Sample records for atf harmonic generation

  1. Inheritance of stress-induced, ATF-2-dependent epigenetic change.

    PubMed

    Seong, Ki-Hyeon; Li, Dong; Shimizu, Hideyuki; Nakamura, Ryoichi; Ishii, Shunsuke

    2011-06-24

    Atf1, the fission yeast homolog of activation transcription factor-2 (ATF-2), contributes to heterochromatin formation. However, the role of ATF-2 in chromatin assembly in higher organisms remains unknown. This study reveals that Drosophila ATF-2 (dATF-2) is required for heterochromatin assembly, whereas the stress-induced phosphorylation of dATF-2, via Mekk1-p38, disrupts heterochromatin. The dATF-2 protein colocalized with HP1, not only on heterochromatin but also at specific loci in euchromatin. Heat shock or osmotic stress induced phosphorylation of dATF-2 and resulted in its release from heterochromatin. This heterochromatic disruption was an epigenetic event that was transmitted to the next generation in a non-Mendelian fashion. When embryos were exposed to heat stress over multiple generations, the defective chromatin state was maintained over multiple successive generations, though it gradually returned to the normal state. The results suggest a mechanism by which the effects of stress are inherited epigenetically via the regulation of a tight chromatin structure. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. EWS/ATF1 expression induces sarcomas from neural crest–derived cells in mice

    PubMed Central

    Yamada, Kazunari; Ohno, Takatoshi; Aoki, Hitomi; Semi, Katsunori; Watanabe, Akira; Moritake, Hiroshi; Shiozawa, Shunichi; Kunisada, Takahiro; Kobayashi, Yukiko; Toguchida, Junya; Shimizu, Katsuji; Hara, Akira; Yamada, Yasuhiro

    2013-01-01

    Clear cell sarcoma (CCS) is an aggressive soft tissue malignant tumor characterized by a unique t(12;22) translocation that leads to the expression of a chimeric EWS/ATF1 fusion gene. However, little is known about the mechanisms underlying the involvement of EWS/ATF1 in CCS development. In addition, the cellular origins of CCS have not been determined. Here, we generated EWS/ATF1-inducible mice and examined the effects of EWS/ATF1 expression in adult somatic cells. We found that forced expression of EWS/ATF1 resulted in the development of EWS/ATF1-dependent sarcomas in mice. The histology of EWS/ATF1-induced sarcomas resembled that of CCS, and EWS/ATF1-induced tumor cells expressed CCS markers, including S100, SOX10, and MITF. Lineage-tracing experiments indicated that neural crest–derived cells were subject to EWS/ATF1-driven transformation. EWS/ATF1 directly induced Fos in an ERK-independent manner. Treatment of human and EWS/ATF1-induced CCS tumor cells with FOS-targeted siRNA attenuated proliferation. These findings demonstrated that FOS mediates the growth of EWS/ATF1-associated sarcomas and suggest that FOS is a potential therapeutic target in human CCS. PMID:23281395

  3. Mixed-Mode Slip Behavior of the Altotiberina Low-Angle Normal Fault System (Northern Apennines, Italy) through High-Resolution Earthquake Locations and Repeating Events

    NASA Astrophysics Data System (ADS)

    Valoroso, Luisa; Chiaraluce, Lauro; Di Stefano, Raffaele; Monachesi, Giancarlo

    2017-12-01

    We generated a 4.5-year-long (2010-2014) high-resolution earthquake catalogue, composed of 37,000 events with ML < 3.9 and MC = 0.5 completeness magnitude, to report on the seismic activity of the Altotiberina (ATF) low-angle normal fault system and to shed light on the mechanical behavior and seismic potential of this fault, which is capable of generating a M7 event. Seismicity defines the geometry of the fault system composed of the low-angle (15°-20°) ATF, extending for 50 km along strike and between 4 and 16 km at depth showing an 1.5 km thick fault zone made of multiple subparallel slipping planes, and a complex network of synthetic/antithetic higher-angle segments located in the ATF hanging wall (HW) that can be traced along strike for up to 35 km. Ninety percent of the recorded seismicity occurs along the high-angle HW faults during a series of minor, sometimes long-lasting (months) seismic sequences with multiple MW3+ mainshocks. Remaining earthquakes (ML < 2.4) are released instead along the low-angle ATF at a constant rate of 2.2 events per day. Within the ATF-related seismicity, we found 97 clusters of repeating earthquakes (RE), mostly consisting of doublets occurring during short interevent time (hours). RE are located within the geodetically recognized creeping portions of the ATF, around the main locked asperity. The rate of occurrence of RE seems quite synchronous with the ATF-HW seismic release, suggesting that creeping may guide the strain partitioning in the ATF system. The seismic moment released by the ATF seismicity accounts for 30% of the geodetic one, implying aseismic deformation. The ATF-seismicity pattern is thus consistent with a mixed-mode (seismic and aseismic) slip behavior.

  4. Submission of FeCrAl Feedstock for Support of AFC ATR-2 Irradiations

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

    Field, Kevin G.; Barrett, Kristine E.; Sun, Zhiqian

    The Advanced Test Reactor (ATR) is currently being used to test accident tolerant fuel (ATF) forms destined for commercial nuclear power plant deployment. One irradiation program using the ATR for ATF concepts, Accident Tolerant Fuel-2 (ATF-2), is a water loop irradiation test using miniaturized fuel pins as test articles. This complicated testing configuration requires a series of pre-test experiments and verification including a flowing loop autoclave test and a sensor qualification test (SQT) prior to full test train deployment within the ATR. In support of the ATF-2 irradiation program, Oak Ridge National Laboratory (ORNL) has supplied two different Generation IImore » FeCrAl alloys in rod stock form to Idaho National Laboratory (INL). These rods will be machined into dummy pins for deployment in the autoclave test and SQT. Post-test analysis of the dummy pins will provide initial insight into the performance of Generation II FeCrAl alloys in the ATF-2 irradiation experiment as well as within a commercial nuclear reactor.« less

  5. ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation

    PubMed Central

    Shan, Yuexin; Akram, Ali; Amatullah, Hajera; Zhou, Dun Yuan; Gali, Patricia L.; Maron-Gutierrez, Tatiana; González-López, Adrian; Zhou, Louis; Rocco, Patricia R.M.; Hwang, David; Albaiceta, Guillermo M.; Haitsma, Jack J.

    2015-01-01

    Abstract Aims: Ventilator-induced lung injury (VILI) contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). Absence of activating transcription factor 3 (ATF3) confers susceptibility to ALI/VILI. To identify cell-specific ATF3-dependent mechanisms of susceptibility to ALI/VILI, we generated ATF3 chimera by adoptive bone marrow (BM) transfer and randomized to inhaled saline or lipopolysacharide (LPS) in the presence of mechanical ventilation (MV). Adenovirus vectors to silence or overexpress ATF3 were used in primary human bronchial epithelial cells and murine BM-derived macrophages from wild-type or ATF3-deficient mice. Results: Absence of ATF3 in myeloid-derived cells caused increased pulmonary cellular infiltration. In contrast, absence of ATF3 in parenchymal cells resulted in loss of alveolar-capillary membrane integrity and increased exudative edema. ATF3-deficient macrophages were unable to limit the expression of pro-inflammatory mediators. Knockdown of ATF3 in resident cells resulted in decreased junctional protein expression and increased paracellular leak. ATF3 overexpression abrogated LPS induced membrane permeability. Despite release of ATF3-dependent Nrf2 transcriptional inhibition, mice that lacked ATF3 expression in resident cells had increased Nrf2 protein degradation. Innovation: In our model, in the absence of ATF3 in parenchymal cells increased Nrf2 degradation is the result of increased Keap-1 expression and loss of DJ-1 (Parkinson disease [autosomal recessive, early onset] 7), previously not known to play a role in lung injury. Conclusion: Results suggest that ATF3 confers protection to lung injury by preventing inflammatory cell recruitment and barrier disruption in a cell-specific manner, opening novel opportunities for cell specific therapy for ALI/VILI. Antioxid. Redox Signal. 22, 651–668. PMID:25401197

  6. The artificial gene Jazz, a transcriptional regulator of utrophin, corrects the dystrophic pathology in mdx mice.

    PubMed

    Di Certo, Maria Grazia; Corbi, Nicoletta; Strimpakos, Georgios; Onori, Annalisa; Luvisetto, Siro; Severini, Cinzia; Guglielmotti, Angelo; Batassa, Enrico Maria; Pisani, Cinzia; Floridi, Aristide; Benassi, Barbara; Fanciulli, Maurizio; Magrelli, Armando; Mattei, Elisabetta; Passananti, Claudio

    2010-03-01

    The absence of the cytoskeletal protein dystrophin results in Duchenne muscular dystrophy (DMD). The utrophin protein is the best candidate for dystrophin replacement in DMD patients. To obtain therapeutic levels of utrophin expression in dystrophic muscle, we developed an alternative strategy based on the use of artificial zinc finger transcription factors (ZF ATFs). The ZF ATF 'Jazz' was recently engineered and tested in vivo by generating a transgenic mouse specifically expressing Jazz at the muscular level. To validate the ZF ATF technology for DMD treatment we generated a second mouse model by crossing Jazz-transgenic mice with dystrophin-deficient mdx mice. Here, we show that the artificial Jazz protein restores sarcolemmal integrity and prevents the development of the dystrophic disease in mdx mice. This exclusive animal model establishes the notion that utrophin-based therapy for DMD can be efficiently developed using ZF ATF technology and candidates Jazz as a novel therapeutic molecule for DMD therapy.

