action as a sequence of inconsecutive and discriminative skeleton poses, named as key skeleton poses. The pairwise relative positions of skeleton joints are used as feature of the skeleton poses which are mined with the aid of the latent support vector machine (latent SVM. The advantage of our method is resisting against intraclass variation such as noise and large nonlinear temporal deformation of human action. We evaluate the proposed approach on three benchmark action datasets captured by Kinect devices: MSR Action 3D dataset, UTKinect Action dataset, and Florence 3D Action dataset. The detailed experimental results demonstrate that the proposed approach achieves superior performance to the state-of-the-art skeleton-based action recognition methods.

  12. Primitive Based Action Representation and recognition

    DEFF Research Database (Denmark)

    Baby, Sanmohan

    The presented work is aimed at designing a system that will model and recognize actions and its interaction with objects. Such a system is aimed at facilitating robot task learning. Activity modeling and recognition is very important for its potential applications in surveillance, human-machine i......The presented work is aimed at designing a system that will model and recognize actions and its interaction with objects. Such a system is aimed at facilitating robot task learning. Activity modeling and recognition is very important for its potential applications in surveillance, human......-machine interface, entertainment, biomechanics etc. Recent developments in neuroscience suggest that all actions are a compositions of smaller units called primitives. Current works based on primitives for action recognition uses a supervised framework for specifying the primitives. We propose a method to extract...... primitives automatically. These primitives are to be used to generate actions based on certain rules for combining. These rules are expressed as a stochastic context free grammar. A model merging approach is adopted to learn a Hidden Markov Model to t the observed data sequences. The states of the HMM...

  13. Bioavailability and pharmacokinetic profile of grape pomace phenolic compounds in humans.

    Science.gov (United States)

    Castello, Fabio; Costabile, Giuseppina; Bresciani, Letizia; Tassotti, Michele; Naviglio, Daniele; Luongo, Delia; Ciciola, Paola; Vitale, Marilena; Vetrani, Claudia; Galaverna, Gianni; Brighenti, Furio; Giacco, Rosalba; Del Rio, Daniele; Mena, Pedro

    2018-05-15

    Grape pomace, the major byproduct of the wine and juice industry, is a relevant source of bioactive phenolic compounds. However, polyphenol bioavailability in humans is not well understood, and the inter-individual variability in the production of phenolic metabolites has not been comprehensively assessed to date. The pharmacokinetic and excretive profiles of phenolic metabolites after the acute administration of a drink made from red grape pomace was here investigated in ten volunteers. A total of 35 and 28 phenolic metabolites were quantified in urine and plasma, respectively. The main circulating metabolites included phenyl-γ-valerolactones, hydroxybenzoic acids, simple phenols, hydroxyphenylpropionic acids, hydroxycinnamates, and (epi)catechin phase II conjugates. A high inter-individual variability was shown both in urine and plasma samples, and different patterns of circulating metabolites were unravelled by applying unsupervised multivariate analysis. Besides the huge variability in the production of microbial metabolites of colonic origin, an important variability was observed due to phase II conjugates. These results are of interest to further understand the potential health benefits of phenolic metabolites on individual basis. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Corrective Action Investigation Plan for Corrective Action Unit 5: Landfills, Nevada Test Site, Nevada (Rev. No.: 0) includes Record of Technical Change No. 1 (dated 9/17/2002)

    Energy Technology Data Exchange (ETDEWEB)

    IT Corporation, Las Vegas, NV

    2002-05-28

    This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 5 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 5 consists of eight Corrective Action Sites (CASs): 05-15-01, Sanitary Landfill; 05-16-01, Landfill; 06-08-01, Landfill; 06-15-02, Sanitary Landfill; 06-15-03, Sanitary Landfill; 12-15-01, Sanitary Landfill; 20-15-01, Landfill; 23-15-03, Disposal Site. Located between Areas 5, 6, 12, 20, and 23 of the Nevada Test Site (NTS), CAU 5 consists of unlined landfills used in support of disposal operations between 1952 and 1992. Large volumes of solid waste were produced from the projects which used the CAU 5 landfills. Waste disposed in these landfills may be present without appropriate controls (i.e., use restrictions, adequate cover) and hazardous and/or radioactive constituents may be present at concentrations and locations that could potentially pose a threat to human health and/or the environment. During the 1992 to 1995 time frame, the NTS was used for various research and development projects including nuclear weapons testing. Instead of managing solid waste at one or two disposal sites, the practice on the NTS was to dispose of solid waste in the vicinity of the project. A review of historical documentation, process knowledge, personal interviews, and inferred activities associated with this CAU identified the following as potential contaminants of concern: volatile organic compounds, semivolatile organic compounds, polychlorinated biphenyls, pesticides, petroleum hydrocarbons (diesel- and gasoline-range organics), Resource Conservation and Recovery Act Metals, plus nickel and zinc. A two-phase approach has been selected to collect information and generate data to satisfy needed resolution

  15. Anaerobes as Sources of Bioactive Compounds and Health Promoting Tools.

    Science.gov (United States)

    Mamo, Gashaw

    Aerobic microorganisms have been sources of medicinal agents for several decades and an impressive variety of drugs have been isolated from their cultures, studied and formulated to treat or prevent diseases. On the other hand, anaerobes, which are believed to be the oldest life forms on earth and evolved remarkably diverse physiological functions, have largely been neglected as sources of bioactive compounds. However, results obtained from the limited research done so far show that anaerobes are capable of producing a range of interesting bioactive compounds that can promote human health. In fact, some of these bioactive compounds are found to be novel in their structure and/or mode of action.Anaerobes play health-promoting roles through their bioactive products as well as application of whole cells. The bioactive compounds produced by these microorganisms include antimicrobial agents and substances such as immunomodulators and vitamins. Bacteriocins produced by anaerobes have been in use as preservatives for about 40 years. Because these substances are effective at low concentrations, encounter relatively less resistance from bacteria and are safe to use, there is a growing interest in these antimicrobial agents. Moreover, several antibiotics have been reported from the cultures of anaerobes. Closthioamide and andrimid produced by Clostridium cellulolyticum and Pantoea agglomerans, respectively, are examples of novel antibiotics of anaerobe origin. The discovery of such novel bioactive compounds is expected to encourage further studies which can potentially lead to tapping of the antibiotic production potential of this fascinating group of microorganisms.Anaerobes are widely used in preparation of fermented foods and beverages. During the fermentation processes, these organisms produce a number of bioactive compounds including anticancer, antihypertensive and antioxidant substances. The well-known health promoting effect of fermented food is mostly due to these

  16. CSR concept implementation vs. political hedonism driven by human action

    Directory of Open Access Journals (Sweden)

    Grzegorz Hoppe

    2014-11-01

    Full Text Available The concept of CSR is a big challenge for organisations striving for business excellence. Nevertheless, a question should be asked whether achieving excellence is possible? I s it possible to become an excellent organisation in contemporary economic, social and political circumstances? Or the efforts to build an excellent organisation are only a PR trick. Unfortunately, nowadays many facts seem to confirm that, while operating in a very unfavourable environment, the majority of organisations which implement – to the full extent – the CSR concept in their strategies and adopt the model of socially responsible business risk business failure. Such a conclusion derives from two key facts. First of all, the legal environment is not ready for the development of socially responsible companies which results from political hedonism being an innate feature of democratic systems. Secondly, the level of customer social responsibility is not satisfactory and hardly any changes are expected in the short-term perspective, which is the consequence of hedonistic nature of human actions.

  17. Riboflavin analogs as antiinfectives: occurrence, mode of action, metabolism and resistance.

    Science.gov (United States)

    Pedrolli, Danielle Biscaro; Jankowitsch, Frank; Schwarz, Julia; Langer, Simone; Nakanishi, Shinobu; Frei, Eva; Mack, Matthias

    2013-01-01

    Antimetabolites are molecules, which are structurally similar to molecules needed to carry out primary metabolic reactions.The inhibitory activity of an antimetabolite depends on its successful competition with the natural substrate, ligand, modulator or cofactor of a given biomolecule. Antimetabolites are indispensable as molecular tools in order to understand biological processes. Beyond that,antimetabolites have a large variety of applications in the pharmaceutical and food industries. The identification of the structural riboflavin(vitamin B2) analog roseoflavin in Streptomyces davawensis demonstrates that anti-vitamins/cofactor analogs may serve as lead structures for the development of novel antibiotics. The latter is supported by the recent finding that roseoflavin had a profound inhibiting effect on the growth and infectivity of the human bacterial pathogen Listeria monocytogenes at very low concentrations. Roseoflavin is studied in our laboratory as a model compound. We investigate the biosynthesis, the possible large-scale production, the metabolization,the mechanism of action and the resistance mechanism of the producer organism in order to pave the way for the structured analysis of other vitamin analogs yet to be discovered. These compounds hopefully will help to replenish the arsenal of antimicrobials urgently needed to fight multiresistant bacterial pathogens.

  18. Effects of the anti-malarial compound cryptolepine and its analogues in human lymphocytes and sperm in the Comet assay.

