Sample records for evaluation system nes

  1. A high-throughput screening system targeting the nuclear export pathway via the third nuclear export signal of influenza A virus nucleoprotein.

    PubMed

    Kakisaka, Michinori; Mano, Takafumi; Aida, Yoko

    2016-06-02

    Two classes of antiviral drugs, M2 channel inhibitors and neuraminidase (NA) inhibitors, are currently approved for the treatment of influenza; however, the development of resistance against these agents limits their efficacy. Therefore, the identification of new targets and the development of new antiviral drugs against influenza are urgently needed. The third nuclear export signal (NES3) of nucleoprotein (NP) is the most important for viral replication among seven NESs encoded by four viral proteins, NP, M1, NS1, and NS2. NP-NES3 is critical for the nuclear export of NP, and targeting NP-NES3 is therefore a promising strategy that may lead to the development of antiviral drugs. However, a high-throughput screening (HTS) system to identify inhibitors of NP nuclear export has not been established. Here, we developed a novel HTS system to evaluate the inhibitory effects of compounds on the nuclear export pathway mediated by NP-NES3 using a MDCK cell line stably expressing NP-NES3 fused to a green fluorescent protein from aequorea coerulescens (AcGFP-NP-NES3) and a cell imaging analyzer. This HTS system was used to screen a 9600-compound library, leading to the identification of several hit compounds with inhibitory activity against the nuclear export of AcGFP-NP-NES3. The present HTS system provides a useful strategy for the identification of inhibitors targeting the nuclear export of NP via its NES3 sequence. Copyright © 2016. Published by Elsevier B.V.

  2. Formulation Development and Evaluation of the Therapeutic Efficacy of Brinzolamide Containing Nanoemulsions

    PubMed Central

    Mahboobian, Mohammad Mehdi; Seyfoddin, Ali; Rupenthal, Ilva D.; Aboofazeli, Reza; Foroutan, Seyed Mohsen

    2017-01-01

    Brinzolamide (BZ) is an intraocular pressure reducing agent with low bioavailability. The purpose of the present study was to overcome this issue by development of BZ containing nanoemulsions (NEs) as an ocular drug delivery system with desirable therapeutic efficacy. Brinzolamide NEs were prepared by the spontaneous emulsification method. Based on initial release studies, twelve formulations with the slowest release characteristics were subjected to further physicochemical investigations such as particle size, polydispersity index, pH, refractive index, osmolality and viscosity. The therapeutic efficacy of these formulations was assessed by measuring the intraocular pressure after instillation of the prepared NEs in normotensive albino rabbit eyes. Nanoemulsions with suitable physicochemical properties exhibited high formulation stability under different conditions. more over biological evaluations indicated that using lower drug concentrations in NE formulations (0.4%) had a similar or even better pharmacodynamic effect compared to the commercial suspension with a higher drug concentration (1%). Our findings suggest that NEs could be effectively used as carriers for enhancing the bioavailability of topically applied ophthalmic drugs. PMID:29201076

  3. Night eating in bipolar disorder.

    PubMed

    Melo, Matias Carvalho Aguiar; de Oliveira Ribeiro, Maximilo; de Araújo, Carolina Freitas Cardeal; de Mesquita, Licia Marah Figueredo; de Bruin, Pedro Felipe Carvalhedo; de Bruin, Veralice Meireles Sales

    2018-05-07

    Night eating syndrome (NES) involves reduced feeding during the day and evening hyperphagia sometimes accompanied by frequent nocturnal awakenings with conscious episodes of compulsive ingestion of food. Previously, NES has not been evaluated in bipolar disorder (BD). The objective of this study was to identify NES in euthymic BD patients. Eighty BD patients and 40 controls were examined using the Night Eating Questionnaire, Hamilton Rating Scale for Depression and Anxiety, Young Mania Rating Scale, Functioning Assessment Short-Test and International Physical Activity Questionnaire. Sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness (Epworth Sleepiness Scale), severity of insomnia (Insomnia Severity Index) and morning-evening preference (Morningness-Eveningness Questionnaire) were also evaluated. BD patients presented NES in 8.8% while the controls showed no NES. Patients with and without NES were not different with respect to gender, disease duration, smoking, heavy drinking, body mass index, waist-to-hip ratio and neck circumference. BD patients with NES scored higher for functioning as well as for the following specific components: occupational functioning, financial issues, interpersonal relationships and leisure time. They also had more anxiety, higher insomnia severity and worse sleep quality. Furthermore, BD patients with NES were more evening type. NES occurs more frequently in BD patients than in controls. BD patients with NES present more disease-related manifestations such as more anxiety, poorer functioning and worse sleep parameters. Patients with NES were more evening type. We speculate whether changing circadian preference in these patients can reduce NES. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Formulation Development and Toxicity Assessment of Triacetin Mediated Nanoemulsions as Novel Delivery Systems for Rapamycin

    PubMed Central

    Sobhani, Hamideh; Tarighi, Parastoo; Ostad, Seyed Nasser; Shafaati, Alireza; Nafissi-Varcheh, Nastaran; Aboofazeli, Reza

    2015-01-01

    The aim of this investigation was to design and develop nanoemulsions (NEs) as novel delivery systems for rapamycin. Phase behavior of quaternary systems composed of Traicetin (as oil), various surfactants and co-surfactants and water at different surfactant/co-surfactant weight ratios was investigated by the construction of phase diagrams. Formulations were taken from the o/w NE region of the phase diagrams, depending upon the extent of NE domain. The spontaneous emulsification method was used to prepare various formulations containing 1 mg/mL of the drug. The NEs were characterized and subjected to stability tests at various temperatures over 9-12 months. Cumulative drug release from the selected formulations was determined for a period of 48 h using a dialysis sac. The assay of rapamycin was carried out using an HPLC technique. The effect of NEs on the viability of SKBR-3 cells was evaluated by MTT assay. The integrity of Caco-2 cell monolayers was measured by Transepithelial Electrical Resistance (TEER) and the transport of rapamycin-loaded NEs across Caco-2 cell monolayers was then assessed. The uptake of NEs by SKBR-3 cells was also investigated using florescence microscopy. Maximum drug release was observed in case of 4 formulations prepared with Tween 80 and Tween 20. MTT test results revealed different toxicity of NEs for SKBR-3 cell line and TEER demonstrated that formulations containing Tween 20 caused a more considerable decrease in cell integrity in comparison with those prepared with Tween 80. The results obtained from cellular uptake experiments were in consistent with those obtained from TEER and cytotoxicity experiments. PMID:26185501

  5. Formulation Development and Toxicity Assessment of Triacetin Mediated Nanoemulsions as Novel Delivery Systems for Rapamycin.

    PubMed

    Sobhani, Hamideh; Tarighi, Parastoo; Ostad, Seyed Nasser; Shafaati, Alireza; Nafissi-Varcheh, Nastaran; Aboofazeli, Reza

    2015-01-01

    The aim of this investigation was to design and develop nanoemulsions (NEs) as novel delivery systems for rapamycin. Phase behavior of quaternary systems composed of Traicetin (as oil), various surfactants and co-surfactants and water at different surfactant/co-surfactant weight ratios was investigated by the construction of phase diagrams. Formulations were taken from the o/w NE region of the phase diagrams, depending upon the extent of NE domain. The spontaneous emulsification method was used to prepare various formulations containing 1 mg/mL of the drug. The NEs were characterized and subjected to stability tests at various temperatures over 9-12 months. Cumulative drug release from the selected formulations was determined for a period of 48 h using a dialysis sac. The assay of rapamycin was carried out using an HPLC technique. The effect of NEs on the viability of SKBR-3 cells was evaluated by MTT assay. The integrity of Caco-2 cell monolayers was measured by Transepithelial Electrical Resistance (TEER) and the transport of rapamycin-loaded NEs across Caco-2 cell monolayers was then assessed. The uptake of NEs by SKBR-3 cells was also investigated using florescence microscopy. Maximum drug release was observed in case of 4 formulations prepared with Tween 80 and Tween 20. MTT test results revealed different toxicity of NEs for SKBR-3 cell line and TEER demonstrated that formulations containing Tween 20 caused a more considerable decrease in cell integrity in comparison with those prepared with Tween 80. The results obtained from cellular uptake experiments were in consistent with those obtained from TEER and cytotoxicity experiments.

  6. Night Eating Syndrome in Major Depression and Anxiety Disorders.

    PubMed

    Küçükgöncü, Suat; Beştepe, Emrem

    2014-12-01

    The purpose of this study is to investigate the prevalence and the clinical features of night eating syndrome (NES) in patients with depression and anxiety disorders. The study was conducted at Bakırköy State Hospital for Mental Health and Neurological Disorders. Three-hundred out-patients who had major depression (MD), panic disorders (PD), general anxiety disorders (GAD) and obsessive-compulsive disorders (OCD) participated in the study. The semi-structured socio-demographic form, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Night Eating Questionnaire, and NES Evaluation Questionnaire were implemented. In our sample, the prevalence of the NES was 15.7% (n=47). NES frequency was significantly higher in the patients diagnosed with major depression (MD 22%, GAD 7.8%, OCD 12.5%, PD 14%). Smoking, presence of past suicide attempts, rates of antipsychotic drugs use, and average scores of body mass index (BMI) were significantly higher in the patients who had NES. In this sample, depression, BMI, and smoking were found to be determinants of NES. This study shows that NES may be frequently observed in patients admitted to psychiatric clinics, especially in those with major depression. Evaluation of NES in psychiatric patients may help the treatment of the primary psychopathology and prevent the adverse effects, like weight gain, which may reduce the quality of life.

  7. Development of Food-Grade Curcumin Nanoemulsion and its Potential Application to Food Beverage System: Antioxidant Property and In Vitro Digestion.

    PubMed

    Joung, Hee Joung; Choi, Mi-Jung; Kim, Jun Tae; Park, Seok Hoon; Park, Hyun Jin; Shin, Gye Hwa

    2016-03-01

    Curcumin nanoemulsions (Cur-NEs) were developed with various surfactant concentrations by using high pressure homogenization and finally applied to the commercial milk system. Characterization of Cur-NEs was performed by measuring the droplet size and polydispersity index value at different Tween 20 concentrations. The morphology of the Cur-NEs was observed by confocal laser scanning microscopy and transmission electron microscopy. Antioxidant activity and in vitro digestion ability were tested using 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, pH-stat method, and thiobarbituric acid reactive substances assays. Cur-NEs were found to be physically stable for 1 mo at room temperature. The surfactant concentration affects particle formation and droplet size. The mean droplet size decreased from 122 to 90 nm when surfactant concentration increased 3 times. Cur-NEs had shown an effective oxygen scavenging activity. Cur-NEs-fortified milk showed significantly lower lipid oxidation than control (unfortified) milk and milk containing curcumin-free nanoemulsions. These properties make Cur-NEs suitable systems for the beverage industry. © 2016 Institute of Food Technologists®

  8. Neurological signs and cognitive performance distinguish between adolescents with and without psychosis.

    PubMed

    Arciniegas, David B; Rojas, Donald C; Kleman, Michelle Ramos; Asherin, Ryan; Reite, Martin L

    2007-01-01

    Neurological and cognitive aspects of adolescent psychotic disorders are understudied. The authors assessed 19 adolescents with psychosis and 16 healthy comparison subjects using the Neurological Evaluation Scale (NES) and age-appropriate Wechsler intelligence quotient (IQ) scales. NES scores were highest and IQ scores were lowest among subjects with psychosis. Subjects with psychosis did not demonstrate age-related decreases in NES score. The combination of NES and IQ scores predicted both the presence of psychosis and psychiatric diagnosis. There were no relationships between medication status and either NES or IQ scores. These results support a broadly conceived neurodevelopmental formulation of adolescent psychotic disorders.

  9. Broadband piezoelectric vibration energy harvesting using a nonlinear energy sink

    NASA Astrophysics Data System (ADS)

    Xiong, Liuyang; Tang, Lihua; Liu, Kefu; Mace, Brian R.

    2018-05-01

    A piezoelectric vibration energy harvester (PVEH) is capable of converting waste or undesirable ambient vibration energy into useful electric energy. However, conventional PVEHs typically work in a narrow frequency range, leading to low efficiency in practical application. This work proposes a PVEH based on the principle of the nonlinear energy sink (NES) to achieve broadband energy harvesting. An alternating current circuit with a resistive load is first considered in the analysis of the dynamic properties and electric performance of the NES-based PEVH. Then, a standard rectifying direct current (DC) interface circuit is developed to evaluate the DC power from the PVEH. To gain insight into the NES mechanism involved, approximate analysis of the proposed PVEH systems under harmonic excitation is sought using the mixed multi-scale and harmonic balance method and the Newton–Raphson harmonic balance method. In addition, an equivalent circuit model (ECM) of the electromechanical system is derived and circuit simulations are conducted to explore and validate the energy harvesting and vibration absorption performance of the proposed NES-based PVEH. The response is also compared with that obtained by direct numerical integration of the equations of motion. Finally, the optimal resistance to obtain the maximum DC power is determined based on the Newton–Raphson harmonic balance method and validated by the ECM. In general, the NES-based PVEH can absorb the vibration from the primary structure and collect electric energy within a broad frequency range effectively.

  10. A cellular reporter to evaluate CRM1 nuclear export activity: functional analysis of the cancer-related mutant E571K.

    PubMed

    García-Santisteban, Iraia; Arregi, Igor; Alonso-Mariño, Marián; Urbaneja, María A; Garcia-Vallejo, Juan J; Bañuelos, Sonia; Rodríguez, Jose A

    2016-12-01

    The exportin CRM1 binds nuclear export signals (NESs), and mediates active transport of NES-bearing proteins from the nucleus to the cytoplasm. Structural and biochemical analyses have uncovered the molecular mechanisms underlying CRM1/NES interaction. CRM1 binds NESs through a hydrophobic cleft, whose open or closed conformation facilitates NES binding and release. Several cofactors allosterically modulate the conformation of the NES-binding cleft through intramolecular interactions involving an acidic loop and a C-terminal helix in CRM1. This current model of CRM1-mediated nuclear export has not yet been evaluated in a cellular setting. Here, we describe SRV100, a cellular reporter to interrogate CRM1 nuclear export activity. Using this novel tool, we provide evidence further validating the model of NES binding and release by CRM1. Furthermore, using both SRV100-based cellular assays and in vitro biochemical analyses, we investigate the functional consequences of a recurrent cancer-related mutation, which targets a residue near CRM1 NES-binding cleft. Our data indicate that this mutation does not necessarily abrogate the nuclear export activity of CRM1, but may increase its affinity for NES sequences bearing a more negatively charged C-terminal end.

  11. Development and characterization of nanostructured mists with potential for actively targeting poorly water-soluble compounds into the lungs.

    PubMed

    Nesamony, Jerry; Kalra, Ashish; Majrad, Mohamed S; Boddu, Sai Hanuman Sagar; Jung, Rose; Williams, Frederick E; Schnapp, Alaina M; Nauli, Surya M; Kalinoski, Andrea L

    2013-10-01

    To formulate nanoemulsions (NE) with potential for delivering poorly water-soluble drugs to the lungs. A self nanoemulsifying composition consisting of cremophor RH 40, PEG 400 and labrafil M 2125 CS was selected after screening potential excipients. The solubility of carbamazepine, a poorly water-soluble drug, was tested in the formulation components. Oil-in-water (o/w) NEs were characterized using dynamic light scattering, electrophoretic light scattering, transmission electron microscopy (TEM) and differential scanning calorimetry. NEs were nebulized into a mist using a commercial nebulizer and characterized using laser diffraction and TEM. An aseptic method was developed for preparing sterile NEs. Biocompatibility of the formulation was evaluated on NIH3T3 cells using MTT assay. In vitro permeability of the formulation was tested in zebra fish eggs, HeLa cells, and porcine lung tissue. NEs had neutrally charged droplets of less than 20 nm size. Nebulized NEs demonstrated an o/w nanostructure. The mist droplets were of size less than 5 μm. Sterility testing and cytotoxicity results validated that the NE was biocompatible and sterile. In vitro tests indicated oil nanodroplets penetrating intracellularly through biological membranes. The nanoemulsion mist has the potential for use as a pulmonary delivery system for poorly water-soluble drugs.

  12. COMPUTERIZED ASSESSMENT OF HUMAN NEUROTOXICITY: SENSITIVITY TO NITROUS OXIDE EXPOSURE

    EPA Science Inventory

    The authors recently developed a flexible, portable, computer based neurobehavioral evaluation system (NES) to standardize data collection in epidemiologic field studies of individuals at risk for neurobehavioral toxicity. The current study was performed to examine the system's s...

  13. Vortex-induced vibrations mitigation through a nonlinear energy sink

    NASA Astrophysics Data System (ADS)

    Dai, H. L.; Abdelkefi, A.; Wang, L.

    2017-01-01

    The passive suppression mechanism of the vortex-induced vibrations (VIV) of the cylinder by means of an essentially nonlinear element, the nonlinear energy sink (NES) is investigated. The flow-induced loads on the cylinder are modeled using a prevalent van der Pol oscillator which is experimentally validated, coupling to the structural vibrations in the presence of the NES structure. Based on the coupled nonlinear governing equations of motion, the performed analysis indicates that the mass and damping of NES have significant effects on the coupled frequency and damping of the aero-elastic system, leading to the shift of synchronization region and mitigation of vibration responses. It is demonstrated that the coupled system of flow-cylinder-NES behaves resonant interactions, showing periodic, aperiodic, and multiple stable responses which depend on the values of the NES parameters. In addition, it is found that the occurrence of multiple stable responses can enhance the nonlinear energy pumping effect, resulting in the increment of transferring energy from the flow via the cylinder to the NES, which is related to the essential nonlinearity of the sink stiffness. This results in a significant reduction in the VIV amplitudes of the primary circular cylinder for appropriate NES parameter values.

  14. Progress in development of neutron energy spectrometer for deuterium plasma operation in KSTARa)

    NASA Astrophysics Data System (ADS)

    Tomita, H.; Yamashita, F.; Nakayama, Y.; Morishima, K.; Yamamoto, Y.; Sakai, Y.; Cheon, M. S.; Isobe, M.; Ogawa, K.; Hayashi, S.; Kawarabayashi, J.; Iguchi, T.

    2014-11-01

    Two types of DD neutron energy spectrometer (NES) are under development for deuterium plasma operation in KSTAR to understand behavior of beam ions in the plasma. One is based on the state-of-the-art nuclear emulsion technique. The other is based on a coincidence detection of a recoiled proton and a scattered neutron caused by an elastic scattering of an incident DD neutron, which is called an associated particle coincidence counting-NES. The prototype NES systems were installed at J-port in KSTAR in 2012. During the 2012 and 2013 experimental campaigns, multiple shots-integrated neutron spectra were preliminarily obtained by the nuclear emulsion-based NES system.

  15. 77 FR 39552 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change With...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... Exchange or NASDAQ Execution Services To Cancel Orders When a Technical or Systems Issue Occurs and To... the authority of BX or NASDAQ Execution Services (``NES'') to cancel orders when a technical or... issue may occur at BX, NES, or a routing destination that causes BX or NES to cancel orders, if BX or...

  16. Neem oil nanoemulsions: characterisation and antioxidant activity.

    PubMed

    Rinaldi, Federica; Hanieh, Patrizia Nadia; Longhi, Catia; Carradori, Simone; Secci, Daniela; Zengin, Gokhan; Ammendolia, Maria Grazia; Mattia, Elena; Del Favero, Elena; Marianecci, Carlotta; Carafa, Maria

    2017-12-01

    The aim of the present work is to develop nanoemulsions (NEs), nanosized emulsions, manufactured for improving the delivery of active pharmaceutical ingredients. In particular, nanoemulsions composed of Neem seed oil, contain rich bioactive components, and Tween 20 as nonionic surfactant were prepared. A mean droplet size ranging from 10 to 100 nm was obtained by modulating the oil/surfactant ratio. Physicochemical characterisation was carried out evaluating size, ζ-potential, microviscosity, polarity and turbidity of the external shell and morphology, along with stability in simulated cerebrospinal fluid (CSF), activity of Neem oil alone and in NEs, HEp-2 cell interaction and cytotoxicity studies. This study confirms the formation of NEs by Tween 20 and Neem oil at different weight ratios with small and homogenous dimensions. The antioxidant activity of Neem oil alone and in NEs was comparable, whereas its cytotoxicity was strongly reduced when loaded in NEs after interaction with HEp-2 cells.

  17. A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women.

    PubMed

    Brache, Vivian; Merkatz, Ruth; Kumar, Narender; Jesam, Cristian; Sussman, Heather; Hoskin, Elena; Roberts, Kevin; Alami, Mohcine; Taylor, Deshawn; Jorge, Aidelis; Croxatto, Horacio; Lorange, Ellen; Mishell, Daniel R; Sitruk-Ware, Regine

    2015-10-01

    This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Eighteen participants were randomized; 16 completed the study. Median NES C(max) values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Evaluation of blast furnace slag as basal media for eelgrass bed.

    PubMed

    Hizon-Fradejas, Amelia B; Nakano, Yoichi; Nakai, Satoshi; Nishijima, Wataru; Okada, Mitsumasa

    2009-07-30

    Two types of blast furnace slag (BFS), granulated (GS) and air-cooled slag (ACS), were evaluated as basal media for eelgrass bed. Evaluation was done by comparing BFS samples with natural eelgrass sediment (NES) in terms of some physico-chemical characteristics and then, investigating growth of eelgrass both in BFS and NES. In terms of particle size, both BFS samples were within the range acceptable for growing eelgrass. However, compared with NES, low silt-clay content for ACS and lack of organic matter content for both BFS samples were found. Growth experiment showed that eelgrass can grow in both types of BFS, although growth rates in BFS samples shown by leaf elongation were slower than that in NES. The possible reasons for stunted growth in BFS were assumed to be lack of organic matter and release of some possible toxins from BFS. Reduction of sulfide content of BFS samples did not result to enhanced growth; though sulfide release was eliminated, release of Zn was greater than before treatment and concentration of that reached to alarming amounts.

  19. Correlation between Gas Bubble Formation and Hydrogen Evolution Reaction Kinetics at Nanoelectrodes.

    PubMed

    Chen, Qianjin; Luo, Long

    2018-04-17

    We report the correlation between H 2 gas bubble formation potential and hydrogen evolution reaction (HER) activity for Au and Pt nanodisk electrodes (NEs). Microkinetic models were formulated to obtain the HER kinetic information for individual Au and Pt NEs. We found that the rate-determining steps for the HER at Au and Pt NEs were the Volmer step and the Heyrovsky step, respectively. More interestingly, the standard rate constant ( k 0 ) of the rate-determining step was found to vary over 2 orders of magnitude for the same type of NEs. The observed variations indicate the HER activity heterogeneity at the nanoscale. Furthermore, we discovered a linear relationship between bubble formation potential ( E bubble ) and log( k 0 ) with a slope of 125 mV/decade for both Au and Pt NEs. As log ( k 0 ) increases, E bubble shifts linearly to more positive potentials, meaning NEs with higher HER activities form H 2 bubbles at less negative potentials. Our theoretical model suggests that such linear relationship is caused by the similar critical bubble formation condition for Au and Pt NEs with varied sizes. Our results have potential implications for using gas bubble formation to evaluate the HER activity distribution of nanoparticles in an ensemble.

  20. Direct observation of nucleocytoplasmic transport by microinjection of GFP-tagged proteins in living cells.

    PubMed

    Rosorius, O; Heger, P; Stelz, G; Hirschmann, N; Hauber, J; Stauber, R H

    1999-08-01

    We established a straightforward experimental system to investigate directly the requirements for nucleocytoplasmic transport in live cells. For this purpose, substrates were created containing nuclear localization signals (NLS) or nuclear export signals (NES) linked to a chimeric protein composed of the glutathione S-transferase (GST) fused to the green fluorescent protein (GFP). The combination of GST/GFP-tagging allowed us to control protein expression in bacteria and to monitor protein purification during chromatography. Following microinjection into somatic cells, nuclear export/import of the highly fluorescent substrates could be observed directly by fluorescence microscopy. This system sets the stage to quantitate, in real time, the kinetics of nuclear import/export in living cells and to evaluate qualitative differences in various NLS/NES signals and pathways.

  1. Quenching chatter instability in turning process with a vibro-impact nonlinear energy sink

    NASA Astrophysics Data System (ADS)

    Gourc, E.; Seguy, S.; Michon, G.; Berlioz, A.; Mann, B. P.

    2015-10-01

    This paper investigates the passive control of chatter instability in turning processes using a vibro-impact nonlinear energy sink (NES). The workpiece is assumed to be rigid and the tool is flexible. A dynamical model including a nonlinear cutting law is presented and the stability lobes diagram is obtained. The behavior of the system with the vibro-impact NES is investigated using an asymptotic analysis. A control mechanism by successive beating is revealed, similarly to the strongly modulated response in the case of NES with cubic stiffness. It is shown that such a response regime may be beneficial for chatter mitigation. An original experimental procedure is proposed to verify the sizing of the vibro-impact NES. An experimental setup is developed with a vibro-impact NES embedded on the lathe tool and the results are analyzed and validated.

  2. Nano Petri dishes: a new polystyrene platform for studying cell-nanoengineered surface interactions

    NASA Astrophysics Data System (ADS)

    Cha, Kyoung Je; Na, Moon-Hee; Kim, Hyung Woo; Kim, Dong Sung

    2014-05-01

    In this study, we fabricated and fully characterized a new type of polystyrene (PS) cell-culture platform containing nanoengineered surfaces (NES), referred to as a nano Petri dish, which can be used at the transition stage of basic cell-NES interaction studies for clinical applications. Nano-injection molding in this study was used for the mass production of the nano Petri dish having nanopore arrays. The effects of processing parameters of the injection molding on the replication quality of the nanopore arrays were quantitatively evaluated by means of design of experiments based on the Taguchi method. This allowed efficient and reliable cell culture studies by providing large numbers of the same dishes, in addition to removing the fixation step of the NES plates inside the cell-culture container. Physical, chemical and mechanical properties of the NES, as well as cell behavior including attachment and proliferation of human osteosarcoma MG-63 cells on the NES, were then characterized, with and without the oxygen plasma surface treatment.

  3. NEUROBEHAVIORAL EFFECTS OF EXPOSURE TO ENVIRONMENTAL POLLUTANTS IN CZECH CHILDREN

    EPA Science Inventory

    Ambient levels of SO2, NOx, PAHs and heavy metals are elevated in Northern Bohemia as a result of intensive mining and combustion of brown coal. To assess the neurotoxicological effects of exposure to these chemicals, tests from the Neurobehavioral Evaluation System (NES2) we...

  4. Growth curves of carcass traits obtained by ultrasonography in three lines of Nellore cattle selected for body weight.

    PubMed

    Coutinho, C C; Mercadante, M E Z; Jorge, A M; Paz, C C P; El Faro, L; Monteiro, F M

    2015-10-30

    The effect of selection for postweaning weight was evaluated within the growth curve parameters for both growth and carcass traits. Records of 2404 Nellore animals from three selection lines were analyzed: two selection lines for high postweaning weight, selection (NeS) and traditional (NeT); and a control line (NeC) in which animals were selected for postweaning weight close to the average. Body weight (BW), hip height (HH), rib eye area (REA), back fat thickness (BFT), and rump fat thickness (RFT) were measured and records collected from animals 8 to 20 (males) and 11 to 26 (females) months of age. The parameters A (asymptotic value) and k (growth rate) were estimated using the nonlinear model procedure of the Statistical Analysis System program, which included fixed effect of line (NeS, NeT, and NeC) in the model, with the objective to evaluate differences in the estimated parameters between lines. Selected animals (NeS and NeT) showed higher growth rates than control line animals (NeC) for all traits. Line effect on curves parameters was significant (P < 0.001) for BW, HH, and REA in males, and for BFT and RFT in females. Selection for postweaning weight was effective in altering growth curves, resulting in animals with higher growth potential.

  5. Utilization of nanoemulsions to enhance bioactivity of pharmaceuticals, supplements, and nutraceuticals: Nanoemulsion delivery systems and nanoemulsion excipient systems.

    PubMed

    Aboalnaja, Khaled Omer; Yaghmoor, Soonham; Kumosani, Taha Abdullah; McClements, David Julian

    2016-09-01

    The efficacy of many hydrophobic bioactives (pharmaceuticals, supplements, and nutraceuticals) is limited due to their relatively low or highly variable bioavailability. Nanoemulsions consisting of small lipid droplets (r < 100 nm) dispersed in water can be designed to improve bioavailability. The major factors limiting the oral bioavailability of hydrophobic bioactive agents are highlighted: bioaccessibility, absorption and transformation. Two nanoemulsion-based approaches to control these processes and improve bioavailability are discussed: nanoemulsion delivery systems (NDS) and nanoemulsion excipient systems (NES). In NDS, hydrophobic bioactives are dissolved within the lipid phase of oil-in-water nanoemulsions. In NES, the bioactives are present within a conventional drug, supplement, or food, which is consumed with an oil-in-water nanoemulsion. Examples of NDS and NES utilization to improve bioactive bioavailability are given. Considerable progress has been made in nanoemulsion design, fabrication, and testing. This knowledge facilitates the design of new formulations to improve the bioavailability of pharmaceuticals, supplements, and nutraceuticals. NDS and NES must be carefully designed based on the major factors limiting the bioavailability of specific bioactives. Research is still required to ensure these systems are commercially viable, and to demonstrate their safety and efficacy using animal and human feeding studies.

  6. [Stress and night eating syndrome: a comparison study between a sample of psychiatric outpatients and healthy subjects].

    PubMed

    Pacitti, Francesca; Maraone, Annalisa; Zazzara, Francesca; Biondi, Massimo; Caredda, Maria

    2011-01-01

    The Night Eating Syndrome (NES) is a disorder characterized by the clinical features of morning anorexia, evening hyperphagia, and insomnia with awakenings followed by nocturnal food ingestion. The core clinical feature appears to be a delay in the circadian timing of food intake. The diagnosis and early treatment of NES may represent an important means of prevention for obesity. Aims. The aim of the present study was to determine the vulnerability to develop NES between a clinical sample of patients with psychiatric disorders and a non clinical sample. We investigated a possible relation between stress and a dysfunctional eating behaviors as NES. Methods. The Night Eating Questionnaire (NEQ) has been administered to 147 psychiatric outpatients and to 531 subjects attending the University of L'Aquila. The NEQ is a questionnaire used to evaluate the prevalence of NES. The sample has been also evaluated through the Stress-related Vulnerability Scale (SVS) to measure both perceived stress and social support. Results. The 8.2% of patients scored above the diagnostic cut-off of the NEQ, compared to the 2.1% in the sample of healthy subjects. The majority of patients who had shown NEQ>25 had a diagnosis of major depressive disorder (MDD). The total scores on the NEQ were strongly associated with the SVS total score and especially with the "lack of social support" subscale. Conclusions. This study shows the increased vulnerability of NES in the sample of psychiatric patients compared to the sample of healthy subjects. The study further confirms the strong association between perceived stress, social support, altered eating behaviors and obesity.

  7. 77 FR 39543 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... the Authority of NASDAQ or NASDAQ Execution Services To Cancel Orders When a Technical or Systems...'') to cancel orders when a technical or systems issue occurs and to describe the operation of an error... causes NASDAQ or NES to cancel orders, if NASDAQ or NES determines that such action is necessary to...

  8. Progress in development of neutron energy spectrometer for deuterium plasma operation in KSTAR

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tomita, H., E-mail: tomita@nagoya-u.jp; Yamashita, F.; Nakayama, Y.

    2014-11-15

    Two types of DD neutron energy spectrometer (NES) are under development for deuterium plasma operation in KSTAR to understand behavior of beam ions in the plasma. One is based on the state-of-the-art nuclear emulsion technique. The other is based on a coincidence detection of a recoiled proton and a scattered neutron caused by an elastic scattering of an incident DD neutron, which is called an associated particle coincidence counting-NES. The prototype NES systems were installed at J-port in KSTAR in 2012. During the 2012 and 2013 experimental campaigns, multiple shots-integrated neutron spectra were preliminarily obtained by the nuclear emulsion-based NESmore » system.« less

  9. Acquisition of a Scanning Laser Vibrometer System for Experimental Studies on Nonparametric Nonlinear System Identification and Aeroelastic Instability Suppression

    DTIC Science & Technology

    2011-03-06

    based LCO suppression system housed in a winglet , specifically designed for the GTW. Upon completion of rehabilitation and modifications to the wing to...accommodate the winglet /NES, the full system will be ready for additional testing in the TDT. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF...University, will result in the design of an NES-based LCO suppression system housed in a winglet , specifically designed for the GTW. Upon completion of

  10. NLSdb-major update for database of nuclear localization signals and nuclear export signals.

    PubMed

    Bernhofer, Michael; Goldberg, Tatyana; Wolf, Silvana; Ahmed, Mohamed; Zaugg, Julian; Boden, Mikael; Rost, Burkhard

    2018-01-04

    NLSdb is a database collecting nuclear export signals (NES) and nuclear localization signals (NLS) along with experimentally annotated nuclear and non-nuclear proteins. NES and NLS are short sequence motifs related to protein transport out of and into the nucleus. The updated NLSdb now contains 2253 NLS and introduces 398 NES. The potential sets of novel NES and NLS have been generated by a simple 'in silico mutagenesis' protocol. We started with motifs annotated by experiments. In step 1, we increased specificity such that no known non-nuclear protein matched the refined motif. In step 2, we increased the sensitivity trying to match several different families with a motif. We then iterated over steps 1 and 2. The final set of 2253 NLS motifs matched 35% of 8421 experimentally verified nuclear proteins (up from 21% for the previous version) and none of 18 278 non-nuclear proteins. We updated the web interface providing multiple options to search protein sequences for NES and NLS motifs, and to evaluate your own signal sequences. NLSdb can be accessed via Rostlab services at: https://rostlab.org/services/nlsdb/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Experimental study of a hybrid electro-acoustic nonlinear membrane absorber

    NASA Astrophysics Data System (ADS)

    Bryk, P. Y.; Bellizzi, S.; Côte, R.

    2018-06-01

    A hybrid electro-acoustic nonlinear membrane absorber working as a nonlinear energy sink (here after named EA-NES) is described. The device is composed of a thin circular visco-elastic membrane working as an essentially cubic oscillator. One face of the membrane is coupled to the acoustic field to be reduced and the other face is enclosed. The enclosure includes a loudspeaker for the control of the acoustic pressure felt by the rear face of the membrane through proportional feedback control. An experimental set-up has been developed where the EA-NES is weakly coupled to a linear acoustic system. The linear acoustic system is an open-ended tube, coupled on one side to the EA-NES by a box, and on the other side to a source loudspeaker by another box. Only sinusoidal forcing is considered. It is shown that the EA-NES is able to perform resonance capture with the acoustic field, resulting in noise reduction by targeted energy transfer, and to operate in a large frequency band, tuning itself passively to any linear system. We demonstrate the ability of the feedback gain defining the active loop to modify the resonance frequency of the EA-NES, which is a key factor to tune the triggering threshold of energy pumping. The novelty of this work is to use active control combined to passive nonlinear transfer energy to improve it. In this paper, only experimental results are analyzed.

  12. Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence

    NASA Astrophysics Data System (ADS)

    Xue, Jingwei; Zhao, Zekai; Zhang, Lei; Xue, Lingjing; Shen, Shiyang; Wen, Yajing; Wei, Zhuoyuan; Wang, Lu; Kong, Lingyi; Sun, Hongbin; Ping, Qineng; Mo, Ran; Zhang, Can

    2017-07-01

    Cell-mediated drug-delivery systems have received considerable attention for their enhanced therapeutic specificity and efficacy in cancer treatment. Neutrophils (NEs), the most abundant type of immune cells, are known to penetrate inflamed brain tumours. Here we show that NEs carrying liposomes that contain paclitaxel (PTX) can penetrate the brain and suppress the recurrence of glioma in mice whose tumour has been resected surgically. Inflammatory factors released after tumour resection guide the movement of the NEs into the inflamed brain. The highly concentrated inflammatory signals in the brain trigger the release of liposomal PTX from the NEs, which allows delivery of PTX into the remaining invading tumour cells. We show that this NE-mediated delivery of drugs efficiently slows the recurrent growth of tumours, with significantly improved survival rates, but does not completely inhibit the regrowth of tumours.

  13. Factors Influencing New Entrant Dairy Farmer's Decision-Making Process around Technology Adoption

    ERIC Educational Resources Information Center

    McDonald, Roberta; Heanue, Kevin; Pierce, Karina; Horan, Brendan

    2016-01-01

    Purpose: The aims of this paper are to (1) evaluate the main factors influencing grazing system technology adoption among new entrant (NE) dairy farmers within Europe and the Irish pasture-based dairy industry, and (2) to determine the extent to which economic factors influence decision-making around technology adoption and use among NEs to the…

  14. Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia.

    PubMed

    Onorati, Marco; Li, Zhen; Liu, Fuchen; Sousa, André M M; Nakagawa, Naoki; Li, Mingfeng; Dell'Anno, Maria Teresa; Gulden, Forrest O; Pochareddy, Sirisha; Tebbenkamp, Andrew T N; Han, Wenqi; Pletikos, Mihovil; Gao, Tianliuyun; Zhu, Ying; Bichsel, Candace; Varela, Luis; Szigeti-Buck, Klara; Lisgo, Steven; Zhang, Yalan; Testen, Anze; Gao, Xiao-Bing; Mlakar, Jernej; Popovic, Mara; Flamand, Marie; Strittmatter, Stephen M; Kaczmarek, Leonard K; Anton, E S; Horvath, Tamas L; Lindenbach, Brett D; Sestan, Nenad

    2016-09-06

    The mechanisms underlying Zika virus (ZIKV)-related microcephaly and other neurodevelopment defects remain poorly understood. Here, we describe the derivation and characterization, including single-cell RNA-seq, of neocortical and spinal cord neuroepithelial stem (NES) cells to model early human neurodevelopment and ZIKV-related neuropathogenesis. By analyzing human NES cells, organotypic fetal brain slices, and a ZIKV-infected micrencephalic brain, we show that ZIKV infects both neocortical and spinal NES cells as well as their fetal homolog, radial glial cells (RGCs), causing disrupted mitoses, supernumerary centrosomes, structural disorganization, and cell death. ZIKV infection of NES cells and RGCs causes centrosomal depletion and mitochondrial sequestration of phospho-TBK1 during mitosis. We also found that nucleoside analogs inhibit ZIKV replication in NES cells, protecting them from ZIKV-induced pTBK1 relocalization and cell death. We established a model system of human neural stem cells to reveal cellular and molecular mechanisms underlying neurodevelopmental defects associated with ZIKV infection and its potential treatment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Childhood family dysfunction and associated abuse in patients with nonepileptic seizures: towards a causal model.

    PubMed

    Salmon, Peter; Al-Marzooqi, Suad M; Baker, Gus; Reilly, James

    2003-01-01

    A history of childhood sexual abuse is thought to characterize patients with nonepileptic seizures (NES). We tested the hypotheses: 1) that history of sexual abuse is more prevalent in patients with NES than in controls with epilepsy; 2) that such abuse is associated with NES, not directly but because it is a marker of family dysfunction; and 3) that family dysfunction and abuse are, in turn, linked to NES because they increase a general tendency to somatize. We compared 81 patients with NES with 81 case-matched epilepsy patients, using questionnaires to elicit recollections of sexual, physical, and psychological abuse and family atmosphere and to quantify current somatization. Although each form of abuse was more prevalent in NES patients, only child psychological abuse uniquely distinguished NES from epilepsy. However, its association with NES was explained by family dysfunction. A general tendency to somatize explained part of the relationship of abuse to NES. Abuse therefore seems to be a marker for aspects of family dysfunction that are associated with--and may therefore cause--somatization and, specifically, NES.

  16. Hospital CEOs, CFOs, and nurse executives: opportunities for a new alliance.

    PubMed

    Dwore, R B; Murray, B P; Fosbinder, D; Parsons, R P; Smith, P; Dalley, K; Vorderer, L; Gustafson, G

    1998-01-01

    This article examines the involvement of Utah acute care hospital nurse executives (NEs) in financial management roles. The authors surveyed NEs and their career supporters and hinderers. Findings suggest that NFs: 1. lack financial management skills, support, involvement, and satisfaction; 2. recognize financial management's importance and desire to improve performance; and 3. consider chief executive officers (CEOs) as their major supporters and chief financial officers (CFOs) their major hinderers in financial management. These "supporters" and "hinderers" of NEs showed consensus regarding the primacy of NEs' leadership and patient advocacy roles. These findings contrast with major professional association policy directives and expert opinions that advocate expanded financial management roles for NEs that will enable them to fully realize their executive potential. CEOs are positioned to establish norms that balance the traditional leadership-patient advocacy roles of NEs with newer financial management roles. CEOs can offer NEs and CFOs opportunities to improve NEs' financial management participation and performance. CEOs can provide empowerment and encourage CFOs to offer NEs "power tools" (for example, information, expertise, resources, and support). The three groups, however, must negotiate reasonable expectations for NEs in financial management and adequate preparation for these consequent responsibilities. Together, CEOs, CFOs, and NEs can successfully take hospitals into the future by leading them in ongoing learning and change.

  17. Biocompatible nanoemulsions based on hemp oil and less surfactants for oral delivery of baicalein with enhanced bioavailability

    PubMed Central

    Yin, Juntao; Xiang, Cuiyu; Wang, Peiqing; Yin, Yuyun; Hou, Yantao

    2017-01-01

    Baicalein (BCL) possesses high pharmacological activities but low solubility and stability in the intestinal tract. This study aimed to probe the potential of nanoemulsions (NEs) consisting of hemp oil and less surfactants in ameliorating the oral bioavailability of BCL. BCL-loaded NEs (BCL-NEs) were prepared by high-pressure homogenization technique to reduce the amount of surfactants. BCL-NEs were characterized by particle size, entrapment efficiency (EE), in vitro drug release, and morphology. Bioavailability was studied in Sprague-Dawley rats following oral administration of BCL suspensions, BCL conventional emulsions, and BCL-NEs. The obtained NEs were ~90 nm in particle size with an EE of 99.31%. BCL-NEs significantly enhanced the oral bioavailability of BCL, up to 524.7% and 242.1% relative to the suspensions and conventional emulsions, respectively. BCL-NEs exhibited excellent intestinal permeability and transcellular transport ability. The cytotoxicity of BCL-NEs was documented to be low and acceptable for oral purpose. Our findings suggest that such novel NEs and preparative process provide a promising alternative to current formulation technologies and suitable for oral delivery of drugs with bioavailability issues. PMID:28435268

  18. Biocompatible nanoemulsions based on hemp oil and less surfactants for oral delivery of baicalein with enhanced bioavailability.

    PubMed

    Yin, Juntao; Xiang, Cuiyu; Wang, Peiqing; Yin, Yuyun; Hou, Yantao

    2017-01-01

    Baicalein (BCL) possesses high pharmacological activities but low solubility and stability in the intestinal tract. This study aimed to probe the potential of nanoemulsions (NEs) consisting of hemp oil and less surfactants in ameliorating the oral bioavailability of BCL. BCL-loaded NEs (BCL-NEs) were prepared by high-pressure homogenization technique to reduce the amount of surfactants. BCL-NEs were characterized by particle size, entrapment efficiency (EE), in vitro drug release, and morphology. Bioavailability was studied in Sprague-Dawley rats following oral administration of BCL suspensions, BCL conventional emulsions, and BCL-NEs. The obtained NEs were ~90 nm in particle size with an EE of 99.31%. BCL-NEs significantly enhanced the oral bioavailability of BCL, up to 524.7% and 242.1% relative to the suspensions and conventional emulsions, respectively. BCL-NEs exhibited excellent intestinal permeability and transcellular transport ability. The cytotoxicity of BCL-NEs was documented to be low and acceptable for oral purpose. Our findings suggest that such novel NEs and preparative process provide a promising alternative to current formulation technologies and suitable for oral delivery of drugs with bioavailability issues.

  19. Night eating syndrome: implications for severe obesity

    PubMed Central

    Cleator, J; Abbott, J; Judd, P; Sutton, C; Wilding, J P H

    2012-01-01

    Night eating syndrome (NES) was first identified in 1955 by Stunkard, a psychiatrist specialising in eating disorders (ED). Over the last 20 years considerable progress has been made in defining NES as a significant clinical entity in its own right and it has now been accepted for inclusion in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) due for publication in 2013. NES is considered a dysfunction of circadian rhythm with a disassociation between eating and sleeping. Core criteria include a daily pattern of eating with a significantly increased intake in the evening and/or night time, as manifested by one or both of the following: at least 25% of food intake is consumed after the evening meal or at least two episodes of nocturnal eating per week. An important recent addition to core criteria includes the presence of significant distress and/or impairment in functioning. Stunkard's team recommend further investigation on the pathogenesis of NES, in particular its relationship with traumatic life events, psychiatric comorbidity, the age of onset of NES and course of NES over time. The relationship between NES and other ED also requires further clarification as night-eaters exhibit some features of other ED; previous guidance to separate NES from other ED may have hindered earlier characterisation of NES. Evidence from European and American studies suggests NES features strongly in populations with severe obesity. The complex interplay between depression, impaired sleep and obesity-related comorbidity in severely obese individuals makes understanding NES in this context even more difficult. This review examines evidence to date on the characterisation of NES and concludes by examining the applicability of current NES criteria to individuals with severe obesity. PMID:23446659

  20. A System for Identifying Named Entities in Biomedical Text: how Results From two Evaluations Reflect on Both the System and the Evaluations

    PubMed Central

    Dingare, Shipra; Nissim, Malvina; Finkel, Jenny; Grover, Claire

    2005-01-01

    We present a maximum entropy-based system for identifying named entities (NEs) in biomedical abstracts and present its performance in the only two biomedical named entity recognition (NER) comparative evaluations that have been held to date, namely BioCreative and Coling BioNLP. Our system obtained an exact match F-score of 83.2% in the BioCreative evaluation and 70.1% in the BioNLP evaluation. We discuss our system in detail, including its rich use of local features, attention to correct boundary identification, innovative use of external knowledge resources, including parsing and web searches, and rapid adaptation to new NE sets. We also discuss in depth problems with data annotation in the evaluations which caused the final performance to be lower than optimal. PMID:18629295

  1. Conservation Priorities in a Biodiversity Hotspot: Analysis of Narrow Endemic Plant Species in New Caledonia

    PubMed Central

    Wulff, Adrien S.; Hollingsworth, Peter M.; Ahrends, Antje; Jaffré, Tanguy; Veillon, Jean-Marie; L’Huillier, Laurent; Fogliani, Bruno

    2013-01-01

    New Caledonia is a global biodiversity hotspot facing extreme environmental degradation. Given the urgent need for conservation prioritisation, we have made a first-pass quantitative assessment of the distribution of Narrow Endemic Species (NES) in the flora to identify species and sites that are potentially important for conservation action. We assessed the distributional status of all angiosperm and gymnosperm species using data from taxonomic descriptions and herbarium samples. We characterised species as being NES if they occurred in 3 or fewer locations. In total, 635 of the 2930 assessed species were classed as NES, of which only 150 have been subjected to the IUCN conservation assessment. As the distributional patterns of un-assessed species from one or two locations correspond well with assessed species which have been classified as Critically Endangered or Endangered respectively, we suggest that our distributional data can be used to prioritise species for IUCN assessment. We also used the distributional data to produce a map of “Hotspots of Plant Narrow Endemism” (HPNE). Combined, we used these data to evaluate the coincidence of NES with mining activities (a major source of threat on New Caledonia) and also areas of conservation protection. This is to identify species and locations in most urgent need of further conservation assessment and subsequent action. Finally, we grouped the NES based on the environments they occurred in and modelled the habitat distribution of these groups with a Maximum Entropy Species Distribution Model (MaxEnt). The NES were separable into three different groups based primarily on geological differences. The distribution of the habitat types for each group coincide partially with the HPNE described above and also indicates some areas which have high habitat suitability but few recorded NES. Some of these areas may represent under-sampled hotspots of narrow endemism and are priorities for further field work. PMID:24058470

  2. [Dental caries distribution in preschool children in an urban area of Argentina, 1992].

    PubMed

    Yankilevich, E R; Cattoni, S T; Cornejo, L S; Battellino, L J

    1993-12-01

    An investigation undertaken into a sample of 1,115 five-year old children attending kindergartens in the city of Córdoba (Argentina) is described. The investigation aimed at establishing the prevalence and distribution of dental caries by socioeconomic level. Research showed that the prevalence of caries had decreased 55.0% in relation to the 1973 figure, while the proportion of children with healthy teeth was 26.7% greater. The frequency and seriousness of the caries increased as the child's social position declined. At the highest socioeconomic level NES I = entrepreneurial and managerial bourgeoisie), the rates of caries were significantly lower than those at the lowest socioeconomic level (NES III = typical proletariat, nontypical proletariat and sub-proletariat) presenting dmf-t of 0.8 and 2.7, and dmf-s of 0.9 and 4.9, respectively. In NES III, the dmf-t main components were decayed and missing teeth, while in NES I filled teeth were the main components. The proportion of children with no experience of caries was 63.1% in NES I and 11.5% in NES III. Inversly, the rate dental health was higher in NES I (8.8) than in NES III (5.1). The cost per child required for the restorative treatment in approximately two and a half times greater in NES III than in NES I. Considering the sample as a whole the expenditure required for NES III would be more than ten times higher than that required for NES I.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Comparative analysis of seven viral nuclear export signals (NESs) reveals the crucial role of nuclear export mediated by the third NES consensus sequence of nucleoprotein (NP) in influenza A virus replication.

    PubMed

    Chutiwitoonchai, Nopporn; Kakisaka, Michinori; Yamada, Kazunori; Aida, Yoko

    2014-01-01

    The assembly of influenza virus progeny virions requires machinery that exports viral genomic ribonucleoproteins from the cell nucleus. Currently, seven nuclear export signal (NES) consensus sequences have been identified in different viral proteins, including NS1, NS2, M1, and NP. The present study examined the roles of viral NES consensus sequences and their significance in terms of viral replication and nuclear export. Mutation of the NP-NES3 consensus sequence resulted in a failure to rescue viruses using a reverse genetics approach, whereas mutation of the NS2-NES1 and NS2-NES2 sequences led to a strong reduction in viral replication kinetics compared with the wild-type sequence. While the viral replication kinetics for other NES mutant viruses were also lower than those of the wild-type, the difference was not so marked. Immunofluorescence analysis after transient expression of NP-NES3, NS2-NES1, or NS2-NES2 proteins in host cells showed that they accumulated in the cell nucleus. These results suggest that the NP-NES3 consensus sequence is mostly required for viral replication. Therefore, each of the hydrophobic (Φ) residues within this NES consensus sequence (Φ1, Φ2, Φ3, or Φ4) was mutated, and its viral replication and nuclear export function were analyzed. No viruses harboring NP-NES3 Φ2 or Φ3 mutants could be rescued. Consistent with this, the NP-NES3 Φ2 and Φ3 mutants showed reduced binding affinity with CRM1 in a pull-down assay, and both accumulated in the cell nucleus. Indeed, a nuclear export assay revealed that these mutant proteins showed lower nuclear export activity than the wild-type protein. Moreover, the Φ2 and Φ3 residues (along with other Φ residues) within the NP-NES3 consensus were highly conserved among different influenza A viruses, including human, avian, and swine. Taken together, these results suggest that the Φ2 and Φ3 residues within the NP-NES3 protein are important for its nuclear export function during viral replication.

  4. Applying Suffix Rules to Organization Name Recognition

    NASA Astrophysics Data System (ADS)

    Inui, Takashi; Murakami, Koji; Hashimoto, Taiichi; Utsumi, Kazuo; Ishikawa, Masamichi

    This paper presents a method for boosting the performance of the organization name recognition, which is a part of named entity recognition (NER). Although gazetteers (lists of the NEs) have been known as one of the effective features for supervised machine learning approaches on the NER task, the previous methods which have applied the gazetteers to the NER were very simple. The gazetteers have been used just for searching the exact matches between input text and NEs included in them. The proposed method generates regular expression rules from gazetteers, and, with these rules, it can realize a high-coverage searches based on looser matches between input text and NEs. To generate these rules, we focus on the two well-known characteristics of NE expressions; 1) most of NE expressions can be divided into two parts, class-reference part and instance-reference part, 2) for most of NE expressions the class-reference parts are located at the suffix position of them. A pattern mining algorithm runs on the set of NEs in the gazetteers, and some frequent word sequences from which NEs are constructed are found. Then, we employ only word sequences which have the class-reference part at the suffix position as suffix rules. Experimental results showed that our proposed method improved the performance of the organization name recognition, and achieved the 84.58 F-value for evaluation data.

  5. A nonlinear energy sink with an energy harvester: Harmonically forced responses

    NASA Astrophysics Data System (ADS)

    Kremer, Daniel; Liu, Kefu

    2017-12-01

    This study intends to achieve simultaneous vibration suppression and energy harvesting using a variant form of nonlinear energy sink (NES). The proposed apparatus is not a true NES as its spring is not essentially nonlinear. In a previous study [22] (Journal of Sound and Vibration, 333 (20) (2014)), it has been shown that the apparatus demonstrates the transient behaviors similar to those of the NES. As a sequel, the present paper focuses on harmonically forced responses of the system. First, the approximate solutions of steady state responses are derived. Using the approximate solutions, the steady state behaviors are investigated by using the numerical continuation method. This is followed by an experimental study. The study has shown that under harmonic excitation, the proposed apparatus functions similarly to the NES with the typical behaviors such as strongly modulated responses, amplitude jumping, excitation level dependence, etc. Overall, the apparatus meets the design objectives: the vibration suppression and energy harvesting in a broadband manner.

  6. Inhibition of mRNA export in vertebrate cells by nuclear export signal conjugates

    PubMed Central

    Pasquinelli, Amy E.; Powers, Maureen A.; Lund, Elsebet; Forbes, Douglass; Dahlberg, James E.

    1997-01-01

    Leucine-rich nuclear export signals (NESs) are recognized by the NES receptor exportin 1 and are central to the export of multiple shuttling proteins and RNAs. The export of messenger RNA in vertebrates was, however, thought to occur by a different pathway, because inhibition by injection of a synthetic Rev NES conjugate could not be demonstrated. Here we find that peptide conjugates composed of the NES of either protein kinase A inhibitor protein (PKI) or the HIV-1 Rev protein, when coupled to human serum albumin, are potent inhibitors of mRNA and small nuclear RNA export. These results provide direct evidence that mRNA export in vertebrates depends on interactions between an NES and its cognate NES receptors. PKI NES conjugates are significantly more efficient at inhibiting RNA export than are REV NES conjugates, indicating that different NESs may have different abilities to promote protein and RNA export. Surprisingly, an expected control conjugate containing the mutant Rev NES sequence M10 strongly inhibited the export of intronless dihydrofolate reductase mRNA. Nuclear injection of NES peptide conjugates led to mislocalization to the nucleus of 10–20% of the cytoplasmic Ran GTPase-binding protein (RanBP1) indicating that RanBP1 shuttles between the nucleus and the cytoplasm via an NES pathway. These results demonstrate that in vertebrates the export of mRNA, like that of small nuclear RNA, 5S rRNA, and transport factors such as RanBP1, employs NES-mediated molecular machinery. PMID:9405623

  7. Prevalence and Clinical Significance of Night Eating Syndrome in University Students

    PubMed Central

    Runfola, Cristin D.; Allison, Kelly C.; Hardy, Kristina K.; Lock, James; Peebles, Rebecka

    2014-01-01

    Purpose Most studies of night eating syndrome (NES) fail to control for binge eating, despite moderate overlap between the two conditions. Establishing the independent clinical significance of NES is imperative for it to be considered worthy of clinical attention. We compared students with and without NES on eating disorder symptomatology, quality of life, and mental health, while exploring the role of binge eating in associations. Methods Students (N=1636) ages 18 to 26 (M=20.9) recruited from ten U.S. universities completed an online survey including the Night Eating Questionnaire (NEQ), Eating Disorder Examination-Questionnaire (EDE-Q), Project Eating Among Teens, and the Health-Related Quality of Life-4. NES was diagnosed according to endorsement of proposed diagnostic criteria on the NEQ. Groups (NES vs. non-NES) were compared on all dependent variables and stratified by binge eating status in secondary analyses. Results The prevalence of NES in our sample was 4.2%; it was 2.9% after excluding those with binge eating. Body mass index did not differ between groups, but students with NES were significantly more likely to have histories of underweight and anorexia nervosa. In students with NES, EDE-Q scores were significantly higher; purging, laxative use, and compulsive exercise were more frequent; quality of life was reduced; and histories of depression, attention-deficit/hyperactivity disorder, and self-injury were more common. Binge eating did not account for all of these differences; the presence of it and NES was associated with additive risk for psychopathology on some items. Conclusions NES may be a distinct clinical entity from other DSM-5 eating disorders. PMID:24485551

  8. Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics

    PubMed Central

    Gavin, Amy; Pham, Jimmy TH; Wang, Dawei; Brownlow, Bill; Elbayoumi, Tamer A

    2015-01-01

    Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety–enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (−28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions. PMID:25759580

  9. Neurologic soft signs in schizophrenic patients treated with conventional and atypical antipsychotics.

    PubMed

    Bersani, Giuseppe; Gherardelli, Simona; Clemente, Roberta; Di Giannantonio, Massimo; Grilli, Alfredo; Conti, Chiara M V; Exton, Michael S; Conti, Pio; Doyle, Robert; Pancheri, Paolo

    2005-08-01

    Neurologic soft signs (NSS) are considered a somatic feature associated with schizophrenia (DSM-IV) that are present in neuroleptic-treated, as well as untreated or first-episode patients. The aim of this study was to determine the incidence and severity of NSS in groups of schizophrenic patients treated with either a conventional neuroleptic medication, haloperidol (n = 37), or atypical antipsychotic medications, risperidone (n = 19), clozapine (n = 34), and olanzapine (n = 18). NSS were assessed with the Neurological Evaluation Scale (NES), whereas extrapyramidal symptoms (EPS), which occur more commonly with conventional neuroleptic treatment, were evaluated using the Simpson-Angus Scale. NES scores were not significantly different between groups. Slight differences were found for 2 items only. The haloperidol group showed higher scores for the "Romberg test," whereas the clozapine group showed higher scores for "short-term memory." There were significant correlations between EPS and NES total score in the haloperidol and risperidone groups. These results demonstrate an overall overlapping of NSS among the groups, confirming their substantial independence from neurologic implications of neuroleptic treatment.

  10. Formulation of vitamin D encapsulated cinnamon oil nanoemulsion: Its potential anti-cancerous activity in human alveolar carcinoma cells.

    PubMed

    Meghani, Nikita; Patel, Pal; Kansara, Krupa; Ranjan, Shivendu; Dasgupta, Nandita; Ramalingam, Chidambaram; Kumar, Ashutosh

    2018-06-01

    Cinnamon oil is used for medicinal purpose since ancient time because of its antioxidant activity. Oil-in-water nanoemulsion (NE) of cinnamon oil was formulated using cinnamon oil, nonionic surfactant Tween 80 and water by ultrasonication technique. Phase diagram was constructed to investigate the influence of oil, water and surfactant concentration. Vitamin D encapsulated cinnamon oil NE was fabricated by wash out method followed by ultrasonication in similar fashion. The hydrodynamic size of cinnamon oil NE and vitamin D encapsulated cinnamon oil NE was observed as 40.52 and 48.96 nm in complete DMEM F12 media respectively. We focused on the cytotoxic and genotoxic responses of NEs in A549 cells in concentration dependent manner. We observed that both NEs induce DNA damage along with corresponding increase in micronucleus frequency that is evident from the comet and CBMN assay. Both the NEs arrested the cell cycle progression in G0/G1 phase, showed increased expression of Bax, capase-3 and caspase-9 and decrease expression of BcL2 proteins along with significant (p < 0.05) increase in apoptotic cell population and loss of mitochondrial membrane potential. NEs were also evaluated for bactericidal efficacy against E. coli. Thus, both NEs have cytotoxic, genotoxic and antibacterial potential and hence can also be used in food industry with cinnamon oil as carrier for lipophilic nutraceutical like vitamin D. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. [What the patient's history tells us about their nonepileptic seizures].

    PubMed

    Reuber, M; Micoulaud-Franchi, J-A; Gülich, E; Bartolomei, F; McGonigal, A

    2014-10-01

    The aetiology of "psychogenic" non-epileptic seizures (NES) remains poorly understood and the differentiation of NES from epilepsy can be a difficult. In the first part of this review article we focus on recent insights into the neurobiological underpinnings of NES. We summarise a number of studies demonstrating the importance of abnormalities of emotion regulation in patients with NES. Evidence for abnormal emotion regulation comes from both self-report and experimental studies of pre-conscious cognitive processes. These studies show that NES are not the only manifestation of abnormal mental processing in these patients and that excessive social threat avoidance and emotional dysregulation are also evident between seizures and may therefore contribute to disability beyond the seizures themselves. In the second part of this review, we describe the findings of a number of studies, which have examined differences between the communication behaviour of patients with NES and those with epilepsy. We argue, that, whilst these studies initially aimed to help clinicians with the differential diagnosis of NES and epilepsy, close sociolinguistic analysis of patient's talk can also provide clues about the aetiology of NES. We conclude that the interaction of patient with NES with the doctor can be interpreted as a manifestation of avoidance and a demonstration of helplessness perhaps intended to secure active support from the doctor. In the third part of this review, we suggest that a close reading of a transcript of the interaction between a patient with NES and her doctor (and perhaps attentive listening to how patients' talk about themselves and their disorder) can yield clues to the causes of NES in individual cases. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  12. Evaluation of Neutron Elastic Scatter (NES) technique for detection of graphitic corrosion in gas cast iron pipe. Final report, March 1996-April 1997

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Charatis, G.; Hugg, E.; McEllistrem, M.

    1997-04-01

    PENETRON, Inc., in two phases, demonstrated the effectiveness of its Neutron elastic Scatter (NES) techniques in detecting the change in the carbon weight percentage (CWt%) as a measure of corrosion in gray cast iron pipe. In Phase I, experiments were performed with synthetic standards supplied by IIT Research Institute (IITRI) to test the applicability of the NES techniques. Irradiation experiments performed at the University of Kentucky showed that CWt% could be detected, ranging from 1.6% to 13%, within an uncertainty of around 4%. In Phase II, experiments were performed on seven (7) corroded pipe sections supplied by MichCon. Tests weremore » made on pipe sliced lengthwise into quarter sections, and in re-assembled whole pipe sections. X-ray films of the quarter sections indicated probable areas of corrosion for each quarter section.« less

  13. NASA's explorer school and spaceward bound programs: Insights into two education programs designed to heighten public support for space science initiatives

    USGS Publications Warehouse

    Allner, Matthew; McKay, Christopher P; Coe, Liza; Rask, Jon; Paradise, Jim; Wynne, J. Judson

    2010-01-01

    IntroductionNASA has played an influential role in bringing the enthusiasm of space science to schools across the United States since the 1980s. The evolution of this public outreach has led to a variety of NASA funded education programs designed to promote student interest in science, technology, engineering, math, and geography (STEM-G) careers.PurposeThis paper investigates the educational outreach initiatives, structure, and impact of two of NASA's largest educational programs: the NASA Explorer School (NES) and NASA Spaceward Bound programs.ResultsSince its induction in 2003 the NES program has networked and provided resources to over 300 schools across the United States. Future directions include further development of mentor schools for each new NES school selected, while also developing a longitudinal student tracking system for NES students to monitor their future involvement in STEM-G careers. The Spaceward Bound program, now in its third year of teacher outreach, is looking to further expand its teacher network and scientific collaboration efforts, while building on its teacher mentorship framework.

  14. CHD3 facilitates vRNP nuclear export by interacting with NES1 of influenza A virus NS2.

    PubMed

    Hu, Yong; Liu, Xiaokun; Zhang, Anding; Zhou, Hongbo; Liu, Ziduo; Chen, Huanchun; Jin, Meilin

    2015-03-01

    NS2 from influenza A virus mediates Crm1-dependent vRNP nuclear export through interaction with Crm1. However, even though the nuclear export signal 1 (NES1) of NS2 does not play a requisite role in NS2-Crm1 interaction, there is no doubt that NES1 is crucial for vRNP nuclear export. While the mechanism of the NES1 is still unclear, it is speculated that certain host partners might mediate the NES1 function through their interaction with NES1. In the present study, chromodomain-helicase-DNA-binding protein 3 (CHD3) was identified as a novel host nuclear protein for locating NS2 and Crm1 on dense chromatin for NS2 and Crm1-dependent vRNP nuclear export. CHD3 was confirmed to interact with NES1 in NS2, and a disruption to this interaction by mutation in NES1 significantly delayed viral vRNPs export and viral propagation. Further, the knockdown of CHD3 would affect the propagation of the wild-type virus but not the mutant with the weakened NS2-CHD3 interaction. Therefore, this study demonstrates that NES1 is required for maximal binding of NS2 to CHD3, and that the NS2-CHD3 interaction on the dense chromatin contributed to the NS2-mediated vRNP nuclear export.

  15. Optimization under uncertainty of parallel nonlinear energy sinks

    NASA Astrophysics Data System (ADS)

    Boroson, Ethan; Missoum, Samy; Mattei, Pierre-Olivier; Vergez, Christophe

    2017-04-01

    Nonlinear Energy Sinks (NESs) are a promising technique for passively reducing the amplitude of vibrations. Through nonlinear stiffness properties, a NES is able to passively and irreversibly absorb energy. Unlike the traditional Tuned Mass Damper (TMD), NESs do not require a specific tuning and absorb energy over a wider range of frequencies. Nevertheless, they are still only efficient over a limited range of excitations. In order to mitigate this limitation and maximize the efficiency range, this work investigates the optimization of multiple NESs configured in parallel. It is well known that the efficiency of a NES is extremely sensitive to small perturbations in loading conditions or design parameters. In fact, the efficiency of a NES has been shown to be nearly discontinuous in the neighborhood of its activation threshold. For this reason, uncertainties must be taken into account in the design optimization of NESs. In addition, the discontinuities require a specific treatment during the optimization process. In this work, the objective of the optimization is to maximize the expected value of the efficiency of NESs in parallel. The optimization algorithm is able to tackle design variables with uncertainty (e.g., nonlinear stiffness coefficients) as well as aleatory variables such as the initial velocity of the main system. The optimal design of several parallel NES configurations for maximum mean efficiency is investigated. Specifically, NES nonlinear stiffness properties, considered random design variables, are optimized for cases with 1, 2, 3, 4, 5, and 10 NESs in parallel. The distributions of efficiency for the optimal parallel configurations are compared to distributions of efficiencies of non-optimized NESs. It is observed that the optimization enables a sharp increase in the mean value of efficiency while reducing the corresponding variance, thus leading to more robust NES designs.

  16. Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity.

    PubMed

    Chen, Chieh V; Brummet, Jennifer L; Jordan, Cynthia L; Breedlove, S Marc

    2016-02-01

    We previously found that androgen receptor (AR) activity mediates two effects of T in adult male mice: reduction of anxiety-like behaviors and dampening of the hypothalamic-pituitary-adrenal response to stress. To determine whether brain ARs mediate these effects, we used the Cre/loxP technology seeking to disable AR throughout the central nervous system (CNS). Female mice carrying the floxed AR allele (ARlox) were crossed with males carrying cre recombinase transgene controlled by the nestin promoter (NesCre), producing cre in developing neurons and glia. Among male offspring, four genotypes resulted: males carrying ARlox and NesCre (NesARko), and three control groups (wild types, NesCre, and ARlox). Reporter mice indicated ubiquitous Cre expression throughout the CNS. Nevertheless, AR immunocytochemistry in NesARko mice revealed efficient knockout (KO) of AR in some brain regions (hippocampus and medial prefrontal cortex [mPFC]), but not others. Substantial AR protein was seen in the amygdala and hypothalamus among other regions, whereas negligible AR remained in others like the bed nucleus of the stria terminalis and dorsal periaqueductal gray. This selective KO allowed for testing the role of AR in hippocampus and mPFC. Males were castrated and implanted with T at postnatal day 60 before testing on postnatal day 90-100. In contrast with males with global KO of AR, T still modulated anxiety-related behavior and hypothalamic-pituitary-adrenal activity in NesARko males. These results leave open the possibility that AR acting in the CNS mediates these effects of T, but demonstrate that AR is not required in the hippocampus or mPFC for T's anxiolytic effects.

  17. Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity

    PubMed Central

    Brummet, Jennifer L.; Jordan, Cynthia L.; Breedlove, S. Marc

    2016-01-01

    We previously found that androgen receptor (AR) activity mediates two effects of T in adult male mice: reduction of anxiety-like behaviors and dampening of the hypothalamic-pituitary-adrenal response to stress. To determine whether brain ARs mediate these effects, we used the Cre/loxP technology seeking to disable AR throughout the central nervous system (CNS). Female mice carrying the floxed AR allele (ARlox) were crossed with males carrying cre recombinase transgene controlled by the nestin promoter (NesCre), producing cre in developing neurons and glia. Among male offspring, four genotypes resulted: males carrying ARlox and NesCre (NesARko), and three control groups (wild types, NesCre, and ARlox). Reporter mice indicated ubiquitous Cre expression throughout the CNS. Nevertheless, AR immunocytochemistry in NesARko mice revealed efficient knockout (KO) of AR in some brain regions (hippocampus and medial prefrontal cortex [mPFC]), but not others. Substantial AR protein was seen in the amygdala and hypothalamus among other regions, whereas negligible AR remained in others like the bed nucleus of the stria terminalis and dorsal periaqueductal gray. This selective KO allowed for testing the role of AR in hippocampus and mPFC. Males were castrated and implanted with T at postnatal day 60 before testing on postnatal day 90–100. In contrast with males with global KO of AR, T still modulated anxiety-related behavior and hypothalamic-pituitary-adrenal activity in NesARko males. These results leave open the possibility that AR acting in the CNS mediates these effects of T, but demonstrate that AR is not required in the hippocampus or mPFC for T's anxiolytic effects. PMID:26562258

  18. Nonepileptic seizures under levetiracetam therapy: a case report of forced normalization process.

    PubMed

    Anzellotti, Francesca; Franciotti, Raffaella; Zhuzhuni, Holta; D'Amico, Aurelio; Thomas, Astrid; Onofrj, Marco

    2014-01-01

    Nonepileptic seizures (NES) apparently look like epileptic seizures, but are not associated with ictal electrical discharges in the brain. NES constitute one of the most important differential diagnoses of epilepsy. They have been recognized as a distinctive clinical phenomenon for centuries, and video/electroencephalogram monitoring has allowed clinicians to make near-certain diagnoses. NES are supposedly unrelated to organic brain lesions, and despite the preponderance of a psychiatric/psychological context, they may have an iatrogenic origin. We report a patient with NES precipitated by levetiracetam therapy; in this case, NES was observed during the disappearance of epileptiform discharges from the routine video/electroencephalogram. We discuss the possible mechanisms underlying NES with regard to alternative psychoses associated with the phenomenon of the forced normalization process.

  19. Nonepileptic seizures under levetiracetam therapy: a case report of forced normalization process

    PubMed Central

    Anzellotti, Francesca; Franciotti, Raffaella; Zhuzhuni, Holta; D’Amico, Aurelio; Thomas, Astrid; Onofrj, Marco

    2014-01-01

    Nonepileptic seizures (NES) apparently look like epileptic seizures, but are not associated with ictal electrical discharges in the brain. NES constitute one of the most important differential diagnoses of epilepsy. They have been recognized as a distinctive clinical phenomenon for centuries, and video/electroencephalogram monitoring has allowed clinicians to make near-certain diagnoses. NES are supposedly unrelated to organic brain lesions, and despite the preponderance of a psychiatric/psychological context, they may have an iatrogenic origin. We report a patient with NES precipitated by levetiracetam therapy; in this case, NES was observed during the disappearance of epileptiform discharges from the routine video/electroencephalogram. We discuss the possible mechanisms underlying NES with regard to alternative psychoses associated with the phenomenon of the forced normalization process. PMID:24926197

  20. Featured Article: Nuclear export of opioid growth factor receptor is CRM1 dependent.

    PubMed

    Kren, Nancy P; Zagon, Ian S; McLaughlin, Patricia J

    2016-02-01

    Opioid growth factor receptor (OGFr) facilitates growth inhibition in the presence of its specific ligand opioid growth factor (OGF), chemically termed [Met(5)]-enkephalin. The function of the OGF-OGFr axis requires the receptor to translocate to the nucleus. However, the mechanism of nuclear export of OGFr is unknown. In this study, endogenous OGFr, as well as exogenously expressed OGFr-EGFP, demonstrated significant nuclear accumulation in response to leptomycin B (LMB), an inhibitor of CRM1-dependent nuclear export, suggesting that OGFr is exported in a CRM1-dependent manner. One consensus sequence for a nuclear export signal (NES) was identified. Mutation of the associated leucines, L217 L220 L223 and L225, to alanine resulted in decreased nuclear accumulation. NES-EGFP responded to LMB, indicating that this sequence is capable of functioning as an export signal in isolation. To determine why the sequence functions differently in isolation than as a full length protein, the localization of subNES was evaluated in the presence and absence of MG132, a potent inhibitor of proteosomal degradation. MG132 had no effect of subNES localization. The role of tandem repeats located at the C-terminus of OGFr was examined for their role in nuclear trafficking. Six of seven tandem repeats were removed to form deltaTR. DeltaTR localized exclusively to the nucleus indicating that the tandem repeats may contribute to the localization of the receptor. Similar to the loss of cellular proliferation activity (i.e. inhibition) recorded with subNES, deltaTR also demonstrated a significant loss of inhibitory activity indicating that the repeats may be integral to receptor function. These experiments reveal that OGFr contains one functional NES, L217 L220 L223 and L225 and can be exported from the nucleus in a CRM1-dependent manner. © 2015 by the Society for Experimental Biology and Medicine.