  7. Receptor-Targeted Nanoparticles for In Vivo Imaging of Breast Cancer

    PubMed Central

    Yang, Lily; Peng, Xiang-Hong; Wang, Y. Andrew; Wang, Xiaoxia; Cao, Zehong; Ni, Chunchun; Karna, Prasanthi; Zhang, Xinjian; Wood, William C.; Gao, Xiaohu; Nie, Shuming; Mao, Hui

    2009-01-01

    Purpose Cell surface receptor-targeted magnetic iron oxide (IO) nanoparticles provide molecular magnetic resonance imaging (MRI) contrast agents for improving specificity of the detection of human cancer. Experimental design The present study reports the development of a novel targeted IO nanoparticle using a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator conjugated to IO nanoparticles (ATF-IO). This nanoparticle targets urokinase plasminogen activator receptor (uPAR), which is overexpressed in breast cancer tissues. Results ATF-IO nanoparticles are able to specifically bind to and be internalized by uPAR-expressing tumor cells. Systemic delivery of ATF-IO nanoparticles into mice bearing subcutaneous and intraperitoneal mammary tumors leads to the accumulation of the particles in tumors, generating a strong MRI contrast detectable by a clinical MRI scanner at a field strength of 3 Tesla. Target specificity of ATF-IO nanoparticles demonstrated by in vivo MRI is further confirmed by near infrared (NIR) fluorescence imaging of the mammary tumors using NIR dye-labeled ATF peptides conjugated to IO nanoparticles. Furthermore, mice administered ATF-IO nanoparticles exhibit lower uptake of the particles in the liver and spleen compared to those receiving non-targeted IO nanoparticles. Conclusions Our results suggest that uPAR-targeted ATF-IO nanoparticles have potential as molecularly-targeted, dual modality imaging agents for in vivo imaging of breast cancer. PMID:19584158

  8. Convective Heat Transfer Coefficients of Automatic Transmission Fluid Jets with Implications for Electric Machine Thermal Management: Preprint

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

    Bennion, Kevin; Moreno, Gilberto

    2015-09-29

    Thermal management for electric machines (motors/ generators) is important as the automotive industry continues to transition to more electrically dominant vehicle propulsion systems. Cooling of the electric machine(s) in some electric vehicle traction drive applications is accomplished by impinging automatic transmission fluid (ATF) jets onto the machine's copper windings. In this study, we provide the results of experiments characterizing the thermal performance of ATF jets on surfaces representative of windings, using Ford's Mercon LV ATF. Experiments were carried out at various ATF temperatures and jet velocities to quantify the influence of these parameters on heat transfer coefficients. Fluid temperatures weremore » varied from 50 degrees C to 90 degrees C to encompass potential operating temperatures within an automotive transaxle environment. The jet nozzle velocities were varied from 0.5 to 10 m/s. The experimental ATF heat transfer coefficient results provided in this report are a useful resource for understanding factors that influence the performance of ATF-based cooling systems for electric machines.« less

  9. Genome interrogation for novel salinity tolerant Arabidopsis mutants.

    PubMed

    van Tol, Niels; Pinas, Johan; Schat, Henk; Hooykaas, Paul J J; van der Zaal, Bert J

    2016-12-01

    Soil salinity is becoming an increasingly large problem in agriculture. In this study, we have investigated whether a capacity to withstand salinity can be induced in the salinity sensitive plant species Arabidopsis thaliana, and whether it can be maintained in subsequent generations. To this end, we have used zinc finger artificial transcription factor (ZF-ATFs) mediated genome interrogation. Already within a relatively small collection Arabidopsis lines expressing ZF-ATFs, we found 41 lines that were tolerant to 100 mM NaCl. Furthermore, ZF-ATF encoding gene constructs rescued from the most strongly salinity tolerant lines were indeed found to act as dominant and heritable agents for salinity tolerance. Altogether, our data provide evidence that a silent capacity to withstand normally lethal levels of salinity exists in Arabidopsis and can be evoked relatively easily by in trans acting transcription factors like ZF-ATFs. © 2016 John Wiley & Sons Ltd.

  10. ATTO SECOND ELECTRON BEAMS GENERATION AND CHARACTERIZATION EXPERIMENT AT THE ACCELERATOR TEST FACILITY.

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

    ZOLOTOREV, M.; ZHOLENTS, A.; WANG, X.J.

    2002-02-01

    We are proposing an Atto-second electron beam generation and diagnostics experiment at the Brookhaven Accelerator Test facility (ATF) using 1 {micro}m Inverse Free Electron Laser (IFEL). The proposed experiment will be carried out by an BNL/LBNL collaboration, and it will be installed at the ATF beam line II. The proposed experiment will employ a one-meter long undulator with 1.8 cm period (VISA undulator). The electron beam energy will be 63 MeV with emittance less than 2 mm-mrad and energy spread less than 0.05%. The ATF photocathode injector driving laser will be used for energy modulation by Inverse Free Electron Lasermore » (IFEL). With 10 MW laser peak power, about 2% total energy modulation is expected. The energy modulated electron beam will be further bunched through either a drift space or a three magnet chicane into atto-second electron bunches. The attosecond electron beam bunches will be analyzed using the coherent transition radiation (CTR).« less

  11. Molecular pathway of near-infrared laser phototoxicity involves ATF-4 orchestrated ER stress

    PubMed Central

    Khan, Imran; Tang, Elieza; Arany, Praveen

    2015-01-01

    High power lasers are used extensively in medicine while lower power applications are popular for optical imaging, optogenetics, skin rejuvenation and a therapeutic modality termed photobiomodulation (PBM). This study addresses the therapeutic dose limits, biological safety and molecular pathway of near-infrared (NIR) laser phototoxicity. Increased erythema and tissue damage were noted in mice skin and cytotoxicity in cell cultures at phototoxic laser doses involving generation of reactive oxygen species (ROS) coupled with a rise in surface temperature (>45 °C). NIR laser phototoxicity results from Activating Transcription Factor-4 (ATF-4) mediated endoplasmic reticulum stress and autophagy. Neutralizations of heat or ROS and overexpressing ATF-4 were noted to rescue NIR laser phototoxicity. Further, NIR laser mediated phototoxicity was noted to be non-genotoxic and non-mutagenic. This study outlines the mechanism of NIR laser phototoxicity and the utility of monitoring surface temperature and ATF4 expression as potential biomarkers to develop safe and effective clinical applications. PMID:26030745

  12. Molecular pathway of near-infrared laser phototoxicity involves ATF-4 orchestrated ER stress.

    PubMed

    Khan, Imran; Tang, Elieza; Arany, Praveen

    2015-06-01

    High power lasers are used extensively in medicine while lower power applications are popular for optical imaging, optogenetics, skin rejuvenation and a therapeutic modality termed photobiomodulation (PBM). This study addresses the therapeutic dose limits, biological safety and molecular pathway of near-infrared (NIR) laser phototoxicity. Increased erythema and tissue damage were noted in mice skin and cytotoxicity in cell cultures at phototoxic laser doses involving generation of reactive oxygen species (ROS) coupled with a rise in surface temperature (>45 °C). NIR laser phototoxicity results from Activating Transcription Factor-4 (ATF-4) mediated endoplasmic reticulum stress and autophagy. Neutralizations of heat or ROS and overexpressing ATF-4 were noted to rescue NIR laser phototoxicity. Further, NIR laser mediated phototoxicity was noted to be non-genotoxic and non-mutagenic. This study outlines the mechanism of NIR laser phototoxicity and the utility of monitoring surface temperature and ATF4 expression as potential biomarkers to develop safe and effective clinical applications.

  13. Steam Oxidation of FeCrAl and SiC in the Severe Accident Test Station (SATS)

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

    Pint, Bruce A.; Unocic, Kinga A.; Terrani, Kurt A.

    2015-08-01

    Numerous research projects are directed towards developing accident tolerant fuel (ATF) concepts that will enhance safety margins in light water reactors (LWR) during severe accident scenarios. In the U.S. program, the high temperature steam oxidation performance of ATF solutions has been evaluated in the Severe Accident Test Station (SATS) at Oak Ridge National Laboratory (ORNL) since 2012 [1-3] and this facility continues to support those efforts in the ATF community. Compared to the current UO2/Zr-based alloy fuel system, alternative cladding materials can offer slower oxidation kinetics and a smaller enthalpy of oxidation that can significantly reduce the rate of heatmore » and hydrogen generation in the core during a coolant-limited severe accident [4-5]. Thus, steam oxidation behavior is a key aspect of the evaluation of ATF concepts. This report summarizes recent work to measure steam oxidation kinetics of FeCrAl and SiC specimens in the SATS.« less

  14. Targeting Serous Epithelial Ovarian Cancer with Designer Zinc Finger Transcription Factors*

    PubMed Central

    Lara, Haydee; Wang, Yuhua; Beltran, Adriana S.; Juárez-Moreno, Karla; Yuan, Xinni; Kato, Sumie; Leisewitz, Andrea V.; Cuello Fredes, Mauricio; Licea, Alexei F.; Connolly, Denise C.; Huang, Leaf; Blancafort, Pilar

    2012-01-01

    Ovarian cancer is the leading cause of death among gynecological malignancies. It is detected at late stages when the disease is spread through the abdominal cavity in a condition known as peritoneal carcinomatosis. Thus, there is an urgent need to develop novel therapeutic interventions to target advanced stages of ovarian cancer. Mammary serine protease inhibitor (Maspin) represents an important metastasis suppressor initially identified in breast cancer. Herein we have generated a sequence-specific zinc finger artificial transcription factor (ATF) to up-regulate the Maspin promoter in aggressive ovarian cancer cell lines and to interrogate the therapeutic potential of Maspin in ovarian cancer. We found that although Maspin was expressed in some primary ovarian tumors, the promoter was epigenetically silenced in cell lines derived from ascites. Transduction of the ATF in MOVCAR 5009 cells derived from ascitic cultures of a TgMISIIR-TAg mouse model of ovarian cancer resulted in tumor cell growth inhibition, impaired cell invasion, and severe disruption of actin cytoskeleton. Systemic delivery of lipid-protamine-RNA nanoparticles encapsulating a chemically modified ATF mRNA resulted in inhibition of ovarian cancer cell growth in nude mice accompanied with Maspin re-expression in the treated tumors. Gene expression microarrays of ATF-transduced cells revealed an exceptional specificity for the Maspin promoter. These analyses identified novel targets co-regulated with Maspin in human short-term cultures derived from ascites, such as TSPAN12, that could mediate the anti-metastatic phenotype of the ATF. Our work outlined the first targeted, non-viral delivery of ATFs into tumors with potential clinical applications for metastatic ovarian cancers. PMID:22782891