    Science.gov (United States)

    Gopalan, Rajendran C; Emerce, Esra; Wright, Colin W; Karahalil, Bensu; Karakaya, Ali E; Anderson, Diana

    2011-12-15

    Malaria is a mosquito-borne infectious disease caused by the genus Plasmodium. It causes one million deaths per year in African children under the age of 5 years. There is an increasing development of resistance of malarial parasites to chloroquine and other currently used anti-malarial drugs. Some plant products such as the indoloquinoline alkaloid cryptolepine have been shown to have potent activity against P. falciparum in vitro. On account of its toxicity, cryptolepine is not suitable for use as an antimalarial drug but a number of analogues of cryptolepine have been synthesised in an attempt to find compounds that have reduced cytotoxicity and these have been investigated in the present study in human sperm and lymphocytes using the Comet assay. The results suggest that cryptolepine and the analogues cause DNA damage in lymphocytes, but appear to have no effect on human sperm at the assessed doses. In the context of antimalarial drug development, the data suggest that all cryptolepine compounds and in particular 2,7-dibromocryptolepine cause DNA damage and therefore may not be suitable for pre clinical development as antimalarial agents. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Environmental contamination and human exposure to dioxin-related compounds in e-waste recycling sites of developing countries.

    Science.gov (United States)

    Tue, Nguyen Minh; Takahashi, Shin; Subramanian, Annamalai; Sakai, Shinichi; Tanabe, Shinsuke

    2013-07-01

    E-waste recycling using uncontrolled processes is a major source of dioxin-related compounds (DRCs), including not only the regulated polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) but also non-regulated brominated and mixed halogenated compounds (PBDD/Fs and PXDD/Fs). Various studies at informal e-waste recycling sites (EWRSs) in Asian developing countries found the soil contamination levels of PCDD/Fs from tens to ten thousand picogram TCDD-equivalents (TEQ) per gram and those of DL-PCBs up to hundreds of picogram TEQ per gram. The air concentration of PCDD/Fs was reported as high as 50 pg TEQ per m(3) in Guiyu, the largest Chinese EWRS. Non-regulated compounds also contributed substantially to the total DL toxicity of the DRC mixtures from e-waste, as evidenced by the high TEQ levels estimated for the currently identifiable PBDD/Fs as well as the large portion of unexplained bioassay-derived TEQ levels in soils/dusts from EWRSs. Considering the high exposure levels estimated for EWRS residents, especially children, comprehensive emission inventories of DRCs from informal e-waste recycling, the identities and toxic potencies of unidentified DRCs released, and their impacts on human health need to be investigated in future studies.

  20. Influence of Laccase and Tyrosinase on the Antioxidant Capacity of Selected Phenolic Compounds on Human Cell Lines

    Directory of Open Access Journals (Sweden)

    Matthias Riebel

    2015-09-01

    Full Text Available Polyphenolic compounds affect the color, odor and taste of numerous food products of plant origin. In addition to the visual and gustatory properties, they serve as radical scavengers and have antioxidant effects. Polyphenols, especially resveratrol in red wine, have gained increasing scientific and public interest due to their presumptive beneficial impact on human health. Enzymatic oxidation of phenolic compounds takes place under the influence of polyphenol oxidases (PPO, including tyrosinase and laccase. Several studies have demonstrated the radical scavenger effect of plants, food products and individual polyphenols in vitro, but, apart from resveratrol, such impact has not been proved in physiological test systems. Furthermore, only a few data exist on the antioxidant capacities of the enzymatic oxidation products of phenolic compounds generated by PPO. We report here first results about the antioxidant effects of phenolic substances, before and after oxidation by fungal model tyrosinase and laccase. In general, the common chemical 2,2-diphenyl-1-picrylhydrazyl assay and the biological tests using two different types of cell cultures (monocytes and endothelial cells delivered similar results. The phenols tested showed significant differences with respect to their antioxidant activity in all test systems. Their antioxidant capacities after enzymatic conversion decreased or increased depending on the individual PPO used.

  1. Cortical drive of low-frequency oscillations in the human nucleus accumbens during action selection.

    Science.gov (United States)

    Stenner, Max-Philipp; Litvak, Vladimir; Rutledge, Robb B; Zaehle, Tino; Schmitt, Friedhelm C; Voges, Jürgen; Heinze, Hans-Jochen; Dolan, Raymond J

    2015-07-01

    The nucleus accumbens is thought to contribute to action selection by integrating behaviorally relevant information from multiple regions, including prefrontal cortex. Studies in rodents suggest that information flow to the nucleus accumbens may be regulated via task-dependent oscillatory coupling between regions. During instrumental behavior, local field potentials (LFP) in the rat nucleus accumbens and prefrontal cortex are coupled at delta frequencies (Gruber AJ, Hussain RJ, O'Donnell P. PLoS One 4: e5062, 2009), possibly mediating suppression of afferent input from other areas and thereby supporting cortical control (Calhoon GG, O'Donnell P. Neuron 78: 181-190, 2013). In this report, we demonstrate low-frequency cortico-accumbens coupling in humans, both at rest and during a decision-making task. We recorded LFP from the nucleus accumbens in six epilepsy patients who underwent implantation of deep brain stimulation electrodes. All patients showed significant coherence and phase-synchronization between LFP and surface EEG at delta and low theta frequencies. Although the direction of this coupling as indexed by Granger causality varied between subjects in the resting-state data, all patients showed a cortical drive of the nucleus accumbens during action selection in a decision-making task. In three patients this was accompanied by a significant coherence increase over baseline. Our results suggest that low-frequency cortico-accumbens coupling represents a highly conserved regulatory mechanism for action selection. Copyright © 2015 the American Physiological Society.

  2. Radioprotective properties of some heterocyclic nitrogenous compounds against changes in hemoglobin concentration and hematocrit value in x-irradiated mice

    International Nuclear Information System (INIS)

    Rousdhy, H.; Pierotti, T.; Polverelli, M.

    1969-01-01

    Radioprotective properties of imidazole and benzimidazole have been proved in previous works. In this study, authors try to demonstrate radioprotective action of these compounds in comparison with cysteamine upon the hematopoietic system after lethal X-irradiation. Results show: no drastic variations of hematologic constants (hemoglobin concentration and hematocrit value) after intraperitoneal injection of radioprotective compounds apart certain apparent reactions with the heterocyclic compounds; the better radioprotective action of benzimidazole. Twenty five days after irradiation, hemoglobin concentration and hematocrit of radio protected mice return to normal values. (author) [fr

  3. Logistic regression models for polymorphic and antagonistic pleiotropic gene action on human aging and longevity

    DEFF Research Database (Denmark)

    Tan, Qihua; Bathum, L; Christiansen, L

    2003-01-01

    In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic...... situation. Genotype and allele-based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture...... the age-dependent or antagonistic pleiotropic effects. The models are applied to HFE genotype data to assess the effects on human longevity by different alleles and to detect if an age-dependent effect exists. Application has shown that these methods can serve as useful tools in searching for important...

  4. Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.

    Science.gov (United States)

    Wang, Lili; Kim, Kyungsoo; Parikh, Shan; Cadar, Adrian Gabriel; Bersell, Kevin R; He, Huan; Pinto, Jose R; Kryshtal, Dmytro O; Knollmann, Bjorn C

    2018-01-01

    Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. To study the effects of the TnT-I79N mutation in human cardiomyocytes. Using CRISPR/Cas9, the TnT-I79N mutation was introduced into human induced pluripotent stem cells (hiPSCs). We then used the matrigel mattress method to generate single rod-shaped cardiomyocytes (CMs) and studied contractility, Ca handling and electrophysiology. Compared to isogenic control hiPSC-CMs, TnT-I79N hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and impaired relaxation. The Ca-dependence of contractility was leftward shifted in mutation containing cardiomyocytes, demonstrating increased myofilament Ca sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca transients by enhancing cytosolic Ca buffering. These changes in Ca handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer EMD57033 produced similar action potential triangulation in control hiPSC-CMs. The TnT-I79N hiPSC-CM model not only reproduces key cellular features of TnT-linked HCM such as myofilament disarray, hypercontractility and diastolic dysfunction, but also suggests that this TnT mutation causes pro-arrhythmic changes of the human ventricular action potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The reactions of anthronylidene carbene with some heterocyclic compounds

    International Nuclear Information System (INIS)

    Divisia, Bernadette

    1970-01-01

    The action of the anthronylidene carbene, generated by photochemical decomposition of 9-diazo 10-anthron, on four heterocyclic compounds (furan, thiophene, 1-methyl-pyrrole and 2,5-dihydrofuran) has been examined. Two classical carbene reactions have been observed: the addition on double bond (furan, thiophene, 1-methylpyrrole) and hydrogen atom abstraction of the heterocyclic compound (2,5-dihydrofuran). In the case of furan and thiophene, the cyclo-propanic compound resulting from the addition is spontaneously transformed into an ethylenic derivative by valence isomerization. The furan derivative undergoes a cis-trans isomerization, while the thiophene one undergoes an extra carbene attack. In the case of 1-methylpyrrole, the corresponding cyclo-propanic compound undergoes a ring cleavage, followed by a hydrogen atom migration leading to the formation of a substituted anthron. Only an allylic hydrogen atom selective abstraction of heterocyclic compound takes place in the reaction of anthronylidene carbene with 2,5-dihydrofuran. The asymmetrical coupling of radicals so obtained yields the corresponding substituted anthron. (author) [fr

  6. 42 CFR 493.1846 - Civil action.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Civil action. 493.1846 Section 493.1846 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Enforcement Procedures § 493.1846 Civil action. If CMS...