  1. A calreticulin-dependent nuclear export signal is involved in the regulation of liver receptor homologue-1 protein folding.

    PubMed

    Yang, Feng-Ming; Feng, Shan-Jung; Lai, Tsai-Chun; Hu, Meng-Chun

    2015-10-15

    As an orphan member of the nuclear receptor family, liver receptor homologue-1 (LRH-1) controls a tremendous range of transcriptional programmes that are essential for metabolism and hormone synthesis. Our previous studies have shown that nuclear localization of the LRH-1 protein is mediated by two nuclear localization signals (NLSs) that are karyopherin/importin-dependent. It is unclear whether LRH-1 can be actively exported from the nucleus to the cytoplasm. In the present study, we describe a nuclear export domain containing two leucine-rich motifs [named nuclear export signal (NES)1 and NES2] within the ligand-binding domain (LBD). Mutation of leucine residues in NES1 or NES2 abolished nuclear export, indicating that both NES1 and NES2 motifs are essential for full nuclear export activity. This NES-mediated nuclear export was insensitive to the chromosomal region maintenance 1 (CRM1) inhibitor leptomycin B (LMB) or to CRM1 knockdown. However, knockdown of calreticulin (CRT) prevented NES-mediated nuclear export. Furthermore, our data show that CRT interacts with LRH-1 and is involved in the nuclear export of LRH-1. With full-length LRH-1, mutation of NES1 led to perinuclear accumulation of the mutant protein. Immunofluorescence analysis showed that these perinuclear aggregates were co-localized with the centrosome marker, microtubule-associated protein 1 light chain 3 (LC3), ubiquitin and heat shock protein 70 (Hsp70), indicating that the mutant was misfolded and sequestered into aggresome-like structures via the autophagic clearance pathway. Our study demonstrates for the first time that LRH-1 has a CRT-dependent NES which is not only required for cytoplasmic trafficking, but also essential for correct protein folding to avoid misfolding-induced aggregation. © 2015 Authors; published by Portland Press Limited.

  2. Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men.

    PubMed

    Mahabadi, Vahid; Amory, John K; Swerdloff, Ronald S; Bremner, William J; Page, Stephanie T; Sitruk-Ware, Regine; Christensen, Peter D; Kumar, Narender; Tsong, Yun-Yen; Blithe, Diana; Wang, Christina

    2009-07-01

    Testosterone (T) plus progestin combinations are the most promising hormonal male contraceptives. Nestorone (NES), a progestin without estrogenic or androgenic activity, when combined with T may be an excellent candidate for male contraception. Our objective was to determine the effect of transdermal NES gel alone or with T gel on gonadotropin suppression. The randomized, unblinded clinical trial was conducted at two academic medical centers. A total of 140 healthy male volunteers participated. One hundred subjects were randomized initially (20 per group) to apply NES gel 2 or 4 mg, T gel 10 g, or T gel 10 g plus NES gel 2 or 4 mg daily for 20 d. Because only about half of the subjects in T plus NES 4 mg group suppressed serum gonadotropins to 0.5 IU/liter or less (suboptimal suppression), two additional groups of 20 men were randomized to apply daily T gel 10 g plus NES gel 6 or 8 mg. Suppression of serum LH and FSH concentrations to 0.5 IU/liter or less after treatment was the main outcome variable. A total of 119 subjects were compliant with gel applications with few study-related adverse events. NES alone reduced gonadotropins significantly but less than T gel alone. Combined T gel 10g plus NES gel 6 or 8 mg suppressed both serum gonadotropins to 0.5 IU/liter or less in significantly more men than either gel alone. Transdermal NES gel alone had gonadotropin suppression activity. Combined transdermal NES (6 or 8 mg) plus T gel demonstrated safe and effective suppression of gonadotropins, justifying a longer-term study of this combination for suppression of spermatogenesis.

  3. Neurological soft signs discriminate schizophrenia from bipolar disorder.

    PubMed

    Rigucci, Silvia; Dimitri-Valente, Giorgia; Mandarelli, Gabriele; Manfredi, Giovanni; Comparelli, Anna; De Filippis, Sergio; Gherardelli, Simona; Bersani, Giuseppe; Girardi, Paolo; Ferracuti, Stefano

    2014-03-01

    Although neurological soft signs have been consistently described in patients with schizophrenia, their diagnostic specificity is not well clarified. To test the hypothesis that neurological soft signs are specifically related to schizophrenia, we examined 305 subjects (patients with schizophrenia-spectrum disorder, n=167; patients with bipolar I disorder, n=88; controls, n=50). Neurological soft signs were assessed using the Neurological Evaluation Scale (NES). Multiple logistic regression analysis was used to compute the diagnostic predictive power of neurological soft signs. Patients in the schizophrenia-spectrum disorder group were found to have significantly greater neurological impairment (NES total score=23.9, standard deviation [SD] 11.2) than those in the bipolar disorder group (NES total score=18.2, SD 7.6; p<0.001). Neurological functioning was closely associated with psychopathology (all p<0.001). The NES total score reliably distinguished patients with schizophrenia spectrum disorders from those with bipolar disorder in 68.7% of the cases (p<0.001). Moreover, a particular set of neurological soft signs showed specificity for the schizophrenia-spectrum disorder diagnostic group. Our findings suggest that schizophrenia and bipolar disorder can be distinguished in terms of neurological impairment. Furthermore, we recommend the utility of neurological soft signs as a useful, quantifiable, sensitive, and inexpensive tool for the diagnostic work-up of schizophrenia.

  4. Occupational competence and its relationship to emotional health in injured workers in return to work programs: a Malaysian study.

    PubMed

    Murad, Mohd Suleiman; O'brien, Lisa; Farnworth, Louise; Chien, Chi-Wen

    2013-03-01

    Workers with musculoskeletal disorders undertaking Malaysia's return to work (RTW) programmes may experience challenges in occupational competence (OC) and negative emotional states (NES). This study aimed to measure and examines the OC and NES of the workers by comparing specific comparison groups and groups of different phases. A total of 76 participants were recruited from a national RTW programme and categorized into three groups based on different RTW phases: off-work (n = 22), re-entry (n = 31), and maintenance (n = 23). Self-report questionnaires consisted of the Occupational Self Assessment version 2.2 and the Depression, Anxiety and Stress Scale-21. Results showed that injured workers exhibited significantly lower OC in comparison with an international group with various disabilities. In contrast, there was significantly higher NES when compared with Malaysia's general population. Significant differences in OC and NES were also found between workers in the three RTW phases. In particular, OC and NES in the off-work and re-entry phases were significantly lower (OC) and higher (NES) than in the maintenance phase. Furthermore, there was a moderate, negative correlation between OC and NES in the off-work and re-entry phase groups. This indicated that low levels of perceived OC were associated with higher levels of NES.

  5. Creating Supportive Environments and Thriving in a Volatile, Uncertain, Complex, and Ambiguous World.

    PubMed

    Pabico, Christine

    2015-10-01

    Nurse executives (NEs) are operating in a volatile, uncertain, complex, and ambiguous world. NEs must create supportive environments that promote staff empowerment, resilience, and alignment, to ensure organizational success. In addition, NEs need to be transparent and create a culture of partnership with their staff. The ability of NEs to create and sustain this environment is vital in supporting teams to successfully navigate in today's healthcare environment.

  6. Structural determinants of nuclear export signal orientation in binding to exportin CRM1

    DOE PAGES

    Fung, Ho Yee Joyce; Fu, Szu -Chin; Brautigam, Chad A.; ...

    2015-09-08

    The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). A comparison of minus and plus NESs identified structural and sequencemore » determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.« less

  7. The stability of AID and its function in class-switching are critically sensitive to the identity of its nuclear-export sequence

    PubMed Central

    Geisberger, Roland; Rada, Cristina; Neuberger, Michael S.

    2009-01-01

    The carboxyterminal region of activation-induced deaminase (AID) is required for its function in Ig class switch recombination (CSR) and also contains a nuclear-export sequence (NES). Here, based on an extensive fine-structure mutation analysis of the AID NES, as well as from AID chimeras bearing heterologous NESs, we show that while a functional NES is indeed essential for CSR, it is not sufficient. The precise nature of the NES is critical both for AID stabilization and CSR function: minor changes in the NES can perturb stabilization and CSR without jeopardizing nuclear export. The results indicate that the AID NES fulfills a function beyond simply providing a signal for nuclear export and suggest the possibility that the quality of exportin-binding may be critical to the stabilization of AID and its activity in CSR. PMID:19351893

  8. Structural phylogenetic analysis of activation-induced deaminase function.

    PubMed

    Ichikawa, H Travis; Sowden, Mark P; Torelli, Andrew T; Bachl, Jürgen; Huang, Pinwei; Dance, Geoffrey S C; Marr, Shauna H; Robert, Jacques; Wedekind, Joseph E; Smith, Harold C; Bottaro, Andrea

    2006-07-01

    In mammals, activation-induced deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) of Ig genes. SHM and CSR activities require separate regions within AID. A chromosome region maintenance 1 (CRM1)-dependent nuclear export signal (NES) at the AID C terminus is necessary for CSR, and has been suggested to associate with CSR-specific cofactors. CSR appeared late in AID evolution, during the emergence of land vertebrates from bony fish, which only display SHM. Here, we show that AID from African clawed frog (Xenopus laevis), but not pufferfish (Takifugu rubripes), can induce CSR in AID-deficient mouse B cells, although both are catalytically active in bacteria and mammalian cell systems, albeit at decreased level. Like mammalian AID, Takifugu AID is actively exported from the cell nucleus by CRM1, and the Takifugu NES can substitute for the equivalent region in human AID, indicating that all the CSR-essential NES motif functions evolutionarily predated CSR activity. We also show that fusion of the Takifugu AID catalytic domain to the entire human noncatalytic domain restores activity in mammalian cells, suggesting that AID features mapping within the noncatalytic domain, but outside the NES, influence its function.

  9. Acoustic characterization of a nonlinear vibroacoustic absorber at low frequencies and high sound levels

    NASA Astrophysics Data System (ADS)

    Chauvin, A.; Monteil, M.; Bellizzi, S.; Côte, R.; Herzog, Ph.; Pachebat, M.

    2018-03-01

    A nonlinear vibroacoustic absorber (Nonlinear Energy Sink: NES), involving a clamped thin membrane made in Latex, is assessed in the acoustic domain. This NES is here considered as an one-port acoustic system, analyzed at low frequencies and for increasing excitation levels. This dynamic and frequency range requires a suitable experimental technique, which is presented first. It involves a specific impedance tube able to deal with samples of sufficient size, and reaching high sound levels with a guaranteed linear response thank's to a specific acoustic source. The identification method presented here requires a single pressure measurement, and is calibrated from a set of known acoustic loads. The NES reflection coefficient is then estimated at increasing source levels, showing its strong level dependency. This is presented as a mean to understand energy dissipation. The results of the experimental tests are first compared to a nonlinear viscoelastic model of the membrane absorber. In a second step, a family of one degree of freedom models, treated as equivalent Helmholtz resonators is identified from the measurements, allowing a parametric description of the NES behavior over a wide range of levels.

  10. Visual Attention to Pictorial Food Stimuli in Individuals With Night Eating Syndrome: An Eye-Tracking Study.

    PubMed

    Baldofski, Sabrina; Lüthold, Patrick; Sperling, Ingmar; Hilbert, Anja

    2018-03-01

    Night eating syndrome (NES) is characterized by excessive evening and/or nocturnal eating episodes. Studies indicate an attentional bias towards food in other eating disorders. For NES, however, evidence of attentional food processing is lacking. Attention towards food and non-food stimuli was compared using eye-tracking in 19 participants with NES and 19 matched controls without eating disorders during a free exploration paradigm and a visual search task. In the free exploration paradigm, groups did not differ in initial fixation position or gaze duration. However, a significant orienting bias to food compared to non-food was found within the NES group, but not in controls. A significant attentional maintenance bias to non-food compared to food was found in both groups. Detection times did not differ between groups in the search task. Only in NES, attention to and faster detection of non-food stimuli were related to higher BMI and more evening eating episodes. The results might indicate an attentional approach-avoidance pattern towards food in NES. However, further studies should clarify the implications of attentional mechanisms for the etiology and maintenance of NES. Copyright © 2017. Published by Elsevier Ltd.

  11. Non-Native Language Use and Risk of Incident Dementia in the Elderly

    PubMed Central

    Sanders, Amy E.; Hall, Charles B.; Katz, Mindy J.; Lipton, Richard B.

    2012-01-01

    Cognitive reserve is invoked to explain the protective effects of education and cognitively-stimulating activities against all-cause dementia and Alzheimer’s disease (AD). For non-native English speakers (n-NES), speaking English may be a cognitive activity associated with lower dementia risk. We hypothesized that n-NES have lower risk of incident dementia/AD and that educational level might modify this relationship. Participants took part in the Einstein Aging Study (Bronx, NY), a longitudinal study of aging and dementia. All (n = 1779) spoke fluent English and self-reported birthplace and whether English was their first language. n-NES additionally reported mother tongue, age of English acquisition, and current percentile-use of a non-English language. Nested Cox proportional hazards models progressively adjusted for gender, race, education, and immigrant and marital status estimated hazard ratios (HR) for incident dementia/AD as a function of n-NES status. 390 (22%) participants were n-NES. 126 incident dementia cases occurred during 4174 person-years of follow-up (median 1.44; range 0–16); 101 individuals met criteria for probable/possible AD. There was no statistically-significant association between n-NES status and incident dementia in the fully-adjusted model (HR 1.26; 95% CI 0.76–2.09; p = 0.36). Results were similar for AD. Stratification of education into three groups revealed increased risk of dementia for n-NES with ≥16 years of education (HR 3.97; 95% CI 1.62–9.75; p = 0.003). We conclude that n-NES status does not appear to have an independent protective effect against incident dementia/AD, and that n-NES status may contribute to risk of dementia in an education-dependent manner. PMID:22232011

  12. Non-native language use and risk of incident dementia in the elderly.

    PubMed

    Sanders, Amy E; Hall, Charles B; Katz, Mindy J; Lipton, Richard B

    2012-01-01

    Cognitive reserve is invoked to explain the protective effects of education and cognitively-stimulating activities against all-cause dementia and Alzheimer's disease (AD). For non-native English speakers (n-NES), speaking English may be a cognitive activity associated with lower dementia risk. We hypothesized that n-NES have lower risk of incident dementia/AD and that educational level might modify this relationship. Participants took part in the Einstein Aging Study (Bronx, NY), a longitudinal study of aging and dementia. All (n = 1779) spoke fluent English and self-reported birthplace and whether English was their first language. n-NES additionally reported mother tongue, age of English acquisition, and current percentile-use of a non-English language. Nested Cox proportional hazards models progressively adjusted for gender, race, education, and immigrant and marital status estimated hazard ratios (HR) for incident dementia/AD as a function of n-NES status. 390 (22%) participants were n-NES. 126 incident dementia cases occurred during 4174 person-years of follow-up (median 1.44; range 0-16); 101 individuals met criteria for probable/possible AD. There was no statistically-significant association between n-NES status and incident dementia in the fully-adjusted model (HR 1.26; 95% CI 0.76-2.09; p = 0.36). Results were similar for AD. Stratification of education into three groups revealed increased risk of dementia for n-NES with ≥ 16 years of education (HR 3.97; 95% CI 1.62-9.75; p = 0.003). We conclude that n-NES status does not appear to have an independent protective effect against incident dementia/AD, and that n-NES status may contribute to risk of dementia in an education-dependent manner.

  13. Night-eating syndrome and the severity of self-reported depressive symptoms from the Korea Nurses' Health Study: analysis of propensity score matching and ordinal regression.

    PubMed

    Kim, O-S; Kim, M S; Lee, J E; Jung, H

    2016-12-01

    The prevalence of night-eating syndrome (NES) and depression is increasing worldwide. Although nurses, in particular, are exposed to work in an environment of irregular eating, shift work, and stressful settings, limited research exist. In fact, the prevalence of NES among Korean nurses has never been reported. The aim of this study was to determine the prevalence of NES as well as the association between NES and severity of self-reported depressive symptoms among South Korean female nurses. The Korea Nurses' Health Study, following the protocols of the Nurses' Health Study led by the Harvard University, collected data on Korean female nurses. Survey responses from 3617 participants were included, and 404 responses were analyzed in this cross-sectional study using propensity score matching. Descriptive, Spearman's and Cramer's correlations, propensity score matching, and multivariable ordinal logistic regression were conducted as statistical analysis. The prevalence of both NES and self-reported depressive symptoms among Korean female nurses were higher compared with nurses in prior studies. Nurses with NES were 1.65 times more likely to have greater severity of depressive symptoms than those without NES (95% confidence interval [1.19-2.10], odds ratio = 1.65) after adjusting for covariates including sociodemographic characteristics, health behavioural factors, and shift work. This study suggests significant association between NES and the severity of self-reported depressive symptoms among Korean female nurses after adjusting for covariates. Policy makers and hospital managers need to develop strategies to reduce depression and NES among nurses for enhancement of nurses' mental and physical health as well as for improvement of care quality. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  14. A New Combination of Testosterone and Nestorone Transdermal Gels for Male Hormonal Contraception

    PubMed Central

    Ilani, Niloufar; Roth, Mara Y.; Amory, John K.; Swerdloff, Ronald S.; Dart, Clint; Page, Stephanie T.; Bremner, William J.; Sitruk-Ware, Regine; Kumar, Narender; Blithe, Diana L.

    2012-01-01

    Context: Combinations of testosterone (T) and nestorone (NES; a nonandrogenic progestin) transdermal gels may suppress spermatogenesis and prove appealing to men for contraception. Objective: The objective of the study was to determine the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis. Design and Setting: This was a randomized, double-blind, comparator clinical trial conducted at two academic medical centers. Participants: Ninety-nine healthy male volunteers participated in the study. Interventions: Volunteers were randomized to one of three treatment groups applying daily transdermal gels (group 1: T gel 10 g + NES 0 mg/placebo gel; group 2: T gel 10 g + NES gel 8 mg; group 3: T gel 10 g + NES gel 12 mg). Main Outcome Variable: The main outcome variable of the study was the percentage of men whose sperm concentration was suppressed to 1 million/ml or less by 20–24 wk of treatment. Results: Efficacy data analyses were performed on 56 subjects who adhered to the protocol and completed at least 20 wk of treatment. The percentage of men whose sperm concentration was 1 million/ml or less was significantly higher for T + NES 8 mg (89%, P < 0.0001) and T + NES 12 mg (88%, P = 0.0002) compared with T + NES 0 mg group (23%). The median serum total and free T concentrations in all groups were maintained within the adult male range throughout the treatment period. Adverse effects were minimal in all groups. Conclusion: A combination of daily NES + T gels suppressed sperm concentration to 1 million/ml or less in 88.5% of men, with minimal adverse effects, and may be further studied as a male transdermal hormonal contraceptive. PMID:22791756

  15. The NS2 proteins of parvovirus minute virus of mice are required for efficient nuclear egress of progeny virions in mouse cells.

    PubMed

    Eichwald, Virginie; Daeffler, Laurent; Klein, Michèle; Rommelaere, Jean; Salomé, Nathalie

    2002-10-01

    The small nonstructural NS2 proteins of parvovirus minute virus of mice (MVMp) were previously shown to interact with the nuclear export receptor Crm1. We report here the analysis of two MVM mutant genomic clones generating NS2 proteins that are unable to interact with Crm1 as a result of amino acid substitutions within their nuclear export signal (NES) sequences. Upon transfection of human and mouse cells, the MVM-NES21 and MVM-NES22 mutant genomic clones were proficient in synthesis of the four virus-encoded proteins. While the MVM-NES22 clone was further able to produce infectious mutant virions, no virus could be recovered from cells transfected with the MVM-NES21 clone. Whereas the defect of MVM-NES21 appeared to be complex, the phenotype of MVM-NES22 could be traced back to a novel distinct NS2 function. Infection of mouse cells with the MVM-NES22 mutant led to stronger nuclear retention not only of the NS2 proteins but also of infectious progeny MVM particles. This nuclear sequestration correlated with a severe delay in the release of mutant virions in the medium and with prolonged survival of the infected cell populations compared with wild-type virus-treated cultures. This defect could explain, at least in part, the small size of the plaques generated by the MVM-NES22 mutant when assayed on mouse indicator cells. Altogether, our data indicate that the interaction of MVMp NS2 proteins with the nuclear export receptor Crm1 plays a critical role at a late stage of the parvovirus life cycle involved in release of progeny viruses.

  16. The NS2 Proteins of Parvovirus Minute Virus of Mice Are Required for Efficient Nuclear Egress of Progeny Virions in Mouse Cells

    PubMed Central

    Eichwald, Virginie; Daeffler, Laurent; Klein, Michèle; Rommelaere, Jean; Salomé, Nathalie

    2002-01-01

    The small nonstructural NS2 proteins of parvovirus minute virus of mice (MVMp) were previously shown to interact with the nuclear export receptor Crm1. We report here the analysis of two MVM mutant genomic clones generating NS2 proteins that are unable to interact with Crm1 as a result of amino acid substitutions within their nuclear export signal (NES) sequences. Upon transfection of human and mouse cells, the MVM-NES21 and MVM-NES22 mutant genomic clones were proficient in synthesis of the four virus-encoded proteins. While the MVM-NES22 clone was further able to produce infectious mutant virions, no virus could be recovered from cells transfected with the MVM-NES21 clone. Whereas the defect of MVM-NES21 appeared to be complex, the phenotype of MVM-NES22 could be traced back to a novel distinct NS2 function. Infection of mouse cells with the MVM-NES22 mutant led to stronger nuclear retention not only of the NS2 proteins but also of infectious progeny MVM particles. This nuclear sequestration correlated with a severe delay in the release of mutant virions in the medium and with prolonged survival of the infected cell populations compared with wild-type virus-treated cultures. This defect could explain, at least in part, the small size of the plaques generated by the MVM-NES22 mutant when assayed on mouse indicator cells. Altogether, our data indicate that the interaction of MVMp NS2 proteins with the nuclear export receptor Crm1 plays a critical role at a late stage of the parvovirus life cycle involved in release of progeny viruses. PMID:12239307

  17. Confirmatory/release survey of the property at 71 Pearce Avenue (Former EAD Building) in Tonawanda, New York

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Salame-Alfie, A.; Alibozek, R.

    1995-12-31

    EAD Metallurgical, Inc., operated a facility in Tonawanda, New York, in which it utilized Americium 241 (Am-241) for the production of foil sources for use in smoke detectors. EAD was in operation between 1977 and 1983. By 1983, the company started losing money, and decided to relocate to Mexico. Before closing down its Tonawanda operation, however, it was required by the New York State Department of Labor (DOL) to decontaminate its facility to limits specified by DOL. No records of discharges to the sewer system were kept during this decontamination effort. Unsuccessful decontamination efforts by several EAD employees and contractorsmore » left the building contaminated, in particular the concrete floors and walls. To determine the scope of work for the decontamination project, staff from the New York State Departments of Health (DOH) and Environmental Conservation (DEC) conducted a Characterization Survey of the facility in 1993. This survey identified contamination levels of Am-241 in excess of release limits throughout the building, in the soil outside the facility, in pipes for sewage and interior drainage, and in an 8 x 8 x 11 foot sump pit in the building. DOH issued a request for proposals in early 1994 for the decontamination and subsequent decommissioning of the former EAD building, and NES/IES Inc. (NES) was awarded the contract to perform the remediation. DOH`s assignment was to provide an on-site presence to insure the completion of all agreed upon tasks, according to the terms of the contract and work plans submitted by NES. Additionally, the DOH staff acted as a liaison between NES, DOH, DEC and DOL central offices to review, comment and approve all changes or modifications to NES`s approach to the decontamination efforts. The assigned staff was also responsible for conducting confirmatory sampling and surveys of all areas deemed releasable to DOL and DEC criteria by NES.« less

  18. NASA's explorer school and spaceward bound programs: Insights into two education programs designed to heighten public support for space science initiatives

    USGS Publications Warehouse

    Allner, Matthew; McKay, C.; Coe, L.; Rask, Jon; Paradise, Jim; Wynne, J.J.

    2008-01-01

    Introduction: NASA has played an influential role in bringing the enthusiasm of space science to schools across the United States since the 1980s. The evolution of this public outreach has led to a variety of NASA funded education programs designed to promote student interest in science, technology, engineering, math, and geography (STEM-G) careers. Purpose: This paper investigates the educational outreach initiatives, structure, and impact of two of NASA's largest educational programs: the NASA Explorer School (NES) and NASA Spaceward Bound programs. Methods: The investigation further provides a detailed overview of the structure of these two NASA education outreach programs, while providing information regarding selection criteria and program developments over time. Results: Since its induction in 2003 the NES program has networked and provided resources to over 300 schools across the United States. Future directions include further development of mentor schools for each new NES school selected, while also developing a longitudinal student tracking system for NES students to monitor their future involvement in STEM-G careers. The Spaceward Bound program, now in its third year of teacher outreach, is looking to further expand its teacher network and scientific collaboration efforts, while building on its teacher mentorship framework.

  19. Energy technology evaluation report: Energy security

    NASA Astrophysics Data System (ADS)

    Koopman, R.; Lamont, A.; Schock, R.

    1992-09-01

    Energy security was identified in the National Energy Strategy (NES) as a major issue for the Department of Energy (DOE). As part of a process designed by the DOE to identify technologies important to implementing the NES, an expert working group was convened to consider which technologies can best contribute to reducing the nation's economic vulnerability to future disruptions of world oil supplies, the working definition of energy security. Other working groups were established to deal with economic growth, environmental quality, and technical foundations. Energy Security working group members were chosen to represent as broad a spectrum of energy supply and end-use technologies as possible and were selected for their established reputations as experienced experts with an ability to be objective. The time available for this evaluation was very short. The group evaluated technologies using criteria taken from the NES which can be summarized for energy security as follows: diversifying sources of world oil supply so as to decrease the increasing monopoly status of the Persian Gulf region; reducing the importance of oil use in the US economy to diminish the impact of future disruptions in oil supply; and increasing the preparedness of the US to deal with oil supply disruptions by having alternatives available at a known price. The result of the first phase of the evaluation process was the identification of technology groups determined to be clearly important for reducing US vulnerability to oil supply disruptions. The important technologies were mostly within the high leverage areas of oil and gas supply and transportation demand but also included hydrogen utilization, biomass, diversion resistant nuclear power, and substitute industrial feedstocks.

  20. Why I eat at night: A qualitative exploration of the development, maintenance and consequences of Night Eating Syndrome.

    PubMed

    Shillito, James A; Lea, James; Tierney, Stephanie; Cleator, Jacqueline; Tai, Sara; Wilding, John P H

    2018-06-01

    Night Eating Syndrome (NES), as a diagnosis, presents as a combination of disordered eating, sleep and mood. Patients identified as having both NES and obesity demonstrate poorer outcomes in terms of weight loss compared to those with NES only. However, research focusing on psychological factors associated with NES remains relatively underdeveloped. This study aimed to explore the relationship between NES and the experience of emotion from the perspective of patients accessing a weight management service. Ten adults who met diagnostic criteria for moderate or full NES took part in a semi-structured interview. Data were analysed using a constructivist approach to grounded theory. A core concept to emerge from the analysis was termed 'emotional hunger'; reflecting an urge or need to satiate a set of underlying unmet emotional needs. It was underpinned by the following interrelated themes: (1) Cultivating a dependency on food; (2) Relying on food to regulate emotions; (3) Understanding the significance of night-time; (4) Acknowledging the consequences of night eating. This study provides an in-depth understanding of the relationship between NES and the experience of emotion from the perspective of patients attending a weight management service. Results have potential to inform future service development, particularly around the adoption of a more holistic approach to night eating behaviours. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Silencing of BCR/ABL Chimeric Gene in Human Chronic Myelogenous Leukemia Cell Line K562 by siRNA-Nuclear Export Signal Peptide Conjugates.

    PubMed

    Shinkai, Yasuhiro; Kashihara, Shinichi; Minematsu, Go; Fujii, Hirofumi; Naemura, Madoka; Kotake, Yojiro; Morita, Yasutaka; Ohnuki, Koichiro; Fokina, Alesya A; Stetsenko, Dmitry A; Filichev, Vyacheslav V; Fujii, Masayuki

    2017-06-01

    Herein we described the synthesis of siRNA-NES (nuclear export signal) peptide conjugates by solid phase fragment coupling and the application of them to silencing of bcr/abl chimeric gene in human chronic myelogenous leukemia cell line K562. Two types of siRNA-NES conjugates were prepared, and both sense strands at 5' ends were covalently linked to a NES peptide derived from TFIIIA and HIV-1 REV, respectively. Significant enhancement of silencing efficiency was observed for both of them. siRNA-TFIIIA NES conjugate suppressed the expression of BCR/ABL gene to 8.3% at 200 nM and 11.6% at 50 nM, and siRNA-HIV-1REV NES conjugate suppressed to 4.0% at 200 nM and 6.3% at 50 nM, whereas native siRNA suppressed to 36.3% at 200 nM and 30.2% at 50 nM. We could also show complex of siRNA-NES conjugate and designed amphiphilic peptide peptideβ7 could be taken up into cells with no cytotoxicity and showed excellent silencing efficiency. We believe that the complex siRNA-NES conjugate and peptideβ7 is a promising candidate for in vivo use and therapeutic applications.

  2. Neurological soft signs in obsessive compulsive disorder with good and poor insight.

    PubMed

    Karadag, Filiz; Tumkaya, Selim; Kırtaş, Duygu; Efe, Muharrem; Alacam, Hüseyin; Oguzhanoglu, Nalan K

    2011-06-01

    Obsessive compulsive disorder (OCD) is a clinically heterogeneous disorder; OCD with poor insight has been suggested to be a specific clinical subtype. Neurological soft signs (NSSs) may be helpful to identify the specific subtypes of OCD patients. In the present study, we aimed to compare OCD patients with poor insight with OCD patients having good insight, and healthy individuals. Sixty-four OCD patients (38 with good insight and 26 with poor insight), and 32 healthy subjects were enrolled in the present study. The Overvalued Ideas Scale (OVIS) was used to determine OCD patients with poor insight. NSSs were assessed by using the Neurological Evaluation Scale (NES). Two OCD groups had significantly higher total NES scores compared to controls (p=.000). Compared to healthy controls, OCD patients with poor insight performed significantly worse on all NES subscales, and they had significantly more NSSs on motor coordination, and sensory integration subscales compared to the OCD with good insight group. Our results suggested that OCD patients with poor insight exhibit more extensive neurodevelopmental impairments compared to OCD patients with good insight. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Conditional N-WASP knockout in mouse brain implicates actin cytoskeleton regulation in hydrocephalus pathology.

    PubMed

    Jain, Neeraj; Lim, Lee Wei; Tan, Wei Ting; George, Bhawana; Makeyev, Eugene; Thanabalu, Thirumaran

    2014-04-01

    Cerebrospinal fluid (CSF) is produced by the choroid plexus and moved by multi-ciliated ependymal cells through the ventricular system of the vertebrate brain. Defects in the ependymal layer functionality are a common cause of hydrocephalus. N-WASP (Neural-Wiskott Aldrich Syndrome Protein) is a brain-enriched regulator of actin cytoskeleton and N-WASP knockout caused embryonic lethality in mice with neural tube and cardiac abnormalities. To shed light on the role of N-WASP in mouse brain development, we generated N-WASP conditional knockout mouse model N-WASP(fl/fl); Nestin-Cre (NKO-Nes). NKO-Nes mice were born with Mendelian ratios but exhibited reduced growth characteristics compared to their littermates containing functional N-WASP alleles. Importantly, all NKO-Nes mice developed cranial deformities due to excessive CSF accumulation and did not survive past weaning. Coronal brain sections of these animals revealed dilated lateral ventricles, defects in ciliogenesis, loss of ependymal layer integrity, reduced thickness of cerebral cortex and aqueductal stenosis. Immunostaining for N-cadherin suggests that ependymal integrity in NKO-Nes mice is lost as compared to normal morphology in the wild-type controls. Moreover, scanning electron microscopy and immunofluorescence analyses of coronal brain sections with anti-acetylated tubulin antibodies revealed the absence of cilia in ventricular walls of NKO-Nes mice indicative of ciliogenesis defects. N-WASP deficiency does not lead to altered expression of N-WASP regulatory proteins, Fyn and Cdc42, which have been previously implicated in hydrocephalus pathology. Taken together, our results suggest that N-WASP plays a critical role in normal brain development and implicate actin cytoskeleton regulation as a vulnerable axis frequently deregulated in hydrocephalus. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Presidential Debate Watching, Issue Knowledge, Character Evaluation, and Vote Choice

    ERIC Educational Resources Information Center

    Benoit, William L.; Hansen, Glenn J.

    2004-01-01

    This study employs NES (National Election Survey) data from several presidential elections to investigate the effects of presidential debate watching on voters' issue knowledge, character evaluation, and vote choice. Debates can instill issue knowledge; however, voters are less likely to learn about incumbent presidents seeking re-election after a…

  5. Splicing Factor Prp8 Interacts With NES(AR) and Regulates Androgen Receptor in Prostate Cancer Cells.

    PubMed

    Wang, Dan; Nguyen, Minh M; Masoodi, Khalid Z; Singh, Prabhpreet; Jing, Yifeng; O'Malley, Katherine; Dar, Javid A; Dhir, Rajiv; Wang, Zhou

    2015-12-01

    Androgen receptor (AR) plays a pivotal role in the development of primary as well as advanced castration-resistant prostate cancer. Previous work in our lab identified a novel nuclear export signal (NES) (NES(AR)) in AR ligand-binding domain essential for AR nucleocytoplasmic trafficking. By characterizing the localization of green fluorescence protein (GFP)-tagged NES(AR), we designed and executed a yeast mutagenesis screen and isolated 7 yeast mutants that failed to display the NES(AR) export function. One of those mutants was identified as the splicing factor pre-mRNA processing factor 8 (Prp8). We further showed that Prp8 could regulate NES(AR) function using short hairpin RNA knockdown of Prp8 coupled with a rapamycin export assay in mammalian cells and knockdown of Prp8 could induce nuclear accumulation of GFP-tagged AR in PC3 cells. Prp8 expression was decreased in castration-resistant LuCaP35 xenograft tumors as compared with androgen-sensitive xenografts. Laser capture microdissection and quantitative PCR showed Prp8 mRNA levels were decreased in human prostate cancer specimens with high Gleason scores. In prostate cancer cells, coimmunoprecipitation and deletion mutagenesis revealed a physical interaction between Prp8 and AR mainly mediated by NES(AR). Luciferase assay with prostate specific antigen promoter-driven reporter demonstrated that Prp8 regulated AR transcription activity in prostate cancer cells. Interestingly, Prp8 knockdown also increased polyubiquitination of endogenous AR. This may be 1 possible mechanism by which it modulates AR activity. These results show that Prp8 is a novel AR cofactor that interacts with NES(AR) and regulates AR function in prostate cancer cells.

  6. Earth Science Resource Teachers: A Mentor Program for NASA's Explorer Schools

    NASA Astrophysics Data System (ADS)

    Ireton, F.; Owens, A.; Steffen, P. L.

    2004-12-01

    Each year, the NASA Explorer Schools (NES) program establishes a three-year partnership between NASA and 50 school teams, consisting of teachers and education administrators from diverse communities across the country. While partnered with NASA, NES teams acquire and use new teaching resources and technology tools for grades 4 - 9 using NASA's unique content, experts and other resources. Schools in the program are eligible to receive funding (pending budget approval) over the three-year period to purchase technology tools that support science and mathematics instruction. Explorer School teams attend a one-week summer institute at one of NASA's field centers each summer. The weeklong institutes are designed to introduce the teachers and administrators to the wealth of NASA information and resources available and to provide them with content background on NASA's exploration programs. During the 2004 summer institutes at Goddard Space Flight Center (GSFC) the National Earth Science Teachers Association (NESTA) entered into a pilot program with NES to test the feasibility of master teachers serving as mentors for the NES teams. Five master teachers were selected as Earth Science Resource Teachers (ESRT) from an application pool and attended the NES workshop at GSFC. During the workshop they participated in the program along side the NES teams which provided the opportunity for them to meet the teams and develop a rapport. Over the next year the ESRT will be in communication with the NES teams to offer suggestions on classroom management, content issues, classroom resources, and will be able to assist them in meeting the goals of NES. This paper will discuss the planning, selection, participation, outcomes, costs, and suggestions for future ESRT mentorship programs.

  7. Nonnormative eating behavior and psychopathology in prebariatric patients with binge-eating disorder and night eating syndrome.

    PubMed

    Baldofski, Sabrina; Tigges, Wolfgang; Herbig, Beate; Jurowich, Christian; Kaiser, Stefan; Stroh, Christine; de Zwaan, Martina; Dietrich, Arne; Rudolph, Almut; Hilbert, Anja

    2015-01-01

    Binge-eating disorder (BED) as a distinct eating disorder category and night eating syndrome (NES) as a form of Other Specified Feeding or Eating Disorders were recently included in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). This study sought to investigate the prevalence of BED and NES and associations with various forms of nonnormative eating behavior and psychopathology in prebariatric patients. Within a consecutive multicenter registry study, patients in 6 bariatric surgery centers in Germany were recruited. Overall, 233 prebariatric patients were assessed using the Eating Disorder Examination and self-report questionnaires. Assessment was unrelated to clinical procedures. Diagnostic criteria for full-syndrome BED and NES were currently met by 4.3% and 8.2% of prebariatric patients, respectively. In addition, 8.6% and 6.9% of patients met subsyndromal BED and NES criteria, respectively. Co-morbid BED and NES diagnoses were present in 3.9% of patients. In comparison to patients without any eating disorder symptoms, patients with BED and NES reported greater emotional eating, eating in the absence of hunger, and more symptoms of food addiction. Moreover, differences between patients with BED and NES emerged with more objective binge-eating episodes and higher levels of eating concern, weight concern, and global eating disorder psychopathology in patients with BED. BED and NES were shown to be prevalent among prebariatric patients, with some degree of overlap between diagnoses. Associations with nonnormative eating behavior and psychopathology point to their clinical significance and discriminant validity. Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  8. nES GEMMA Analysis of Lectins and Their Interactions with Glycoproteins - Separation, Detection, and Sampling of Noncovalent Biospecific Complexes

    NASA Astrophysics Data System (ADS)

    Engel, Nicole Y.; Weiss, Victor U.; Marchetti-Deschmann, Martina; Allmaier, Günter

    2017-01-01

    In order to better understand biological events, lectin-glycoprotein interactions are of interest. The possibility to gather more information than the mere positive or negative response for interactions brought mass spectrometry into the center of many research fields. The presented work shows the potential of a nano-electrospray gas-phase electrophoretic mobility molecular analyzer (nES GEMMA) to detect weak, noncovalent, biospecific interactions besides still unbound glycoproteins and unreacted lectins without prior liquid phase separation. First results for Sambucus nigra agglutinin, concanavalin A, and wheat germ agglutinin and their retained noncovalent interactions with glycoproteins in the gas phase are presented. Electrophoretic mobility diameters (EMDs) were obtained by nES GEMMA for all interaction partners correlating very well with molecular masses determined by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) of the individual molecules. Moreover, EMDs measured for the lectin-glycoprotein complexes were in good accordance with theoretically calculated mass values. Special focus was laid on complex formation for different lectin concentrations and binding specificities to evaluate the method with respect to results obtained in the liquid phase. The latter was addressed by capillary electrophoresis on-a-chip (CE-on-a-chip). Of exceptional interest was the fact that the formed complexes could be sampled according to their size onto nitrocellulose membranes after gas-phase separation. Subsequent immunological investigation further proved that the collected complex actually retained its native structure throughout nES GEMMA analysis and sampling.

  9. Involvement of extracellular factors in maintaining self-renewal of neural stem cell by nestin.

    PubMed

    Di, Chun Guang; Xiang, Andy Peng; Jia, Lei; Liu, Jun Feng; Lahn, Bruce T; Ma, Bao Feng

    2014-07-09

    Nestin knockout leads to embryonic lethality and self-renewal deficiency in neural stem cells (NSCs). However, how nestin maintains self-renewal remains uncertain. Here, we used the dosage effect of nestin in heterozygous mice (Nes+/-) to study self-renewal of NSCs. With existing extracellular signaling in vivo or in vitro, nestin levels do not affect proliferation ability or apoptosis when compared between Nes+/- and Nes+/+ NSCs. However, self-renewal ability of Nes+/- NSCs is impaired when plated at a low cell density and completely lost at a clonal density. This deficiency in self-renewal at a clonal density is rescued using a medium conditioned by Nes+/+ NSCs. In addition, the Akt signaling pathway is altered at low density and reversed by conditioned medium. Our data show that secreted factors contribute toward maintaining self-renewal of NSCs by nestin, potentially through Akt signaling.

  10. Tornado hazard communication disparities among Spanish-speaking individuals in an English-speaking community.

    PubMed

    Ahlborn, Leslie; Franc, Jeffrey Michael

    2012-02-01

    The state of Oklahoma, known for destructive tornados, has a native Spanish-speaking (NSS) population of approximately 180,241, of which 50% report being able to speak English "very well" (US Census Bureau). With almost 50% of these native Spanish-speaking persons being limited English proficient (LEP), their reception of tornado hazard communications may be restricted. This study conducted in northeast Oklahoma (USA) evaluates the association between native language and receiving tornado hazard communications. This study was a cross-sectional survey conducted among a convenience sample of NSS and native English-speaking (NES) adults at Xavier Clinic and St. Francis Trauma Emergency Center in Tulsa, OK, USA from September 2009 through December 2009. Of the 82 surveys administered, 80 were returned, with 40 NES and 40 NSS participants. A scoring system (Severe Weather Information Reception (SWIR)) was developed to quantify reception of hazard information among the study participants (1-3 points=poor reception, 4-5=adequate reception, 6-8=excellent reception). Pearson's chi-squared test was used to calculate differences between groups with Yates' continuity correction applied where appropriate, and SWIR scores were analyzed using ANOVA. P-values<.05 were considered significant. NSS fluency in English was 25.6%. No significant association was found between native language and those who watch television, listen to radio, have a National Oceanic and Atmospheric Administration (NOAA) All Hazards radio or telephone, or are in audible range of a tornado siren. NSS were less likely to have Internet access (P<.004), and less likely to know of local telephone warning programs (P<.03). The mean NSS SWIR score was 3.2 (95% CI, 2.8-3.7) while LEP NSS averaged 2.8 (95% CI, 2.4-3.2). The mean NES SWIR score was 4.5 (95% CI, 4.1-5.0). Results demonstrate a disparity in tornado warning reception between NSS and NES. Poor English proficiency was noted to be 75% among NSS, which is approximately 25% more than estimated by the US Census Bureau. This study demonstrates a need for emergency managers to recognize when appropriate and overcome communication disparities among limited English proficient populations.

  11. Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

    PubMed

    Behrens, Ryan T; Aligeti, Mounavya; Pocock, Ginger M; Higgins, Christina A; Sherer, Nathan M

    2017-02-01

    HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide, thereby biasing its trafficking to and retention within the nucleus. Targeted pharmacological disruption of Rev-Rev interactions should perturb multiple Rev activities, both Rev-RNA binding and Rev's trafficking to the nucleus in the first place. Copyright © 2017 American Society for Microbiology.

  12. Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export

    PubMed Central

    Behrens, Ryan T.; Aligeti, Mounavya; Pocock, Ginger M.; Higgins, Christina A.

    2016-01-01

    ABSTRACT HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. IMPORTANCE HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide, thereby biasing its trafficking to and retention within the nucleus. Targeted pharmacological disruption of Rev-Rev interactions should perturb multiple Rev activities, both Rev-RNA binding and Rev's trafficking to the nucleus in the first place. PMID:27852860

  13. Autonomous requirements of the Menkes disease protein in the nervous system.

    PubMed

    Hodgkinson, Victoria L; Zhu, Sha; Wang, Yanfang; Ladomersky, Erik; Nickelson, Karen; Weisman, Gary A; Lee, Jaekwon; Gitlin, Jonathan D; Petris, Michael J

    2015-11-15

    Menkes disease is a fatal neurodegenerative disorder arising from a systemic copper deficiency caused by loss-of-function mutations in a ubiquitously expressed copper transporter, ATP7A. Although this disorder reveals an essential role for copper in the developing human nervous system, the role of ATP7A in the pathogenesis of signs and symptoms in affected patients, including severe mental retardation, ataxia, and excitotoxic seizures, remains unknown. To directly examine the role of ATP7A within the central nervous system, we generated Atp7a(Nes) mice, in which the Atp7a gene was specifically deleted within neural and glial cell precursors without impairing systemic copper homeostasis, and compared these mice with the mottled brindle (mo-br) mutant, a murine model of Menkes disease in which Atp7a is defective in all cells. Whereas mo-br mice displayed neurodegeneration, demyelination, and 100% mortality prior to weaning, the Atp7a(Nes) mice showed none of these phenotypes, exhibiting only mild sensorimotor deficits, increased anxiety, and susceptibility to NMDA-induced seizure. Our results indicate that the pathophysiology of severe neurological signs and symptoms in Menkes disease is the result of copper deficiency within the central nervous system secondary to impaired systemic copper homeostasis and does not arise from an intrinsic lack of ATP7A within the developing brain. Furthermore, the sensorimotor deficits, hypophagia, anxiety, and sensitivity to NMDA-induced seizure in the Atp7a(Nes) mice reveal unique autonomous requirements for ATP7A in the nervous system. Taken together, these data reveal essential roles for copper acquisition in the central nervous system in early development and suggest novel therapeutic approaches in affected patients. Copyright © 2015 the American Physiological Society.

  14. Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jacobsen, A. S., E-mail: Ajsen@fysik.dtu.dk; Salewski, M.; Korsholm, S. B.

    2014-11-15

    The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR.

  15. Energy models and national energy policy

    NASA Astrophysics Data System (ADS)

    Bloyd, Cary N.; Streets, David G.; Fisher, Ronald E.

    1990-01-01

    As work begins on the development of a new National Energy Strategy (NES), the role of energy models is becoming increasingly important. Such models are needed to determine and assess both the short and long term effects of new policy initiatives on U.S. energy supply and demand. A central purpose of the model is to translate overall energy strategy goals into policy options while identifying potential costs and environmental benefits. Three models currently being utilized in the NES process are described, followed by a detailed listing of the publicly identified NES goals. These goals are then viewed in light of the basic modeling scenarios that were proposed as part of the NES development process.

  16. Inverse gene-for-gene interactions contribute additively to tan spot susceptibility in wheat.

    PubMed

    Liu, Zhaohui; Zurn, Jason D; Kariyawasam, Gayan; Faris, Justin D; Shi, Gongjun; Hansen, Jana; Rasmussen, Jack B; Acevedo, Maricelis

    2017-06-01

    Tan spot susceptibility is conferred by multiple interactions of necrotrophic effector and host sensitivity genes. Tan spot of wheat, caused by Pyrenophora tritici-repentis, is an important disease in almost all wheat-growing areas of the world. The disease system is known to involve at least three fungal-produced necrotrophic effectors (NEs) that interact with the corresponding host sensitivity (S) genes in an inverse gene-for-gene manner to induce disease. However, it is unknown if the effects of these NE-S gene interactions contribute additively to the development of tan spot. In this work, we conducted disease evaluations using different races and quantitative trait loci (QTL) analysis in a wheat recombinant inbred line (RIL) population derived from a cross between two susceptible genotypes, LMPG-6 and PI 626573. The two parental lines each harbored a single known NE sensitivity gene with LMPG-6 having the Ptr ToxC sensitivity gene Tsc1 and PI 626573 having the Ptr ToxA sensitivity gene Tsn1. Transgressive segregation was observed in the population for all races. QTL mapping revealed that both loci (Tsn1 and Tsc1) were significantly associated with susceptibility to race 1 isolates, which produce both Ptr ToxA and Ptr ToxC, and the two genes contributed additively to tan spot susceptibility. For isolates of races 2 and 3, which produce only Ptr ToxA and Ptr ToxC, only Tsn1 and Tsc1 were associated with tan spot susceptibility, respectively. This work clearly demonstrates that tan spot susceptibility in this population is due primarily to two NE-S interactions. Breeders should remove both sensitivity genes from wheat lines to obtain high levels of tan spot resistance.

  17. Differences in serotonin transporter binding affinity in patients with major depressive disorder and night eating syndrome.

    PubMed

    Lundgren, J D; Amsterdam, J; Newberg, A; Allison, K C; Wintering, N; Stunkard, A J

    2009-03-01

    We examined serotonin transporter (SERT) binding affinity using single photon emission computed tomography (SPECT) in patients with major depressive disorder (MDD) and night eating syndrome (NES). There are similarities between MDD and NES in affective symptoms, appetite disturbance, nighttime awakenings, and, particularly, response to selective serotonin reuptake inhibitors (SSRIs). Six non-depressed patients with NES and seven patients with MDD underwent SPECT brain imaging with 123I-ADAM, a radiopharmaceutical agent selective for SERT sites. Uptake ratios of 123I-ADAM SERT binding were obtained for the midbrain, basal ganglia, and temporal lobe regions compared to the cerebellum reference region. Patients with NES had significantly greater SERT uptake ratios (effect size range 0.64-0.84) in the midbrain, right temporal lobe, and left temporal lobe regions than those with MDD whom we had previously studied. Pathophysiological differences in SERT uptake between patients with NES and MDD suggest these are distinct clinical syndromes.

  18. A Novel Nuclear Trafficking Module Regulates the Nucleocytoplasmic Localization of the Rabies Virus Interferon Antagonist, P Protein*

    PubMed Central

    Oksayan, Sibil; Wiltzer, Linda; Rowe, Caitlin L.; Blondel, Danielle; Jans, David A.; Moseley, Gregory W.

    2012-01-01

    Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export (nuclear export signals, NESs). Rabies virus (RabV) phospho (P) protein, which is largely responsible for antagonising the host anti-viral response, is expressed as five isoforms (P1–P5). The subcellular trafficking of these isoforms is thought to depend on a balance between the activities of a dominant N-terminal NES (N-NES) and a distinct C-terminal NLS (C-NLS). Specifically, the N-NES-containing isoforms P1 and P2 are cytoplasmic, whereas the shorter P3–P5 isoforms, which lack the N-NES, are believed to be nuclear through the activity of the C-NLS. Here, we show for the first time that RabV P contains an additional strong NLS in the N-terminal region (N-NLS), which, intriguingly, overlaps with the N-NES. This arrangement represents a novel nuclear trafficking module where the N-NLS is inactive in P1 but becomes activated in P3, concomitant with truncation of the N-NES, to become the principal targeting signal conferring nuclear accumulation. Understanding this unique switch arrangement of overlapping, co-regulated NES/NLS sequences is vital to delineating the critical role of RabV P protein in viral infection. PMID:22700958

  19. The population of natural Earth satellites

    NASA Astrophysics Data System (ADS)

    Granvik, Mikael; Vaubaillon, Jeremie; Jedicke, Robert

    2012-03-01

    We have for the first time calculated the population characteristics of the Earth’s irregular natural satellites (NESs) that are temporarily captured from the near-Earth-object (NEO) population. The steady-state NES size-frequency and residence-time distributions were determined under the dynamical influence of all the massive bodies in the Solar System (but mainly the Sun, Earth, and Moon) for NEOs of negligible mass. To this end, we compute the NES capture probability from the NEO population as a function of the latter’s heliocentric orbital elements and combine those results with the current best estimates for the NEO size-frequency and orbital distribution. At any given time there should be at least one NES of 1-m diameter orbiting the Earth. The average temporarily-captured orbiter (TCO; an object that makes at least one revolution around the Earth in a co-rotating coordinate system) completes (2.88 ± 0.82) rev around the Earth during a capture event that lasts (286 ± 18) d. We find a small preference for capture events starting in either January or July. Our results are consistent with the single known natural TCO, 2006 RH120, a few-meter diameter object that was captured for about a year starting in June 2006. We estimate that about 0.1% of all meteors impacting the Earth were TCOs.

  20. The creation and integration of a nurse educator position in two hospitals in Haiti.

    PubMed

    Mahon, Abbey; Valcourt, Roodeline; Merry, Lisa; Dieudonné, Fabiola; Tuck, Jodi

    2018-04-01

    Continuing education is an integral part of nursing professional development and improving healthcare delivery, but literature on continuing education initiatives in low-resource settings is limited. To describe the creation and integration of a nurse educator (NE) position in two Haitian hospitals and highlight barriers and facilitators experienced by the NEs in their role. Four NEs and three support staff involved in the creation and integration of the NE positions were interviewed. Supplementary data were gathered through participant observation and document review. Data were compiled and summarized. NEs were hired to assess learning needs, evaluate skills, train and mentor nurses, and provide ongoing support to assure application of new knowledge. Barriers included lack of specialized training and limited informational resources to develop education activities, role confusion and heavy workload, poor attendance and disparate education needs of nurses, and insufficient hospital resources and support to implement practice changes. Facilitators included previous management experience, peer support, and a perception of being valued by patients and colleagues and making a difference regarding nursing care and patient outcomes. The NE is a leadership role and a promising, sustainable initiative for developing the nursing profession in Haiti. © 2018 Wiley Periodicals, Inc.

  1. Mutation of a Conserved Nuclear Export Sequence in Chikungunya Virus Capsid Protein Disrupts Host Cell Nuclear Import.

    PubMed

    Jacobs, Susan C; Taylor, Adam; Herrero, Lara J; Mahalingam, Suresh; Fazakerley, John K

    2017-10-20

    Transmitted by mosquitoes; chikungunya virus (CHIKV) is responsible for frequent outbreaks of arthritic disease in humans. CHIKV is an arthritogenic alphavirus of the Togaviridae family. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleus. In encephalitic alphaviruses nuclear translocation induces host cell shut off; however, the role of capsid protein nuclear localisation in arthritogenic alphaviruses remains unclear. Using replicon systems, we investigated a nuclear export sequence (NES) in the N-terminal region of capsid protein; analogous to that found in encephalitic alphavirus capsid but uncharacterised in CHIKV. The chromosomal maintenance 1 (CRM1) export adaptor protein mediated CHIKV capsid protein export from the nucleus and a region within the N-terminal part of CHIKV capsid protein was required for active nuclear targeting. In contrast to encephalitic alphaviruses, CHIKV capsid protein did not inhibit host nuclear import; however, mutating the NES of capsid protein (∆NES) blocked host protein access to the nucleus. Interactions between capsid protein and the nucleus warrant further investigation.

  2. Education, progressive muscle relaxation therapy, and exercise for the treatment of night eating syndrome. A pilot study.

    PubMed

    Vander Wal, Jillon S; Maraldo, Toni M; Vercellone, Allison C; Gagne, Danielle A

    2015-06-01

    Night eating syndrome (NES) is a circadian rhythm disorder in which food intake is shifted toward the end of the day, interfering with sleep. According to the biobehavioral model of NES, the disorder is the result of a genetic predisposition that, coupled with stress, leads to enhanced reuptake of serotonin, thereby dysregulating circadian rhythms and decreasing satiety. Using the biobehavioral model as a guide, we developed a brief behavioral intervention using education, relaxation strategies, and exercise to address the core symptoms of NES. In this pilot randomized controlled clinical trial, 44 participants with NES were randomly assigned to an educational group (E; n = 14), E plus progressive muscle relaxation therapy (PMR; n = 15); or PMR plus exercise (PMR Plus, n = 15). Participants received a baseline intervention with 1- and 3-week follow-up sessions. Effectiveness analyses showed that participants in all three groups evidenced significant reductions on measures of NES symptoms (p < .001), depression (p < .05), anxiety (p < .01), and perceived stress (p < .05). However, the only significant between group change was for the percent of food eaten after the evening meal, with the PMR group showing the greatest reduction (-30.54%), followed by the PMR Plus group (-20.42%) and the E group (-9.5%); only the difference between the PMR and E groups was statistically significant (p = .012). Reductions in NES scores were significantly associated with reductions on measures of depression (r = .47; p < .01) and perceived stress (r = .37; p < .05), but not anxiety (r = .26, p = ns). Results support the role of education and relaxation in the behavioral treatment of NES. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. "Food addiction" is associated with night eating severity.

    PubMed

    Nolan, Laurence J; Geliebter, Allan

    2016-03-01

    Night eating syndrome (NES) and "food addiction" (FA) are associated with elevated body mass index (BMI) and disturbed eating behavior. The present study was conducted to examine whether NES is associated with FA, and whether BMI, depression and sleep quality contribute to any relationship between NES and FA. Two groups were studied: a sample of 254 university students and a sample of 244 older adults. All completed the Yale Food Addiction Scale (YFAS), the Night Eating Questionnaire (NEQ), the Zung Self-report Depression Scale, and the Pittsburgh Sleep Quality Index, and BMI was computed from height and weight. In both samples, higher global NEQ scores were significantly correlated with more FA symptoms, elevated depression, and poorer sleep quality, and these correlations were significantly higher in the older adult sample than in the younger student sample. Higher BMI was significantly correlated with NEQ score only in the older adult sample. The hypothesis that the prediction of NEQ by YFAS was moderated by BMI and group membership (moderated moderation) was tested; while the prediction of NEQ by YFAS was not moderated by BMI, elevated YFAS predicted higher NEQ in the adult sample than it did in the student sample. In addition, multiple regression revealed that "continued use of food despite adverse effects" was the sole FA symptom predictive of NES symptoms in students while in older adults food tolerance was the only predictor of NES. Thus, NES appears to be associated with FA, more strongly in an older community sample; higher food tolerance in NES may contribute to a desire to eat late in the evening and/or when awakening at night. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Night Eating is Associated with Emotional and External Eating in College Students

    PubMed Central

    Nolan, Laurence J.; Geliebter, Allan

    2012-01-01

    The night eating syndrome (NES) consists of evening hyperphagia and/or nocturnal eating and has been associated with depressed mood, that worsens in the evening. However, it is not consistently related to elevated BMI. The present study was conducted to examine whether a relationship exists between NES and emotional, external, and restrained eating. BMI and sleep quality were also obtained. A sample of 246 students completed the Night Eating Diagnostic Questionnaire (NEDQ), Night Eating Syndrome History and Inventory (NESHI), Sleep Quality Index (SQI), and Dutch Eating Behavior Questionnaire (DEBQ), containing subscales for emotional, external, and restrained eating. They also provided demographic information, including height and weight. Participants were grouped by severity of NES features using the NEDQ and NESHI: normal, mild night eater, moderate night eater, and full night eater syndrome. MANOVA was used to compare DEBQ subscores for the groups; those in the full syndrome category had significantly higher emotional eating scores and external eating scores than those in the normal and mild categories. There was no difference in restrained eating between the normal and full syndrome groups. Those with moderate and full syndrome NES symptoms also reported significantly lower sleep quality. No significant relationship was found between NES and BMI. The results show that NES is associated with more eating in response to negative mood and in response to food cues. PMID:22664397

  5. Dual function of the nuclear export signal of the Borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.

    PubMed

    Yanai, Mako; Sakai, Madoka; Makino, Akiko; Tomonaga, Keizo

    2017-07-11

    Borna disease virus (BoDV), which has a negative-sense, single-stranded RNA genome, causes persistent infection in the cell nucleus. The nuclear export signal (NES) of the viral nucleoprotein (N) consisting of leucine at positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one of two predicted binding sites for the viral phosphoprotein (P). A previous study demonstrated that higher expression of BoDV-P inhibits nuclear export of N; however, the function of N NES in the interaction with P remains unclear. We examined the subcellular localization, viral polymerase activity, and P-binding ability of BoDV-N NES mutants. We also characterized a recombinant BoDV (rBoDV) harboring an NES mutation of N. BoDV-N with four alanine-substitutions in the leucine and isoleucine residues of the NES impaired its cytoplasmic localization and abolished polymerase activity and P-binding ability. Although an alanine-substitution at position 131 markedly enhanced viral polymerase activity as determined by a minigenome assay, rBoDV harboring this mutation showed expression of viral RNAs and proteins relative to that of wild-type rBoDV. Our results demonstrate that BoDV-N NES has a dual function in BoDV replication, i.e., nuclear export of N and an interaction with P, affecting viral polymerase activity in the nucleus.

  6. A new active variable stiffness suspension system using a nonlinear energy sink-based controller

    NASA Astrophysics Data System (ADS)

    Anubi, Olugbenga Moses; Crane, Carl D.

    2013-10-01

    This paper presents the active case of a variable stiffness suspension system. The central concept is based on a recently designed variable stiffness mechanism which consists of a horizontal control strut and a vertical strut. The horizontal strut is used to vary the load transfer ratio by actively controlling the location of the point of attachment of the vertical strut to the car body. The control algorithm, effected by a hydraulic actuator, uses the concept of nonlinear energy sink (NES) to effectively transfer the vibrational energy in the sprung mass to a control mass, thereby reducing the transfer of energy from road disturbance to the car body at a relatively lower cost compared to the traditional active suspension using the skyhook concept. The analyses and simulation results show that a better performance can be achieved by subjecting the point of attachment of a suspension system, to the chassis, to the influence of a horizontal NES system.

  7. Efficacy of head space solid-phase microextraction coupled to gas chromatography-mass spectrometry method for determination of the trace extracellular hydrocarbons of cyanobacteria.

    PubMed

    Guan, Wenna; Zhu, Tao; Wang, Yuejie; Zhang, Zhongyi; Jin, Zhao; Wang, Cong; Bai, Fali

    2016-09-01

    Hydrocarbons are widespread in cyanobacteria, and the biochemical synthetic pathways were recently identified. Intracellular fatty alka(e)nes of cyanobacteria have been detected by liquid-liquid extraction (LLE) coupled to gas chromatography-mass spectrometry (GC/MS). However, whether fatty alka(e)nes can be released to cyanobacterial culture media remains to be clarified. This work develops a sensitive method for analyzing the trace level of extracellular hydrocarbons in cyanobacterial culture media by head space solid-phase microextraction (HS-SPME) coupled to GC/MS. Headspace (HS) extraction mode using polydimethylsiloxane fiber to extract for 30min at 50°C was employed as the optimal extraction conditions. Five cyanobacterial fatty alka(e)nes analogs including pentadecene (C15:1), pentadecane (C15:0), heptadecene (C17:1), heptadecane (C17:0), nonadecane (C19:0) were analyzed, and the data obtained from HS-SPME-GC/MS method were quantified using internal standard peak area comparisons. Limits of detection (LOD), limits of quantitation (LOQ), linear dynamic range, precisions (RSD) and recovery for the analysis of extracellular fatty alka(e)nes of cyanobacteria by HS-SPME-GC/MS were evaluated. The LODs limits of detection (S/N = 3) varied from 10 to 21 ng L-1. The correlation coefficients (r) of the calibration curves ranged from 0.9873 to 0.9977 with a linearity from 0.1 to 50 μg L-1. The RSD values were ranging from 7.8 to 14.0% and from 4.0 to 8.8% at 1.0 μg L-1 and 10.0 μg L-1 standard solutions, respectively. Comparative analysis of extracellular fatty alka(e)nes in the culture media of model cyanobacteria Synechocystis sp. PCC 6803 demonstrated that sensitivity of HS-SPME-GC/MS method was significantly higher than LLE method. Finally, we found that heptadecane can be released into the culture media of Synechocystis sp. PCC 6803 at the later growth period. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Improved operation of the nonambipolar electron source.

    PubMed

    Longmier, Ben; Hershkowitz, Noah

    2008-09-01

    Significant improvements have been made to the nonambipolar electron source (NES), a radio frequency (rf) plasma-based electron source that does not rely on electron emission at a cathode surface [B. Longmier, S. Baalrud, and N. Hershkowitz, Rev. Sci. Instrum. 77, 113504 (2006)]. A prototype NES has produced 30 A of continuous electron current, using 2 SCCM (SCCM denotes cubic centimeter per minute at STP) Xe, 1300 W rf power at 13.56 MHz, yielding a 180 times gas utilization factor. A helicon mode transition has also been identified during NES operation with an argon propellant, using 15 SCCM Ar, 1000 W rf, and 100 G magnetic field. This NES technology has the ability to replace hollow cathode electron sources and to enable high power electric propulsion missions, eliminating one of the lifetime restrictions that many ion thrusters have previously been faced with.

  9. Identification, functional characterization, and regulation of the enzyme responsible for floral (E)-nerolidol biosynthesis in kiwifruit (Actinidia chinensis).

    PubMed

    Green, Sol A; Chen, Xiuyin; Nieuwenhuizen, Niels J; Matich, Adam J; Wang, Mindy Y; Bunn, Barry J; Yauk, Yar-Khing; Atkinson, Ross G

    2012-03-01

    Flowers of the kiwifruit species Actinidia chinensis produce a mixture of sesquiterpenes derived from farnesyl diphosphate (FDP) and monoterpenes derived from geranyl diphosphate (GDP). The tertiary sesquiterpene alcohol (E)-nerolidol was the major emitted volatile detected by headspace analysis. Contrastingly, in solvent extracts of the flowers, unusually high amounts of (E,E)-farnesol were observed, as well as lesser amounts of (E)-nerolidol, various farnesol and farnesal isomers, and linalool. Using a genomics-based approach, a single gene (AcNES1) was identified in an A. chinensis expressed sequence tag library that had significant homology to known floral terpene synthase enzymes. In vitro characterization of recombinant AcNES1 revealed it was an enzyme that could catalyse the conversion of FDP and GDP to the respective (E)-nerolidol and linalool terpene alcohols. Enantiomeric analysis of both AcNES1 products in vitro and floral terpenes in planta showed that (S)-(E)-nerolidol was the predominant enantiomer. Real-time PCR analysis indicated peak expression of AcNES1 correlated with peak (E)-nerolidol, but not linalool accumulation in flowers. This result, together with subcellular protein localization to the cytoplasm, indicated that AcNES1 was acting as a (S)-(E)-nerolidol synthase in A. chinensis flowers. The synthesis of high (E,E)-farnesol levels appears to compete for the available pool of FDP utilized by AcNES1 for sesquiterpene biosynthesis and hence strongly influences the accumulation and emission of (E)-nerolidol in A. chinensis flowers.

  10. High-frequency vibration energy harvesting from impulsive excitation utilizing intentional dynamic instability caused by strong nonlinearity

    NASA Astrophysics Data System (ADS)

    Remick, Kevin; Dane Quinn, D.; Michael McFarland, D.; Bergman, Lawrence; Vakakis, Alexander

    2016-05-01

    The authors investigate a vibration-based energy harvesting system utilizing essential (nonlinearizable) nonlinearities and electromagnetic coupling elements. The system consists of a grounded, weakly damped linear oscillator (primary system) subjected to a single impulsive load. This primary system is coupled to a lightweight, damped oscillating attachment (denoted as nonlinear energy sink, NES) via a neodymium magnet and an inductance coil, and a piano wire, which generates an essential geometric cubic stiffness nonlinearity. Under impulsive input, the transient damped dynamics of this system exhibit transient resonance captures (TRCs) causing intentional large-amplitude and high-frequency instabilities in the response of the NES. These TRCs result in strong energy transfer from the directly excited primary system to the light-weight attachment. The energy is harvested by the electromagnetic elements in the coupling and, in the present case, dissipated in a resistive element in the electrical circuit. The primary goal of this work is to numerically, analytically, and experimentally demonstrate the efficacy of employing this type of intentional high-frequency dynamic instability to achieve enhanced vibration energy harvesting under impulsive excitation.

  11. Concurrent Transmission Based on Channel Quality in Ad Hoc Networks: A Game Theoretic Approach

    NASA Astrophysics Data System (ADS)

    Chen, Chen; Gao, Xinbo; Li, Xiaoji; Pei, Qingqi

    In this paper, a decentralized concurrent transmission strategy in shared channel in Ad Hoc networks is proposed based on game theory. Firstly, a static concurrent transmissions game is used to determine the candidates for transmitting by channel quality threshold and to maximize the overall throughput with consideration of channel quality variation. To achieve NES (Nash Equilibrium Solution), the selfish behaviors of node to attempt to improve the channel gain unilaterally are evaluated. Therefore, this game allows each node to be distributed and to decide whether to transmit concurrently with others or not depending on NES. Secondly, as there are always some nodes with lower channel gain than NES, which are defined as hunger nodes in this paper, a hunger suppression scheme is proposed by adjusting the price function with interferences reservation and forward relay, to fairly give hunger nodes transmission opportunities. Finally, inspired by stock trading, a dynamic concurrent transmission threshold determination scheme is implemented to make the static game practical. Numerical results show that the proposed scheme is feasible to increase concurrent transmission opportunities for active nodes, and at the same time, the number of hunger nodes is greatly reduced with the least increase of threshold by interferences reservation. Also, the good performance on network goodput of the proposed model can be seen from the results.

  12. Resveratrol-Loaded Lipid Nanocarriers: Correlation between In Vitro Occlusion Factor and In Vivo Skin Hydrating Effect

    PubMed Central

    Parenti, Carmela; Turnaturi, Rita

    2017-01-01

    Lipid nanocarriers show occlusive properties that may be related to their ability to improve skin hydration. The aim of this work was to evaluate the relationship between in vitro occlusion factor and in vivo skin hydration for three types of lipid nanocarriers: nanoemulsions (NEs), solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These lipid nanocarriers were loaded with trans-resveratrol (RSV) and incorporated in gel vehicles. In vitro occlusion factor was in the order SLNs > NLCs > NEs. Gels containing unloaded or RSV loaded lipid nanocarriers were applied on the back of a hand of 12 healthy volunteers twice a day for one week, recording skin hydration changes using the instrument Soft Plus. An increase of skin hydration was observed for all lipid nanocarriers (SLNs > NLCs > NEs). RSV loading into these nanocarriers did not affect in vitro and in vivo lipid nanocarriers effects. A linear relationship (r2 = 0.969) was observed between occlusion factor and in vivo increase of skin hydration. Therefore, the results of this study showed the feasibility of using the occlusion factor to predict in vivo skin hydration resulting from topical application of different lipid nanocarriers loading an active ingredient with no inherent hydrating activity. PMID:29232856

  13. “ Blaming, shaming, humiliation”: Stigmatising medical interactions among people with non-epileptic seizures

    PubMed Central

    Robson, Catherine; Lian, Olaug S.

    2017-01-01

    Background: People with non-epileptic seizures (NES) describe challenging relationships with health professionals, and explain negative interactions as common and expected. Despite these difficulties, little is known about how people with NES experience difficult healthcare encounters. Methods: Using a thematic discourse analysis approach, we analysed the free-text survey responses of 135 people with NES and asked: what kind of challenges do people living with this condition encounter when interacting with health professionals, and how do they experience the consequences of difficult interactions? We explore their experiences by interpreting the latent meaning of participants’ texts from a social-constructionist perspective on health and illness. Results: The overarching narrative depicts a fundamental breakdown in patient-provider relationships. According to our data, the negative experiences of study participants emerge from more than practitioners’ lack of awareness of NES and access to information about the condition - to the extent that it is available. In examining the challenges people with NES encounter when interacting with health professionals, their main experiences centre on blame and humiliation. When exploring their experiences, theories of stigma serve as a useful theoretical framework. Conclusions: Normative judgements arising from psychogenic understandings of NES are stigmatising and restrict professional displays of respectful (patient-centred) care. Those with the condition depict being negatively stereotyped, illegitimated and held morally culpable by health professionals. Perceived to lack medical, moral and credible status, participants describe practitioners who treat them with disrespect, and some recount conduct that defies all ethical and professional obligations and standards. These encounters can have wide-ranging adverse consequences for patients: emotionally, physically, and for their future healthcare. The quality of healthcare interactions for people with NES requires urgent improvements. In addition to increased awareness of the condition, practitioners need to be conscious of making and acting on adverse moral appraisals when interacting with this patient group. PMID:29152594

  14. " Blaming, shaming, humiliation": Stigmatising medical interactions among people with non-epileptic seizures.