  15. ATF3 represses PPARγ expression and inhibits adipocyte differentiation

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

    Jang, Min-Kyung; Jung, Myeong Ho, E-mail: jung0603@pusan.ac.kr

    Highlights: • ATF3 decrease the expression of PPARγ and its target gene in 3T3-L1 adipocytes. • ATF3 represses the promoter activity of PPARγ2 gene. • ATF/CRE (−1537/−1530) is critical for ATF3-mediated downregulation of PPARγ. • ATF3 binds to the promoter region containing the ATF/CRE. • ER stress inhibits adipocyte differentiation through downregulation of PPARγ by ATF3. - Abstract: Activating transcription factor 3 (ATF3) is a stress-adaptive transcription factor that mediates cellular stress response signaling. We previously reported that ATF3 represses CCAAT/enhancer binding protein α (C/EBPα) expression and inhibits 3T3-L1 adipocyte differentiation. In this study, we explored potential role of ATF3more » in negatively regulating peroxisome proliferator activated receptor-γ (PPARγ). ATF3 decreased the expression of PPARγ and its target gene in 3T3-L1 adipocytes. ATF3 also repressed the activity of −2.6 Kb promoter of mouse PPARγ2. Overexpression of PPARγ significantly prevented the ATF3-mediated inhibition of 3T3-L1 differentiation. Transfection studies with 5′ deleted-reporters showed that ATF3 repressed the activity of −2037 bp promoter, whereas it did not affect the activity of −1458 bp promoter, suggesting that ATF3 responsive element is located between the −2037 and −1458. An electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that ATF3 binds to ATF/CRE site (5′-TGACGTTT-3′) between −1537 and −1530. Mutation of the ATF/CRE site abrogated ATF3-mediated transrepression of the PPARγ2 promoter. Treatment with thapsigargin, endoplasmic reticulum (ER) stress inducer, increased ATF3 expression, whereas it decreased PPARγ expression. ATF3 knockdown significantly blocked the thapsigargin-mediated downregulation of PPARγ expression. Furthermore, overexpression of PPARγ prevented inhibition of 3T3-L1 differentiation by thapsigargin. Collectively, these results suggest that ATF3-mediated inhibition of PPARγ expression may contribute to inhibition of adipocyte differentiation during cellular stress including ER stress.« less

  16. In vacuum diamond sensor scanner for beam halo measurements in the beam line at the KEK Accelerator Test Facility

    NASA Astrophysics Data System (ADS)

    Liu, S.; Bogard, F.; Cornebise, P.; Faus-Golfe, A.; Fuster-Martínez, N.; Griesmayer, E.; Guler, H.; Kubytskyi, V.; Sylvia, C.; Tauchi, T.; Terunuma, N.; Bambade, P.

    2016-10-01

    The investigation of beam halo transverse distributions is important for the understanding of beam losses and the control of backgrounds in Future Linear Colliders (FLC). A novel in vacuum diamond sensor (DSv) scanner with four strips has been designed and developed for the investigation of the beam halo transverse distributions and also for the diagnostics of Compton recoil electrons after the interaction point (IP) of ATF2, a low energy (1.3 GeV) prototype of the final focus system for the ILC and CLIC linear collider projects. Using the DSv, a dynamic range of ∼106 has been successfully demonstrated and confirmed for the first time in simultaneous beam core (∼109 electrons) and beam halo (∼103 electrons) measurements at ATF2. This report presents the characterization, performance studies and tests of diamond sensors using an α source, as well as using the electron beams at PHIL, a low energy < 5 MeV photo-injector at LAL, and at ATF2. First beam halo measurement results using the DSv at ATF2 with different beam intensities and vacuum levels are also presented. Such measurements not only allow one to evaluate the different sources of beam halo generation but also to define the requirements for a suitable collimation system to be installed at ATF2, as well as to optimize its performance during future operation.

  17. Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway.

    PubMed

    Fan, Zhigang; Duan, Xiaoyi; Cai, Hui; Wang, Li; Li, Min; Qu, Jingkun; Li, Wanjun; Wang, Yongheng; Wang, Jiansheng

    2015-08-01

    Invasion and metastasis are the major causes of tumor-related mortality in lung cancer. It is believed that curcumin is an effective drug possessing anti-invasive and anti-metastatic activities in the treatment of cancer. However, the specific mechanisms remain unclear. In the present study, we investigated whether the PKCα/Nox-2/ATF-2/MMP-9 signaling pathway is involved in the invasive behavior of lung cancer and whether curcumin could inhibit invasion by modulating this pathway. The cytotoxic effect of curcumin was evaluated by MTT assay and the capacity of invasion was assessed by Transwell assay. siRNA and plasmid transfection techniques were used to study the function of targeted genes. Real-time PCR and western blot analysis were used to evaluate the expression levels of PKCα, Nox-2, MMP-9 and the phosphorylation of ATF-2. The results showed that curcumin inhibited the proliferation and invasion of A549 cells in a dose-dependent manner. Overexpression of MMP-9 enhanced the invasion of A549 cells. However, inhibition of MMP-9 by siRNA or curcumin suppressed cell invasion. Moreover, we also demonstrated the catalytic role of PKCα in expression of MMP-9 and cellular invasion in A549 cells, which was dependent on the expression of Nox-2 and phosphorylation of ATF-2. Finally, we also showed that curcumin dose-dependently reduced the expression of PKCα, P47phox, Nox-2 and phosphorylated ATF-2, as well as intracellular ROS generation, suggesting the inhibitory effect of curcumin on the activation of the PKCα/Nox-2/ROS/ATF-2 pathway. In conclusion, the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway is activated in lung cancer A549 cells, which could be modulated by curcumin to inhibit cell invasiveness.

  18. Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

    PubMed Central

    Umemura, Mariko; Ogura, Tae; Matsuzaki, Ayako; Nakano, Haruo; Takao, Keizo; Miyakawa, Tsuyoshi; Takahashi, Yuji

    2017-01-01

    Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/-) mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders. PMID:28744205

  19. The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43.

    PubMed

    Hurst, H C; Masson, N; Jones, N C; Lee, K A

    1990-12-01

    Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We demonstrated that CREB and ATF-47 are identical and that CREB and ATF-43 form protein-protein complexes. We also found that the cis requirements for stable DNA binding by ATF-43 and CREB are different. Using antibodies to ATF-43 we have identified a group of polypeptides (ATF-43) in the size range from 40 to 43 kDa. ATF-43 polypeptides are related by their reactivity with anti-ATF-43, DNA-binding specificity, complex formation with CREB, heat stability, and phosphorylation by protein kinase A. Certain cell types vary in their ATF-43 complement, suggesting that CREB activity is modulated in a cell-type-specific manner through interaction with ATF-43. ATF-43 polypeptides do not appear simply to correspond to the gene products of the ATF multigene family, suggesting that the size of the ATF family at the protein level is even larger than predicted from cDNA-cloning studies.

  20. Expression Levels of the Yeast Alcohol Acetyltransferase Genes ATF1, Lg-ATF1, and ATF2 Control the Formation of a Broad Range of Volatile Esters

    PubMed Central

    Verstrepen, Kevin J.; Van Laere, Stijn D. M.; Vanderhaegen, Bart M. P.; Derdelinckx, Guy; Dufour, Jean-Pierre; Pretorius, Isak S.; Winderickx, Joris; Thevelein, Johan M.; Delvaux, Freddy R.

    2003-01-01

    Volatile aroma-active esters are responsible for the fruity character of fermented alcoholic beverages such as beer and wine. Esters are produced by fermenting yeast cells in an enzyme-catalyzed intracellular reaction. In order to investigate and compare the roles of the known Saccharomyces cerevisiae alcohol acetyltransferases, Atf1p, Atf2p and Lg-Atf1p, in volatile ester production, the respective genes were either deleted or overexpressed in a laboratory strain and a commercial brewing strain. Subsequently, the ester formation of the transformants was monitored by headspace gas chromatography and gas chromatography combined with mass spectroscopy (GC-MS). Analysis of the fermentation products confirmed that the expression levels of ATF1 and ATF2 greatly affect the production of ethyl acetate and isoamyl acetate. GC-MS analysis revealed that Atf1p and Atf2p are also responsible for the formation of a broad range of less volatile esters, such as propyl acetate, isobutyl acetate, pentyl acetate, hexyl acetate, heptyl acetate, octyl acetate, and phenyl ethyl acetate. With respect to the esters analyzed in this study, Atf2p seemed to play only a minor role compared to Atf1p. The atf1Δ atf2Δ double deletion strain did not form any isoamyl acetate, showing that together, Atf1p and Atf2p are responsible for the total cellular isoamyl alcohol acetyltransferase activity. However, the double deletion strain still produced considerable amounts of certain other esters, such as ethyl acetate (50% of the wild-type strain), propyl acetate (50%), and isobutyl acetate (40%), which provides evidence for the existence of additional, as-yet-unknown ester synthases in the yeast proteome. Interestingly, overexpression of different alleles of ATF1 and ATF2 led to different ester production rates, indicating that differences in the aroma profiles of yeast strains may be partially due to mutations in their ATF genes. PMID:12957907

  1. Auxiliary Salvage Tow and Rescue: T-STAR

    DTIC Science & Technology

    2011-08-01

    These agencies also operate four ships of the T-ATF class (Fleet Ocean Tug): Catawba (T-ATF 168), Navajo (T-ATF 169), Sioux (T-ATF 171), and Apache (T...Ocean Tug): CATAWBA (T-ATF 168), NAVAJO (T-ATF 169), SIOUX (T-ATF 171), and APACHE (T-ATF 172). These ships were commissioned during the 1980’s and...Bottles 1 0.6 Portable HP Air Plant 10’x18’x10’ 1 40.2 200 Amp Welder 2 0.4 Power Pack Unit 1 8.4 Salvage Equipment 400 Amp

  2. Activating transcription factor 3 promotes loss of the acinar cell phenotype in response to cerulein-induced pancreatitis in mice.