  7. Viewpoint Manifolds for Action Recognition

    Directory of Open Access Journals (Sweden)

    Souvenir Richard

    2009-01-01

    Full Text Available Abstract Action recognition from video is a problem that has many important applications to human motion analysis. In real-world settings, the viewpoint of the camera cannot always be fixed relative to the subject, so view-invariant action recognition methods are needed. Previous view-invariant methods use multiple cameras in both the training and testing phases of action recognition or require storing many examples of a single action from multiple viewpoints. In this paper, we present a framework for learning a compact representation of primitive actions (e.g., walk, punch, kick, sit that can be used for video obtained from a single camera for simultaneous action recognition and viewpoint estimation. Using our method, which models the low-dimensional structure of these actions relative to viewpoint, we show recognition rates on a publicly available dataset previously only achieved using multiple simultaneous views.

  8. Evaluation of phenolic compounds in mate (Ilex paraguariensis) processed by gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Furgeri, C.; Nunes, T.C.F.; Fanaro, G.B. [Instituto de Pesquisas Energeticas Nucleares, IPEN-CNEN/SP, Centro de Tecnologia das Radiacoes-Laboratory de Deteccao de Alimentos Irradiados, Av. Professor Lineu Prestes, 2242, Cidade Universitaria, CEP: 05508-900 Sao Paulo (Brazil); Souza, M.F.F.; Bastos, D.H.M. [Faculdade de Saude Publica, FSP/USP, Departamento de Nutricao-Av. Dr. Arnaldo, 715, CEP: 01246-904 Sao Paulo (Brazil); Villavicencio, A.L.C.H. [Instituto de Pesquisas Energeticas Nucleares, IPEN-CNEN/SP, Centro de Tecnologia das Radiacoes-Laboratory de Deteccao de Alimentos Irradiados, Av. Professor Lineu Prestes, 2242, Cidade Universitaria, CEP: 05508-900 Sao Paulo (Brazil)], E-mail: villavic@ipen.br

    2009-07-15

    The radiation food processing has been demonstrating great effectiveness in the attack of pathogenic agents, while little compromising nutritional value and sensorial properties of foods. The mate (Ilex paraguariensis), widely consumed product in South America, generally in the form of infusions with hot or cold water, calls of chimarrao or terere, it is cited in literature as one of the best sources phenolic compounds. The antioxidants action of these constituent has been related to the protection of the organism against the free radicals, generated in alive, currently responsible for the sprouting of some degenerative illness as cancer, arteriosclerosis, rheumatic arthritis and cardiovascular clutters among others. The objective of that work was to evaluate the action of the processing for gamma radiation in phenolic compounds of terere beverage in the doses of 0, 3, 5, 7 and 10 kGy. The observed results do not demonstrate significant alterations in phenolic compounds of terere beverage processed by gamma radiation.

  9. Evaluation of phenolic compounds in mate (Ilex paraguariensis) processed by gamma radiation

    International Nuclear Information System (INIS)

    Furgeri, C.; Nunes, T.C.F.; Fanaro, G.B.; Souza, M.F.F.; Bastos, D.H.M.; Villavicencio, A.L.C.H.

    2009-01-01

    The radiation food processing has been demonstrating great effectiveness in the attack of pathogenic agents, while little compromising nutritional value and sensorial properties of foods. The mate (Ilex paraguariensis), widely consumed product in South America, generally in the form of infusions with hot or cold water, calls of chimarrao or terere, it is cited in literature as one of the best sources phenolic compounds. The antioxidants action of these constituent has been related to the protection of the organism against the free radicals, generated in alive, currently responsible for the sprouting of some degenerative illness as cancer, arteriosclerosis, rheumatic arthritis and cardiovascular clutters among others. The objective of that work was to evaluate the action of the processing for gamma radiation in phenolic compounds of terere beverage in the doses of 0, 3, 5, 7 and 10 kGy. The observed results do not demonstrate significant alterations in phenolic compounds of terere beverage processed by gamma radiation.

  10. Imprescribility of the action and the disciplinary sanction by violation of human rigths and infractions to the humanitarian international right.

    Directory of Open Access Journals (Sweden)

    Tania Milena Daza-Márquez

    2010-06-01

    Full Text Available This article puts forward an analysis of the problem of the imprescriptibility of action and disciplinary sanctions for grave violations of human rights and international humanitarian law, committed by civil servants, particularly, members of the Military Forces and the National Police. The study deals with the regulation of disciplinary action for grave conduct within the disciplinary regime applicable to the Public Forces over the past thirty years and in the current Code of Practice on Disciplinary and Grievance Proceedures. I also illustrate the legal, political, social and economic consequences—for the Colombian State—of investigation and disciplinary sanctions for crimes against humanity or war crimes being ommitted or delayed through negligence of State offi- cials. The declaration of a prescription may be considered a means to impunity for administrative sanctions and, in turn, provides proof of the State’s failure to comply with International committments that guarantee and protect Human Rights and International Humanitarian Law. Finally, given the controversy regarding diciplinary imprescriptibility, this paper proposes a llegal reform which extends the term of prescription in order to preserve the rights of victims and the disciplined.

  11. Motion Primitives for Action Recognition

    DEFF Research Database (Denmark)

    Fihl, Preben; Holte, Michael Boelstoft; Moeslund, Thomas B.

    2007-01-01

    the actions as a sequence of temporal isolated instances, denoted primitives. These primitives are each defined by four features extracted from motion images. The primitives are recognized in each frame based on a trained classifier resulting in a sequence of primitives. From this sequence we recognize......The number of potential applications has made automatic recognition of human actions a very active research area. Different approaches have been followed based on trajectories through some state space. In this paper we also model an action as a trajectory through a state space, but we represent...... different temporal actions using a probabilistic Edit Distance method. The method is tested on different actions with and without noise and the results show recognition rates of 88.7% and 85.5%, respectively....

  12. Action Recognition using Motion Primitives

    DEFF Research Database (Denmark)

    Moeslund, Thomas B.; Fihl, Preben; Holte, Michael Boelstoft

    the actions as a sequence of temporal isolated instances, denoted primitives. These primitives are each defined by four features extracted from motion images. The primitives are recognized in each frame based on a trained classifier resulting in a sequence of primitives. From this sequence we recognize......The number of potential applications has made automatic recognition of human actions a very active research area. Different approaches have been followed based on trajectories through some state space. In this paper we also model an action as a trajectory through a state space, but we represent...... different temporal actions using a probabilistic Edit Distance method. The method is tested on different actions with and without noise and the results show recognizing rates of 88.7% and 85.5%, respectively....

  13. The human taste receptor hTAS2R14 responds to a variety of different bitter compounds

    International Nuclear Information System (INIS)

    Behrens, Maik; Brockhoff, Anne; Kuhn, Christina; Bufe, Bernd; Winnig, Marcel; Meyerhof, Wolfgang

    2004-01-01

    The recent advances in the functional expression of TAS2Rs in heterologous systems resulted in the identification of bitter tastants that specifically activate receptors of this family. All bitter taste receptors reported to date exhibit a pronounced selectivity for single substances or structurally related bitter compounds. In the present study we demonstrate the expression of the hTAS2R14 gene by RT-PCR analyses and in situ hybridisation in human circumvallate papillae. By functional expression in HEK-293T cells we show that hTAS2R14 displays a, so far, unique broad tuning towards a variety of structurally diverse bitter compounds, including the potent neurotoxins, (-)-α-thujone, the pharmacologically active component of absinthe, and picrotoxinin, a poisonous substance of fishberries. The observed activation of heterologously expressed hTAS2R14 by low concentrations of (-)-α-thujone and picrotoxinin suggests that the receptor is sufficiently sensitive to caution us against the ingestion of toxic amounts of these substances

  14. REVIEW PAPER-MARINE MICROBIAL BIOACTIVE COMPOUNDS

    OpenAIRE

    Kalyani. P*, Hemalatha. K. P. J

    2016-01-01

    Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and...