    PubMed

    Robson, Catherine; Lian, Olaug S

    2017-01-01

    Background : People with non-epileptic seizures (NES) describe challenging relationships with health professionals, and explain negative interactions as common and expected. Despite these difficulties, little is known about how people with NES experience difficult healthcare encounters. Methods : Using a thematic discourse analysis approach, we analysed the free-text survey responses of 135 people with NES and asked: what kind of challenges do people living with this condition encounter when interacting with health professionals, and how do they experience the consequences of difficult interactions? We explore their experiences by interpreting the latent meaning of participants' texts from a social-constructionist perspective on health and illness. Results : The overarching narrative depicts a fundamental breakdown in patient-provider relationships. According to our data, the negative experiences of study participants emerge from more than practitioners' lack of awareness of NES and access to information about the condition - to the extent that it is available. In examining the challenges people with NES encounter when interacting with health professionals, their main experiences centre on blame and humiliation. When exploring their experiences, theories of stigma serve as a useful theoretical framework. Conclusions : Normative judgements arising from psychogenic understandings of NES are stigmatising and restrict professional displays of respectful (patient-centred) care. Those with the condition depict being negatively stereotyped, illegitimated and held morally culpable by health professionals. Perceived to lack medical, moral and credible status, participants describe practitioners who treat them with disrespect, and some recount conduct that defies all ethical and professional obligations and standards. These encounters can have wide-ranging adverse consequences for patients: emotionally, physically, and for their future healthcare. The quality of healthcare interactions for people with NES requires urgent improvements. In addition to increased awareness of the condition, practitioners need to be conscious of making and acting on adverse moral appraisals when interacting with this patient group.

  15. Proposed Diagnostic Criteria for Night Eating Syndrome

    PubMed Central

    Allison, Kelly C.; Lundgren, Jennifer D.; O’Reardon, John P.; Geliebter, Allan; Gluck, Marci E.; Vinai, Piergiuseppe; Mitchell, James E.; Schenck, Carlos H.; Howell, Michael J.; Crow, Scott J.; Engel, Scott; Latzer, Yael; Tzischinsky, Orna; Mahowald, Mark W.; Stunkard, Albert J.

    2015-01-01

    Objective To propose criteria for diagnosis of the night eating syndrome (NES). Method An international research meeting was held in April 2008, and consensus criteria for NES diagnosis were determined. Results The core criterion is an abnormally increased food intake in the evening and nighttime, manifested by (1) consumption of at least 25% of intake after the evening meal, and/or (2) nocturnal awakenings with ingestions at least twice per week. Awareness of the eating episodes is required, as is distress or impairment in functioning. Three of five modifiers must also be endorsed. These criteria must be met for a minimum duration of 3 months. Discussion These criteria help standardize the definition of NES. Additional aspects of the nosology of NES yet to be fully elaborated include its relationship to other eating and sleep disorders. Assessment and analytic tools are needed to assess these new criteria more accurately. PMID:19378289

  16. Stability of Mixed-Strategy-Based Iterative Logit Quantal Response Dynamics in Game Theory

    PubMed Central

    Zhuang, Qian; Di, Zengru; Wu, Jinshan

    2014-01-01

    Using the Logit quantal response form as the response function in each step, the original definition of static quantal response equilibrium (QRE) is extended into an iterative evolution process. QREs remain as the fixed points of the dynamic process. However, depending on whether such fixed points are the long-term solutions of the dynamic process, they can be classified into stable (SQREs) and unstable (USQREs) equilibriums. This extension resembles the extension from static Nash equilibriums (NEs) to evolutionary stable solutions in the framework of evolutionary game theory. The relation between SQREs and other solution concepts of games, including NEs and QREs, is discussed. Using experimental data from other published papers, we perform a preliminary comparison between SQREs, NEs, QREs and the observed behavioral outcomes of those experiments. For certain games, we determine that SQREs have better predictive power than QREs and NEs. PMID:25157502

  17. Identification, functional characterization, and regulation of the enzyme responsible for floral (E)-nerolidol biosynthesis in kiwifruit (Actinidia chinensis)

    PubMed Central

    Green, Sol A.; Chen, Xiuyin; Nieuwenhuizen, Niels J.; Matich, Adam J.; Wang, Mindy Y.; Bunn, Barry J.; Yauk, Yar-Khing; Atkinson, Ross G.

    2012-01-01

    Flowers of the kiwifruit species Actinidia chinensis produce a mixture of sesquiterpenes derived from farnesyl diphosphate (FDP) and monoterpenes derived from geranyl diphosphate (GDP). The tertiary sesquiterpene alcohol (E)-nerolidol was the major emitted volatile detected by headspace analysis. Contrastingly, in solvent extracts of the flowers, unusually high amounts of (E,E)-farnesol were observed, as well as lesser amounts of (E)-nerolidol, various farnesol and farnesal isomers, and linalool. Using a genomics-based approach, a single gene (AcNES1) was identified in an A. chinensis expressed sequence tag library that had significant homology to known floral terpene synthase enzymes. In vitro characterization of recombinant AcNES1 revealed it was an enzyme that could catalyse the conversion of FDP and GDP to the respective (E)-nerolidol and linalool terpene alcohols. Enantiomeric analysis of both AcNES1 products in vitro and floral terpenes in planta showed that (S)-(E)-nerolidol was the predominant enantiomer. Real-time PCR analysis indicated peak expression of AcNES1 correlated with peak (E)-nerolidol, but not linalool accumulation in flowers. This result, together with subcellular protein localization to the cytoplasm, indicated that AcNES1 was acting as a (S)-(E)-nerolidol synthase in A. chinensis flowers. The synthesis of high (E,E)-farnesol levels appears to compete for the available pool of FDP utilized by AcNES1 for sesquiterpene biosynthesis and hence strongly influences the accumulation and emission of (E)-nerolidol in A. chinensis flowers. PMID:22162874

  18. Risk evaluation of possible human hazards by chemicals, particles, and infectious units

    NASA Astrophysics Data System (ADS)

    Weber, Lothar W.; Spleiss, Martin

    1996-12-01

    Formation of laser plume by laser-tissue interaction means an inhomogeneous, pluriphasic and dynamic multicomponent system of biological material and induced modifications. While IR_laser applications often simulate processes of thermal food preservation, UV-lasers favor formation of aromatic organic compounds as VOC. Along with traces of PAH, nitriles and O-/N-containing heterocyclic compounds two classes of dialkyldiketopyrroli(di)nes are special formed VOC as laser solvents. Inhalable particles or partially dried and modified biomass contain - along with infectious particles - a lot of temperature degradation products. Ames tests and Comet-assays gave hint to some mutagenic activities present in laser smoke.

  19. Passive broadband targeted energy transfers and control of self-excited vibrations

    NASA Astrophysics Data System (ADS)

    Lee, Young S.

    This work consists of the three main parts---Nonlinear energy pumping (that is, passive broadband targeted energy transfers---TETs), and its applications to theoretical and experimental suppression of aeroelastic instabilities. In the first part, nonlinear energy pumping (or TETs) in coupled oscillators is studied. The system is composed of a primary linear subsystem coupled through an essentially nonlinear stiffness and a linear viscous damper to an additional mass (which is called, as a whole, a nonlinear energy sink---NES). By considering the linear damping as a perturbation to the system, periodic solutions of the underlying Hamiltonian system are formulated by means of the non-smooth temporal transformation and solved numerically by a shooting method. The special periodic orbits, which are corresponding to the impulsive initial conditions for the primary subsystem, bear their importance as baits for initiating localized transfers of a significant portion of energy to the NES. The second part theoretically deals with suppression of limit cycle oscillations (LCOs) in self-excited systems by means of passive energy localizations. As a pilot scheme, suppression or even complete elimination of the LCO in a van der Pol (VDP) oscillator coupled with two types of NESS---grounded and ungrounded---is studied. Computational parametric study proves the efficacy of LCO elimination by means of passive nonlinear energy pumping from the VDP oscillator to appropriately designed NESs. The numerical study of the transient dynamics of the system showed that the dynamical mechanism for LCO suppression is a series of 1:1 and 1:3 transient resonance captures, with the damped transient dynamics following closely corresponding resonant manifolds of the underlying Hamiltonian system. It is through the TRCs that energy gets transferred from the VDP oscillator to the NES, thus causing LCO suppression. By performing an additional bifurcation analysis of the steady state responses through a numerical continuation of equilibria and periodic solutions, the parameter dependence and bifurcations of the steady-state solutions are examined. It is also proved that a Hopf bifurcation is the global dynamical mechanism for generation and elimination of the LCOs in the configurations considered. The bifurcation analysis revealed that it is possible to design grounded or ungrounded NESs that robustly and completely eliminate the LCO instability of the system. This should be possible when the system parameters are chosen such that a subcritical Hopf bifurcation occurs, thus assuring the existence of a unique global trivial attractor of the dynamics in the parameter ranges of interest. Then, triggering mechanisms of aeroelastic instability is investigated for a two-DOF rigid wing model in subsonic flow with cubic nonlinear stiffnesses at the support. Based on the observation of the instability triggering, a single-degree-of-freedom (SDOF) NES is applied to the wing model. The NES is attached at an offset from the elastic axis for its additional interaction with the pitch mode, as well as being parallel with the heave mode, primarily to hinder initial triggering of the heave mode by the flow. It is shown that it is feasible to partially or even completely suppress aeroelastic instabilities of the wing by passively transferring vibration energy from the wing to the NES in a one-way irreversible fashion. Moreover, this aeroelastic instability suppression is performed by partially or completely eliminating the triggering mechanists for aeroelastic suppression. Through numerical parametric studies three main mechanisms for suppressing aeroelastic instability are identified: (i) Recurring burst-out and suppression; (ii) intermediate suppression; (iii) complete elimination of instability. In general, the relative occurrence of one of the two limit point cycle (LPC) bifurcations with respect to the Hopf bifurcation decides whether or not the suppression mechanisms are robust. In order to improve robustness of instability suppression, several types of multi-DOF NES configurations are introduced. In the last part, experimental suppression of aeroelastic instability by means of targeted energy transfers is investigated. In order to gain insights into the experiments, theoretical triggering mechanism of the aeroelastic instability in the nonlinear aeroelastic test apparatus (NATA) in a low-speed wind tunnel at Texas A&M University is studied. Finally, experimental results are presented in connection to the theoretical investigation, and all the predictions on the instability suppression mechanisms are demonstrated experimentally. It is also revealed that the dry friction affects only the robustness of an instability suppression by changing the unstable trivial equilibrium into an equilibrium set. (Abstract shortened by UMI.)

  20. Unprecedented NES non-antagonistic inhibitor for nuclear export of Rev from Sida cordifolia.

    PubMed

    Tamura, Satoru; Kaneko, Masafumi; Shiomi, Atsushi; Yang, Guang-Ming; Yamaura, Toshiaki; Murakami, Nobutoshi

    2010-03-15

    Bioassay-guided separation from the MeOH extract of the South American medicinal plant Sida cordifolia resulted in isolation of (10E,12Z)-9-hydroxyoctadeca-10,12-dienoic acid (1) as an unprecedented NES non-antagonistic inhibitor for nuclear export of Rev. This mechanism of action was established by competitive experiment by the biotinylated probe derived from leptomycin B, the known NES antagonistic inhibitor. Additionally, structure-activity relationship analysis by use of the synthesized analogs clarified cooperation of several functionalities in the Rev-export inhibitory activity of 1. Copyright 2010 Elsevier Ltd. All rights reserved.

  1. Morbillivirus nucleoprotein possesses a novel nuclear localization signal and a CRM1-independent nuclear export signal

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sato, Hiroki; Masuda, Munemitsu; Miura, Ryuichi

    2006-08-15

    Morbilliviruses, which belong to the Mononegavirales, replicate its RNA genome in the cytoplasm of the host cell. However, they also form characteristic intranuclear inclusion bodies, consisting of nucleoprotein (N), in infected cells. To analyze the mechanisms of nucleocytoplasmic transport of N protein, we characterized the nuclear localization (NLS) and nuclear export (NES) signals of canine distemper virus (CDV) N protein by deletion mutation and alanine substitution of the protein. The NLS has a novel leucine/isoleucine-rich motif (TGILISIL) at positions 70-77, whereas the NES is composed of a leucine-rich motif (LLRSLTLF) at positions 4-11. The NLS and NES of the Nmore » proteins of other morbilliviruses, that is, measles virus (MV) and rinderpest virus (RPV), were also analyzed. The NLS of CDV-N protein is conserved at the same position in MV-N protein, whereas the NES of MV-N protein is located in the C-terminal region. The NES of RPV-N protein is also located at the same position as CDV-N protein, whereas the NLS motif is present not only at the same locus as CDV-N protein but also at other sites. Interestingly, the nuclear export of all these N proteins appears to proceed via a CRM1-independent pathway.« less

  2. A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis

    PubMed Central

    Craig, Errol; Zhang, Zhi-Kai; Davies, Kelvin P.; Kalpana, Ganjam V.

    2002-01-01

    INI1 (integrase interactor 1)/hSNF5 is a component of the mammalian SWI/SNF complex and a tumor suppressor mutated in malignant rhabdoid tumors (MRT). We have identified a nuclear export signal (NES) in the highly conserved repeat 2 domain of INI1 that is unmasked upon deletion of a downstream sequence. Mutation of conserved hydrophobic residues within the NES, as well as leptomycin B treatment abrogated the nuclear export. Full-length INI1 specifically associated with hCRM1/exportin1 in vivo and in vitro. A mutant INI1 [INI1(1–319) delG950] found in MRT lacking the 66 C-terminal amino acids mislocalized to the cytoplasm. Full-length INI1 but not the INI1(1–319 delG950) mutant caused flat cell formation and cell cycle arrest in cell lines derived from MRT. Disruption of the NES in the delG950 mutant caused nuclear localization of the protein and restored its ability to cause cell cycle arrest. These observations demonstrate that INI1 has a masked NES that mediates regulated hCRM1/exportin1-dependent nuclear export and we propose that mutations that cause deregulated nuclear export of the protein could lead to tumorigenesis. PMID:11782423

  3. Natural Environments and Childhood Experiences Promoting Physical Activity, Examining the Mediational Effects of Feelings about Nature and Social Networks.

    PubMed

    Calogiuri, Giovanna

    2016-04-21

    The importance of natural environments (NEs) for physical activity (PA) has been studied extensively. However, there is scant evidence to explain the motivational processes underlying the NE-PA relation. The aim of this study was to investigate the NE-PA relation using an ecological framework, focusing on perception of NEs, childhood experiences and possible intra- and inter-individual mediators. Data were retrieved from a cross-sectional survey among 2168 adults from all over Norway. In addition, the coverage of NEs by municipalities was retrieved from national registers. Logistic regression showed that, unlike the self-reported proximity to NEs, higher ratings of perceived supportiveness of NEs for PA predicted participation in NE-based PA for at least 60 min/week or 150 min/week, before and after controlling for socio-demographic characteristics. Reporting frequent experiences in nature during childhood was also an important predictor of higher levels of NE-based PA. Furthermore, a mediational analysis showed that the effect of both predictors was mediated by "feelings about nature" and "social networks". These findings indicate that to encourage the use of local NE for PA, not only should environmental perceptions be taken into account, positive feelings towards nature alongside opportunities to share activity in nature with others should also be promoted.

  4. Clinically translatable nanotheranostic platforms for peripheral nerve regeneration: design with outcome in mind

    NASA Astrophysics Data System (ADS)

    Janjic, Jelena M.; Gorantla, Vijay S.

    2018-02-01

    Neuroinflammation is a dynamic immune phenomenon that changes in severity with time after neurotrauma and has a profound impact on neuroregeneration, tissue healing and neuropathic pain, which is a common consequence of peripheral nerve injury (PNI). Macrophages are key cellular mediators of neuroinflammation. Macrophage-targeted nanotherapies, such as complex (perfluorocarbon/hydrocarbon) multimodal nanoemulsions (NEs) provide highly specific imaging signatures of neuroinflammation and hence indirect surrogate metrics of regeneration. We present a novel strategy where these NEs incorporating multiple imaging modalities and biosensors are delivered locally to directly target key cellular players of neuroregeneration. Two representative formulations of a nanotheranostic platform for local delivery of cell targeted NEs are presented: 1) A dual (macrophage and neuronal) targeted nanoparticle laden hydrogel for synergistic modulation of neuroinflammation and analgesia following PNI; and 2) neurotherapeutic loaded nanoparticles with extended release profile for sustained support of neuroregeneration. Each platform is capable of dual imaging payloads (NIRF, MRI and/or PET) and/or cell specific targeting moieties for controlled drug release. In vitro and pilot in vivo results will be presented. Theranostic nanosystem based platforms offer a unique opportunity to sequentially monitor cellular and molecular events at the site of neuronal injury, enabling dynamic, in-vivo mechanistic insights rather than static, ex-vivo histopathologic evaluation. Given their targeted capabilities, these platforms can help achieve personalized treatments that are customized and optimized for patients with PNI.

  5. Insecure attachment style as a vulnerability factor for depression: recent findings in a community-based study of Malay single and married mothers.

    PubMed

    Abdul Kadir, Nor Ba'yah; Bifulco, Antonia

    2013-12-30

    The role of marital breakdown in women's mental health is of key concern in Malaysia and internationally. A cross-sectional questionnaire study of married and separated/divorced and widowed women examined insecure attachment style as an associated risk factor for depression among 1002 mothers in an urban community in Malaysia. A previous report replicated a UK-based vulnerability-provoking agent model of depression involving negative evaluation of self (NES) and negative elements in close relationships (NECRs) interacting with severe life events to model depression. This article reports on the additional contribution of insecure attachment style to the model using the Vulnerable Attachment Style Questionnaire (VASQ). The results showed that VASQ scores were highly correlated with NES, NECR and depression. A multiple regression analysis of depression with backward elimination found that VASQ scores had a significant additional effect. Group comparisons showed different risk patterns for single and married mothers. NES was the strongest risk factor for both groups, with the 'anxious style' subset of the VASQ being the best additional predictor for married mothers and the total VASQ score (general attachment insecurity) for single mothers. The findings indicate that attachment insecurity adds to a psychosocial vulnerability model of depression among mothers cross-culturally and is important in understanding and identifying risk. © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals.

    PubMed

    Fung, Ho Yee Joyce; Fu, Szu-Chin; Chook, Yuh Min

    2017-03-10

    Nuclear export receptor CRM1 binds highly variable nuclear export signals (NESs) in hundreds of different cargoes. Previously we have shown that CRM1 binds NESs in both polypeptide orientations (Fung et al., 2015). Here, we show crystal structures of CRM1 bound to eight additional NESs which reveal diverse conformations that range from loop-like to all-helix, which occupy different extents of the invariant NES-binding groove. Analysis of all NES structures show 5-6 distinct backbone conformations where the only conserved secondary structural element is one turn of helix that binds the central portion of the CRM1 groove. All NESs also participate in main chain hydrogen bonding with human CRM1 Lys568 side chain, which acts as a specificity filter that prevents binding of non-NES peptides. The large conformational range of NES backbones explains the lack of a fixed pattern for its 3-5 hydrophobic anchor residues, which in turn explains the large array of peptide sequences that can function as NESs.

  7. NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1.

    PubMed

    Güttler, Thomas; Madl, Tobias; Neumann, Piotr; Deichsel, Danilo; Corsini, Lorenzo; Monecke, Thomas; Ficner, Ralf; Sattler, Michael; Görlich, Dirk

    2010-11-01

    Classic nuclear export signals (NESs) confer CRM1-dependent nuclear export. Here we present crystal structures of the RanGTP-CRM1 complex alone and bound to the prototypic PKI or HIV-1 Rev NESs. These NESs differ markedly in the spacing of their key hydrophobic (Φ) residues, yet CRM1 recognizes them with the same rigid set of five Φ pockets. The different Φ spacings are compensated for by different conformations of the bound NESs: in the case of PKI, an α-helical conformation, and in the case of Rev, an extended conformation with a critical proline docking into a Φ pocket. NMR analyses of CRM1-bound and CRM1-free PKI NES suggest that CRM1 selects NES conformers that pre-exist in solution. Our data lead to a new structure-based NES consensus, and explain why NESs differ in their affinities for CRM1 and why supraphysiological NESs bind the exportin so tightly.

  8. Transdermal water-in-oil nanocarriers of nitric oxide for triggering penile erection.

    PubMed

    Nam, Eunryel; Yoo, Saejong; Kim, Hwi-Yool; Kim, Young-Rok; Heo, Yun Jung

    2018-05-09

    Men's sexual health can have significant effects on a man's self-esteem, sexual relationship and male reproductive functions. Although commercially available drugs (e.g., VIAGRA and CIALIS) show effective treatment of erectile dysfunction (ED), patients with severe ED fail to respond to these medicines. Topical nitric-oxide (NO) delivery to penis can be a painless, alternative solution with severe ED because NO triggers erection and diffuses to the trabecular arteries and smooth muscles in the penis. We here develop water-in-oil (W/O) nanoemulsions (NEs) that contain NO and can directly spread on the penis. We optimize NE formation conditions including hydrophilic-lipophilic balance (HLB) and ratio of oil, water and surfactants. Then, by spreading NEs on penis skin of intact middle aged dogs, we verify medication effects and safety of the NEs in vivo. The water-in-oil NEs can be a promising non-invasive medication for ED patients with low response to a phosphodiesterase type 5 (PDE5) inhibitor, thus increasing quality of life in the aging society.

  9. Impact on hepatic estrogen-sensitive proteins by a 1-year contraceptive vaginal ring delivering Nestorone® and ethinyl estradiol.

    PubMed

    Archer, D F; Thomas, M A; Conard, J; Merkatz, R B; Creasy, G W; Roberts, K; Plagianos, M; Blithe, D; Sitruk-Ware, R

    2016-01-01

    Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vaginal ring (CVR) delivering 150mcg Nestorone® (NES) and 15mcg ethinyl estradiol (EE). A substudy of the Contraceptive Clinical Trials Network of the National Institute of Child Health and Human Development enrolled 129 participants, with assessments of factor VIII, fibrinogen, protein S (PS) and sex hormone binding globulin (SHBG). Thirty-six participants had used combined hormonal contraceptives (CHCs) in the cycle preceding first CVR use (recent users) and 70 had no history of recent use (nonusers). Mean values at baseline were within the normal range for all four proteins but were higher for factor VIII, fibrinogen and SHBG and significantly lower for PS in recent compared to nonusers. During NES/EE CVR use, factor VIII, fibrinogen and PS were within the normal range; however, SHBG levels were increased by nearly 100% at Cycle 13. The change from baseline to final evaluation was statistically significant for all proteins in nonusers. The change in recent users was significant for factor VIII at Cycle 6 and for SHBG at Cycles 6 and 13, but not for PS or fibrinogen. NES/EE CVR for up to 13cycles was associated with changes from baseline in plasma levels of factor VIII, fibrinogen and PS that were within the normal range, with SHBG levels above the normal range by Cycle 6. Nonusers of CHC before CVR showed wider changes in values versus recent users whose baseline values were increased by previous EE exposure. Recent use of CHCs demonstrated significant changes in all four measured hepatic proteins at baseline compared to nonusers. Use of the NES/EE CVR further changed these hepatic protein markers, but values remained within the normal range. Prebaseline exposure to estrogen can obscure interpretation of hepatic proteins changes associated with a second CHC. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Natural Environments and Childhood Experiences Promoting Physical Activity, Examining the Mediational Effects of Feelings about Nature and Social Networks

    PubMed Central

    Calogiuri, Giovanna

    2016-01-01

    The importance of natural environments (NEs) for physical activity (PA) has been studied extensively. However, there is scant evidence to explain the motivational processes underlying the NE-PA relation. The aim of this study was to investigate the NE-PA relation using an ecological framework, focusing on perception of NEs, childhood experiences and possible intra- and inter-individual mediators. Data were retrieved from a cross-sectional survey among 2168 adults from all over Norway. In addition, the coverage of NEs by municipalities was retrieved from national registers. Logistic regression showed that, unlike the self-reported proximity to NEs, higher ratings of perceived supportiveness of NEs for PA predicted participation in NE-based PA for at least 60 min/week or 150 min/week, before and after controlling for socio-demographic characteristics. Reporting frequent experiences in nature during childhood was also an important predictor of higher levels of NE-based PA. Furthermore, a mediational analysis showed that the effect of both predictors was mediated by “feelings about nature” and “social networks”. These findings indicate that to encourage the use of local NE for PA, not only should environmental perceptions be taken into account, positive feelings towards nature alongside opportunities to share activity in nature with others should also be promoted. PMID:27110802

  11. Characterization of Nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction

    PubMed Central

    Jiang, Mei Hua; Cai, Bing; Tuo, Ying; Wang, Jiancheng; Zang, Zhi Jun; Tu, Xiang'an; Gao, Yong; Su, Zhijian; Li, Weiqiang; Li, Guilan; Zhang, Min; Jiao, Jianwei; Wan, Zi; Deng, Chunhua; Lahn, Bruce T; Xiang, Andy Peng

    2014-01-01

    The ability to identify and isolate lineage-specific stem cells from adult tissues could facilitate cell replacement therapy. Leydig cells (LCs) are the primary source of androgen in the mammalian testis, and the prospective identification of stem Leydig cells (SLCs) may offer new opportunities for treating testosterone deficiency. Here, in a transgenic mouse model expressing GFP driven by the Nestin (Nes) promoter, we observed Nes-GFP+ cells located in the testicular interstitial compartment where SLCs normally reside. We showed that these Nes-GFP+ cells expressed LIFR and PDGFR-α, but not LC lineage markers. We further observed that these cells were capable of clonogenic self-renewal and extensive proliferation in vitro and could differentiate into neural or mesenchymal cell lineages, as well as LCs, with the ability to produce testosterone, under defined conditions. Moreover, when transplanted into the testes of LC-disrupted or aging models, the Nes-GFP+ cells colonized the interstitium and partially increased testosterone production, and then accelerated meiotic and post-meiotic germ cell recovery. In addition, we further demonstrated that CD51 might be a putative cell surface marker for SLCs, similar with Nestin. Taken together, these results suggest that Nes-GFP+ cells from the testis have the characteristics of SLCs, and our study would shed new light on developing stem cell replacement therapy for testosterone deficiency. PMID:25418539

  12. Relative Performance of English Second Language Students in University Accounting Courses

    ERIC Educational Resources Information Center

    Wagner, Robin M.; Huang, Jiunn C.

    2011-01-01

    This paper explores the relative performances of Native English Speaking ("NES") students and English Second Language ("ESL") students in accounting courses at a large urban state university. Based upon a longitudinal study, we conclude that the relative performance between NES and ESL students depends upon the particular…

  13. Development of an Online Climate and Fisheries Data Dashboard for Stakeholders in the Northeast Shelf Large Marine Ecosystem

    NASA Astrophysics Data System (ADS)

    Young Morse, R.

    2016-12-01

    Fisheries managers make decisions that shape the future of ecosystems and the communities that depend on them. These decisions are often made without reference to environmental conditions, or are made assuming that past conditions (physical conditions, productivity, and species distributions) will persist. The rapid changes experienced in the Northeast Shelf Large Marine Ecosystem (NES LME), as well as the high degree of natural variability in this system, are prompting new discussions about how to incorporate environmental information into fisheries policy and management and into the industry. Through this project, we are facilitating access to fisheries and climate data for fisheries stakeholders in the Northeast through the creation of an online dynamic data dashboard. The primary goal is to make complex climate-relevant data accessible and easy to understand. Information on past, present, and future environmental conditions in the NES LME are presented in the context of fisheries dependent data. Working with marine fisheries stakeholders, including fisheries management council members, industry leaders and non-profits, we have developed a suite of open source processes and tools to acquire and subset climate relevant data from a variety of sources (satellites, sensors, models), develop long range climatologies, and display through dynamically updated interactive data visualizations. The resulting dashboard allows users to quickly assess conditions in the ocean and evaluate them in the context of past and projected change.

  14. A Generic Framework of Performance Measurement in Networked Enterprises

    NASA Astrophysics Data System (ADS)

    Kim, Duk-Hyun; Kim, Cheolhan

    Performance measurement (PM) is essential for managing networked enterprises (NEs) because it greatly affects the effectiveness of collaboration among members of NE.PM in NE requires somewhat different approaches from PM in a single enterprise because of heterogeneity, dynamism, and complexity of NE’s. This paper introduces a generic framework of PM in NE (we call it NEPM) based on the Balanced Scorecard (BSC) approach. In NEPM key performance indicators and cause-and-effect relationships among them are defined in a generic strategy map. NEPM could be applied to various types of NEs after specializing KPIs and relationships among them. Effectiveness of NEPM is shown through a case study of some Korean NEs.

  15. Using LOTOS for Formalizing Wireless Sensor Network Applications

    PubMed Central

    Rosa, Nelson Souto; Cunha, Paulo Roberto Freire

    2007-01-01

    The number of wireless sensor network (WSN) applications is rapidly increasing and becoming an integral part of sensor nodes. These applications have been widely developed on TinyOS operating system using the nesC programming language. However, due to the tight integration to physical world, limited node power and resources (CPU and memory) and complexity of combining components into an application, to build such applications is not a trivial task. In this context, we present an approach for treating with this complexity adopting a formal description technique, namely LOTOS, for formalising the WSN applications ‘behaviour. The formalisation has three main benefits: better understanding on how the application actually works, checking of desired properties of the application's behaviour, and simulation facilities. In order to illustrate the proposed approach, we apply it to two nesC traditional applications, namely BLink and Sense.

  16. Chinese Students' Perceptions of Native English-Speaking Teachers in EFL Teaching

    ERIC Educational Resources Information Center

    Rao, Zhenhui

    2010-01-01

    The article reports the views of 20 Chinese English as a foreign Language (EFL) students on the strengths and weaknesses of native English-speaking (NES) teachers in EFL teaching. Responding to an open-ended questionnaire and in-depth interviews, EFL students named the following as NES teachers' strengths: native language authenticity, cultural…

  17. Binge Eating Disorder and Night Eating Syndrome: A Comparative Study of Disordered Eating

    ERIC Educational Resources Information Center

    Allison, Kelly C.; Grilo, Carlos M.; Masheb, Robin M.; Stunkard, Albert J.

    2005-01-01

    The authors compared eating patterns, disordered eating, features of eating disorders, and depressive symptoms in persons with binge eating disorder (BED; n = 177), with night eating syndrome (NES; n = 68), and in an overweight comparison group without BED or NES (comparison; n = 45). Participants completed semistructured interviews and several…

  18. Development of criteria for a diagnosis: lessons from the night eating syndrome

    PubMed Central

    Stunkard, Albert J.; Allison, Kelly C.; Geliebter, Allan; Lundgren, Jennifer D.; Gluck, Marci E.; O’Reardon, John P.

    2013-01-01

    Criteria for inclusion of diagnoses of Axis I disorders in the forthcoming Diagnostic and Statistical Manual (DSM-V) of the American Psychiatric Association are being considered. The 5 criteria that were proposed by Blashfield et al as necessary for inclusion in DSM-IV are reviewed and are met by the night eating syndrome (NES). Seventy-seven publications in refereed journals in the last decade indicate growing recognition of NES. Two core diagnostic criteria have been established: evening hyperphagia (consumption of at least 25% of daily food intake after the evening meal) and/or the presence of nocturnal awakenings with ingestions. These criteria have been validated in studies that used self-reports, structured interviews, and symptom scales. Night eating syndrome can be distinguished from binge eating disorder and sleep-related eating disorder. Four additional features attest to the usefulness of the diagnosis of NES: (1) its prevalence, (2) its association with obesity, (3) its extensive comorbidity, and (4) its biological aspects. In conclusion, research on NES supports the validity of the diagnosis and its inclusion in DSM-V. PMID:19683608

  19. Active nuclear import and passive nuclear export are the primary determinants of TDP-43 localization.

    PubMed

    Pinarbasi, Emile S; Cağatay, Tolga; Fung, Ho Yee Joyce; Li, Ying C; Chook, Yuh Min; Thomas, Philip J

    2018-05-04

    ALS (Amyotrophic Lateral Sclerosis) is a neurodegenerative disease characterized by the redistribution of the RNA binding protein TDP-43 in affected neurons: from predominantly nuclear to aggregated in the cytosol. However, the determinants of TDP-43 localization and the cellular insults that promote redistribution are incompletely understood. Here, we show that the putative Nuclear Export Signal (NES) is not required for nuclear egress of TDP-43. Moreover, when the TDP-43 domain which contains the putative NES is fused to a reporter protein, YFP, the presence of the NES is not sufficient to mediate nuclear exclusion of the fusion protein. We find that the previously studied "∆NES" mutant, in which conserved hydrophobic residues are mutated to alanines, disrupts both solubility and splicing function. We further show that nuclear export of TDP-43 is independent of the exportin XPO1. Finally, we provide evidence that nuclear egress of TDP-43 is size dependent; nuclear export of dTomato TDP-43 is significantly impaired compared to Flag TDP-43. Together, these results suggest nuclear export of TDP-43 is predominantly driven by passive diffusion.

  20. Processing of Nonconjugative Resistance Plasmids by Conjugation Nicking Enzyme of Staphylococci

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pollet, Rebecca M.; Ingle, James D.; Hymes, Jeff P.

    Antimicrobial resistance inStaphylococcus aureuspresents an increasing threat to human health. This resistance is often encoded on mobile plasmids, such as pSK41; however, the mechanism of transfer of these plasmids is not well understood. In this study, we first examine key protein-DNA interactions formed by the relaxase enzyme, NES, which initiates and terminates the transfer of the multidrug resistance plasmid pSK41. Two loops on the NES protein, hairpin loops 1 and 2, form extensive contacts with the DNA hairpin formed at theoriTregion of pSK41, and here we establish that these contacts are essential for proper DNA cleavage and religation by themore » full 665-residue NES proteinin vitro. Second, pSK156 and pCA347 are nonconjugativeStaphylococcus aureusplasmids that contain sequences similar to theoriTregion of pSK41 but differ in the sequence predicted to form a DNA hairpin. We show that pSK41-encoded NES is able to bind, cleave, and religate theoriTsequences of these nonconjugative plasmidsin vitro. Although pSK41 could mobilize a coresident plasmid harboring its cognateoriT, it was unable to mobilize plasmids containing the pSK156 and pCA347 variantoriTmimics, suggesting that an accessory protein like that previously shown to confer specificity in the pWBG749 system may also be involved in transmission of plasmids containing a pSK41-likeoriT. These data indicate that the conjugative relaxase intransmechanism recently described for the pWBG749 family of plasmids also applies to the pSK41 family of plasmids, further heightening the potential significance of this mechanism in the horizontal transfer of staphylococcal plasmids. IMPORTANCEUnderstanding the mechanism of antimicrobial resistance transfer in bacteria such asStaphylococcus aureusis an important step toward potentially slowing the spread of antimicrobial-resistant infections. This work establishes protein-DNA interactions essential for the transfer of theStaphylococcus aureusmultiresistance plasmid pSK41 by its relaxase, NES. This enzyme also processed variantoriT-like sequences found on numerous plasmids previously considered nontransmissible, suggesting that in conjunction with an uncharacterized accessory protein, these plasmids may be transferred horizontally via a relaxase intransmechanism. These findings have important implications for our understanding of staphylococcal resistance plasmid evolution.« less

  1. Identification of a Signal-Responsive Nuclear Export Sequence in Class II Histone Deacetylases

    PubMed Central

    McKinsey, Timothy A.; Zhang, Chun Li; Olson, Eric N.

    2001-01-01

    Activation of muscle-specific genes by the MEF2 transcription factor is inhibited by class II histone deacetylases (HDACs) 4 and 5, which contain carboxy-terminal deacetylase domains and amino-terminal extensions required for association with MEF2. The inhibitory action of HDACs is overcome by myogenic signals which disrupt MEF2-HDAC interactions and stimulate nuclear export of these transcriptional repressors. Nucleocytoplasmic trafficking of HDAC5 is mediated by binding of the chaperone protein 14-3-3 to two phosphoserine residues (Ser-259 and Ser-498) in its amino-terminal extension. Here we show that HDAC4 and -5 each contain a signal-responsive nuclear export sequence (NES) at their extreme carboxy termini. The NES is conserved in another class II HDAC, HDAC7, but is absent in class I HDACs and the HDAC-related corepressor, MEF2-interacting transcription repressor. Our results suggest that this conserved NES is inactive in unphosphorylated HDAC5, which is localized to the nucleus, and that calcium-calmodulin-dependent protein kinase (CaMK)-dependent binding of 14-3-3 to phosphoserines 259 and 498 activates the NES, with consequent export of the transcriptional repressor to the cytoplasm. A single amino acid substitution in this NES is sufficient to retain HDAC5 in the nucleus in the face of CaMK signaling. These findings provide molecular insight into the mechanism by which extracellular cues alter chromatin structure to promote muscle differentiation and other MEF2-regulated processes. PMID:11509672

  2. H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair

    PubMed Central

    Carotenuto, Felicia; Khashoggi, Haneen A.; Nanni, Francesca; Melino, Sonia

    2016-01-01

    The improvement of solubility and/or dissolution rate of poorly soluble natural compounds is an ideal strategy to make them optimal candidates as new potential drugs. Accordingly, the allyl sulfur compounds and omega-3 fatty acids are natural hydrophobic compounds that exhibit two important combined properties: cardiovascular protection and antitumor activity. Here, we have synthesized and characterized a novel formulation of diallyl disulfide (DADS) and α-linolenic acid (ALA) as protein-nanoemulsions (BAD-NEs), using ultrasounds. BAD-NEs are stable over time at room temperature and show antioxidant and radical scavenging property. These NEs are also optimal H2S slow-release donors and show a significant anti-proliferative effect on different human cancer cell lines: MCF-7 breast cancer and HuT 78 T-cell lymphoma cells. BAD-NEs are able to regulate the ERK1/2 pathway, inducing apoptosis and cell cycle arrest at the G0/G1 phase. We have also investigated their effect on cell proliferation of human adult stem/progenitor cells. Interestingly, BAD-NEs are able to improve the Lin– Sca1+ human cardiac progenitor cells (hCPC) proliferation. This stem cell growth stimulation is combined with the expression and activation of proteins involved in tissue-repair, such as P-AKT, α-sma and connexin 43. Altogether, our results suggest that these antioxidant nanoemulsions might have potential application in selective cancer therapy and for promoting the muscle tissue repair. PMID:27741519

  3. Sequence and structural analyses of nuclear export signals in the NESdb database

    PubMed Central

    Xu, Darui; Farmer, Alicia; Collett, Garen; Grishin, Nick V.; Chook, Yuh Min

    2012-01-01

    We compiled >200 nuclear export signal (NES)–containing CRM1 cargoes in a database named NESdb. We analyzed the sequences and three-dimensional structures of natural, experimentally identified NESs and of false-positive NESs that were generated from the database in order to identify properties that might distinguish the two groups of sequences. Analyses of amino acid frequencies, sequence logos, and agreement with existing NES consensus sequences revealed strong preferences for the Φ1-X3-Φ2-X2-Φ3-X-Φ4 pattern and for negatively charged amino acids in the nonhydrophobic positions of experimentally identified NESs but not of false positives. Strong preferences against certain hydrophobic amino acids in the hydrophobic positions were also revealed. These findings led to a new and more precise NES consensus. More important, three-dimensional structures are now available for 68 NESs within 56 different cargo proteins. Analyses of these structures showed that experimentally identified NESs are more likely than the false positives to adopt α-helical conformations that transition to loops at their C-termini and more likely to be surface accessible within their protein domains or be present in disordered or unobserved parts of the structures. Such distinguishing features for real NESs might be useful in future NES prediction efforts. Finally, we also tested CRM1-binding of 40 NESs that were found in the 56 structures. We found that 16 of the NES peptides did not bind CRM1, hence illustrating how NESs are easily misidentified. PMID:22833565

  4. Dynamically orthogonal field equations for stochastic flows and particle dynamics

    DTIC Science & Technology

    2011-02-01

    where uncertainty ‘lives’ as well as a system of Stochastic Di erential Equations that de nes how the uncertainty evolves in the time varying stochastic ... stochastic dynamical component that are both time and space dependent, we derive a system of field equations consisting of a Partial Differential Equation...a system of Stochastic Differential Equations that defines how the stochasticity evolves in the time varying stochastic subspace. These new

  5. Children and the Nintendo.

    ERIC Educational Resources Information Center

    Keller, Suzanne M.

    The four reports contained in this document examine the effects of the Nintendo Entertainment System (NES), which entered the lives of many children in the United States in 1986. The first report discusses a study of children's interaction with the game hardware. The study of fourth- and fifth-grade students indicated that children's interaction…

  6. Generation of the neutron response function of an NE213 scintillator for fusion applications

    NASA Astrophysics Data System (ADS)

    Binda, F.; Eriksson, J.; Ericsson, G.; Hellesen, C.; Conroy, S.; Nocente, M.; Sundén, E. Andersson; JET Contributors

    2017-09-01

    In this work we present a method to evaluate the neutron response function of an NE213 liquid scintillator. This method is particularly useful when the proton light yield function of the detector has not been measured, since it is based on a proton light yield function taken from literature, MCNPX simulations, measurements of gamma-rays from a calibration source and measurements of neutrons from fusion experiments with ohmic plasmas. The inclusion of the latter improves the description of the proton light yield function in the energy range of interest (around 2.46 MeV). We apply this method to an NE213 detector installed at JET, inside the radiation shielding of the magnetic proton recoil (MPRu) spectrometer, and present the results from the calibration along with some examples of application of the response function to perform neutron emission spectroscopy (NES) of fusion plasmas. We also investigate how the choice of the proton light yield function affects the NES analysis, finding that the result does not change significantly. This points to the fact that the method for the evaluation of the neutron response function is robust and gives reliable results.

  7. Bringing School-to-Work to Scale: What Employers Report.

    ERIC Educational Resources Information Center

    Consortium for Policy Research in Education, Philadelphia, PA.

    In summer 1997, the National Employer Survey (NES-II) was administered as a telephone survey to 6,971 private employers with more than 20 employees. The response rate was 78%. Two versions of the survey--one for manufacturing establishments and one for nonmanufacturing industries--were used. According to the NES-II, roughly 25% of establishments…

  8. 76 FR 8391 - Self-Regulatory Organizations; NASDAQ OMX BX LLC; Notice of Filing of Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-14

    ... BX and NES Inbound Routing Relationship February 7, 2011. Pursuant to Section 19(b)(1) of the... Commission seeking permanent approval of the BX and NES routing relationship.\\7\\ The Exchange hereby seeks... relationship on a pilot basis. During this pilot period, BX committed to the following conditions: 1. The...

  9. Developing and testing the nurse educator scale: a robust measure of students' intentions to pursue an educator role.

    PubMed

    Abou Samra, Haifa; McGrath, Jacqueline M; Estes, Tracy

    2013-06-01

    No instrument exists that measures student perceptions of the faculty role. Such a measure is necessary to evaluate the efficacy of interventions aimed at attracting students to the faculty career path. We developed the Nurse Educator Scale (NES). The initial scale items were generated using the social cognitive career theory (SCCT) constructs and were reviewed by an expert panel to ensure content validity. Exploratory factor analysis was used. The optimized 25-item, 7-point Likert scale has a Cronbach's alpha reliability coefficient of 0.85, with a total variance of 42%. The underlying factor structure supported three defining characteristics congruent with SCCT: outcome expectations (alpha = 0.79), relevant knowledge (alpha = 0.67), and social influence (alpha = 0.80). A stand-alone, item-measuring goal setting was also supported. The NES provides a valid and reliable measure of students' intentions and motivations to pursue a future career as a nurse educator or scientist. Copyright 2013, SLACK Incorporated.

  10. Knowledge of healthy foods does not translate to healthy snack consumption among exercise science undergraduates.

    PubMed

    McArthur, Laura H; Valentino, Antonette; Holbert, Donald

    2017-06-01

    This cross-sectional survey study compared the on- and off-campus snack choices and related correlates of convenience samples of exercise science (ES) ( n = 165, M = 45%, F = 55%) and non-exercise science (NES) ( n =160, M = 43%, F = 57%) undergraduates. The hypothesis posed was that knowledge of healthy foods will not translate to healthier snack consumption by the ES students, and that the snack choices and related correlates of ES and NES students will be similar. Data were collected using self-administered questionnaires completed in classrooms (ES sample) and at high-traffic locations on-campus (NES sample). Chi-square and t-test analyses compared ES and NES students on snack correlates. Snacks consumed most often by the ES and NES students on-campus were health bars/squares ( n = 56 vs. n = 48) and savory snacks ( n = 55 vs. n = 71), and off-campus were savory snacks ( n = 60 vs. n = 71) and fruits ( n = 41 vs. n = 34). Over half of both samples believed their snack choices were a mix of unhealthy and healthy. Fruits were considered healthier snacks and chips less healthy by both samples, and fruits were the most often recommended snack. About 20% believed these choices would impact their health unfavorably, and about two thirds self-classified in the action stages for healthy snacking. Since knowledge about healthy food choices did not translate to healthy snack selection, these students would benefit from interventions that teach selection and preparation of healthy snacks on a restricted budget.

  11. Conditional loss of progranulin in neurons is not sufficient to cause neuronal ceroid lipofuscinosis-like neuropathology in mice.

    PubMed

    Petkau, Terri L; Blanco, Jake; Leavitt, Blair R

    2017-10-01

    Progranulin deficiency due to heterozygous null mutations in the GRN gene is a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations cause neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. Progranulin is a secreted glycoprotein expressed in both neurons and microglia, but not astrocytes, in the brain. We generated conditional progranulin-knockout mice that lack progranulin in nestin-expressing cells (Nes-cKO mice), which include most neurons as well as astrocytes. We confirmed near complete knockout of progranulin in neurons in Nes-cKO mice, while microglial progranulin levels remained similar to that of wild-type animals. Overall brain progranulin levels were reduced by about 50% in Nes-cKO, and no Grn was detected in primary Nes-cKO neurons. Nes-cKO mice aged to 12months did not display any increase in lipofuscin deposition, microgliosis, or astrogliosis in the four brain regions examined, though increases were observed for most of these measures in Grn-null animals. We conclude that neuron-specific loss of progranulin is not sufficient to cause similar neuropathological changes to those seen in constitutive Grn-null animals. Our results suggest that increased lipofuscinosis and gliosis in Grn-null animals are not caused by intrinsic progranulin deficiency in neurons, and that microglia-derived progranulin may be sufficient to maintain neuronal health and homeostasis in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The Application of Fishbone Diagram Analysis to Improve School Quality

    ERIC Educational Resources Information Center

    Slameto

    2016-01-01

    With the enactment of the National Education Standards (NES), the measurement of the school quality was clear; NES became a reference for school development program to improve the school quality. However, the form of the program that exist still in problematic, so that a good proposal need to be prepared. In the real condition, the school shows,…

  13. Dissemination of Election Returns Information: The News Election Service during Election 1980.

    ERIC Educational Resources Information Center

    Garrison, Bruce

    In 1964, the Associated Press, ABC News, CBS News, NBC News, and United Press International formed a consortium called the News Election Service (NES) that was designed to collect one set of election returns for the entire United States. A study was made of NES operations during the presidential election year of 1980 to determine (1) the nature of…

  14. Teaching Experiences of Native and Nonnative English-Speaking Graduate Teaching Assistants and Their Perceptions of Preservice Teachers

    ERIC Educational Resources Information Center

    Ates, B.; Eslami, Z. R.

    2012-01-01

    The authors report on a qualitative multiple case study exploring the perceptions of nonnative English-speaking (NNES) and native English-speaking (NES) graduate teaching assistants (GTAs) toward undergraduate preservice teachers at a university located in the Southwestern United States. Three NNES GTAs and one NES GTA participated in the study.…

  15. Shades of Cosmopolitanism: EFL Teachers' Perspectives on English Accents and Pronunciation Teaching in the Gulf

    ERIC Educational Resources Information Center

    Buckingham, Louisa

    2015-01-01

    Research suggests that passing for a native English speaker (NES) is often perceived as desirable by teachers of English as a Foreign Language (EFL) and employers, and students may claim to prefer certain NES accents as learning models. While this may be partly motivated by the prevalence of a particular regional accent in ESL contexts or…

  16. Inverse gene-for-gene interactions contribute additively to tan spot susceptibility in wheat

    USDA-ARS?s Scientific Manuscript database

    Tan spot of wheat, caused by Pyrenophora tritici-repentis, is an important disease in almost all wheat-growing areas of the world. The disease system is known to involve at least three fungal-produced necrotrophic effectors (NEs) that interact with corresponding host sensitivity (S) genes in an inv...

  17. Expert System Design Aid for Applications of Human Factors in Robotics.

    DTIC Science & Technology

    1986-06-12

    user and formulate an intelligent response. This need for English fluency has spurred the development of commercially available natural language...1.5.7) Those aspects of a copo- . Critical controls cement he cats "go" condition . (2.1.5.1) * Searing Conservation Program nes t t hat could

  18. Delivery, Student Engagement and the Implementation of Good Practice in Entrepreneurship Education: Learning from the UK's New Entrepreneur Scholarship Initiative

    ERIC Educational Resources Information Center

    Lam, Wing

    2010-01-01

    This paper presents and discusses the results of a research-informed teaching project carried out to identify key factors in the content and delivery of a successful UK government initiative, the New Entrepreneur Scholarship (NES), from 2001 to 2008. The aim of the project was to evaluate the feasibility of implementing appropriate changes to…

  19. Anatomical characteristics of teats and premilking bacterial counts of teat skin swabs of primiparous cows exposed to different types of bedding.

    PubMed

    Guarín, J F; Baumberger, C; Ruegg, P L

    2017-02-01

    Bacterial populations of teat skin are associated with risk of intramammary infection and may be influenced by anatomical characteristics of teats. The objective of this study was to evaluate associations of selected anatomical characteristics of teats with bacterial counts of teat skin of cows exposed to different types of bedding. Primarily primiparous Holstein cows (n = 128) were randomly allocated to 4 pens within a single barn. Each pen contained 1 type of bedding [new sand (NES), recycled sand (RS), deep-bedded manure solids (DBMS), and shallow-bedded manure solids over foam core mattresses (SBMS)]. During a single farm visit udders (n = 112) were scored for hygiene and 1 front (n = 112) and 1 rear teat (n = 111) of each enrolled cow were scored for hyperkeratosis (HK). Teat length, teat barrel diameter, and teat apex diameter were measured and teat skin swabs were systematically collected for microbiological analysis. Linear type evaluation data for udders of each cow were retrieved for each cow. Teat position (front or rear) was associated with occurrence of clinical mastitis during the 12 mo before the farm visit and more cases occurred in front quarters. The proportion of udders that were classified as clean (score 1 or 2) was 68, 82, 54, and 95% for cows housed in pens containing NES, RS, SBMS, and DBMS, respectively. No association was found between HK score and teat position and no association was found between HK score and teat skin bacterial count. Bacterial counts of teat skin swabs from front teats of cows in pens containing RS and SBMS were significantly less than those of rear teats of cows in pens containing DBMS or NES. Teat skin bacterial counts were significantly greater for swabs obtained from teats of cows with udder hygiene scores of 3 and 4 as compared with swabs obtained from cows with cleaner udders. Of all udder conformation traits evaluated, only narrower rear teat placement was positively associated with bacterial counts on teat skin. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Gain and Loss of Fruit Flavor Compounds Produced by Wild and Cultivated Strawberry Species

    PubMed Central

    Aharoni, Asaph; Giri, Ashok P.; Verstappen, Francel W.A.; Bertea, Cinzia M.; Sevenier, Robert; Sun, Zhongkui; Jongsma, Maarten A.; Schwab, Wilfried; Bouwmeester, Harro J.

    2004-01-01

    The blends of flavor compounds produced by fruits serve as biological perfumes used to attract living creatures, including humans. They include hundreds of metabolites and vary in their characteristic fruit flavor composition. The molecular mechanisms by which fruit flavor and aroma compounds are gained and lost during evolution and domestication are largely unknown. Here, we report on processes that may have been responsible for the evolution of diversity in strawberry (Fragaria spp) fruit flavor components. Whereas the terpenoid profile of cultivated strawberry species is dominated by the monoterpene linalool and the sesquiterpene nerolidol, fruit of wild strawberry species emit mainly olefinic monoterpenes and myrtenyl acetate, which are not found in the cultivated species. We used cDNA microarray analysis to identify the F. ananassa Nerolidol Synthase1 (FaNES1) gene in cultivated strawberry and showed that the recombinant FaNES1 enzyme produced in Escherichia coli cells is capable of generating both linalool and nerolidol when supplied with geranyl diphosphate (GPP) or farnesyl diphosphate (FPP), respectively. Characterization of additional genes that are very similar to FaNES1 from both the wild and cultivated strawberry species (FaNES2 and F. vesca NES1) showed that only FaNES1 is exclusively present and highly expressed in the fruit of cultivated (octaploid) varieties. It encodes a protein truncated at its N terminus. Green fluorescent protein localization experiments suggest that a change in subcellular localization led to the FaNES1 enzyme encountering both GPP and FPP, allowing it to produce linalool and nerolidol. Conversely, an insertional mutation affected the expression of a terpene synthase gene that differs from that in the cultivated species (termed F. ananassa Pinene Synthase). It encodes an enzyme capable of catalyzing the biosynthesis of the typical wild species monoterpenes, such as α-pinene and β-myrcene, and caused the loss of these compounds in the cultivated strawberries. The loss of α-pinene also further influenced the fruit flavor profile because it was no longer available as a substrate for the production of the downstream compounds myrtenol and myrtenyl acetate. This phenomenon was demonstrated by cloning and characterizing a cytochrome P450 gene (Pinene Hydroxylase) that encodes the enzyme catalyzing the C10 hydroxylation of α-pinene to myrtenol. The findings shed light on the molecular evolutionary mechanisms resulting in different flavor profiles that are eventually selected for in domesticated species. PMID:15522848

  1. Nonepileptic seizures in the pediatric population: A qualitative study of patient and family experiences.

    PubMed

    McWilliams, Andrew; Reilly, Colin; McFarlane, Fiona A; Booker, Emily; Heyman, Isobel

    2016-06-01

    The objective of this study was to characterize the experience of nonepileptic seizures (NES) in young people (0-19years) and their families, referred to a UK specialist (tertiary) pediatric hospital. The topics investigated include: accessing healthcare, how the diagnosis was first explained, impact on home life and school, coping strategies, and ideas about naming and causes. Ten young people with NES and 29 family members took part in focus groups and telephone interviews. The data generated were analyzed qualitatively with thematic analysis. Six themes were identified from participant experiences: upset and afraid, missing out, feeling misunderstood, confusion and uncertainty, less than epilepsy, and making sense and moving on. Participants described severe disruption to multiple domains of functioning at home, educationally, and in social activities. Young people felt guilty but also overprotected, while family members felt that they were failing as parents. The journey to diagnosis and treatment was seen as unnecessarily tortuous, with access to care and treatment pathways poorly defined. Participants described feeling that a wide variety of professionals did not believe their experiences, showed pejorative attitudes, and left them feeling isolated and marginalized. The young people and family members found NES a difficult disorder to understand and sometimes could not differentiate it from epilepsy. Epilepsy was used as a benchmark for several comparisons, including highlighting the lack of support for and information about NES. Families disliked being told that it was "good news" that their child did not have epilepsy and questioned if their child should be present during initial diagnostic discussions. Participants described stressful situations as a common trigger for NES. Young people showed ambivalence towards the need to understand the condition or the choice of name used for it, whereas family members considered this crucial for achieving recovery. Young people and families who live with NES experience considerable distress and impairment. Pathways to diagnosis need to be streamlined, and better integration of pediatric, mental health, and educational services is required. The use of the "good news" story to discuss the diagnosis with families should be reconsidered, as families seem to interpret this as indicating that there is no effective treatment. Educational resources and support groups for young people and families are needed. Greater understanding of experiences may allow investigation of the pathogenic mechanism and inform possible management approaches. Training of health professionals in communicating with young people and families with NES must be improved. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Design, Synthesis, and Characterization of Folate-Targeted Platinum-Loaded Theranostic Nanoemulsions for Therapy and Imaging of Ovarian Cancer.

    PubMed

    Patel, Niravkumar R; Piroyan, Aleksandr; Nack, Abbegial H; Galati, Corin A; McHugh, Mackenzi; Orosz, Samantha; Keeler, Amanda W; O'Neal, Sara; Zamboni, William C; Davis, Barbara; Coleman, Timothy P

    2016-06-06

    Platinum (Pt) based chemotherapy is widely used to treat many types of cancer. Pt therapy faces challenges such as dose limiting toxicities, cumulative side effects, and multidrug resistance. Nanoemulsions (NEs) have tremendous potential in overcoming these challenges as they can be designed to improve circulation time, limit non-disease tissue uptake, and enhance tumor uptake by surface modification. We designed novel synthesis of three difattyacid platins, dimyrisplatin, dipalmiplatin, and distearyplatin, suitable for encapsulation in the oil core of an NE. The dimyrisplatin, dipalmiplatin, and distearyplatin were synthesized, characterized, and loaded into the oil core of our NEs, NMI-350, NMI-351, and NMI-352 respectively. Sequestration of the difattyacid platins was accomplished through high energy microfluidization. To target the NE, FA-PEG3400-DSPE was incorporated into the surface during microfluidization. The FA-NEs selectively bind the folate receptor α (FR-α) and utilize receptor mediated endocytosis to deliver Pt past cell surface resistance mechanisms. FR-α is overexpressed in a number of oncological conditions including ovarian cancer. The difattyacid platins, lipidated Gd-DTPA, and lipidated folate were characterized by nuclear magnetic resonance (NMR), mass spectrometry (MS), and elemental analysis. NEs were synthesized using high shear microfluidization process and characterized for size, zeta-potential, and loading efficiency. In vitro cytotoxicity was determined using KB-WT (Pt-sensitive) and KBCR-1000 (Pt-resistant) cancer cells and measured by MTT assay. Pharmacokinetic profiles were studied in CD-1 mice. NEs loaded with difattyacid platins are highly stable and had size distribution in the range of ∼120 to 150 nm with low PDI. Cytotoxicity data indicates the longer the fatty acid chains, the less potent the NEs. The inclusion of C6-ceramide, an apoptosis enhancer, and surface functionalization with folate molecules significantly increased in vitro potency. Pharmacokinetic studies show that the circulation time for all three difattyacid platins encapsulated in NE remained identical, thus indicating that chain length did not influence circulation time. A stable NMI-350 family of NEs were successfully designed, formulated, and characterized. The Pt-resistance in KBCR-1000 cells was reversed with the NMI-350 family. Dimyrisplatin loaded NE (NMI-350) was most potent in vitro. The NMI-350 family demonstrated identical pharmacokinetic profiles to one another and circulated much longer than cisplatin. These data indicate that NMI-350 warrants further preclinical and clinical development as a replacement for current Pt regimens especially for those afflicted with multi drug resistant cancers.

  3. NASA Explorer School

    NASA Image and Video Library

    2007-11-08

    The NASA Explorer School-East Oktibbeha County School District team recently celebrated the start of its three-year partnership with NASA during a two-part kickoff event Nov. 7 and 8. Pictured from left are, Oktibbeha County School District Superintendent Dr. Walter Conley; NES Team Administrator James Covington; Stennis Space Center Deputy Director Gene Goldman; Sharon Bonner; NES Team Lead Yolanda Magee; Andrea Temple; Carolyn Rice; and special guest astronaut Roger Crouch.

  4. NASA Explorer School

    NASA Technical Reports Server (NTRS)

    2007-01-01

    The NASA Explorer School-East Oktibbeha County School District team recently celebrated the start of its three-year partnership with NASA during a two-part kickoff event Nov. 7 and 8. Pictured from left are, Oktibbeha County School District Superintendent Dr. Walter Conley; NES Team Administrator James Covington; Stennis Space Center Deputy Director Gene Goldman; Sharon Bonner; NES Team Lead Yolanda Magee; Andrea Temple; Carolyn Rice; and special guest astronaut Roger Crouch.

  5. KSC-04pd2020

    NASA Image and Video Library

    2004-09-21

    KENNEDY SPACE CENTER, FLA. - Shawn McCollough, principal of Gainesville Elementary School, a NASA Explorer School (NES) in Gainesville, Ga., and a teacher sign a Memorandum of Understanding between KSC and the school for the NES program. Schools from across the country are eligible to apply online for an opportunity to partner with NASA in a program designed to bring engaging mathematics, science and technology learning to educators, students and families.

  6. KSC-04PD-2020

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. Shawn McCollough, principal of Gainesville Elementary School, a NASA Explorer School (NES) in Gainesville, Ga., and a teacher sign a Memorandum of Understanding between KSC and the school for the NES program. Schools from across the country are eligible to apply online for an opportunity to partner with NASA in a program designed to bring engaging mathematics, science and technology learning to educators, students and families.

  7. Emulsification Increases the Acute Ketogenic Effect and Bioavailability of Medium-Chain Triglycerides in Humans

    PubMed Central

    Courchesne-Loyer, Alexandre; Lowry, Carolyn-Mary; St-Pierre, Valérie; Vandenberghe, Camille; Fortier, Mélanie; Castellano, Christian-Alexandre; Wagner, J Richard; Cunnane, Stephen C

    2017-01-01

    Abstract Background: Lower-brain glucose uptake is commonly present before the onset of cognitive deterioration associated with aging and may increase the risk of Alzheimer disease. Ketones are the brain's main alternative energy substrate to glucose. Medium-chain triglycerides (MCTs) are rapidly β-oxidized and are ketogenic but also have gastrointestinal side effects. We assessed whether MCT emulsification into a lactose-free skim-milk matrix [emulsified MCTs (MCT-Es)] would improve ketogenesis, reduce side effects, or both compared with the same oral dose of MCTs consumed without emulsification [nonemulsified MCTs (MCT-NEs)]. Objectives: Our aims were to show that, in healthy adults, MCT-Es will induce higher ketonemia and have fewer side effects than MCT-NEs and the effects of MCT-NEs and MCT-Es on ketogenesis and plasma medium-chain fatty acids (MCFAs) will be dose-dependent. Methods: Using a metabolic study day protocol, 10 healthy adults were each given 3 separate doses (10, 20, or 30 g) of MCT-NEs or MCT-Es with a standard breakfast or no treatment [control (CTL)]. Blood samples were taken every 30 min for 4 h to measure plasma ketones (β-hydroxybutyrate and acetoacetate), octanoate, decanoate, and other metabolites. Participants completed a side-effects questionnaire at the end of each study day. Results: Compared with CTL, MCT-NEs increased ketogenesis by 2-fold with no significant differences between doses. MCT-Es increased total plasma ketones by 2- to 4-fold in a dose-dependent manner. Compared with MCT-NEs, MCT-Es increased plasma MCFA bioavailability (F) by 2- to 3-fold and decreased the number of side effects by ∼50%. Conclusions: Emulsification increased the ketogenic effect and decreased side effects in a dose-dependent manner for single doses of MCTs ≤30 g under matching conditions. Further investigation is needed to establish whether emulsification could sustain ketogenesis and minimize side effects and therefore be used as a treatment to change brain ketone availability over a prolonged period of time. This trial was registered at clinicaltrials.gov as NCT02409927.

  8. Ada (Trademark) Reusability Guidelines.

    DTIC Science & Technology

    1985-04-01

    generators. Neighbors discusses another approach to reusable software using models. He describes a particular modeling technique using the Draco System ...experience with the Draco system . Is Fx~~~~flP7 7. 4 .~-’ b.r SECTION 4 DESIGN GUIDEUiNES As noted earlier, reusability is first and foremost a design issue...to be reused in another system that had a different type of physical data storage device, only this layer needs to be changed to deal with the new

  9. Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax.

    PubMed

    Alefantis, Timothy; Barmak, Kate; Harhaj, Edward W; Grant, Christian; Wigdahl, Brian

    2003-06-13

    Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I transactivator protein Tax plays an integral role in the etiology of adult T cell leukemia, as expression of Tax in T lymphocytes has been shown to result in immortalization. In addition, Tax is known to interface with numerous transcription factor families, including activating transcription factor/cAMP response element-binding protein and nuclear factor-kappaB, requiring Tax to localize to both the nucleus and cytoplasm. In this report, the nucleocytoplasmic localization of Tax was examined in Jurkat, HeLa, and U-87 MG cells. The results reported herein indicate that Tax contains a leucine-rich nuclear export signal (NES) that, when fused to green fluorescent protein (GFP), can direct nuclear export via the CRM-1 pathway, as determined by leptomycin B inhibition of nuclear export. However, cytoplasmic localization of full-length Tax was not altered by treatment with leptomycin B, suggesting that native Tax utilizes another nuclear export pathway. Additional support for the presence of a functional NES has also been shown because the NES mutant Tax(L200A)-GFP localized to the nuclear membrane in the majority of U-87 MG cells. Evidence has also been provided suggesting that the Tax NES likely exists as a conditionally masked signal because the truncation mutant TaxDelta214-GFP localized constitutively to the cytoplasm. These results suggest that Tax localization may be directed by specific changes in Tax conformation or by specific interactions with cellular proteins leading to changes in the availability of the Tax NES and nuclear localization signal.

  10. Comparisons of The Habitat Utilization Of Top Predators In The Southern Ocean And The North Pacific

    NASA Astrophysics Data System (ADS)

    Costa, D. P.; Robinson, P.; Huckstadt, L. E.; Crocker, D. E.; Goebel, M. E.

    2010-12-01

    Northern and Southern elephant seals (Mirounga angustirostris, M. leonina) separated some 4 MYA. While these congeners are physiologically very similar and thus have the potential to forage in similar ways they inhabit very different habitats. While southern elephant seals (SES) are distributed throughout the southern ocean, northern elephant seals (NES) are limited to the Northeast Pacific Ocean and range over lower latitudes than SES. In order to compare and contrast the physiological capability and response to different habitats we compared the foraging behavior of 167 adult female northern elephant seals (Año Nuevo and San Benitos Islands) and 55 southern elephant seals (Livingston Island, Antarctic Peninsula) using satellite telemetry and dive recorders. As expected both species carried out very similar dive depths (NES 509m ± 166 vs SES 345m±79) and dive durations (NES 23.0 min ± 6.7; SES 22.5 min ± 5.0). However, there were significant differences in their foraging pattern that we attribute to differences in the availability of continental shelf and suitable foraging habitat. While 85% of NES females foraged offshore, the dominant strategy for SES was benthic foraging on the continental shelf. Even with the differences in habitat, the fundamental components of their foraging patterns remained the same as when they foraged pelagically they both species relied on persistent large scale oceanographic features where mixing enhances productivity such as the North Pacific Transition zone (NES) and the Southern Antarctic Circumpolar Current Front (SES). Given the very different habitats and prey species consumed by these two species their overall foraging behavior is surprisingly similar suggesting that as a mesopelagic predator the elephant seal design is rather robust.

  11. KSC-04PD-2047

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. Astronaut Terry Virts questions students from Immokalee Middle School in Naples, Fla., which is part of NASAs Explorer School (NES) Program. Virts spoke about what it takes for mission success and the importance of teamwork. Virts accompanied Center Director Jim Kennedy on the visit to the school to share the vision for space exploration with the next generation of explorers. Immokalee is part of NASAs Explorer School (NES) Program and is teamed with Pine Ridge Middle School. Kennedy is talking with students about our destiny as explorers, NASAs stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space. NES establishes a three- year partnership annually between NASA and 50 NASA Explorer Schools teams, consisting of teachers and education administrators from diverse communities nationwide.

  12. Distinct zooplankton regime shift patterns across ecoregions of the U.S. Northeast continental shelf Large Marine Ecosystem

    NASA Astrophysics Data System (ADS)

    Morse, R. E.; Friedland, K. D.; Tommasi, D.; Stock, C.; Nye, J.

    2017-01-01

    We investigated regime shifts in seasonal zooplankton communities of the Northeast continental shelf Large Marine Ecosystem (NES) and its subcomponent ecoregions over a multi-decadal period (1977-2013). Our cross ecoregion analysis shows that regime shifts in different ecoregions often exhibited very distinct characteristics, emphasizing more granular fluctuations in NES plankton communities relative to previous work. Shifts early in the time series generally reflected an increase in abundance levels. The response of zooplankton abundance within fall communities was more similar among ecoregions than for spring communities. The Gulf of Maine exhibited highly distinct patterns from other ecoregions, with regime shifts identified in the early 1980s, early 2000s, and mid-2000s for spring communities. Regime shifts were identified in the early to mid-1990s for the NES, Georges Bank, and the Mid-Atlantic Bight ecoregions, while the fall communities experienced shifts in the early 1990s and late 1980s for the NES and Georges Bank, but in the late 1990s in the Mid-Atlantic Bight. A constrained correspondence analysis of zooplankton community against local and basin-scale climatological indices suggests that water temperature, stratification, and the Atlantic multidecadal oscillation (AMO) were the predominant factors in driving the zooplankton community composition.

  13. Ecosystem-Based Management and the Sustainable Delivery of Marine Ecosystem Services

    NASA Astrophysics Data System (ADS)

    Fogarty, M.; Schwing, F. B.

    2016-12-01

    Ecosystem-Based Management can provide an essential framework for the sustainable delivery of a broad spectrum of marine Ecosystem Services (ES) essential to human well being. Key elements of the approach involve the specification of clearly articulated goals for EBM; the development of an accompanying Marine Ecosystem Services Assessment (MESA) designed to evaluate the status of delivery of these services; and strategies for the implementation of management options designed to achieve the stated goals of the program. The specification of goals is the purview of managers. In the United States under the provisions of the National Ocean Policy, Regional Planning Bodies are charged with the responsibility of articulating goals and developing strategies to meet these goals. Government agencies, in concert with the broader scientific community, hold the responsibility for assessing the status of the delivery of ecosystem services in relation to designated objectives and advising on appropriate management strategies. In this presentation, I will illustrate the specification of a MESA for the Northwest U.S Continental Shelf Large Marine Ecosystem (NES LME). The approach focuses on the evaluation of ES indicators and additional metrics related to threats and impacts to the sustainable delivery of these services. Results are combined into an overall index of status of the NES LME.

  14. Neurobehavioral effects of ambient air pollution on cognitive performance in US adults.

    PubMed

    Chen, Jiu-Chiuan; Schwartz, Joel

    2009-03-01

    In vivo animal experiments demonstrate neurotoxicity of exposures to particulate matter (PM) and ozone, but only one small epidemiological study had linked ambient air pollution with central nervous system (CNS) functions in children. To examine the neurobehavioral effects associated with long-term exposure to ambient PM and ozone in adults. We conducted a secondary analysis of the Neurobehavioral Evaluation System-2 (NES2) data (including a simple reaction time test [SRTT] measuring motor response speed to a visual stimulus; a symbol-digit substitution test [SDST] for coding ability; and a serial-digit learning test [SDLT] for attention and short-term memory) from 1764 adult participants (aged 37.5+/-10.9 years) of the Third National Health and Nutrition Examination Survey in 1988-1991. Based on ambient PM(10) (PM with aerodynamic diameter <10microm) and ozone data from the EPA Aerometric Information Retrieval System database, estimated annual exposure prior to the examination were aggregated at the centroid of each census-block group of geocoded residences, using distance-weighted averages from all monitors in the residing and adjoining counties. Generalized linear models were constructed to examine the associations, adjusting for potential confounders. In age- and sex-adjusted models, PM(10) predicted reduced CNS functions, but the association disappeared after adjustment for sociodemographic factors. There were consistent associations between ozone and reduced performance in NES2. In models adjusting for demographics, socioeconomic status, lifestyle, household and neighborhood characteristics, and cardiovascular risk factors, ozone predicted high scores in SDST and SDLT, but not in SRTT. Each 10-ppb increase in annual ozone was associated with increased SDST and SDLT scores by 0.16 (95%CI: 0.01, 0.23) and 0.56 (95%CI: 0.07, 1.05), equivalent to 3.5 and 5.3 years of aging-related decline in cognitive performance. Our study provides the first epidemiological data supporting the adverse neurobehavioral effects of ambient air pollutants in adults.