    PubMed

    Fazio, Elena N; Young, Claire C; Toma, Jelena; Levy, Michael; Berger, Kurt R; Johnson, Charis L; Mehmood, Rashid; Swan, Patrick; Chu, Alphonse; Cregan, Sean P; Dilworth, F Jeffrey; Howlett, Christopher J; Pin, Christopher L

    2017-09-01

    Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of >30% of differentially expressed genes during the initiation of pancreatitis. Of importance, ATF3-dependent regulation of these genes was observed only upon induction of pancreatitis, with pathways involved in inflammation, acinar cell differentiation, and cell junctions being specifically targeted. Characterizing expression of transcription factors that affect acinar cell differentiation suggested that acinar cells lacking ATF3 maintain a mature cell phenotype during pancreatitis, a finding supported by maintenance of junctional proteins and polarity markers. As a result, Atf3 -/- pancreatic tissue displayed increased tissue damage and inflammatory cell infiltration at early time points during injury but, at later time points, showed reduced acinar-to-duct cell metaplasia. Thus our results reveal a critical role for ATF3 as a key regulator of the acinar cell transcriptional response during injury and may provide a link between chronic pancreatitis and PDAC. © 2017 Fazio et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. Identification and Small Molecule Inhibition of an Activating Transcription Factor 4 (ATF4)-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy*

    PubMed Central

    Ebert, Scott M.; Dyle, Michael C.; Bullard, Steven A.; Dierdorff, Jason M.; Murry, Daryl J.; Fox, Daniel K.; Bongers, Kale S.; Lira, Vitor A.; Meyerholz, David K.; Talley, John J.; Adams, Christopher M.

    2015-01-01

    Aging reduces skeletal muscle mass and strength, but the underlying molecular mechanisms remain elusive. Here, we used mouse models to investigate molecular mechanisms of age-related skeletal muscle weakness and atrophy as well as new potential interventions for these conditions. We identified two small molecules that significantly reduce age-related deficits in skeletal muscle strength, quality, and mass: ursolic acid (a pentacyclic triterpenoid found in apples) and tomatidine (a steroidal alkaloid derived from green tomatoes). Because small molecule inhibitors can sometimes provide mechanistic insight into disease processes, we used ursolic acid and tomatidine to investigate the pathogenesis of age-related muscle weakness and atrophy. We found that ursolic acid and tomatidine generate hundreds of small positive and negative changes in mRNA levels in aged skeletal muscle, and the mRNA expression signatures of the two compounds are remarkably similar. Interestingly, a subset of the mRNAs repressed by ursolic acid and tomatidine in aged muscle are positively regulated by activating transcription factor 4 (ATF4). Based on this finding, we investigated ATF4 as a potential mediator of age-related muscle weakness and atrophy. We found that a targeted reduction in skeletal muscle ATF4 expression reduces age-related deficits in skeletal muscle strength, quality, and mass, similar to ursolic acid and tomatidine. These results elucidate ATF4 as a critical mediator of age-related muscle weakness and atrophy. In addition, these results identify ursolic acid and tomatidine as potential agents and/or lead compounds for reducing ATF4 activity, weakness, and atrophy in aged skeletal muscle. PMID:26338703

  4. Identification and Small Molecule Inhibition of an Activating Transcription Factor 4 (ATF4)-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy.

    PubMed

    Ebert, Scott M; Dyle, Michael C; Bullard, Steven A; Dierdorff, Jason M; Murry, Daryl J; Fox, Daniel K; Bongers, Kale S; Lira, Vitor A; Meyerholz, David K; Talley, John J; Adams, Christopher M

    2015-10-16

    Aging reduces skeletal muscle mass and strength, but the underlying molecular mechanisms remain elusive. Here, we used mouse models to investigate molecular mechanisms of age-related skeletal muscle weakness and atrophy as well as new potential interventions for these conditions. We identified two small molecules that significantly reduce age-related deficits in skeletal muscle strength, quality, and mass: ursolic acid (a pentacyclic triterpenoid found in apples) and tomatidine (a steroidal alkaloid derived from green tomatoes). Because small molecule inhibitors can sometimes provide mechanistic insight into disease processes, we used ursolic acid and tomatidine to investigate the pathogenesis of age-related muscle weakness and atrophy. We found that ursolic acid and tomatidine generate hundreds of small positive and negative changes in mRNA levels in aged skeletal muscle, and the mRNA expression signatures of the two compounds are remarkably similar. Interestingly, a subset of the mRNAs repressed by ursolic acid and tomatidine in aged muscle are positively regulated by activating transcription factor 4 (ATF4). Based on this finding, we investigated ATF4 as a potential mediator of age-related muscle weakness and atrophy. We found that a targeted reduction in skeletal muscle ATF4 expression reduces age-related deficits in skeletal muscle strength, quality, and mass, similar to ursolic acid and tomatidine. These results elucidate ATF4 as a critical mediator of age-related muscle weakness and atrophy. In addition, these results identify ursolic acid and tomatidine as potential agents and/or lead compounds for reducing ATF4 activity, weakness, and atrophy in aged skeletal muscle. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Critical processes and parameters in the development of accident tolerant fuels drop-in capsule irradiation tests

    DOE PAGES

    Barrett, K. E.; Ellis, K. D.; Glass, C. R.; ...

    2015-12-01

    The goal of the Accident Tolerant Fuel (ATF) program is to develop the next generation of Light Water Reactor (LWR) fuels with improved performance, reliability, and safety characteristics during normal operations and accident conditions and with reduced waste generation. An irradiation test series has been defined to assess the performance of proposed ATF concepts under normal LWR operating conditions. The Phase I ATF irradiation test series is planned to be performed as a series of drop-in capsule tests to be irradiated in the Advanced Test Reactor (ATR) operated by the Idaho National Laboratory (INL). Design, analysis, and fabrication processes formore » ATR drop-in capsule experiment preparation are presented in this paper to demonstrate the importance of special design considerations, parameter sensitivity analysis, and precise fabrication and inspection techniques for figure innovative materials used in ATF experiment assemblies. A Taylor Series Method sensitivity analysis approach was used to identify the most critical variables in cladding and rodlet stress, temperature, and pressure calculations for design analyses. The results showed that internal rodlet pressure calculations are most sensitive to the fission gas release rate uncertainty while temperature calculations are most sensitive to cladding I.D. and O.D. dimensional uncertainty. The analysis showed that stress calculations are most sensitive to rodlet internal pressure uncertainties, however the results also indicated that the inside radius, outside radius, and internal pressure were all magnified as they propagate through the stress equation. This study demonstrates the importance for ATF concept development teams to provide the fabricators as much information as possible about the material properties and behavior observed in prototype testing, mock-up fabrication and assembly, and chemical and mechanical testing of the materials that may have been performed in the concept development phase. Special handling, machining, welding, and inspection of materials, if known, should also be communicated to the experiment fabrication and inspection team.« less

  6. ATF5 regulates β-cell survival during stress.

    PubMed

    Juliana, Christine A; Yang, Juxiang; Rozo, Andrea V; Good, Austin; Groff, David N; Wang, Shu-Zong; Green, Michael R; Stoffers, Doris A

    2017-02-07

    The stress response and cell survival are necessary for normal pancreatic β-cell function, glucose homeostasis, and prevention of diabetes. The homeodomain transcription factor and human diabetes gene pancreas/duodenum homeobox protein 1 (Pdx1) regulates β-cell survival and endoplasmic reticulum stress susceptibility, in part through direct regulation of activating transcription factor 4 (Atf4). Here we show that Atf5, a close but less-studied relative of Atf4, is also a target of Pdx1 and is critical for β-cell survival under stress conditions. Pdx1 deficiency led to decreased Atf5 transcript, and primary islet ChIP-sequencing localized PDX1 to the Atf5 promoter, implicating Atf5 as a PDX1 target. Atf5 expression was stress inducible and enriched in β cells. Importantly, Atf5 deficiency decreased survival under stress conditions. Loss-of-function and chromatin occupancy experiments positioned Atf5 downstream of and parallel to Atf4 in the regulation of eIF4E-binding protein 1 (4ebp1), a mammalian target of rapamycin (mTOR) pathway component that inhibits protein translation. Accordingly, Atf5 deficiency attenuated stress suppression of global translation, likely enhancing the susceptibility of β cells to stress-induced apoptosis. Thus, we identify ATF5 as a member of the transcriptional network governing pancreatic β-cell survival during stress.

  7. Coffee Polyphenols Change the Expression of STAT5B and ATF-2 Modifying Cyclin D1 Levels in Cancer Cells

    PubMed Central

    Oleaga, Carlota; Ciudad, Carlos J.; Noé, Véronique; Izquierdo-Pulido, Maria

    2012-01-01

    Background. Epidemiological studies suggest that coffee consumption reduces the risk of cancer, but the molecular mechanisms of its chemopreventive effects remain unknown. Objective. To identify differentially expressed genes upon incubation of HT29 colon cancer cells with instant caffeinated coffee (ICC) or caffeic acid (CA) using whole-genome microarrays. Results. ICC incubation of HT29 cells caused the overexpression of 57 genes and the underexpression of 161, while CA incubation induced the overexpression of 12 genes and the underexpression of 32. Using Venn-Diagrams, we built a list of five overexpressed genes and twelve underexpressed genes in common between the two experimental conditions. This list was used to generate a biological association network in which STAT5B and ATF-2 appeared as highly interconnected nodes. STAT5B overexpression was confirmed at the mRNA and protein levels. For ATF-2, the changes in mRNA levels were confirmed for both ICC and CA, whereas the decrease in protein levels was only observed in CA-treated cells. The levels of cyclin D1, a target gene for both STAT5B and ATF-2, were downregulated by CA in colon cancer cells and by ICC and CA in breast cancer cells. Conclusions. Coffee polyphenols are able to affect cyclin D1 expression in cancer cells through the modulation of STAT5B and ATF-2. PMID:22919439

  8. ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish

    PubMed Central

    Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L.; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi

    2013-01-01

    ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra. PMID:23447699

  9. ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.