  15. Inhibitory mechanism of chroman compound on LPS-induced nitric oxide production and nuclear factor-κB activation

    International Nuclear Information System (INIS)

    Kim, Byung Hak; Reddy, Alavala Matta; Lee, Kum-Ho; Chung, Eun Yong; Cho, Sung Min; Lee, Heesoon; Min, Kyung Rak; Kim, Youngsoo

    2004-01-01

    6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (KL-1156) is a novel chemically synthetic compound. In the present study, the chroman KL-1156 compound was found to inhibit lipopolysaccharide (LPS)-induced nitric oxide production in macrophages RAW 264.7. KL-1156 compound attenuated LPS-induced synthesis of both mRNA and protein of inducible nitric oxide synthase (iNOS), in parallel, and inhibited LPS-induced iNOS promoter activity, indicating that the chroman compound down-regulated iNOS expression at transcription level. As a mechanism of the anti-inflammatory action shown by KL-1156 compound, suppression of nuclear factor (NF)-κB has been documented. KL-1156 compound exhibited a dose-dependent inhibitory effect on LPS-induced NF-κB transcriptional activity in macrophages RAW 264.7. Furthermore, the compound inhibited LPS-induced nuclear translocation of NF-κB p65 and DNA binding activity of NF-κB complex, in parallel, but did not affect IκBα degradation. Taken together, this study demonstrated that chroman KL-1156 compound interfered with nuclear translocation step of NF-κB p65, which was attributable to its anti-inflammatory action

  16. From energy-rich phosphate compounds to warfare agents: A review on the chemistry of organic phosphate compounds

    Directory of Open Access Journals (Sweden)

    Luciano Albino Giusti

    2008-12-01

    Full Text Available The chemistry of the phosphorus-oxygen bond is widely used in biological systems in many processes, such as energy transduction and the storage, transmission and expression of genetic information, which are essential to living beings in relation to a wide variety of functions. Compounds containing this bond have been designed for many purposes, ranging from agricultural defense systems, in order to increase food production, to nerve agents, for complaining use in warfare. In this review, features related to the chemistry of organic phosphate compounds are discussed, with particular emphasis on the role of phosphate compounds in biochemical events and in nerve agents. To this aim, the energy-rich phosphate compounds are focused, particularly the mode of their use as energy currency in cells. Historical and recent studies carried out by research groups have tried to elucidate the mechanism of action of enzymes responsible for energy transduction through the use of biochemical studies, enzyme models, and artificial enzymes. Finally, recent studies on the detoxification of nerve agents based on phosphorous esters are presented, and on the utilization of chromogenic and fluorogenic chemosensors for the detection of these phosphate species.

  17. Screening and identification of phytotoxic volatile compounds in medicinal plants and characterizations of a selected compound, eucarvone.

    Science.gov (United States)

    Sunohara, Yukari; Baba, Yohei; Matsuyama, Shigeru; Fujimura, Kaori; Matsumoto, Hiroshi

    2015-07-01

    Screening and identification of phytotoxic volatile compounds were performed using 71 medicinal plant species to find new natural compounds, and the characterization of the promising compound was investigated to understand the mode of action. The volatile compounds from Asarum sieboldii Miq. showed the strongest inhibitory effect on the hypocotyl growth of lettuce seedlings (Lactuca sativa L.cv. Great Lakes 366), followed by those from Schizonepeta tenuifolia Briquet and Zanthoxylum piperitum (L.) DC.. Gas chromatography-mass spectrometry (GC/MS) identified four volatile compounds, α-pinene (2,6,6-trimethylbicyclo[3.1.1]hept-2-ene), β-pinene (6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane), 3-carene (3,7,7-trimethylbicyclo[4.1.0]hept-3-ene), and eucarvone (2,6,6-trimethy-2,4-cycloheptadien-1-one), from A. sieboldii, and three volatile compounds, limonene (1-methyl-4-(1-methylethenyl)-cyclohexene), menthone (5-methyl-2-(propan-2-yl)cyclohexan-1-one), and pulegone (5-methyl-2-propan-2-ylidenecyclohexan-1-one), from S. tenuifolia. Among these volatile compounds, eucarvone, menthone, and pulegone exhibited strong inhibitory effects on both the root and shoot growth of lettuce seedlings. Eucarvone-induced growth inhibition was species-selective. Cell death, the generation of reactive oxygen species (ROS), and lipid peroxidation were induced in susceptible finger millet seedlings by eucarvone treatment, whereas this compound (≤158 μM) did not cause the increase of lipid peroxidation and ROS production in tolerant maize. The results of the present study show that eucarvone can have strong phytotoxic activity, which may be due to ROS overproduction and subsequent oxidative damage in finger millet seedlings.

  18. Clinical breath analysis: Discriminating between human endogenous compounds and exogenous (environmental) chemical confounders

    Science.gov (United States)

    Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous ...

  19. Side effect of acting on the world: Acquisition of action-outcome statistic relation alters visual interpretation of action outcome

    Directory of Open Access Journals (Sweden)

    Takahiro eKawabe

    2013-09-01

    Full Text Available Humans can acquire the statistical features of the external world and employ them to control behaviors. Some external events occur in harmony with an agent’s action, and thus humans should also be able to acquire the statistical features between an action and its external outcome. We report that the acquired action-outcome statistical features alter the visual appearance of the action outcome. Pressing either of two assigned keys triggered visual motion whose direction was statistically biased either upward or downward, and observers judged the stimulus motion direction. Points of subjective equality (PSE for judging motion direction were shifted repulsively from the mean of the distribution associated with each key. Our Bayesian model accounted for the PSE shifts, indicating the optimal acquisition of the action-effect statistical relation. The PSE shifts were moderately attenuated when the action-outcome contingency was reduced. The Bayesian model again accounted for the attenuated PSE shifts. On the other hand, when the action-outcome contiguity was greatly reduced, the PSE shifts were greatly attenuated, and however, the Bayesian model could not accounted for the shifts. The results indicate that visual appearance can be modified by prediction based on the optimal acquisition of action-effect causal relation.

  20. Stereoscopically Observing Manipulative Actions.

    Science.gov (United States)

    Ferri, S; Pauwels, K; Rizzolatti, G; Orban, G A

    2016-08-01

    The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors "stimulus type" (action, static control, and dynamic control), "stereopsis" (present, absent) and "viewpoint" (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior. © The Author 2016. Published by Oxford University Press.

  1. Ontario's Clean Air Action Plan : protecting environmental and human health in Ontario

    International Nuclear Information System (INIS)

    2004-01-01

    Ontario's Clean Air Action Plan was launched in June 2000 in an effort to improve air quality and comply with the Canada-Wide Standards for Particulate Matter and Ozone. This paper describes Ontario's approach to reducing smog. Smog-related air pollution is linked to health problems such as premature death, respiratory and heart problems. Smog also contributes to environmental problems such as damage to forests, agricultural crops and natural vegetation. The two main ingredients of smog are ground level ozone and particulate matter. In order to reduce the incidence of smog, the following four key smog-causing pollutants must be reduced: nitrogen oxides, volatile organic compounds, sulphur dioxide and particular matter. This paper includes the 2001 estimates for Ontario's emissions inventory along with Ontario's smog reduction targets. It was noted that approximately half of all smog in Ontario comes from sources in the midwestern United States. The province of Ontario is committed to replacing coal-fired power plants with cleaner sources of energy. It is also considering emission caps for key industrial sectors. The key players in reducing smog include municipalities, industry, individuals, the federal government and programs that reduce emissions in the United States. 3 figs., 8 tabs., 1 appendix

  2. Corrective action investigation plan for Corrective Action Unit Number 427: Area 3 septic waste system numbers 2 and 6, Tonopah Test Range, Nevada

    International Nuclear Information System (INIS)

    1997-01-01

    This Corrective Action Investigation Plan (CAIP) contains the environmental sample collection objectives and the criteria for conducting site investigation activities at the Area 3 Compound, specifically Corrective Action Unit (CAU) Number 427, which is located at the Tonopah Test Range (TTR). The TTR, included in the Nellis Air Force Range, is approximately 255 kilometers (140 miles) northwest of Las Vegas, Nevada. The Corrective Action Unit Work Plan, Tonopah Test Range, Nevada divides investigative activities at TTR into Source Groups. The Septic Tanks and Lagoons Group consists of seven CAUs. Corrective Action Unit Number 427 is one of three septic waste system CAUs in TTR Area 3. Corrective Action Unit Numbers 405 and 428 will be investigated at a future data. Corrective Action Unit Number 427 is comprised of Septic Waste Systems Number 2 and 6 with respective CAS Numbers 03-05-002-SW02 and 03-05-002-SW06

  3. Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells

    International Nuclear Information System (INIS)

    Cho, Sung-Hee; Chung, Kyung-Sook; Choi, Jung-Hye; Kim, Dong-Hyun; Lee, Kyung-Tae

    2009-01-01

    Compound K [20-O-β-(D-glucopyranosyl)-20(S)-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells. We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis. Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC 50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1) the activation of caspases-3, -8, and -9; (2) the loss of mitochondrial membrane potential; (3) the release of cytochrome c and Smac/DIABLO to the cytosol; (4) the translocation of Bid and Bax to mitochondria; and (5) the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis. The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation

  4. Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells

    Directory of Open Access Journals (Sweden)

    Choi Jung-Hye

    2009-12-01

    Full Text Available Abstract Background Compound K [20-O-β-(D-glucopyranosyl-20(S-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells. Methods We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis. Results Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1 the activation of caspases-3, -8, and -9; (2 the loss of mitochondrial membrane potential; (3 the release of cytochrome c and Smac/DIABLO to the cytosol; (4 the translocation of Bid and Bax to mitochondria; and (5 the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis. Conclusions The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through

  5. Toxicological perspectives on perfluorinated compounds in avian species

    Energy Technology Data Exchange (ETDEWEB)

    Giesy, J.; Jones, P. [Michigan State Univ., East Lansing, MI (United States)

    2004-09-15

    Perfluorinated chemicals have been widely used in commerce for the last few decades. Until recently little was known about their environmental fate and even less was known about their potential environmental effects. Since Giesy and co-workers first demonstrated the widespread occurrence of perfluorooctane sulfonic acid (PFOS) in wildlife there has been renewed interest in determining the biological and possible ecological effects of these compounds. The assessment of possible effects of these chemicals has been hampered by a limited understanding of their mode of action and by a lack of toxicological data for wildlife species. Here we summarize recently obtained toxicological studies available for perfluorinated compounds (PFCs) in two avian species and use this information and environmental concentration data to evaluate the potential for environmental risk that these compounds pose.