  15. Effect of electrical stimulation and hot boning on the eating quality of Gannan yak longissimus lumborum.

    PubMed

    Lang, Yumiao; Sha, Kun; Zhang, Rui; Xie, Peng; Luo, Xin; Sun, Baozhong; Li, Haipeng; Zhang, Li; Zhang, Songshan; Liu, Xuan

    2016-02-01

    The objective of this study was to evaluate the effects of electrical stimulation (ES) versus non-electrical stimulation (NES) and type of boning (hot versus cold) on the eating quality of Gannan yak longissimus lumborum. Eighteen Gannan yak bulls were randomly divided into two groups: ES and NES. Hot boning (HB) and cold boning (CB) were applied to the left and right side of the carcasses, respectively. All of the four treatments missed the "ideal" pH/temperature window. HB reduced the rate of pH decline, decreased meat tenderness and water holding capacity. ES increased the rate of pH decline and improved yak meat tenderness (P<0.05); however, ES explained only 1% of the variation in WBSF. HB and ES had no significant effects on cooking loss, L* or b* values of yak meat. Postmortem aging increased yak meat tenderness and improved meat color parameters. HB had negative effects on yak meat quality, while ES could not reverse these deleterious effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Nuclear export of ubiquitinated proteins via the UBIN-POST system

    PubMed Central

    Sugihara, Munechika; Morito, Daisuke; Iemura, Shun-ichiro; Natsume, Tohru; Nagata, Kazuhiro

    2018-01-01

    Although mechanisms for protein homeostasis in the cytosol have been studied extensively, those in the nucleus remain largely unknown. Here, we identified that a protein complex mediates export of polyubiquitinated proteins from the nucleus to the cytosol. UBIN, a ubiquitin-associated (UBA) domain-containing protein, shuttled between the nucleus and the cytosol in a CRM1-dependent manner, despite the lack of intrinsic nuclear export signal (NES). Instead, the UBIN binding protein polyubiquitinated substrate transporter (POST) harboring an NES shuttled UBIN through nuclear pores. UBIN bound to polyubiquitin chain through its UBA domain, and the UBIN-POST complex exported them from the nucleus to the cytosol. Ubiquitinated proteins accumulated in the cytosol in response to proteasome inhibition, whereas cotreatment with CRM1 inhibitor led to their accumulation in the nucleus. Our results suggest that ubiquitinated proteins are exported from the nucleus to the cytosol in the UBIN-POST complex-dependent manner for the maintenance of nuclear protein homeostasis. PMID:29666234

  17. Nuclear export of ubiquitinated proteins via the UBIN-POST system.

    PubMed

    Hirayama, Shoshiro; Sugihara, Munechika; Morito, Daisuke; Iemura, Shun-Ichiro; Natsume, Tohru; Murata, Shigeo; Nagata, Kazuhiro

    2018-05-01

    Although mechanisms for protein homeostasis in the cytosol have been studied extensively, those in the nucleus remain largely unknown. Here, we identified that a protein complex mediates export of polyubiquitinated proteins from the nucleus to the cytosol. UBIN, a ubiquitin-associated (UBA) domain-containing protein, shuttled between the nucleus and the cytosol in a CRM1-dependent manner, despite the lack of intrinsic nuclear export signal (NES). Instead, the UBIN binding protein polyubiquitinated substrate transporter (POST) harboring an NES shuttled UBIN through nuclear pores. UBIN bound to polyubiquitin chain through its UBA domain, and the UBIN-POST complex exported them from the nucleus to the cytosol. Ubiquitinated proteins accumulated in the cytosol in response to proteasome inhibition, whereas cotreatment with CRM1 inhibitor led to their accumulation in the nucleus. Our results suggest that ubiquitinated proteins are exported from the nucleus to the cytosol in the UBIN-POST complex-dependent manner for the maintenance of nuclear protein homeostasis. Copyright © 2018 the Author(s). Published by PNAS.

  18. Providing a Full Circle of Support to Teachers in an Inclusive Elementary School

    ERIC Educational Resources Information Center

    Waldron, Nancy L.; Redd, Lacy

    2011-01-01

    Providing a full circle of support to teachers in an inclusive elementary school, the Newberry Elementary School (NES) principal and staff have worked for 5 years to ensure the inclusion of students with disabilities in general education classrooms. The authors would like to share their perceptions of how this full circle (the multiple systems) of…

  19. Technology-Enhanced Formative Assessment in Mathematics for English Language Learners

    ERIC Educational Resources Information Center

    Lekwa, Adam Jens

    2012-01-01

    This paper reports the results of a descriptive study on the use of a technology-enhanced formative assessment system called Accelerated Math (AM) for ELLs and their native-English-speaking (NES) peers. It was comprised of analyses of an extant database of 18,549 students, including 2,057 ELLs, from grades 1 through 8 across 30 U.S. states. These…

  20. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.

    PubMed

    Sabbagh, Ubadah; Mullegama, Saman; Wyckoff, Gerald J

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  1. Nanosized Building Blocks for Customizing Novel Antibiofilm Approaches

    PubMed Central

    Paula, A.J.; Koo, H.

    2016-01-01

    Recent advances in nanotechnology provide unparalleled flexibility to control the composition, size, shape, surface chemistry, and functionality of materials. Currently available engineering approaches allow precise synthesis of nanocompounds (e.g., nanoparticles, nanostructures, nanocrystals) with both top-down and bottom-up design principles at the submicron level. In this context, these “nanoelements” (NEs) or “nanosized building blocks” can 1) generate new nanocomposites with antibiofilm properties or 2) be used to coat existing surfaces (e.g., teeth) and exogenously introduced surfaces (e.g., restorative or implant materials) for prevention of bacterial adhesion and biofilm formation. Furthermore, functionalized NEs 3) can be conceived as nanoparticles to carry and selectively release antimicrobial agents after attachment or within oral biofilms, resulting in their disruption. The latter mechanism includes “smart release” of agents when triggered by pathogenic microenvironments (e.g., acidic pH or low oxygen levels) for localized and controlled drug delivery to simultaneously kill bacteria and dismantle the biofilm matrix. Here we discuss inorganic, metallic, polymeric, and carbon-based NEs for their outstanding chemical flexibility, stability, and antibiofilm properties manifested when converted into bioactive materials, assembled on-site or delivered at biofilm-surface interfaces. Details are provided on the emerging concept of the rational design of NEs and recent technological breakthroughs for the development of a new generation of nanocoatings or functional nanoparticles for biofilm control in the oral cavity. PMID:27856967

  2. Nanosized Building Blocks for Customizing Novel Antibiofilm Approaches.

    PubMed

    Paula, A J; Koo, H

    2017-02-01

    Recent advances in nanotechnology provide unparalleled flexibility to control the composition, size, shape, surface chemistry, and functionality of materials. Currently available engineering approaches allow precise synthesis of nanocompounds (e.g., nanoparticles, nanostructures, nanocrystals) with both top-down and bottom-up design principles at the submicron level. In this context, these "nanoelements" (NEs) or "nanosized building blocks" can 1) generate new nanocomposites with antibiofilm properties or 2) be used to coat existing surfaces (e.g., teeth) and exogenously introduced surfaces (e.g., restorative or implant materials) for prevention of bacterial adhesion and biofilm formation. Furthermore, functionalized NEs 3) can be conceived as nanoparticles to carry and selectively release antimicrobial agents after attachment or within oral biofilms, resulting in their disruption. The latter mechanism includes "smart release" of agents when triggered by pathogenic microenvironments (e.g., acidic pH or low oxygen levels) for localized and controlled drug delivery to simultaneously kill bacteria and dismantle the biofilm matrix. Here we discuss inorganic, metallic, polymeric, and carbon-based NEs for their outstanding chemical flexibility, stability, and antibiofilm properties manifested when converted into bioactive materials, assembled on-site or delivered at biofilm-surface interfaces. Details are provided on the emerging concept of the rational design of NEs and recent technological breakthroughs for the development of a new generation of nanocoatings or functional nanoparticles for biofilm control in the oral cavity.

  3. A putative N-terminal nuclear export sequence is sufficient for Mps1 nuclear exclusion during interphase.

    PubMed

    Jia, Haiwei; Zhang, Xiaojuan; Wang, Wenjun; Bai, Yuanyuan; Ling, Youguo; Cao, Cheng; Ma, Runlin Z; Zhong, Hui; Wang, Xue; Xu, Quanbin

    2015-02-27

    Mps1, an essential component of the mitotic checkpoint, is also an important interphase regulator and has roles in DNA damage response, cytokinesis and centrosome duplication. Mps1 predominantly resides in the cytoplasm and relocates into the nucleus at the late G2 phase. So far, the mechanism underlying the Mps1 translocation between the cytoplasm and nucleus has been unclear. In this work, a dynamic export process of Mps1 from the nucleus to cytoplasm in interphase was revealed- a process blocked by the Crm1 inhibitor, Leptomycin B, suggesting that export of Mps1 is Crm1 dependent. Consistent with this speculation, a direct association between Mps1 and Crm1 was found. Furthermore, a putative nuclear export sequence (pNES) motif at the N-terminal of Mps1 was identified by analyzing the motif of Mps1. This motif shows a high sequence similarity to the classic NES, a fusion of this motif with EGFP results in dramatic exclusion of the fusion protein from the nucleus. Additionally, Mps1 mutant loss of pNES integrity was shown by replacing leucine with alanine which produced a diffused subcellular distribution, compared to the wild type protein which resides predominantly in cytoplasm. Taken these findings together, it was concluded that the pNES sequence is sufficient for the Mps1 export from nucleus during interphase.

  4. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona, E-mail: moroianu@bc.edu

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP–8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), {sub 76}IRTFQELLF{sub 84}, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7more » interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. - Highlights: • HPV8 E7 has a leucine-rich NES within its zinc-binding domain that mediates its nuclear export. • CRM1 nuclear export receptor interacts with HPV8 E7 and mediates its export. • Identification of the critical hydrophobic amino acids of the NES of HPV8 E7.« less

  5. Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka

    An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 bindsmore » at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.« less

  6. [The factors related to job satisfaction and professional burnout in the primary care physicians of Asturias].

    PubMed

    Olivar Castrillón, C; González Morán, S; Martínez Suárez, M M

    1999-10-15

    To determine the level of work satisfaction and professional wear and tear among primary care doctors, and related factors. Crossover descriptive study. Asturias PC. General doctors (GD), family doctors (FD), residents, and PC paediatricians (n = 810). A survey for self-administration with social and demographic variables and suggestions. The Font Roja-PC questionnaire (FR). The Maslach Burnout Inventory (MBI). 497 (55.6% male) responded (61.35%). Mean age was 41 (SD = 7.18) 57.3% worked in an urban environment. 42% were FD, 35% GD, 15% paediatricians, 7% residents. The PC model was: 84% PC teams, 9% traditional model, 7% normal emergency service (NES). Mean seniority was 14 years (SD = 7.5). 89% worked solely in PC. 59% had a permanent contract, 31% provisional contracts, 7% were residents and 3% temporary. Overall mean satisfaction (OMS): 73.73 points. 43% had high professional wear and tear, 23% moderate and 32% low. Statistically significant associations: OMS/social and demographic variables: greater in men, the rural environment, paediatrics, NES, without stand-by, with less bureaucracy and less case pressure. Satisfaction/FR: greater NES, without stand-by, without sole dedication. Case pressure/FR: greater in men, rural environment, paediatrics, without sole dedication, NES, without stand-by and with less demand. Control/FR: greater in permanent and provisional posts. Relationship/FR: greater in men, FD, without stand-by. Suitability/FR: greater in men, paediatricians, permanent doctors, without stand-by. Relaxation/FR: greater in residents, young people, without sole dedication, NES. Variety/FR: greater in young people, those without children, residents, with sole dedication, those with stand-by. MBI/social and demographic variables: greater level of low emotional tiredness in workers in a rural environment and those with children. Greater low level of alienation in women. The older the doctor, the less the professional burnout. 1. High level of work satisfaction. 2. High-moderate professional wear and tear.

  7. Three computational mise-en-scènes of red- and blue-shifted hydrogen bonding motifs: Concept of negative intramolecular coupling-What else?

    NASA Astrophysics Data System (ADS)

    Kryachko, Eugene S.

    This work is a kind of attempt to rethink some problems which are related to the blue-shifted "hydrogen bonds" and which have been left in the past decade as not yet fully resolved. The impetus for such rethink is originated from the three computational mise-en-scènes on red- and blue-shifted hydrogen bonding motifs, which are aimed to be thoroughly studied in this work, thus resolving the above problems.

  8. A Language-Based Approach To Wireless Sensor Network Security

    DTIC Science & Technology

    2014-03-06

    128 – RPC 119 7.0 Secure RPC 87 32.0 Figure 1: SpartanRPC Memory Overhead (L) and Impact on Messaging (R) Figure 2: Scalaness /nesT Compilation and...language for developing real WSN applica- tions. This language, called Scalaness /nesT, extends Scala with staging features for executing programs on hubs...particular note here is the fact that cross-stage type safety of Scalaness source code ensures that compiled bytecode can be deployed to, and run on

  9. [Anthropogenic sources of radiation hazard in the near-Earth space].

    PubMed

    Fedoseev, G A

    2004-01-01

    All plausible artificial radioactive sources entering the near-Earth space (NES) were systematized and consequences of various large radiation accidents and catastrophes to Earth and NES were analyzed. Aggressive "population" of near-Earth orbits by space stations with rotating crews, unmanned research platforms and observatories extends "borderlines" of the noosphere raising at the same time concerns about the noosphere radiation safety and global radioecology. Specifically, consideration is given to the facts of negative effects of space power reactor facilities on results of orbital astrophysical investigations.

  10. Nerolidol production in agroinfiltrated tobacco: Impact of protein stability and membrane targeting of strawberry (Fragraria ananassa) NEROLIDOL SYNTHASE1.

    PubMed

    Andrade, Paola; Manzano, David; Ramirez-Estrada, Karla; Caudepon, Daniel; Arro, Montserrat; Ferrer, Albert; Phillips, Michael A

    2018-02-01

    The sesquiterpene alcohol nerolidol, synthesized from farnesyl diphosphate (FDP), mediates plant-insect interactions across multiple trophic levels with major implications for pest management in agriculture. We compared nerolidol engineering strategies in tobacco using agroinfiltration to transiently express strawberry (Fragraria ananassa) linalool/nerolidol synthase (FaNES1) either at the endoplasmic reticulum (ER) or in the cytosol as a soluble protein. Using solid phase microextraction and gas chromatography-mass spectrometry (SPME-GCMS), we have determined that FaNES1 directed to the ER via fusion to the transmembrane domain of squalene synthase or hydroxymethylglutaryl - CoA reductase displayed significant improvements in terms of transcript levels, protein accumulation, and volatile production when compared to its cytosolic form. However, the highest levels of nerolidol production were observed when FaNES1 was fused to GFP and expressed in the cytosol. This SPME-GCMS method afforded a limit of detection and quantification of 1.54 and 5.13 pg, respectively. Nerolidol production levels, which ranged from 0.5 to 3.0 μg/g F.W., correlated more strongly to the accumulation of recombinant protein than transcript level, the former being highest in FaNES-GFP transfected plants. These results indicate that while the ER may represent an enriched source of FDP that can be exploited in metabolic engineering, protein accumulation is a better predictor of sesquiterpene production. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Targeted energy transfer in laminar vortex-induced vibration of a sprung cylinder with a nonlinear dissipative rotator

    NASA Astrophysics Data System (ADS)

    Blanchard, Antoine; Bergman, Lawrence A.; Vakakis, Alexander F.

    2017-07-01

    We computationally investigate the dynamics of a linearly-sprung circular cylinder immersed in an incompressible flow and undergoing transverse vortex-induced vibration (VIV), to which is attached a rotational nonlinear energy sink (NES) consisting of a mass that freely rotates at constant radius about the cylinder axis, and whose motion is restrained by a rotational linear viscous damper. The inertial coupling between the rotational motion of the attached mass and the rectilinear motion of the cylinder is ;essentially nonlinear;, which, in conjunction with dissipation, allows for one-way, nearly irreversible targeted energy transfer (TET) from the oscillating cylinder to the nonlinear dissipative attachment. At the intermediate Reynolds number Re = 100, the NES-equipped sprung cylinder undergoes repetitive cycles of slowly decaying oscillations punctuated by intervals of chaotic instabilities. During the slowly decaying portion of each cycle, the dynamics of the cylinder is regular and, for large enough values of the ratio ε of the NES mass to the total mass (i.e., NES mass plus cylinder mass), can lead to significant vortex street elongation with partial stabilization of the wake. As ε approaches zero, no such vortex elongation is observed and the wake patterns appear similar to that for a sprung cylinder with no NES. We apply proper orthogonal decomposition (POD) to the velocity flow field during a slowly decaying portion of the solution and show that, in situations where vortex elongation occurs, the NES, though not in direct contact with the surrounding fluid, has a drastic effect on the underlying flow structures, imparting significant and continuous passive redistribution of energy among POD modes. We construct a POD-based reduced-order model for the lift coefficient to characterize energy transactions between the fluid and the cylinder throughout the slowly decaying cycle. We introduce a quantitative signed measure of the work done by the fluid on the cylinder over one quasi-period of the slowly decaying response and find that vortex elongation is associated with a sign change of that measure, indicating that a reversal of the direction of energy transfer, with the cylinder ;leaking energy back; to the flow, is responsible for partial stabilization and elongation of the wake. We interpret these findings in terms of the spatial structure and energy distribution of the POD modes, and relate them to the mechanism of transient resonance capture into a slow invariant manifold of the fluid-structure interaction dynamics.

  12. An exploratory study of the relationship between neurological soft signs and theory of mind deficits in schizophrenia.

    PubMed

    Romeo, Stefano; Chiandetti, Alessio; Siracusano, Alberto; Troisi, Alfonso

    2014-08-15

    Indirect evidence suggests partially common pathogenetic mechanisms for Neurological Soft Signs (NSS), neurocognition, and social cognition in schizophrenia. However, the possible association between NSS and mentalizing impairments has not yet been examined. In the present study, we assessed the ability to attribute mental states to others in patients with schizophrenia and predicted that the presence of theory of mind deficits would be significantly related to NSS. Participants were 90 clinically stable patients with a DSM-IV diagnosis of schizophrenia. NSS were assessed using the Neurological Evaluation Scale (NES). Theory of mind deficits were assessed using short verbal stories designed to measure false belief understanding. The findings of the study confirmed our hypothesis. Impaired sequencing of complex motor acts was the only neurological abnormality correlated with theory of mind deficits. By contrast, sensory integration, motor coordination and the NES Others subscale had no association with patients׳ ability to pass first- or second-order false belief tasks. If confirmed by future studies, the current findings provide the first preliminary evidence for the claim that specific NSS and theory of mind deficits may reflect overlapping neural substrates. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. The Multi-Player Performance-Enhancing Drug Game

    PubMed Central

    Haugen, Kjetil K.; Nepusz, Tamás; Petróczi, Andrea

    2013-01-01

    This paper extends classical work on economics of doping into a multi-player game setting. Apart from being among the first papers formally formulating and analysing a multi-player doping situation, we find interesting results related to different types of Nash-equilibria (NE). Based mainly on analytic results, we claim at least two different NE structures linked to the choice of prize functions. Linear prize functions provide NEs characterised by either everyone or nobody taking drugs, while non-linear prize functions lead to qualitatively different NEs with significantly more complex predictive characteristics. PMID:23691018

  14. A Hybrid Neuromechanical Ambulatory Assist System

    DTIC Science & Technology

    2016-08-01

    provide real- time closed-loop control using brace mounted sensors to deliver the stimulation needed to stand up and walk while coordinating exoskeletal...target PC during real- time implementation. The muscle stimulator unit delivered the NES to target paralyzed muscles to drive limb motion. The activity...manual adjustment of thresholds used in the GED and stimulation pattern lengths (Figure 26b). The time for a right or left step could be decreased

  15. The impact of conveying the diagnosis when using a biopsychosocial approach: A qualitative study among adolescents and young adults with NES (non-epileptic seizures).

    PubMed

    Karterud, Hilde Nordahl; Risør, Mette Bech; Haavet, Ole Rikard

    2015-01-01

    This qualitative study explored the impact of using a biopsychosocial approach to explain the diagnosis of non-epileptic seizures (NES). Semi-structured interviews of eleven adolescents and young adults who had participated in an inpatient follow-up stay of the diagnosis were used. The interviews were taped, transcribed, and analysed using systematic text condensation. Three key themes were identified:1."Threatened self-image": Patients initially perceived their diagnosis as being purely psychological. As they did not accept that they had mental disorders, they interpreted this as frightening and threatening, and resisted the diagnosis.2."Being believed and belief in oneself": Participants had many experiences of being suspected by healthcare providers of staging their seizures. Some had even begun to have doubts themselves as to whether the attacks were voluntary or not. Explaining that unconscious processes are involved in NES contributed towards increasing patients' feelings of being believed, and thereby acceptance of the diagnosis.3."Getting an explanation that makes sense": Some participants identified connections between their personal histories and their seizures and became seizure-free. Others found that the explanatory models gave personal meaning, but did not become seizure-free, while a few continued to doubt whether NES was the correct diagnosis. Being believed was the most elemental factor for coping with the condition. Using a biopsychosocial approach to explain the diagnosis may facilitate identification with the explanatory models, and thus acceptance of the diagnosis. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  16. Formation of (E)-nerolidol in tea (Camellia sinensis) leaves exposed to multiple stresses during tea manufacturing.

    PubMed

    Zhou, Ying; Zeng, Lanting; Liu, Xiaoyu; Gui, Jiadong; Mei, Xin; Fu, Xiumin; Dong, Fang; Tang, Jingchi; Zhang, Lingyun; Yang, Ziyin

    2017-09-15

    (E)-Nerolidol is a volatile sesquiterpene that contributes to the floral aroma of teas (Camellia sinensis). The unique manufacturing process for oolong tea involves multiple stresses, resulting in a high content of (E)-nerolidol, which is not known to form in tea leaves. This study aimed to determine the formation mechanism of (E)-nerolidol in tea exposed to multiple stresses during tea manufacture. C. sinensis (E)-nerolidol synthase (CsNES) recombinant protein, found in the cytosol, was found to transform farnesyl diphosphate into (E)-nerolidol. CsNES was highly expressed during the oolong tea turn over process, resulting in (E)-nerolidol accumulation. Continuous mechanical damage, simulating the turn over process, significantly enhanced CsNES expression level and (E)-nerolidol content. The combination of low temperature stress and mechanical damage had a synergistic effect on (E)-nerolidol formation. This is the first evidence of (E)-nerolidol formation mechanism in tea leaves and a characteristic example of plant volatile formation in response to dual stresses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Neutron spectroscopy as a fuel ion ratio diagnostic: lessons from JET and prospects for ITER.

    PubMed

    Ericsson, G; Conroy, S; Gatu Johnson, M; Andersson Sundén, E; Cecconello, M; Eriksson, J; Hellesen, C; Sangaroon, S; Weiszflog, M

    2010-10-01

    The determination of the fuel ion ratio n(t)/n(d) in ITER is required at a precision of 20%, time resolution of 100 ms, spatial resolution of a/10, and over a range of 0.016 keV and for n(T)/n(D)<0.6. A crucial issue is the signal-to-background situation in the measurement of the weak 2.5 MeV emission from DD reactions in the presence of a background of scattered 14 MeV DT neutrons. Important experimental input and corroboration for this assessment are presented from the time-of-flight neutron spectrometer at JET where the presence of a strong component of backscattered neutrons is observed. Neutron emission components on ITER due to beam-thermal and tritium-tritium reactions can further enhance the prospects for NES.

  18. Characteristics of acetaminophen absorption in healthy unweaned calves as an indirect measurement of the oroduodenal transit rate of liquid meals.

    PubMed

    Schaer, S; Herrli-Gygi, M; Kosmeas, N; Boschung, H; Steiner, A

    2005-09-01

    Abomasal emptying plays an important role in the incidence of digestive problems in calves. Our aim was to evaluate the acetaminophen absorption test (APAT) for characterization of the oroduodenal transit (ODT) of liquid meals in unweaned calves. Six healthy, unweaned Simmental x Red Holstein crossbred calves were involved in the project. The study was performed in three blocks at 3, 6 and 9 weeks of the calves' age. Within blocks, APAT was performed twice at an interval of at least 24 h. Once per each block, liquid transit was carried out with non-coagulating electrolyte solution (NES). The second test within a block was performed either while atropine sulphate was administered (block I), or by feeding a coagulating milk replacer (block II), or by administration of NES by ruminal tube (block III). Data were compared within and among blocks. Significant differences of several APAT traits were present for the different types of feeding, the different types of meals, the administration of atropine sulphate and the different ages of the calves. The emptying index T(max)/C(max) was suggested to be a valuable kinetic parameter for the characterization of ODT in these calves. We conclude that APAT represents a valid technique for characterization of ODT of liquid meals in healthy unweaned calves and may be a valuable tool for the evaluation of the reticular groove mechanism, the abomasal emptying and the absorption capacity of the duodenum.

  19. Promising ion-sensitive in situ ocular nanoemulsion gels of terbinafine hydrochloride: design, in vitro characterization and in vivo estimation of the ocular irritation and drug pharmacokinetics in the aqueous humor of rabbits.

    PubMed

    Tayel, Saadia Ahmed; El-Nabarawi, Mohamed Ahmed; Tadros, Mina Ibrahim; Abd-Elsalam, Wessam Hamdy

    2013-02-25

    Terbinafine hydrochloride (T-HCl) is recommended for the management of fungal keratitis. To maintain effective aqueous humor concentrations, frequent instillation of T-HCl drops is necessary. This work aimed to develop alternative controlled-release in situ ocular drug-loaded nanoemulsion (NE) gels. Twelve pseudoternary-phase diagrams were constructed using oils (isopropyl myristate/Miglyol 812), surfactants (Tween 80/Cremophor EL), a co-surfactant (polyethylene glycol 400) and water. Eight drug-loaded (0.5%, w/v) NEs were evaluated for thermodynamic stability, morphology, droplet size and drug release in simulated tear fluid (pH 7.4). Following dispersion in gellan gum solution (0.2%, w/w), the in situ NE gels were characterized for transparency, rheological behavior, mucoadhesive force, drug release and histopathological assessment of ocular irritation. Drug pharmacokinetics of sterilized F31 [Miglyol 812, Cremophor EL: polyethylene glycol 400 (1:2) and water (5, 55 and 40%, w/w, respectively)] in situ NE gel and oily drug solution were evaluated in rabbit aqueous humor. The NEs were thermodynamically stable and have spherical droplets (<30 nm). The gels were transparent, pseudoplastic, mucoadhesive and showed more retarded zero-order drug release rates. F31 in situ NE gel showed the least ocular irritation potential and significantly (P<0.01) higher C(max), delayed T(max), prolonged mean residence time and increased bioavailability. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Characterization of Essential Oil Composition in Different Basil Species and Pot Cultures by a GC-MS Method.

    PubMed

    Muráriková, Andrea; Ťažký, Anton; Neugebauerová, Jarmila; Planková, Alexandra; Jampílek, Josef; Mučaji, Pavel; Mikuš, Peter

    2017-07-20

    Basil ( Ocimum L.) species are used as medicinal plants due to their essential oils exhibiting specific biological activity. The present work demonstrated that both the variety and season/conditions of cultivation had a significant effect on (i) the produced amount (extraction yield), (ii) qualitative, as well as (iii) quantitative profile of basil essential oil. Among studied basil varieties, a new variety, 'Mánes', was characterized for the first time. Based on our quantitative evaluation of GC-MS profiles, the following chemotypes and average concentrations of a main component were detected in the studied basil varieties: 'Ohře', 'Lettuce Leaf', 'Purple Opaal', 'Dark Green' (linalool, 5.99, 2.49, 2.34, 2.01 mg/mL, respectively), and 'Mammolo Genovese', 'Mánes', 'Red Rubin' (eucalyptol, 1.34, 0.96, 0.76 mg/mL, respectively). At the same time, when considering other compounds identified in GC-MS profiles, all the studied varieties, except from 'Lettuce Leaf', were methyl eugenol-rich with a strong dependence of the eugenol:methyl eugenol ratio on the seasonal changes (mainly solar irradiation, but also temperature and relative humidity). More complex and/or variable (depending on the season and cultivation) chemotypes were observed with 'Lettuce Leaf' (plus estragole, 2.27 mg/mL), 'Dark Green' (plus eucalyptol, 1.36 mg/mL), 'Mammolo Genovese' (plus eugenol, 1.19 mg/mL), 'Red Rubin' (plus linalool and eugenol, 0.46 and 0.56 mg/mL, respectively), and 'Mánes' (plus linalool and eugenol, 0.58 and 0.40 mg/mL, respectively). When considering superior extraction yield (ca. 17 mL·kg -1 , i.e., two to five times higher than other examined varieties) and consistent amounts (yields) of essential oil when comparing inter-seasonal or inter-year data (RSD and inter-year difference in mean yield values ˂2.5%), this new basil variety is very promising for use in the pharmaceutical, food, and cosmetic industries.

  1. Effects of a One Year Reusable Contraceptive Vaginal Ring on Vaginal Microflora and the Risk of Vaginal Infection: An Open-Label Prospective Evaluation.

    PubMed

    Huang, Yongmei; Merkatz, Ruth B; Hillier, Sharon L; Roberts, Kevin; Blithe, Diana L; Sitruk-Ware, Régine; Creinin, Mitchell D

    2015-01-01

    A contraceptive vaginal ring (CVR) containing Nestorone® (NES) and ethinyl estradiol (EE) that is reusable for 1- year (13 cycles) is under development. This study assessed effects of this investigational CVR on the incidence of vaginal infections and change in vaginal microflora. There were 120 women enrolled into a NES/EE CVR Phase III trial and a microbiology sub-study for up to 1- year of cyclic product use. Gynecological examinations were conducted at baseline, the first week of cycle 6 and last week of cycle 13 (or during early discontinuation visits). Vaginal swabs were obtained for wet mount microscopy, Gram stain and culture. The CVR was removed from the vagina at the last study visit and cultured. Semi-quantitative cultures for Lactobacillus, Gardnerella vaginalis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, anaerobic gram negative rods (GNRs), Candida albicans and other yeasts were performed on vaginal and CVR samples. Vaginal infections were documented throughout the study. Over 1- year of use, 3.3% of subjects were clinically diagnosed with bacterial vaginosis, 15.0% with vulvovaginal candidiasis, and 0.8% with trichomoniasis. The detection rate of these three infections did not change significantly from baseline to either Cycle 6 or 13. Nugent scores remained stable. H2O2-positive Lactobacillus dominated vaginal flora with a non-significant prevalence increase from 76.7% at baseline to 82.7% at cycle 6 and 90.2% at cycle 13, and a median concentration of 107 colony forming units (cfu) per gram. Although anaerobic GNRs prevalence increased significantly, the median concentration decreased slightly (104 to 103cfu per gram). There were no significant changes in frequency or concentrations of other pathogens. High levels of agreement between vaginal and ring surface microbiota were observed. Sustained use of the NES/EE CVR did not increase the risk of vaginal infection and was not disruptive to the vaginal ecosystem. ClinicalTrials.gov NCT00263341, NCT00455156.

  2. Gaussian Random Fields Methods for Fork-Join Network with Synchronization Constraints

    DTIC Science & Technology

    2014-12-22

    substantial efforts were dedicated to the study of the max-plus recursions [21, 3, 12]. More recently, Atar et al. [2] have studied a fork-join...feedback and NES, Atar et al. [2] show that a dynamic priority discipline achieves throughput optimal- ity asymptotically in the conventional heavy...2011) Patient flow in hospitals: a data-based queueing-science perspective. Submitted to Stochastic Systems, 20. [2] R. Atar , A. Mandelbaum and A

  3. KSC-04pd1155

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Center Director Jim Kennedy addresses students and faculty of Howard A. Doolin Middle School, Miami, Fla. Doolin Middle School is one of 100 to take part in the NASA Explorer Schools (NES) program. Kennedy is visiting NES schools in Florida and Georgia to share America’s new vision for space exploration with the next generation of explorers. He is talking with students, about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  4. Induction of sensory neurons from neuroepithelial stem cells by the ISX9 small molecule

    PubMed Central

    Ali, Rouknuddin Qasim; Blomberg, Evelina; Falk, Anna; Ährlund-Richter, Lars; Ulfendahl, Mats

    2016-01-01

    Hearing impairment most often involves loss of sensory hair cells and auditory neurons. As this loss is permanent in humans, a cell therapy approach has been suggested to replace damaged cells. It is thus of interest to generate lineage restricted progenitor cells appropriate for cell based therapies. Human long-term self-renewing neuroepithelial stem (lt-NES) cell lines exhibit in vitro a developmental potency to differentiate into CNS neural lineages, and importantly lack this potency in vivo, i.e do not form teratomas. Small-molecules-driven differentiation is today an established route obtain specific cell derivatives from stem cells. In this study, we have investigated the effects of three small molecules SB431542, ISX9 and Metformin to direct differentiation of lt-NES cells into sensory neurons. Exposure of lt-NES cells to Metformin or SB431542 did not induce any marked induction of markers for sensory neurons. However, a four days exposure to the ISX9 small molecule resulted in reduced expression of NeuroD1 mRNA as well as enhanced mRNA levels of GATA3, a marker and important player in auditory neuron specification and development. Subsequent culture in the presence of the neurotrophic factors BDNF and NT3 for another seven days yielded a further increase of mRNA expression for GATA3. This regimen resulted in a frequency of up to 25-30% of cells staining positive for Brn3a/Tuj1. We conclude that an approach with ISX9 small molecule induction of lt-NES cells into auditory like neurons may thus be an attractive route for obtaining safe cell replacement therapy of sensorineural hearing loss. PMID:27335699

  5. Neuronal suppressor of cytokine signaling-3 deficiency enhances hypothalamic leptin-dependent phosphatidylinositol 3-kinase signaling.

    PubMed

    Metlakunta, Anantha S; Sahu, Maitrayee; Yasukawa, Hideo; Dhillon, Sandeep S; Belsham, Denise D; Yoshimura, Akihiko; Sahu, Abhiram

    2011-05-01

    Suppressor of cytokine signaling-3 (SOCS3) is thought to be involved in the development of central leptin resistance and obesity by inhibiting STAT3 pathway. Because phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in transducing leptin action in the hypothalamus, we examined whether SOCS3 exerted an inhibition on this pathway. We first determined whether leptin sensitivity in the hypothalamic PI3K pathway was increased in brain-specific Socs3-deficient (NesKO) mice. In NesKO mice, hypothalamic insulin receptor substrate-1 (IRS1)-associated PI3K activity was significantly increased at 30 min and remained elevated up to 2 h after leptin intraperitoneal injection, but in wild-type (WT) littermates, the significant increase was only at 30 min. Hypothalamic p-STAT3 levels were increased up to 5 h in NesKO as opposed to 2 h in WT mice. In food-restricted WT mice with reduced body weight, leptin increased hypothalamic PI3K activity only at 30 min, and p-STAT3 levels at 30-120 min postinjection. These results suggest increased leptin sensitivity in both PI3K and STAT3 pathways in the hypothalamus of NesKO mice, which was not due to a lean phenotype. In the next experiment with a clonal hypothalamic neuronal cell line expressing proopiomelanocortin, we observed that whereas leptin significantly increased IRS1-associated PI3K activity and p-JAK2 levels in cells transfected with control vector, it failed to do so in SOCS3-overexpressed cells. Altogether, these results imply a SOCS3 inhibition of the PI3K pathway of leptin signaling in the hypothalamus, which may be one of the mechanisms behind the development of central leptin resistance and obesity.

  6. Neuronal suppressor of cytokine signaling-3 deficiency enhances hypothalamic leptin-dependent phosphatidylinositol 3-kinase signaling

    PubMed Central

    Metlakunta, Anantha S.; Sahu, Maitrayee; Yasukawa, Hideo; Dhillon, Sandeep S.; Belsham, Denise D.; Yoshimura, Akihiko

    2011-01-01

    Suppressor of cytokine signaling-3 (SOCS3) is thought to be involved in the development of central leptin resistance and obesity by inhibiting STAT3 pathway. Because phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in transducing leptin action in the hypothalamus, we examined whether SOCS3 exerted an inhibition on this pathway. We first determined whether leptin sensitivity in the hypothalamic PI3K pathway was increased in brain-specific Socs3-deficient (NesKO) mice. In NesKO mice, hypothalamic insulin receptor substrate-1 (IRS1)-associated PI3K activity was significantly increased at 30 min and remained elevated up to 2 h after leptin intraperitoneal injection, but in wild-type (WT) littermates, the significant increase was only at 30 min. Hypothalamic p-STAT3 levels were increased up to 5 h in NesKO as opposed to 2 h in WT mice. In food-restricted WT mice with reduced body weight, leptin increased hypothalamic PI3K activity only at 30 min, and p-STAT3 levels at 30–120 min postinjection. These results suggest increased leptin sensitivity in both PI3K and STAT3 pathways in the hypothalamus of NesKO mice, which was not due to a lean phenotype. In the next experiment with a clonal hypothalamic neuronal cell line expressing proopiomelanocortin, we observed that whereas leptin significantly increased IRS1-associated PI3K activity and p-JAK2 levels in cells transfected with control vector, it failed to do so in SOCS3-overexpressed cells. Altogether, these results imply a SOCS3 inhibition of the PI3K pathway of leptin signaling in the hypothalamus, which may be one of the mechanisms behind the development of central leptin resistance and obesity. PMID:21325649

  7. Genome Editing in Neuroepithelial Stem Cells to Generate Human Neurons with High Adenosine-Releasing Capacity.

    PubMed

    Poppe, Daniel; Doerr, Jonas; Schneider, Marion; Wilkens, Ruven; Steinbeck, Julius A; Ladewig, Julia; Tam, Allison; Paschon, David E; Gregory, Philip D; Reik, Andreas; Müller, Christa E; Koch, Philipp; Brüstle, Oliver

    2018-06-01

    As a powerful regulator of cellular homeostasis and metabolism, adenosine is involved in diverse neurological processes including pain, cognition, and memory. Altered adenosine homeostasis has also been associated with several diseases such as depression, schizophrenia, or epilepsy. Based on its protective properties, adenosine has been considered as a potential therapeutic agent for various brain disorders. Since systemic application of adenosine is hampered by serious side effects such as vasodilatation and cardiac suppression, recent studies aim at improving local delivery by depots, pumps, or cell-based applications. Here, we report on the characterization of adenosine-releasing human embryonic stem cell-derived neuroepithelial stem cells (long-term self-renewing neuroepithelial stem [lt-NES] cells) generated by zinc finger nuclease (ZFN)-mediated knockout of the adenosine kinase (ADK) gene. ADK-deficient lt-NES cells and their differentiated neuronal and astroglial progeny exhibit substantially elevated release of adenosine compared to control cells. Importantly, extensive adenosine release could be triggered by excitation of differentiated neuronal cultures, suggesting a potential activity-dependent regulation of adenosine supply. Thus, ZFN-modified neural stem cells might serve as a useful vehicle for the activity-dependent local therapeutic delivery of adenosine into the central nervous system. Stem Cells Translational Medicine 2018;7:477-486. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  8. High Dengue Case Capture Rate in Four Years of a Cohort Study in Nicaragua Compared to National Surveillance Data

    PubMed Central

    Standish, Katherine; Kuan, Guillermina; Avilés, William; Balmaseda, Angel; Harris, Eva

    2010-01-01

    Dengue is a major public health problem in tropical and subtropical regions; however, under-reporting of cases to national surveillance systems hinders accurate knowledge of disease burden and costs. Laboratory-confirmed dengue cases identified through the Nicaraguan Pediatric Dengue Cohort Study (PDCS) were compared to those reported from other health facilities in Managua to the National Epidemiologic Surveillance (NES) program of the Nicaraguan Ministry of Health. Compared to reporting among similar pediatric populations in Managua, the PDCS identified 14 to 28 (average 21.3) times more dengue cases each year per 100,000 persons than were reported to the NES. Applying these annual expansion factors to national-level data, we estimate that the incidence of confirmed pediatric dengue throughout Nicaragua ranged from 300 to 1000 cases per 100,000 persons. We have estimated a much higher incidence of dengue than reported by the Ministry of Health. A country-specific expansion factor for dengue that allows for a more accurate estimate of incidence may aid governments and other institutions calculating disease burden, costs, resource needs for prevention and treatment, and the economic benefits of drug and vaccine development. PMID:20300515

  9. KSC-2011-3367

    NASA Image and Video Library

    2011-05-06

    Cape Canaveral, Fla. -- Students from across the nation gathered at NASA's Kennedy Space Center in Florida for the NASA Explorer Schools (NES) symposium. At the microphone is NASA Explorer Schools Lead Education Specialist Alicia Baturoni from NASA's Glenn Research Center. From left, the panel includes aerospace engineer with NASA's Launch Services Program Caley Burke, Gary Letchworth who is working on the Orion multipurpose crew vehicle, NASA Contract Specialist Nicole Rivera, wildlife ecologist with Innovative Heath Applications Becky Bolt, Tim Griffin who works in Kennedy's Chemical Analysis Branch, Xaivian Raymond with NASA Human Resources, aerospace engineer Sarah Cox who works on the space shuttle's thermal protection system, and chemical engineer Annie Caraccio. During the NES event, students presented their investigation project to their peers, scientists, engineers and education specialists. About 60 fourth- through 12-grade students nationwide are at the center May 4-7 participating in tours of processing and launch facilities and the U.S. Astronaut Hall of Fame, as well as several educational activities and a career panel question-and-answer session. About 30 teachers will receive professional development opportunities during the symposium. The participants were competitively selected after they completed an original investigation focused on existing NASA missions or research interests. Photo Credit: NASA/Kim Shiflett

  10. KSC-04pd1154

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Eduardo Tillet, principal of Howard A. Doolin Middle School, Miami, Fla., welcomes Center Director Jim Kennedy, plus NASA and KSC representatives, to the school. Doolin Middle School is one of 100 to take part in the NASA Explorer Schools (NES) program. Kennedy is talking with students, about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space. He is visiting NES schools in Florida and Georgia to share America’s new vision for space exploration with the next generation of explorers.

  11. New-Generation BeiDou (BDS-3) Experimental Satellite Precise Orbit Determination with an Improved Cycle-Slip Detection and Repair Algorithm

    PubMed Central

    Hu, Chao; Wang, Qianxin; Wang, Zhongyuan; Hernández Moraleda, Alberto

    2018-01-01

    Currently, five new-generation BeiDou (BDS-3) experimental satellites are working in orbit and broadcast B1I, B3I, and other new signals. Precise satellite orbit determination of the BDS-3 is essential for the future global services of the BeiDou system. However, BDS-3 experimental satellites are mainly tracked by the international GNSS Monitoring and Assessment Service (iGMAS) network. Under the current constraints of the limited data sources and poor data quality of iGMAS, this study proposes an improved cycle-slip detection and repair algorithm, which is based on a polynomial prediction of ionospheric delays. The improved algorithm takes the correlation of ionospheric delays into consideration to accurately estimate and repair cycle slips in the iGMAS data. Moreover, two methods of BDS-3 experimental satellite orbit determination, namely, normal equation stacking (NES) and step-by-step (SS), are designed to strengthen orbit estimations and to make full use of the BeiDou observations in different tracking networks. In addition, a method to improve computational efficiency based on a matrix eigenvalue decomposition algorithm is derived in the NES. Then, one-year of BDS-3 experimental satellite precise orbit determinations were conducted based on iGMAS and Multi-GNSS Experiment (MGEX) networks. Furthermore, the orbit accuracies were analyzed from the discrepancy of overlapping arcs and satellite laser range (SLR) residuals. The results showed that the average three-dimensional root-mean-square error (3D RMS) of one-day overlapping arcs for BDS-3 experimental satellites (C31, C32, C33, and C34) acquired by NES and SS are 31.0, 36.0, 40.3, and 50.1 cm, and 34.6, 39.4, 43.4, and 55.5 cm, respectively; the RMS of SLR residuals are 55.1, 49.6, 61.5, and 70.9 cm and 60.5, 53.6, 65.8, and 73.9 cm, respectively. Finally, one month of observations were used in four schemes of BDS-3 experimental satellite orbit determination to further investigate the reliability and advantages of the improved methods. It was suggested that the scheme with improved cycle-slip detection and repair algorithm based on NES was optimal, which improved the accuracy of BDS-3 experimental satellite orbits by 34.07%, 41.05%, 72.29%, and 74.33%, respectively, compared with the widely-used strategy. Therefore, improved methods for the BDS-3 experimental satellites proposed in this study are very beneficial for the determination of new-generation BeiDou satellite precise orbits. PMID:29724062

  12. Measurements and theoretical interpretation of points of zero charge/potential of BSA protein.

    PubMed

    Salis, Andrea; Boström, Mathias; Medda, Luca; Cugia, Francesca; Barse, Brajesh; Parsons, Drew F; Ninham, Barry W; Monduzzi, Maura

    2011-09-20

    The points of zero charge/potential of proteins depend not only on pH but also on how they are measured. They depend also on background salt solution type and concentration. The protein isoelectric point (IEP) is determined by electrokinetical measurements, whereas the isoionic point (IIP) is determined by potentiometric titrations. Here we use potentiometric titration and zeta potential (ζ) measurements at different NaCl concentrations to study systematically the effect of ionic strength on the IEP and IIP of bovine serum albumin (BSA) aqueous solutions. It is found that high ionic strengths produce a shift of both points toward lower (IEP) and higher (IIP) pH values. This result was already reported more than 60 years ago. At that time, the only available theory was the purely electrostatic Debye-Hückel theory. It was not able to predict the opposite trends of IIP and IEP with ionic strength increase. Here, we extend that theory to admit both electrostatic and nonelectrostatic (NES) dispersion interactions. The use of a modified Poisson-Boltzmann equation for a simple model system (a charge regulated spherical colloidal particle in NaCl salt solutions), that includes these ion specific interactions, allows us to explain the opposite trends observed for isoelectric point (zero zeta potential) and isoionic point (zero protein charge) of BSA. At higher concentrations, an excess of the anion (with stronger NES interactions than the cation) is adsorbed at the surface due to an attractive ionic NES potential. This makes the potential relatively more negative. Consequently, the IEP is pushed toward lower pH. But the charge regulation condition means that the surface charge becomes relatively more positive as the surface potential becomes more negative. Consequently, the IIP (measuring charge) shifts toward higher pH as concentration increases, in the opposite direction from the IEP (measuring potential). © 2011 American Chemical Society

  13. Navy Activity-Level Energy Systems Planning Procedure (A-LESP) Users Manual.

    DTIC Science & Technology

    1986-01-01

    1-in. stucco, air space 1.95 0.512 0.5-in. gypsum or plasterboard 0.56 1.78 Insulating drapes 1.72 0.58 ROOFS 2-in. insulation, 1-in. wood, air space...3 Annual Dry Bulb Degree Hours Above 780 F ............................ 267 -’ Table SDI Energy Conversion Units...A-LESP SURVEY DATE 5/83 Langleys 400 OPT. FEASIBILITY (YES/NO) Yes Dry bulb degree hours greater NES 180 MBtu/yr than 780 F 10,000 SIR 1.81_ Cooling

  14. KSC-2011-3369

    NASA Image and Video Library

    2011-05-06

    Cape Canaveral, Fla. -- Students and teachers from across the nation gathered for a photo opportunity during closing events of the NASA Explorer Schools (NES) symposium. During the NES gathering, students presented their investigation project to their peers, scientists, engineers and education specialists. About 60 fourth- through 12-grade students nationwide are at the center May 4-7 participating in tours of processing and launch facilities and the U.S. Astronaut Hall of Fame, as well as several educational activities and a career panel question-and-answer session. About 30 teachers will receive professional development opportunities during the symposium. The participants were competitively selected after they completed an original investigation focused on existing NASA missions or research interests. Photo Credit: NASA/Kim Shiflett

  15. KSC-2011-3372

    NASA Image and Video Library

    2011-05-06

    Cape Canaveral, Fla. -- Students and teachers from across the nation gathered for a photo opportunity during closing events of the NASA Explorer Schools (NES) symposium. During the NES gathering, students presented their investigation project to their peers, scientists, engineers and education specialists. About 60 fourth- through 12-grade students nationwide are at the center May 4-7 participating in tours of processing and launch facilities and the U.S. Astronaut Hall of Fame, as well as several educational activities and a career panel question-and-answer session. About 30 teachers will receive professional development opportunities during the symposium. The participants were competitively selected after they completed an original investigation focused on existing NASA missions or research interests. Photo Credit: NASA/Kim Shiflett

  16. KSC-2011-3370

    NASA Image and Video Library

    2011-05-06

    Cape Canaveral, Fla. -- Students and teachers from across the nation gathered for a photo opportunity during closing events of the NASA Explorer Schools (NES) symposium. During the NES gathering, students presented their investigation project to their peers, scientists, engineers and education specialists. About 60 fourth- through 12-grade students nationwide are at the center May 4-7 participating in tours of processing and launch facilities and the U.S. Astronaut Hall of Fame, as well as several educational activities and a career panel question-and-answer session. About 30 teachers will receive professional development opportunities during the symposium. The participants were competitively selected after they completed an original investigation focused on existing NASA missions or research interests. Photo Credit: NASA/Kim Shiflett

  17. KSC-2011-3371

    NASA Image and Video Library

    2011-05-06

    Cape Canaveral, Fla. -- Students and teachers from across the nation gathered for a photo opportunity during closing events of the NASA Explorer Schools (NES) symposium. During the NES gathering, students presented their investigation project to their peers, scientists, engineers and education specialists. About 60 fourth- through 12-grade students nationwide are at the center May 4-7 participating in tours of processing and launch facilities and the U.S. Astronaut Hall of Fame, as well as several educational activities and a career panel question-and-answer session. About 30 teachers will receive professional development opportunities during the symposium. The participants were competitively selected after they completed an original investigation focused on existing NASA missions or research interests. Photo Credit: NASA/Kim Shiflett

  18. Effects of a One Year Reusable Contraceptive Vaginal Ring on Vaginal Microflora and the Risk of Vaginal Infection: An Open-Label Prospective Evaluation

    PubMed Central

    Huang, Yongmei; Merkatz, Ruth B.; Hillier, Sharon L.; Roberts, Kevin; Blithe, Diana L.; Sitruk-Ware, Régine; Creinin, Mitchell D.

    2015-01-01

    Background A contraceptive vaginal ring (CVR) containing Nestorone® (NES) and ethinyl estradiol (EE) that is reusable for 1- year (13 cycles) is under development. This study assessed effects of this investigational CVR on the incidence of vaginal infections and change in vaginal microflora. Methods There were 120 women enrolled into a NES/EE CVR Phase III trial and a microbiology sub-study for up to 1- year of cyclic product use. Gynecological examinations were conducted at baseline, the first week of cycle 6 and last week of cycle 13 (or during early discontinuation visits). Vaginal swabs were obtained for wet mount microscopy, Gram stain and culture. The CVR was removed from the vagina at the last study visit and cultured. Semi-quantitative cultures for Lactobacillus, Gardnerella vaginalis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, anaerobic gram negative rods (GNRs), Candida albicans and other yeasts were performed on vaginal and CVR samples. Vaginal infections were documented throughout the study. Results Over 1- year of use, 3.3% of subjects were clinically diagnosed with bacterial vaginosis, 15.0% with vulvovaginal candidiasis, and 0.8% with trichomoniasis. The detection rate of these three infections did not change significantly from baseline to either Cycle 6 or 13. Nugent scores remained stable. H2O2-positive Lactobacillus dominated vaginal flora with a non-significant prevalence increase from 76.7% at baseline to 82.7% at cycle 6 and 90.2% at cycle 13, and a median concentration of 107 colony forming units (cfu) per gram. Although anaerobic GNRs prevalence increased significantly, the median concentration decreased slightly (104 to 103cfu per gram). There were no significant changes in frequency or concentrations of other pathogens. High levels of agreement between vaginal and ring surface microbiota were observed. Conclusion Sustained use of the NES/EE CVR did not increase the risk of vaginal infection and was not disruptive to the vaginal ecosystem. Trial Registration ClinicalTrials.gov NCT00263341, NCT00455156 PMID:26267119

  19. A CNGB1 Frameshift Mutation in Papillon and Phalène Dogs with Progressive Retinal Atrophy

    PubMed Central

    Ahonen, Saija J.; Arumilli, Meharji; Lohi, Hannes

    2013-01-01

    Progressive retinal degenerations are the most common causes of complete blindness both in human and in dogs. Canine progressive retinal atrophy (PRA) or degeneration resembles human retinitis pigmentosa (RP) and is characterized by a progressive loss of rod photoreceptor cells followed by a loss of cone function. The primary clinical signs are detected as vision impairment in a dim light. Although several genes have been associated with PRAs, there are still PRAs of unknown genetic cause in many breeds, including Papillons and Phalènes. We have performed a genome wide association and linkage studies in cohort of 6 affected Papillons and Phalènes and 14 healthy control dogs to map a novel PRA locus on canine chromosome 2, with a 1.9 Mb shared homozygous region in the affected dogs. Parallel exome sequencing of a trio identified an indel mutation, including a 1-bp deletion, followed by a 6-bp insertion in the CNGB1 gene. This mutation causes a frameshift and premature stop codon leading to probable nonsense mediated decay (NMD) of the CNGB1 mRNA. The mutation segregated with the disease and was confirmed in a larger cohort of 145 Papillons and Phalènes (PFisher = 1.4×10−8) with a carrier frequency of 17.2 %. This breed specific mutation was not present in 334 healthy dogs from 10 other breeds or 121 PRA affected dogs from 44 other breeds. CNGB1 is important for the photoreceptor cell function its defects have been previously associated with retinal degeneration in both human and mouse. Our study indicates that a frameshift mutation in CNGB1 is a cause of PRA in Papillons and Phalènes and establishes the breed as a large functional animal model for further characterization of retinal CNGB1 biology and possible retinal gene therapy trials. This study enables also the development of a genetic test for breeding purposes. PMID:24015210

  20. Associations of selected bedding types with incidence rates of subclinical and clinical mastitis in primiparous Holstein dairy cows.

    PubMed

    Rowbotham, R F; Ruegg, P L

    2016-06-01

    The objective of this observational study was to determine the association of exposure to selected bedding types with incidence of subclinical (SM) and clinical mastitis (CM) in primiparous Holstein dairy cows housed in identical pens at a single facility. At parturition, primiparous cows were randomly assigned to pens containing freestalls with 1 of 4 bedding materials: (1) deep-bedded new sand (NES, n=27 cows), (2) deep-bedded recycled sand (RS, n=25 cows), (3) deep-bedded manure solids (DBMS, n=31 cows), and (4) shallow-bedded manure solids over foam-core mattresses (SBMS, n=26 cows). For 12mo, somatic cell counts of quarter milk samples were determined every 28d and duplicate quarter milk samples were collected for microbiological analysis from all quarters with SM (defined as somatic cell count >200,000 cells/mL). During this period, duplicate quarter milk samples were also collected for microbial analysis from all cases of CM. For an additional 16mo, cases of CM were recorded; however, no samples were collected. Quarter days at risk (62,980) were distributed among bedding types and most quarters were enrolled for >150d. Of 135 cases of SM, 63% resulted in nonsignificant growth and 87% of recovered pathogens (n=33) were identified as coagulase-negative staphylococci. The distribution of etiologies of pathogens recovered from cases of SM was associated with bedding type. Coagulase-negative staphylococci were recovered from 12, 38, 11, and 46% of quarters with SM from cows in pens containing NES, RS, DBMS, and SBMS, respectively. A result of nonsignificant growth was obtained for 81, 59, 89, and 46% of quarters with SM from cows in pens containing NES, RS, DBMS, and SBMS, respectively. Quarters of primiparous cows bedded with NES tended to have greater survival time to incidence of CM than quarters of primiparous cows bedded with RS or DBMS. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. The processed isoform of the translation termination factor eRF3 localizes to the nucleus to interact with the ARF tumor suppressor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hashimoto, Yoshifumi; Kumagai, Naomichi; Hosoda, Nao

    2014-03-14

    Highlights: • So far, eRF3 has been thought to function exclusively in the cytoplasm. • eRF3 is a nucleo-cutoplasmic shuttling protein. • eRF3 has a leptomycin-sensitive nuclear export signal (NES). • Removal of NES by proteolytic cleavage allows eRF3 to translocate to the nucleus. • The processed eRF3 (p-eRF3) interacts with a nuclear tumor suppressor ARF. - Abstract: The eukaryotic releasing factor eRF3 is a multifunctional protein that plays pivotal roles in translation termination as well as the initiation of mRNA decay. eRF3 also functions in the regulation of apoptosis; eRF3 is cleaved at Ala73 by an as yet unidentifiedmore » protease into processed isoform of eRF3 (p-eRF3), which interacts with the inhibitors of apoptosis proteins (IAPs). The binding of p-eRF3 with IAPs leads to the release of active caspases from IAPs, which promotes apoptosis. Although full-length eRF3 is localized exclusively in the cytoplasm, p-eRF3 localizes in the nucleus as well as the cytoplasm. We here focused on the role of p-eRF3 in the nucleus. We identified leptomycin-sensitive nuclear export signal (NES) at amino acid residues 61–71 immediately upstream of the cleavage site Ala73. Thus, the proteolytic cleavage of eRF3 into p-eRF3 leads to release an amino-terminal fragment containing NES to allow the relocalization of eRF3 into the nucleus. Consistent with this, p-eRF3 more strongly interacted with the nuclear ARF tumor suppressor than full-length eRF3. These results suggest that while p-eRF3 interacts with IAPs to promote apoptosis in the cytoplasm, p-eRF3 also has some roles in regulating cell death in the nucleus.« less

  2. Identification of a Functional, CRM-1-Dependent Nuclear Export Signal in Hepatitis C Virus Core Protein

    PubMed Central

    Cerutti, Andrea; Maillard, Patrick; Minisini, Rosalba; Vidalain, Pierre-Olivier; Roohvand, Farzin; Pecheur, Eve-Isabelle; Pirisi, Mario; Budkowska, Agata

    2011-01-01

    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS), but no nuclear export signal (NES) has yet been identified. We show here that the aa(109–133) region directs the translocation of core from the nucleus to the cytoplasm by the CRM-1-mediated nuclear export pathway. Mutagenesis of the three hydrophobic residues (L119, I123 and L126) in the identified NES or in the sequence encoding the mature core aa(1–173) significantly enhanced the nuclear localisation of the corresponding proteins in transfected Huh7 cells. Both the NES and the adjacent hydrophobic sequence in domain II of core were required to maintain the core protein or its fragments in the cytoplasmic compartment. Electron microscopy studies of the JFH1 replication model demonstrated that core was translocated into the nucleus a few minutes after the virus entered the cell. The blockade of nucleocytoplasmic export by leptomycin B treatment early in infection led to the detection of core protein in the nucleus by confocal microscopy and coincided with a decrease in virus replication. Our data suggest that the functional NLS and NES direct HCV core protein shuttling between the cytoplasmic and nuclear compartments, with at least some core protein transported to the nucleus. These new properties of HCV core may be essential for virus multiplication and interaction with nuclear molecules, influence cell signaling and the pathogenesis of HCV infection. PMID:22039426

  3. Vertical Object Layout and Compression for Fixed Heaps

    NASA Astrophysics Data System (ADS)

    Titzer, Ben L.; Palsberg, Jens

    Research into embedded sensor networks has placed increased focus on the problem of developing reliable and flexible software for microcontroller-class devices. Languages such as nesC [10] and Virgil [20] have brought higher-level programming idioms to this lowest layer of software, thereby adding expressiveness. Both languages are marked by the absence of dynamic memory allocation, which removes the need for a runtime system to manage memory. While nesC offers code modules with statically allocated fields, arrays and structs, Virgil allows the application to allocate and initialize arbitrary objects during compilation, producing a fixed object heap for runtime. This paper explores techniques for compressing fixed object heaps with the goal of reducing the RAM footprint of a program. We explore table-based compression and introduce a novel form of object layout called vertical object layout. We provide experimental results that measure the impact on RAM size, code size, and execution time for a set of Virgil programs. Our results show that compressed vertical layout has better execution time and code size than table-based compression while achieving more than 20% heap reduction on 6 of 12 benchmark programs and 2-17% heap reduction on the remaining 6. We also present a formalization of vertical object layout and prove tight relationships between three styles of object layout.

  4. A mediational model of obesity related disordered eating: The roles of childhood emotional abuse and self-perception.

    PubMed

    Hymowitz, Genna; Salwen, Jessica; Salis, Katie Lee

    2017-08-01

    The extant literature indicates negative self-perceptions are a risk factor for disordered eating (DE) and DE is a risk factor for overweight and obesity. While childhood emotional abuse (EA) is often linked to DE and obesity, it is typically not included in comprehensive models of these health problems. Further investigation of interactions among EA, self-perception, and DE is needed to refine treatments for overweight, obesity, and DE. This study evaluated a model of DE and weight difficulties in which negative self-perception mediate the relationship between EA and DE, and DE predicts body mass index (BMI) in a population of emerging adults. Further, this study investigated the utility of history of EA for prediction of DE and classification of individuals with and without DE. Self-report questionnaires on childhood trauma, psychopathology, and eating behaviors were administered to 598 undergraduate students. Latent variable analysis confirmed the hypothesized model. Recursive partitioning determined that individuals reporting a high level of EA likely meet criteria for night eating syndrome (NES) or binge eating disorder (BED), and history of EA has a moderate to high level of specificity as a predictor of BED and NES. These findings confirm the necessity of evaluating EA and DE in emerging adults with weight difficulties, and the importance of assessing self-perception and DE in individuals with a history of EA. Future studies should investigate the utility of addressing EA and self-perception in interventions for DE and obesity and to determine whether these findings can be generalized to a clinical population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. KSC-2011-3366

    NASA Image and Video Library

    2011-05-06

    Cape Canaveral, Fla. -- Students from across the nation gathered at NASA's Kennedy Space Center in Florida for the NASA Explorer Schools (NES) symposium. Here, the panel and students participate in a question-and-answer session. During the NES event, students presented their investigation project to their peers, scientists, engineers and education specialists. About 60 fourth- through 12-grade students nationwide are at the center May 4-7 participating in tours of processing and launch facilities and the U.S. Astronaut Hall of Fame, as well as several educational activities and a career panel question-and-answer session. About 30 teachers will receive professional development opportunities during the symposium. The participants were competitively selected after they completed an original investigation focused on existing NASA missions or research interests. Photo Credit: NASA/Kim Shiflett

  6. KSC-2011-3373

    NASA Image and Video Library

    2011-05-06

    Cape Canaveral, Fla. -- Priscilla Moore, NASA Education Programs Specialist, speaks to students from across the nation gathered for the closing events of the NASA Explorer Schools (NES) symposium. During the NES gathering, students presented their investigation project to their peers, scientists, engineers and education specialists. About 60 fourth- through 12-grade students nationwide are at the center May 4-7 participating in tours of processing and launch facilities and the U.S. Astronaut Hall of Fame, as well as several educational activities and a career panel question-and-answer session. About 30 teachers will receive professional development opportunities during the symposium. The participants were competitively selected after they completed an original investigation focused on existing NASA missions or research interests. Photo Credit: NASA/Kim Shiflett

  7. KSC-06pd0142

    NASA Image and Video Library

    2006-01-23

    KENNEDY SPACE CENTER, FLA. — At Warrington Middle School in Pensacola, Fla., astronaut Alan Poindexter explains a science principal to students. Poindexter joined Center Director Jim Kennedy and others on a visit to the school, which has been named one of NASA’s Explorer Schools (NES). Kennedy is visiting the school to share the vision for space exploration with the next generation. He is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space. NES establishes a three-year partnership annually between NASA and 50 NASA Explorer School teams, consisting of teachers and education administrators from diverse communities nationwide. Photo credit: NASA/Cory Huston

  8. KSC-04PD-2041

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. Students at Immokalee Middle School in Naples, Fla., walk to Immokalee High School for a special presentation in the auditorium by Center Director Jim Kennedy and astronaut Terry Virts. Immokalee is part of NASAs Explorer School (NES) Program and is teamed with Pine Ridge Middle School. Kennedy is visiting the school to share the vision for space exploration with the next generation of explorers. He is talking with students about our destiny as explorers, NASAs stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space. NES establishes a three-year partnership annually between NASA and 50 NASA Explorer Schools teams, consisting of teachers and education administrators from diverse communities nationwide.

  9. Modélisation des phénomènes électromagnétiques dans les matériaux supraconducteurs

    NASA Astrophysics Data System (ADS)

    Maslouh, M.; Bouillault, F.

    1998-03-01

    This paper describes a numerical method to determine the losses in a solid superconductor plunged in transverse magnetic field or in transport current. The model which is based on the Bean critical state, shows that the hysteretic phenomena are taken in account. Cet article présente une méthode de calcul permettant la détermination des pertes dans un matériau massif supraconducteur soumis à un champ magnétique transversal ou parcouru par un courant de transport. Le modèle, basé sur celui de l'état critique de Bean, met en évidence le caractère hystérétique des phénomènes.

  10. Operational Definitions of Ambulatory Care Nursing Activities; Phase 2 of the Workload Management System for Nursing Ambulatory Care Project.

    DTIC Science & Technology

    1987-04-01

    around the extremity, assess measurement, mark area for future measurement (S 0M04) x206 FETAL HEART ’NES, DOPPLER: expose abdominal area, assess fetal ... heart tones utilizing the doptone with lubricant, clean abdomen (S 2413) x209 FETAL HEART TONES, LANUAL: position patient in left lateral or semi...recumbent position, find best quadrant for FHT’s, place fingers over mother’s raoial pulse; count fetal heart tones for one minute (S 2412) x210 HEAD

  11. Convergence analysis of evolutionary algorithms that are based on the paradigm of information geometry.

    PubMed

    Beyer, Hans-Georg

    2014-01-01

    The convergence behaviors of so-called natural evolution strategies (NES) and of the information-geometric optimization (IGO) approach are considered. After a review of the NES/IGO ideas, which are based on information geometry, the implications of this philosophy w.r.t. optimization dynamics are investigated considering the optimization performance on the class of positive quadratic objective functions (the ellipsoid model). Exact differential equations describing the approach to the optimizer are derived and solved. It is rigorously shown that the original NES philosophy optimizing the expected value of the objective functions leads to very slow (i.e., sublinear) convergence toward the optimizer. This is the real reason why state of the art implementations of IGO algorithms optimize the expected value of transformed objective functions, for example, by utility functions based on ranking. It is shown that these utility functions are localized fitness functions that change during the IGO flow. The governing differential equations describing this flow are derived. In the case of convergence, the solutions to these equations exhibit an exponentially fast approach to the optimizer (i.e., linear convergence order). Furthermore, it is proven that the IGO philosophy leads to an adaptation of the covariance matrix that equals in the asymptotic limit-up to a scalar factor-the inverse of the Hessian of the objective function considered.

  12. Combining gas-phase electrophoretic mobility molecular analysis (GEMMA), light scattering, field flow fractionation and cryo electron microscopy in a multidimensional approach to characterize liposomal carrier vesicles

    PubMed Central

    Gondikas, Andreas; von der Kammer, Frank; Hofmann, Thilo; Marchetti-Deschmann, Martina; Allmaier, Günter; Marko-Varga, György; Andersson, Roland

    2017-01-01

    For drug delivery, characterization of liposomes regarding size, particle number concentrations, occurrence of low-sized liposome artefacts and drug encapsulation are of importance to understand their pharmacodynamic properties. In our study, we aimed to demonstrate the applicability of nano Electrospray Gas-Phase Electrophoretic Mobility Molecular Analyser (nES GEMMA) as a suitable technique for analyzing these parameters. We measured number-based particle concentrations, identified differences in size between nominally identical liposomal samples, and detected the presence of low-diameter material which yielded bimodal particle size distributions. Subsequently, we compared these findings to dynamic light scattering (DLS) data and results from light scattering experiments coupled to Asymmetric Flow-Field Flow Fractionation (AF4), the latter improving the detectability of smaller particles in polydisperse samples due to a size separation step prior detection. However, the bimodal size distribution could not be detected due to method inherent limitations. In contrast, cryo transmission electron microscopy corroborated nES GEMMA results. Hence, gas-phase electrophoresis proved to be a versatile tool for liposome characterization as it could analyze both vesicle size and size distribution. Finally, a correlation of nES GEMMA results with cell viability experiments was carried out to demonstrate the importance of liposome batch-to-batch control as low-sized sample components possibly impact cell viability. PMID:27639623

  13. Measuring epistemic curiosity and its diversive and specific components.

    PubMed

    Litman, Jordan A; Spielberger, Charles D

    2003-02-01

    A questionnaire constructed to assess epistemic curiosity (EC) and perceptual curiosity (PC) curiosity was administered to 739 undergraduates (546 women, 193 men) ranging in age from 18 to 65. The study participants also responded to the trait anxiety, anger, depression, and curiosity scales of the State-Trait Personality Inventory (STPI; Spielberger et al., 1979) and selected subscales of the Sensation Seeking (SSS; Zuckerman, Kolin, Price, & Zoob, 1964) and Novelty Experiencing (NES; Pearson, 1970) scales. Factor analyses of the curiosity items with oblique rotation identified EC and PC factors with clear simple structure. Subsequent analyses of the EC items provided the basis for developing an EC scale, with Diversive and Specific Curiosity subscales. Moderately high correlations of the EC scale and subscales with other measures of curiosity provided strong evidence of convergent validity. Divergent validity was demonstrated by minimal correlations with trait anxiety and the sensation-seeking measures, and essentially zero correlations with the STPI trait anger and depression scales. Male participants had significantly higher scores on the EC scale and the NES External Cognition subscale (effect sizes of r =.16 and.21, respectively), indicating that they were more interested than female participants in solving problems and discovering how things work. Male participants also scored significantly higher than female participants on the SSS Thrill-and-Adventure and NES External Sensation subscales (r =.14 and.22, respectively), suggesting that they were more likely to engage in sensation-seeking activities.

  14. Association between DNA methylation in cord blood and maternal smoking: The Hokkaido Study on Environment and Children's Health.

    PubMed

    Miyake, Kunio; Kawaguchi, Akio; Miura, Ryu; Kobayashi, Sachiko; Tran, Nguyen Quoc Vuong; Kobayashi, Sumitaka; Miyashita, Chihiro; Araki, Atsuko; Kubota, Takeo; Yamagata, Zentaro; Kishi, Reiko

    2018-04-04

    Maternal smoking is reported to cause adverse effects on the health of the unborn child, the underlying mechanism for which is thought to involve alterations in DNA methylation. We examined the effects of maternal smoking on DNA methylation in cord blood, in 247 mother-infant pairs in the Sapporo cohort of the Hokkaido Study, using the Infinium HumanMethylation 450K BeadChip. We first identified differentially methylated CpG sites with a false discovery rate (FDR) of <0.05 and the magnitude of DNA methylation changes (|β| >0.02) from the pairwise comparisons of never-smokers (Ne-S), sustained-smokers (Su-S), and stopped-smokers (St-S). Subsequently, secondary comparisons between St-S and Su-S revealed nine common sites that mapped to ACSM3, AHRR, CYP1A1, GFI1, SHANK2, TRIM36, and the intergenic region between ANKRD9 and RCOR1 in Ne-S vs. Su-S, and one common CpG site mapping to EVC2 in Ne-S vs. St-S. Further, we verified these CpG sites and examined neighbouring sites using bisulfite next-generation sequencing, except for AHRR cg21161138. These changes in DNA methylation implicate the effect of smoking cessation. Our findings add to the current knowledge of the association between DNA methylation and maternal smoking and suggest future studies for clarifying this relationship in disease development.

  15. KSC-2011-3365

    NASA Image and Video Library

    2011-05-06

    Cape Canaveral, Fla. -- Students from across the nation gathered at NASA's Kennedy Space Center in Florida for the NASA Explorer Schools (NES) symposium In the Center for Space Education at Kennedy, a student participates in a hands-on activity as education specialists assist. During the NES event, students presented their investigation project to their peers, scientists, engineers and education specialists. About 60 fourth- through 12-grade students nationwide are at the center May 4-7 participating in tours of processing and launch facilities and the U.S. Astronaut Hall of Fame, as well as several educational activities and a career panel question-and-answer session. About 30 teachers will receive professional development opportunities during the symposium. The participants were competitively selected after they completed an original investigation focused on existing NASA missions or research interests. Photo Credit: NASA/Kim Shiflett

  16. KSC-04pd2052

    NASA Image and Video Library

    2004-09-28

    KENNEDY SPACE CENTER, FLA. - Les Gold, Aerospace Education specialist with KSC, speaks to students at Immokalee Middle School in Naples, Fla. At right is astronaut Terry Virts. Gold and Virts accompanied Center Director Jim Kennedy for a presentation at the school to share the vision for space exploration with the next generation of explorers. Immokalee is part of NASA’s Explorer School (NES) Program and is teamed with Pine Ridge Middle School. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space. NES establishes a three-year partnership annually between NASA and 50 NASA Explorer Schools teams, consisting of teachers and education administrators from diverse communities nationwide.

  17. Fluorescent recovery after photobleaching (FRAP) analysis of nuclear export rates identifies intrinsic features of nucleocytoplasmic transport.

    PubMed

    Cardarelli, Francesco; Tosti, Luca; Serresi, Michela; Beltram, Fabio; Bizzarri, Ranieri

    2012-02-17

    A quantitative description of carrier-mediated nuclear export in live cells is presented. To this end, we fused a prototypical leucine-rich nuclear export signal (NES) to GFP as a cargo model and expressed the fluorescent chimera in live CHO-K1 cells. By modeling FRAP data, we calculate the NES affinity for the export machinery and the maximum rate of nuclear export achievable at saturation of endogenous carriers. The measured active-export time through the Nuclear Pore Complex (NPC) is 18 ms, remarkably similar to the previously determined active-import rate. Also, our results reveal that active export/import and active export/passive diffusion fluxes are uncoupled, thus complementing previous reports on active import/passive diffusion uncoupling. These findings suggest differential gating at the NPC level.