    PubMed

    Ishikawa, Tokiro; Okada, Tetsuya; Ishikawa-Fujiwara, Tomoko; Todo, Takeshi; Kamei, Yasuhiro; Shigenobu, Shuji; Tanaka, Minoru; Saito, Taro L; Yoshimura, Jun; Morishita, Shinichi; Toyoda, Atsushi; Sakaki, Yoshiyuki; Taniguchi, Yoshihito; Takeda, Shunichi; Mori, Kazutoshi

    2013-05-01

    ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra.

  10. Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury

    PubMed Central

    Gey, Manuel; Wanner, Renate; Schilling, Corinna; Pedro, Maria T.; Sinske, Daniela

    2016-01-01

    Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce ‘effector’ RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types. PMID:27581653

  11. ATF5 regulates β-cell survival during stress

    PubMed Central

    Juliana, Christine A.; Yang, Juxiang; Rozo, Andrea V.; Good, Austin; Groff, David N.; Wang, Shu-Zong; Stoffers, Doris A.

    2017-01-01

    The stress response and cell survival are necessary for normal pancreatic β-cell function, glucose homeostasis, and prevention of diabetes. The homeodomain transcription factor and human diabetes gene pancreas/duodenum homeobox protein 1 (Pdx1) regulates β-cell survival and endoplasmic reticulum stress susceptibility, in part through direct regulation of activating transcription factor 4 (Atf4). Here we show that Atf5, a close but less-studied relative of Atf4, is also a target of Pdx1 and is critical for β-cell survival under stress conditions. Pdx1 deficiency led to decreased Atf5 transcript, and primary islet ChIP-sequencing localized PDX1 to the Atf5 promoter, implicating Atf5 as a PDX1 target. Atf5 expression was stress inducible and enriched in β cells. Importantly, Atf5 deficiency decreased survival under stress conditions. Loss-of-function and chromatin occupancy experiments positioned Atf5 downstream of and parallel to Atf4 in the regulation of eIF4E-binding protein 1 (4ebp1), a mammalian target of rapamycin (mTOR) pathway component that inhibits protein translation. Accordingly, Atf5 deficiency attenuated stress suppression of global translation, likely enhancing the susceptibility of β cells to stress-induced apoptosis. Thus, we identify ATF5 as a member of the transcriptional network governing pancreatic β-cell survival during stress. PMID:28115692

  12. ATF3 activates Stat3 phosphorylation through inhibition of p53 expression in skin cancer cells.

    PubMed

    Hao, Zhen-Feng; Ao, Jun-Hong; Zhang, Jie; Su, You-Ming; Yang, Rong-Ya

    2013-01-01

    ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.

  13. Vitex rotundifolia Fruit Extract Induces Apoptosis Through the Downregulation of ATF3-Mediated Bcl-2 Expression in Human Colorectal Cancer Cells.

    PubMed

    Song, Hun Min; Park, Gwang Hun; Koo, Jin Suk; Jeong, Hyung Jin; Jeong, Jin Boo

    2017-01-01

    Fruit from Vitex rotundifolia L. (VF) has been reported to initiate apoptosis in human colorectal cancer cells through the accumulation of reactive oxygen species. Since various regulatory factors are involved in the apoptotic pathway, further study of the potential mechanisms of VF associated with the induction of apoptosis may be important despite the fact that the molecular target of VF for apoptosis has already been elucidated. In this study, we showed a new potential mechanism for the relationship between VF-mediated ATF3 expression and apoptosis to better understand the apoptotic mechanism of VF in human colorectal cancer cells. VF reduced the cell viability and induced apoptosis in human colorectal cancer cells. VF treatment increased both the protein and mRNA level of ATF3 and upregulated ATF3 promoter activity. The cis-element responsible for ATF3 transcriptional activation by VF was CREB which is located between [Formula: see text]147 to [Formula: see text]85 of ATF3 promoter. Inhibitions of ERK1/2, p38, JNK and GSK3[Formula: see text] blocked VF-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated the cleavage of PARP by VF, while ATF3 overexpression increased VF-mediated cleaved PARP. ATF3 knockdown also attenuated VF-mediated cell viability and cell death. In addition, VF downregulated Bcl-2 expression at both protein and mRNA level. ATF3 knockdown by ATF3 siRNA blocked VF-mediated downregulation of Bcl-2. In conclusion, VF may activate ATF3 expression through transcriptional regulation and subsequently suppress Bcl-2 expression as an anti-apoptotic protein, which may result in the induction of apoptosis in human colorectal cancer cells.

  14. Deciphering the role of the signal- and Sty1 kinase-dependent phosphorylation of the stress-responsive transcription factor Atf1 on gene activation.

    PubMed

    Salat-Canela, Clàudia; Paulo, Esther; Sánchez-Mir, Laura; Carmona, Mercè; Ayté, José; Oliva, Baldo; Hidalgo, Elena

    2017-08-18

    Adaptation to stress triggers the most dramatic shift in gene expression in fission yeast ( Schizosaccharomyces pombe ), and this response is driven by signaling via the MAPK Sty1. Upon activation, Sty1 accumulates in the nucleus and stimulates expression of hundreds of genes via the nuclear transcription factor Atf1, including expression of atf1 itself. However, the role of stress-induced, Sty1-mediated Atf1 phosphorylation in transcriptional activation is unclear. To this end, we expressed Atf1 phosphorylation mutants from a constitutive promoter to uncouple Atf1 activity from endogenous, stress-activated Atf1 expression. We found that cells expressing a nonphosphorylatable Atf1 variant are sensitive to oxidative stress because of impaired transcription of a subset of stress genes whose expression is also controlled by another transcription factor, Pap1. Furthermore, cells expressing a phospho-mimicking Atf1 mutant display enhanced stress resistance, and although expression of the Pap1-dependent genes still relied on stress induction, another subset of stress-responsive genes was constitutively expressed in these cells. We also observed that, in cells expressing the phospho-mimicking Atf1 mutant, the presence of Sty1 was completely dispensable, with all stress defects of Sty1-deficient cells being suppressed by expression of the Atf1 mutant. We further demonstrated that Sty1-mediated Atf1 phosphorylation does not stimulate binding of Atf1 to DNA but, rather, establishes a platform of interactions with the basal transcriptional machinery to facilitate transcription initiation. In summary, our results provide evidence that Atf1 phosphorylation by the MAPK Sty1 is required for oxidative stress responses in fission yeast cells by promoting transcription initiation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Fuel Cycle Research and Development Accident Tolerant Fuels Series 1 (ATF-1) Irradiation Testing FY 2016 Status Report

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

    Core, Gregory Matthew

    This report contains a summary of irradiation testing of Fuel Cycle Research and Development (FCRD) Accident Tolerant Fuels Series 1 (ATF 1) experiments performed at Idaho National Laboratory (INL) in FY 2016. ATF 1 irradiation testing work performed in FY 2016 included design, analysis, and fabrication of ATF-1B drop in capsule ATF 1 series experiments and irradiation testing of ATF-1 capsules in the ATR.

  16. Severe Accident Scoping Simulations of Accident Tolerant Fuel Concepts for BWRs

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

    Robb, Kevin R.

    2015-08-01

    Accident-tolerant fuels (ATFs) are fuels and/or cladding that, in comparison with the standard uranium dioxide Zircaloy system, can tolerate loss of active cooling in the core for a considerably longer time period while maintaining or improving the fuel performance during normal operations [1]. It is important to note that the currently used uranium dioxide Zircaloy fuel system tolerates design basis accidents (and anticipated operational occurrences and normal operation) as prescribed by the US Nuclear Regulatory Commission. Previously, preliminary simulations of the plant response have been performed under a range of accident scenarios using various ATF cladding concepts and fully ceramicmore » microencapsulated fuel. Design basis loss of coolant accidents (LOCAs) and station blackout (SBO) severe accidents were analyzed at Oak Ridge National Laboratory (ORNL) for boiling water reactors (BWRs) [2]. Researchers have investigated the effects of thermal conductivity on design basis accidents [3], investigated silicon carbide (SiC) cladding [4], as well as the effects of ATF concepts on the late stage accident progression [5]. These preliminary analyses were performed to provide initial insight into the possible improvements that ATF concepts could provide and to identify issues with respect to modeling ATF concepts. More recently, preliminary analyses for a range of ATF concepts have been evaluated internationally for LOCA and severe accident scenarios for the Chinese CPR1000 [6] and the South Korean OPR-1000 [7] pressurized water reactors (PWRs). In addition to these scoping studies, a common methodology and set of performance metrics were developed to compare and support prioritizing ATF concepts [8]. A proposed ATF concept is based on iron-chromium-aluminum alloys (FeCrAl) [9]. With respect to enhancing accident tolerance, FeCrAl alloys have substantially slower oxidation kinetics compared to the zirconium alloys typically employed. During a severe accident, FeCrAl would tend to generate heat and hydrogen from oxidation at a slower rate compared to the zirconium-based alloys in use today. The previous study, [2], of the FeCrAl ATF concept during station blackout (SBO) severe accident scenarios in BWRs was based on simulating short term SBO (STSBO), long term SBO (LTSBO), and modified SBO scenarios occurring in a BWR-4 reactor with MARK-I containment. The analysis indicated that FeCrAl had the potential to delay the onset of fuel failure by a few hours depending on the scenario, and it could delay lower head failure by several hours. The analysis demonstrated reduced in-vessel hydrogen production. However, the work was preliminary and was based on limited knowledge of material properties for FeCrAl. Limitations of the MELCOR code were identified for direct use in modeling ATF concepts. This effort used an older version of MELCOR (1.8.5). Since these analyses, the BWR model has been updated for use in MELCOR 1.8.6 [10], and more representative material properties for FeCrAl have been modeled. Sections 2 4 present updated analyses for the FeCrAl ATF concept response during severe accidents in a BWR. The purpose of the study is to estimate the potential gains afforded by the FeCrAl ATF concept during BWR SBO scenarios.« less

  17. Cardiac Fibroblast-Specific Activating Transcription Factor 3 Protects Against Heart Failure by Suppressing MAP2K3-p38 Signaling.