  6. Plant-associated bacterial degradation of toxic organic compounds in soil.

    LENUS (Irish Health Repository)

    McGuinness, Martina

    2009-08-01

    A number of toxic synthetic organic compounds can contaminate environmental soil through either local (e.g., industrial) or diffuse (e.g., agricultural) contamination. Increased levels of these toxic organic compounds in the environment have been associated with human health risks including cancer. Plant-associated bacteria, such as endophytic bacteria (non-pathogenic bacteria that occur naturally in plants) and rhizospheric bacteria (bacteria that live on and near the roots of plants), have been shown to contribute to biodegradation of toxic organic compounds in contaminated soil and could have potential for improving phytoremediation. Endophytic and rhizospheric bacterial degradation of toxic organic compounds (either naturally occurring or genetically enhanced) in contaminated soil in the environment could have positive implications for human health worldwide and is the subject of this review.

  7. Volatile compounds emitted by diverse phytopathogenic microorganisms promote plant growth and flowering through cytokinin action

    Czech Academy of Sciences Publication Activity Database

    Sanchez-Lopez, A.; Baslam, M.; De Diego, N.; Jose Munoz, F.; Bahaji, A.; Almagro, G.; Ricarte-Bermejo, A.; Garcia-Gomez, P.; Li, J.; Humplík, J.F.; Novák, Ondřej; Spíchal, L.; Doležal, Karel; Baroja-Fernandez, E.; Pozueta-Romero, J.

    2016-01-01

    Roč. 39, č. 12 (2016), s. 2592-2608 ISSN 0140-7791 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : exceptionally high-levels * tandem mass-spectrometry * arabidopsis-thaliana * nitric-oxide * bacterial volatiles * floral transition * anthocyanin biosynthesis * transgenic arabidopsis * liquid-chromatography * organic-compounds * cytokinin * flowering * growth promotion * microbial volatile compounds * photoregulation * photosynthesis * plant-microbe interaction * starch Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.173, year: 2016

  8. Phenolic Compounds in Brassica Vegetables

    Directory of Open Access Journals (Sweden)

    Pablo Velasco

    2010-12-01

    Full Text Available Phenolic compounds are a large group of phytochemicals widespread in the plant kingdom. Depending on their structure they can be classified into simple phenols, phenolic acids, hydroxycinnamic acid derivatives and flavonoids. Phenolic compounds have received considerable attention for being potentially protective factors against cancer and heart diseases, in part because of their potent antioxidative properties and their ubiquity in a wide range of commonly consumed foods of plant origin. The Brassicaceae family includes a wide range of horticultural crops, some of them with economic significance and extensively used in the diet throughout the world. The phenolic composition of Brassica vegetables has been recently investigated and, nowadays, the profile of different Brassica species is well established. Here, we review the significance of phenolic compounds as a source of beneficial compounds for human health and the influence of environmental conditions and processing mechanisms on the phenolic composition of Brassica vegetables.

  9. Identification of the key pathway of oxazolinoanthracyclines mechanism of action in cells derived from human solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Denel-Bobrowska, Marta, E-mail: mdenel@biol.uni.lodz.pl [Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland); Łukawska, Małgorzata [Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, 5 Staroscinska St., 02-516 Warsaw (Poland); Rogalska, Aneta [Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland); Forma, Ewa; Bryś, Magdalena [Department of Cytobiochemistry, Institute of Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland); Oszczapowicz, Irena [Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, 5 Staroscinska St., 02-516 Warsaw (Poland); Marczak, Agnieszka [Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland)

    2016-12-15

    Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are novel anthracycline derivatives with a modified daunosamine moiety. In the present study, we evaluated the cytotoxicities, genotoxicities and abilities of O-DOX and O-DAU to induce apoptosis in cancer cell lines (SKOV-3; A549; HepG2), and compared the results with their parent drugs. We assessed antiproliferative activity by MTT assay. We evaluated apoptosis-inducing ability by double-staining with fluorescent probes (Hoechst 33258/propidium iodide), and by determining expression levels of genes involved in programmed cell death by reverse transcription-polymerase chain reaction. Genotoxicities of the compounds were tested by comet assays. Oxazolinoanthracyclines demonstrated high anti-tumor activity. O-DOX had significantly higher cytotoxicity, apoptosis-inducing ability, and genotoxicity compared with parental doxorubicin (DOX) in all tested conditions, while O-DAU activity differed among cell lines. The mechanism of oxazoline analog action appeared to involve the mitochondrial pathway of programmed cell death. These results provide further information about oxazoline derivatives of commonly used anthracycline chemotherapy agents. O-DOX and O-DAU have the ability to induce apoptosis in tumor cells. - Highlights: • Substituted amino group increased the anticancer activity of anthracyclines. • Mitochondrial apoptotic pathway seems to be involved in the mechanism of action. • Favorable biological properties of oxazoline derivatives were confirmed.

  10. [Factors behind action, emotion, and decision making].

    Science.gov (United States)

    Watanabe, Katsumi

    2009-12-01

    Human actions, emotions, and decision making are products of complex interactions between explicit and implicit processes at various levels of spatial and temporal scales. Although it may not be possible to obtain to experimental data for all the complexity of human behavioral and emotional processes in our everyday life, recent studies have investigated the effects of social contexts on actions, emotions, and decision making; these studies include those in the fields of experimental psychology, cognitive science, and neuroscience. In this paper, we review several empirical studies that exemplify how our actions, social emotions, and decision making are influenced by the presence of implicit external, rather than internal factors, particularly by presence of other individuals. The following are the main principles identified. (1) Unconscious behavioral contagion: Individuals tend to mimic others' actions. This tendency occurs unconsciously even when the observed and the to-be-executed movements are unrelated at various levels and aspects of behaviors (e. g., behavioral tempo and speed). (2) Neural substrates of social emotions: Various social emotions, including admiration, compassion, envy, and schadenfreude, are represented in neuronal networks that are similar to those of basic emotional processes. (3) Evasive nature of human decision making: Individuals tend to overrate their own subjective impression of and emotional reaction in forecasting affective reaction to events in the future, even though the predictive power of information from peer group is much larger in this regard. Individuals are seldom aware of the dissociation between their intended choice and excuted actions and are willing to give elaborate explanations for the choices they, in fact, did not make. Using these empirical examples, I will illustrate the considerable influences of implicit, unconscious processes on human actions, emotions, and decision making.

  11. Perspectives on object manipulation and action grammar for percussive actions in primates.

    Science.gov (United States)

    Hayashi, Misato

    2015-11-19

    The skill of object manipulation is a common feature of primates including humans, although there are species-typical patterns of manipulation. Object manipulation can be used as a comparative scale of cognitive development, focusing on its complexity. Nut cracking in chimpanzees has the highest hierarchical complexity of tool use reported in non-human primates. An analysis of the patterns of object manipulation in naive chimpanzees after nut-cracking demonstrations revealed the cause of difficulties in learning nut-cracking behaviour. Various types of behaviours exhibited within a nut-cracking context can be examined in terms of the application of problem-solving strategies, focusing on their basis in causal understanding or insightful intentionality. Captive chimpanzees also exhibit complex forms of combinatory manipulation, which is the precursor of tool use. A new notation system of object manipulation was invented to assess grammatical rules in manipulative actions. The notation system of action grammar enabled direct comparisons to be made between primates including humans in a variety of object-manipulation tasks, including percussive-tool use. © 2015 The Author(s).

  12. Spontaneous processing of functional and non-functional action sequences

    DEFF Research Database (Denmark)

    Nielbo, Kristoffer Laigaard; Sørensen, Jesper

    2011-01-01

    as sub-categories of non-functional behavior (i.e., actions lacking causal coherence and a necessary integration between subparts). New insights in human action processing can help us explain how cognition might vary depending on the type of behavior processed. Using an event segmentation paradigm, we...... conducted two experiments eliciting differences in participants' response patterns to functional and non-functional actions. Participants consistently segmented non-functional action sequences into smaller units indicating either an attentional shift to the level of gesture analysis or a problem...... of representational integration. Experimental studies of non-functional behavior can strengthen explanations of recurrent features of human action processing, such as ritual and ritualized behavior, as well as indicate potential sources and effects of breakdown of the system....