  18. KSC-04PD-2048

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. Astronaut Terry Virts talks to students and staff of Immokalee Middle School in Naples, Fla., about what it takes for mission success and the importance of teamwork. Virts accompanied Center Director Jim Kennedy on the visit to the school to share the vision for space exploration with the next generation of explorers. Immokalee is part of NASAs Explorer School (NES) Program and is teamed with Pine Ridge Middle School. Kennedy is talking with students about our destiny as explorers, NASAs stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space. NES establishes a three-year partnership annually between NASA and 50 NASA Explorer Schools teams, consisting of teachers and education administrators from diverse communities nationwide.

  19. KSC-04PD-2046

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. Astronaut Terry Virts talks to students and staff of Immokalee Middle School in Naples, Fla., about what it takes for mission success and the importance of teamwork. Virts accompanied Center Director Jim Kennedy on the visit to the school to share the vision for space exploration with the next generation of explorers. Immokalee is part of NASAs Explorer School (NES) Program and is teamed with Pine Ridge Middle School. Kennedy is talking with students about our destiny as explorers, NASAs stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space. NES establishes a three-year partnership annually between NASA and 50 NASA Explorer Schools teams, consisting of teachers and education administrators from diverse communities nationwide.

  20. Cortical processing during smartphone text messaging.

    PubMed

    Tatum, William O; DiCiaccio, Benedetto; Yelvington, Kirsten H

    2016-06-01

    The objective of this study was to report the EEG features of text messaging using smartphones. One hundred twenty-nine patients were prospectively evaluated during video-EEG monitoring (VEM) over 16months. A reproducible texting rhythm (TR) present during active text messaging with a smartphone was compared with passive and forced audio telephone use, thumb/finger movements, cognitive testing/calculation, scanning eye movements, and speech/language tasks in patients with and without epilepsy. Statistical significance was set at p<0.05. Twenty-seven patients with a TR were identified from a cohort of 129 (93 female, mean age: 36; range: 18-71) unselected VEM patients. Fifty-three out of 129 patients had epileptic seizures (ES), 74/129 had nonepileptic seizures (NES), and 2/129 were dual-diagnosed. A reproducible TR was present in 27/129 (20.9%) specific to text messaging (p<0.0001) and present in 28% of patients with ES and 16% of patients with NES (p=NS). The TR was absent during independent tasks and audio cellular telephone use (p<0.0001). Age, gender, epilepsy type, MRI results, and EEG lateralization in patients with focal seizures were unrelated (p=NS). Our results suggest that the TR on scalp EEG represents a novel technology-specific neurophysiological alteration of brain networks. We propose that cortical processing in the contemporary brain is uniquely activated by the use of PEDs. These findings have practical implications that could impact industry and research in nonverbal communication. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pavlikova, Nela, E-mail: nela.pavlikova@lf3.cuni.cz; Smetana, Pavel; Halada, Petr

    Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cellmore » line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE. - Highlights: • Epidemiologic studies connect pollution with incidence of diabetes mellitus. • We explored the effect of DDT and DDE on protein expression in the NES2Y pancreatic beta cell line. • One month exposure to three sublethal concentrations of DDT and DDE was employed. • Expression of alpha-enolase, actin, cytokeratin 8 and 18 was reduced in NES2Y/DDT. • Expression of HNRH1 and cytokeratin 18 was reduced in NES2Y/DDE.« less

  2. Reversible Oxidation of a Conserved Methionine in the Nuclear Export Sequence Determines Subcellular Distribution and Activity of the Fungal Nitrate Regulator NirA.

    PubMed

    Gallmetzer, Andreas; Silvestrini, Lucia; Schinko, Thorsten; Gesslbauer, Bernd; Hortschansky, Peter; Dattenböck, Christoph; Muro-Pastor, María Isabel; Kungl, Andreas; Brakhage, Axel A; Scazzocchio, Claudio; Strauss, Joseph

    2015-07-01

    The assimilation of nitrate, a most important soil nitrogen source, is tightly regulated in microorganisms and plants. In Aspergillus nidulans, during the transcriptional activation process of nitrate assimilatory genes, the interaction between the pathway-specific transcription factor NirA and the exportin KapK/CRM1 is disrupted, and this leads to rapid nuclear accumulation and transcriptional activity of NirA. In this work by mass spectrometry, we found that in the absence of nitrate, when NirA is inactive and predominantly cytosolic, methionine 169 in the nuclear export sequence (NES) is oxidized to methionine sulfoxide (Metox169). This oxidation depends on FmoB, a flavin-containing monooxygenase which in vitro uses methionine and cysteine, but not glutathione, as oxidation substrates. The function of FmoB cannot be replaced by alternative Fmo proteins present in A. nidulans. Exposure of A. nidulans cells to nitrate led to rapid reduction of NirA-Metox169 to Met169; this reduction being independent from thioredoxin and classical methionine sulfoxide reductases. Replacement of Met169 by isoleucine, a sterically similar but not oxidizable residue, led to partial loss of NirA activity and insensitivity to FmoB-mediated nuclear export. In contrast, replacement of Met169 by alanine transformed the protein into a permanently nuclear and active transcription factor. Co-immunoprecipitation analysis of NirA-KapK interactions and subcellular localization studies of NirA mutants lacking different parts of the protein provided evidence that Met169 oxidation leads to a change in NirA conformation. Based on these results we propose that in the presence of nitrate the activation domain is exposed, but the NES is masked by a central portion of the protein (termed nitrate responsive domain, NiRD), thus restricting active NirA molecules to the nucleus. In the absence of nitrate, Met169 in the NES is oxidized by an FmoB-dependent process leading to loss of protection by the NiRD, NES exposure, and relocation of the inactive NirA to the cytosol.

  3. The fate and origin of the nuclear envelope during and after mitosis in Amoeba proteus. I. Synthesis and behavior of phospholipids of the nuclear envelope during the cell life cycle

    PubMed Central

    1975-01-01

    The synthesis and behavior of Amoeba proteus nuclear envelope (NE) phospholipids were studied. Most NE phospholipid synthesis occurs during G2 and little during mitosis or S. (A. proteus has no G1 phase). Autoradiographic observations after implantation of [3-H] choline nuclei into unlabeled cells reveal little turnover of NE phospholipid during interphase but during mitosis all the label is dispersed through the cytoplasm. Beginning at telophase all the label is dispersed through the cytoplasm. Beginning at telophase all the NE phospholipid label returns to the daughter NEs. This observation, along with the finding that no NE phospholipid synthesis occurs during mitosis or S, indicates that no de novo NE phospholipid production is required for newly forming NEs. Similarlyemetine, at concentrations that inhibit 97 percent of protein synthesis, does not prevent the post mitotic formation of NEs, suggesting that previously manufactured proteins are used in making new NEs. If a nucleus containing labeled NE phospholipids is transplanted into an unlabeled nucleate cell and the cell is allowed to grow and divide, the resultant four nuclei are equally labeled. This finding supports, but does not prove (see next paragraph), the conclusion that there probably is no continuity of the A. proteus NE during mitosis. When a phospholipid-labeled nucleus is implanted into a cell in mitosis, the grafted nucleus is not induced to enter mitosis. There is, however, a marked increase in the turnover of that nucleus's NE phospholipids with no apparent breakdown of the NE; this indicated that the mitotic cytoplasm possesses a factor that stimulates NE phospholipid exchange with the cytoplasm. That enhanced turnover is not accompanied by visible structural alteration makes less certain the earlier conclusion that no NE continuity exists during mitosis. Perhaps the most important finding in this study is that there are present, at restricted times in the cell cycle, factors capable of inducing accelerated exchange of structural components without microscopically detectable disruptions of structure. PMID:805790

  4. Design of a Lunar Quick-Attach Mechanism to Hummer Vehicle Mounting Interface

    NASA Technical Reports Server (NTRS)

    Grismore, David A.

    2010-01-01

    This report presents my work experiences while I was an intern with NASA (National Aeronautic and Space Administration) in the Spring of2010 at the Kennedy Space Center (KSC) launch facility in Cape Canaveral, Florida as a member of the NASA USRP (Undergraduate Student Research Program) program. I worked in the Surface Systems (NE-S) group during the internship. Within NE-S, two ASRC (Arctic Slope Regional Corporation) contract engineers, A.J. Nick and Jason Schuler, had developed a "Quick-Attach" mechanism for the Chariot Rover, the next generation lunar rover. My project was to design, analyze, and possibly fabricate a mounting interface between their "Quick-Attach" and a Hummer vehicle. This interface was needed because it would increase their capabilities to test the Quick Attach and its various attachments, as they do not have access to a Chariot Rover at KSC. I utilized both Pro Engineer, a 3D CAD software package, and a Coordinate Measuring Machine (CMM) known as a FAROarm to collect data and create my design. I relied on hand calculations and the Mechanica analysis tool within Pro Engineer to perform stress analysis on the design. After finishing the design, I began working on creating professional level CAD drawings and issuing them into the KSC design database known as DDMS before the end of the internship.

  5. Sphingosine 1-phosphate lyase ablation disrupts presynaptic architecture and function via an ubiquitin- proteasome mediated mechanism.

    PubMed

    Mitroi, Daniel N; Deutschmann, André U; Raucamp, Maren; Karunakaran, Indulekha; Glebov, Konstantine; Hans, Michael; Walter, Jochen; Saba, Julie; Gräler, Markus; Ehninger, Dan; Sopova, Elena; Shupliakov, Oleg; Swandulla, Dieter; van Echten-Deckert, Gerhild

    2016-11-24

    The bioactive lipid sphingosine 1-phosphate (S1P) is a degradation product of sphingolipids that are particularly abundant in neurons. We have shown previously that neuronal S1P accumulation is toxic leading to ER-stress and an increase in intracellular calcium. To clarify the neuronal function of S1P, we generated brain-specific knockout mouse models in which S1P-lyase (SPL), the enzyme responsible for irreversible S1P cleavage was inactivated. Constitutive ablation of SPL in the brain (SPL fl/fl/Nes ) but not postnatal neuronal forebrain-restricted SPL deletion (SPL fl/fl/CaMK ) caused marked accumulation of S1P. Hence, altered presynaptic architecture including a significant decrease in number and density of synaptic vesicles, decreased expression of several presynaptic proteins, and impaired synaptic short term plasticity were observed in hippocampal neurons from SPL fl/fl/Nes mice. Accordingly, these mice displayed cognitive deficits. At the molecular level, an activation of the ubiquitin-proteasome system (UPS) was detected which resulted in a decreased expression of the deubiquitinating enzyme USP14 and several presynaptic proteins. Upon inhibition of proteasomal activity, USP14 levels, expression of presynaptic proteins and synaptic function were restored. These findings identify S1P metabolism as a novel player in modulating synaptic architecture and plasticity.

  6. Imaging evaluation of traumatic thoracolumbar spine injuries: Radiological review

    PubMed Central

    Gamanagatti, Shivanand; Rathinam, Deepak; Rangarajan, Krithika; Kumar, Atin; Farooque, Kamran; Sharma, Vijay

    2015-01-01

    Spine fractures account for a large portion of musculoskeletal injuries worldwide. A classification of spine fractures is necessary in order to develop a common language for treatment indications and outcomes. Several classification systems have been developed based on injury anatomy or mechanisms of action, but they have demonstrated poor reliability, have yielded little prognostic information, and have not been widely used. For this reason, the Arbeitsgemeinschaftfür Osteosynthesefragen (AO) committee has classified thorocolumbar spine injuries based on the pathomorphological criteria into3 types (A: Compression; B: Distraction; C: Axial torque and rotational deformity). Each of these types is further divided into 3 groups and 3 subgroups reflecting progressive scale of morphological damage and the degree of instability. Because of its highly detailed sub classifications, the AO system has shown limited interobserver variability. It is similar to its predecessors in that it does not incorporate the patient’s neurologic status.The need for a reliable, reproducible, clinically relevant, prognostic classification system with an optimal balance of ease of use and detail of injury description contributed to the development of a new classification system, the thoracolumbar injury classification and severity score (TLICS). The TLICS defines injury based on three clinical characteristics: injury morphology, integrity of the posterior ligamentous complex, and neurologic status of the patient. The severity score offers prognostic information and is helpful in decision making about surgical vs nonsurgical management. PMID:26435776

  7. KSC-2011-3364

    NASA Image and Video Library

    2011-05-06

    Cape Canaveral, Fla. -- Students from across the nation gathered at NASA's Kennedy Space Center in Florida for the NASA Explorer Schools (NES) symposium. In the Center for Space Education at Kennedy, a student participates in a hands-on activity as an education specialist looks on. During the NES event, students presented their investigation project to their peers, scientists, engineers and education specialists. About 60 fourth- through 12-grade students nationwide are at the center May 4-7 participating in tours of processing and launch facilities and the U.S. Astronaut Hall of Fame, as well as several educational activities and a career panel question-and-answer session. About 30 teachers will receive professional development opportunities during the symposium. The participants were competitively selected after they completed an original investigation focused on existing NASA missions or research interests. Photo Credit: NASA/Kim Shiflett

  8. Fluorescent Recovery after Photobleaching (FRAP) Analysis of Nuclear Export Rates Identifies Intrinsic Features of Nucleocytoplasmic Transport*

    PubMed Central

    Cardarelli, Francesco; Tosti, Luca; Serresi, Michela; Beltram, Fabio; Bizzarri, Ranieri

    2012-01-01

    A quantitative description of carrier-mediated nuclear export in live cells is presented. To this end, we fused a prototypical leucine-rich nuclear export signal (NES) to GFP as a cargo model and expressed the fluorescent chimera in live CHO-K1 cells. By modeling FRAP data, we calculate the NES affinity for the export machinery and the maximum rate of nuclear export achievable at saturation of endogenous carriers. The measured active-export time through the Nuclear Pore Complex (NPC) is 18 ms, remarkably similar to the previously determined active-import rate. Also, our results reveal that active export/import and active export/passive diffusion fluxes are uncoupled, thus complementing previous reports on active import/passive diffusion uncoupling. These findings suggest differential gating at the NPC level. PMID:22190681

  9. Leadership skills and attributes of women and nurse executives: challenges for the 21st century.

    PubMed

    Carroll, Theresa L

    2005-01-01

    This study used a descriptive comparative design in which the skills/attributes identified by women leaders were compared to the skills/attributes identified by the nurse executives (NEs). For the women leaders and NEs, 6 factors were identified through principal components analysis: (1) personal integrity, (2) strategic vision/action orientation, (3) team building/communication skills, (4) management and technical competencies, (5) people skills (eg, empowering others, networking, valuing diversity, working collaboratively), and (6) personal survival skills/attributes (eg, political sensitivity, self-direction, self-reliance, courage, and candor). The items that received the highest level of agreement regarding importance for both groups were contained in the personal integrity factor, which included ethical standards, trustworthiness, and credibility. These factors are discussed and implications for leadership development and nursing administration graduate programs are identified.

  10. Nmd3p Is a Crm1p-Dependent Adapter Protein for Nuclear Export of the Large Ribosomal Subunit

    PubMed Central

    Ho, Jennifer Hei-Ngam; Kallstrom, George; Johnson, Arlen W.

    2000-01-01

    In eukaryotic cells, nuclear export of nascent ribosomal subunits through the nuclear pore complex depends on the small GTPase Ran. However, neither the nuclear export signals (NESs) for the ribosomal subunits nor the receptor proteins, which recognize the NESs and mediate export of the subunits, have been identified. We showed previously that Nmd3p is an essential protein from yeast that is required for a late step in biogenesis of the large (60S) ribosomal subunit. Here, we show that Nmd3p shuttles and that deletion of the NES from Nmd3p leads to nuclear accumulation of the mutant protein, inhibition of the 60S subunit biogenesis, and inhibition of the nuclear export of 60S subunits. Moreover, the 60S subunits that accumulate in the nucleus can be coimmunoprecipitated with the NES-deficient Nmd3p. 60S subunit biogenesis and export of truncated Nmd3p were restored by the addition of an exogenous NES. To identify the export receptor for Nmd3p we show that Nmd3p shuttling and 60S export is blocked by the Crm1p-specific inhibitor leptomycin B. These results identify Crm1p as the receptor for Nmd3p export. Thus, export of the 60S subunit is mediated by the adapter protein Nmd3p in a Crm1p-dependent pathway. PMID:11086007

  11. Combining gas-phase electrophoretic mobility molecular analysis (GEMMA), light scattering, field flow fractionation and cryo electron microscopy in a multidimensional approach to characterize liposomal carrier vesicles.

    PubMed

    Urey, Carlos; Weiss, Victor U; Gondikas, Andreas; von der Kammer, Frank; Hofmann, Thilo; Marchetti-Deschmann, Martina; Allmaier, Günter; Marko-Varga, György; Andersson, Roland

    2016-11-20

    For drug delivery, characterization of liposomes regarding size, particle number concentrations, occurrence of low-sized liposome artefacts and drug encapsulation are of importance to understand their pharmacodynamic properties. In our study, we aimed to demonstrate the applicability of nano Electrospray Gas-Phase Electrophoretic Mobility Molecular Analyser (nES GEMMA) as a suitable technique for analyzing these parameters. We measured number-based particle concentrations, identified differences in size between nominally identical liposomal samples, and detected the presence of low-diameter material which yielded bimodal particle size distributions. Subsequently, we compared these findings to dynamic light scattering (DLS) data and results from light scattering experiments coupled to Asymmetric Flow-Field Flow Fractionation (AF4), the latter improving the detectability of smaller particles in polydisperse samples due to a size separation step prior detection. However, the bimodal size distribution could not be detected due to method inherent limitations. In contrast, cryo transmission electron microscopy corroborated nES GEMMA results. Hence, gas-phase electrophoresis proved to be a versatile tool for liposome characterization as it could analyze both vesicle size and size distribution. Finally, a correlation of nES GEMMA results with cell viability experiments was carried out to demonstrate the importance of liposome batch-to-batch control as low-sized sample components possibly impact cell viability. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Real-Time Wavefront Control for the PALM-3000 High Order Adaptive Optics System

    NASA Technical Reports Server (NTRS)

    Truong, Tuan N.; Bouchez, Antonin H.; Dekany, Richard G.; Guiwits, Stephen R.; Roberts, Jennifer E.; Troy, Mitchell

    2008-01-01

    We present a cost-effective scalable real-time wavefront control architecture based on off-the-shelf graphics processing units hosted in an ultra-low latency, high-bandwidth interconnect PC cluster environment composed of modules written in the component-oriented language of nesC. The architecture enables full-matrix reconstruction of the wavefront at up to 2 KHz with latency under 250 us for the PALM-3000 adaptive optics systems, a state-of-the-art upgrade on the 5.1 meter Hale Telescope that consists of a 64 x 64 subaperture Shack-Hartmann wavefront sensor and a 3368 active actuator high order deformable mirror in series with a 241 active actuator tweeter DM. The architecture can easily scale up to support much larger AO systems at higher rates and lower latency.

  13. 15 CFR Supplement No. 8 to Part 742 - Self-Classification Report for Encryption Items

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... forensics (v) Cryptographic accelerator (vi) Data backup and recovery (vii) Database (viii) Disk/drive... (MAN) (xxii) Modem (xxiii) Network convergence or infrastructure n.e.s. (xxiv) Network forensics (xxv...

  14. 15 CFR Supplement No. 8 to Part 742 - Self-Classification Report for Encryption Items

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... forensics (v) Cryptographic accelerator (vi) Data backup and recovery (vii) Database (viii) Disk/drive... (MAN) (xxii) Modem (xxiii) Network convergence or infrastructure n.e.s. (xxiv) Network forensics (xxv...

  15. 15 CFR Supplement No. 8 to Part 742 - Self-Classification Report for Encryption Items

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... forensics (v) Cryptographic accelerator (vi) Data backup and recovery (vii) Database (viii) Disk/drive... (MAN) (xxii) Modem (xxiii) Network convergence or infrastructure n.e.s. (xxiv) Network forensics (xxv...

  16. 15 CFR Supplement No. 8 to Part 742 - Self-Classification Report for Encryption Items

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... forensics (v) Cryptographic accelerator (vi) Data backup and recovery (vii) Database (viii) Disk/drive... (MAN) (xxii) Modem (xxiii) Network convergence or infrastructure n.e.s. (xxiv) Network forensics (xxv...

  17. Risk Reduction for Use of Complex Devices in Space Projects

    NASA Technical Reports Server (NTRS)

    Berg, Melanie; Poivey, Christian; Friendlich, Mark; Petrick, Dave; LaBel, Kenneth; Stansberry, Scott

    2007-01-01

    We present guidel!nes to reduce risk to an acceptable level when using complex devices in space applications. Application to Virtex 4 Field Programmable Gate Array (FPGA) on Express Logistic Carrier (ELC) project is presented.

  18. Recherches sur l'histoire de l'astronomie ancienne

    NASA Astrophysics Data System (ADS)

    Tannery, Paul

    2015-04-01

    Préface; 1. Ce que les Hellènes ont appelé astronomie; 2. Ce que les Hellènes ont appelé astrologie (cont.); 3. Les mathématiciens alexandrins; 4. Les postulats de l'astronomie d'après Ptlolémée et les auteurs élémentaires; 5. La sphéricité de la terre et la mesure de sa circonférence; 6. Le mouvement général des planètes; 7. Les cercles de la sphère; 8. La longueur de l'année solaire; 9. Les tables du soleil; 10. Les périodes d'Hipparque pour les mouvements lunaires; 11. Les tables de la lune; 12. Les parallaxes du soleil et de la lune; 13. Les prédictions d'éclipses; 14. La théorie des planètes; 15. Le catalogue des fixes; Appendice; Errata.

  19. Long-Range Correlation in alpha-Wave Predominant EEG in Human

    NASA Astrophysics Data System (ADS)

    Sharif, Asif; Chyan Lin, Der; Kwan, Hon; Borette, D. S.

    2004-03-01

    The background noise in the alpha-predominant EEG taken from eyes-open and eyes-closed neurophysiological states is studied. Scale-free characteristic is found in both cases using the wavelet approach developed by Simonsen and Nes [1]. The numerical results further show the scaling exponent during eyes-closed is consistently lower than eyes-open. We conjecture the origin of this difference is related to the temporal reconfiguration of the neural network in the brain. To further investigate the scaling structure of the EEG background noise, we extended the second order statistics to higher order moments using the EEG increment process. We found that the background fluctuation in the alpha-predominant EEG is predominantly monofractal. Preliminary results are given to support this finding and its implication in brain functioning is discussed. [1] A.H. Simonsen and O.M. Nes, Physical Review E, 58, 2779¡V2748 (1998).

  20. An analysis of curriculum implementation on high schools in Yogyakarta

    NASA Astrophysics Data System (ADS)

    Febriana, Beta Wulan; Arlianty, Widinda Normalia; Diniaty, Artina; Fauzi'ah, Lina

    2017-12-01

    This study aims to find out how the implementation of the curriculum at three schools in Yogyakarta. The selection of these three schools is based on the use of different curriculum in each school. The analysis was done by distributing questionnaire analysis of eight national education standards (NES). The purpose of this questionnaire is to find out how the curriculum implemented in the schools. In addition, to find out whether or not the implementation was done in accordance with the expectations of the curriculum. The questionnaire distributed in the form of indicators on each NES. These indicators include, Content Standards, Process Standards, Graduates Competency Standards, Teacher and Education Staff Standards, Facility and Infrastructure Standards, Management Standards, Financing Standards and Assessment Standards. Results of the observation indicate that there is a discrepancy between the expectations and the reality of the three schools observed.

  1. KENNEDY SPACE CENTER, FLA. - Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla., is the site where Center Director Jim Kennedy and astronaut Kay Hire shared the agency’s new vision for space exploration with the next generation of explorers. Kennedy talked with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

    NASA Image and Video Library

    2004-02-20

    KENNEDY SPACE CENTER, FLA. - Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla., is the site where Center Director Jim Kennedy and astronaut Kay Hire shared the agency’s new vision for space exploration with the next generation of explorers. Kennedy talked with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  2. Cost-effectiveness assessment in outpatient sinonasal surgery.

    PubMed

    Mortuaire, G; Theis, D; Fackeure, R; Chevalier, D; Gengler, I

    2018-02-01

    To assess the cost-effectiveness of outpatient sinonasal surgery in terms of clinical efficacy and control of expenses. A retrospective study was conducted from January 2014 to January 2016. Patients scheduled for outpatient sinonasal surgery were systematically included. Clinical data were extracted from surgical and anesthesiology computer files. The cost accounting methods applied in our institution were used to evaluate logistic and technical costs. The standardized hospital fees rating system based on hospital stay and severity in diagnosis-related groups (Groupes homogènes de séjours: GHS) was used to estimate institutional revenue. Over 2years, 927 outpatient surgical procedures were performed. The crossover rate to conventional hospital admission was 2.9%. In a day-1 telephone interview, 85% of patients were very satisfied with the procedure. All outpatient cases showed significantly lower costs than estimated for conventional management with overnight admission, while hospital revenue did not differ between the two. This study confirmed the efficacy of outpatient surgery in this indication. Lower costs could allow savings for the health system by readjusting the rating for the procedure. More precise assessment of cost-effectiveness will require more fine-grained studies based on micro costing at hospital level and assessment of impact on conventional surgical activity and post-discharge community care. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Rapid Electrical Stimulation Increased Cardiac Apoptosis Through Disturbance of Calcium Homeostasis and Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    PubMed

    Geng, Le; Wang, Zidun; Cui, Chang; Zhu, Yue; Shi, Jiaojiao; Wang, Jiaxian; Chen, Minglong

    2018-06-15

    Heart failure induced by tachycardia, the most common arrhythmia, is frequently observed in clinical practice. This study was designed to investigate the underlying mechanisms. Rapid electrical stimulation (RES) at a frequency of 3 Hz was applied on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for 7 days, with 8 h/day and 24 h/day set to represent short-term and long-term tachycardia, respectively. Age-matched hiPSC-CMs without electrical stimulation or with slow electrical stimulation (1 Hz) were set as no electrical stimulation (NES) control or low-frequency electrical stimulation (LES) control. Following stimulation, JC-1 staining flow cytometry analysis was performed to examine mitochondrial conditions. Apoptosis in hiPSC-CMs was evaluated using Hoechst staining and Annexin V/propidium iodide (AV/PI) staining flow cytometry analysis. Calcium transients and L-type calcium currents were recorded to evaluate calcium homeostasis. Western blotting and qPCR were performed to evaluate the protein and mRNA expression levels of apoptosis-related genes and calcium homeostasis-regulated genes. Compared to the controls, hiPSC-CMs following RES presented mitochondrial dysfunction and an increased apoptotic percentage. Amplitudes of calcium transients and L-type calcium currents were significantly decreased in hiPSC-CMs with RES. Molecular analysis demonstrated upregulated expression of Caspase3 and increased Bax/Bcl-2 ratio. Genes related to calcium re-sequence were downregulated, while phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) was significantly upregulated following RES. There was no significant difference between the NES control and LES control groups in these aspects. Inhibition of CaMKII with 1 µM KN93 partly reversed these adverse effects of RES. RES on hiPSC-CMs disturbed calcium homeostasis, which led to mitochondrial stress, promoted cell apoptosis and caused electrophysiological remodeling in a time-dependent manner. CaMKII played a central role in the damages induced by RES, pharmacological inhibition of CaMKII activity partly reversed the adverse effects of RES on both structural and electrophysiological properties of cells. © 2018 The Author(s). Published by S. Karger AG, Basel.

  4. Renal effects of fresh water-induced hypo-osmolality in a marine adapted seal

    NASA Technical Reports Server (NTRS)

    Ortiz, R. M.; Wade, C. E.; Costa, D. P.; Ortiz, C. L.

    2002-01-01

    With few exceptions, marine mammals are not exposed to fresh water; however quantifying the endocrine and renal responses of a marine-adapted mammal to the infusion of fresh water could provide insight on the evolutionary adaptation of kidney function and on the renal capabilities of these mammals. Therefore, renal function and hormonal changes associated with fresh water-induced diuresis were examined in four, fasting northern elephant seal ( Mirounga angustirostris) (NES) pups. A series of plasma samples and 24-h urine voids were collected prior to (control) and after the infusion of water. Water infusion resulted in an osmotic diuresis associated with an increase in glomerular filtration rate (GFR), but not an increase in free water clearance. The increase in excreted urea accounted for 96% of the increase in osmotic excretion. Following infusion of fresh water, plasma osmolality and renin activity decreased, while plasma aldosterone increased. Although primary regulators of aldosterone release (Na(+), K(+) and angiotensin II) were not significantly altered in the appropriate directions to individually stimulate aldosterone secretion, increased aldosterone may have resulted from multiple, non-significant changes acting in concert. Aldosterone release may also be hypersensitive to slight reductions in plasma Na(+), which may be an adaptive mechanism in a species not known to drink seawater. Excreted aldosterone and urea were correlated suggesting aldosterone may regulate urea excretion during hypo-osmotic conditions in NES pups. Urea excretion appears to be a significant mechanism by which NES pups sustain electrolyte resorption during conditions that can negatively affect ionic homeostasis such as prolonged fasting.

  5. Wave behaviour of sporadic E-layer variations at the latitudes 30-70N

    NASA Astrophysics Data System (ADS)

    Ryabchenko, E. Yu.; Sherstyukov, O. N.

    A wave behaviour of sporadic E-layer variations was investigated by analysing time series of twenty European ionosonde stations (30°N--80°N, 15°W--45°E) for 1985-1988. Wavelet transform was used to explore 3-30 periodicities in variations of Es-layer relative electron density δ NEs defined here as (foEs2--foE2)/foE2. Such compound parameter allowed us to partly exclude solar ionisation factor and concentrate on meteorological nature of Es-layer synoptical oscillations. A typical synoptical atmospheric 3-30 day oscillations were discovered in foEs and also in δ NEs. Due to nonorthgonal wavelet transform used in this work, it is advisable to divide frequency domain into several optimal intervals. Five periods 4,6,10,16 and 24 day were chosen which cover 3-5, 5-7, 8-12, 13-20 and 20-30 day intervals. Low value of oscillation amplitude not greater than 1.5 is typical for most of European ionospheric stations in January-March and September-December. A higher values were observed at latitudes higher than 60°N. A wave vortex were discovered during the analysis of dynamics of δ NEs spatio-temporal variations in summer for each period interval. In May and June we observed wave penetration from north and south into the middle latitudes 45°N--55°N with amplitudes up to 5.0 for the most of considered years. In Jule and August all amplitudes reach their average values.

  6. Identification of Novel Saccharomyces cerevisiae Proteins with Nuclear Export Activity: Cell Cycle-Regulated Transcription Factor Ace2p Shows Cell Cycle-Independent Nucleocytoplasmic Shuttling

    PubMed Central

    Jensen, Torben Heick; Neville, Megan; Rain, Jean Christophe; McCarthy, Terri; Legrain, Pierre; Rosbash, Michael

    2000-01-01

    Nuclear export of proteins containing leucine-rich nuclear export signals (NESs) is mediated by the NES receptor CRM1/Crm1p. We have carried out a yeast two-hybrid screen with Crm1p as a bait. The Crm1p-interacting clones were subscreened for nuclear export activity in a visual assay utilizing the Crm1p-inhibitor leptomycin B (LMB). This approach identified three Saccharomyces cerevisiae proteins not previously known to have nuclear export activity. These proteins are the 5′ RNA triphosphatase Ctl1p, the cell cycle-regulated transcription factor Ace2p, and a protein encoded by the previously uncharacterized open reading frame YDR499W. Mutagenesis analysis show that YDR499Wp contains an NES that conforms to the consensus sequence for leucine-rich NESs. Mutagenesis of Ctl1p and Ace2p were unable to identify specific NES residues. However, a 29-amino-acid region of Ace2p, rich in hydrophobic residues, contains nuclear export activity. Ace2p accumulates in the nucleus at the end of mitosis and activates early-G1-specific genes. We now provide evidence that Ace2p is nuclear not only in late M-early G1 but also during other stages of the cell cycle. This feature of Ace2p localization explains its ability to activate genes such as CUP1, which are not expressed in a cell cycle-dependent manner. PMID:11027275

  7. Fostering Students' Conceptual Knowledge in Biology in the Context of German National Education Standards

    NASA Astrophysics Data System (ADS)

    Förtsch, Christian; Dorfner, Tobias; Baumgartner, Julia; Werner, Sonja; von Kotzebue, Lena; Neuhaus, Birgit J.

    2018-04-01

    The German National Education Standards (NES) for biology were introduced in 2005. The content part of the NES emphasizes fostering conceptual knowledge. However, there are hardly any indications of what such an instructional implementation could look like. We introduce a theoretical framework of an instructional approach to foster students' conceptual knowledge as demanded in the NES (Fostering Conceptual Knowledge) including instructional practices derived from research on single core ideas, general psychological theories, and biology-specific features of instructional quality. First, we aimed to develop a rating manual, which is based on this theoretical framework. Second, we wanted to describe current German biology instruction according to this approach and to quantitatively analyze its effectiveness. And third, we aimed to provide qualitative examples of this approach to triangulate our findings. In a first step, we developed a theoretically devised rating manual to measure Fostering Conceptual Knowledge in videotaped lessons. Data for quantitative analysis included 81 videotaped biology lessons of 28 biology teachers from different German secondary schools. Six hundred forty students completed a questionnaire on their situational interest after each lesson and an achievement test. Results from multilevel modeling showed significant positive effects of Fostering Conceptual Knowledge on students' achievement and situational interest. For qualitative analysis, we contrasted instruction of four teachers, two with high and two with low student achievement and situational interest using the qualitative method of thematic analysis. Qualitative analysis revealed five main characteristics describing Fostering Conceptual Knowledge. Therefore, implementing Fostering Conceptual Knowledge in biology instruction seems promising. Examples of how to implement Fostering Conceptual Knowledge in instruction are shown and discussed.

  8. Regulation of Nuclear Import and Export of Negative Cofactor 2*S⃞

    PubMed Central

    Kahle, Joerg; Piaia, Elisa; Neimanis, Sonja; Meisterernst, Michael; Doenecke, Detlef

    2009-01-01

    The negative cofactor 2 (NC2) is a protein complex composed of two subunits, NC2α and NC2β, and plays a key role in transcription regulation. Here we investigate whether each subunit contains a nuclear localization signal (NLS) that permits individual crossing of the nuclear membrane or whether nuclear import of NC2α and NC2β depends on heterodimerization. Our results from in vitro binding studies and transfection experiments in cultured cells show that each subunit contains a classical NLS (cNLS) that is recognized by the importin α/β heterodimer. Regardless of the individual cNLSs the two NC2 subunits are translocated as a preassembled complex as co-transfection experiments with wild-type and cNLS-deficient NC2 subunits demonstrate. Ran-dependent binding of the nuclear export receptor Crm1/exportin 1 confirmed the presence of a leucine-rich nuclear export signal (NES) in NC2β. In contrast, NC2α does not exhibit a NES. Our results from interspecies heterokaryon assays suggest that heterodimerization with NC2α masks the NES in NC2β, which prevents nuclear export of the NC2 complex. A mutation in either one of the two cNLSs decreases the extent of importin α/β-mediated nuclear import of the NC2 complex. In addition, the NC2 complex can enter the nucleus via a second pathway, facilitated by importin 13. Because importin 13 binds exclusively to the NC2 complex but not to the individual subunits this alternative import pathway depends on sequence elements distributed among the two subunits. PMID:19204005

  9. Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents

    PubMed Central

    Turner, Joel G.; Dawson, Jana; Cubitt, Christopher L.; Baz, Rachid; Sullivan, Daniel M.

    2014-01-01

    Nuclear-cytoplasmic trafficking of proteins is a significant factor in the development of cancer and drug resistance. Subcellular localization of exported proteins linked to cancer development include those involved in cell growth and proliferation, apoptosis, cell cycle regulation, transformation, angiogenesis, cell adhesion, invasion, and metastasis. Here, we examined the basic mechanisms involved in the export of proteins from the nucleus to the cytoplasm. All proteins over 40 kDa use the nuclear pore complex to gain entry or exit from the nucleus, with the primary nuclear export molecule involved in these processes being chromosome region maintenance 1 (CRM1, exportin 1 or XPO1). Proteins exported from the nucleus must possess a hydrophobic nuclear export signal (NES) peptide that binds to a hydrophobic groove containing an active-site Cys528 in the CRM1 protein. CRM1 inhibitors function largely by covalent modification of the active site Cys528 and prevent binding to the cargo protein NES. In the absence of a CRM1 inhibitor, CRM1 binds cooperatively to the NES of the cargo protein and RanGTP, forming a trimer that is actively transported out of the nucleus by facilitated diffusion. Nuclear export can be blocked by CRM1 inhibitors, NES peptide inhibitors or by preventing post-translational modification of cargo proteins. Clinical trials using the classic CRM1 inhibitor leptomycin B proved too toxic for patients; however, a new generation of less toxic small molecule inhibitors are being used in clinical trials in patients with both hematological malignancies and solid tumors. Additional trials are being initiated using small-molecule CRM1 inhibitors in combination with chemotherapeutics such as pegylated liposomal doxorubicin. In this review, we present evidence that combining the new CRM1 inhibitors with other classes of therapeutics may prove effective in the treatment of cancer. Potential combinatorial therapies discussed include the use of CRM1 inhibitors and the addition of alkylating agents (melphalan), anthracyclines (doxorubicin and daunomycin), BRAF inhibitors, platinum drugs (cisplatin and oxaliplatin), proteosome inhibitors (bortezomib and carfilzomib), or tyrosine-kinase inhibitors (imatinib). Also, the sequence of treatment may be important for combination therapy. We found that the most effective treatment regimen involved first priming the cancer cells with the CRM1 inhibitor followed by doxorubicin, bortezomib, carfilzomib, or melphalan. This order sensitized both de novo and acquired drug-resistant cancer cell lines. PMID:24631834

  10. Bacterial counts on teat skin and in new sand, recycled sand, and recycled manure solids used as bedding in freestalls.

    PubMed

    Rowbotham, R F; Ruegg, P L

    2016-08-01

    On modern dairy farms, environmental mastitis pathogens are usually the predominant cause of mastitis, and bedding often serves as a point of exposure to these organisms. The objective of this longitudinal study was to determine bacterial populations of 4 different bedding types [deep-bedded new sand (NES), deep-bedded recycled sand (RS), deep-bedded manure solids (DBMS), and shallow-bedded manure solids over foam core mattresses (SBMS)] and of teat skin swabs of primarily primiparous cows housed in a single facility over all 4 seasons. Samples of bedding were collected weekly (n=49wk) from pens that each contained 32 lactating dairy cows. Throughout the length of the same period, composite swabs of teat skin were collected weekly from all cows before and after premilking teat sanitation. Median numbers of streptococci and streptococci-like organisms (SSLO) were >8.6×10(6) cfu/g and >6.9×10(3) cfu/teat swab for all bedding types and teat swabs, respectively. Numbers of SSLO were greatest in samples of SBMS (2.1×10(8) cfu/g) and least in samples of NES (8.6×10(6) cfu/g), RS (1.3×10(7) cfu/g), and DBMS (1.7×10(7) cfu/g). Numbers of gram-negative bacteria in bedding (5.5×10(4) to 1.2×10(7) cfu/g) were fewer than numbers of SSLO (8.6×10(6) to 2.1×10(8) cfu/g). Numbers of coliform bacteria were greatest in samples of DBMS (2.2×10(6) cfu/g) and least in samples of NES (3.6×10(3) cfu/g). In general, the relative number of bacteria on teat skin corresponded to exposure in bedding. Numbers of gram-negative bacteria recovered from prepreparation teat swabs were greatest for cows bedded with DBMS (1.0×10(4) cfu/swab) and RS (2.5×10(3) cfu/swab) and least for cows bedded with NES (5.8×10(2) cfu/swab). Median numbers of coliform and Klebsiella spp. recovered from prepreparation teat swabs were below the limit of detection for all cows except those bedded with DBMS. Numbers of SSLO recovered from prepreparation teat swabs were least for cows bedded with DBMS (6.9×10(3) cfu/swab) and greatest for cows bedded with RS (5.1×10(4) cfu/swab) or SBMS (1.6×10(5) cfu/swab). The numbers of all types of measured bacteria (total gram-negative, coliforms, Klebsiella spp., SSLO) on postpreparation teat swabs were reduced by up to 2.6 logs from numbers of bacteria on prepreparation swabs, verifying effective preparation procedures. Significant correlations between bacterial counts of bedding samples and teat skin swabs were observed for several types of bacteria. As compared with other bedding types, the least amount of gram-negative bacteria were recovered from NES and may indicate that cows on NES have a reduced risk of exposure to pathogens that are typically a cause of clinical mastitis. In contrast, exposure to large numbers of SSLO was consistent across all bedding types and may indicate that risk of subclinical mastitis typically associated with streptococci is not as influenced by bedding type; however, significantly greater numbers of SSLO were found in SBMS than in other bedding types. These findings indicate that use of different bedding types results in exposure to different distributions of mastitis pathogens that may alter the proportion of etiologies of clinical mastitis, although the incidence rate of clinical mastitis did not differ among bedding types. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Scotland's GP Rural Fellowship: an initiative that has impacted on rural recruitment and retention.

    PubMed

    MacVicar, Ronald; Clarke, Gillian; Hogg, David R

    2016-01-01

    In Scotland 20% of the population live in a remote or rural area spread across 94% of the land mass that is defined as remote and rural. NHS Education for Scotland (NES), NHS Scotland's training and education body, works in partnership with territorial health boards and medical schools to address rural recruitment and retention through a variety of initiatives. The longest established of these is the GP Rural Fellowship, which has been in place since 2002. This article describes this program and reports on a survey of the output of the Fellowship from 2002 to 2013. The Fellowship is aimed at newly qualified GPs, who are offered a further year of training in and exposure to rural medicine. The Fellowship has grown and undergone several modifications since its inception. The current model involves co-funding arrangements between NES and participating boards, supporting a maximum of 12 fellows per year. The Health Boards' investment in the Fellowship is returned through the service commitment that the Fellows provide, and the funding share from NES allows Fellows to have protected educational time to meet their educational needs in relation to rural medicine. Given this level of funding support it is important that the outcome of the Fellowship experience is understood, in particular its influence on recruitment to and retention in general practice in rural Scotland. To address this need a survey of all previous rural Fellows was undertaken in the first quarter of 2014, including all Fellows that had undertaken the Fellowship between 2002-03 and 2012-13. A total of 69 GPs were recruited to the Fellowship in this period, of which 66 were able to be included in the survey. There was a response rate of 98% to the survey and 63 of those that responded (97%) were working currently in general practice, 53 of whom were doing so in Scotland. A total of 46 graduates of the Fellowship in the period surveyed (71%) were working in rural areas or accessible small towns in Scotland, 39 in substantive general practice roles (60%). Scotland's GP Rural Fellowship program represents a successful collaboration between education and service, and the results of the survey reported in this article underline previously unpublished data that suggest that approximately three-quarters of graduates are retained in important roles in rural Scotland. It is unclear however whether the Fellowship confirms a prior intention to work in rural practice, or whether it provides a new opportunity through protected exposure. This will form the basis of further evaluation.

  12. Negative experiences and pre-donation blood pressure: the role of attitude and anxiety.

    PubMed

    Hoogerwerf, M D; van Dongen, A; Middelburg, R A; Merz, E-M; de Kort, W L A M; Frings-Dresen, M H W; Sluiter, J K; Veldhuizen, I J T

    2017-04-01

    Negative experiences (NEs) have been shown to result in an increased stress response, as indicated by blood pressure, at the subsequent donation. This response might be influenced by how the donor rates the donation in terms of importance and pleasantness [affective attitude (AA)/cognitive attitude (CA)] or by anxiety about donating blood. We investigated the effect of AA/CA/anxiety on the impact of NEs on pre-donation blood pressure (pd-BP) in the subsequent donation. pd-BP at visit 3 was compared between donors with and without a history of NEs during or after their first two visits (visit 1: medical check, visit 2: first donation). The effect of AA/CA/anxiety (measured 1 month prior to visit 1 on a 7-point scale) on visit 3 pd-BP was explored using linear regression and interaction analyses. Analyses were stratified for gender, age and pd-BP at visit 1, which were taken into account as confounders. In 1106 first-time blood donors (70% female), 632 donors (57% of total) indicated an NE at their first donation. Mean scores for AA/CA/anxiety were 5·2/6·5/2·2 (men without NE), 4·8/6·3/3·0 (men with NE), 5·2/6·6/2·6 (women without NE) and 4·8/6·6/3·2 (women with NE). No significant associations were found for NE and pd-BP at visit 3 after adjusting for confounding. Of 48 interaction effects, four were significant, but effects were small and inconsistent. In donors who had had negative experiences during their first donation, anxiety and attitude to donation did not influence their pre-donation blood pressure at their subsequent visit. © 2016 British Blood Transfusion Society.

  13. Nucleocytoplasmic shuttling of the rabies virus P protein requires a nuclear localization signal and a CRM1-dependent nuclear export signal

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pasdeloup, David; Poisson, Nicolas; Raux, Helene

    2005-04-10

    Rabies virus P protein is a co-factor of the viral RNA polymerase. It has been shown previously that P mRNA directs the synthesis of four N-terminally truncated P products P2, P3, P4, and P5 due to translational initiation by a leaky scanning mechanism at internal Met codons. Whereas P and P2 are located in the cytoplasm, P3, P4, and P5 are found in the nucleus. Here, we have analyzed the molecular basis of the subcellular localization of these proteins. Using deletion mutants fused to GFP protein, we show the presence of a nuclear localization signal (NLS) in the C-terminal partmore » of P (172-297). This domain contains a short lysine-rich stretch ({sup 211}KKYK{sup 214}) located in close proximity with arginine 260 as revealed by the crystal structure of P. We demonstrate the critical role of lysine 214 and arginine 260 in NLS activity. In the presence of Leptomycin B, P is retained in the nucleus indicating that it contains a CRM1-dependent nuclear export signal (NES). The subcellular distribution of P deletion mutants indicates that the domain responsible for export is the amino-terminal part of the protein. The use of fusion proteins that have amino terminal fragments of P fused to {beta}-galactosidase containing the NLS of SV40 T antigen allows us to identify a NES between residues 49 and 58. The localization of NLS and NES determines the cellular distribution of the P gene products.« less

  14. Selecting native perennial plants for ecological intensification in Mediterranean greenhouse horticulture.

    PubMed

    Rodríguez, E; González, M; Paredes, D; Campos, M; Benítez, E

    2017-12-04

    Natural control by predators and parasitoids provides an important and often unnoticed ecosystem service to agricultural landscapes by reducing pest populations in crops. The current model of horticultural intensification in south-eastern Spain produces high yields but has also resulted in a landscape almost completely covered by plastic. Promoting natural areas among greenhouses could enhance biodiversity, by being beneficial insects, and reduce pest pressure outdoors. The first step is to ascertain how pests and their natural enemies (NEs) use Mediterranean vegetation for selecting the best plants for pest suppression outdoors. The abundance of the two major horticultural pests, the tobacco whitefly, Bemisia tabaci, and the western flower thrips, Frankliniella occidentalis, together with their NEs, were assayed in 22 flowering perennial plants, which were newly planted in an experimental field surrounded by greenhouses. Eight plant species were identified as the most critical species for sustaining pest populations outdoors. A set of five plant species supported a medium level of pests, and another set of ten plant species supported the lowest level of both pests. Tobacco whitefly occurred in a few plants species, whereas western flower thrips occurred on almost all the plant species studied, and was favoured by the presence of flowers in perennial plants. The results suggest that plant diversity may provide relatively few acceptable host plants for tobacco whitefly than for western flower thrips. NEs were generally collected in plants that also supported abundance of pests, indicating that host/prey availability, more than food resources from flowers, was a stronger predictor of NE abundance in perennial plants. Field trials using the plants with the lowest host acceptance by pests are needed in order to ascertain whether pest abundance outdoors is reduced.

  15. The Effects of Binge Drinking on College Students’ Next-Day Academic Test-Taking Performance and Mood State

    PubMed Central

    Howland, Jonathan; Rohsenow, Damaris J; Greece, Jacey A; Littlefield, Caroline A; Almeida, Alissa; Heeren, Timothy; Winter, Michael; Bliss, Caleb A.; Hunt, Sarah; Hermos, John

    2010-01-01

    Aim To assess the effects of binge drinking on students’ next-day academic test-taking performance. Design A placebo-controlled cross-over design with randomly assigned order of conditions. Participants were randomized to either alcoholic beverage (mean =.12 g% breath alcohol concentration [BrAC]) or placebo on the first night and then received the other beverage a week later. The next day, participants were assessed on test-taking, neurocognitive performance and mood state. Participants 193 college students (≥ 21 years) recruited from greater Boston. Setting The trial was conducted at the General Clinical Research Center at the Boston Medical Center. Measurements The Graduate Record Exams © (GREs) and a quiz on a lecture presented the previous day measured test-taking performance; the Neurobehavioral Evaluation System (NES3) and the Psychomotor Vigilance Test (PVT) measured neurocognitive performance; and, the Profile of Mood States (POMS) measured mood. Findings Test-taking performance was not affected the morning after alcohol administration, but mood state and attention/reaction time were. Conclusion Drinking to a level of .12 g% BrAC does not affect next-day test-taking performance, but does affect some neurocognitive measures and mood state. PMID:20403018

  16. The National Eutrophication Survey: lake characteristics and historical nutrient concentrations

    NASA Astrophysics Data System (ADS)

    Stachelek, Joseph; Ford, Chanse; Kincaid, Dustin; King, Katelyn; Miller, Heather; Nagelkirk, Ryan

    2018-01-01

    Historical ecological surveys serve as a baseline and provide context for contemporary research, yet many of these records are not preserved in a way that ensures their long-term usability. The National Eutrophication Survey (NES) database is currently only available as scans of the original reports (PDF files) with no embedded character information. This limits its searchability, machine readability, and the ability of current and future scientists to systematically evaluate its contents. The NES data were collected by the US Environmental Protection Agency between 1972 and 1975 as part of an effort to investigate eutrophication in freshwater lakes and reservoirs. Although several studies have manually transcribed small portions of the database in support of specific studies, there have been no systematic attempts to transcribe and preserve the database in its entirety. Here we use a combination of automated optical character recognition and manual quality assurance procedures to make these data available for analysis. The performance of the optical character recognition protocol was found to be linked to variation in the quality (clarity) of the original documents. For each of the four archival scanned reports, our quality assurance protocol found an error rate between 5.9 and 17 %. The goal of our approach was to strike a balance between efficiency and data quality by combining entry of data by hand with digital transcription technologies. The finished database contains information on the physical characteristics, hydrology, and water quality of about 800 lakes in the contiguous US (Stachelek et al.(2017), https://doi.org/10.5063/F1639MVD). Ultimately, this database could be combined with more recent studies to generate meta-analyses of water quality trends and spatial variation across the continental US.

  17. Potential Application of Nanoemulsions for Skin Delivery of Pomegranate Peel Polyphenols.

    PubMed

    Baccarin, Thaisa; Lemos-Senna, Elenara

    2017-11-01

    Pomegranate peel and seeds have demonstrated to possess antioxidant compounds with potential application to protect the skin against the ultraviolet radiation damage. However, the photoprotection activity is dependent on the amount of these compounds that reach the viable skin layers. In this paper, we describe the in vitro skin permeation and retention of the major pomegranate peel polyphenols using Franz diffusion cells, after entrapping a ethyl acetate fraction (EAF) from Punica granatum peel extract into nanoemulsions (NEs) prepared with pomegranate seed oil (PSO) or medium chain triglyceride oil (MCT). The in vitro skin permeation of gallic acid (GA), ellagic acid (EA), and punicalagin (PC) was evaluated using a HPLC-DAD validated method. After 8 h of skin permeation, all polyphenol compounds were mostly retained in the skin and did not reach the receptor compartment. However, a 2.2-fold enhancement of the retained amount of gallic acid in the stratum corneum was verified after EAF-loaded NEs are applied, when compared with the free EAF. GA and EA were delivered to the viable epidermis and dermis only when nanoemulsions were applied onto the skin. The mean retained amounts of GA and EA in the EP and DE after applying the EAF-loaded PSO-NE were 1.78 and 1.36 μg cm -2 and 1.10 and 0.97 μg cm -2 , respectively. Similar values were obtained after applying the EAF-loaded MCT-NE. The skin permeation results were supported by the confocal microscopy images. These results evidenced the promising application of nanoemulsions to deliver the pomegranate polyphenols into the deeper skin layers.

  18. Analysis and prediction of leucine-rich nuclear export signals.

    PubMed

    la Cour, Tanja; Kiemer, Lars; Mølgaard, Anne; Gupta, Ramneek; Skriver, Karen; Brunak, Søren

    2004-06-01

    We present a thorough analysis of nuclear export signals and a prediction server, which we have made publicly available. The machine learning prediction method is a significant improvement over the generally used consensus patterns. Nuclear export signals (NESs) are extremely important regulators of the subcellular location of proteins. This regulation has an impact on transcription and other nuclear processes, which are fundamental to the viability of the cell. NESs are studied in relation to cancer, the cell cycle, cell differentiation and other important aspects of molecular biology. Our conclusion from this analysis is that the most important properties of NESs are accessibility and flexibility allowing relevant proteins to interact with the signal. Furthermore, we show that not only the known hydrophobic residues are important in defining a nuclear export signals. We employ both neural networks and hidden Markov models in the prediction algorithm and verify the method on the most recently discovered NESs. The NES predictor (NetNES) is made available for general use at http://www.cbs.dtu.dk/.

  19. Depression and Disordered Eating in the Obese Person

    PubMed Central

    Faulconbridge, Lucy F.; Bechtel, Colleen F.

    2014-01-01

    Three mental health problems commonly associated with obesity are major depression, binge eating disorder (BED), and Night Eating Syndrome (NES). Evidence from both cross-sectional and longitudinal studies support independent relationships between obesity and depression, and between obesity and binge eating. These problems are most prevalent in severely obese individuals (Class III obesity; a body mass index (BMI) of >40kgm2), many of whom seek bariatric surgery, and we briefly review whether the presence of pre-operative depression, BED or NES affects post-operative outcomes. Historically depressed individuals have been screened out of weight loss trials due to concerns of worsening mood with weight loss. Such practices have precluded the development of effective treatments for depressed, obese individuals, leaving large numbers of people without appropriate care. We present recent advances in this area, and attempt to answer whether depressed individuals can lose clinically significant amounts of weight, show improvements in mood, and adhere to the demands of a weight loss intervention. PMID:24678445

  20. KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy talks to students in Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. Kennedy made the trip with NASA astronaut Kay Hire to share the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

    NASA Image and Video Library

    2004-02-20

    KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy talks to students in Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. Kennedy made the trip with NASA astronaut Kay Hire to share the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  1. KENNEDY SPACE CENTER, FLA. - Astronaut Kay Hire talks to students in Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. She joined Center Director Jim Kennedy in sharing the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

    NASA Image and Video Library

    2004-02-20

    KENNEDY SPACE CENTER, FLA. - Astronaut Kay Hire talks to students in Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. She joined Center Director Jim Kennedy in sharing the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  2. KENNEDY SPACE CENTER, FLA. - Students at Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla., listen attentively to astronaut Kay Hire. She and Center Director Jim Kennedy were at the school to share the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

    NASA Image and Video Library

    2004-02-20

    KENNEDY SPACE CENTER, FLA. - Students at Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla., listen attentively to astronaut Kay Hire. She and Center Director Jim Kennedy were at the school to share the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  3. JPRS Report, East Europe.

    DTIC Science & Technology

    1990-02-05

    Jersey, Philadelphia, Chicago, and to Ismet Abdulahu, Hasan Ramadani , and Haljimi Mrati Canada, to organize receptions and parties for Yugoslav had fled...by (rhetorical) attack. When they did He com h course o studie at tecelopoeit-not avethe ourge-te oly nes n Eropeto ign He completed the course of

  4. Students' Self-Perceptions of Apologies to Instructors

    ERIC Educational Resources Information Center

    Cheng, Dongmei

    2017-01-01

    Adopting retrospective verbal report, or RVR as the instrument, this study reports an analysis of the perceptions of native-English-speaking (NES) and non-native-English-speaking (NNES) students, who apologised to their instructors in coursework-related situations. Sixty NESs from different levels and disciplinary areas and 63 NNESs (Arabic and…

  5. Binge eating disorder and night eating syndrome in adults with type 2 diabetes

    USDA-ARS?s Scientific Manuscript database

    To determine the prevalence of binge eating disorder (BED) and night eating syndrome (NES) among applicants to the Look AHEAD (Action for Health in Diabetes) study. The Eating Disorders Examination-Questionnaire (EDE-Q) and the Night Eating Questionnaire (NEQ) were used to screen patients. Phone int...

  6. Texas Papers in Foreign Language Education, 1996.

    ERIC Educational Resources Information Center

    Texas Papers in Foreign Language Education, 1996

    1996-01-01

    Papers on foreign language education include: "The Message Is the Medium: Using Video Materials To Facilitate Foreign Language Performance" (Thomas J. Garza), which explores the use of this medium to enhance commonly-used non-communicative or text-bound teaching materials; "Product and Process Aspects of NES/EFL Students' Persuasive…

  7. Design of a nonlinear torsional vibration absorber

    NASA Astrophysics Data System (ADS)

    Tahir, Ammaar Bin

    Tuned mass dampers (TMD) utilizing linear spring mechanisms to mitigate destructive vibrations are commonly used in practice. A TMD is usually tuned for a specific resonant frequency or an operating frequency of a system. Recently, nonlinear vibration absorbers attracted attention of researchers due to some potential advantages they possess over the TMDs. The nonlinear vibration absorber, or the nonlinear energy sink (NES), has an advantage of being effective over a broad range of excitation frequencies, which makes it more suitable for systems with several resonant frequencies, or for a system with varying excitation frequency. Vibration dissipation mechanism in an NES is passive and ensures that there is no energy backflow to the primary system. In this study, an experimental setup of a rotational system has been designed for validation of the concept of nonlinear torsional vibration absorber with geometrically induced cubic stiffness nonlinearity. Dimensions of the primary system have been optimized so as to get the first natural frequency of the system to be fairly low. This was done in order to excite the dynamic system for torsional vibration response by the available motor. Experiments have been performed to obtain the modal parameters of the system. Based on the obtained modal parameters, the design optimization of the nonlinear torsional vibration absorber was carried out using an equivalent 2-DOF modal model. The optimality criterion was chosen to be maximization of energy dissipation in the nonlinear absorber attached to the equivalent 2-DOF system. The optimized design parameters of the nonlinear absorber were tested on the original 5-DOF system numerically. A comparison was made between the performance of linear and nonlinear absorbers using the numerical models. The comparison showed the superiority of the nonlinear absorber over its linear counterpart for the given set of primary system parameters as the vibration energy dissipation in the former is larger than that in the latter. A nonlinear absorber design has been proposed comprising of thin beams as elastic elements. The geometric configuration of the proposed design has been shown to provide cubic stiffness nonlinearity in torsion. The values of design variables, namely the strength of nonlinearity alpha and torsional stiffness kalpha, were obtained by optimizing dimensions and material properties of the beams for a maximum vibration energy dissipation in the nonlinear absorber. A parametric study has also been conducted to analyze the effect of the magnitude of excitation provided to the system on the performance of a nonlinear absorber. It has been shown that the nonlinear absorber turns out to be more effective in terms of energy dissipation as compared to a linear absorber with an increase in the excitation level applied to the system.

  8. Quantification of disease expression conferred by three host gene-necrotrophic effector interactions in the wheat-Parastagonospora nodorum pathosystem

    USDA-ARS?s Scientific Manuscript database

    Septoria nodorum blotch (SNB), which is a major foliar disease on wheat is caused by the necrotrophic fungus Parastagonospora nodorum. The wheat-P. nodorum pathosystem involves the recognition of necrotrophic effectors (NEs) secreted by P. nodorum by corresponding wheat NE sensitivity genes. Recogni...

  9. Black Teachers of English in South Korea

    ERIC Educational Resources Information Center

    Charles, Quanisha D.

    2017-01-01

    This study used narrative inquiry as a methodological tool and Critical Race Theory (CRT) as a lens to examine how the term native English speaker (NES) is socially constructed when subscribed by Black teachers of English (BTE) in South Korea. In addition to examining how Black teachers of English interpret the term native English speaker, this…

  10. "Every Experience Is a Moving Force": Identity and Growth through Mentoring

    ERIC Educational Resources Information Center

    Johnson, Kimberly A.

    2003-01-01

    This narrative of the experience of a native English speaking (NES) cooperating teacher working with a nonnative English speaking (NNES) student teacher in an MA Teaching English as a Second Language practicum begins with a discussion of teacher identity, then outlines the significance of caring in teacher-student relations Noddings (Caring: A…

  11. Nurse Educators' Preceptions of Preparedness to Guide Clinical Learning

    ERIC Educational Resources Information Center

    Jenkins-Cameron, Stella L.

    2014-01-01

    The purpose of the study was to examine nurse educators' (NEs) perceptions of their level of preparedness to guide learning in clinical rotations of associate degree pre-licensure nursing programs of a South Atlantic state. The study also sought to determine the relationship between clinical experience, formal education, and teaching experience to…

  12. Toward the molecular cloning of the Septoria nodorum blotch susceptibility gene Snn2 in wheat

    USDA-ARS?s Scientific Manuscript database

    Septoria nodorum blotch is a disease of wheat caused by the necrotrophic fungus Parastagonospora nodorum. In the wheat-P. nodorum pathosystem, recognition of pathogen-produced necrotrophic effectors (NEs) by dominant host genes leads to host cell death, which allows the pathogen to gain nutrients an...

  13. 78 FR 10666 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing of Proposed Rule Change for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-14

    ... PHLX. BX, NASDAQ, PHLX and NES are affiliates. Accordingly, the affiliate relationship between PHLX and... conflicts of interest between an exchange's self-regulatory obligations and its commercial interests.\\7\\ \\7...). Recognizing that the Commission has previously expressed concern regarding the potential for conflicts of...

  14. Vocabulary Acquisition in an Academic Discipline: ESL Learners and Theology.

    ERIC Educational Resources Information Center

    Lessard-Clouston, Michael

    A study investigated and compared the acquisition of specialized vocabulary among English-as-a-Second Language (ESL) and native English-speaking (NES) graduate students in theology. Research was undertaken in an anglophone city in central Canada. Subjects were 12 students (5 Chinese ESLs, 7 NESs) enrolled in an introductory core theology course. A…

  15. Global diversity and distribution of three necrotrophic effectors in Phaeosphaeria nodorum and related species

    USDA-ARS?s Scientific Manuscript database

    Population genetic and phylogenetic studies showed that P. nodorum is a member of a species-complex that likely shares its center of origin with wheat. We examined the evolutionary history of three known necrotrophic effectors (NEs) produced by Phaeosphaeria nodorum and compared it to neutral loci. ...

  16. Quantification of disease expression conferred by three host gene-necrotrophic effector interactions in the wheat-Parastagonospora nodorum pathosystem

    USDA-ARS?s Scientific Manuscript database

    The disease Septoria nodorum blotch (SNB) is caused by the necrotrophic fungal pathogen Parastagonospora nodorum, which induces cell death in wheat through the production of necrotrophic effectors (NEs). The objective of this project is to determine the relative importance of three host gene-NE int...

  17. Effect of novel bioactive edible coatings based on jujube gum and nettle oil-loaded nanoemulsions on the shelf-life of Beluga sturgeon fillets.

    PubMed

    Gharibzahedi, Seyed Mohammad Taghi; Mohammadnabi, Sara

    2017-02-01

    Effect of jujube gum (JG; 4, 8 and 12% wt)-based nanoemulsions (NEs) containing nettle essential oil (NEO; 2, 3.5 and 5% wt) as new edible coatings was investigated to preserve Beluga sturgeon fillets (BSFs) during 15 day-refrigerated storage at 4°C. Physical (weight loss, cooking loss, color and texture), chemical (pH, FFA, PV, TBARS and TVB-N), microbiological (total and psychrotrophic bacterial counts), and sensorial characteristics of BSFs were kinetically analyzed. Preliminary studies showed that the NEs formulated with NEO lower than 5% at all JG concentrations were able to form stable coating solutions owing to the highest short-term stability (>90%) and entrapment efficiency (94.4-98.3%). Edible NE coating formulated with 12% JG and 3.5% NEO as a novel antimicrobial and antioxidant biomaterial exhibited the lowest weight and cooking losses, pH changes, textural and color deterioration, lipid oxidation and microbial growth in BSFs refrigerated over a period of 15days (P<0.05). Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Night eating in patients with type 2 diabetes. Associations with glycemic control, eating patterns, sleep, and mood.

    PubMed

    Hood, Megan M; Reutrakul, Sirimon; Crowley, Stephanie J

    2014-08-01

    Night eating is a complex behavior associated with disruptions in eating, sleep, and mood regulation. While night eating has been associated with alterations in neuroendocrine functioning, night eating and Night Eating Syndrome (NES) are not well understood in patients with prevalent metabolic conditions, such as diabetes. In this study, 194 adults with Type 2 diabetes completed questionnaires assessing night eating symptoms as well as eating, sleep, and depressive symptoms. Glycemic control data, as measured by hemoglobin A1c (HbA1c), were gathered from patient medical charts. Results indicated that 7% of participants met criteria for NES. Increased symptoms of night eating were associated with poorer glycemic control and disruptions in eating, sleep, and mood, including significantly increased likelihood of having HbA1c levels >7% and endorsing clinical levels of depressive symptoms. Increasing understanding of the relationship between night eating and metabolic and psychosocial functioning in patients with diabetes may provide new avenues for treatment of these patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. A non-canonical mechanism for Crm1-export cargo complex assembly.

    PubMed

    Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Faza, Marius Boulos; Panse, Vikram Govind

    2015-04-21

    The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export.

  20. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway.

    PubMed

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP-8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), 76IRTFQELLF84, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Vents stellaires chauds et nébuleuses éjectées des étoiles chaudes: nécessaire inclusion des phénomènes radiatifs dans les simulations hydrodynamiques

    NASA Astrophysics Data System (ADS)

    Grosdidier, Y.; Garcia-Segura, G.; Acker, A.; Moffat, A. F. J.

    Nous décrivons, à l'instar de la formation et de l'évolution des nébuleuses planétaires, comment l'histoire des vents stellaires issus d'une même étoile chaude (massive ou non) détermine la morphologie des nébuleuses éjectées. Ensuite, nous présentons sommairement la structure et la dynamique des vents accélérés radiativement au sein des étoiles massives (O, Wolf-Rayet) et des étoiles centrales de nébuleuses planétaires de type [WC]. Enfin, nous tâchong d'illustrer en quoi la prise en compte des phénomènes radiatifs est nécessaire pour effectuer toute simulation hydrodynamique sensée reproduire les observations dans les deux contextes, i.e. les vents stellaires chauds eux-mêmes, la persistance de surdensités en leur sein, et les nébuleuses éjectées qui en résultent.

  2. KENNEDY SPACE CENTER, FLA. - Astronaut Kay Hire poses with 8th grader Kristy Wiggins at Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. Hire joined Center Director Jim Kennedy at the school in sharing the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

    NASA Image and Video Library

    2004-02-20

    KENNEDY SPACE CENTER, FLA. - Astronaut Kay Hire poses with 8th grader Kristy Wiggins at Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. Hire joined Center Director Jim Kennedy at the school in sharing the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  3. KENNEDY SPACE CENTER, FLA. - Warren Elly (left), with WTVT-TV, Fox News, talks with Center Director Jim Kennedy at Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. Kennedy was joined by astronaut Kay Hire in sharing the agency’s new vision for space exploration with the next generation of explorers. Kennedy talked with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

    NASA Image and Video Library

    2004-02-20

    KENNEDY SPACE CENTER, FLA. - Warren Elly (left), with WTVT-TV, Fox News, talks with Center Director Jim Kennedy at Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. Kennedy was joined by astronaut Kay Hire in sharing the agency’s new vision for space exploration with the next generation of explorers. Kennedy talked with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  4. KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy talks to WTSP-ABC News about his trip to Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. Kennedy made the trip with NASA astronaut Kay Hire to share the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

    NASA Image and Video Library

    2004-02-20

    KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy talks to WTSP-ABC News about his trip to Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. Kennedy made the trip with NASA astronaut Kay Hire to share the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  5. Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway.

    PubMed

    Saito, Shoko; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2016-07-01

    Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Hippocampal CA1 Transcriptional Profile of Sleep Deprivation: Relation to Aging and Stress

    PubMed Central

    Porter, Nada M.; Bohannon, Julia H.; Curran-Rauhut, Meredith; Buechel, Heather M.; Dowling, Amy L. S.; Brewer, Lawrence D.; Popovic, Jelena; Thibault, Veronique; Kraner, Susan D.; Chen, Kuey Chu; Blalock, Eric M.

    2012-01-01

    Background Many aging changes seem similar to those elicited by sleep-deprivation and psychosocial stress. Further, sleep architecture changes with age suggest an age-related loss of sleep. Here, we hypothesized that sleep deprivation in young subjects would elicit both stress and aging-like transcriptional responses. Methodology/Principal Findings F344 rats were divided into control and sleep deprivation groups. Body weight, adrenal weight, corticosterone level and hippocampal CA1 transcriptional profiles were measured. A second group of animals was exposed to novel environment stress (NES), and their hippocampal transcriptional profiles measured. A third cohort exposed to control or SD was used to validate transcriptional results with Western blots. Microarray results were statistically contrasted with prior transcriptional studies. Microarray results pointed to sleep pressure signaling and macromolecular synthesis disruptions in the hippocampal CA1 region. Animals exposed to NES recapitulated nearly one third of the SD transcriptional profile. However, the SD -aging relationship was more complex. Compared to aging, SD profiles influenced a significant subset of genes. mRNA associated with neurogenesis and energy pathways showed agreement between aging and SD, while immune, glial, and macromolecular synthesis pathways showed SD profiles that opposed those seen in aging. Conclusions/Significance We conclude that although NES and SD exert similar transcriptional changes, selective presynaptic release machinery and Homer1 expression changes are seen in SD. Among other changes, the marked decrease in Homer1 expression with age may represent an important divergence between young and aged brain response to SD. Based on this, it seems reasonable to conclude that therapeutic strategies designed to promote sleep in young subjects may have off-target effects in the aged. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel therapeutic targets to counter effects of SD in young subjects. PMID:22792227

  7. Neurobehavioral effects of transportation noise in primary schoolchildren: a cross-sectional study

    PubMed Central

    2010-01-01

    Background Due to shortcomings in the design, no source-specific exposure-effect relations are as yet available describing the effects of noise on children's cognitive performance. This paper reports on a study investigating the effects of aircraft and road traffic noise exposure on the cognitive performance of primary schoolchildren in both the home and the school setting. Methods Participants were 553 children (age 9-11 years) attending 24 primary schools around Schiphol Amsterdam Airport. Cognitive performance was measured by the Neurobehavioral Evaluation System (NES), and a set of paper-and-pencil tests. Multilevel regression analyses were applied to estimate the association between noise exposure and cognitive performance, accounting for demographic and school related confounders. Results Effects of school noise exposure were observed in the more difficult parts of the Switching Attention Test (SAT): children attending schools with higher road or aircraft noise levels made significantly more errors. The correlational pattern and factor structure of the data indicate that the coherence between the neurobehavioral tests and paper-and-pencil tests is high. Conclusions Based on this study and previous scientific literature it can be concluded that performance on simple tasks is less susceptible to the effects of noise than performance on more complex tasks. PMID:20515466

  8. Vocabulary Learning Strategies for Specialized Vocabulary Acquisition: A Case Study.

    ERIC Educational Resources Information Center

    Lessard-Clouston, Michael

    A study investigated and compared the vocabulary learning strategies (VLSs) of five non-native English-speaking and six native English-speaking (NES) graduate students of theology in a core course. The students of English as a Second Language (ESL) were all native speakers of Cantonese or Mandarin Chinese. Specifically, the research explored (1)…

  9. 77 FR 50187 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Approving a Proposed Rule Change With...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-20

    ... nondiscriminatory fashion.\\14\\ \\14\\ See Phlx Rule 3315(d)(3). Phlx and NES will be required to assign all error... will be required to establish and enforce policies and procedures that are reasonably designed to... exchange be designed to prevent fraudulent and manipulative acts and practices, to promote just and...

  10. 76 FR 16462 - Self-Regulatory Organizations; NASDAQ OMX BX LLC; Order Approving a Proposed Rule Change Relating...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64090; File No. SR-BX-2011-007] Self-Regulatory Organizations; NASDAQ OMX BX LLC; Order Approving a Proposed Rule Change Relating to Permanent Approval of the BX and NES Inbound Routing Relationship March 17, 2011. I. Introduction On January 28, 2011, NASDAQ...

  11. 15 CFR 742.11 - Specially designed implements of torture, thumbscrews, and thumbcuffs; and parts and accessories...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Specially designed implements of torture, thumbscrews, and thumbcuffs; and parts and accessories, n.e.s. 742.11 Section 742.11 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND...