    PubMed

    Li, Yulin; Li, Zhenya; Zhang, Congcong; Li, Ping; Wu, Yina; Wang, Chunxiao; Bond Lau, Wayne; Ma, Xin-Liang; Du, Jie

    2017-05-23

    Hypertensive ventricular remodeling is a common cause of heart failure. However, the molecular mechanisms regulating ventricular remodeling remain poorly understood. We used a discovery-driven/nonbiased approach to identify increased activating transcription factor 3 (ATF3) expression in hypertensive heart. We used loss/gain of function approaches to understand the role of ATF3 in heart failure. We also examined the mechanisms through transcriptome, chromatin immunoprecipitation sequencing analysis, and in vivo and in vitro experiments. ATF3 expression increased in murine hypertensive heart and human hypertrophic heart. Cardiac fibroblast cells are the primary cell type expressing high ATF3 levels in response to hypertensive stimuli. ATF3 knockout (ATF3KO) markedly exaggerated hypertensive ventricular remodeling, a state rescued by lentivirus-mediated/miRNA-aided cardiac fibroblast-selective ATF3 overexpression. Conversely, conditional cardiac fibroblast cell-specific ATF3 transgenic overexpression significantly ameliorated ventricular remodeling and heart failure. We identified Map2K3 as a novel ATF3 target. ATF3 binds with the Map2K3 promoter, recruiting HDAC1, resulting in Map2K3 gene-associated histone deacetylation, thereby inhibiting Map2K3 expression. Genetic Map2K3 knockdown rescued the profibrotic/hypertrophic phenotype in ATF3KO cells. Last, we demonstrated that p38 is the downstream molecule of Map2K3 mediating the profibrotic/hypertrophic effects in ATF3KO animals. Inhibition of p38 signaling reduced transforming growth factor-β signaling-related profibrotic and hypertrophic gene expression, and blocked exaggerated cardiac remodeling in ATF3KO cells. Our study provides the first evidence that ATF3 upregulation in cardiac fibroblasts in response to hypertensive stimuli protects the heart by suppressing Map2K3 expression and subsequent p38-transforming growth factor-β signaling. These results suggest that positive modulation of cardiac fibroblast ATF3 may represent a novel therapeutic approach against hypertensive cardiac remodeling. © 2017 American Heart Association, Inc.

  18. Bim and VDAC1 are hierarchically essential for mitochondrial ATF2 mediated cell death.

    PubMed

    Liu, Zhaoyun; Luo, Qianfu; Guo, Chunbao

    2015-01-01

    ATF2 mediated cytochrome c release is the formation of a channel with some unknown factors larger than that of the individual proteins. BHS-only proteins (BH3s), such as Bim, could induce BAX and VDAC, forming a new channel. According to this facts, we can speculated that there is possible signal relationship with BH3s and ATF2, which is associated with mitochondrial-based death programs. The growth inhibitory effects of mitochondrial ATF2 were tested in cancer cell lines B16F10, A549, EG7, and LL2. Apoptosis was measured by flow cytometry. The effects of ATF2 and levels of apoptosis regulatory proteins were measured by Western blotting. The interaction of proteins were evaluated by immunoprecipitation analysis. The in vivo antitumor activity of mitochondrial ATF2 were tested in xenograft B16F10 models. Genotoxic stress enabled mitochondrial ATF2 accumulation, perturbing the HK1-VDAC1 complex, increasing mitochondrial permeability, and promoting apoptosis. ATF2 inhibition strongly reduced the conformational activation of Bim, suggesting that Bim acts downstream of ATF2. Although Bim downregulation had no effect on ATF2 activation, Bim knockdown abolished VDAC1 activation; the failure of VDAC1 activation in Bim-depleted cells could be reversed by the BH3-only protein mimic ABT-737. We also demonstrate that silencing of ATF2 in B16F10 cells increases both the incidence and prevalence of tumor xenografts in vivo, whereas stably mitochondrial ATF2 transfection inhibited B16F10 tumor xenografts growth. Altogether, these results show that ATF2 is a component of the apoptosis machinery that involves a hierarchical contribution of ATF2, Bim, and VDAC1. Our data offer new insight into the mechanism of mitochondrial ATF2 in mitochondrial apoptosis.

  19. Silencing of ATF2 inhibits growth of pancreatic cancer cells and enhances sensitivity to chemotherapy.

    PubMed

    Li, Mu; Wu, Xingda; Liu, Ning; Li, Xiaoying; Meng, Fanbin; Song, Shaowei

    2017-06-01

    Pancreatic cancer is one of the leading causes of cancer-related death worldwide. Activating transcription factor 2 (ATF2) is a multifunctional transcription factor, and is implicated in tumor progress, yet its role in pancreatic cancer remains unclear. In the present study, the level of ATF2 in pancreatic cancer tissues and the adjacent non-tumorous tissues was detected by quantitative real-time PCR and Western blot. The roles of ATF2 in the proliferation, cell cycle, and apoptosis of pancreatic cancer cells were investigated through ATF2 silencing, and the effect of ATF2 shRNA on the sensitivity of pancreatic cancer cells to gemcitabine, an anti-tumor drug, was explored. The results of our study showed that the ATF2 level in the pancreatic cancer tissues was higher than that in the adjacent non-tumorous tissues. Silencing of ATF2 was found to inhibit proliferation, arrest cell cycle at G1 phase and induce apoptosis in pancreatic cancer cells. Moreover, ATF2 silencing enhanced gemcitabine-induced growth-inhibition and apoptosis-induction effects in pancreatic cancer cells. In summary, silencing of ATF2 inhibited the growth of pancreatic cancer cells and enhanced the anti-tumor effects of gemcitabine, suggesting that ATF2 plays a pro-survival role in pancreatic cancer. Our results also propose that a high level of ATF2 may serve as a potential biomarker of pancreatic cancer, and that ATF2 may become a potential target for anti-tumor therapy. © 2017 International Federation for Cell Biology.

  20. Post-translational regulation of gene expression using the ATF4 oxygen-dependent degradation domain for hypoxia-specific gene therapy.

    PubMed

    Cho, Su Hee; Oh, Binna; Kim, Hyun Ah; Park, Jeong Hyun; Lee, Minhyung

    2013-11-01

    Solid tumors have hypoxic regions in their cores, due to low blood supply levels. Therefore, hypoxia-specific gene regulation systems have been developed for tumor-specific gene therapy. In this study, the oxygen-dependent degradation (ODD) domain on activating transcription factor-4 (ATF4) was evaluated for post-translational regulation of proteins. The ATF4 ODD cDNA was amplified by RT-PCR, and a luciferase plasmid containing the ATF4 ODD domain, pSV-Luc-ATF4-ODD, was constructed. Luciferase expression was induced under hypoxia by the ATF4 ODD domain in transfection assays into N2A neuroblastoma cells, C6 glioblastoma cells, and U87 glioblastoma cells. In the transfection assay with pSV-Luc-ATF4-ODD, RT-PCR results showed that the mRNA level did not change under hypoxia. This suggests that the induction of luciferase under hypoxia was mediated by post-translational regulation. A plasmid expressing thymidine kinase from herpes simplex virus (HSV-tk), pSV-HSVtk-ATF4-ODD, was constructed with the ATF4 ODD cDNA. The transfection assay with pSV-TK-ATF4-ODD showed that the ATF4 ODD domain induced HSV-tk expression under hypoxia and facilitated the death of C6 cells in the presence of ganciclovir (GCV). Furthermore, pSV-HSVtk-ATF4-ODD induced caspase-3 activity in the hypoxic cells. In conclusion, the ATF4 ODD may be useful for hypoxia-specific gene therapy by post-translational regulation of gene expression.

  1. 75 FR 80845 - Agency Information Collection Activities: Proposed Collection; Comments Requested

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-23

    ... of Information Collection Under Review: ATF F 5630.5R, NFA Special Tax Renewal Registration and Return, ATF F 5630.5RC, NFA Special Tax Location Registration Listing, ATF F 5630.7, NFA Special Tax.../Collection: ATF F 5630.5R, NFA Special Tax Renewal Registration and Return, ATF F 5630.5RC, NFA Special Tax...

  2. The CDK inhibitor p21 is a novel target gene of ATF4 and contributes to cell survival under ER stress.

    PubMed

    Inoue, Yasumichi; Kawachi, Shiori; Ohkubo, Tsubasa; Nagasaka, Mai; Ito, Shogo; Fukuura, Keishi; Itoh, Yuka; Ohoka, Nobumichi; Morishita, Daisuke; Hayashi, Hidetoshi

    2017-11-01

    Activating transcription factor 4 (ATF4) is well known for its role in the endoplasmic reticulum (ER) stress response. ATF4 also transcriptionally induces multiple effectors that determine cell fate depending on cellular context. In addition, ATF4 can communicate both pro-apoptotic and pro-survival signals. How ATF4 mediates its prosurvival roles, however, requires further investigation. Here, we report that the CDK inhibitor p21 is a novel target gene of ATF4. We identified two ATF4-responsive elements, one of which directly binds ATF4, within the first intron of the p21 gene. Importantly, overexpression of p21 enhances cell survival following ER stress induction, while p21 knockdown increases cell death. These results suggest that p21 induction plays a vital role in the cellular response to ER stress and indicate that p21 is a prosurvival effector of ATF4. © 2017 Federation of European Biochemical Societies.