  13. In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives

    Science.gov (United States)

    Rocha e Silva, Luiz Francisco; Nogueira, Karla Lagos; Pinto, Ana Cristina da Silva; Katzin, Alejandro Miguel; Sussmann, Rodrigo A. C.; Muniz, Magno Perêa; Neto, Valter Ferreira de Andrade; Chaves, Francisco Célio Maia; Coutinho, Julia Penna; Lima, Emerson Silva; Krettli, Antoniana Ursine; Tadei, Wanderli Pedro

    2015-01-01

    4-Nerolidylcatechol (1) is an abundant antiplasmodial metabolite that is isolated from Piper peltatum roots. O-Acylation or O-alkylation of compound 1 provides derivatives exhibiting improved stability and significant in vitro antiplasmodial activity. The aim of this work was to study the in vitro inhibition of hemozoin formation, inhibition of isoprenoid biosynthesis in Plasmodium falciparum cultures, and in vivo antimalarial activity of several 4-nerolidylcatechol derivatives. 1,2-O,O-Diacetyl-4-nerolidylcatechol (2) inhibited in vitro hemozoin formation by up to 50%. In metabolic labeling studies using [1-(n)-3H]geranylgeranyl pyrophosphate, diester 2 significantly inhibited the biosynthesis of isoprenoid metabolites ubiquinone 8, menaquinone 4, and dolichol 12 in cultures of P. falciparum 3D7. Similarly, 2-O-benzyl-4-nerolidylcatechol (3) significantly inhibited the biosynthesis of dolichol 12. P. falciparum in vitro protein synthesis was not affected by compounds 2 or 3. At oral doses of 50 mg per kg of body weight per day, compound 2 suppressed Plasmodium berghei NK65 in infected BALB/c mice by 44%. This in vivo result for derivative 2 represents marked improvement over that obtained previously for natural product 1. Compound 2 was not detected in mouse blood 1 h after oral ingestion or in mixtures with mouse blood/blood plasma in vitro. However, it was detected after in vitro contact with human blood or blood plasma. Derivatives of 4-nerolidylcatechol exhibit parasite-specific modes of action, such as inhibition of isoprenoid biosynthesis and inhibition of hemozoin formation, and they therefore merit further investigation for their antimalarial potential. PMID:25801563

  14. Bioprocesses for the Removal of Volatile Sulfur Compounds from Gas Streams

    NARCIS (Netherlands)

    Janssen, A.J.H.; bosch, van den P.L.M.; Leerdam, van R.C.; Graaff, de C.M.

    2013-01-01

    This chapter describes the biological removal of sulphur compounds from gas streams. First, an overview is given of the toxicity of sulphur compounds to animals and humans whereafter biological and industrial formation routes for (organic) sulphur compounds are given. Microbial degradation routes of

  15. Post-Colonial Theory and Action Research

    Directory of Open Access Journals (Sweden)

    Jim Parsons

    2011-02-01

    Full Text Available This essay explores connections between post-colonial theory and action research. Post-colonial theory is committed to addressing the plague of colonialism. Action research, at its core, promises to problematize uncontested ‘colonial’ hegemonies of any form. Both post-colonial theory and action research engage dialogic, critically reflective and collaborative values to offer a fuller range of human wisdom. The authors contend that post-colonialism theory calls for justice and seeks to speak to social and psychological suffering, exploitation, violence and enslavement done to the powerless victims of colonization around the world by challenging the superiority of dominant perspectives and seeking to re-position and empower the marginalized and subordinated. In similar ways, action research works to eradicate oppression, powerlessness and worthlessness by affirming solidarity with the oppressed, helping humans move from passive to active and by fundamentally reshaping power. Because both post-colonial theory and action research position the insider or oppressed in an ethic of efficacy, it values community, relationships, communication and equality, and is committed to reciprocity, reflexivity and reflection. Thus, both hold the potential to help reconstruct conditions for a more democratic and just society

  16. Post-Colonial Theory and Action Research

    Directory of Open Access Journals (Sweden)

    Jim B. Parsons

    2011-04-01

    Full Text Available This essay explores connections between post-colonial theory and action research. Post-colonial theory is committed to addressing the plague of colonialism. Action research, at its core, promises to problematize uncontested ‘colonial’ hegemonies of any form. Both post-colonial theory and action research engage dialogic, critically reflective and collaborative values to offer a fuller range of human wisdom. The authors contend that post-colonialism theory calls for justice and seeks to speak to social and psychological suffering, exploitation, violence and enslavement done to the powerless victims of colonization around the world by challenging the superiority of dominant perspectives and seeking to re-position and empower the marginalized and subordinated. In similar ways, action research works to eradicate oppression, powerlessness and worthlessness by affirming solidarity with the oppressed, helping humans move from passive to active and by fundamentally reshaping power. Because both post-colonial theory and action research position the insider or oppressed in an ethic of efficacy, it values community, relationships, communication and equality, and is committed to reciprocity, reflexivity and reflection. Thus, both hold the potential to help reconstruct conditions for a more democratic and just society.

  17. DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp

    2015-05-15

    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.

  18. DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

    International Nuclear Information System (INIS)

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya

    2015-01-01

    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action

  19. Learning a Mid-Level Representation for Multiview Action Recognition

    Directory of Open Access Journals (Sweden)

    Cuiwei Liu

    2018-01-01

    Full Text Available Recognizing human actions in videos is an active topic with broad commercial potentials. Most of the existing action recognition methods are supposed to have the same camera view during both training and testing. And thus performances of these single-view approaches may be severely influenced by the camera movement and variation of viewpoints. In this paper, we address the above problem by utilizing videos simultaneously recorded from multiple views. To this end, we propose a learning framework based on multitask random forest to exploit a discriminative mid-level representation for videos from multiple cameras. In the first step, subvolumes of continuous human-centered figures are extracted from original videos. In the next step, spatiotemporal cuboids sampled from these subvolumes are characterized by multiple low-level descriptors. Then a set of multitask random forests are built upon multiview cuboids sampled at adjacent positions and construct an integrated mid-level representation for multiview subvolumes of one action. Finally, a random forest classifier is employed to predict the action category in terms of the learned representation. Experiments conducted on the multiview IXMAS action dataset illustrate that the proposed method can effectively recognize human actions depicted in multiview videos.

  20. 24 CFR 7.37 - Final action.

    Science.gov (United States)

    2010-04-01

    ..., Color Religion, Sex, National Origin, Age, Disability or Reprisal Complaints § 7.37 Final action. (a... consult with the General Counsel, the Assistant Secretary of Administration, the Office of Human Resources... shall contain notice of the right to appeal the final action to the EEOC, the right to file a civil...

  1. Veterinary Compounding: Regulation, Challenges, and Resources

    OpenAIRE

    Davidson, Gigi

    2017-01-01

    The spectrum of therapeutic need in veterinary medicine is large, and the availability of approved drug products for all veterinary species and indications is relatively small. For this reason, extemporaneous preparation, or compounding, of drugs is commonly employed to provide veterinary medical therapies. The scope of veterinary compounding is broad and focused primarily on meeting the therapeutic needs of companion animals and not food-producing animals in order to avoid human exposure to ...

  2. Body posture modulates action perception.

    Science.gov (United States)

    Zimmermann, Marius; Toni, Ivan; de Lange, Floris P

    2013-04-03

    Recent studies have highlighted cognitive and neural similarities between planning and perceiving actions. Given that action planning involves a simulation of potential action plans that depends on the actor's body posture, we reasoned that perceiving actions may also be influenced by one's body posture. Here, we test whether and how this influence occurs by measuring behavioral and cerebral (fMRI) responses in human participants predicting goals of observed actions, while manipulating postural congruency between their own body posture and postures of the observed agents. Behaviorally, predicting action goals is facilitated when the body posture of the observer matches the posture achieved by the observed agent at the end of his action (action's goal posture). Cerebrally, this perceptual postural congruency effect modulates activity in a portion of the left intraparietal sulcus that has previously been shown to be involved in updating neural representations of one's own limb posture during action planning. This intraparietal area showed stronger responses when the goal posture of the observed action did not match the current body posture of the observer. These results add two novel elements to the notion that perceiving actions relies on the same predictive mechanism as planning actions. First, the predictions implemented by this mechanism are based on the current physical configuration of the body. Second, during both action planning and action observation, these predictions pertain to the goal state of the action.