  12. Comparaison des théories des mouvements des satellites de Saturne avec des observations de phénomènes.

    NASA Astrophysics Data System (ADS)

    Thuillot, W.; Arlot, J.-E.; Colas, F.; Berthier, J.; Vu, D. T.; Descamps, P.; Ruatti, C.

    As every fifteen years, phenomena occurred among the Saturnian system of satellites in 1995. Because the Sun and Earth passed through the equatorial plane of the planet which is close to the orbital planes of its main satellites, eclipses and occultations by Saturn occur as well as eclipses and occultations of a satellite by another. These phenomena lead to accurate astrometric observations; therefore the authors organized an international campaign to observe them. At the present time, they have collected one hundred of such mutual events and have analyzed half of them. In this preliminar analysis they got precisions of 0″048 by comparing the observed data either with the Dourneau's theory or with the Vienne and Duriez TASS theory.

  13. Quantifying patterns of change in marine ecosystem response to multiple pressures.

    PubMed

    Large, Scott I; Fay, Gavin; Friedland, Kevin D; Link, Jason S

    2015-01-01

    The ability to understand and ultimately predict ecosystem response to multiple pressures is paramount to successfully implement ecosystem-based management. Thresholds shifts and nonlinear patterns in ecosystem responses can be used to determine reference points that identify levels of a pressure that may drastically alter ecosystem status, which can inform management action. However, quantifying ecosystem reference points has proven elusive due in large part to the multi-dimensional nature of both ecosystem pressures and ecosystem responses. We used ecological indicators, synthetic measures of ecosystem status and functioning, to enumerate important ecosystem attributes and to reduce the complexity of the Northeast Shelf Large Marine Ecosystem (NES LME). Random forests were used to quantify the importance of four environmental and four anthropogenic pressure variables to the value of ecological indicators, and to quantify shifts in aggregate ecological indicator response along pressure gradients. Anthropogenic pressure variables were critical defining features and were able to predict an average of 8-13% (up to 25-66% for individual ecological indicators) of the variation in ecological indicator values, whereas environmental pressures were able to predict an average of 1-5 % (up to 9-26% for individual ecological indicators) of ecological indicator variation. Each pressure variable predicted a different suite of ecological indicator's variation and the shapes of ecological indicator responses along pressure gradients were generally nonlinear. Threshold shifts in ecosystem response to exploitation, the most important pressure variable, occurred when commercial landings were 20 and 60% of total surveyed biomass. Although present, threshold shifts in ecosystem response to environmental pressures were much less important, which suggests that anthropogenic pressures have significantly altered the ecosystem structure and functioning of the NES LME. Gradient response curves provide ecologically informed transformations of pressure variables to explain patterns of ecosystem structure and functioning. By concurrently identifying thresholds for a suite of ecological indicator responses to multiple pressures, we demonstrate that ecosystem reference points can be evaluated and used to support ecosystem-based management.

  14. A Simple Engineering Analysis of Solar Particle Event High Energy Tails and Their Impact on Vehicle Design

    NASA Technical Reports Server (NTRS)

    Singleterry, Robert C., Jr.; Walker, Steven A.; Clowdsley, Martha S.

    2016-01-01

    The mathematical models for Solar Particle Event (SPE) high energy tails are constructed with several di erent algorithms. Since limited measured data exist above energies around 400 MeV, this paper arbitrarily de nes the high energy tail as any proton with an energy above 400 MeV. In order to better understand the importance of accurately modeling the high energy tail for SPE spectra, the contribution to astronaut whole body e ective dose equivalent of the high energy portions of three di erent SPE models has been evaluated. To ensure completeness of this analysis, simple and complex geometries were used. This analysis showed that the high energy tail of certain SPEs can be relevant to astronaut exposure and hence safety. Therefore, models of high energy tails for SPEs should be well analyzed and based on data if possible.

  15. Natural Experiments: An Overview of Methods, Approaches, and Contributions to Public Health Intervention Research.

    PubMed

    Craig, Peter; Katikireddi, Srinivasa Vittal; Leyland, Alastair; Popham, Frank

    2017-03-20

    Population health interventions are essential to reduce health inequalities and tackle other public health priorities, but they are not always amenable to experimental manipulation. Natural experiment (NE) approaches are attracting growing interest as a way of providing evidence in such circumstances. One key challenge in evaluating NEs is selective exposure to the intervention. Studies should be based on a clear theoretical understanding of the processes that determine exposure. Even if the observed effects are large and rapidly follow implementation, confidence in attributing these effects to the intervention can be improved by carefully considering alternative explanations. Causal inference can be strengthened by including additional design features alongside the principal method of effect estimation. NE studies often rely on existing (including routinely collected) data. Investment in such data sources and the infrastructure for linking exposure and outcome data is essential if the potential for such studies to inform decision making is to be realized.

  16. Assessing Taiwanese College Students' Intercultural Sensitivity, EFL Interests, Attitudes toward Native English Speakers, Ethnocentrism, and Their Interrelation

    ERIC Educational Resources Information Center

    Su, Ya-Chen

    2018-01-01

    The development of travel opportunities and technology in the 21st century has brought people from different cultures and countries more opportunities to closely interact. The purposes of the study are to assess the degree of Taiwanese college students' intercultural sensitivities, ethnocentrism, and attitudes toward native English speakers (NES)…

  17. Learner Outcomes for English Language Learner Low Readers in an Early Intervention

    ERIC Educational Resources Information Center

    Kelly, Patricia R.; Gomez-Bellenge, Francisco-Xavier; Chen, Jing; Schulz, Melissa M.

    2008-01-01

    This study investigated the efficacy of Reading Recovery[R] (RR) with first grade English language learners (ELLs) in U.S. schools by examining the literacy outcomes of ELLs compared with their native English-speaking (NES) peers, who were also enrolled in RR. We also explored how ELLs' fall oral English proficiency levels were related to their…

  18. Final Draft Feedback in First-Year Composition: A Case Study of Non-Native English Speaking Students in North America

    ERIC Educational Resources Information Center

    Nash, J. Gail

    2012-01-01

    Scope and Methods: This dissertation examines final draft feedback in a semester long first-year composition class consisting of both native and non-native speakers of English (NES & NNES) attending university. In addition to examining the teacher's commentary on final drafts and the students' responses to it, this study investigated effects…

  19. Are house counts reliable estimators of dusky-footed woodrat population size?

    Treesearch

    WILLIAM F. LAUDENSLAYER; ROBERTA FARGO

    1999-01-01

    Dusky-footed woodrat (Neotoma jiocipes) abundance is often esti~nated using housc counts; a house rypically being described as a large pilc of sticks, usually built on the ground, but occasionally on tree limbs. For purposes of thc count, it is somcti~nes assunlccl that each "active" house represents one woodrat. An activc woodrat house is indicated by its...

  20. Marker development, saturation mapping, and high-resolution mapping of the Septoria nodorum blotch susceptibility gene Snn3-B1 in wheat

    USDA-ARS?s Scientific Manuscript database

    Septoria nodorum blotch (SNB), caused by Parastagonospora nodorum, is a severe foliar and glume disease on durum and common wheat. Pathogen-produced necrotrophic effectors (NEs) are the major determinants for SNB on leaves. One such NE is SnTox3, which evokes programmed cell death and leads to dis...

  1. Cytoplasmic localization and ubiquitination of p21{sup Cip1} by reactive oxygen species

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hwang, Chae Young; Kim, Ick Young; Kwon, Ki-Sun

    2007-06-22

    Reactive oxygen species were previously shown to trigger p21{sup Cip1} protein degradation through a proteasome-dependent pathway, however the detailed mechanism of degradation remains to be elucidated. In this report, we showed that p21{sup Cip1} was degraded at an early phase after low dose H{sub 2}O{sub 2} treatment of a variety of cell types and that preincubation of cells with the antioxidant, N-acetylcysteine, prolonged p21{sup Cip1} half-life. A mutant p21{sup Cip1} in which all six lysines were changed to arginines was protected against H{sub 2}O{sub 2} treatment. Direct interaction between p21{sup Cip1} and Skp2 was elevated in the H{sub 2}O{sub 2}-treatedmore » cells. Disruption of the two nuclear export signal (NES) sequences in p21{sup Cip1}, or treatment with leptomycin B blocked H{sub 2}O{sub 2}-induced p21{sup Cip1} degradation. Altogether, these results demonstrate that reactive oxygen species induce p21{sup Cip1} degradation through an NES-, Skp2-, and ubiquitin-dependent pathway.« less

  2. Phosphorylation acts positively and negatively to regulate MRTF-A subcellular localisation and activity

    PubMed Central

    Panayiotou, Richard; Miralles, Francesc; Pawlowski, Rafal; Diring, Jessica; Flynn, Helen R; Skehel, Mark; Treisman, Richard

    2016-01-01

    The myocardin-related transcription factors (MRTF-A and MRTF-B) regulate cytoskeletal genes through their partner transcription factor SRF. The MRTFs bind G-actin, and signal-regulated changes in cellular G-actin concentration control their nuclear accumulation. The MRTFs also undergo Rho- and ERK-dependent phosphorylation, but the function of MRTF phosphorylation, and the elements and signals involved in MRTF-A nuclear export are largely unexplored. We show that Rho-dependent MRTF-A phosphorylation reflects relief from an inhibitory function of nuclear actin. We map multiple sites of serum-induced phosphorylation, most of which are S/T-P motifs and show that S/T-P phosphorylation is required for transcriptional activation. ERK-mediated S98 phosphorylation inhibits assembly of G-actin complexes on the MRTF-A regulatory RPEL domain, promoting nuclear import. In contrast, S33 phosphorylation potentiates the activity of an autonomous Crm1-dependent N-terminal NES, which cooperates with five other NES elements to exclude MRTF-A from the nucleus. Phosphorylation thus plays positive and negative roles in the regulation of MRTF-A. DOI: http://dx.doi.org/10.7554/eLife.15460.001 PMID:27304076

  3. A non-canonical mechanism for Crm1-export cargo complex assembly

    PubMed Central

    Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Boulos Faza, Marius; Panse, Vikram Govind

    2015-01-01

    The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export. DOI: http://dx.doi.org/10.7554/eLife.05745.001 PMID:25895666

  4. Characterization of carrier erythrocytes for biosensing applications

    NASA Astrophysics Data System (ADS)

    Bustamante López, Sandra C.; Meissner, Kenith E.

    2017-09-01

    Erythrocyte abundance, mobility, and carrying capacity make them attractive as a platform for blood analyte sensing as well as for drug delivery. Sensor-loaded erythrocytes, dubbed erythrosensors, could be reinfused into the bloodstream, excited noninvasively through the skin, and used to provide measurement of analyte levels in the bloodstream. Several techniques to load erythrocytes, thus creating carrier erythrocytes, exist. However, their cellular characteristics remain largely unstudied. Changes in cellular characteristics lead to removal from the bloodstream. We hypothesize that erythrosensors need to maintain native erythrocytes' (NEs) characteristics to serve as a long-term sensing platform. Here, we investigate two loading techniques and the properties of the resulting erythrosensors. For loading, hypotonic dilution requires a hypotonic solution while electroporation relies on electrical pulses to perforate the erythrocyte membrane. We analyze the resulting erythrosensor signal, size, morphology, and hemoglobin content. Although the resulting erythrosensors exhibit morphological changes, their size was comparable with NEs. The hypotonic dilution technique was found to load erythrosensors much more efficiently than electroporation, and the sensors were loaded throughout the volume of the erythrosensors. Finally, both techniques resulted in significant loss of hemoglobin. This study points to the need for continued development of loading techniques that better preserve NE characteristics.

  5. KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy talks to radio station WFLA-AM and Florida Radio Network about his trip to Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. Kennedy made the trip with NASA astronaut Kay Hire to share the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

    NASA Image and Video Library

    2004-02-20

    KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy talks to radio station WFLA-AM and Florida Radio Network about his trip to Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. Kennedy made the trip with NASA astronaut Kay Hire to share the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  6. Volatile organic chemicals of a shore-dwelling cyanobacterial mat community.

    PubMed

    Evans, W G

    1994-02-01

    The main components of a cyanobacterial mat community of a hypersaline lake shore consist of edaphic, mat-forming strains (ecophenes), and littoral strains ofOscillatoria animalis Agardh andO. subbrevis Schmidle, other microorganisms associated with these cyanobacteria, several species ofBembidion (Carabidae: Coleoptera), and two halophytic flowering plants:Puccinellia nuttalliana (salt meadow grass) andSalicornia europaea rubra (samphire). The volatile organic compounds of this community are a blend of those emitted by each of these components such as the C17 alka(e)nes, geosmin, 2-methylisoborneol,β-cyclocitral,β-ionone, dimethyl sulfide, and dimethyl trisulfide of cyanobacteria and associated microorganisms; alcohols, esters, and aldehydes usually associated with flowering plants; and possibly some insect-derived esters, particularly isopropyl tetradecanoate. The dominant compounds were: C11, C13, C15, and C17 alka(e)nes, methyl esters of C16 and C18:2 acids, isopropyl tetradecanoate, heptanal, 3-octanone and 2-nonanone, the acyclic terpene linalool, and the alcohols 1-heptanol, 1-hexanol, 1-octanol, 3-hexen-1-ol, and 2-octen-1-ol. It is concluded that this community may be distinguished from related communities by its repertoire of volatile organic compounds.

  7. Etude des phenomenes chimiques au contact entre le bloc cathodique et la barre collectrice d'une cellule d'electrolyse d'aluminium

    NASA Astrophysics Data System (ADS)

    Lebeuf, Martin

    La production d'aluminium est une industrie importante au Québec. Les propriétés de ce métal le vouent à de multiples usages présents et futurs dans le cadre d'une économie moderne durable. Toutefois, le procédé Hall-Héroult est très énergivore et des progrès demeurent donc nécessaires pour en diminuer les coûts financiers et environnementaux. Parmi les améliorations envisageables de la cellule d'électrolyse se trouve le contact entre la cathode et la barre collectrice, qui doit offrir une faible résistivité au passage du courant électrique. En cours d'opération de la cellule, ce contact a tendance à se dégrader, générant des pertes énergétiques significatives. Les causes de cette dégradation, pouvant provenir de phénomènes chimiques, thermiques, mécaniques et/ou électriques, demeurent mal comprises. Le but du présent projet était donc d'étudier les phénomènes chimiques se produisant au contact bloc-barre de la cellule d'électrolyse Hall-Héroult. En premier lieu, un aspect crucial à considérer est la pénétration du bain électrolytique dans la cathode, car des composés de bain atteignent éventuellement la barre collectrice et peuvent y réagir. A cet effet, une méthode novatrice a été développée afin d'étudier les cathodes et la pénétration du bain dans celles-ci à l'aide de la microtomographie à rayons X. Cette méthode rapide et efficace s'est avérée fort utile dans le projet et a un potentiel important pour l'étude future des cathodes et des phénomènes qui s'y produisent. Ensuite, une cellule d'électrolyse rectangulaire à petite échelle a été développée. Plusieurs phénomènes observés 'en industrie sur des autopsies de cellules post-opération et rapportés dans la littérature ont été reproduis avec succès à l'aide de cette cellule expérimentale. Puis, des tests sans électrolyse, ciblant l'effet du bain électrolytique sur l'acier, ont aussi été conçus et complétés afin de ségréger l'influence des différents paramètres en jeu. L'analyse des résultats de l'ensemble de ces tests a permis de constater différents phénomènes au contact bloc-barre, dont la présence systématique de NaF et, surtout, de β-Al 2O3. Outre la carburation inévitable de la barre collectrice, la formation d'une couche Fe-Al a aussi été observée, favorisée par une pénétration rapide du bain électrolytique dans la cathode ainsi que par une composition de bain acide en surface de la barre. Cette couche comportait par ailleurs des cristaux de β-Al 2O3 pouvant nuire à sa conductivité électrique. Ensuite, à des ratios de bain entre 2.5 et 4.9, une mince couche contenant les éléments Al et N peut se former en surface de la barre. Pour un bain très basique (> 6.0), c'est plutôt une couche Na 2O qui a été observée. En conditions d'électrolyse mais sans une pénétration rapide du bain dans la cathode, du Na a pu carrément pénétrer dans la barre collectrice, préférentiellement avec le carbone. De plus, de la corrosion ainsi que des couches de fer et d'oxyde de fer peuvent se former sur la barre et potentiellement dégrader la qualité du contact électrique. Pour la suite des travaux, des mesures de résistivité ainsi que l'analyse des échantillons industriels permettraient d'évaluer l'impact de ces phénomènes sur la qualité du contact. Mots-clés : Électrolyse, aluminium, Hall-Héroult, interface barre-cathode, bain électrolytique.

  8. Effect of Vector Asymmetry of Radially Polarized Beams in Solid Immersion Microscopy (Open Access, Publisher’s Version)

    DTIC Science & Technology

    2014-03-21

    Sheppard and A. Choudhury, “Annular pupils, radial polarization, and superresolution ,” Appl. Opt. 43(22), 4322–4327 (2004). 7. S. F. Pereira and A. S...van de Nes, “ Superresolution by means of polarisation, phase and amplitude pupil masks,” Opt. Commun. 234(1-6), 119–124 (2004). 8. R. Chen, K

  9. Reprographics Career Ladder AFSC 703X0.

    DTIC Science & Technology

    1981-07-01

    LINEUP AND REGISTER TABLES 39 BINDING MACHINES 36 FLOURESCENT LAMPS 36 WET PROCESS PLATEMAKERS 36 ELECTRIC STAPLERS 32 MANUAL PAPER CUTTERS 32...ELECTROSTATIC COPIERS/PLATEMAKERS 78% PAPER CUTTERS 57% ELECTRIC STAPLERS 47% BINDING MACHINES 42% SINGLE HEAD DRILLS 37% PADDING RACKS 31% PLATEMAKING...HEAD DRILLS 78% MANUAL PAPER CUTTERS 71% STATION COLLATORS 51% BINDING MACHiNES 46% ELECTRIC STAPLERS 46% PLATEMAKING CAMERAS 44% SADDLE STITCHERS 42

  10. More than Just Language Advising: Rapport in University English Writing Consultations and Implications for Tutor Training

    ERIC Educational Resources Information Center

    Lee, Cynthia

    2015-01-01

    Adopting a case study approach with multiple data sources, this paper explores the ways in which rapport is built, and its impact on the learning process based on five successive writing support consultations between a native English-speaking (NES) tutor and her second language (L2) tutee in a Hong Kong university. With reference to the prepared…

  11. Military Intelligence Professional Bulletin (MIPB). Volume 37, Number 2, April-June 2011

    DTIC Science & Technology

    2011-04-01

    holds an MA in Anthropology from California State University, Fullerton. 14 Military Intelligence “Harder to Do Than I Thought” Developing...intelligence is anthropological intelligence, no matter what forms it may take. Intelligence is an- thropological because it defi nes what it means...enlightenment. What we anthropologically call culture underlies and contextualizes all of our intelligence. We are culturally dependent creatures of

  12. 76 FR 62486 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-07

    ... Rule, these tests are designed to reject orders that NES deems to be erroneous or duplicative, would... returning to the PSX book, a PSTG order will subsequently route out to another market center if it posts a... PSCN order will not subsequently route out to another market center if it posts a bid or offer that...

  13. Facteurs de risque de l'inobservance thérapeutique chez les patients schizophrènes: étude cas- témoins'

    PubMed Central

    Aarab, Chadya; Elghazouani, Fatima; Aalouane, Rachid; Rammouz, Ismail

    2015-01-01

    Les progrès réalisés dans le traitement de la schizophrénie n'ont jusqu'ici pas modifié de manière radicale l'importance de l'adhésion des patients à leur médication. L'objectif de ce travail est d'identifier les facteurs de risque de l'abandon du traitement sur un échantillon marocain de malades schizophrènes. C'est une étude transversale menée au centre psychiatrique universitaire de Fès sur une période de 4 mois. Les malades inclus présentaient une schizophrénie ou un trouble schizo-affectif, sélectionnés en deux groupes observant et non observant. L’évaluation de l'observance a été faite par un hétéro-questionnaire comprenant une liste de causes d'abandon du traitement avec des réponses par oui ou non et à l'aide de l’échelle MARS (Medication Adherence Rating Scale). Le traitement statistique des résultats a été réalisé par le logiciel Epi Info version 3.5.1. On a recruté 164 participants, 112 étaient des malades non observants à leur traitement (cas) et 52 patients bien observants (témoins). L’âge moyen est 31 ans, avec une prédominance masculine. Les facteurs de risque d'inobservance thérapeutique sont: l’âge jeune, le sexe masculin, le célibat, les troubles addictifs. Les principales raisons d'abandon du traitement sont le changement fréquent du médecin, le manque d'informations sur la maladie, un mauvais insight et les effets secondaires des antipsychotiques. Le groupe de schizophrènes non adhérents à leur traitement pharmacologique avait un score élevé à l’échelle MARS dans 80% cas. Ces résultats doivent être pris en considération par le personnel soignant pour optimiser l'observance thérapeutique chez les patients souffrant de schizophrénie. PMID:26161196

  14. Body water handling in response to hypertonic-saline induced diuresis in fasting northern elephant seal pups (Mirounga angustirostris)

    NASA Technical Reports Server (NTRS)

    Ortiz, Rudy M.; Wade, Charles E.; Ortiz, C. Leo

    2003-01-01

    During natural fasting conditions in postweaned northern elephant seal (NES) (Mirounga angustirostris) pups, urinary water loss is minimized and percent total body water (TBW) is maintained constant. However, following infusion of hypertonic saline, glomerular filtration rate (GFR) and urine output increased in fasting pups. Therefore, we quantified the magnitude of the hypernatremia-induced diuresis relative to the animal's total body water (TBW) pool and the percentage of filtered water reabsorbed. Following a 24 h control period, naturally fasting NES pups (n=7) were infused (4 ml min(-1)) with hypertonic saline (16.7%) at a dose of 3 mmol NaCl kg(-1) body mass. Total body water was estimated prior to infusion by tritium dilution, GFR was estimated by standard creatinine clearance, and urine output (V) was measured for 24 h during the control and post infusion periods. Percentage of filtered water reabsorbed was calculated as (1-(V/GFR))x100. Twenty-four hours following the infusion, GFR (control: 69+/-12 ml min(-1) and post-infusion: 118+/-19 ml min(-1); mean+/-S.E.) increased 77+/-28% above control and the percentage of filtered water reabsorbed was decreased 0.4+/-0.1%. The increase in urine output (control: 218+/-47 ml d(-1) and post-infusion: 883+/-92 ml d(-1)) accounted for 1.7+/-0.2% of the pups' TBW. The hypernatremia-induced diuresis was accompanied by the loss of body water indicating the lack of water retention. Although the 77% increase in GFR was only associated with a 0.4% decrease in the percentage of filtered water reabsorbed, this decrease was significant enough to result in a 4-fold increase in urine output. Despite the observed diuresis, fasting NES pups appear to possess an efficient water recycling mechanism requiring only a small percentage of body water to excrete an excess salt load. This water recycling mechanism may allow pups to avoid negative perturbations in body water as they initiate feeding in a marine environment following the fast.

  15. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Synthetic Biology Research Program, National University of Singapore, Singapore

    Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fattymore » acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.« less

  16. Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

    PubMed Central

    Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

    2014-01-01

    Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes. PMID:25566540

  17. Nuclear routing networks span between nuclear pore complexes and genomic DNA to guide nucleoplasmic trafficking of biomolecules

    PubMed Central

    Malecki, Marek; Malecki, Bianca

    2012-01-01

    In health and disease, biomolecules, which are involved in gene expression, recombination, or reprogramming have to traffic through the nucleoplasm, between nuclear pore complexes (NPCs) and genomic DNA (gDNA). This trafficking is guided by the recently revealed nuclear routing networks (NRNs). In this study, we aimed to investigate, if the NRNs have established associations with the genomic DNA in situ and if the NRNs have capabilities to bind the DNA de novo. Moreover, we aimed to study further, if nucleoplasmic trafficking of the histones, rRNA, and transgenes’ vectors, between the NPCs and gDNA, is guided by the NRNs. We used Xenopus laevis oocytes as the model system. We engineered the transgenes’ DNA vectors equipped with the SV40 LTA nuclear localization signals (NLS) and/or HIV Rev nuclear export signals (NES). We purified histones, 5S rRNA, and gDNA. We rendered all these molecules superparamagnetic and fluorescent for detection with nuclear magnetic resonance (NMR), total reflection x-ray fluorescence (TXRF), energy dispersive x-ray spectroscopy (EDXS), and electron energy loss spectroscopy (EELS). The NRNs span between the NPCs and genomic DNA. They form firm bonds with the gDNA in situ. After complete digestion of the nucleic acids with the RNases and DNases, the newly added DNA - modified with the dNTP analogs, bonds firmly to the NRNs. Moreover, the NRNs guide the trafficking of the DNA transgenes’ vectors - modified with the SV40 LTA NLS, following their import into the nuclei through the NPCs. The pathway is identical to that of histones. The NRNs also guide the trafficking of the DNA transgenes’ vectors, modified with the HIV Rev NES, to the NPCs, followed by their export out of the nuclei. Ribosomal RNAs follow the same pathway. To summarize, the NRNs are the structures connecting the NPCs and the gDNA. They guide the trafficking of the biomolecules between the NPCs and the gDNA. PMID:23275893

  18. Native and Non-Native Writers' Use of First Person Pronouns in the Different Sections of Biology Research Articles in English

    ERIC Educational Resources Information Center

    Martinez, Iliana A.

    2005-01-01

    Various authors have shown the first person to play a key role in the construction of the writer's persona in research articles. This paper compares the use of first person in a corpus of biology articles produced by native English-speaking (NES) writers and a corpus of research article manuscripts produced by non-native English-speaking (NNES)…

  19. Transient Signal Distortion and Coupling in Multilayer Multiconductor MIC Microstrips

    DTIC Science & Technology

    1990-05-22

    cess.ar1 and identify by block number) I FIELD GROUP I $..)3-{; ’\\0-:: Transient signals, distortion, dispersion, microstrip J 1 i nes , multi...printed circuit design; complex microstrip structures {multiple lines and/or dielectric layers), coupling between lines, distortion of non -periodic...signals on complex structures, and a new method to control coupling on multilayer structures, as well as presenting numerical results for each of these

  20. Proteome-wide search for functional motifs altered in tumors: Prediction of nuclear export signals inactivated by cancer-related mutations

    PubMed Central

    Prieto, Gorka; Fullaondo, Asier; Rodríguez, Jose A.

    2016-01-01

    Large-scale sequencing projects are uncovering a growing number of missense mutations in human tumors. Understanding the phenotypic consequences of these alterations represents a formidable challenge. In silico prediction of functionally relevant amino acid motifs disrupted by cancer mutations could provide insight into the potential impact of a mutation, and guide functional tests. We have previously described Wregex, a tool for the identification of potential functional motifs, such as nuclear export signals (NESs), in proteins. Here, we present an improved version that allows motif prediction to be combined with data from large repositories, such as the Catalogue of Somatic Mutations in Cancer (COSMIC), and to be applied to a whole proteome scale. As an example, we have searched the human proteome for candidate NES motifs that could be altered by cancer-related mutations included in the COSMIC database. A subset of the candidate NESs identified was experimentally tested using an in vivo nuclear export assay. A significant proportion of the selected motifs exhibited nuclear export activity, which was abrogated by the COSMIC mutations. In addition, our search identified a cancer mutation that inactivates the NES of the human deubiquitinase USP21, and leads to the aberrant accumulation of this protein in the nucleus. PMID:27174732

  1. Reengineering ribosome export.

    PubMed

    Lo, Kai-Yin; Johnson, Arlen W

    2009-03-01

    Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages.

  2. Reengineering Ribosome Export

    PubMed Central

    Lo, Kai-Yin

    2009-01-01

    Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages. PMID:19144820

  3. A Critical Role for CRM1 in Regulating HOXA Gene Transcription in CALM-AF10 Leukemias

    PubMed Central

    Conway, Amanda E.; Haldeman, Jonathan M.; Wechsler, Daniel S.; Lavau, Catherine P.

    2014-01-01

    The leukemogenic CALM-AF10 fusion protein is found in patients with immature acute myeloid and T-lymphoid malignancies. CALM-AF10 leukemias display abnormal H3K79 methylation and increased HOXA cluster gene transcription. Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear. We previously determined that CALM contains a CRM1-dependent nuclear export signal (NES), which is both necessary and sufficient for CALM-AF10-mediated leukemogenesis. Here, we find that interaction of CALM-AF10 with the nuclear export receptor CRM1 is necessary for activating HOXA gene expression. We show that CRM1 localizes to HOXA loci where it recruits CALM-AF10, leading to transcriptional and epigenetic activation of HOXA genes. Genetic and pharmacological inhibition of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin, resulting in immediate loss of transcription. These results provide a comprehensive mechanism by which the CALM-AF10 translocation activates the critical HOXA cluster genes. Furthermore, this report identifies a novel function of CRM1: the ability to bind chromatin and recruit the NES-containing CALM-AF10 transcription factor. PMID:25027513

  4. Comportement instationnaire des thermoéléments à effet Peltier multi-étages

    NASA Astrophysics Data System (ADS)

    Monchoux, F.; Zély, D.; Cordier, A.

    1995-01-01

    The analysis of thermoelectric phenomena is possible based on non-equilibrium thermodynamics. Integration of the thermal balance equation leads to an analytical solution for the non-stationnary behaviour. The influence to Thomson effect is commmented. The model, introduced in the complete software TRNSYS, permits the modelling of complex systems including such elements in their thermal regulation. La thermodynamique des processus irréversibles permet l'analyse des phénomènes thermoélectriques. Par intégration de l'équation de bilan thermique, on a obtenu une solution analytique pour le régime non stationnaire donnant la température en tous points et le flux absorbé. On a analysé l'influence de l'effet Thomson. Le modèle a été inclu dans le code plus général TRNSYS qui permet la modélisation de systèmes complexes.

  5. Nuclear networking.

    PubMed

    Xie, Wei; Burke, Brian

    2017-07-04

    Nuclear lamins are intermediate filament proteins that represent important structural components of metazoan nuclear envelopes (NEs). By combining proteomics and superresolution microscopy, we recently reported that both A- and B-type nuclear lamins form spatially distinct filament networks at the nuclear periphery of mouse fibroblasts. In particular, A-type lamins exhibit differential association with nuclear pore complexes (NPCs). Our studies reveal that the nuclear lamina network in mammalian somatic cells is less ordered and more complex than that of amphibian oocytes, the only other system in which the lamina has been visualized at high resolution. In addition, the NPC component Tpr likely links NPCs to the A-type lamin network, an association that appears to be regulated by C-terminal modification of various A-type lamin isoforms. Many questions remain, however, concerning the structure and assembly of lamin filaments, as well as with their mode of association with other nuclear components such as peripheral chromatin.

  6. GEODSS Tracking Results on Asteroid 2012 DA14

    DTIC Science & Technology

    2013-06-12

    PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Air...Force Space Command,Det 3, 21st Operations Group (OG),Maui,HI,96753 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME...they performed utilizing known cases of this occurrence, they had concluded that a Natural Earth Satellite (NES) of 1meter diameter should be

  7. Microbiological Water Quality of Impoundments: A Literature Review.

    DTIC Science & Technology

    1982-12-01

    A123-470 MICROBIOLOGICAL WATER QUALITY OF IMPOUNDMENTS:A i/i LITERATURE REYIEU(U) TEX S UNJY AT DALLAS RICHRDSON G BURTON DEC 82 NES/MP/E-82-6...REPORT G PERIOD COVERED . MICROBIOLOGICAL WATER QUALITY OF IMPOUNDMENTS: Final report A LITERATURE REVIEW 6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR...Va. 22151. IS. KEY WORDS (Continue an reverse side It necessary mid Identify by black numnber) Bacteria Water quality S Impoundments Water sampling

  8. Aerobic Treatability of Waste Effluent from the Leather Finishing Industry

    DTIC Science & Technology

    1993-12-01

    Thesis in Environmental Engineering by Jeffery A. Vinger Submitted in Partial Fulfillment / of the Requirements Acceslon -for [ for the Degree of NeS CRA...respirometer tests of the raw wastes and mass balance analysis. The results of Phase I were published in a report to the Seton Company as Environmental ...Randall (1992) states that the main driving forces behind the changes in paints and coatings toward water-based mixtures has been the environmental

  9. Targeting International Terrorism with the Law of Armed Conflict: An Alternative Strategy

    DTIC Science & Technology

    1991-02-11

    AD-A236 582 D TIC III IBII IH IH JUNI 1. 1991. (Unclassified Paper) NAVAL WAR COLLEGE Newport, R.I. TARGETING INTERNATIONAL TERRORISM WITH THE LAW OF...11. TITLE OWN11110 Secrty Ceu4ifction) TARGETING INTERNATIONAL TERRORISM WITH THE LAW OF ARMED CONFLICT: AN ALTERNATIVE STRATEGY (1.) 12, PERSONAL...lawegieforcoperatiosb re forcdaigwt nes.nItiofurther rorimmendgfral rbetos msesnt ofte thkede easuc-tresa en ocnrotadrsodttate-sponsored terrorism . Ti a

  10. Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial.

    PubMed

    Zitzmann, M; Rohayem, J; Raidt, J; Kliesch, S; Kumar, N; Sitruk-Ware, R; Nieschlag, E

    2017-05-01

    Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone ® (NES), all in combination with transdermal testosterone (T). Randomized clinical trial testing was performed with four progestins at two doses each. After a 2-week progestin-only treatment, transdermal T was added for further 4 weeks and was followed by a 3-week recovery period. Progestin-dose per day: CPA 10 mg/20 mg, NES 2 mg/3 mg/dose e.g. 200/300 μg/day absorbed, NETA 5 mg/10 mg, LNG 120 μg/240 μg. From an andrology outpatient clinic, 56 healthy men aged 18-50 years, with body mass index ≤33 kg × m -2 were included in the study. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied. Secondary outcome measure included were serum testosterone concentrations, sperm concentrations, and safety parameters. Intergroup comparisons demonstrated that CPA and LNG had the strongest effect on LH/FSH suppression. Nevertheless, every substance showed significant inhibitory effects on gonadotropin secretion, especially in combination with transdermal T. A decrease in hematocrit and insulin sensitivity as well as cholesterol subfractions and triglycerides was uniformly seen for every group. The combination of oral or transdermal progestins with a transdermal testosterone preparation is able to suppress gonadotropins. Further dose titration studies with sperm suppression as an end-point should be conducted to determine the lowest effective dose for hormonal male contraception. © 2017 American Society of Andrology and European Academy of Andrology.

  11. Nature exposure sufficiency and insufficiency: The benefits of environmental preservation.

    PubMed

    Reddon, John R; Durante, Salvatore B

    2018-01-01

    Increasing industrialization, urbanization, and a failure of many world leaders to appreciate the consequences of climate change are deleteriously impacting quality of life as well as diminishing the prospects for long term survival. Economic competitiveness and corporate profitability often pre-empt environmental concerns. The calving of an iceberg in Antarctica and the hurricane activity in the Caribbean during 2017 are unfortunate illustrations of the continuing escalation of environmental issues. We provide historical and current evidence for the importance of Nature Exposure (NE) and introduce the continuum Nature Exposure Sufficiency (NES) and Insufficiency (NEI). Insufficiency includes impoverished environments (e.g., slums and prisons) where nature exposure is very limited. Nature Exposure Sufficiency (NES) is an optimal amount of exposure to nature where many benefits such as reinvigoration can be obtained by everyone. NES also has several benefits for individuals with various health conditions such as arthritis, dementia, or depression. The benefits of NE are not just derivable from parks, forests, and other natural settings. Interiors of buildings and homes can be enhanced with plants and even pictures or objects from nature. Additionally, there is abundant evidence indicating that virtual and artificial environments depicting nature can provide substantial NE and therefore contribute to general wellbeing. Besides the difficulty in achieving cooperation amongst nations, corporations, and other collectives in developing and implementing long range plans to deal with climate change, there is also sometimes an aversion at the individual level whereby people are unwilling to experience nature due to insects and other discomforts. Such individuals are often averse to supplanting the comforts of home, even temporarily, with inadequate facilities that are seemingly less pleasant than their typical dwellings. We propose using the term Nature Exposure Aversion (NEA) to describe such behavior and propose that the aversion is largely due to conditioning. Such behavior may be addressed through desensitization in virtual environments which in turn may contribute to an endorsement of the view that climate change is occurring and must be dealt with. The issues of Nature Exposure Sufficiency and Insufficiency are intertwined with the sustainability of the planet and future planning and efforts to deal with the environment. If the outcome is unfavorable, the descent of civilization will be more rapid than the ascent. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Stochastic resonance in a time-delayed feedback tristable system and its application in fault diagnosis

    NASA Astrophysics Data System (ADS)

    Shi, Peiming; Yuan, Danzhen; Han, Dongying; Zhang, Ying; Fu, Rongrong

    2018-06-01

    Stochastic resonance (SR) phenomena in a time-delayed feedback tristable system driven by Gaussian white noise are investigated by simulating the potential function, mean first-passage time (MFPT), and signal-to-noise ratio (SNR) of the system. Through the use of a short delay time, the generalized potential function and stationary probability density function (PDF) are obtained. The delay feedback term has a significant effect on both equations, and that the parameters b, c, and d have different effects on the three wells of the potential function. The MFPT is calculated, which plays an extremely important role in research on particles escape rates. We find that the delay feedback term can affect the noise enhanced stability (NES). In addition, the SR characteristics are studied by the index of SNR. The simulation demonstrates that SNR is a non-monotonic distributed and that the peak SNR value can be attained by adjusting the appropriate parameters. Finally, the proposed theory is combined with a variable step method and applied to the detection of high frequencies in experiments. The result indicates that the fault frequency can be identified, and that the energy of the fault signal can be enhanced under suitable delay feedback parameters.

  13. Synthesis of 6-Substituted-2,4-Diamino-5,6,7,8-Tetrahydropyrimido(4-5-d)Pyrimidines.

    DTIC Science & Technology

    1979-10-01

    triaminopyrihidifle with substituted Andines 2, 1. Anilines 2 2. 0-Arylhydroxylami nes 3 3. Benzylamines 4 4. O-Benzyl hydroxylamines 4 5. PhenylethylamineS 5 6...by hydrazinolysis of the phthaliinide intermediate. 5. Phenylethylamines The reaction of 2,4,6-triaminopyrimidine with phenylethyl- amines and...5,6,7,8-tetrahydropyrimido L!,5-d_1 pyrimidines were excellent. These products were summarized in Table 1. The phenylethylamines were usually prepared

  14. Bibliography on Cold Regions Science and Technology. Volume 42

    DTIC Science & Technology

    1988-12-01

    Mdcaniimea de l’interaction glace/ouvraaes en mer], Putot, C. Imiiwi Fnnstis du Pttrole. Revue, May-June 1987, 42(3), p.347-373. In French with...resistance and prediction. [La route en presence de verglas. Ph6nom6nes. adherence, provisions], Uvet, J., Revue gtottnle des routes et des »Prodromes...M£todo de predieeiön del drenaje aubglaciar, sus perspectivas en los glaciares subpolares de la AnUrtidai, Eraao, A., Actas del segundo Symposium

  15. The Recombinant Inhibitor of DNA Binding Id2 Forms Multimeric Structures via the Helix-Loop-Helix Domain and the Nuclear Export Signal.

    PubMed

    Roschger, Cornelia; Schubert, Mario; Regl, Christof; Andosch, Ancuela; Marquez, Augusto; Berger, Thomas; Huber, Christian G; Lütz-Meindl, Ursula; Cabrele, Chiara

    2018-04-07

    The inhibitor of DNA binding and cell differentiation 2 (Id2) is a helix-loop-helix (HLH) protein that acts as negative dominant regulator of basic-HLH transcription factors during development and in cancer. The structural properties of Id2 have been investigated so far by using synthetic or recombinant fragments reproducing single domains (N-terminus, HLH, C-terminus): the HLH domain tends to dimerize into a four-helix bundle, whereas the flanking regions are flexible. In this work, the intact protein was expressed in E. coli , solubilized from inclusion bodies with urea, purified and dissolved in water at pH~4. Under these conditions, Id2 was obtained with both cysteine residues disulfide-bonded to β-mercaptoethanol that was present during the solubilization process. Moreover, it existed in a self-assembled state, in which the N-terminus remained highly flexible, while the HLH domain and, surprisingly, part of the C-terminus, which corresponds to the nuclear export signal (NES), both were involved in slowly tumbling, rigid structures. The protein oligomers also formed twisted fibrils that were several micrometers long and up to 80 nm thick. These results show that self-assembly decreases the backbone flexibility of those two protein regions (HLH and NES) that are important for interaction with basic-HLH transcription factors or for nucleocytoplasmic shuttling.

  16. Congress likely to approve energy legislation by fall

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Crow, P.

    This paper reports that Congress is likely to pass broad energy legislation this fall that paradoxically seeks to reduce US dependence on oil imports without increasing domestic oil production. The House of Representatives approved 381-37 and the Senate 94-4 their separate but similar energy bills, so it appears Congress will approve a compromise bill by an overwhelming margin. A presidential veto is not threatened. A single massive bill is a different approach for congressional energy committees, the first such attempt in at least a dozen years. Energy Sec. James Watkins launched the national energy strategy (NES) effort 3 years ago.more » After taking office, he found many energy policy statements on Department of Energy shelves but no real plans. Watkins then began developing a proposed NES complete with timetables and specific goals. Oil producers complain that, other than a tax provision for independents in the House bill, the two bills do nothing to promote US oil exploration or production. The bills restrict offshore exploration, do not aid onshore drilling on federal lands, and do not allow exploration of the nation's best oil prospect, the Arctic National Wildlife Refuge Coastal Plain east of Alaska's Prudhoe Bay field. The oil industry successfully fought provisions in the bills to require it, rather than the government, to pay for filling the Strategic petroleum Reserve.« less

  17. Structure of the Mesophases Formed by a Perfluoroalkyl/Biphenyl Compound. Amphiphilic and Steric Effects

    NASA Astrophysics Data System (ADS)

    Pensec, Sandrine; Tournilhac, François-Genès; Bassoul, Pierre

    1996-11-01

    We describe the synthesis and mesomorphic behaviour of 4-(1H,1H-perfluorooctyloxy)- 4'-methoxy biphenyl. Two mesophases of smectic E and smectic A types were observed. X-ray diffraction study of the smectic E phase indicates a herringbone arrangement of the biphenyl cores, the perfluoroalkyl chains being in a molten state. The {S_E to S_A} transition is related to the melting of the biphenyl sublattice. In both phases, the flexibility of perfluoroalkyl chains permits the area matching between the two segregated sublayers. Nous décrivons la synthèse et les propriétés mésomorphes du 4-(1H,1H-perfluorooctyloxy)- 4'-méthoxy biphényle. Ce composé forme deux mésophases de type smectique E et smectique A. L'analyse par diffraction des rayons X révèle, dans le cas de la phase smectique E un arrangement en chevrons des coeurs biphényles, les chaînes perfluoroalkyles se trouvant dans un état désordonné. La transition {S_E to S_A} correspond à la fusion partielle de la sous-couche biphényle. Dans les deux phases smectiques, la flexibilité des chaînes perfluoroalkyles permet l'adéquation des aires moléculaires entre les deux sous-couches ségrégées.

  18. The Complexity of Neuroenhancement and the Adoption of a Social Cognitive Perspective

    PubMed Central

    Zelli, Arnaldo; Lucidi, Fabio; Mallia, Luca

    2015-01-01

    This contribution attempts to provide a broad perspective to the psychological study of neuroenhancement (NE). It departs from the assumption that, as the use of performance enhancing substances in sport, the use of substances with the aim of improving one’s cognitive, motivational and affective functioning in academic domains is a goal-directed behavior. As such, its scientific study may very well benefit from an analysis taking into account the psychological processes regulating people’s behavioral intentions and decisions. Within this broad framework, this contribution addresses several issues that currently seem to characterize the debate in the literature on neuroenhancement substances (NES) use. The first conceptual issue seeks to determine and define the “boundaries” of the phenomenon. The second issue concerns the empirical evidence on the prevalence of using certain substances for the purpose of NE. Finally, there is a debate around the ethical and moral implications of NE. Along these lines, the existing psychological research on NE has adopted mainly sociological and economic decision-making perspectives, greatly contributing to the psychological discourse about the phenomenon of NE. However, we argue that the existing psychological literature does not offer a common, explicit and integrated theoretical framework. Borrowing from the framework of doping research, we recommend the adoption of a social cognitive model for pursuing a systematic analysis of the psychological processes that dynamically regulate students’ use of NES over time. PMID:26648906

  19. Yeast Nucleoporins Involved in Passive Nuclear Envelope Permeability

    PubMed Central

    Shulga, Nataliya; Mosammaparast, Nima; Wozniak, Richard; Goldfarb, David S.

    2000-01-01

    The vertebrate nuclear pore complex (NPC) harbors an ∼10-nm diameter diffusion channel that is large enough to admit 50-kD polypeptides. We have analyzed the permeability properties of the Saccharomyces cerevisiae nuclear envelope (NE) using import (NLS) and export (NES) signal-containing green fluorescent protein (GFP) reporters. Compared with wild-type, passive export rates of a classical karyopherin/importin (Kap) Kap60p/Kap95p-targeted NLS-GFP reporter (cNLS-GFP) were significantly faster in nup188-Δ and nup170-Δ cells. Similar results were obtained using two other NLS-GFP reporters, containing either the Kap104p-targeted Nab2p NLS (rgNLS) or the Kap121p-targeted Pho4p NLS (pNLS). Elevated levels of Hsp70 stimulated cNLS-GFP import, but had no effect on the import of rgNLS-GFP. Thus, the role of Hsp70 in NLS-directed import may be NLS- or targeting pathway-specific. Equilibrium sieving limits for the diffusion channel were assessed in vivo using NES-GFP reporters of 36–126 kD and were found to be greater than wild-type in nup188-Δ and nup170-Δ cells. We propose that Nup170p and Nup188p are involved in establishing the functional resting diameter of the NPC's central transport channel. PMID:10831607

  20. Coalition Formation and Spectrum Sharing of Cooperative Spectrum Sensing Participants.

    PubMed

    Zhensheng Jiang; Wei Yuan; Leung, Henry; Xinge You; Qi Zheng

    2017-05-01

    In cognitive radio networks, self-interested secondary users (SUs) desire to maximize their own throughput. They compete with each other for transmit time once the absence of primary users (PUs) is detected. To satisfy the requirement of PU protection, on the other hand, they have to form some coalitions and cooperate to conduct spectrum sensing. Such dilemma of SUs between competition and cooperation motivates us to study two interesting issues: 1) how to appropriately form some coalitions for cooperative spectrum sensing (CSS) and 2) how to share transmit time among SUs. We jointly consider these two issues, and propose a noncooperative game model with 2-D strategies. The first dimension determines coalition formation, and the second indicates transmit time allocation. Considering the complexity of solving this game, we decompose the game into two more tractable ones: one deals with the formation of CSS coalitions, and the other focuses on the allocation of transmit time. We characterize the Nash equilibria (NEs) of both games, and show that the combination of these two NEs corresponds to the NE of the original game. We also develop a distributed algorithm to achieve a desirable NE of the original game. When this NE is achieved, the SUs obtain a Dhp-stable coalition structure and a fair transmit time allocation. Numerical results verify our analyses, and demonstrate the effectiveness of our algorithm.

  1. Kerr effect in the isotropic phase of a side-chain polymeric liquid crystal

    NASA Astrophysics Data System (ADS)

    Reys, V.; Dormoy, Y.; Collin, D.; Keller, P.; Martinoty, P.

    1992-02-01

    The birefringence induced by a pulsed electrical field was used to study the pretransitional effects associated with the isotropic phase of a side-chain polysiloxane. The results obtained show that these effects are characterised by a conventional value of the static exponent and an abnormal value of the dynamic exponent, which shows that the dynamic theory of low molecular weight liquid crystals does not apply. The results also reveal competition between the dipolar moments induced by the electrical field and the permanent moments of the mesogenic molecules. La biréfringence induite par un champ électrique impulsionnel a été utilisée pour étudier les effets prétransitionnels associés à la phase isotrope d'un polysiloxane à chaînes latérales. Les résultats obtenus montrent que ces effets sont caractérisés par une valeur classique de l'exposant statique et une valeur anormale de l'exposant dynamique. Ce dernier résultat montre que la théorie dynamique des cristaux liquides de bas poids moléculaire n'est pas applicable au cas présent. Les expériences mettent également en évidence une compétition entre les moments dipolaires induits par le champ électrique et les moments permanents des molécules mésogènes.

  2. A new way of controlling NesCOPOs (nested cavity doubly resonant OPO) for faster and more efficient high resolution spectrum measurement

    NASA Astrophysics Data System (ADS)

    Georges des Aulnois, Johann; Szymanski, Benjamin; Grimieau, Axel; Sillard, Léo.

    2018-02-01

    Optical Parametric Oscillator (OPO) is a well-known solution when wide tunability in the mid-infrared is needed. A specific design called NesCOPO (Nested Cavity doubly resonant OPO) is currently integrated in the X-FLR8 portable gas analyzer from Blue Industry and Science. Thanks to its low threshold this OPO can be pumped by a micro-chip nanosecond YAG (4 kHz repetition rate and a 30 GHz bandwidth). To achieve very high resolution spectra (10 pm of resolution or better), the emitted wavelength has to be finely controlled. Commercial Wavemeter do not meet price and compactness required in the context of an affordable and portable gas analyzer. To overcome this issue, Blue first integrated an active wavelength controller using multiple tunable Fabry-Perot (FP) interferometers. The required resolution was achieved at a 10 Hz measurement rate. We now present an enhanced Wavemeter architecture, based on fixed FP etalons, that is 100 times faster and 2 times smaller. We avoid having FP `blind zones' thanks to one source characteristic: the knowledge of the FSR (Free Spectral Range) of the OPO source and thus, the fact that only discrete wavelengths can be emitted. First results are displayed showing faster measurement for spectroscopic application, and potential future improvement of the device are discussed.

  3. Shortening and Improving the Embryonic Stem Cell Test through the Use of Gene Biomarkers of Differentiation

    PubMed Central

    Romero, Andrea C.; Vilanova, Eugenio; Sogorb, Miguel A.

    2011-01-01

    The embryonic Stem cell Test (EST) is a validated assay for testing embryotoxicity in vitro. The total duration of this protocol is 10 days, and its main end-point is based on histological determinations. It is suggested that improvements on EST must be focused toward molecular end-points and, if possible, to reduce the total assay duration. Five days of exposure of D3 cells in monolayers under spontaneous differentiation to 50 ng/mL of the strong embryotoxic 5-fluorouracil or to 75 μg/mL of the weak embryotoxic 5,5-diphenylhydeantoin caused between 20 and 74% of reductions in the expression of the following genes: Pnpla6, Afp, Hdac7, Vegfa, and Nes. The exposure to 1 mg/mL of nonembryotoxic saccharin only caused statistically significant reductions in the expression of Nes. These exposures reduced cell viability of D3 cells by 15, 28, and 34%. We applied these records to the mathematical discriminating function of the EST method to find that this approach is able to correctly predict the embryotoxicity of all three above-mentioned chemicals. Therefore, this work proposes the possibility of improve EST by reducing its total duration and by introducing gene expression as biomarker of differentiation, which might be very interesting for in vitro risk assessment embryotoxicity. PMID:21876691

  4. Nuclear export signal of PRRSV NSP1α is necessary for type I IFN inhibition

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Zhi

    2016-12-15

    The nonstructural protein 1α (NSP1α) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1α and its inhibition of type I IFN. NSP1α was found to contain the classical nuclear export signal (NES) and NSP1α nuclear export was CRM-1-mediated. NSP1α was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. NSP1α was also found to interact with CBP, which impliesmore » a possible mechanism of CBP degradation by NSP1α. Taken together, our results describe a novel mechanism of PRRSV NSP1α for type I IFN inhibition and suppression of the host innate antiviral response. - Highlights: •NSP1α contains the NES and NSP1α nuclear export was CRM-1-mediated. •NSP1α was shuttling between the nucleus and cytoplasm continuously. •The nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. •NSP1α interacts with CBP, which implies the mechanism of CBP degradation by NSP1α.« less

  5. Simultaneous determination of suspended particulate trace metals (Co, Ni, Cu, Zn, Cd and Pb) in seawater with small volume filtration assisted by microwave digestion and flow injection inductively coupled plasma mass spectrometer.

    PubMed

    Nakatsuka, Seiji; Okamura, Kei; Norisuye, Kazuhiro; Sohrin, Yoshiki

    2007-06-26

    A new technique for the determination of suspended particulate trace metals (P-metals >0.2 microm), such as Co, Ni, Cu, Zn, Cd and Pb, in open ocean seawater has been developed by using microwave digestion coupled with flow injection inductively coupled plasma mass spectrometry (FI-ICP-MS). Suspended particulate matter (SPM) was collected from 500 mL of seawater on a Nuclepore filter (0.2 microm) using a closed filtration system. Both the SPM and filter were completely dissolved by microwave digestion. Reagents for the digestion were evaporated using a clean evaporation system, and the metals were redissolved in 0.8 M HNO3. The solution was diluted with buffer solution to give pH 5.0 and the metals were determined by FI-ICP-MS using a chelating adsorbent of 8-hydroxyquinoline immobilized on fluorinated metal alkoxide glass (MAF-8HQ). The procedure blanks with a filter were found to be 0.048+/-0.008, 10.3+/-0.3, 0.27+/-0.05, 3.3+/-1.8, 0.02+/-0.03 and 0.85+/-0.09 ng L(-1) for Co, Ni, Cu, Zn, Cd and Pb, respectively (n=14). Detection limits defined as 3 times the standard deviation of the blanks were 0.023, 0.90, 0.14, 5.3, 0.078 and 0.28 ng L(-1) for Co, Ni, Cu, Zn, Cd and Pb, respectively. Accuracy was evaluated using certified reference materials of chlorella (NES CRM No. 3) and marine sediment (HISS-1). The method was applied to the determination of vertical distributions for P-Co, Ni, Cu, Zn, Cd and Pb in the Western North Pacific.

  6. Ensuring standards for the extended role of optometry.

    PubMed

    Jarvis, Ian; Ker, Jean

    2014-06-01

    In optometry, as in other health professions, such as pharmacy and nursing, there has been an expansion in the role of the optometrist in primary eye care, taking on aspects of care such as prescribing, which was traditionally undertaken by general practitioners. In optometry, this extended role involves monitoring eye conditions that do not require treatment or monitoring in secondary care, roles that were traditionally referred on. However, any extended role requires educational support. The development of a national educational programme can prevent any duplication of effort and provide a system of disseminating support to practitioners, who often work in isolation. The National Education Programme was developed and supported by the National Health Service (NHS) Education for Scotland (NES). This a national body responsible for supporting NHS services in Scotland, by developing and delivering education and training for those who work in NHS Scotland. Optometrists were given educational support in three main stages: simulation of component skills; safe learning in a simulated health care context; and support for the transfer of those skills to practice, including the use of mentoring via e-mail. The evaluation of this three-stage process has been positive. To further develop any expanded role in health care practice, safe guidelines for practice are required. Simulation can provide support at the start of this process in setting standards. However, mentorship in the practice area, as reported in this study, was required to embed newly acquired skills. © 2014 John Wiley & Sons Ltd.

  7. KSC-04pd0307

    NASA Image and Video Library

    2004-02-20

    KENNEDY SPACE CENTER, FLA. - Astronaut Kay Hire talks to students in Garland V. Stewart Magnet Middle School, a NASA Explorer School (NES) in Tampa, Fla. She joined Center Director Jim Kennedy in sharing the agency’s new vision for space exploration with the next generation of explorers. Kennedy is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  8. Matching and Vertex Packing: How Hard Are They?

    DTIC Science & Technology

    1991-01-01

    Theory, 29, Ann. Discrete Math ., North-Holland, Amsterdam, 1986. [2] M.D. Plummer, Matching theory - a sampler: from D~nes K~nig to the present...Ser. B, 28, 1980, 284-304. [20i N. Sbihi, Algorithme de recherche d’un stable de cardinalit6 maximum dans un graphe sans 6toile, Discrete Math ., 29...cliques and by finite families of graphs, Discrete Math ., 49, 1984, 45-59. [92] G. Cornu~jols, D. Hartvigsen and W.R. Pulleyblank, Packing subgraphs in

  9. Impuretés et systèmes corrélés. Des chaînes aux cuprates supraconducteurs

    NASA Astrophysics Data System (ADS)

    Bobroff, J.

    2005-01-01

    Impurities and correlated systems Discovery of high TC superconductors has opened the new field of strongly correlated fermions physics. In these compounds, mostly transition metal oxides, strong correlations between electrons affect sharply their electronic properties. In order to determine accurately these correlations and their possible link with superconductivity, we study the effect of local defects such as non magnetic impurities. In fact, in the more simple case of insulating spin chains and ladders, these impurities induce a staggered magnetism in their neighborhood which reveals the underlying electronic correlations. Similar effects are observed in high TC superconductors, using local probes such as nuclear magnetic resonance. These observations allow to get a better understanding of both normal and superconducting state of these oxides, both full of surprises. La découverte des supraconducteurs à haute température critique a ouvert la voie à une nouvelle physique, celle des fermions fortement corrélés. Dans ces systèmes, le plus souvent des oxydes de métaux de transition, les fortes corrélations entre électrons affectent profondément leurs propriétés électroniques et induisent de nouveaux états originaux : liquides de spins, supraconductivité, etc. Pour mesurer ces corrélations et ainsi déterminer leur lien éventuel avec la supraconductivité, nous proposons d'étudier l'effet de défauts ponctuels tels que des impuretés non magnétiques. En effet, dans le cas plus simple de chaînes ou d'échelles de spin isolantes, ces impuretés induisent dans leur voisinage immédiat un magnétisme alterné révélateur des corrélations électroniques. Des effets semblables sont observés dans les supraconducteurs à haute température critique, grâce à des sondes locales comme la résonance magnétique nucléaire. Ces observations permettent de mieux comprendre à la fois l'état normal et supraconducteur de ces oxydes, tous deux riches en surprises.

  10. Teaching, Testing, and Evaluating Roger D. Mc Leod's Models for Vision, and its Repair, by Patent-pending Naturoptics.

    NASA Astrophysics Data System (ADS)

    Niemi, Paul R.; D., O.; Mc Leod, David M.; Mc Leod, Roger D.

    2007-04-01

    RDM taught a health professional how to recover her previously impaired near vision in one session, also bringing a similar male from 20/30 to 20/10, distance vision, in about ten minutes; another health professional's improvement went from 20/300 to 20/20 in three sessions. A former athlete achieved a distance improvement from 20/800 to 20/100, again, in three sessions. RDM offers to replicate these types of improvements, using patent-pending Naturoptics under monitored conditions, and non-disclosure restraints, to protect franchising and patent-pending rights. Evening atropine use, controlled, at Singapore's National Eye Center, demonstrated an effect against myopia. Does this actually constitute an experimental verification of Mc Leod's Airy-disk radius-formula explanation of how vision works, and predicts how it can be damaged/repaired? Evaluation and documentation is to be by close and distance vision standard charts, or their equivalents, with guaranteed ``chart'' improvements of one line per session, after the beginning visit, or the session is free. Patent-pending Naturoptics differs from all vision-boosting competitors by safely re-eliciting vision's feedback control self-repairs, including astigmatism and presbyopia. To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2007.NES07.C2.4

  11. Biopharmaceutical insights of particulate emulsified systems - a prospective overview.

    PubMed

    Katamreddy, Jyothshna Devi; Yalavarthi, Prasanna Raju; D, Subba Rao; Battu, Sowjanya; Peesa, Jaya Preethi

    2018-05-10

    During the twenty-first century, drug discovery is expanding rapidly and a large number of chemical moieties are recognized. Many of them are poorly soluble and hence related biopharmaceutical constraints are to be addressed systematically. Among novel approaches to resolving biopharmaceutical issues, micro- and nano-emulsified systems serve as the best strategy for delivering both hydrophobic and hydrophilic drugs owing to their greater solubilization and transportation capabilities. Of late, the unique physical and biopharmaceutical properties of these liquid isotropic homogenous systems have gained substantive research importance. In addition nano/micro lipid systems share structural and functional similarity with that of the physiological lipids which offer better tolerance ability in the body. In this context, this article provides information on the historical emergence of particulate emulsified systems, importance and rationale of selection of carriers. It also encompasses the physicochemical principles that are responsible for the elevation of therapeutic outcomes of delivery systems. Detailed and schematic absorption of these drug delivery systems is explained here. Gastro-intestinal biochemistry necessary in the understanding of digestion process, lipolytic products formed, micellar structures, enzymes, transporters, mechanism of cell uptake involved after subsequent oral absorption are also emphasized. In addition, this article also explains disposition and pharmacokinetic properties of emulsified systems with real-time therapeutic research outcomes. The influence of biochemical compositions and biopharmaceutical principles on absorption and disposition patterns of ME/NEs was described in the article for the interest of readers and young researchers.

  12. NMR Investigations into Polydimethylsiloxane Adsorption on Silica Aggregates

    NASA Astrophysics Data System (ADS)

    Cohen Addad, J. P.; Morel, N.

    1996-02-01

    Adsorption properties of polydimethylsiloxane on the surface of silica aggregates are studied from chemical microanalysis combined with proton magnetic relaxation measurements and from swelling measurements performed on mixtures. It is shown that polymer molecules, observed right after the preparation of mixtures, are strongly adsorbed on about 1/4 of the silica surface, only; they form islets. It is also shown that the number of contact points of a chain with the surface is proportional to sqrt{N} during the progressive saturation of the silica surface; N is the number of monometric units in one chain. Les propriétés d'adsorption du polydimethylsiloxane sur la surface d'agrégats de silice sont étudiées par microanalyse chimique, par des mesures de relaxation magnétique des protons liés aux chaînes et par des mesures de gonflement des mélanges polymères-particules, utilisant un bon solvant. On montre qu'immédiatement après la préparation des mélanges, les chaînes solidement adsorbées n'occupent, sous la forme d'ilôts, que le quart de la surface de silice. On montre aussi que, pendant la saturation progressive de la surface, qui dure environ 3 mois à 343 K, le nombre de points de contacts d'une chaîne avec la silice est proportionnel à sqrt{N} ; N étant le nombre de maillons dans la chaîne.

  13. Sexual function in adolescent and young adult survivors of lower extremity bone tumors.

    PubMed

    Barrera, Maru; Teall, Tanya; Barr, Ronald; Silva, Mariana; Greenberg, Mark

    2010-12-15

    Improving survival rates and new surgical options have led to increased interest regarding late effects and quality of life in adolescent and young adult survivors of bone cancers, including their sexual functioning. This study investigated sexual functioning in adolescent and young adult survivors of lower limb bone tumors, in relation to surgical treatments, gender differences, depressive symptoms, global self worth, and physical disability. Twenty-eight participants (age range 18-32 years) completed measures of gender specific sexual function, depressive symptoms, global self worth, and physical disability. For analysis, surgical intervention was grouped into limb sparing surgeries (LS; allograft fusion and endoprosthesis) and amputation or Van Nes rotationplasty (AMP). Male survivors reported significantly higher scores than females on total sexual function scores (P = 0.050), sexual drive (P = 0.002), and frequency of sexual thoughts, fantasies or erotic dreams (P = 0.021). Men also reported significantly better physical functioning scores than women (P = 0.012). LS scored significantly lower on frequency of sexual thoughts, fantasies and erotic dreams (P = 0.048) and frequency of sexual experiences (P = 0.016) compared with AMP. In addition, LS reported significantly more depressive symptoms scores (P = 0.004) and lower self worth scores (P = 0.037), than AMP. These results suggest that male survivors of lower extremity bone tumors experience better sexual functioning than women. Survivors of limb sparing surgeries struggle with sexual function, depressive symptoms, and poor self-perception compared to Van Nes rotationplasty and amputation survivors. Copyright © 2010 Wiley-Liss, Inc.

  14. Notch intracellular domain deficiency in nuclear localization activity retains the ability to enhance neural stem cell character and block neurogenesis in mammalian brain development.

    PubMed

    Jang, Jiwon; Byun, Sung-Hyun; Han, Dasol; Lee, Junsub; Kim, Juwan; Lee, Nayeon; Kim, Inhee; Park, Soojeong; Ha, Soobong; Kwon, Mookwang; Ahn, Jyhyun; Chung, Woo-Jae; Kweon, Dae-Hyuk; Cho, Jae Youl; Kim, Sunyoung; Yoon, Keejung

    2014-12-01

    Notch has a broad range of regulatory functions in many developmental processes, including hematopoiesis, neurogenesis, and angiogenesis. Notch has several key functional regions such as the RBP-Jκ/CBF1 association module (RAM) domain, nuclear localization signals (NLS), and ankyrin (ANK) repeats. However, previous reports assessing the level of importance of these domains in the Notch signaling pathway are controversial. In this study, we have assessed the level of contribution of each Notch domain to the regulation of mammalian neural stem cells in vivo as well as in vitro. Reporter assays and real-time polymerase chain reactions show that the ANK repeats and RAM domain are indispensable to the transactivation of Notch target genes, whereas a nuclear export signal (NES)-fused Notch intracellular domain (NICD) mutant defective in nuclear localization exerts a level of activity comparable to unmodified NICD. Transactivational ability appears to be tightly coupled to Notch functions during brain development. Unlike ANK repeats and RAM domain deletion mutants, NES-NICD recapitulates NICD features such as promotion of astrogenesis at the expense of neurogenesis in vitro and enhancement of neural stem cell character in vivo. Our data support the previous observation that intranuclear localization is not essential to the oncogenesis of Notch1 in certain types of cells and imply the importance of the noncanonical Notch signaling pathway in the regulation of mammalian neural stem cells.

  15. Analysis of Performance of Selected AFC, ATF Fuels, and Lanthanide Transport

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Unal, Cetin; Galloway, Jack D.

    2015-09-29

    We started to look at the performance of ATF concept in LWRs late in FY14 and finish our studies in FY15. The work has been presented in AFC review meetings, ICAPP and TOPFUEL conferences. The final version of the work is accepted for publication in Nuclear Engineering and Science Journal (NES). The copy of ICAPP and NES papers are attached separately to this document as our milestone deliverables. We made an important progress in the modeling of lanthanide transport in FY15. This work produced an ANS Winter Meeting paper and GLOBAL 2015 paper. GLOBAL 2015 paper is also attached asmore » deliverable of FY15. The work on the lanthanide transport is preliminary. We are exploring other potential mechanisms, in addition to “liquid-like” diffusion mechanisms, proposed by Robert Mariani [1] before we analyze data that will be taken by Ohio State University. This year, we concentrate on developing diffusion kernels and principles of modeling. Next year, this work will continue and analyze the Ohio State data and develop approaches to solve multicomponent diffusion. In addition to three papers we attached to this report, we have done some research on coupling and the development of gas release model for metallic fuels in FY15. They are also preliminary in nature; therefore, we give the summary of what we found rather than an extended report that will be done in FY16.« less

  16. Identification of a Plastid-Localized Bifunctional Nerolidol/Linalool Synthase in Relation to Linalool Biosynthesis in Young Grape Berries

    PubMed Central

    Zhu, Bao-Qing; Cai, Jian; Wang, Zhi-Qun; Xu, Xiao-Qing; Duan, Chang-Qing; Pan, Qiu-Hong

    2014-01-01

    Monoterpenoids are a diverse class of natural products and contribute to the important varietal aroma of certain Vitis vinifera grape cultivars. Among the typical monoterpenoids, linalool exists in almost all grape varieties. A gene coding for a nerolidol/linalool (NES/LINS) synthase was evaluated in the role of linalool biosynthesis in grape berries. Enzyme activity assay of this recombinant protein revealed that it could convert geranyl diphosphate and farnesyl diphosphate into linalool and nerolidol in vitro, respectively, and thus it was named VvRILinNer. However, localization experiment showed that this enzyme was only localized to chloroplasts, which indicates that VvRILinNer functions in the linalool production in vivo. The patterns of gene expression and linalool accumulation were analyzed in the berries of three grape cultivars (“Riesling”, “Cabernet Sauvignon”, “Gewurztraminer”) with significantly different levels of monoterpenoids. The VvRILinNer was considered to be mainly responsible for the synthesis of linalool at the early developmental stage. This finding has provided us with new knowledge to uncover the complex monoterpene biosynthesis in grapes. PMID:25470020

  17. A new web-based system to improve the monitoring of snow avalanche hazard in France

    NASA Astrophysics Data System (ADS)

    Bourova, Ekaterina; Maldonado, Eric; Leroy, Jean-Baptiste; Alouani, Rachid; Eckert, Nicolas; Bonnefoy-Demongeot, Mylene; Deschatres, Michael

    2016-05-01

    Snow avalanche data in the French Alps and Pyrenees have been recorded for more than 100 years in several databases. The increasing amount of observed data required a more integrative and automated service. Here we report the comprehensive web-based Snow Avalanche Information System newly developed to this end for three important data sets: an avalanche chronicle (Enquête Permanente sur les Avalanches, EPA), an avalanche map (Carte de Localisation des Phénomènes d'Avalanche, CLPA) and a compilation of hazard and vulnerability data recorded on selected paths endangering human settlements (Sites Habités Sensibles aux Avalanches, SSA). These data sets are now integrated into a common database, enabling full interoperability between all different types of snow avalanche records: digitized geographic data, avalanche descriptive parameters, eyewitness reports, photographs, hazard and risk levels, etc. The new information system is implemented through modular components using Java-based web technologies with Spring and Hibernate frameworks. It automates the manual data entry and improves the process of information collection and sharing, enhancing user experience and data quality, and offering new outlooks to explore and exploit the huge amount of snow avalanche data available for fundamental research and more applied risk assessment.

  18. 3D Additive Construction with Regolith for Surface Systems

    NASA Technical Reports Server (NTRS)

    Mueller, Robert P.

    2014-01-01

    Planetary surface exploration on Asteroids, the Moon, Mars and Martian Moons will require the stabilization of loose, fine, dusty regolith to avoid the effects of vertical lander rocket plume impingement, to keep abrasive and harmful dust from getting lofted and for dust free operations. In addition, the same regolith stabilization process can be used for 3 Dimensional ( 3D) printing, additive construction techniques by repeating the 2D stabilization in many vertical layers. This will allow in-situ construction with regolith so that materials will not have to be transported from Earth. Recent work in the NASA Kennedy Space Center (KSC) Surface Systems Office (NE-S) Swamp Works and at the University of Southern California (USC) under two NASA Innovative Advanced Concept (NIAC) awards have shown promising results with regolith (crushed basalt rock) materials for in-situ heat shields, bricks, landing/launch pads, berms, roads, and other structures that could be fabricated using regolith that is sintered or mixed with a polymer binder. The technical goals and objectives of this project are to prove the feasibility of 3D printing additive construction using planetary regolith simulants and to show that they have structural integrity and practical applications in space exploration.

  19. Relationships between middle childhood outdoor experiences and an adult individual's knowledge of the environment

    NASA Astrophysics Data System (ADS)

    Gillette, Brandon A.

    During the last several decades, the nature of childhood has changed. There is not much nature in it anymore. Numerous studies in environmental education, environmental psychology, and conservation psychology show that the time children spend outdoors encourages healthy physical development, enriches creativity and imagination, and enhances classroom performance. Additional research shows that people's outdoor experiences as children, and adults can lead to more positive attitudes and behavior towards the environment, along with more environmental knowledge with which to guide public policy decisions. The overall purpose of this study was to examine the effect of middle childhood (age 6-11) outdoor experiences on an individual's current knowledge of the environment. This correlational study evaluated the following potential relationships: 1) The effect of "outdoorsiness" (defined as a fondness or enjoyment of the outdoors and related activities) on an individual's environmental knowledge; 2) The effect of gender on an individual's level of outdoorsiness; 3) The effect of setting (urban, suburban, rural, farm) on an individual's level of outdoorsiness and environmental knowledge; 4) The effect of formal [science] education on an individual's level of outdoorsiness and environmental knowledge; and 5) The effect of informal, free-choice learning on an individual's level of outdoorsiness and environmental knowledge. Outdoorsiness was measured using the Natural Experience Scale (NES), which was developed through a series of pilot surveys and field-tested in this research study. Participants included 382 undergraduate students at the University of Kansas with no preference or bias given to declared or undeclared majors. The information from this survey was used to analyze the question of whether outdoor experiences as children are related in some way to an adult's environmental knowledge after accounting for other factors of knowledge acquisition such as formal education, media, and free-choice learning. Though a statistically significant positive correlation was found between an individual's NES and their level of environmental knowledge as an adult, the relationship was weak (r= .112). One-on-one interviews also were conducted with 15 individuals selected from a random sample of the 382 participants. A post-survey focus group comprised of experts from the fields of environmental science and environmental education was also conducted to discuss results from the quantitative portion of the study and provide face validity to the questionnaire.