  3. Multidimensional Anodized Titanium Foam Photoelectrode for Efficient Utilization of Photons in Mesoscopic Solar Cells.

    PubMed

    Kang, Jin Soo; Choi, Hyelim; Kim, Jin; Park, Hyeji; Kim, Jae-Yup; Choi, Jung-Woo; Yu, Seung-Ho; Lee, Kyung Jae; Kang, Yun Sik; Park, Sun Ha; Cho, Yong-Hun; Yum, Jun-Ho; Dunand, David C; Choe, Heeman; Sung, Yung-Eun

    2017-09-01

    Mesoscopic solar cells based on nanostructured oxide semiconductors are considered as a promising candidates to replace conventional photovoltaics employing costly materials. However, their overall performances are below the sufficient level required for practical usages. Herein, this study proposes an anodized Ti foam (ATF) with multidimensional and hierarchical architecture as a highly efficient photoelectrode for the generation of a large photocurrent. ATF photoelectrodes prepared by electrochemical anodization of freeze-cast Ti foams have three favorable characteristics: (i) large surface area for enhanced light harvesting, (ii) 1D semiconductor structure for facilitated charge collection, and (iii) 3D highly conductive metallic current collector that enables exclusion of transparent conducting oxide substrate. Based on these advantages, when ATF is utilized in dye-sensitized solar cells, short-circuit photocurrent density up to 22.0 mA cm -2 is achieved in the conventional N719 dye-I 3 - /I - redox electrolyte system even with an intrinsically inferior quasi-solid electrolyte. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. ATF4 is involved in the regulation of simulated microgravity induced integrated stress response

    NASA Astrophysics Data System (ADS)

    Li, Yingxian; Li, Qi; Wang, Xiaogang; Sun, Qiao; Wan, Yumin; Li, Yinghui; Bai, Yanqiang

    Objective: Many important metabolic and signaling pathways have been identified as being affected by microgravity, thereby altering cellular functions such as proliferation, differentiation, maturation and cell survival. It has been demonstrated that microgravity could induce all kinds of stress response such as endoplasmic reticulum stress and oxidative stress et al. ATF4 belongs to the ATF/CREB family of basic region leucine zipper transcription factors. ATF4 is induced by stress signals including anoxia/hypoxia, ER stress, amino acid deprivation and oxidative stress. ATF4 regulates the expression of genes involved in oxidative stress, amino acid synthesis, differentiation, metastasis and angiogenesis. The aim of this study was to examine the changes of ATF4 under microgravity, and to investigate the role of ATF4 in microgravity induced stress. MethodsMEF cells were cultured in clinostat to simulate microgravity. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting were used to examine mRNA and protein levels of ATF4 expression under simulated microgravity in MEF cells. ROS levels were measured with the use of the fluorescent signal H2DCF-DA. GFP-XBP1 stably transfected cell lines was used to detect the extent of ER stress under microgravity by the intensity of GFP. Dual luciferase reporter assay was used to detect the activity of ATF4. Co-immunoprecipitation was performed to analyze protein interaction. Results: ATF4 protein levels in MEF cells increased under simulated microgravity. However, ATF4 mRNA levels were consistent. XBP1 splicing can be induced due to ER stress caused by simulated microgravity. At the same time, ROS levels were also increased. Increased ATF4 could promote the expression of CHOP, which is responsible for cell apoptosis. ATF4 also play an important role in cellular anti-oxidant stress. In ATF4 -/-MEF cells, the ROS levels after H2O2 treatment were obviously higher than that of wild type cells. HDAC4 was identified to be ATF4 interaction protein. Under microgravity, HDAC4 levels were also increased. However, the increased HDAC4 could suppress the activity of ATF4. Conclusions: These results indicated that microgravity could induce both ER stress and oxidative stress. ATF4 is involved in the regulation of these processes by activating both pro-apoptosis and pro-survival signaling. The dual role of ATF4 could be coordinated by increased HDAC4 levels under microgravity through their direct interaction.

  5. Transcriptional Repression of ATF4 Gene by CCAAT/Enhancer-binding Protein β (C/EBPβ) Differentially Regulates Integrated Stress Response*

    PubMed Central

    Dey, Souvik; Savant, Sudha; Teske, Brian F.; Hatzoglou, Maria; Calkhoven, Cornelis F.; Wek, Ronald C.

    2012-01-01

    Different environmental stresses induce the phosphorylation of eIF2 (eIF2∼P), repressing global protein synthesis coincident with preferential translation of ATF4. ATF4 is a transcriptional activator of genes involved in metabolism and nutrient uptake, antioxidation, and regulation of apoptosis. Because ATF4 is a common downstream target that integrates signaling from different eIF2 kinases and their respective stress signals, the eIF2∼P/ATF4 pathway is collectively referred to as the integrated stress response. Although eIF2∼P elicits translational control in response to many different stresses, there are selected stresses, such as exposure to UV irradiation, that do not increase ATF4 expression despite robust eIF2∼P. The rationale for this discordant induction of ATF4 expression and eIF2∼P in response to UV irradiation is that transcription of ATF4 is repressed, and therefore ATF4 mRNA is not available for preferential translation. In this study, we show that C/EBPβ is a transcriptional repressor of ATF4 during UV stress. C/EBPβ binds to critical elements in the ATF4 promoter, resulting in its transcriptional repression. Expression of C/EBPβ increases in response to UV stress, and the liver-enriched inhibitory protein (LIP) isoform of C/EBPβ, but not the liver-enriched activating protein (LAP) version, represses ATF4 transcription. Loss of the liver-enriched inhibitory protein isoform results in increased ATF4 mRNA levels in response to UV irradiation and subsequent recovery of ATF4 translation, leading to enhanced expression of its target genes. Together these results illustrate how eIF2∼P and translational control combined with transcription factors regulated by alternative signaling pathways can direct programs of gene expression that are specifically tailored to each environmental stress. PMID:22556424

  6. The Stress-responsive Gene ATF3 Mediates Dichotomous UV Responses by Regulating the Tip60 and p53 Proteins*

    PubMed Central

    Cui, Hongmei; Li, Xingyao; Han, Chunhua; Wang, Qi-En; Wang, Hongbo; Ding, Han-Fei; Zhang, Junran; Yan, Chunhong

    2016-01-01

    The response to UV irradiation is important for a cell to maintain its genetic integrity when challenged by environmental genotoxins. An immediate early response to UV irradiation is the rapid induction of activating transcription factor 3 (ATF3) expression. Although emerging evidence has linked ATF3 to stress pathways regulated by the tumor suppressor p53 and the histone acetyltransferase Tip60, the role of ATF3 in the UV response remains largely unclear. Here, we report that ATF3 mediated dichotomous UV responses. Although UV irradiation enhanced the binding of ATF3 to Tip60, knockdown of ATF3 expression decreased Tip60 stability, thereby impairing Tip60 induction by UV irradiation. In line with the role of Tip60 in mediating UV-induced apoptosis, ATF3 promoted the death of p53-defective cells in response to UV irradiation. However, ATF3 could also activate p53 and promote p53-mediated DNA repair, mainly through altering histone modifications that could facilitate recruitment of DNA repair proteins (such as DDB2) to damaged DNA sites. As a result, ATF3 rather protected the p53 wild-type cells from UV-induced apoptosis. Our results thus indicate that ATF3 regulates cell fates upon UV irradiation in a p53-dependent manner. PMID:26994140

  7. Development and quality assessments of commercial heat production of ATF FeCrAl tubes

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

    Yamamoto, Yukinori

    2015-09-01

    Development and quality assessment of the 2 nd generation ATF FeCrAl tube production with commercial manufacturers were conducted. The manufacturing partners include Sophisticated Alloys, Inc. (SAI), Butler, PA for FeCrAl alloy casting via vacuum induction melting, Oak Ridge National Laboratory (ORNL) for extrusion process to prepare the master bars/tubes to be tube-drawn, and Rhenium Alloys, Inc. (RAI), North Ridgeville, OH, for tube-drawing process. The masters bars have also been provided to Los Alamos National Laboratory (LANL) who works with Century Tubes, Inc., (CTI), San Diego, CA, as parallel tube production effort under the current program.

  8. ATF3 mediates the inhibitory action of TNF-α on osteoblast differentiation through the JNK signaling pathway.

    PubMed

    Jeong, Byung-Chul

    2018-05-15

    Tumor necrosis factor (TNF)-α, which is a proinflammatory cytokine, inhibits osteoblast differentiation under diverse inflammatory conditions. Activating transcription factor 3 (ATF3), which is a member of the ATF/cAMP response element-binding protein family of transcription factors, has been implicated in the regulation of cell proliferation and differentiation. However, the precise interactions between ATF3 and the TNF-α signaling pathway in the regulation of osteoblast differentiation remain unclear. In this study, we examined the role of ATF3 in the TNF-α-mediated inhibition of osteoblast differentiation and investigated the signaling pathways involved. The treatment of cells with TNF-α downregulated osteogenic markers, but significantly upregulated the expression of Atf3. The inhibition of Atf3 by small interfering RNAs rescued osteogenesis, which was inhibited by TNF-α. Conversely, the enforced expression of Atf3 enhanced the TNF-α-mediated inhibition of osteoblast differentiation, as revealed by the measurement of osteogenic markers and alkaline phosphatase staining. Mechanistically, TNF-α-induced Atf3 expression was significantly suppressed by the inhibition of the c-Jun N-terminal kinase (JNK) pathway. Furthermore, the overexpression of Atf3 did not affect the rescue effect that inhibiting TNF-α expression using a JNK inhibitor had on alkaline phosphatase activity and mineralization. Taken together, these results indicate that ATF3 mediates the inhibitory action of TNF-α on osteoblast differentiation and that the TNF-α-activated JNK pathway is responsible for the induction of Atf3 expression. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Determination of nonlinear resistance voltage-current relationships by measuring harmonics

    NASA Technical Reports Server (NTRS)

    Stafford, J. M.