  3. Multidrug-Resistant Enterococcal Infections: New Compounds, Novel Antimicrobial Therapies?

    Science.gov (United States)

    van Harten, Roel M; Willems, Rob J L; Martin, Nathaniel I; Hendrickx, Antoni P A

    2017-06-01

    Over the past two decades infections due to antibiotic-resistant bacteria have escalated world-wide, affecting patient morbidity, mortality, and health care costs. Among these bacteria, Enterococcus faecium and Enterococcus faecalis represent opportunistic nosocomial pathogens that cause difficult-to-treat infections because of intrinsic and acquired resistance to a plethora of antibiotics. In recent years, a number of novel antimicrobial compound classes have been discovered and developed that target Gram-positive bacteria, including E. faecium and E. faecalis. These new antibacterial agents include teixobactin (targeting lipid II and lipid III), lipopeptides derived from nisin (targeting lipid II), dimeric vancomycin analogues (targeting lipid II), sortase transpeptidase inhibitors (targeting the sortase enzyme), alanine racemase inhibitors, lipoteichoic acid synthesis inhibitors (targeting LtaS), various oxazolidinones (targeting the bacterial ribosome), and tarocins (interfering with teichoic acid biosynthesis). The targets of these novel compounds and mode of action make them very promising for further antimicrobial drug development and future treatment of Gram-positive bacterial infections. Here we review current knowledge of the most favorable anti-enterococcal compounds along with their implicated modes of action and efficacy in animal models to project their possible future use in the clinical setting. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Modeling Interdependent and Periodic Real-World Action Sequences

    Science.gov (United States)

    Kurashima, Takeshi; Althoff, Tim; Leskovec, Jure

    2018-01-01

    Mobile health applications, including those that track activities such as exercise, sleep, and diet, are becoming widely used. Accurately predicting human actions in the real world is essential for targeted recommendations that could improve our health and for personalization of these applications. However, making such predictions is extremely difficult due to the complexities of human behavior, which consists of a large number of potential actions that vary over time, depend on each other, and are periodic. Previous work has not jointly modeled these dynamics and has largely focused on item consumption patterns instead of broader types of behaviors such as eating, commuting or exercising. In this work, we develop a novel statistical model, called TIPAS, for Time-varying, Interdependent, and Periodic Action Sequences. Our approach is based on personalized, multivariate temporal point processes that model time-varying action propensities through a mixture of Gaussian intensities. Our model captures short-term and long-term periodic interdependencies between actions through Hawkes process-based self-excitations. We evaluate our approach on two activity logging datasets comprising 12 million real-world actions (e.g., eating, sleep, and exercise) taken by 20 thousand users over 17 months. We demonstrate that our approach allows us to make successful predictions of future user actions and their timing. Specifically, TIPAS improves predictions of actions, and their timing, over existing methods across multiple datasets by up to 156%, and up to 37%, respectively. Performance improvements are particularly large for relatively rare and periodic actions such as walking and biking, improving over baselines by up to 256%. This demonstrates that explicit modeling of dependencies and periodicities in real-world behavior enables successful predictions of future actions, with implications for modeling human behavior, app personalization, and targeting of health interventions. PMID

  5. Corrective action investigation plan for CAU No. 424: Area 3 Landfill Complex, Tonopah Test Range, Nevada

    International Nuclear Information System (INIS)

    1997-04-01

    This Correction Action Investigation Plan contains the environmental sample collection objectives and the criteria for conducting site investigation activities at the Area 3 Landfill Complex, CAU No. 424, which is located at the Tonopah Test Range (TTR). The TTR, included in the Nellis Air Force Range, is approximately 255 kilometers (140 miles) northwest of Las Vegas, nevada. The CAU 424 is comprised of eight individual landfill sites that are located around and within the perimeter of the Area 3 Compound. Due to the unregulated disposal activities commonly associated with early landfill operations, an investigation will be conducted at each CAS to complete the following tasks: identify the presence and nature of possible contaminant migration from the landfills; determine the vertical and lateral extent of possible contaminant migration; ascertain the potential impact to human health and the environment; and provide sufficient information and data to develop and evaluate appropriate corrective action strategies for each CAS

  6. High content image-based screening of a protease inhibitor library reveals compounds broadly active against Rift Valley fever virus and other highly pathogenic RNA viruses.

    Directory of Open Access Journals (Sweden)

    Rajini Mudhasani

    2014-08-01

    Full Text Available High content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against Rift Valley fever virus (RVFV and to determine their mechanism of action. RVFV is the causative agent of severe disease of humans and animals throughout Africa and the Arabian Peninsula. Of the 849 compounds screened, 34 compounds exhibited ≥ 50% inhibition against RVFV. All of the hit compounds could be classified into 4 distinct groups based on their unique chemical backbone. Some of the compounds also showed broad antiviral activity against several highly pathogenic RNA viruses including Ebola, Marburg, Venezuela equine encephalitis, and Lassa viruses. Four hit compounds (C795-0925, D011-2120, F694-1532 and G202-0362, which were most active against RVFV and showed broad-spectrum antiviral activity, were selected for further evaluation for their cytotoxicity, dose response profile, and mode of action using classical virological methods and high-content imaging analysis. Time-of-addition assays in RVFV infections suggested that D011-2120 and G202-0362 targeted virus egress, while C795-0925 and F694-1532 inhibited virus replication. We showed that D011-2120 exhibited its antiviral effects by blocking microtubule polymerization, thereby disrupting the Golgi complex and inhibiting viral trafficking to the plasma membrane during virus egress. While G202-0362 also affected virus egress, it appears to do so by a different mechanism, namely by blocking virus budding from the trans Golgi. F694-1532 inhibited viral replication, but also appeared to inhibit overall cellular gene expression. However, G202-0362 and C795-0925 did not alter any of the morphological features that we examined and thus may prove to be good candidates for antiviral drug development. Overall this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals and to determine their

  7. Comparative Cognition: Action Imitation Using Episodic Memory.

    Science.gov (United States)

    Crystal, Jonathon D

    2016-12-05

    Humans encounter a myriad of actions or events and later recall some of these events using episodic memory. New research suggests that dogs can imitate recently encountered actions using episodic memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Central Antinociceptive and Mechanism of Action of Pereskia bleo Kunth Leaves Crude Extract, Fractions, and Isolated Compounds

    Directory of Open Access Journals (Sweden)

    Carolina Carvalho Guilhon

    2015-01-01

    Full Text Available Pereskia bleo (Kunth DC. (Cactaceae is a plant commonly used in popular medicine in Malaysia. In this work, we evaluate the antinociceptive effect of P. bleo leaf extracts and isolated compounds in central antinociceptive model. Ethanol extract (E, hexane (H, ethyl acetate (EA, or butanol (B fractions (30, 50, or 100 mg/kg, p.o., sitosterol (from hexane and vitexin (from ethyl acetate, were administered to mice. Antinociceptive effect was evaluated in the hot plate and capsaicin- or glutamate-induced licking models. Morphine (1 mg/kg, p.o. was used as reference drug. Naloxone (1 mg/kg, i.p., atropine (1 mg/kg, i.p., and L-nitro arginine methyl ester (L-NAME, 3 mg/kg, i.p. were administered 30 min earlier (100 mg/kg, p.o. in order to evaluate the mechanism of the antinociceptive action. Higher dose of B developed an effect significantly superior to morphine-treated group. Naloxone prevented the antinociceptive effect of all fractions. L-NAME demonstrated effect against E, EA, and B. In all fractions, sitosterol and vitexin reduced the licking time after capsaicin injection. Glutamate-induced licking response was blocked by H, EA, and B. Our results indicate that Pereskia bleo fractions, sitosterol and vitexin, possessed a central antinociceptive effect. Part of this effect is mediated by opioid receptors and nitrergic pathway.

  9. SST: Single-Stream Temporal Action Proposals

    KAUST Repository

    Buch, Shyamal; Escorcia, Victor; Shen, Chuanqi; Ghanem, Bernard; Niebles, Juan Carlos

    2017-01-01

    Our paper presents a new approach for temporal detection of human actions in long, untrimmed video sequences. We introduce Single-Stream Temporal Action Proposals (SST), a new effective and efficient deep architecture for the generation of temporal action proposals. Our network can run continuously in a single stream over very long input video sequences, without the need to divide input into short overlapping clips or temporal windows for batch processing. We demonstrate empirically that our model outperforms the state-of-the-art on the task of temporal action proposal generation, while achieving some of the fastest processing speeds in the literature. Finally, we demonstrate that using SST proposals in conjunction with existing action classifiers results in improved state-of-the-art temporal action detection performance.

  10. SST: Single-Stream Temporal Action Proposals

    KAUST Repository

    Buch, Shyamal

    2017-11-09

    Our paper presents a new approach for temporal detection of human actions in long, untrimmed video sequences. We introduce Single-Stream Temporal Action Proposals (SST), a new effective and efficient deep architecture for the generation of temporal action proposals. Our network can run continuously in a single stream over very long input video sequences, without the need to divide input into short overlapping clips or temporal windows for batch processing. We demonstrate empirically that our model outperforms the state-of-the-art on the task of temporal action proposal generation, while achieving some of the fastest processing speeds in the literature. Finally, we demonstrate that using SST proposals in conjunction with existing action classifiers results in improved state-of-the-art temporal action detection performance.

  11. On action- and affectpsychology of human reliability. An access by training simulators for complex man-machine systems

    International Nuclear Information System (INIS)

    Schuette, M.