  20. Forecasting and Hindcasting Waves In and Near the Marginal Ice Zone: Wave Modeling and the ONR Sea State Field Experiment

    DTIC Science & Technology

    2018-04-12

    non-directional) wave spectra, but we consider the energy at high frequencies to be unreliable, so we only use significant waveheight Hs and dominant...spectral density, N=E/s), which is a function of wavenumber or frequency (k or s), direction (θ), space (x,y), and time (t), with spectral density...Elgar 1987). As the spectra are now co-located in time, space , and frequency , the inversion is simply a minimization process for |logVR(6jvH>w(9

  1. KSC-04pd0845

    NASA Image and Video Library

    2004-04-13

    KENNEDY SPACE CENTER, FLA. - Astronaut Rick Linnehan shares his experiences in space with students and faculty at Ralph Bunche Middle School, a NASA Explorer School, in Atlanta, Ga. Linnehan accompanied Center Director Jim Kennedy, who is visiting NES sites to share America’s new vision for space exploration with the next generation of explorers. The purpose of the school visit is to talk with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  2. Relation between the Surface Friction of Plates and their Statistical Microgeometry

    DTIC Science & Technology

    1980-01-01

    3-6 and 𔃽-7. Calibration-- are taken for each of the Uicr~r unit exponent values and best fit li;nes by least squares fitted through each"n set of...parameter, [ = 1.de (2-43) (Clauser 1954, 1956). Data from near equilibrium flows (Coles & Hurst 1968) was plotted along with some typical non-equilibrium...too bad a fit even for the non equilibrium flows. Coles and Hurst (1968) recommended that the fit of the law of the wake to velocity profiles should be

  3. The Dirigible: A Catalyst for Resource Exploitation in Remote Areas?

    DTIC Science & Technology

    1985-04-01

    ir’ship (26’.: 13). .. Hybrid . A he ,vi er than air vehiLile which Lomb nes.’-. s.tar~ it (gas) anrid cly ,mi L (pro~pel 1er s, jet e, g ines ) li ft...another test with a hybrid airship (8:.33). TABLE 1. - Airships Rejected p The three remaining airships will be discussed next. All arc? hybrid LTAs...heavy-lift markets. (Drawing at Appendix 3.) The Cyclo-Crane is a hybrid aircraft utilizing aerostatic lift from a helium filled centerbody to support

  4. Intracellular Protein Delivery for Treating Breast Cancer

    DTIC Science & Technology

    2014-08-01

    protein derived from chicken anemia virus (Backendorf et al., 2008). When transgenically expressed, apoptin can induce p53-independent apoptosis in a...and sho quantified b each figure cell lines He nes HeLa er S-S Rho signals rem re well-shie cessible to rong red flu pping of rh e of the nuc s...Jochemsen, A.G., Vandereb, A.J., and Noteborn, M.H.M. (1995). Apoptin, a Protein- Derived from Chicken Anemia Virus, Induces P53-Independent Apoptosis in Human Osteosarcoma Cells. Cancer Res 55, 486-489.

  5. Distortion Products Otoacoustic Emissions as Markers of Tinnitus Persistence after Acute Acoustic Trauma

    DTIC Science & Technology

    2005-04-01

    recovery in animal models ( Lamm and Arnold 1998; Gervais d’Aldin et al. 1999) and in human ( Suc and Asperge 1988; Suc et al. 1994). Afterwards they were...1309-1316, 1990. [36] Suc B, Asperge A. Les acouphènes des traumatismes sonores par FAMAS. Médecine et Armées, 16 :207-210. 1988. [37] Suc B...Poulet M, Asperge A, Vix J, Barberot J-P, Doucet F. Evolution clinique des traumatismes sonores aigus. Bilan d’une étude de 250 cas. Ann. Otolaryngol

  6. Bioaccumulation of hydroxylated polychlorinated biphenyls and pentachlorophenol in the serum of northern elephant seal pups (Mirounga angustirostris)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Louis, Caroline, E-mail: caroline.louis@uclouvain.be; Covaci, Adrian; Stas, Marie

    Northern elephant seals (NES) (Mirounga angustirostris) from the Año Nuevo State Reserve (CA, USA) were sampled at 1-, 4-, 7- and 10-week post-weaning. Concentrations of hydroxylated polychlorinated biphenyls (HO-PCBs) and their parent PCBs were measured in the serum of each individual. The ΣHO-PCB concentrations in the serum increased significantly between early and late fast (from 282±20 to 529±31 pg/mL). This increase might result from a mobilisation of HO-PCBs transferred from the mother during gestation and/or lactation and stored in the pup's liver. Food deprivation has been shown to exacerbate biotransformation capacities in mammals, birds and fish. The HO-penta-CBs was themore » predominant homologue group, followed by HO-hexa-CBs and HO-hepta-CBs. No preferential pathway for the metabolism of HO-PCBs (HO-direct insertion or NIH-shift of a chlorine atom) could be evidenced. The concentrations of pentachlorophenol (PCP) in the serum of weaned NES increased from 103±7 pg/mL at early fast to 246±41 pg/mL at late fast, which is within the range of PCP concentrations usually encountered in marine mammals. - Highlights: • Σ HO-PCB concentrations in serum significantly increased between early and late fast. • The HO-penta-CBs were the predominant homologue group measured in serum. • No preferential pathway for the metabolism of HO-PCBs could be evidenced. • PCP concentrations in serum significantly increased between early and late fast.« less

  7. Opportunity for change in the future roles for the health library and information professional: meeting the challenges in NHS Scotland.

    PubMed

    Maclean, Gerry

    2006-12-01

    NHS Education for Scotland (NES) is the Special Health Board responsible for supporting best practice in education, training and development for all staff groups within NHS Scotland. As part of its remit, the Knowledge Services Group within NES is responsible for the e-Library, a national electronic resource providing and supporting access to the evidence base. The Knowledge Services Group also supports the national development of library services to NHS Scotland. This article aims to provide a reflective overview of some recent challenges within the health library and information field in Scotland, and the positive role opportunities these have afforded. The information was gathered through extensive professional interaction with staff across the sector over the first year of establishing the new role of Librarian Staff Development Manager. New roles have emerged for health library and information professionals generally; for example, in response to new technology or new user groups. The development of the NHS Scotland e-Library provides examples of role development that emerges symbiotically from core skills applied to a new situation or applied in an innovative way. Role development among health library and information professionals operating at the local service level can be both reactive and proactive. Working together, the partnership between the national Knowledge Services Group and local library and knowledge services for NHS Scotland has resulted in the emergence of additional new roles, extending the role portfolio of the local professional (for example, the Librarian-Tutor role) and supported by other national infrastructures (for example, the competency framework initiative).

  8. Human forniceal region is the stem cell-rich zone of the conjunctival epithelium.

    PubMed

    Harun, Mohd Hairul Nizam; Sepian, Siti Norzalehawati; Chua, Kien-Hui; Ropilah, Abd Rahman; Abd Ghafar, Norzana; Che-Hamzah, Jemaima; Bt Hj Idrus, Ruszymah; Annuar, Faridah Hanom

    2013-03-01

    The anterior surface of the eye is covered by several physically contiguous but histologically distinguishable epithelia overlying the cornea, limbus, bulbar conjunctiva, fornix conjunctiva, and palpebral conjunctiva. The self-renewing nature of the conjunctival epithelia makes their long-term survival ultimately dependent on small populations of stem cells. Hence, the objective of this study was to investigate the expression of the stem cell genes Sox2, OCT4, NANOG, Rex1, NES, and ABCG2 in cultured human conjunctival epithelium from different conjunctival zones, namely, the bulbar, palpebral and fornix zones. Three samples were taken from patients with primary pterygium and cataract (age range 56-66 years) who presented to our eye clinic at the UKM Medical Centre. The eye was examined with slit lamp to ensure there was no underlying ocular surface diseases and glaucoma. Conjunctival tissue was taken from patients who underwent a standard cataract or pterygium operation as a primary procedure. Tissues were digested, cultured, and propagated until an adequate number of cells was obtained. Total RNA was extracted and subjected to expression analysis of conjunctival epithelium genes (KRT4, KRT13, KRT19) and stem cell genes (Sox2, OCT4, NANOG, Rex1, NES, ABCG2) by reverse transcriptase-PCR and 2% agarose gel electrophoresis. The expression of Sox2, OCT4, and NANOG genes were detected in the fornical cells, while bulbar cells only expressed Sox2 and palpebral cells only expressed OCT4. Based on these results, the human forniceal region expresses a higher number of stem cell genes than the palpebral and bulbar conjunctiva.

  9. Differential PAX3 functions in normal skin melanocytes and melanoma cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Medic, Sandra; Rizos, Helen; Ziman, Mel, E-mail: m.ziman@ecu.edu.au

    2011-08-12

    Highlights: {yields} PAX3 retains embryonic roles in adult melanocytes and melanoma cells. {yields} Promotes 'stem' cell-like phenotype via NES and SOX9 in both cells types. {yields} Regulates melanoma and melanocyte migration through MCAM and CSPG4. {yields} PAX3 regulates melanoma but not melanocyte proliferation via TPD52. {yields} Regulates melanoma cell (but not melanocyte) survival via BCL2L1 and PTEN. -- Abstract: The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if itsmore » function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as 'stem' cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated 'stem' cell like phenotype, PAX3 may contribute to melanoma development and progression.« less

  10. Cortical Recruitment and Nuclear–Cytoplasmic Shuttling of Scd5p, a Protein Phosphatase-1-targeting Protein Involved in Actin Organization and EndocytosisD⃞

    PubMed Central

    Chang, Ji Suk; Henry, Kenneth; Geli, María Isabel; Lemmon, Sandra K.

    2006-01-01

    Scd5p regulates endocytosis and cortical actin organization as a targeting subunit for the Ser/Thr protein phosphatase-1 (PP1) in yeast. To identify localization signals in Scd5p required for cell surface recruitment, visualization of GFP-tagged Scd5 truncations and deletions was performed. Scd5p contains a PP1 binding site, a 3-repeat region of 20 amino acids (3R), and a 9-repeat region of 12 amino acids (9R). We found that the 9R is critical for cortical localization of Scd5p, but cortical recruitment is not essential for Scd5p's function in actin organization and endocytosis. We propose that Scd5p can target PP1 to endocytic factors in the cytoplasm that have been disassembled and/or inactivated by phosphorylation. We also found that Scd5p undergoes nuclear-cytoplasmic shuttling in a Crm1p-dependent manner. Scd5p-ΔCT lacking the 9R region and its nuclear export signal (NES) accumulates in the nucleus, causing cortical actin and endocytic defects. Cytoplasmic localization and function of Scd5p-ΔCT is restored by NES addition. However, removal of Scd5p's nuclear localization signal prevents nuclear entry, but endocytosis and actin organization remain relatively normal. These results indicate that nuclear-cytoplasmic shuttling is not required for regulation of Scd5p's cortical function and suggest that Scd5p has an independent nuclear function. PMID:16251346

  11. Nuclear Import and Export of the Thyroid Hormone Receptor.

    PubMed

    Zhang, Jibo; Roggero, Vincent R; Allison, Lizabeth A

    2018-01-01

    The thyroid hormone receptors, TRα1 and TRβ1, are members of the nuclear receptor superfamily that forms one of the most abundant classes of transcription factors in multicellular organisms. Although primarily localized to the nucleus, TRα1 and TRβ1 shuttle rapidly between the nucleus and cytoplasm. The fine balance between nuclear import and export of TRs has emerged as a critical control point for modulating thyroid hormone-responsive gene expression. Mutagenesis studies have defined two nuclear localization signal (NLS) motifs that direct nuclear import of TRα1: NLS-1 in the hinge domain and NLS-2 in the N-terminal A/B domain. Three nuclear export signal (NES) motifs reside in the ligand-binding domain. A combined approach of shRNA-mediated knockdown and coimmunoprecipitation assays revealed that nuclear entry of TRα1 is facilitated by importin 7, likely through interactions with NLS-2, and importin β1 and the adapter importin α1 interacting with both NLS-1 and NLS-2. Interestingly, TRβ1 lacks NLS-2 and nuclear import depends solely on the importin α1/β1 heterodimer. Heterokaryon and fluorescence recovery after photobleaching shuttling assays identified multiple exportins that play a role in nuclear export of TRα1, including CRM1 (exportin 1), and exportins 4, 5, and 7. Even single amino acid changes in TRs dramatically alter their intracellular distribution patterns. We conclude that mutations within NLS and NES motifs affect nuclear shuttling activity, and propose that TR mislocalization contributes to the development of some types of cancer and Resistance to Thyroid Hormone syndrome. © 2018 Elsevier Inc. All rights reserved.

  12. Core neurological examination items for neurology clerks: A modified Delphi study with a grass-roots approach

    PubMed Central

    Liu, Chi-Hung; Hsu, Li-Ling; Hsiao, Cheng-Ting; Hsieh, Suh-Ing; Chang, Chun-Wei; Huang, Elaine Shinwei; Chang, Yeu-Jhy

    2018-01-01

    Background With the evolution of treatments for neurological diseases, the contents of core neurological examinations (NEs) for medical students may need to be modified. We aimed to establish a consensus on the core NE items for neurology clerks and compare viewpoints between different groups of panelists. Methods First, a pilot group proposed the core contents of NEs for neurology clerks. The proposed core NE items were then subject to a modified web-based Delphi process using the online software “SurveyMonkey”. A total of 30 panelists from different backgrounds (tutors or learners, neurologists or non-neurologists, community hospitals or medical centers, and different academic positions) participated in the modified Delphi process. Each panelist was asked to agree or disagree on the inclusion of each item using a 9-point Likert scale and was encouraged to provide feedback. We also compared viewpoints between different groups of panelists using the Mann-Whitney U test. Results Eighty-three items were used for the first round of the Delphi process. Of them, 18 without consensus of being a core NE item for the neurology clerks in the first round and another 14 items suggested by the panelists were further discussed in the second round. Finally, 75 items with different grades were included in the recommended NE items for neurology clerks. Conclusions Our findings provide a reference regarding the core NE items for milestone development for neurology clerkships. We hope that prioritizing the NE items in this order can help medical students to learn NE more efficiently. PMID:29771997

  13. The Influence of Cultivars and Phenological Phases on the Accumulation of Nevadensin and Salvigenin in Basil (Ocimum basilicum).

    PubMed

    Bernhardt, Botond; Bernáth, Jenő; Gere, Attila; Kókai, Zoltán; Komáromi, Bonifác; Tavaszi-Sárosi, Szilvia; Varga, László; Sipos, László; Szabó, Krisztina

    2015-10-01

    According to the earlier literature the optimum harvest time for basil is at the full flowering stage if accumulation of essential oil is taken into account. In this research we have investigated our gene-bank stored basil accessions to determine whether the harvest timing is variety specific or not considering their flavonoid accumulation pattern. In our work we have determined by HPLC the content of two main flavonoid compounds, salvigenin and nevadensin, of eight different gene bank accessions from 2013 of Ocimum basilicum L. Data were analysed with the nonparametric Kruskal-Wallis test. Multiple pairwise comparisons were made using the Conover-Iman procedure where the significance level was 5%. We have observed that the optimum harvest time is at the full flowering stage in the case of accessions 'Genovese' and 'Piros', but this was not verified for the others. The result of our experiment has shown that the maximum salvigenin and nevadensin content was detected both at the full- and early flowering period. Almost in all phenological phases the accession 'M. Grünes' accumulated the highest level of nevadensin, while accession 'Lengyel' produced the lowest results in all phenological phases. Generally it could be observed that compared with nevadensin more salvigenin is accumulated, and it is independent of the phenological phases. In the case of salvigenin, 'M. Grünes' accession produced the largest quantity and accession 'Dark Opal' showed the lowest values. Our analyses demonstrated that harvest at different phenological phases may result in different amounts of active agents according to the cultivar.

  14. Conversation analysis can help to distinguish between epilepsy and non-epileptic seizure disorders: a case comparison.

    PubMed

    Plug, Leendert; Sharrack, Basil; Reuber, Markus

    2009-01-01

    Factual items in patients' histories are of limited discriminating value in the differential diagnosis of epilepsy and non-epileptic seizures (NES). A number of studies using a transcript-based sociolinguistic research method inspired by Conversation Analysis (CA) suggest that it is helpful to focus on how patients talk. Previous reports communicated these findings by using particularly clear examples of diagnostically relevant interactional, linguistic and topical features from different patients. They did not discuss the sequential display of different features although this is crucially important from a conversation analytic point of view. This case comparison aims to show clinicians how the discriminating features are displayed by individual patients over the course of a clinical encounter. CA-inspired brief sequential analysis of two first 30-min doctor-patient encounters by a linguist blinded to all medical information. A gold standard diagnosis was made by the recording of a typical seizure with video-EEG. The patient with epilepsy volunteered detailed first person accounts of seizures. The NES patient exhibited resistance to focusing on individual seizure episodes and only provided a detailed seizure description after repeated prompting towards the end of the interview. Although both patients also displayed some linguistic features favouring the alternative diagnosis, the linguist's final diagnostic hypothesis matched the diagnosis made by video-EEG in both cases. This study illustrates the importance of the time point at which patients share information with the doctor. It supports the notion that close attention to how patients communicate can help in the differential diagnosis of seizures.

  15. Workshop on Higher-Order Spectral Analysis Held at Vail, Colorado on 28- 30 June 1989

    DTIC Science & Technology

    1989-11-28

    8217’ Academic Press, 1..~ndonr 19111 7) 1. Sui± Ri- P !, M’’ LI I . (3 :br, Anr Intirodclio(n to Bisrpctal Analysis1. 𔄃 /1.- - -ir , qe nc 5 dc/s...a single equauon (2.8) (with m=() has clearly resulted in a severe Series Analysis. II, D.F. Findles, Ed. Nes, York: Academic , 1981. loss of accuracy...New York, Academic : 1966. 48-69:1965, (331 M. R. Rosenblatt, "Energy transfer for the Burgers’ equa- [15] K. Hasselman, W. Munk and G. J. F

  16. Environmental Constraints in Earth-Space Propagaton.

    DTIC Science & Technology

    1980-11-20

    medium. The earth-space refractivity may be written N(s) - (n-l) x 106 - Nt + NJ 77.6 [p(s) + 81O e (s) 1 - 4o.28 x o-6 Ne(s) () T(s) [" T(s) f- 2 where...T(s) is the aIr temperature (OK), p(s) is the atmospheric pressure (mb), e (s) is the partial vapor pressure (mb , f is the radiofrequency (MHz), Ne is...to Predict the Total Atmospheric Bending of Radiowaves at Small Angles", Proc. IRE 45, 145-6. BEAN B. R. and R. E . MCGAVIN, 1965, "A Review of

  17. KSC-04pd0837

    NASA Image and Video Library

    2004-04-13

    KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy (right) talks to Aaron Fernander, principal of Ralph Bunche Middle School, a NASA Explorer School, in Atlanta, Ga. Kennedy is visiting NES sites to share America’s new vision for space exploration with the next generation of explorers. He was accompanied by astronaut Rick Linnehan on the visit. The purpose of the school visit is to talk with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  18. KSC-04pd0839

    NASA Image and Video Library

    2004-04-13

    KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy talks to students and faculty at Ralph Bunche Middle School, a NASA Explorer School, in Atlanta, Ga. Kennedy is visiting NES sites to share America’s new vision for space exploration with the next generation of explorers. He was accompanied by astronaut Rick Linnehan on the visit. The purpose of the school visit is to talk with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  19. KSC-04pd0848

    NASA Image and Video Library

    2004-04-13

    KENNEDY SPACE CENTER, FLA. - Astronaut Rick Linnehan talks to a classroom teacher at Ralph Bunche Middle School, a NASA Explorer School, in Atlanta, Ga. Linnehan accompanied Center Director Jim Kennedy, who was visiting the school to share America’s new vision for space exploration with the next generation of explorers. The visit is one of many Kennedy has made to NES sites in Florida and Georgia to talk with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  20. Stall/Spin Problems of Military Aircraft

    DTIC Science & Technology

    1976-06-01

    AVIONS DE COMBAT par C. I Burthe 15A SPIN INVESTIGATION OF THI; HANSA JET by H. Nep rt 15B METHODES D’ESSAIS DE VRILLES EN VOL par J.P. Duval 16 F-14A...General Dynamics’ Fort Worth Division F.O. Box 748, Fort Worth, Texas 16Ol SUMMARY In this paper the stall/spin problem as ,.iewed by American industry...nous pouvaI~s le constater, l’amblioratirn esp~r~o n’a Pu 9cre acquise. Les ph~norn~nes obtenus iont onicure comparables 6 ceux trouvite pr~cdemvi~ rt

  1. KSC-04pd1173

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- After his presentation at Howard A. Doolin Middle School, Miami, Fla., astronaut David Wolf signs a memento for a student. The school is one of 100 taking part in the NASA Explorer Schools (NES) program. Center Director Jim Kennedy and Wolf visited the school to share America’s new vision for space exploration with the next generation of explorers. They talked with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  2. KSC-04pd1174

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- After his presentation at Howard A. Doolin Middle School, Miami, Fla., astronaut David Wolf signs a memento for a student. The school is one of 100 taking part in the NASA Explorer Schools (NES) program. Center Director Jim Kennedy and Wolf visited the school to share America’s new vision for space exploration with the next generation of explorers. They talked with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  3. KSC-04pd1169

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- After his presentation, Center Director Jim Kennedy signs a memento for a student at Howard A. Doolin Middle School, Miami, Fla. The school is one of 100 taking part in the NASA Explorer Schools (NES) program. Kennedy visited the school to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  4. KSC-04pd1166

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Center Director Jim Kennedy (center) greets a student after his presentation at Howard A. Doolin Middle School, Miami, Fla. The school is one of 100 taking part in the NASA Explorer Schools (NES) program. The purpose of Kennedy’s visit is to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  5. KSC-04pd1170

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- After his presentation, astronaut David Wolf signs a memento for a student at Howard A. Doolin Middle School, Miami, Fla. The school is one of 100 taking part in the NASA Explorer Schools (NES) program. Center Director Jim Kennedy and Wolf visited the school to share America’s new vision for space exploration with the next generation of explorers. They talked with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  6. KSC-04pd1157

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Center Director Jim Kennedy addresses students and faculty of Howard A. Doolin Middle School, Miami, Fla. Doolin Middle School is one of 100 to take part in the NASA Explorer Schools (NES) program. Kennedy is visiting Explorer Schools in Florida and Georgia to share America’s new vision for space exploration with the next generation of explorers. He is talking with students, about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  7. KSC-04pd1175

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- After his presentation at Howard A. Doolin Middle School, Miami, Fla., astronaut David Wolf signs a memento for a student. The school is one of 100 taking part in the NASA Explorer Schools (NES) program. Center Director Jim Kennedy and Wolf visited the school to share America’s new vision for space exploration with the next generation of explorers. They talked with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  8. KSC-04pd1171

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- After his presentation, Center Director Jim Kennedy signs a memento for a student at Howard A. Doolin Middle School, Miami, Fla. The school is one of 100 taking part in the NASA Explorer Schools (NES) program. Kennedy visited the school to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  9. KSC-04pd1168

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Center Director Jim Kennedy poses for a photo with students at Howard A. Doolin Middle School, Miami, Fla. The school is one of 100 taking part in the NASA Explorer Schools (NES) program. The purpose of Kennedy’s visit is to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  10. Cloning and functional characterization of the guinea pig apoptosis inhibitor protein Survivin.

    PubMed

    Habtemichael, Negusse; Wünsch, Desiree; Bier, Carolin; Tillmann, Sarah; Unruhe, Britta; Frauenknecht, Katrin; Heinrich, Ulf-Rüdiger; Mann, Wolf J; Stauber, Roland H; Knauer, Shirley K

    2010-12-01

    The guinea pig is widely used as a model to study (patho)physiological processes, such as neurodegenerative disorders. Survivin's dual function as an apoptosis inhibitor and a mitotic regulator is crucial not only for ordered development but its modulation seems crucial also under disease conditions. However, data on the expression and function of the guinea pig Survivin protein (Survivin(Gp)) are currently lacking. Here, we here report the cloning and functional characterization of Survivin(Gp). The respective cDNA was cloned from spleen mRNA, containing a 426 bp open reading frame encoding for a protein of 142aa. Survivin(Gp) displays a high homology to the human and murine orthologue, especially in domains critical for function, such as binding sites for chromosomal passenger complex (CPC) proteins and the nuclear export signal (NES). Notably, phylogenetic analyses revealed that Survivin(Gp) is more related to humans than to rodents. Ectopic expression studies of a Survivin(Gp)-GFP fusion confirmed its dynamic intracellular localization, analogous to the human and murine counterparts. In interphase cells, Survivin(Gp)-GFP was predominantly cytoplasmic and accumulated in the nucleus following export inhibition with leptomycin B (LMB). A typical CPC protein localization during mitosis was observed for Survivin(Gp)-GFP. Microinjection experiments together with genetic knockout demonstrated that the NES is essential for the anti-apoptotic and regulatory role of Survivin(Gp) during cell division. In vivo protein interaction assays further demonstrated its dimerization with human Survivin and its interaction with human CPC proteins. Importantly, RNAi-depletion studies show that Survivin(Gp) can fully substitute for human Survivin as an apoptosis inhibitor and a mitotic effector. Immunohistochemistry, immunofluorescence, and western blotting were employed to detect Survivin expression in guinea pig tissues. Besides its expression in proliferating tissues, such as spleen and liver, we also found Survivin in terminally differentiated cell types. Importantly, Survivin was detectable also in the cochlea, suggesting a potential role for Survivin in the auditory system. We provide the first experimental evidence for the expression of Survivin in the guinea pig. As Survivin(Gp) can substitute for known functions of human Survivin, the guinea pig model will now also allow investigating Survivin's (patho)physiological role and to test Survivin-directed potential therapeutic strategies. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Electromagnetic field analysis and modeling of a relative position detection sensor for high speed maglev trains.

    PubMed

    Xue, Song; He, Ning; Long, Zhiqiang

    2012-01-01

    The long stator track for high speed maglev trains has a tooth-slot structure. The sensor obtains precise relative position information for the traction system by detecting the long stator tooth-slot structure based on nondestructive detection technology. The magnetic field modeling of the sensor is a typical three-dimensional (3-D) electromagnetic problem with complex boundary conditions, and is studied semi-analytically in this paper. A second-order vector potential (SOVP) is introduced to simplify the vector field problem to a scalar field one, the solution of which can be expressed in terms of series expansions according to Multipole Theory (MT) and the New Equivalent Source (NES) method. The coefficients of the expansions are determined by the least squares method based on the boundary conditions. Then, the solution is compared to the simulation result through Finite Element Analysis (FEA). The comparison results show that the semi-analytical solution agrees approximately with the numerical solution. Finally, based on electromagnetic modeling, a difference coil structure is designed to improve the sensitivity and accuracy of the sensor.

  12. Electromagnetic Field Analysis and Modeling of a Relative Position Detection Sensor for High Speed Maglev Trains

    PubMed Central

    Xue, Song; He, Ning; Long, Zhiqiang

    2012-01-01

    The long stator track for high speed maglev trains has a tooth-slot structure. The sensor obtains precise relative position information for the traction system by detecting the long stator tooth-slot structure based on nondestructive detection technology. The magnetic field modeling of the sensor is a typical three-dimensional (3-D) electromagnetic problem with complex boundary conditions, and is studied semi-analytically in this paper. A second-order vector potential (SOVP) is introduced to simplify the vector field problem to a scalar field one, the solution of which can be expressed in terms of series expansions according to Multipole Theory (MT) and the New Equivalent Source (NES) method. The coefficients of the expansions are determined by the least squares method based on the boundary conditions. Then, the solution is compared to the simulation result through Finite Element Analysis (FEA). The comparison results show that the semi-analytical solution agrees approximately with the numerical solution. Finally, based on electromagnetic modeling, a difference coil structure is designed to improve the sensitivity and accuracy of the sensor. PMID:22778652

  13. A cross sectional study of the association between walnut consumption and cognitive function among adult US populations represented in NHANES.

    PubMed

    Arab, L; Ang, A

    2015-03-01

    To examine the association between walnut consumption and measures of cognitive function in the US population. Nationally representative cross sectional study using 24 hour dietary recalls of intakes to assess walnut and other nut consumption as compared to the group reporting no nut consumption. 1988-1994 and 1999-2002 rounds of the National Health and Nutrition Examination Survey (NHANES). Representative weighted sample of US adults 20 to 90 years of age. The Neurobehavioral Evaluation System 2 (NES2), consisting of simple reaction time (SRTT), symbol digit substitution (SDST), the single digit learning (SDLT), Story Recall (SRT) and digit-symbol substitution (DSST) tests. Adults 20-59 years old reporting walnut consumption of an average of 10.3 g/d required 16.4ms less time to respond on the SRTT, P=0.03, and 0.39s less for the SDST, P=0.01. SDLT scores were also significantly lower by 2.38s (P=0.05). Similar results were obtained when tertiles of walnut consumption were examined in trend analyses. Significantly better outcomes were noted in all cognitive test scores among those with higher walnut consumption (P < 0.01). Among adults 60 years and older, walnut consumers averaged 13.1 g/d, scored 7.1 percentile points higher, P=0.03 on the SRT and 7.3 percentile points higher on the DSST, P=0.05. Here also trend analyses indicate significant improvements in all cognitive test scores (P < 0.01) except for SRTT (P = 0.06) in the fully adjusted models. These significant, positive associations between walnut consumption and cognitive functions among all adults, regardless of age, gender or ethnicity suggest that daily walnut intake may be a simple beneficial dietary behavior.

  14. Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance

    PubMed Central

    Olmstead, Keedrian I.; La Frano, Michael R.; Fahrmann, Johannes; Grapov, Dmitry; Viscarra, Jose A.; Newman, John W.; Fiehn, Oliver; Crocker, Daniel E.; Filipp, Fabian V.; Ortiz, Rudy M.

    2017-01-01

    Introduction Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical elevation in FFA despite comparable increases in insulin during both periods suggestive of a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion. Objective To better assess the contribution of insulin to this fasting-associated shift in substrate metabolism. Methods We compared the responses of plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late-fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS technologies. Results In early fasting, the majority (72%) of metabolite trajectories return to baseline levels within 2 h, but not in late fasting indicative of an increase in tissue sensitivity to insulin. In late-fasting, increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased protein catabolism. Conversely, insulin increased PCM AUC in late fasting suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA AUC between early and late fasting suggesting that insulin suppresses triglyceride hydrolysis. Conclusion Naturally adapted tolerance to prolonged fasting in these mammals is likely accomplished by suppressing insulin levels and activity, providing novel insight on the evolution of insulin during a condition of temporary, reversible insulin resistance. PMID:28757815

  15. Terpenoid Metabolism in Wild-Type and Transgenic Arabidopsis PlantsW⃞

    PubMed Central

    Aharoni, Asaph; Giri, Ashok P.; Deuerlein, Stephan; Griepink, Frans; de Kogel, Willem-Jan; Verstappen, Francel W. A.; Verhoeven, Harrie A.; Jongsma, Maarten A.; Schwab, Wilfried; Bouwmeester, Harro J.

    2003-01-01

    Volatile components, such as terpenoids, are emitted from aerial parts of plants and play a major role in the interaction between plants and their environment. Analysis of the composition and emission pattern of volatiles in the model plant Arabidopsis showed that a range of volatile components are released, primarily from flowers. Most of the volatiles detected were monoterpenes and sesquiterpenes, which in contrast to other volatiles showed a diurnal emission pattern. The active terpenoid metabolism in wild-type Arabidopsis provoked us to conduct an additional set of experiments in which transgenic Arabidopsis overexpressing two different terpene synthases were generated. Leaves of transgenic plants constitutively expressing a dual linalool/nerolidol synthase in the plastids (FaNES1) produced linalool and its glycosylated and hydroxylated derivatives. The sum of glycosylated components was in some of the transgenic lines up to 40- to 60-fold higher than the sum of the corresponding free alcohols. Surprisingly, we also detected the production and emission of nerolidol, albeit at a low level, suggesting that a small pool of its precursor farnesyl diphosphate is present in the plastids. Transgenic lines with strong transgene expression showed growth retardation, possibly as a result of the depletion of isoprenoid precursors in the plastids. In dual-choice assays with Myzus persicae, the FaNES1-expressing lines significantly repelled the aphids. Overexpression of a typical cytosolic sesquiterpene synthase resulted in the production of only trace amounts of the expected sesquiterpene, suggesting tight control of the cytosolic pool of farnesyl diphosphate, the precursor for sesquiterpenoid biosynthesis. This study further demonstrates the value of Arabidopsis for studies of the biosynthesis and ecological role of terpenoids and provides new insights into their metabolism in wild-type and transgenic plants. PMID:14630967

  16. Inhibition of Early Stages of HIV-1 Assembly by INI1/hSNF5 Transdominant Negative Mutant S6 ▿

    PubMed Central

    Cano, Jennifer; Kalpana, Ganjam V.

    2011-01-01

    INI1/hSNF5 is an HIV-1 integrase (IN) binding protein specifically incorporated into virions. A truncated mutant of INI1 (S6, amino acids 183 to 294) harboring the minimal IN binding Rpt1 domain potently inhibits HIV-1 particle production in a transdominant manner. The inhibition requires interaction of S6 with IN within Gag-Pol. While INI1 is a nuclear protein and harbors a masked nuclear export signal (NES), the transdominant negative mutant S6 is cytoplasmic, due to the unmasking of NES. Here, we examined the effects of subcellular localization of S6 on HIV-1 inhibition and further investigated the stages of assembly that are affected. We found that targeting a nuclear localization signal-containing S6 variant [NLS-S6(Rpt1)] to the nucleoplasm (but not to the nucleolus) resulted in complete reversal of inhibition of particle production. Electron microscopy indicated that although no electron-dense particles at any stage of assembly were seen in cells expressing S6, virions were produced in cells expressing the rescue mutant NLS-S6(Rpt1) to wild-type levels. Immunofluorescence analysis revealed that p24 exhibited a diffuse pattern of localization within the cytoplasm in cells expressing S6 in contrast to accumulation along the membrane in controls. Pulse-chase analysis indicated that in S6-expressing cells, although Gag(Pr55gag) protein translation was unaffected, processing and release of p24 were defective. Together, these results indicate that expression of S6 in the cytoplasm interferes with trafficking of Gag-Pol/Gag to the membrane and causes a defective processing leading to inhibition of assembly at an early stage prior to particle formation and budding. PMID:21159874

  17. Microalgae Synthesize Hydrocarbons from Long-Chain Fatty Acids via a Light-Dependent Pathway1[OPEN

    PubMed Central

    Légeret, Bertrand; Mirabella, Boris; Guédeney, Geneviève; Jetter, Reinhard; Peltier, Gilles

    2016-01-01

    Microalgae are considered a promising platform for the production of lipid-based biofuels. While oil accumulation pathways are intensively researched, the possible existence of a microalgal pathways converting fatty acids into alka(e)nes has received little attention. Here, we provide evidence that such a pathway occurs in several microalgal species from the green and the red lineages. In Chlamydomonas reinhardtii (Chlorophyceae), a C17 alkene, n-heptadecene, was detected in the cell pellet and the headspace of liquid cultures. The Chlamydomonas alkene was identified as 7-heptadecene, an isomer likely formed by decarboxylation of cis-vaccenic acid. Accordingly, incubation of intact Chlamydomonas cells with per-deuterated D31-16:0 (palmitic) acid yielded D31-18:0 (stearic) acid, D29-18:1 (oleic and cis-vaccenic) acids, and D29-heptadecene. These findings showed that loss of the carboxyl group of a C18 monounsaturated fatty acid lead to heptadecene formation. Amount of 7-heptadecene varied with growth phase and temperature and was strictly dependent on light but was not affected by an inhibitor of photosystem II. Cell fractionation showed that approximately 80% of the alkene is localized in the chloroplast. Heptadecane, pentadecane, as well as 7- and 8-heptadecene were detected in Chlorella variabilis NC64A (Trebouxiophyceae) and several Nannochloropsis species (Eustigmatophyceae). In contrast, Ostreococcus tauri (Mamiellophyceae) and the diatom Phaeodactylum tricornutum produced C21 hexaene, without detectable C15-C19 hydrocarbons. Interestingly, no homologs of known hydrocarbon biosynthesis genes were found in the Nannochloropsis, Chlorella, or Chlamydomonas genomes. This work thus demonstrates that microalgae have the ability to convert C16 and C18 fatty acids into alka(e)nes by a new, light-dependent pathway. PMID:27288359

  18. Fourth-Generation Progestins Inhibit 3β-Hydroxysteroid Dehydrogenase Type 2 and Modulate the Biosynthesis of Endogenous Steroids

    PubMed Central

    Louw-du Toit, Renate; Perkins, Meghan S.; Snoep, Jacky L.; Storbeck, Karl-Heinz; Africander, Donita

    2016-01-01

    Progestins used in contraception and hormone replacement therapy are synthetic compounds designed to mimic the actions of the natural hormone progesterone and are classed into four consecutive generations. The biological actions of progestins are primarily determined by their interactions with steroid receptors, and factors such as metabolism, pharmacokinetics, bioavailability and the regulation of endogenous steroid hormone biosynthesis are often overlooked. Although some studies have investigated the effects of select progestins on a few steroidogenic enzymes, studies comparing the effects of progestins from different generations are lacking. This study therefore explored the putative modulatory effects of progestins on de novo steroid synthesis in the adrenal by comparing the effects of select progestins from the respective generations, on endogenous steroid hormone production by the H295R human adrenocortical carcinoma cell line. Ultra-performance liquid chromatography/tandem mass spectrometry analysis showed that the fourth-generation progestins, nestorone (NES), nomegestrol acetate (NoMAC) and drospirenone (DRSP), unlike the progestins selected from the first three generations, modulate the biosynthesis of several endogenous steroids. Subsequent assays performed in COS-1 cells expressing human 3βHSD2, suggest that these progestins modulate the biosynthesis of steroid hormones by inhibiting the activity of 3βHSD2. The Ki values determined for the inhibition of human 3βHSD2 by NES (9.5 ± 0.96 nM), NoMAC (29 ± 7.1 nM) and DRSP (232 ± 38 nM) were within the reported concentration ranges for the contraceptive use of these progestins in vivo. Taken together, our results suggest that newer, fourth-generation progestins may exert both positive and negative physiological effects via the modulation of endogenous steroid hormone biosynthesis. PMID:27706226

  19. Shuttling imbalance of MLF1 results in p53 instability and increases susceptibility to oncogenic transformation.

    PubMed

    Yoneda-Kato, Noriko; Kato, Jun-Ya

    2008-01-01

    Myeloid leukemia factor 1 (MLF1) stabilizes the activity of the tumor suppressor p53 by suppressing its E3 ubiquitin ligase, COP1, through a third component of the COP9 signalosome (CSN3). However, little is known about how MLF1 functions upstream of the CSN3-COP1-p53 pathway and how its deregulation by the formation of the fusion protein nucleophosmin (NPM)-MLF1, generated by t(3;5)(q25.1;q34) chromosomal translocation, leads to leukemogenesis. Here we show that MLF1 is a cytoplasmic-nuclear-shuttling protein and that its nucleolar localization on fusing with NPM prevents the full induction of p53 by both genotoxic and oncogenic cellular stress. The majority of MLF1 was located in the cytoplasm, but the treatment of cells with leptomycin B rapidly induced a nuclear accumulation of MLF1. A mutation of the nuclear export signal (NES) motif identified in the MLF1 sequence enhanced the antiproliferative activity of MLF1. The fusion of MLF1 with NPM translocated MLF1 to the nucleolus and abolished the growth-suppressing activity. The introduction of NPM-MLF1 into early-passage murine embryonic fibroblasts allowed the cells to escape from cellular senescence at a markedly earlier stage and induced neoplastic transformation in collaboration with the oncogenic form of Ras. Interestingly, disruption of the MLF1-derived NES sequence completely abolished the growth-promoting activity of NPM-MLF1 in murine fibroblasts and hematopoietic cells. Thus, our results provide important evidence that the shuttling of MLF1 is critical for the regulation of cell proliferation and a disturbance in the shuttling balance increases the cell's susceptibility to oncogenic transformation.

  20. Shuttling Imbalance of MLF1 Results in p53 Instability and Increases Susceptibility to Oncogenic Transformation▿ †

    PubMed Central

    Yoneda-Kato, Noriko; Kato, Jun-ya

    2008-01-01

    Myeloid leukemia factor 1 (MLF1) stabilizes the activity of the tumor suppressor p53 by suppressing its E3 ubiquitin ligase, COP1, through a third component of the COP9 signalosome (CSN3). However, little is known about how MLF1 functions upstream of the CSN3-COP1-p53 pathway and how its deregulation by the formation of the fusion protein nucleophosmin (NPM)-MLF1, generated by t(3;5)(q25.1;q34) chromosomal translocation, leads to leukemogenesis. Here we show that MLF1 is a cytoplasmic-nuclear-shuttling protein and that its nucleolar localization on fusing with NPM prevents the full induction of p53 by both genotoxic and oncogenic cellular stress. The majority of MLF1 was located in the cytoplasm, but the treatment of cells with leptomycin B rapidly induced a nuclear accumulation of MLF1. A mutation of the nuclear export signal (NES) motif identified in the MLF1 sequence enhanced the antiproliferative activity of MLF1. The fusion of MLF1 with NPM translocated MLF1 to the nucleolus and abolished the growth-suppressing activity. The introduction of NPM-MLF1 into early-passage murine embryonic fibroblasts allowed the cells to escape from cellular senescence at a markedly earlier stage and induced neoplastic transformation in collaboration with the oncogenic form of Ras. Interestingly, disruption of the MLF1-derived NES sequence completely abolished the growth-promoting activity of NPM-MLF1 in murine fibroblasts and hematopoietic cells. Thus, our results provide important evidence that the shuttling of MLF1 is critical for the regulation of cell proliferation and a disturbance in the shuttling balance increases the cell's susceptibility to oncogenic transformation. PMID:17967869

  1. Differential DNA methylation profile of key genes in malignant prostate epithelial cells transformed by inorganic arsenic or cadmium.

    PubMed

    Pelch, Katherine E; Tokar, Erik J; Merrick, B Alex; Waalkes, Michael P

    2015-08-01

    Previous work shows altered methylation patterns in inorganic arsenic (iAs)- or cadmium (Cd)-transformed epithelial cells. Here, the methylation status near the transcriptional start site was assessed in the normal human prostate epithelial cell line (RWPE-1) that was malignantly transformed by 10μM Cd for 11weeks (CTPE) or 5μM iAs for 29weeks (CAsE-PE), at which time cells showed multiple markers of acquired cancer phenotype. Next generation sequencing of the transcriptome of CAsE-PE cells identified multiple dysregulated genes. Of the most highly dysregulated genes, five genes that can be relevant to the carcinogenic process (S100P, HYAL1, NTM, NES, ALDH1A1) were chosen for an in-depth analysis of the DNA methylation profile. DNA was isolated, bisulfite converted, and combined bisulfite restriction analysis was used to identify differentially methylated CpG sites, which was confirmed with bisulfite sequencing. Four of the five genes showed differential methylation in transformants relative to control cells that was inversely related to altered gene expression. Increased expression of HYAL1 (>25-fold) and S100P (>40-fold) in transformants was correlated with hypomethylation near the transcriptional start site. Decreased expression of NES (>15-fold) and NTM (>1000-fold) in transformants was correlated with hypermethylation near the transcriptional start site. ALDH1A1 expression was differentially expressed in transformed cells but was not differentially methylated relative to control. In conclusion, altered gene expression observed in Cd and iAs transformed cells may result from altered DNA methylation status. Published by Elsevier Inc.

  2. A brief conversation analytic communication intervention can change history-taking in the seizure clinic.

    PubMed

    Jenkins, Laura; Cosgrove, Jeremy; Ekberg, Katie; Kheder, Ammar; Sokhi, Dilraj; Reuber, Markus

    2015-11-01

    Question design during history-taking has clear implications for patients' ability to share their concerns in general and their seizure experiences in particular. Studies have shown that unusually open questions at the start of the consultation enable patients to display interactional and linguistic markers which may help with the otherwise challenging differentiation of epileptic from nonepileptic seizures (NES). In this study, we compared the problem presentation approach taken by trainee neurologists in outpatient encounters with new patients before and after a one-day conversation analytic training intervention in which doctors were taught to adopt an open format of question design and recognize diagnostically relevant linguistic features. We audio/video-recorded clinical encounters between ten doctors, their patients, and accompanying persons; transcribed the interactions; and carried out quantitative and qualitative analyses. We studied 39 encounters before and 55 after the intervention. Following the intervention, doctors were significantly more likely to use nondirective approaches to soliciting patient accounts of their presenting complaints that invited the patient to describe their problems from their own point of view and gave them better opportunity to determine the initial agenda of the encounter. The time to first interruption by the doctor increased (from 52 to 116 s, p<.001). While patients were given more time to describe their seizure experiences, the overall appointment length did not increase significantly (19 vs 21 min, n.s.). These changes gave patients more conversational space to express their concerns and, potentially, to demonstrate the interactional and linguistic features previously found to help differentiate between epilepsy and NES, without impacting the length of the consultations. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Geothermal Progress Monitor, report No. 13

    NASA Astrophysics Data System (ADS)

    1992-02-01

    Geothermal Progress Monitor (GPM) Issue No. 13 documents that most related factors favor the growth and geographic expansion of the US geothermal industry and that the industry is being technologically prepared to meet those challenges into the next century. It is the function of GPM to identify trends in the use of this resource and to provide a historical record of its development pathway. The information assembled for this issue of GPM indicates that trends in the use of geothermal energy in this country and abroad continue to be very positive. Favorable sentiments as well as pertinent actions on the part of both government and industry are documented in almost every section. The FEDERAL BEAT points up that the National Energy Strategy (NES) developed at the highest levels of the US government recognizes the environmental and energy security advantages of renewable energy, including geothermal, and makes a commitment to 'substantial diversification' of US sources of energy. With the announcement of the construction of several new plants and plant expansions, the INDUSTRY SCENE illustrates industry's continued expectation that the use of geothermal energy will prove profitable to investors. In DEVELOPMENT STATUS, spokesmen for both an investor-owned utility and a major geothermal developer express strong support for geothermal power, particularly emphasizing its environmental advantages. DEVELOPMENT STATUS also reports that early successes have been achieved by joint DOE/industry R & D at The Geysers which will have important impacts on the future management of this mature field. Also there is increasing interest in hot dry rock. Analyses conducted in support of the NES indicate that if all the postulated technology developments occur in this field, the price of energy derived from hot dry rock in the US could drop.

  4. Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance.

    PubMed

    Olmstead, Keedrian I; La Frano, Michael R; Fahrmann, Johannes; Grapov, Dmitry; Viscarra, Jose A; Newman, John W; Fiehn, Oliver; Crocker, Daniel E; Filipp, Fabian V; Ortiz, Rudy M

    2017-05-01

    Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical elevation in FFA despite comparable increases in insulin during both periods suggestive of a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion. To better assess the contribution of insulin to this fasting-associated shift in substrate metabolism. We compared the responses of plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late-fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS technologies. In early fasting, the majority (72%) of metabolite trajectories return to baseline levels within 2 h, but not in late fasting indicative of an increase in tissue sensitivity to insulin. In late-fasting, increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased protein catabolism. Conversely, insulin increased PCM AUC in late fasting suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA AUC between early and late fasting suggesting that insulin suppresses triglyceride hydrolysis. Naturally adapted tolerance to prolonged fasting in these mammals is likely accomplished by suppressing insulin levels and activity, providing novel insight on the evolution of insulin during a condition of temporary, reversible insulin resistance.

  5. Electromagnetic processes at low momentum transfer : a review for users

    NASA Astrophysics Data System (ADS)

    Parizet, M. J.; Borie, E.; Grossetête, B.; Isabelle, D. B.; Proriol, J.

    Electromagnetic processes at low momentum transfer are often sources of background in many experiments. To be removed these effects must be calculated by the experimentalist, who must have a good knowledge of the validity of the theoretical formulas that he must use. Then we thought that it will be useful to prepare this review whose presentation is such that it should allow everyone to appreciate the accuracy of formulas that he must use in very complex situations. In this paper, we examine the problem related to bremsstrahlung, pair production and radiative corrections. The first part is devoted to kinematic and to the methods used to establish the corresponding cross sections. Les phénomènes électromagnétiques à faible transfert d'impulsion interviennent dans de nombreuses expériences comme des phénomènes parasites. Pour les éliminer, l'expérimentateur doit les calculer, mais il connait généralement mal la validité des formules théoriques qu'il doit alors utiliser. Il nous a donc paru utile de faire une revue dont la présentation doit permettre à chacun d'apprécier la précision des formules qu'il doit appliquer dans des situations très souvent complexes. Dans cet article, nous faisons le point, tant pour la théorie que pour l'expérience, en ce qui concerne : le rayonnement de freinage, la production de paires et les corrections radiatives. La première partie est consacrée à la cinématique des processus appréciés et aux méthodes permettant d'établir les sections efficaces correspondantes.

  6. The X11L/X11{beta}/MINT2 and X11L2/X11{gamma}/MINT3 scaffold proteins shuttle between the nucleus and cytoplasm

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sumioka, Akio; Saito, Yuhki; Sakuma, Megumi

    2008-03-10

    The X11/MINT family proteins are adaptor scaffolding proteins involved in formation of multiprotein complexes, and trafficking and metabolism of membrane proteins such as the beta-amyloid precursor protein. We found that a significant portion of X11L and X11L2 are recovered in nuclear fraction of mouse brain homogenates. EGFP-X11s were not detected in the nucleus of N2a neuroblastoma cells; however, administration of leptomycin B (LMB) induced substantial nuclear accumulation of EGFP-X11L and EGFP-X11L2, while EGFP-X11 showed little accumulation. Fluorescence loss in photobleaching (FLIP) analysis indicated that EGFP-X11L2 and EGFP-X11L are shuttled between the cytoplasm and nucleus, the former more effectively than themore » latter. We identified a nuclear export signal (NES) in the N-terminus of X11L2, mutation of which induces nuclear accumulation of EGFP-X11L2 in the absence of LMB. X11L2 fused to the Gal4 DNA binding domain (DBD) showed transcriptional activity, suggesting that X11L2 could function as a transcriptional activator if tethered near a promoter. Interestingly, attenuation of the nucleo-cytoplasmic shuttling of GAL4-DBD-X11L2 by mutating the NES or attaching the SV40 nuclear localization signal significantly decreased the apparent transcriptional activity. Our observations suggest that X11L2 functions in the nucleus by a mechanism distinct from conventional transactivators.« less

  7. In vitro evaluation of antitumor activity of doxorubicin-loaded nanoemulsion in MCF-7 human breast cancer cells

    NASA Astrophysics Data System (ADS)

    Alkhatib, Mayson H.; AlBishi, Hayat M.

    2013-03-01

    Doxorubicin (DOX) is an anticancer drug used to treat several cancer diseases. However, it has several dose limitation aspects because of its poor bioavailability, hydrophobicity, and cytotoxicity. In this study, five nanoemulsion (NE) formulations, containing soya phosphatidylcholine/polyoxyethylenglycerol trihydroxy-stearate 40 (EU)/sodium oleate as surfactant, cholesterol (CHO) as oil phase, and Tris-HCl buffer (pH 7.22), were produced. The NE droplets morphologies of the entire blank and DOX-loaded formulations, revealed by the transmission electron microscope, were spherical. The droplet sizes of blank NEs, obtained between 2.9 and 6.4 nm, decreased significantly with the increase in the ratio of surfactant-to-oil, whereas the droplets sizes of DOX-loaded NE formulations were significantly higher and found in the range of 7.7-15.9 nm. The evaluation for both blank and DOX-loaded NE formulations proved that the NE carrier had improved the DOX efficacy and reduced its cytotoxicity. It showed that the cell growth inhibition of the breast cancer cells (MCF-7) have exceeded the commercial DOX by a factor of 1.7 with increased apoptosis activity and minimal cytotoxicity against the normal human foreskin cells (HFS). In contrast, commercial DOX was found to exhibit a significant non-selective toxicity against both MCF-7 and HFS cells. In conclusion, we have developed DOX-loaded NE formulations which selectively and significantly inhibited cell proliferation of MCF-7 cells and increased apoptosis.

  8. KSC-04pd0847

    NASA Image and Video Library

    2004-04-13

    KENNEDY SPACE CENTER, FLA. - A teacher (right) at Ralph Bunche Middle School, a NASA Explorer School, in Atlanta, Ga., shows a science project to astronaut Rick Linnehan (left) and Center Director Jim Kennedy (center). Linnehan and Kennedy were at the school to share America’s new vision for space exploration with the next generation of explorers. The visit is one of many Kennedy has made to NES sites in Florida and Georgia to talk with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  9. KSC-04pd1172

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- After his presentation, students at Howard A. Doolin Middle School, Miami, Fla., gather around Center Director Jim Kennedy as he signs a memento for a student. The school is one of 100 taking part in the NASA Explorer Schools (NES) program. Kennedy visited the school to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  10. KSC-04pd1159

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Astronaut David Wolf addresses students and faculty of Howard A. Doolin Middle School, Miami, Fla., about his experiences in space. Doolin Middle School is one of 100 to take part in the NASA Explorer Schools (NES) program. Wolf joins Center Director Jim Kennedy on his visit to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  11. KSC-04pd1158

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Astronaut David Wolf addresses students and faculty of Howard A. Doolin Middle School, Miami, Fla., about his experiences in space. Doolin Middle School is one of 100 to take part in the NASA Explorer Schools (NES) program. Wolf joins Center Director Jim Kennedy on his visit to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  12. KSC-04pd1165

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Center Director Jim Kennedy (left) is thanked by Principal Eduardo Tillet for his presentation to the faculty and students of Howard A. Doolin Middle School, Miami, Fla. The school is one of 100 taking part in the NASA Explorer Schools (NES) program. The purpose of Kennedy’s visit is to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  13. Dermatomyosite du sujet âgé: étude de 4 observations dans le sud tunisien

    PubMed Central

    Frikha, Faten; Snoussi, Mouna; Salah, Raida Ben; Saidi, Noura; Kaddour, Neila; Bahloul, Zouhir

    2012-01-01

    La dermatomyosite (DM) touche essentiellement l’adolescent et l’adulte jeune, elle est très rare chez le sujet âgé, le plus souvent associée à des complications iatrogènes et à une pathologie cancéreuse. Nous avons étudié les caractéristiques de la DM du sujet âgé à travers une étude rétrospective dans laquelle nous avons comparé 4 patients âgés de plus de 65 ans au début de la myosite avec 40 sujets jeunes. PMID:23308331

  14. Uncapped mRNA introduced into tobacco protoplasts can be imported into the nucleus and is trapped by leptomycin B.

    PubMed

    Stuger, Rogier; Forreiter, Christoph

    2004-08-01

    The mechanism of nuclear export of RNAs in yeast and animal cells is rapidly being uncovered, but RNA export in plants has received little attention. We introduced capped and uncapped fluorescent mRNAs into tobacco (Nicotiana plumbaginifolia) protoplasts and studied their cellular localization. Following insertion, capped transcripts were found in the cytoplasm, while uncapped messengers transiently appeared in the nucleus in about one-quarter to one-third of the cells. These mRNAs were trapped by the nuclear export-inhibiting drug leptomycin B, pointing to an export mechanism in plants similar to Rev-NES-mediated RNP export in other organisms.

  15. Réduction in situ des ions nitrate dans des eaux par les bactéries indigènes

    NASA Astrophysics Data System (ADS)

    Abdelouas, Abdesselam; Deng, Lijun; Nuttall, Eric; Lutze, Werner; Fritz, Bertrand; Crovisier, Jean-Louis

    1999-02-01

    We studied the possibility of cleaning groundwater contaminated with nitrate ions using indigenous bacteria. The groundwater occurs in a site located near a former vegetable farm near Albuquerque, New Mexico (USA) and contains up to 500 mg·L -1 of nitrate ion. Batch and column experiments using groundwater and local sediment showed that indigenous bacteria catalyzed the nitrate ions reduction. Sodium acetate was selected as the best carbon source for the in situ application. As expected, the best conditions for denitrification were encountered in situ. Nitrate ions and their byproducts were reduced to nitrogen gas within 5 days.

  16. Transcriptional changes in organoculture of full-thickness human skin following topical application of all-trans retinoic acid

    PubMed Central

    Gillbro, J M; Al-Bader, T; Westman, M; Olsson, M J; Mavon, A

    2014-01-01

    Synopsis Objective Retinoids are used as therapeutic agents for numerous skin diseases, for example, psoriasis, acne and keratinization disorders. The same substances have also been recognized in the treatment for hyperpigmentation disorders such as melasma. Other studies on photo-damaged skin have shown that retinoids reduce wrinkles, surface roughness, mottled pigmentation, and visual skin appearance as a whole. We tested the hypothesis that an organoculture of full-thickness human skin could be used as a preclinical model to investigate the retinoid transcriptional profile in human skin in vitro. Methods Full-thickness skin explants were exposed to topically applied all-trans retinoic acid (RA) for 24 h. The gene expression profile was analysed using oligonucleotide microarrays, and data were validated with real-time (RT) PCR. Results We showed that the expression of 93 genes was significantly altered more than twofold. Several of the altered genes, for example, KRT4, CYP26 and LCN2, have previously been shown to be affected by RA in keratinocyte monocultures, reconstructed epidermis and skin biopsies from patients treated topically or orally with RA. In addition, genes, such as SCEL, NRIP1, DGAT2, RDH12 EfnB2, MAPK14, SAMD9 and CEACAM6 not previously reported to be affected by RA in human skin, were identified for the first time in this study. Conclusion The results in the present study show that full-thickness human explants represent a valuable pre-clinical model for studying the effects of retinoids in skin. Résumé Objectif Les rétinoïdes sont utilisés comme agents thérapeutiques pour de nombreuses maladies de la peau, p.ex. le psoriasis, l'acné et les troubles de la kératinisation. Les mêmes substances ont également été reconnues dans le traitement des troubles de l' hyperpigmentation tels que le melasma. D'autres études sur la peau photo-endommagée ont montré que les rétinoïdes réduisent les rides, la rugosité de la surface, la pigmentation tachetée, et l'aspect visuel de la peau dans son ensemble. Nous avons testé l'hypothèse selon laquelle une organoculture de épaisseur intégrale de la peau humaine pourrait être utilisée comme modèle préclinique pour étudier le profil transcriptionnel des rétinoïdes dans la peau humaine in vitro. Méthodes Des explants de peau intégrale ont été exposés à l'application topique de all-trans acide rétinoïque (RA) pendant 24 heures. Le profil d' expression des gènes a été analysé en utilisant des puces DNA array et les données ont été validées par (RT) -PCR. Resultats Nous avons montré que l'expression de 93 gènes a été modifiée de façon significative par plus d'un facteur 2. Plusieurs des gènes modifiés par exemple KRT4, CYP26 et LCN2 ont été montrés précédemment d'être affectés par RA dans les monocultures de kératinocytes, dans l'épiderme reconstruit et dans des biopsies cutanées de patients traités par voie topique ou par voie orale avec RA. En outre, des gènes tels que SCEL, NRIP1, DGAT2, RDH12 EfnB2, MAPK14, SAMD9 et CEACAM6 non signalés précédemment, sont touchés par RA dans la peau humaine, et ont été identifiés pour la première fois dans cette étude. Conclusion Les résultats de la présente étude montrent que les explants humains de pleine épaisseur représentent un modèle préclinique précieux pour l'étude des effets des rétinoïdes dans la peau. PMID:24697191

  17. [Prediction of life expectancy for prostate cancer patients based on the kinetic theory of aging of living systems].

    PubMed

    Viktorov, A A; Zharinov, G M; Neklasova, N Ju; Morozova, E E

    2017-01-01

    The article presents a methodical approach for prediction of life expectancy for people diagnosed with prostate cancer based on the kinetic theory of aging of living systems. The life expectancy is calculated by solving the differential equation for the rate of aging for three different stage of life - «normal» life, life with prostate cancer and life after combination therapy for prostate cancer. The mathematical model of aging for each stage of life has its own parameters identified by the statistical analysis of healthcare data from the Zharinov's databank and Rosstat CDR NES databank. The core of the methodical approach is the statistical correlation between growth rate of the prostate specific antigen level (PSA-level) or the PSA doubling time (PSA DT) before therapy, and lifespan: the higher the PSA DT is, the greater lifespan. The patients were grouped under the «fast PSA DT» and «slow PSA DT» categories. The satisfactory matching between calculations and experiment is shown. The prediction error of group life expectancy is due to the completeness and reliability of the main data source. A detailed monitoring of the basic health indicators throughout the each person life in each analyzed group is required. The absence of this particular information makes it impossible to predict the individual life expectancy.

  18. Influence of the strength of the smectic order on the backbone anisotropy of side-chain liquid crystal polymers as revealed by SANS

    NASA Astrophysics Data System (ADS)

    Noirez, L.; Keller, P.; Cotton, J. P.

    1992-06-01

    It is proposed that the strength of the smectic order determines the backbone anisotropy of side-chain liquid crystal polymers. Here this strength increases with the length of the alkyl terminal group of the mesogens. Two liquid crystal polymethacrylates differing only by the mesogenic tails —OCH3 and —OC4H9 are considered. The backbone anisotropy of these polymers is measured by small angle neutron scattering (SANS) whereas the smectic order is evaluated from the intensity of the 001 Bragg peak. Il est proposé que la qualité de l'ordre smectique détermine l'anisotropie du squelette de polymères mésomorphes en peigne confinés dans les lamelles. Ici l'ordre smectique est augmenté en allongeant le groupe alkyl terminal des mésogènes. Nous étudions deux polyméthacrylates cristal liquide qui ne différent que par leurs groupes terminaux : —OCH3 et —OC4H9. L'anisotropie du squellete est mesurée par diffusion de neutrons aux petits angles tandis que l'ordre smectique est évalué à l'aide de l'intensité du pic de Bragg 001.

  19. Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development.

    PubMed

    Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

    2017-07-01

    An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. KSC-04PD-1167

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. -- Astronaut David Wolf (left) and Center Director Jim Kennedy (right, with boy) pose for a photo with students and faculty in Howard A. Doolin Middle School, Miami, Fla., plus other NASA and KSC representatives (rear). The school is one of 100 taking part in the NASA Explorer Schools (NES) program. The purpose of Kennedys visit is to share Americas new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASAs stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  1. Les nanostructures pour créer de la couleur, un art inspiré par la nature

    NASA Astrophysics Data System (ADS)

    Ball, Philip

    2018-02-01

    Les reflets changeants des plumes de la queue du paon ont captivé plus d'un esprit curieux. Le scientifique anglais Robert Hooke les qualifiait en 1665 de « surnaturelles » en constatant que, mouillées, elles perdaient leurs couleurs. À l'aide du microscope inventé depuis peu, il observa ces plumes, et découvrit qu'elles étaient couvertes de stries - qu'il suspecta d'être à l'origine des couleurs. Aujourd'hui, la recherche tente de s'inspirer de ces phénomènes : des applications « bio-inspirées » sont en voie de concrétisation. ARRAY(0x29ad218)

  2. KSC-04pd0851

    NASA Image and Video Library

    2004-04-13

    KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy (center) and Principal Aaron Fernander (right) visit a classroom in Ralph Bunche Middle School, a NASA Explorer School, in Atlanta, Ga. At left is Ralph Thomas, assistant administrator for Small and Disadvantaged Business Utilization at NASA. Kennedy is visiting NES sites to share America’s new vision for space exploration with the next generation of explorers. He was accompanied by astronaut Rick Linnehan on the visit. The purpose of the school visit is to talk with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  3. Ice Atlas 1985 - 1986. Monongahela River, Allegheny River, Ohio River, Illinois River and Kankakee River.

    DTIC Science & Technology

    1987-11-01

    Des P/o,,nes River Grant Cut -off V 1Kankrokee Cut- off Drsdn slndCountyI Line Bordwell Isi. V _ KankakeKRiver 2 */0 7r Prairle Cr 6 0 1 M1 Survey date...2 x 10 6t 81 279 River 279 13 February 1986 275 Kankak Des P/amnes RIver Gran7 Cree Cut-off DrsenIladCount y Line Bordwell Isr. 0 1 M1 ’kornkokee A...Gat Cut - off KankakeeFiver ’e Drsdn slndCounty Line Bordwell s 1 mi 2urve date FerarM1,i Kankakee River :2.4 oCr. 󈧢 X9Kankakcee River :14 ML 0- 5𔃿

  4. KSC-04pd1164

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Astronaut David Wolf answers questions from a student on stage at Howard A. Doolin Middle School, Miami, Fla., during his talk about his experiences in space. Doolin Middle School is one of 100 to take part in the NASA Explorer Schools (NES) program. Wolf joins Center Director Jim Kennedy (seated at lower left) on his visit to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  5. KSC-04pd1163

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Astronaut David Wolf answers questions from a student on stage at Howard A. Doolin Middle School, Miami, Fla., during his talk about his experiences in space. Doolin Middle School is one of 100 to take part in the NASA Explorer Schools (NES) program. Wolf joins Center Director Jim Kennedy (seated at lower left) on his visit to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  6. KSC-04pd1162

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Astronaut David Wolf answers questions from a student on stage at Howard A. Doolin Middle School, Miami, Fla., during his talk about his experiences in space. Doolin Middle School is one of 100 to take part in the NASA Explorer Schools (NES) program. Wolf joins Center Director Jim Kennedy (seated at lower left) on his visit to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  7. KSC-04pd1167

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Astronaut David Wolf (left) and Center Director Jim Kennedy (right, with boy) pose for a photo with students and faculty in Howard A. Doolin Middle School, Miami, Fla., plus other NASA and KSC representatives (rear). The school is one of 100 taking part in the NASA Explorer Schools (NES) program. The purpose of Kennedy’s visit is to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  8. KSC-04pd1161

    NASA Image and Video Library

    2004-05-14

    KENNEDY SPACE CENTER, FLA. -- Astronaut David Wolf answers questions from a student on stage at Howard A. Doolin Middle School, Miami, Fla., during his talk about his experiences in space. Doolin Middle School is one of 100 to take part in the NASA Explorer Schools (NES) program. Wolf joins Center Director Jim Kennedy (seated at lower left) on his visit to share America’s new vision for space exploration with the next generation of explorers. He is talking with students in Florida and Georgia Explorer Schools about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space.

  9. Première découverte de Cricetidae (Rodentia, Mammalia) oligocènes dans le synclinal sud de Gandoï (Bugti Hills, Balouchistan, Pakistan)

    NASA Astrophysics Data System (ADS)

    Marivaux, Laurent; Vianey-Liaud, Monique; Welcomme, Jean-Loup

    1999-12-01

    The preliminary analysis of a new continental vertebrate locality from the basal part of the Bugti Member (Baluchistan) focuses on the Cricetidae. From dental remains, two new species are described here, and related to genera Pseudocricetodon and Atavocricetodon, well known in the Early Oligocène from Europe. Compared to the European and Chinese Late Eocene specimen, their evolutionary stage suggests the Bugti locality to be Early Oligocène in age. These species are the first but also the oldest Paleogene record of the family on the Indian subcontinent and represent the originating ancestor group of the European cricetids.

  10. Effect of feed supplementation with live yeast on the intestinal transcriptome profile of weaning pigs orally challenged with Escherichia coli F4.

    PubMed

    Trevisi, P; Latorre, R; Priori, D; Luise, D; Archetti, I; Mazzoni, M; D'Inca, R; Bosi, P

    2017-01-01

    The ability of live yeasts to modulate pig intestinal cell signals in response to infection with Escherichia coli F4ac (ETEC) has not been studied in-depth. The aim of this trial was to evaluate the effect of Saccharomyces cerevisiae CNCM I-4407 (Sc), supplied at different times, on the transcriptome profile of the jejunal mucosa of pigs 24 h after infection with ETEC. In total, 20 piglets selected to be ETEC-susceptible were weaned at 24 days of age (day 0) and allotted by litter to one of following groups: control (CO), CO+colistin (AB), CO+5×1010 colony-forming unit (CFU) Sc/kg feed, from day 0 (PR) and CO+5×1010 CFU Sc/kg feed from day 7 (CM). On day 7, the pigs were orally challenged with ETEC and were slaughtered 24 h later after blood sampling for haptoglobin (Hp) and C-reactive protein (CRP) determination. The jejunal mucosa was sampled (1) for morphometry; (2) for quantification of proliferation, apoptosis and zonula occludens (ZO-1); (3) to carry out the microarray analysis. A functional analysis was carried out using Gene Set Enrichment Analysis. The normalized enrichment score (NES) was calculated for each gene set, and statistical significance was defined when the False Discovery Rate % was <25 and P-values of NES were <0.05. The blood concentration of CRP and Hp, and the score for ZO-1 integrity on the jejunal villi did not differ between groups. The intestinal crypts were deeper in the AB (P=0.05) and the yeast groups (P<0.05) than in the CO group. Antibiotic treatment increased the number of mitotic cells in intestinal villi as compared with the control group (P<0.05). The PR group tended to increase the mitotic cells in villi and crypts and tended to reduce the cells in apoptosis as compared with the CM group. The transcriptome profiles of the AB and PR groups were similar. In both groups, the gene sets involved in mitosis and in mitochondria development ranked the highest, whereas in the CO group, the gene sets related to cell junction and anion channels were affected. In the CM group, the gene sets linked to the metabolic process, and transcription ranked the highest; a gene set linked with a negative effect on growth was also affected. In conclusion, the constant supplementation in the feed with the strain of yeast tested was effective in counteracting the detrimental effect of ETEC infection in susceptible pigs limits the early activation of the gene sets related to the impairment of the jejunal mucosa.

  11. Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms.

    PubMed Central

    Zhao, Xiangshan; Gan, Lixia; Pan, Haiyun; Kan, Donghui; Majeski, Michael; Adam, Stephen A; Unterman, Terry G

    2004-01-01

    FOXO1, a Forkhead transcription factor, is an important target of insulin and growth factor action. Phosphorylation of Thr-24, Ser-256 and Ser-319 promotes nuclear exclusion of FOXO1, yet the mechanisms regulating nuclear/cytoplasmic shuttling of FOXO1 are poorly understood. Previous studies have identified an NLS (nuclear localization signal) in the C-terminal basic region of the DBD (DNA-binding domain), and a leucine-rich, leptomycin-B sensitive NES (nuclear export signal) located further downstream. Here, we find that other elements in the DBD also contribute to nuclear localization, and that multiple mechanisms contribute to nuclear exclusion of FOXO1. Phosphorylation of Ser-319 and a cluster of nearby residues (Ser-322, Ser-325 and Ser-329) functions co-operatively with the nearby NES to promote nuclear exclusion. The N-terminal region of FOXO1 (amino acids 1-149) also is sufficient to promote nuclear exclusion, and does so through multiple mechanisms. Amino acids 1-50 are sufficient to promote nuclear exclusion of green fluorescent protein fusion proteins, and the phosphorylation of Thr-24 is required for this effect. A leucine-rich, leptomycin B-sensitive export signal is also present nearby. Phosphorylated FOXO1 binds 14-3-3 proteins, and co-precipitation studies with tagged proteins indicate that 14-3-3 binding involves co-operative interactions with both Thr-24 and Ser-256. Ser-256 is located in the C-terminal region of the DBD, where 14-3-3 proteins may interfere both with DNA-binding and with nuclear-localization functions. Together, these studies demonstrate that multiple elements contribute to nuclear/cytoplasmic shuttling of FOXO1, and that phosphorylation and 14-3-3 binding regulate the cellular distribution and function of FOXO1 through multiple mechanisms. The presence of these redundant mechanisms supports the concept that the regulation of FOXO1 function plays a critical role in insulin and growth factor action. PMID:14664696

  12. Sacroiliites infectieuses dans le centre tunisien: étude rétrospective de 25 cas

    PubMed Central

    Bellazreg, Foued; Alaya, Zeineb; Hattab, Zouhour; Lasfar, Nadia Ben; Ayeche, Mohamed Laziz Ben; Bouajina, Elyes; Letaief, Amel; Hachfi, Wissem

    2016-01-01

    Les sacroiliites infectieuses sont rares mais peuvent se compliquer de séquelles fonctionnelles invalidantes. Décrire les caractéristiques cliniques et bactériologiques des sacroiliites infectieuses chez les patients suivis à Sousse, Centre Tunisien. Etude rétrospective, descriptive, des cas de sacroiliites infectieuses chez les patients hospitalisés à Sousse entre 2000 et 2015. Le diagnostic a été retenu devant des signes cliniques, d'imagerie, et microbiologiques évocateurs. Vingt-cinq patients, 10 hommes et 15 femmes, d’âge moyen 41 ans (19-78) ont été inclus. Les sacroiliites étaient dues à des bactéries pyogènes dans 14 cas (56%), brucelliennes dans 6 cas (24%), et tuberculeuses dans 5 cas (20%). La durée moyenne d’évolution était de 61, 45 et 402 jours respectivement. Les signes cliniques les plus fréquents étaient les douleurs fessières (92%) et la fièvre (88%). La radiographie standard était anormale dans 75% des cas. La TDM et l'IRM sacro-iliaques dans tous les cas. Le diagnostic a été confirmé bactériologiquement dans 24 cas (96%). La durée moyenne d'antibiothérapie était de 83 jours dans les sacroiliites à pyogènes, et de 102 jours dans les SI brucelliennes. L’évolution était favorable chez 12 patients (48%), 9 patients (36%) ont gardé une douleur sacro-iliaque séquellaire, et 4 patients (16%) sont décédés. Dans notre étude, la durée d’évolution de la sacroiliite infectieuse ne permettait pas de prédire la bactérie responsable, d'où la nécessité d'obtenir une documentation bactériologique afin de prescrire une antibiothérapie appropriée. PMID:27583067

  13. Modélisation de matériaux chiraux à structures hétérogènes (modèle MTWC) : théorie, validations expérimentales et applications

    NASA Astrophysics Data System (ADS)

    Mariotte, F.; Sauviac, B.; Héliot, J. Ph.