    2002-02-01

    Theoretical part and its topics: errors at the interface between man and machine; reliability analysis for man; the psychological explanation of action reliability of man (intention and control); a paradigma for human reliability (frustration and regression). Empirical part: Control room in a nuclear power plant: Influences on repeated blockages on component care in case of start-up operation; ship bridge: Frustration and regression while steering in a bight. Appendix: analysis of a social interaction.(GL)

  12. Carcinogenicity of individual and a mixture of dioxin-like compounds in female Harlan Sprague Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Walker, N.; Nyska, A. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Crockett, P. [Constella Group, Research Triangle Park, NC (US)] (and others)

    2004-09-15

    The human health risk posed by exposure to persistent organochlorine pollutants (POPs), including polychlorinated-dioxins (PCDDs), -furans (PCDFs) and - biphenyls (PCBs), present in the food and the environment is one of widespread concern throughout the industrialized world. The dioxin Toxic Equivalency Factor (TEF) approach is currently the most feasible interim approach for assessing and managing the risk posed by exposure to mixtures of these compounds and has been formally adopted by regulatory bodies in many countries, the International Programme on Chemical Safety and the World Health Organization. The TEF methodology is a relative potency scheme that estimates the total exposure and biological effects of a mixture of chemicals based on a common mechanism of action involving an initial binding of the compound to the Aryl hydrocarbon receptor (AhR). An implicit assumption of the TEF methodology is that the combined risk of effects of the different congeners is dose additive. Therefore, the total dioxin toxic equivalents (TEQs) of a mixture of PCDDs, PCDFs, and PCBs may be estimated by the summation of the mass of each compound in the mixture after adjustment for its potency relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While dose additivity is supported for certain mixtures for some biological endpoints in some experimental models, this has never been evaluated for cancer risk. Here we present a summary of four chronic rodent bioassay conducted by the National Toxicology Program (US Department of Health and Human Services) that evaluated the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3.3',4,4',5- pentachlorobiphenyl (PCB126) and 2,3,4,7,8 pentachlorodibenzofuran (PeCDF) and a mixture of these three dioxin-like compounds in female Harlan Sprague Dawley rats. Data from these studies will be used to test the hypothesis of dose-additivity of carcinogenicity by a defined mixture of dioxin-like compounds.

  13. Antiviral Screening of Multiple Compounds against Ebola Virus.

    Science.gov (United States)

    Dowall, Stuart D; Bewley, Kevin; Watson, Robert J; Vasan, Seshadri S; Ghosh, Chandradhish; Konai, Mohini M; Gausdal, Gro; Lorens, James B; Long, Jason; Barclay, Wendy; Garcia-Dorival, Isabel; Hiscox, Julian; Bosworth, Andrew; Taylor, Irene; Easterbrook, Linda; Pitman, James; Summers, Sian; Chan-Pensley, Jenny; Funnell, Simon; Vipond, Julia; Charlton, Sue; Haldar, Jayanta; Hewson, Roger; Carroll, Miles W

    2016-10-27

    In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

  14. Antiviral Screening of Multiple Compounds against Ebola Virus

    Directory of Open Access Journals (Sweden)

    Stuart D. Dowall

    2016-10-01

    Full Text Available In light of the recent outbreak of Ebola virus (EBOV disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine. A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna. The three most promising compounds (17-DMAG; BGB324; and NCK-8 were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

  15. Corrective Action Investigation Plan for Corrective Action Unit 252: Area 25 Engine Test Stand 1 Decontamination Pad, Nevada Test Site, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    U.S. Department of Energy, Nevada Operations Office

    1999-08-20

    This Corrective Action Investigation Plan contains the U.S. Department of Energy, Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit 252 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 252 consists of Corrective Action Site (CAS) 25-07-02, Engine Test Stand-1 (ETS-1) Decontamination Pad. Located in Area 25 at the intersection of Road H and Road K at the Nevada Test Site, ETS-1 was designed for use as a mobile radiation checkpoint and for vehicle decontamination. The CAS consists of a concrete decontamination pad with a drain, a gravel-filled sump, two concrete trailer pads, and utility boxes. Constructed in 1966, the ETS-1 facility was part of the Nuclear Rocket Development Station (NRDS) complex and used to test nuclear rockets. The ETS-1 Decontamination Pad and mobile radiation check point was built in 1968. The NRDS complex ceased primary operations in 1973. Based on site history, the focus of the field investigation activities will be to determine if any primary contaminants of potential concern (COPCs) (including radionuclides, total volatile organic compounds, total semivolatile organic compounds, total petroleum hydrocarbons as diesel-range organics, Resource Conservation and Recovery Act metals, total pesticides, and polychlorinated biphenyls) are present at this site. Vertical extent of migration of suspected vehicle decontamination effluent COPCs is expected to be less than 12 feet below ground surface. Lateral extent of migration of COPCs is expected to be limited to the sump area or near the northeast corner of the decontamination pad. Using a biased sampling approach, near-surface and subsurface sampling will be conducted at the suspected worst-case areas including the sump and soil near the northeast corner of the decontamination pad. The results of this field investigation will support a defensible e

  16. Applying Quality by Design Concepts to Pharmacy Compounding.

    Science.gov (United States)

    Timko, Robert J

    2015-01-01

    Compounding of medications is an important part of the practice of the pharmacy profession. Because compounded medications do not have U.S. Food and Drug Administration approval, a pharmacist has the responsibility to ensure that compounded medications are of suitable quality, safety, and efficacy. The Federal Government and numerous states have updated their laws and regulations regarding pharmacy compounding as a result of recent quality issues. Compounding pharmacists are expected to follow good preparation prodecures in their compounding practices in much the same way pharmaceutical manufacturers are required to follow Current Good Manufacturing Procedures as detailed in the United States Code of Federal Regulations. Application of Quality by Design concepts to the preparation process for a compounded medication can help in understanding the potential pitfalls and the means to mitigate their impact. The goal is to build quality into the compounding process to ensure that the resultant compounded prescription meets the human or animal patients' requirements.

  17. Action recognition is sensitive to the identity of the actor.

    Science.gov (United States)

    Ferstl, Ylva; Bülthoff, Heinrich; de la Rosa, Stephan

    2017-09-01

    Recognizing who is carrying out an action is essential for successful human interaction. The cognitive mechanisms underlying this ability are little understood and have been subject of discussions in embodied approaches to action recognition. Here we examine one solution, that visual action recognition processes are at least partly sensitive to the actor's identity. We investigated the dependency between identity information and action related processes by testing the sensitivity of neural action recognition processes to clothing and facial identity information with a behavioral adaptation paradigm. Our results show that action adaptation effects are in fact modulated by both clothing information and the actor's facial identity. The finding demonstrates that neural processes underlying action recognition are sensitive to identity information (including facial identity) and thereby not exclusively tuned to actions. We suggest that such response properties are useful to help humans in knowing who carried out an action. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  18. Developmental impairment of compound action potential in the optic nerve of myelin mutant taiep rats.

    Science.gov (United States)

    Roncagliolo, Manuel; Schlageter, Carol; León, Claudia; Couve, Eduardo; Bonansco, Christian; Eguibar, José R

    2006-01-05

    The taiep rat is a myelin mutant with an initial hypomyelination, followed by a progressive demyelination of the CNS. The neurological correlates start with tremor, followed by ataxia, immobility episodes, epilepsy and paralysis. The optic nerve, an easily-isolable central tract fully myelinated by oligodendrocytes, is a suitable preparation to evaluate the developmental impairment of central myelin. We examined the ontogenic development of optic nerve compound action potentials (CAP) throughout the first 6 months of life of control and taiep rats. Control optic nerves (ON) develop CAPs characterized by three waves. Along the first month, the CAPs of taiep rats showed a delayed maturation, with lower amplitudes and longer latencies than controls; at P30, the conduction velocity has only a third of the normal value. Later, as demyelination proceeds, the conduction velocity of taiep ONs begins to decrease and CAPs undergo a gradual temporal dispersion. CAPs of control and taiep showed differences in their pharmacological sensitivity to TEA and 4-AP, two voltage dependent K+ channel-blockers. As compared with TEA, 4-AP induced a significant increase of the amplitudes and a remarkable broadening of CAPs. After P20, unlike controls, the greater sensitivity to 4-AP exhibited by taiep ONs correlates with the detachment and retraction of paranodal loops suggesting that potassium conductances could regulate the excitability as demyelination of CNS axons progresses. It is concluded that the taiep rat, a long-lived mutant, provides a useful model to study the consequences of partial demyelination and the mechanisms by which glial cells regulate the molecular organization and excitability of axonal membranes during development and disease.

  19. A Contribution of Beef to Human Health: A Review of the Role of the Animal Production Systems

    Directory of Open Access Journals (Sweden)

    Dario Pighin

    2016-01-01

    Full Text Available Meat and meat products constitute important source of protein, fat, and several functional compounds. Although beef consumption may implicate possible negative impacts on human health, its consumption can also contribute to human health. Quality traits of beef, as well as its nutritional properties, depend on animal genetics, feeding, livestock practices, and post mortem procedures. Available data show that emerging beef production systems are able to improve both, quality and nutritional traits of beef in a sustainable way. In this context, Argentina’s actions are aimed at maximising beef beneficial effects and minimising its negative impact on human health, in a way of contributing to global food security.

  20. Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review.

    Science.gov (United States)

    Giulivo, Monica; Lopez de Alda, Miren; Capri, Ettore; Barceló, Damià

    2016-11-01

    Endocrine disrupting chemicals (EDCs) are released into the environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDCs have major risks for humans by targeting different organs and systems in the body (e.g. reproductive system, breast tissue, adipose tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds the aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children. The interactions and mechanisms of toxicity of EDCs in relation to human general health problems, especially those broadening the term of endocrine disruption to 'metabolic disruption', should be deeply investigated. These include endocrine disturbances, with particular reference to reproductive problems and breast, testicular and ovarian cancers, and metabolic diseases such as obesity or diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.