    1995-10-01

    After a brief overview of the concept of electromagnetic chirality, this paper deals with a numerical simulation of isotropic composites with metallic chiral inclusions: computations of permittivity, permeability and chirality parameter as functions of frequency are presented. The theoretical results are, step by step, compared with measurements of chiral composites at microwave frequencies. The application of such media in Radar Cross-Section (RCS) management and control is discussed. The introduction of chiral inclusions seems to make impedance matching possible and may lead to attractive shields with lower reflectivity and larger bandwidth. However the optimization of material characteristics necessary to get a specific absorber remains a difficult task. Après un bref rappel du principe de la chiralité, cet article présente une modélisation des propriétés effectives des matériaux hétérogènes à inclusions chirales métalliques : calcul de la permittivité, perméabilité et coefficient de chiralité du composite en fonction de la fréquence. Les résultats théoriques sont validés, pas à pas, par des mesures effectuées sur des composites chiraux de natures différentes. L'application de tels matériaux à la conception de matériaux absorbant les ondes électromagnétiques est ensuite envisagée. Les inclusions chirales semblent offrir la possibilité de régler l'impédance à l'interface air-milieu absorbant permettant ainsi de concevoir des absorbants micro-ondes plus performants en terme d'atténuation ou de largeur de bande. L'optimisation des caractéristiques des matériaux pour obtenir des performances données restent néanmoins très délicate.

  14. La tectonique active de la région nord-algérienne

    NASA Astrophysics Data System (ADS)

    Yelles-Chaouche, AbdelKrim; Boudiaf, Azzedine; Djellit, Hamou; Bracene, Rabah

    2006-01-01

    En Algérie, la tectonique active est localisée dans la région nord du pays, essentiellement dans le Tell. Dans cette région, frontière entre les plaques Africaine et Eurasiatique, la déformation tectonique est l'expression de la convergence actuelle des ces deux plaques et se traduit par la fermeture progressive des bassins néogènes et par la poursuite de l'édification de la chaîne. Le long de la marge, la déformation s'exprime dans la partie de la plaine abyssale proche du continent, par le plissement de la couverture plio-quaternaire. Au niveau de la pente et sur le plateau continental, la sismicité est générée par des accidents qui se prolongent parfois à terre. Cette tectonique littorale active est à l'origine de la surrection de la côte, comme cela fut le cas lors du dernier séisme de Boumerdes du 21 mai 2003, où le soulèvement cosismique a été estimé en moyenne à 0,50 m. À terre, la sismicité s'exprime surtout le long des bordures des bassins néogènes qui longent la côte. Ces bassins se déforment en donnant des structures plicatives (synclinaux, anticlinaux) et parfois cassantes (pli-failles, failles inverses, chevauchements) orientées NE-SW à NNE-SSW. Ces dernières sont le plus souvent à l'origine des violents tremblements de terre que connaît l'Algérie. Plus au sud, la sismicité s'exprime, tout le long du Tell, le long des faisceaux de plis de direction NE-SW. Actuellement, dans les régions des Hauts Plateaux et la région de l'Atlas saharien, l'activité sismique est faible. Pour citer cet article : A. Yelles-Chaouche et al., C. R. Geoscience 338 (2006).

  15. Copolymères (carbazolylène-pyrrolylène) : synthèse par oxydation chimique et propriétés

    NASA Astrophysics Data System (ADS)

    Boucard, V.; Adès, D.; Siove, A.

    1998-06-01

    Conditions in which (carbazolylene-pyrrolylene) random copolymers could be synthetized directly by chemical oxidation by FeCl3 were studied. A substantial amount of soluble copolymers is obtained after work-up in the conditions corresponding to carbazole/pyrrole/2 FeCl3 molar proportions. An important fraction of polypyrrole was obtained beside a fraction of species soluble in ethanol (carbazole and dimer) and an other fraction of products soluble in water (pyrrole accompanied by the first terms of the oligomeric series). Soluble copolymers were characterized by means of SEC, NMR and UV-Visible spectroscopies. Cyclic voltammetry analysis disclosed that these copolymers exhibit both the carbazolic and the pyrrolic features. Les conditions dans lesquelles des copolymères statistiques (carbazo lylène-pyrrolylène) pouvaient être synthétisés directement par oxydation chimique par FeCl3 ont été étudiées. Des quantités substantielles de copolymères solubles en milieu organique sont obtenues par extraction lorsque les proportions molaires en réactifs carbazole/pyrrole/2 FeCl3 sont utilisées. Une fraction importante de polypyrrole est obtenue à côté d'une fraction d'espèces solubles dans l'éthanol (carbazole et son dimère) et d'une fraction de produits solubles dans l'eau (pyrrole et les premiers termes oligomères). Les copolymères solubles ont été caractérisés par CES, spectroscopies RMN et UV-Visible. L'analyse voltampérométrique de ces matériaux révèle qu'ils possèdent à la fois les caractéristiques des entités carbazolylènes et celles des entités pyrrolylènes.

  16. SGPL1 (sphingosine phosphate lyase 1) modulates neuronal autophagy via phosphatidylethanolamine production.

    PubMed

    Mitroi, Daniel N; Karunakaran, Indulekha; Gräler, Markus; Saba, Julie D; Ehninger, Dan; Ledesma, María Dolores; van Echten-Deckert, Gerhild

    2017-05-04

    Macroautophagy/autophagy defects have been identified as critical factors underlying the pathogenesis of neurodegenerative diseases. The roles of the bioactive signaling lipid sphingosine-1-phosphate (S1P) and its catabolic enzyme SGPL1/SPL (sphingosine phosphate lyase 1) in autophagy are increasingly recognized. Here we provide in vitro and in vivo evidence for a previously unidentified route through which SGPL1 modulates autophagy in neurons. SGPL1 cleaves S1P into ethanolamine phosphate, which is directed toward the synthesis of phosphatidylethanolamine (PE) that anchors LC3-I to phagophore membranes in the form of LC3-II. In the brains of SGPL1 fl/fl/Nes mice with developmental neural specific SGPL1 ablation, we observed significantly reduced PE levels. Accordingly, alterations in basal and stimulated autophagy involving decreased conversion of LC3-I to LC3-II and increased BECN1/Beclin-1 and SQSTM1/p62 levels were apparent. Alterations were also noticed in downstream events of the autophagic-lysosomal pathway such as increased levels of lysosomal markers and aggregate-prone proteins such as APP (amyloid β [A4] precursor protein) and SNCA/α-synuclein. In vivo profound deficits in cognitive skills were observed. Genetic and pharmacological inhibition of SGPL1 in cultured neurons promoted these alterations, whereas addition of PE was sufficient to restore LC3-I to LC3-II conversion, and control levels of SQSTM1, APP and SNCA. Electron and immunofluorescence microscopy showed accumulation of unclosed phagophore-like structures, reduction of autolysosomes and altered distribution of LC3 in SGPL1 fl/fl/Nes brains. Experiments using EGFP-mRFP-LC3 provided further support for blockage of the autophagic flux at initiation stages upon SGPL1 deficiency due to PE paucity. These results emphasize a formerly overlooked direct role of SGPL1 in neuronal autophagy and assume significance in the context that autophagy modulators hold an enormous therapeutic potential in the treatment of neurodegenerative diseases.

  17. Occupation and mental health in a national UK survey.

    PubMed

    Stansfeld, Stephen Alfred; Rasul, F R; Head, J; Singleton, N

    2011-02-01

    To measure the prevalence of common mental disorder (CMD) by occupation in a representative sample of Great Britain and to identify occupations with increased and decreased risk of CMD. A cross-sectional interview-based survey was carried out including 5,497 working male and female respondents, 16-64 years from a stratified random survey of private households in Britain. Occupations were classified by the Standard Occupational Classification (SOC) into four groups: major, sub-major, minor and constituent unit groups. Common Mental Disorder was measured by the Revised Clinical Interview Schedule. Major SOC groups with higher prevalence of common mental disorder included clerical and secretarial, sales, and personal and protective services whereas craft and related, 'other' professional occupations and plant and machine operatives had lower prevalence compared to 13% overall prevalence in all adults. In sub-major SOC groups managers and administrators, teaching professionals, clerical and secretarial, 'other' sales and personal service occupations had higher prevalence whereas many professional and skilled occupations had lower prevalence. Specific SOC unit groups with higher prevalence included primary and secondary teachers, welfare community, youth workers, security staff, waiters, bar staff, nurse auxiliaries and care assistants. General managers in government and large organizations (OR=2.79, 95% CI 1.41-5.54), managers in transport and storing (OR=2.44, 95% CI 1.18-5.03), buyers and mobile sales persons (OR=2.48, 95% CI 1.09-5.60), sales occupations (NES) (OR=2.78, 95% CI 1.25-6.19) and clerks (NES) (OR=2.71, 95% CI 1.59-4.61) had increased risk of common mental disorder relative to specialist managers adjusting for social and financial factors and physical ill-health. Occupations with higher risk of common mental disorder may be typified by high levels of job demands, especially emotional demands and lack of job security. The reasons why occupations have low rates of common mental disorder are varied and may include high levels of job discretion, good job training and clearly defined job tasks.

  18. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pelch, Katherine E.; Tokar, Erik J.; Merrick, B. Alex

    Previous work shows altered methylation patterns in inorganic arsenic (iAs)- or cadmium (Cd)-transformed epithelial cells. Here, the methylation status near the transcriptional start site was assessed in the normal human prostate epithelial cell line (RWPE-1) that was malignantly transformed by 10 μM Cd for 11 weeks (CTPE) or 5 μM iAs for 29 weeks (CAsE-PE), at which time cells showed multiple markers of acquired cancer phenotype. Next generation sequencing of the transcriptome of CAsE-PE cells identified multiple dysregulated genes. Of the most highly dysregulated genes, five genes that can be relevant to the carcinogenic process (S100P, HYAL1, NTM, NES, ALDH1A1)more » were chosen for an in-depth analysis of the DNA methylation profile. DNA was isolated, bisulfite converted, and combined bisulfite restriction analysis was used to identify differentially methylated CpG sites, which was confirmed with bisulfite sequencing. Four of the five genes showed differential methylation in transformants relative to control cells that was inversely related to altered gene expression. Increased expression of HYAL1 (> 25-fold) and S100P (> 40-fold) in transformants was correlated with hypomethylation near the transcriptional start site. Decreased expression of NES (> 15-fold) and NTM (> 1000-fold) in transformants was correlated with hypermethylation near the transcriptional start site. ALDH1A1 expression was differentially expressed in transformed cells but was not differentially methylated relative to control. In conclusion, altered gene expression observed in Cd and iAs transformed cells may result from altered DNA methylation status. - Highlights: • Cd and iAs are known human carcinogens, yet neither appears directly mutagenic. • Prior data suggest epigenetic modification plays a role in Cd or iAs induced cancer. • Altered methylation of four misregulated genes was found in Cd or iAs transformants. • The resulting altered gene expression may be relevant to cellular transformation.« less

  19. Génétique humaine de la tuberculose

    PubMed Central

    El Baghdadi, J.; Grant, A.V.; Sabri, A.; El Azbaoui, S.; Zaidi, H.; Cobat, A.; Schurr, E.; Boisson-Dupuis, S.; Casanova, J.L.; Abel, L.

    2013-01-01

    RESUME La tuberculose, causée par Mycobacterium tuberculosis, demeure un problème majeur de santé publique avec plus de 8,7 millions de nouveaux cas et 1,4 millions de décès par an. Après exposition, la plupart des individus, mais pas la totalité, deviennent infectés par le bacille. Parmi les sujets infectés, seule une minorité (environ 10%) développera une tuberculose clinique, qui est typiquement soit une tuberculose primaire, extra-pulmonaire, chez l’enfant, soit une tuberculose de réactivation, pulmonaire, chez l’adulte. Il existe de très nombreuses observations montrant que cette variabilité dépend pour une large part de facteurs génétiques de l’hôte. Dans la tuberculose pulmonaire, des études d’association avec de multiples gènes candidats ont été réalisées mais avec des résultats peu convaincants. Les récentes études d’association génome entier n’ont retrouvé qu’un rôle très modeste de deux variants intergéniques. Néanmoins, un premier locus majeur de prédisposition à la tuberculose pulmonaire a été identifié dans la région du chromosome 8q12–q13 par analyse de liaison génétique dans une population marocaine. En utilisant cette même stratégie d’analyse de liaison, deux autres gènes majeurs contrôlant l’infection tuberculeuse (en particulier la résistance à l’infection) ont été identifiés. Alors que l’identification précise de ces gènes est en cours, l’autre observation fascinante de ces dernières années a été la découverte que la tuberculose pouvait également relever d’une prédisposition mendélienne, en particulier liée à un défaut complet d’un des récepteurs de l’IL-12, IL12Rβ1. Au total, l’ensemble de ces études fournissent la preuve du concept d’un spectre continu de prédisposition génétique à la tuberculose, allant d’un contrôle monogénique simple à une hérédité polygénique complexe en passant par des effets intermédiaires de gène majeur. L’identification des facteurs génétiques prédisposant à la tuberculose est fondamentale pour comprendre la physiopathologie de cette maladie et permettre ainsi le développement de nouvelles stratégies vaccinales et thérapeutiques. Mots clés: tuberculose, mycobactérie, variant génétique, polymorphisme, génétique humaine, susceptibilité/résistance, étude d’association, analyse de liaison génétique, prédisposition mendélienne PMID:23399414

  20. KSC-2011-3368

    NASA Image and Video Library

    2011-05-06

    Cape Canaveral, Fla. -- Rachael Power, education specialist sets up a display for fourth- through 12-grade students and their teachers from across the nation during closing events at the NASA Explorer Schools Symposium in Florida. During the NES gathering, students presented their investigation project to their peers, scientists, engineers and education specialists. About 60 fourth- through 12-grade students nationwide are at the center May 4-7 participating in tours of processing and launch facilities and the U.S. Astronaut Hall of Fame, as well as several educational activities and a career panel question-and-answer session. About 30 teachers will receive professional development opportunities during the symposium. The participants were competitively selected after they completed an original investigation focused on existing NASA missions or research interests. Photo Credit: NASA/Kim Shiflett

  1. KSC-06pd0137

    NASA Image and Video Library

    2006-01-23

    KENNEDY SPACE CENTER, FLA. — During kickoff of the NASA Explorer School program at Warrington Middle School in Pensacola, Fla., NASA aerospace specialist Les Gold involves a student in a demonstration on stage. Gold, Center Director Jim Kennedy, astronaut Alan Poindexter and others are visiting the school to share the vision for space exploration with the next generation. He is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space. NES establishes a three-year partnership annually between NASA and 50 NASA Explorer School teams, consisting of teachers and education administrators from diverse communities nationwide. Photo credit: NASA/Cory Huston

  2. KSC-06pd0136

    NASA Image and Video Library

    2006-01-23

    KENNEDY SPACE CENTER, FLA. — During kickoff of the NASA Explorer School program at Warrington Middle School in Pensacola, Fla., NASA aerospace specialist Les Gold involves a student in a demonstration on stage. Gold, Center Director Jim Kennedy, astronaut Alan Poindexter and others are visiting the school to share the vision for space exploration with the next generation. He is talking with students about our destiny as explorers, NASA’s stepping stone approach to exploring Earth, the moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space. NES establishes a three-year partnership annually between NASA and 50 NASA Explorer School teams, consisting of teachers and education administrators from diverse communities nationwide. Photo credit: NASA/Cory Huston

  3. The NES strikes a dry hole

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Heede, R.

    1991-12-31

    Thanks to widespread use of more efficient automobiles, aircraft, buildings, computers, appliances, and factories, US energy expenditures are $200 billion lower today that if the economy had remained at the level of energy productivity in 1973, and $400 billion annual energy expenditures could be trimmed in the future. However if energy saving are cheap and effective and environmentally beneficial, the question remains of why we don`t take better advantage of them. The speed of technological advances and resistance to change coupled with several varieties of political myopia explain the bulk of the slow adoption of energy savings. The central issuemore » is not technology or even cost, but sound implementation strategies and education, the focus of this article.« less

  4. MANOVA for distinguishing experts' perceptions about entrepreneurship using NES data from GEM

    NASA Astrophysics Data System (ADS)

    Correia, Aldina; Costa e Silva, Eliana; Lopes, Isabel C.; Braga, Alexandra

    2016-12-01

    Global Entrepreneurship Monitor is a large scale database for internationally comparative entrepreneurship that includes information about many aspects of entrepreneurship activities, perceptions, conditions, national and regional policy, among others, of a large number of countries. This project has two main sources of primary data: the Adult Population Survey and the National Expert Survey. In this work the 2011 and 2012 National Expert Survey datasets are studied. Our goal is to analyze the effects of the different type of entrepreneurship expert specialization on the perceptions about the Entrepreneurial Framework Conditions. For this purpose the multivariate analysis of variance is used. Some similarities between the results obtained for the 2011 and 2012 datasets were found, however the differences between experts still exist.

  5. Nouvelles découvertes de Vertébrés miocènes dans le synclinal de Dera Bugti (Balouchistan, Pakistan)

    NASA Astrophysics Data System (ADS)

    Welcomme, Jean-Loup; Antoine, Pierre-Olivier; Duranthon, Francis; Mein, Pierre; Ginsburg, Léonard

    1997-10-01

    Since Forster-Cooper in 1910, no paleontologist bas visited the area of Dera Bugti in Baluchistan (Pakistan). In 1995 and 1996, two small French expeditions prospected the syncline of Dera Bugti. They established stratigraphical sections ana discovered many fossils, mainly reptiles, and mammals. On top of the Eocene marine limestone of the Kirthar there lies a Burdigalian marine falun. Above, about 250 m of continental marls, sands and sandstones are deposited. The first 100 m have yielded five fossiliferous levels of MN3 b in age, and one of MN4, surrounded by a more sandy series. The top of the series has yielded Hipparion of the Upper Miocene.

  6. Atypical Genetic Locus Associated with Constitutive Production of Enterocin B by Enterococcus faecium BFE 900

    PubMed Central

    Franz, Charles M. A. P.; Worobo, Randy W.; Quadri, Luis E. N.; Schillinger, Ulrich; Holzapfel, Wilhelm H.; Vederas, John C.; Stiles, Michael E.

    1999-01-01

    A purified bacteriocin produced by Enterococcus faecium BFE 900 isolated from black olives was shown by Edman degradation and mass spectrometric analyses to be identical to enterocin B produced by E. faecium T136 from meat (P. Casaus, T. Nilsen, L. M. Cintas, I. F. Nes, P. E. Hernández, and H. Holo, Microbiology 143:2287–2294, 1997). The structural gene was located on a 2.2-kb HindIII fragment and a 12.0-kb EcoRI chromosomal fragment. The genetic characteristics and production of EntB by E. faecium BFE 900 differed from that described so far by the presence of a conserved sequence like a regulatory box upstream of the EntB gene, and its production was constitutive and not regulated. The 2.2-kb chromosomal fragment contained the hitherto undetected immunity gene for EntB in an atypical orientation that is the reverse of that of the structural gene. Typical transport and other genes associated with bacteriocin production were not detected on the 12.0-kb chromosomal fragment containing the EntB structural gene. This makes the EntB genetic system different from most other bacteriocin systems, where transport and possible regulatory genes are clustered. EntB was subcloned and expressed by the dedicated secretion machinery of Carnobacterium piscicola LV17A. The structural gene was amplified by PCR, fused to the divergicin A signal peptide, and expressed by the general secretory pathway in Enterococcus faecalis ATCC 19433. PMID:10224016

  7. UV Induced Degradation of Polycarbonate-Based Lens Materials and Implications for the Heath Care Field

    NASA Astrophysics Data System (ADS)

    Harkay, J. Russell; Henry, Jerry

    2007-04-01

    Experimental undergraduate research at Keene State College has utilized facilities in physics and chemistry and at Polyonics, a local firm to study the effects of mono- and polychromatic UV radiation from various sources, including a Deuterium lamp, a solarization unit, a monochromator, and natural sunlight to study the photodegradation of polycarbonate-based lens materials used to produce eyewear using spectrophotometry and FTIR analysis. Ophthalmologic literature indicates a correlation between exposure to the UVB band of sunlight and the onset of cataract formation and macular degeneration. It is well known that polycarbonate plastic ``yellows'' when exposed to intense sunlight and, particularly, UV light either via photo-Fries rearrangement or by a photo oxidative process, forming polyconjugated systems and is a concern primarily for cosmetic reasons. Our data indicates that the ``yellowing'' is an indication of a more sinister problem in the case of eyeglasses in that spectrophotometric comparison shows it is accompanied by an increase in transmissivity in the UVB band where the wearer expects and needs protection. FTIR results indicate a degradation of molecular stabilizers and the appearance of free radicals that indicate a breakdown of the resin's chemical structure. To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2007.NES07.B1.4

  8. Exoplanet studies. Spectral confirmation of photometric exoplanet candidates discovered by the "Kepler" mission

    NASA Astrophysics Data System (ADS)

    Gadelshin, D. R.; Valyavin, G. G.; Yushkin, M. V.; Semenko, E. A.; Galazutdinov, G. A.; Maryeva, O. V.; Valeev, A. F.; Lee, Byeong-Cheol

    2017-07-01

    We present the results of spectroscopic confirmation of exoplanet candidates from the "Kepler" space mission catalog. We used the NES spectrometer of the 6-m Russian BTA telescope to investigate the Doppler variability of the radial velocities of the host stars of KOI-974.01, KOI-2687.01/02, and KOI-2706.01. According to the derived upper limits, KOI-2706.01 has a mass significantly smaller than 12 Jupiter masses, which directly indicates its planetary nature. We show that KOI-2687.01 and KOI-2687.02, which have Earth-size or white dwarf-size radii according to photometric data, cannot be white dwarfs, and are therefore exoplanets. Radial velocity analysis for KOI-974, an F-type star, has shown noticeable variations with a half-amplitude of 400 ms-1, which correlate poorly with the phase of its orbital rotation. This can indicate a presence of other massive planets in the system, with orbits closer or farther from the host star than the orbit of KOI-974.01, or a low mass star in a distant outer orbit. Using the method of synthetic spectra, we obtained more accurate atmospheric parameter and radius estimates for all the program host stars, which, in turn, allowed us to refine the radii of the studied exoplanet candidates.

  9. Modeling the Influences of Electrostatic Discharge in Materials on a Failures of Onboard Electronic Equipment in under Microgcrogravity

    NASA Astrophysics Data System (ADS)

    Grichshenko, Valentina; Zhantayev, Zhumabek; Mukushev, Acemhan

    2016-07-01

    It is known, that during SV exploitation failures of automated systems happens as the result of complex influence of Space leading to SV's shorter life span, sometimes to their lose. All of the SV, functioning in the near-Earth Space (NES), subjected to influence of different Space factors. Causes and character of failure onboard equipment are different. Many researchers think that failures of onboard electronics connected to changing solar activity level. However, by the numerous onboard experiments established that even in the absence of solar burst in magnetostatic days there are registered failures of onboard electronics. In this paper discussed the results of modeling the impact of electrostatic discharge (ESD), occurring in the materials, on a failures of electronic onboard equipment in microgravity. The paper discusses the conditions of formation and influence of electrostatic discharge in microgravity on the elements of the onboard electronics in Space. Developed technique using circuit simulation in ISIS Proteus environment is discussed. Developed the recommendations for noise immunity of on-board equipment from ESD in Space. The results are used to predict the failure rate on-board electronics with the long term of space mission. Key words: microgravity, materials, failures, onboard electronics, Space

  10. Histone Deacetylase 3 Is Necessary for Proper Brain Development*

    PubMed Central

    Norwood, Jordan; Franklin, Jade M.; Sharma, Dharmendra; D'Mello, Santosh R.

    2014-01-01

    The functional role of histone deacetylase 3 (HDAC3) in the developing brain has yet to be elucidated. We show that mice lacking HDAC3 in neurons and glia of the central nervous system, Nes-Cre/HDAC3 conditional KO mice, show major abnormalities in the cytoarchitecture of the neocortex and cerebellum and die within 24 h of birth. Later-born neurons do not localize properly in the cortex. A similar mislocalization is observed with cerebellar Purkinje neurons. Although the proportion of astrocytes is higher than normal, the numbers of oligodendrocytes are reduced. In contrast, conditional knockout of HDAC3 in neurons of the forebrain and certain other brain regions, using Thy1-Cre and calcium/calmodulin dependent protein kinase II α-Cre for ablation, produces no overt abnormalities in the organization of cells within the cortex or of cerebellar Purkinje neurons at birth. However, both lines of conditional knockout mice suffer from progressive hind limb paralysis and ataxia and die around 6 weeks after birth. The mice display an increase in overall numbers of cells, higher numbers of astrocytes, and Purkinje neuron degeneration. Taken together, our results demonstrate that HDAC3 plays an essential role in regulating brain development, with effects on both neurons and glia in different brain regions. PMID:25339172

  11. Can Applied Naturoptics Fund Associates Degrees in Applied Optics Graduates, in the Americas and Elsewhere, into BS/MS/PhD Physics/Applied Physics Programs?

    NASA Astrophysics Data System (ADS)

    Ferreira, Nadja; Andrade, Jennifer; Mc Leod, Roger D.

    2007-04-01

    Youthful females and other disadvantaged minority members sometimes develop visual handicaps when educational and/or other stressors are present. Special methods already available, effective, and underutilized, can be marshaled towards correcting current technologic and academic systems demand-supply mismatches in the sciences. More efficient harvesting of intellectually advantaged youthful students may represent more-highly-productive global scientific output. RDM has found that it is possible to motivate, stimulate, teach, and foster increased science interest by interacting with students at the earliest possible academic moments. The same applied optics of burning paper with a magnifying glass, and prismatic dispersing of light, allows understanding how vision operates, and can be damaged. Providing information to all students that they safely can self-repair damaged vision could only increase their interest in physics and special work-study programs. ``Indians'' are the most poorly represented group at all levels of education and its support services. MOLLOCKET/MULLAH indicates extra-human/higher-power interactions. Why? Obvious survival value suggests possible information-transmission attempts like those accessed by ``Indians.'' To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2007.NES07.C2.2

  12. Enabling the Integrated Assessment of Large Marine Ecosystems: Informatics to the Forefront of Science-Based Decision Support

    NASA Astrophysics Data System (ADS)

    Di Stefano, M.; Fox, P. A.; Beaulieu, S. E.; Maffei, A. R.; West, P.; Hare, J. A.

    2012-12-01

    Integrated assessments of large marine ecosystems require the understanding of interactions between environmental, ecological, and socio-economic factors that affect production and utilization of marine natural resources. Assessing the functioning of complex coupled natural-human systems calls for collaboration between natural and social scientists across disciplinary and national boundaries. We are developing a platform to implement and sustain informatics solutions for these applications, providing interoperability among very diverse and heterogeneous data and information sources, as well as multi-disciplinary organizations and people. We have partnered with NOAA NMFS scientists to facilitate the deployment of an integrated ecosystem approach to management in the Northeast U.S. (NES) and California Current Large Marine Ecosystems (LMEs). Our platform will facilitate the collaboration and knowledge sharing among NMFS natural and social scientists, promoting community participation in integrating data, models, and knowledge. Here, we present collaborative software tools developed to aid the production of the Ecosystem Status Report (ESR) for the NES LME. The ESR addresses the D-P-S portion of the DPSIR (Driver-Pressure-State-Impact-Response) management framework: reporting data, indicators, and information products for climate drivers, physical and human (fisheries) pressures, and ecosystem state (primary and secondary production and higher trophic levels). We are developing our tools in open-source software, with the main tool based on a web application capable of providing the ability to work on multiple data types from a variety of sources, providing an effective way to share the source code used to generate data products and associated metadata as well as track workflow provenance to allow in the reproducibility of a data product. Our platform retrieves data, conducts standard analyses, reports data quality and other standardized metadata, provides iterative and interactive visualization, and enables the download of data plotted in the ESR. Data, indicators, and information products include time series, geographic maps, and uni-variate and multi-variate analyses. Also central to the success of this initiative is the commitment to accommodate and train scientists of multiple disciplines who will learn to interact effectively with this new integrated and interoperable ecosystem assessment capability. Traceability, repeatability, explanation, verification, and validation of data, indicators, and information products are important for cross-disciplinary understanding and sharing with managers, policymakers, and the public. We are also developing an ontology to support the implementation of the DPSIR framework. These new capabilities will serve as the essential foundation for the formal synthesis and quantitative analysis of information on relevant natural and socio-economic factors in relation to specified ecosystem management goals which can be applied in other LMEs.

  13. Study of the chain conformation of thermotropic nematic main chain polyesters

    NASA Astrophysics Data System (ADS)

    Li, M. H.; Brûlet, A.; Cotton, J. P.; Davidson, P.; Strazielle, C.; Keller, P.

    1994-10-01

    The conformation of main chain mesomorphic polyesters is studied by small angle neutron scattering (SANS) in the isotropic and in the nematic phases, by using mixtures of deuterated and undeuterated polymers. Particular attention is given to neglect the transesterification effects occurring mainly at high temperature for these LC polymers. In the isotropic phase, despite the presence of long rigid mesogenic groups, the LC polyester chains have a Gaussian conformation shown by the variation of the radius of gyration as a function of the molecular weight. This result is confirmed from the scattering variation in the intermediate range of the scattering vector. In the nematic phase, the SANS data are well fitted to a model of cylinder, in which the main chain polymer is confined. In the unoriented phase, the measurements in the intermediate range give the values of the radii of cylinders : they lie in between 10 Å and 19 Å depending on the degree of polymerization of chains. In the oriented nematic phase, the scattering patterns are highly anisotropic : they correspond to very long, thin and well-oriented cylinders. We have calculated the fully extended chain lengths using for the monomer length that measured in situ by X-ray diffraction. Then the comparison of this length with the measured height of the cylinders gives the existence of hairpins and their number per chain. For the short chain, the conformation is almost completely elongated in the nematic direction, whereas hairpin defects appear in longer chains. Their number decreases slightly with decreasing temperature. The orientational fluctuations of cylinders relatively to the nematic director are weak as shown from the high values of their order parameter (P_2 > 0.9). These results are discussed for two spacer lengths as a function of the molecular weight and of the temperature. La conformation de polyesters linéaires mésomorphes est étudiée par diffusion de neutrons aux petits angles (DNPA) dans les phases isotrope et nématique sur des mélanges de polymères hydrogénés et deutériés. Les conditions expérimentales ont été choisies afin de pouvoir négliger les effets de la transestérification obtenus à haute température avec cette famille de polymères cristaux liquides. Dans la phase isotrope, en dépit de la présence de longs et rigides groupements mésogènes, les chaînes de polymères ont une conformation gaussienne, comme le montre la variation du rayon de giration en fonction de la masse moléculaire. Ce résultat est confirmé par les mesures faites dans le domaine intermédiaire du vecteur de diffusion. Dans la phase nématique, les données de DNPA sont bien ajustées par un modèle de cylindre dans lequel la chaîne de polymère est confinée. Dans la phase non orientée, les mesures faites dans le domaine intermédiaire donnent les valeurs des rayons des cylindres (compris entre 10 Å et 19 Å selon le degré de polymérisation des chaînes). Dans la phase nématique orientée, les figures de diffusion sont très anisotropes et correspondent à de longs et étroits cylindres bien orientés. La longueur de la chaîne totalement étirée est calculée à partir de la longueur du monomère mesurée par diffraction de rayons X. Par comparaison avec la hauteur du cylindre mesurée en DNPA, nous déduisons l'existence des épingles à cheveux et leur nombre par chaîne. La conformation d'une chaîne courte est complètement étirée dans la direction du champ nématique, alors que des défauts du type épingles à cheveux apparaissent dans les chaînes plus longues. Le nombre de ces défauts décroît légèrement en diminuant la température. Les fluctuations d'orientation des cylindres autour de la direction du champ nématique sont faibles comme le montrent les valeurs élevées des paramètres d'ordre des cylindres (P_2 > 0,9). Les résultats sont discutés, pour deux longueurs d'espaceur, en fonction de la masse moléculaire et de la température.

  14. Venus transits - A French view

    NASA Astrophysics Data System (ADS)

    Débarbat, Suzanne

    2005-04-01

    After a careful study of Mars observations obtained by Tycho Brahé (1546-1601), Kepler (1571-1630) discovered the now-called Kepler's third law. In 1627 he published his famous Tabulae Rudolphinae, a homage to his protector Rudolph II (1552-1612), tables (Kepler 1609, 1627) from which he predicted Mercury and Venus transits over the Sun. In 1629 Kepler published his Admonitio ad Astronomos Advertisement to Astronomers (Kepler 1630), Avertissement aux Astronomes in French Au sujet de phénomènes rares et étonnants de l'an 1631: l'incursion de Vénus et de Mercure sur le Soleil. This was the beginning of the interest of French astronomers, among many others, in such transits, mostly for Venus, the subject of this paper in which dates are given in the Gregorian calendar.

  15. Diffusion thermique et de porteurs de courant au voisinage d'un joint de grain

    NASA Astrophysics Data System (ADS)

    Lepoutre, F.

    1993-07-01

    The photothermal methods (indirect detection of the temperature increase of a sample after absorption of a pulsed or modulated light beam) allow to measure the thermal and electronic diffusions that follow the optical absorption. We report the main applications of a photothermal microscope that we have built to provide informations about these diffusion phenomena at a micronic scale. Comparisons between the photothermal observations and microanalysis data associated with electronic microscopy have been achieved to get qualitative informations. In the case of a purely thermal diffusion this apparatus is able to detect the resistances which may appear at grain boundaries or inside the grains themselves. We present some interesting experimental features which seem to be closely related to the physical origins of these resistances (crystal orientation, dislocation, segregation, secondary phases, cracks). Using a theoretical model developed by other authors we also report quantitative values of the detected thermal resistances that we relate to macroscopic thermal diffusivities measurements of the inspected materials. When electronic carriers are photogenerated by the light excitation, the photothermal microscope can be used to follow the diffusion and the recombination of these carriers. A competition between plasma and heat diffusions is then observed. Such a competition is illustrated in the case of silicon bicristals containing metallic impurities. Les méthodes phototherrniques (détection indirecte de l'accroissement de température d'un échantillon après absorption d'un flux lumineux modulé ou pulsé de lumière) permettent d'étudier les diffusions thermique et électronique qui suivent l'absorption optique. Nous présentons dans cet article les principales applications d'un microscope photothermique que nous avons construit pour suivre les phénomènes de diffusion à l'échelle du micromètre. Des comparaisons entre les observations photothermiques et des résultats de microanalyse permettent d'obtenir des informations qualitatives. Dans les cas où les phénomènes observés sont purement thermiques, cet appareil permet de détecter les résistances thermiques qui apparaissent aux joints de grain ou à l'intérieur des grains eux-mêmes. Nous présentons des résultats expérimentaux qui semblent reliés à l'origine physique de ces résistances thermiques de contact (orientation cristalline, ségrégation, phase secondaire, dislocation, fissuration). En utilisant un modèle théorique développé par d'autres auteurs, nous rapportons également des valeurs quantitatives de résistances thermiques qui ont pu être reliées à des mesures macroscopiques de la diffusivité thermique des matériaux inspectés. Lorsque l'excitation lumineuse génère des porteurs électroniques, le microscope photothermique peut être utilisé pour suivre la diffusion et la recombinaison de ces porteurs. La compétition entre les diffusions électronique et thermique est alors observée. Une illustration de ces phénomènes est donnée dans le cas des bicristaux de silicium contenant des impuretés métalliques.

  16. Mechanical Behavior of Side-Chain Liquid Crystalline Networks

    NASA Astrophysics Data System (ADS)

    Gallani, J. L.; Hilliou, L.; Martinoty, P.; Doublet, F.; Mauzac, M.

    1996-03-01

    The mechanical properties of a homologue series of side-chain mesomorphic networks were studied with a piezo-rheometer over frequencies ranging from 10^{-2} Hz to 10^4 Hz. The results show that the compound's response is governed essentially by the dynamic glass transition. It is sensitive to the N-SmA transition, but insensitive to the N-I transition, with the result that the empirical principle of time-temperature superposition can be applied throughout the N-I transition. The influence of the crosslinking density and the amount of mesogenic side groups was also studied. For each of the samples, the static rigidity modulus G_0, the infinite-frequency dynamic rigidity modulus G_infty, and the characteristic frequencies respectively associated with the longest visco-elastic mode and the glass transition, were determined. Les propriétés mécaniques d'une série homologue de réseaux mésomorphes à chaînes latérales ont été étudiées avec un piézo-rhéomètre entre 10^{-2} Hz et 10^4 Hz. Les résultas obtenus montrent que la réponse du matériau est essentiellement gouvernée par la transition vitreuse dynamique; elle est sensible à la transition N-SmA mais insensible à la transition N-I de sorte qu'il est possible d'appliquer le principe empirique de superposition temps-température au travers de la transition N-I. L'influence du taux de réticulation et du taux de mésogènes a également été étudiée. Le module de rigidité statique G_0, le module de rigidité dynamique à fréquence infinie G_infty et les fréquences caractéristiques associées respectivement au mode viscoélastique le plus long et à la transition vitreuse, ont été déterminées pour chaque échantillon.

  17. Identification of plant cells in black pigments of prehistoric Spanish Levantine rock art by means of a multi-analytical approach. A new method for social identity materialization using chaîne opératoire.

    PubMed

    López-Montalvo, Esther; Roldán, Clodoaldo; Badal, Ernestina; Murcia-Mascarós, Sonia; Villaverde, Valentín

    2017-01-01

    We present a new multi-analytical approach to the characterization of black pigments in Spanish Levantine rock art. This new protocol seeks to identify the raw materials that were used, as well as reconstruct the different technical gestures and decision-making processes involved in the obtaining of these black pigments. For the first of these goals, the pictorial matter of the black figurative motifs documented at the Les Dogues rock art shelter (Ares del Maestre, Castellón, Spain) was characterized through the combination of physicochemical and archeobotanical analyses. During the first stage of our research protocol, in situ and non-destructive analyses were carried out by means of portable Energy Dispersive X-Ray Fluorescence spectrometry (EDXRF); during the second stage, samples were analyzed by Optical Microscopy (OM), Raman spectroscopy, and Scanning Electron Microscopy coupled with Energy Dispersive X-ray spectroscopy (SEM-EDX). Two major conclusions have been drawn from these analyses: first, charred plant matter has been identified as a main component of these prehistoric black pigments; and second, angiosperm and conifer charcoal was a primary raw material for pigment production, identified by means of the archaeobotanical study of plant cells. For the second goal, black charcoal pigments were replicated in the laboratory by using different raw materials and binders and by reproducing two main chaînes opératoires. The comparative study of the structure and preservation of plant tissues of both prehistoric and experimental pigments by means of SEM-EDX underlines both a complex preparation process and the use of likely pigment recipes, mixing raw material with fatty or oily binders. Finally, the formal and stylistic analysis of the motifs portrayed at Les Dogues allowed us to explore the relationship between identified stylistic phases and black charcoal pigment use, raising new archaeological questions concerning the acquisition of know-how and the transfer of traditionally learned chaînes opératoires in Spanish Levantine rock art.

  18. Small Molecule DFPM Derivative-Activated Plant Resistance Protein Signaling in Roots Is Unaffected by EDS1 Subcellular Targeting Signal and Chemical Genetic Isolation of victr R-Protein Mutants

    PubMed Central

    Mevers, Emily; García, Ana V.; Highhouse, Samantha; Gerwick, William H.; Parker, Jane E.; Schroeder, Julian I.

    2016-01-01

    The small molecule DFPM ([5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione) was recently shown to trigger signal transduction via early effector-triggered immunity signaling genes including EDS1 and PAD4 in Arabidopsis thaliana accession Col-0. Chemical genetic analyses of A. thaliana natural variants identified the plant Resistance protein-like Toll/Interleukin1 Receptor (TIR)-Nucleotide Binding (NB)-Leucine-Rich Repeat (LRR) protein VICTR as required for DFPM-mediated root growth arrest. Here a chemical genetic screen for mutants which disrupt DFPM-mediated root growth arrest in the Col-0 accession identified new mutant alleles of the TIR-NB-LRR gene VICTR. One allele, victr-6, carries a Gly216-to-Asp mutation in the Walker A domain supporting an important function of the VICTR nucleotide binding domain in DFPM responses consistent with VICTR acting as a canonical Resistance protein. The essential nucleo-cytoplasmic regulator of TIR-NB-LRR-mediated effector-triggered immunity, EDS1, was reported to have both nuclear and cytoplasmic actions in pathogen resistance. DFPM was used to investigate the requirements for subcellular EDS1 localization in DFPM-mediated root growth arrest. EDS1-YFP fusions engineered to localize mainly in the cytoplasm or the nucleus by tagging with a nuclear export signal (NES) or a nuclear localization signal (NLS), respectively, were tested. We found that wild-type EDS1-YFP and both the NES and NLS-tagged EDS1 variants were induced by DFPM treatments and fully complemented eds1 mutant plants in root responses to DFPM, suggesting that enrichment of EDS1 in either compartment could confer DFPM-mediated root growth arrest. We further found that a light and O2-dependent modification of DFPM is necessary to mediate DFPM signaling in roots. Chemical analyses including Liquid Chromatography-Mass Spectrometry and High-Resolution Atmospheric Pressure Chemical Ionization Mass Spectrometry identified a DFPM modification product that is likely responsible for bioactivity mediating root growth arrest. We propose a chemical structure of this product and a possible reaction mechanism for DFPM modification. PMID:27219122

  19. Nucleocytoplasmic Distribution and Dynamics of the Autophagosome Marker EGFP-LC3

    PubMed Central

    Drake, Kimberly R.; Kang, Minchul; Kenworthy, Anne K.

    2010-01-01

    The process of autophagy involves the formation of autophagosomes, double-membrane structures that encapsulate cytosol. Microtubule-associated protein light chain 3 (LC3) was the first protein shown to specifically label autophagosomal membranes in mammalian cells, and subsequently EGFP-LC3 has become one of the most widely utilized reporters of autophagy. Although LC3 is currently thought to function primarily in the cytosol, the site of autophagosome formation, EGFP-LC3 often appears to be enriched in the nucleoplasm relative to the cytoplasm in published fluorescence images. However, the nuclear pool of EGFP-LC3 has not been specifically studied in previous reports, and mechanisms by which LC3 shuttles between the cytoplasm and nucleoplasm are currently unknown. In this study, we therefore investigated the regulation of the nucleo-cytoplasmic distribution of EGFP-LC3 in living cells. By quantitative fluorescence microscopy analysis, we demonstrate that soluble EGFP-LC3 is indeed enriched in the nucleus relative to the cytoplasm in two commonly studied cell lines, COS-7 and HeLa. Although LC3 contains a putative nuclear export signal (NES), inhibition of active nuclear export or mutation of the NES had no effect on the nucleo-cytoplasmic distribution of EGFP-LC3. Furthermore, FRAP analysis indicates that EGFP-LC3 undergoes limited passive nucleo-cytoplasmic transport under steady state conditions, and that the diffusional mobility of EGFP-LC3 was substantially slower in the nucleus and cytoplasm than predicted for a freely diffusing monomer. Induction of autophagy led to a visible decrease in levels of soluble EGFP-LC3 relative to autophagosome-bound protein, but had only modest effects on the nucleo-cytoplasmic ratio or diffusional mobility of the remaining soluble pools of EGFP-LC3. We conclude that the enrichment of soluble EGFP-LC3 in the nucleus is maintained independently of active nuclear export or induction of autophagy. Instead, incorporation of soluble EGFP-LC3 into large macromolecular complexes within both the cytoplasm and nucleus may prevent its rapid equilibrium between the two compartments. PMID:20352102

  20. The impact of the natural environment on the promotion of active living: an integrative systematic review.

    PubMed

    Calogiuri, Giovanna; Chroni, Stiliani

    2014-08-24

    An understanding of how the living environment influences physical activity (PA) is of great importance for health promotion. Researchers have reported increased PA when there is a greater availability of nature within people's living environment. However, little has been said about underlying motivational processes. The aim of this study was to review the existing literature on the relationship between the natural environment (NE) and PA, integrating it into a conceptual model that depicts the motivational process underlying this relationship. Through a systematic literature search in line with PRISMA guidelines, peer-reviewed articles were sought using PubMed (search updated to October 2013) and scrutiny of reference lists. In addition, we contacted experts within our network. We reviewed papers in which the research question(s) concerned: 1) Effects of PA in NE on individuals' feelings and beliefs; 2) Relationships between PA and availability of NEs; and 3) Motivational processes underlying visits to NEs in association with PA. Analysis and integration of the 90 selected studies were performed using the theory of planned behaviour (TPB). People's experiences in using the NE can enhance attitudes toward PA and perceived behavioural control via positive psychological states and stress-relieving effects, which lead to firmer intentions to engage in PA. Individual and environmental barriers, as expressions of social support and actual behavioural control, impact the process via subjective norm and perceived behavioural control. Instrumental beliefs such as a desire to enjoy nature and the expected health benefits also influence the process via attitudes. Different patterns have been identified for neighbourhood-based PA and outdoor recreations that take place in a NE. The availability of a NE and attractive views of nature within an individual's living environment are important contributors to PA, yet attention should focus on personal characteristics and environmental barriers. Policy and infrastructural interventions should aim to guarantee access and maintenance of the NE, as well as information and programming of social activities. Social campaigns via media and health institutions should highlight how nature can be a source of motivation for maintaining a PA routine, reducing stress and achieving aesthetic and health goals.

  1. Identification of plant cells in black pigments of prehistoric Spanish Levantine rock art by means of a multi-analytical approach. A new method for social identity materialization using chaîne opératoire

    PubMed Central

    Roldán, Clodoaldo; Badal, Ernestina; Murcia-Mascarós, Sonia; Villaverde, Valentín

    2017-01-01

    We present a new multi-analytical approach to the characterization of black pigments in Spanish Levantine rock art. This new protocol seeks to identify the raw materials that were used, as well as reconstruct the different technical gestures and decision-making processes involved in the obtaining of these black pigments. For the first of these goals, the pictorial matter of the black figurative motifs documented at the Les Dogues rock art shelter (Ares del Maestre, Castellón, Spain) was characterized through the combination of physicochemical and archeobotanical analyses. During the first stage of our research protocol, in situ and non-destructive analyses were carried out by means of portable Energy Dispersive X-Ray Fluorescence spectrometry (EDXRF); during the second stage, samples were analyzed by Optical Microscopy (OM), Raman spectroscopy, and Scanning Electron Microscopy coupled with Energy Dispersive X-ray spectroscopy (SEM-EDX). Two major conclusions have been drawn from these analyses: first, charred plant matter has been identified as a main component of these prehistoric black pigments; and second, angiosperm and conifer charcoal was a primary raw material for pigment production, identified by means of the archaeobotanical study of plant cells. For the second goal, black charcoal pigments were replicated in the laboratory by using different raw materials and binders and by reproducing two main chaînes opératoires. The comparative study of the structure and preservation of plant tissues of both prehistoric and experimental pigments by means of SEM-EDX underlines both a complex preparation process and the use of likely pigment recipes, mixing raw material with fatty or oily binders. Finally, the formal and stylistic analysis of the motifs portrayed at Les Dogues allowed us to explore the relationship between identified stylistic phases and black charcoal pigment use, raising new archaeological questions concerning the acquisition of know-how and the transfer of traditionally learned chaînes opératoires in Spanish Levantine rock art. PMID:28207835

  2. Occupation and mental health in a national UK survey

    PubMed Central

    Rasul, F. R.; Head, J.; Singleton, N.

    2009-01-01

    Objectives To measure the prevalence of common mental disorder (CMD) by occupation in a representative sample of Great Britain and to identify occupations with increased and decreased risk of CMD. Methods A cross-sectional interview-based survey was carried out including 5,497 working male and female respondents, 16–64 years from a stratified random survey of private households in Britain. Occupations were classified by the Standard Occupational Classification (SOC) into four groups: major, sub-major, minor and constituent unit groups. Common Mental Disorder was measured by the Revised Clinical Interview Schedule. Results Major SOC groups with higher prevalence of common mental disorder included clerical and secretarial, sales, and personal and protective services whereas craft and related, ‘other’ professional occupations and plant and machine operatives had lower prevalence compared to 13% overall prevalence in all adults. In sub-major SOC groups managers and administrators, teaching professionals, clerical and secretarial, ‘other’ sales and personal service occupations had higher prevalence whereas many professional and skilled occupations had lower prevalence. Specific SOC unit groups with higher prevalence included primary and secondary teachers, welfare community, youth workers, security staff, waiters, bar staff, nurse auxiliaries and care assistants. General managers in government and large organizations (OR = 2.79, 95% CI 1.41–5.54), managers in transport and storing (OR = 2.44, 95% CI 1.18–5.03), buyers and mobile sales persons (OR = 2.48, 95% CI 1.09–5.60), sales occupations (NES) (OR = 2.78, 95% CI 1.25–6.19) and clerks (NES) (OR = 2.71, 95% CI 1.59–4.61) had increased risk of common mental disorder relative to specialist managers adjusting for social and financial factors and physical ill-health. Conclusions Occupations with higher risk of common mental disorder may be typified by high levels of job demands, especially emotional demands and lack of job security. The reasons why occupations have low rates of common mental disorder are varied and may include high levels of job discretion, good job training and clearly defined job tasks. PMID:20033130

  3. Functional Comparison of Neuronal Cells Differentiated from Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells under Different Oxygen and Medium Conditions.

    PubMed

    Yamazaki, Kazuto; Fukushima, Kazuyuki; Sugawara, Michiko; Tabata, Yoshikuni; Imaizumi, Yoichi; Ishihara, Yasuharu; Ito, Masashi; Tsukahara, Kappei; Kohyama, Jun; Okano, Hideyuki

    2016-12-01

    Because neurons are difficult to obtain from humans, generating functional neurons from human induced pluripotent stem cells (hiPSCs) is important for establishing physiological or disease-relevant screening systems for drug discovery. To examine the culture conditions leading to efficient differentiation of functional neural cells, we investigated the effects of oxygen stress (2% or 20% O 2 ) and differentiation medium (DMEM/F12:Neurobasal-based [DN] or commercial [PhoenixSongs Biologicals; PS]) on the expression of genes related to neural differentiation, glutamate receptor function, and the formation of networks of neurons differentiated from hiPSCs (201B7) via long-term self-renewing neuroepithelial-like stem (lt-NES) cells. Expression of genes related to neural differentiation occurred more quickly in PS and/or 2% O 2 than in DN and/or 20% O 2 , resulting in high responsiveness of neural cells to glutamate, N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and ( S)-3,5-dihydroxyphenylglycine (an agonist for mGluR 1/5 ), as revealed by calcium imaging assays. NMDA receptors, AMPA receptors, mGluR 1 , and mGluR 5 were functionally validated by using the specific antagonists MK-801, NBQX, JNJ16259685, and 2-methyl-6-(phenylethynyl)-pyridine, respectively. Multielectrode array analysis showed that spontaneous firing occurred earlier in cells cultured in 2% O 2 than in 20% O 2 . Optimization of O 2 tension and culture medium for neural differentiation of hiPSCs can efficiently generate physiologically relevant cells for screening systems.

  4. Arginyltransferase ATE1 is targeted to the neuronal growth cones and regulates neurite outgrowth during brain development.

    PubMed

    Wang, Junling; Pavlyk, Iuliia; Vedula, Pavan; Sterling, Stephanie; Leu, N Adrian; Dong, Dawei W; Kashina, Anna

    2017-10-01

    Arginylation is an emerging protein modification mediated by arginyltransferase ATE1, shown to regulate embryogenesis and actin cytoskeleton, however its functions in different physiological systems are not well understood. Here we analyzed the role of ATE1 in brain development and neuronal growth by producing a conditional mouse knockout with Ate1 deletion in the nervous system driven by Nestin promoter (Nes-Ate1 mice). These mice were weaker than wild type, resulting in low postnatal survival rates, and had abnormalities in the brain that suggested defects in neuronal migration. Cultured Ate1 knockout neurons showed a reduction in the neurite outgrowth and the levels of doublecortin and F-actin in the growth cones. In wild type, ATE1 prominently localized to the growth cones, in addition to the cell bodies. Examination of the Ate1 mRNA sequence reveals the existence of putative zipcode-binding sequences involved in mRNA targeting to the cell periphery and local translation at the growth cones. Fluorescence in situ hybridization showed that Ate1 mRNA localized to the tips of the growth cones, likely due to zipcode-mediated targeting, and this localization coincided with spots of localization of arginylated β-actin, which disappeared in the presence of protein synthesis inhibitors. We propose that zipcode-mediated co-targeting of Ate1 and β-actin mRNA leads to localized co-translational arginylation of β-actin that drives the growth cone migration and neurite outgrowth. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Brain Targeted Intranasal Zaleplon Nano-emulsion: In-Vitro Characterization and Assessment of Gamma Aminobutyric Acid Levels in rabbits' Brain and Plasma at low and high Doses.

    PubMed

    Abd-Elrasheed, Eman; El-Helaly, Sara Nageeb; El-Ashmoony, Manal M; Salah, Salwa

    2017-11-30

    Zaleplon is a pyrazolopyrimidin derivative hypnotic drug indicated for the short-term management of insomnia. Zaleplon belongs to Class II drugs, according to the biopharmaceutical classification system (BCS), showing poor solubility and high permeability. It undergoes extensive first-pass hepatic metabolism after oral absorption, with only 30% of Zaleplon being systemically available. It is available in tablet form which is unable to overcome the previous problems. The aim of this study is to enhance solubility and bioavailability via utilizing nanotechnology in the formulation of intranasal Zaleplon nano-emulsion (ZP-NE) to bypass the barriers and deliver an effective therapy to the brain. Screening studies were carried out wherein the solubility of zaleplon in various oils, surfactants(S) and co-surfactants(CoS) were estimated. Pseudo-ternary phase diagrams were constructed and various nano-emulsion formulations were prepared. These formulations were subjected to thermodynamic stability, in-vitro characterization, histopathological studies and assessment of the gamma aminobutyric acid (GABA) level in plasma and brain in rabbits compared to the market product (Sleep aid®). Stable NEs were successfully developed with a particle size range of 44.57±3.351 to 136.90±1.62 nm. A NE composed of 10% Miglyol® 812, 40%Cremophor® RH40 40%Transcutol® HP and 10% water successfully enhanced the bioavailability and brain targeting in the rabbits, showing a three to four folds increase than the marketed product. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Enhanced effectiveness of tocotrienol-based nano-emulsified system for topical delivery against skin carcinomas.

    PubMed

    Pham, Jimmy; Nayel, Amy; Hoang, Christina; Elbayoumi, Tamer

    2016-06-01

    The potent anti-proliferative and pro-apoptotic actions of tocotrienols (T3) against cancer, but not normal tissues, have been hampered by their limited systemic bioavailabilty. Recent expansive development of diverse nanoemulsion (NE) vehicles emphasized their vast potential to improve the effective dosing of different clinical and experimental drugs of lipophilic nature, such as T3. The emphasis of the present work is to develop a pharmaceutically scalable, low-energy nano-emulsification approach for optimized incorporation of T3-rich palm oil (Tocomin®), possessing anticancer activity as a potential cutaneous delivery platform for adjunctive therapy of skin carcinomas, either alone or in combination with other chemotherapeutic agents. Different Tocomin®-NEs, obtained with different homogenization strategies, were screened based on physicochemical uniformity (droplet size, charge and polydispersity) and subjected to stress physical stability testing, along with chemical content analysis (≥90% Tocomin® - incorporation efficiency). Adopted hybrid nano-emulsification of Tocomin®, correlated with highest preservation of DPPH-radical scavenging capacity of active T3 in prototype formulation, Tocomin®-NE, which effectively permeated diffusion cell membranes 4-folds higher than propyleneglycol (PG)-admixed Tocomin® control. Against two different cell models of human cutaneous carcinoma, Tocomin®-hybrid NE demonstrated significantly stronger cytotoxic profiles (p ≤ 0.01), visible in both concentration- and time- dependent manners, with at least 5-folds lower IC50 values, compared to those estimated for the closest Tocomin®-control. The proposed hybrid nano-emulsified formulation of Tocomin® provides simple and stable delivery platform, for effective topical application against keratinocyte tumors.

  7. Night eating syndrome. Preliminary results.

    PubMed

    Mazzetti di Pietralata, M; Florentino, M T; Guidi, M; Leonardi, C

    2000-06-01

    Clinical aspects of the "night eating syndrome" (NES) are described. Recent studies, also referred to in the present report, have revealed certain triggering factors of this syndrome, but do not reveal the nature of the relationship between awakening and compulsory need for food. According to the psychodynamic interpretation, these subjects eat at night to replace dreaming, to which they offer strong resistance, whilst according to the psychobiological interpretation, motivational stimuli develop the irresistible and repeated desire for food. Within a post-rational cognitive theoretical model, the compulsion to food would be the mode through which subjects obtain a modified conscious state necessary to appease the suffering due to an experience of emptiness and incapacity. Psychological support associated with pharmacological treatment (benzodiazepine, gamma-hydroxybutyric acid) has been shown, in a personal series, to be effective both upon the sleep disorder and craving.

  8. Identification of essential sequences for cellular localization in the muscle-specific ubiquitin E3 ligase MAFbx/Atrogin 1.

    PubMed

    Julie, Lagirand-Cantaloube; Sabrina, Batonnet-Pichon; Marie-Pierre, Leibovitch; Leibovitch, Serge A

    2012-02-17

    In skeletal muscle atrophy, upregulation and nuclear accumulation of the Ubiquitin E3 ligase MAFbx is essential for accelerated muscle protein loss, but the nuclear/cytoplasmic shuttling of MAFbx is undefined. Here we found that MAFbx contains two functional nuclear localization signals (NLS). Mutation or deletion of only one NLS induced cytoplasmic localization of MAFbx. We identified a non-classical NES located in the leucine charged domain (LCD) of MAFbx, which is leptomycin B insensitive. We demonstrated that mutation (L169Q) in LLXXL motif of LCD suppressed cytoplasmic retention of MAFbx. Nucleocytoplasmic shuttling of MAFbx represents a novel mechanism for targeting its substrates and its cytosolic partners in muscle atrophy. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  9. Lumpy species coexistence arises robustly in fluctuating resource environments.

    PubMed

    Sakavara, Athanasia; Tsirtsis, George; Roelke, Daniel L; Mancy, Rebecca; Spatharis, Sofie

    2018-01-23

    The effect of life-history traits on resource competition outcomes is well understood in the context of a constant resource supply. However, almost all natural systems are subject to fluctuations of resources driven by cyclical processes such as seasonality and tidal hydrology. To understand community composition, it is therefore imperative to study the impact of resource fluctuations on interspecies competition. We adapted a well-established resource-competition model to show that fluctuations in inflow concentrations of two limiting resources lead to the survival of species in clumps along the trait axis, consistent with observations of "lumpy coexistence" [Scheffer M, van Nes EH (2006) Proc Natl Acad Sci USA 103:6230-6235]. A complex dynamic pattern in the available ambient resources arose very early in the self-organization process and dictated the locations of clumps along the trait axis by creating niches that promoted the growth of species with specific traits. This dynamic pattern emerged as the combined result of fluctuations in the inflow of resources and their consumption by the most competitive species that accumulated the bulk of biomass early in assemblage organization. Clumps emerged robustly across a range of periodicities, phase differences, and amplitudes. Given the ubiquity in the real world of asynchronous fluctuations of limiting resources, our findings imply that assemblage organization in clumps should be a common feature in nature. Copyright © 2018 the Author(s). Published by PNAS.

  10. Sea Surface Temperature Records Using Sr/Ca Ratios in a Siderastrea siderea Coral from SE Cuba

    NASA Astrophysics Data System (ADS)

    Fargher, H. A.; Hughen, K. A.; Ossolinski, J. E.; Bretos, F.; Siciliano, D.; Gonzalez, P.

    2015-12-01

    Sea surface temperature (SST) variability from Cuba remains relatively unknown compared to the rest of the Caribbean. Cuba sits near an inflection point in the spatial pattern of SST from the North Atlantic Oscillation (NAO), and long SST records from the region could reveal changes in the influence of this climate system through time. A Siderastrea siderea coral from the Jardínes de la Reina in southern Cuba was drilled to obtain a 220 year long archive of environmental change. The genus Siderastrea has not been extensively studied as an SST archive, yet Sr/Ca ratios in the Cuban core show a clear seasonal signal and strong correlation to instrumental SST data (r2 = 0.86 and 0.36 for monthly and interannual (winter season) timescales, respectively). Annual growth rates (linear extension) of the coral are observed to have a minor influence on Sr/Ca variability, but do not show a direct correlation to SST on timescales from annual to multidecadal. Sr/Ca measurements from the Cuban coral are used to reconstruct monthly and seasonal (winter, summer) SST extending back more than two centuries. Wintertime SST in southern Cuba is compared to other coral Sr/Ca records of winter-season SST from locations sensitive to the NAO in order to investigate the stationarity of the NAO SST 'fingerprint' through time.

  11. The formulation of a nasal nanoemulsion zaleplon in situ gel for the treatment of insomnia.

    PubMed

    Hosny, Khaled Mohamed; Banjar, Zainy Mohammed

    2013-08-01

    Zaleplon is a drug used for the treatment of insomnia and is available in tablet form; however, it has two major problems. First, the drug undergoes extensive first pass metabolism, resulting in only 30% bioavailability, and second, the drug has a poor aqueous solubility, which delays the onset of action. The objective of this study is to utilise nanotechnology to formulate zaleplon into a nasal in situ nanoemulsion gel (NEG) to provide a solution for the previously mentioned problems. The solubility of zaleplon in various oils, surfactants and co-surfactants was estimated. Pseudo-ternary phase diagrams were developed and various nanoemulsion (NE) formulations were prepared; these formulations were subjected to visual characterisation, thermodynamic stability study and droplet size and conductivity measurements. Carbopol 934 was used as an in situ gelling agent. The gel strength, pH, gelation time, in vitro release and ex vivo nasal permeation were determined. The pharmacokinetic study of the NEG was carried out in rabbits. Stable NEs were successfully developed with a droplet size range of 35 to 73 nm. A NEG composed of 15% Miglyol, 30% Labrasol and 10% PEG 200 successfully provided the maximum in vitro and ex vivo permeation and enhanced the bioavailability in the rabbits by eightfold, when compared with the marketed tablets. The nasal NEG is a promising novel formula for zaleplon that has higher nasal tissue permeability and enhanced systemic bioavailability.

  12. Dynamics of merging: post-merger mixing and relaxation of an Illustris galaxy

    NASA Astrophysics Data System (ADS)

    Young, Anthony M.; Williams, Liliya L. R.; Hjorth, Jens

    2018-02-01

    During the merger of two galaxies, the resulting system undergoes violent relaxation and seeks stable equilibrium. However, the details of this evolution are not fully understood. Using Illustris simulation, we probe two physically related processes, mixing and relaxation. Though the two are driven by the same dynamics—global time-varying potential for the energy, and torques caused by asymmetries for angular momentum—we measure them differently. We define mixing as the redistribution of energy and angular momentum between particles of the two merging galaxies. We assess the degree of mixing as the difference between the shapes of their energy distributions, N(E)s, and their angular momentum distributions, N(L2)s. We find that the difference is decreasing with time, indicating mixing. To measure relaxation, we compare N(E) of the newly merged system to N(E) of a theoretical prediction for relaxed collisionless systems, DARKexp, and witness the system becoming more relaxed, in the sense that N(E) approaches DARKexp N(E). Because the dynamics driving mixing and relaxation are the same, the timescale is similar for both. We measure two sequential timescales: a rapid, 1 Gyr phase after the initial merger, during which the difference in N(E) of the two merging halos decreases by ~ 80%, followed by a slow phase, when the difference decreases by ~ 50% over ~ 8.5 Gyrs. This is a direct measurement of the relaxation timescale. Our work also draws attention to the fact that when a galaxy has reached Jeans equilibrium it may not yet have reached a fully relaxed state given by DARKexp, in that it retains information about its past history. This manifests itself most strongly in stars being centrally concentrated. We argue that it is particularly difficult for stars, and other tightly bound particles, to mix because they have less time to be influenced by the fluctuating potential, even across multiple merger events.

  13. Habitat Suitability Index Models: Forster's tern (breeding) - Gulf and Atlantic coasts

    USGS Publications Warehouse

    Martin, Richard P.; Zwank, Phillip J.

    1987-01-01

    The nesting range of Forster's terns hosts three allopatric breeding populations. The first and most important breeding area, in terms of the number of nes t i ng pairs, includes the western guIf coas t from the Louisiana-Mississippi border to northern Tamaulipas, Mexico (American Ornithologists' Union [AOUJ 1983). In addition, small numbers of Forster's terns have nested in Mobile County, Alabama (Imhof 1976). Although this species has not been recorded nesting in Mississippi (J. Jackson, Mississippi State University, Starkville; pers. comm.), it is observed in the coastal regions of that State every summer, and several thousand nest in adjacent Louisiana (Portnoy 1977; Clapp et ale 1983). The two largest colonies of Forster's terns documented in the literature were both in Louisiana: one of 2,750 pairs in Lake Borgne on the Louisiana-Mississippi border and one of 2,263 pairs in Calcasieu Lake (Portnoy 1977).

  14. MicroRNA-432 contributes to dopamine cocktail and retinoic acid induced differentiation of human neuroblastoma cells by targeting NESTIN and RCOR1 genes.

    PubMed

    Das, Eashita; Bhattacharyya, Nitai Pada

    2014-05-02

    MicroRNA (miRNA) regulates expression of protein coding genes and has been implicated in diverse cellular processes including neuronal differentiation, cell growth and death. To identify the role of miRNA in neuronal differentiation, SH-SY5Y and IMR-32 cells were treated with dopamine cocktail and retinoic acid to induce differentiation. Detection of miRNAs in differentiated cells revealed that expression of many miRNAs was altered significantly. Among the altered miRNAs, human brain expressed miR-432 induced neurite projections, arrested cells in G0-G1, reduced cell proliferation and could significantly repress NESTIN/NES, RCOR1/COREST and MECP2. Our results reveal that miR-432 regulate neuronal differentiation of human neuroblastoma cells. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  15. Atmospheric boundary layer CO2 remote sensing with a direct detection LIDAR instrument based on a widely tunable optical parametric source.

    PubMed

    Cadiou, Erwan; Mammez, Dominique; Dherbecourt, Jean-Baptiste; Gorju, Guillaume; Pelon, Jacques; Melkonian, Jean-Michel; Godard, Antoine; Raybaut, Myriam

    2017-10-15

    We report on the capability of a direct detection differential absorption lidar (DIAL) for range resolved and integrated path (IPDIAL) remote sensing of CO 2 in the atmospheric boundary layer (ABL). The laser source is an amplified nested cavity optical parametric oscillator (NesCOPO) emitting approximately 8 mJ at the two measurement wavelengths selected near 2050 nm. Direct detection atmospheric measurements are taken from the ground using a 30 Hz frequency switching between emitted wavelengths. Results show that comparable precision measurements are achieved in DIAL and IPDIAL modes (not better than a few ppm) on high SNR targets such as near range ABL aerosol and clouds, respectively. Instrumental limitations are analyzed and degradation due to cloud scattering variability is discussed to explain observed DIAL and IPDIAL limitations.

  16. A Spectroscopic Study of the High-Latitude Far Evolved Star V534 Lyr

    NASA Astrophysics Data System (ADS)

    Sendzikas, E. G.; Chentsov, E. L.

    2017-06-01

    We study a pulsating variable post-AGB star V534 Lyr = HD172324 based on five high resolution spectra (R=60000) obtained with the NES echelle spectrograph of the 6-meter Russian telescope (BTA) in 2010 and 2013. Using the atmosphere modeling method and the Kurucz model set, we obtained the effective temperature Teff=10500 K, surface gravity log g=2.5, and microturbulent velocity ξt=4.0 km/s. The underabundance of the iron group elements [Met/H]⊙ = -0.50 was detected. This fact in combination with high spatial velocity indicates that V534 Lyr does not belong to the disk population. The radial velocity gradient in the V534 Lyr atmosphere is minimum: differential shifts of lines are close to measurement errors. The spectral class A0 Iab corresponds to the distance to V534 Lyr, d≍6 kpc.

  17. Evidence for a jacketed nematic polymer

    NASA Astrophysics Data System (ADS)

    Hardouin, F.; Mery, S.; Achard, M. F.; Noirez, L.; Keller, P.

    1991-05-01

    The evidence for a “jacketed” structure at the scale of the chain dimensions in the nematic phase of a “side-on fixed” liquid crystal polysiloxane is reported by using small angle neutron scattering. We relate this anisotropy of chain conformation to the first measurements of the rotational viscosity coefficient in this new type of liquid crystal side-chain polymer. Par des mesures de diffusion des neutrons aux petits angles nous montrons l'existence, pour un polysiloxane “ en haltère ”, d'une structure “ chemisée ” à l'échelle de l'organisation global d'une chaîne en phase nématique. On constate que cette anisotropie de forme du polymère a des conséquences sur l'évolution du coefficient de viscosité de torsion mesuré pour la première fois dans ce nouveau type de polymère à chaînes latérales.

  18. Phelps-Collins, Alpena, Michigan. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1982-05-19

    1.1’ , 9 .95 5 4 3, q9I . Y . I’ 65 0 33O . 10 J 5+/ 55 1, .z 1. o0’ .5j . 36. 1.7 .4 4 8 48 45. 20 ’ 4/ 53 .1 1.3u . obi 610 4, .o .21 42, 4 so8...W I _ __4 I TOTA 0 _ _ _ 1_ _ _ _ _ LO PAC_ -UL 040-S 10 l 48 D ON L S T A UL O TH N I-Ai I L G, AC /i "-A- SURFACE WINDS PERCENTAGE FREQUENCY OF...3.27 M 33 24.46 41.-y 48 -55 It" % WIND NNE .4- led ob . 8 ___ ___ 4.6 NEs .4 .7 s1 .6 lea_ 6__ .? 7.9 Id *~ b .7 *2 .2ob_ _________ 1.8 6.7 ISE .5 IOU .9

  19. KSC-04PD-1993

    NASA Technical Reports Server (NTRS)

    2004-01-01

    KENNEDY SPACE CENTER, FLA. Julian Earls (left), a school board member of Ronald E. McNair High School in Atlanta, and Sarah Copelin-Wood (far left), chair of the Board of Education, sign a Memorandum of Understanding after a presentation by KSC Deputy Director Dr. Woodrow Whitlow Jr., astronaut Leland Melvin and Dr. Julian Earls, director of NASA Glenn Research Center. McNair is a NASA Explorer School (NES). Whitlow visited the school to share the vision for space exploration with the next generation of explorers. He talked with students about our destiny as explorers, NASAs stepping stone approach to exploring Earth, the Moon, Mars and beyond, how space impacts our lives, and how people and machines rely on each other in space. Dr. Earls discussed the future and the vision for space, plus the NASA careers needed to meet the vision. Melvin talked about the importance of teamwork and what it takes for mission success.

  20. Mécanismes de la non-stœchiométrie dans les nouveaux supraconducteurs à haute Tboldmath_c

    NASA Astrophysics Data System (ADS)

    Hervieu, M.; Michel, C.; Martin, C.; Huvé, M.; van Tendeloo, G.; Maignan, A.; Pelloquin, D.; Goutenoire, F.; Raveau, B.

    1994-11-01

    Two new families of high T_c superconductors have been recently discovered : ll the mercury based oxides gg and the ll oxycarbonates gg. The main characteristics of the structural mechanisms were studied by high resolution electron microscopy. This paper deals with the description of the numerous order-disorder phenomena which have been observed on the cation and anion networks. Deux nouvelles familles de supraconducteurs ont récemment vu le jour : ll les oxydes à base de mercure gg et les ll oxycarbonates gg. Les caractéristiques essentielles des mécanismes structuraux ont été étudiées par microscopie électronique haute résolution. Les nombreux phénomènes ordre-désordre observés tant sur le réseau des cations que sur celui des anions sont exposés.

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