    1971-01-01

    Test configuration measures harmonic signal amplitudes generated in nonlinear resistance. Vacuum-type voltmeter measures low frequency sinusoidal input signal amplitude and wave-analyzer measures amplitude of harmonic signals generated in junction. Input signal harmonics amplitude must not exceed that of harmonics generated in nonlinear resistance.

  10. 27 CFR 555.23 - List of explosive materials.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Explosive Materials” (ATF Publication 5400.8) is available at no cost upon request from the ATF Distribution Center (See § 555.21). [T.D. ATF-290, 54 FR 53054, Dec. 27, 1989, as amended by T.D. ATF-446, 66 FR 16602...

  11. Biological Effects of Laser Radiation. Volume IV. Optical Second Harmonic Generation in Biological Tissues.

    DTIC Science & Technology

    1978-10-17

    characteristics for optical second- harmonic generation. The collage component of conective tissue may be the principal site for the observed harmonic...Generation in Tissue ; Second Harmonic Generation in Collage; Glutathione, 5MB; Mechanisms; Conversion Efficiency; Significance of order UL AIM UY#m~wmev...sclera, and skin on 694 im. Q-switched ruby laser irradiation. A possible source of this second-harmonic generation was tissue collagen; because of

  12. High Harmonic Radiation Generation and Attosecond pulse generation from Intense Laser-Solid Interactions

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

    Thomas, Alexander Roy; Krushelnick, Karl

    2016-09-08

    We have studied ion motion effects in high harmonic generation, including shifts to the harmonics which result in degradation of the attosecond pulse train, and how to mitigate them. We have examined the scaling with intensity of harmonic emission. We have also switched the geometry of the interaction to measure, for the first time, harmonics from a normal incidence interaction. This was performed by using a special parabolic reflector with an on axis hole and is to allow measurements of the attosecond pulses using standard techniques. Here is a summary of the findings: First high harmonic generation in laser-solid interactionsmore » at 10 21 Wcm -2, demonstration of harmonic focusing, study of ion motion effects in high harmonic generation in laser-solid interactions, and demonstration of harmonic amplification.« less

  13. Analysis of Even Harmonics Generation in an Isolated Electric Power System

    NASA Astrophysics Data System (ADS)

    Kanao, Norikazu; Hayashi, Yasuhiro; Matsuki, Junya

    Harmonics bred from loads are mainly odd order because the current waveform has half-wave symmetry. Since the even harmonics are negligibly small, those are not generally measured in electric power systems. However, even harmonics were measured at a 500/275/154kV substation in Hokuriku Electric Power Company after removal of a transmission line fault. The even harmonics caused malfunctions of protective digital relays because the relays used 4th harmonics at the input filter as automatic supervisory signal. This paper describes the mechanism of generation of the even harmonics by comparing measured waveforms with ATP-EMTP simulation results. As a result of analysis, it is cleared that even harmonics are generated by three causes. The first cause is a magnetizing current of transformers due to flux deviation by DC component of a fault current. The second one is due to harmonic conversion of a synchronous machine which generates even harmonics when direct current component or even harmonic current flow into the machine. The third one is that increase of harmonic impedance due to an isolated power system produces harmonic voltages. The design of the input filter of protective digital relays should consider even harmonics generation in an isolated power system.

  14. Functional Contribution of the Transcription Factor ATF4 to the Pathogenesis of Amyotrophic Lateral Sclerosis

    PubMed Central

    Matus, Soledad; Lopez, Estefanía; Valenzuela, Vicente; Nassif, Melissa; Hetz, Claudio

    2013-01-01

    Endoplasmic reticulum (ER) stress represents an early pathological event in amyotrophic lateral sclerosis (ALS). ATF4 is a key ER stress transcription factor that plays a role in both adaptation to stress and the activation of apoptosis. Here we investigated the contribution of ATF4 to ALS. ATF4 deficiency reduced the rate of birth of SOD1G86R transgenic mice. The fraction of ATF4−/−-SOD1G85R transgenic mice that were born are more resistant to develop ALS, leading to delayed disease onset and prolonged life span. ATF4 deficiency completely attenuated the induction of pro-apoptotic genes, including BIM and CHOP, and also led to quantitative changes in the ER protein homeostasis network. Unexpectedly, ATF4 deficiency enhanced mutant SOD1 aggregation at the end stage of the disease. Studies in the motoneuron cell line NSC34 demonstrated that knocking down ATF4 enhances mutant SOD1 aggregation possibly due to alteration in the redox status of the cell. Our results support a functional role of ATF4 in ALS, offering a novel target for disease intervention. PMID:23874395

  15. Three-dimensional structural imaging of starch granules by second-harmonic generation circular dichroism.

    PubMed

    Zhuo, G-Y; Lee, H; Hsu, K-J; Huttunen, M J; Kauranen, M; Lin, Y-Y; Chu, S-W

    2014-03-01

    Chirality is one of the most fundamental and essential structural properties of biological molecules. Many important biological molecules including amino acids and polysaccharides are intrinsically chiral. Conventionally, chiral species can be distinguished by interaction with circularly polarized light, and circular dichroism is one of the best-known approaches for chirality detection. As a linear optical process, circular dichroism suffers from very low signal contrast and lack of spatial resolution in the axial direction. It has been demonstrated that by incorporating nonlinear interaction with circularly polarized excitation, second-harmonic generation circular dichroism can provide much higher signal contrast. However, previous circular dichroism and second-harmonic generation circular dichroism studies are mostly limited to probe chiralities at surfaces and interfaces. It is known that second-harmonic generation, as a second-order nonlinear optical effect, provides excellent optical sectioning capability when combined with a laser-scanning microscope. In this work, we combine the axial resolving power of second-harmonic generation and chiral sensitivity of second-harmonic generation circular dichroism to realize three-dimensional chiral detection in biological tissues. Within the point spread function of a tight focus, second-harmonic generation circular dichroism could arise from the macroscopic supramolecular packing as well as the microscopic intramolecular chirality, so our aim is to clarify the origins of second-harmonic generation circular dichroism response in complicated three-dimensional biological systems. The sample we use is starch granules whose second-harmonic generation-active molecules are amylopectin with both microscopic chirality due to its helical structure and macroscopic chirality due to its crystallized packing. We found that in a starch granule, the second-harmonic generation for right-handed circularly polarized excitation is significantly different from second-harmonic generation for left-handed one, offering excellent second-harmonic generation circular dichroism contrast that approaches 100%. In addition, three-dimensional visualization of second-harmonic generation circular dichroism distribution with sub-micrometer spatial resolution is realized. We observed second-harmonic generation circular dichroism sign change across the starch granules, and the result suggests that in thick biological tissue, second-harmonic generation circular dichroism arises from macroscopic molecular packing. Our result provides a new method to visualize the organization of three-dimensional structures of starch granules. The second-harmonic generation circular dichroism imaging method expands the horizon of nonlinear chiroptical studies from simplified surface/solution environments to complicated biological tissues. © 2014 The Authors Journal of Microscopy © 2014 Royal Microscopical Society.

  16. Elevated ATF4 Expression, in the Absence of Other Signals, Is Sufficient for Transcriptional Induction via CCAAT Enhancer-binding Protein-activating Transcription Factor Response Elements*

    PubMed Central

    Shan, Jixiu; Örd, Daima; Örd, Tõnis; Kilberg, Michael S.

    2009-01-01

    Protein limitation in vivo or amino acid deprivation of cells in culture causes a signal transduction cascade consisting of activation of the kinase GCN2 (general control nonderepressible 2), phosphorylation of eukaryotic initiation factor 2, and increased synthesis of activating transcription factor (ATF) 4 by a translational control mechanism. In a self-limiting transcriptional program, ATF4 transiently activates a wide range of downstream target genes involved in transport, cellular metabolism, and other cell functions. Simultaneous activation of other signal transduction pathways by amino acid deprivation led to the question of whether or not the increased abundance of ATF4 alone was sufficient to trigger the transcriptional control mechanisms. Using 293 cells that ectopically express ATF4 in a tetracycline-inducible manner showed that ATF4 target genes were activated in the absence of amino acid deprivation. Ectopic expression of ATF4 alone resulted in effective recruitment of the general transcription machinery, but some reduction in histone modification was observed. These data document that ATF4 alone is sufficient to trigger the amino acid-responsive transcriptional control program. However, the absolute amount of ectopic ATF4 required to achieve the same degree of transcriptional activation observed after amino acid limitation was greater, suggesting that other factors may serve to enhance ATF4 function. PMID:19509279

  17. Protective upregulation of activating transcription factor-3 against glutamate neurotoxicity in neuronal cells under ischemia.

    PubMed

    Takarada, Takeshi; Kou, Miki; Hida, Miho; Fukumori, Ryo; Nakamura, Saki; Kutsukake, Takaya; Kuramoto, Nobuyuki; Hinoi, Eiichi; Yoneda, Yukio

    2016-05-01

    This study evaluates the pathological role of the stress sensor activating transcription factor-3 (ATF3) in ischemic neurotoxicity. Upregulation of the transcript and protein for ATF3 was seen 2-10 hr after reperfusion in the ipsilateral cerebral hemisphere of mice with transient middle cerebral artery occlusion for 2 hr. Immunohistochemical analysis confirmed the expression of ATF3 by cells immunoreactive for a neuronal marker in neocortex, hippocampus, and striatum within 2 hr after reperfusion. In murine neocortical neurons previously cultured under ischemic conditions for 2 hr, transient upregulation of both Atf3 and ATF3 expression was similarly found during subsequent culture for 2-24 hr under normoxia. Lentiviral overexpression of ATF3 ameliorated the neurotoxicity of glutamate (Glu) in cultured murine neurons along with a slight but statistically significant inhibition of both Fluo-3 and rhodamine-2 fluorescence increases by N-methyl-D-aspartate. Similarly, transient upregulation was seen in Atf3 and ATF3 expression during the culture for 48 hr in neuronal Neuro2A cells previously cultured under ischemic conditions for 2 hr. Luciferase reporter analysis with ATF3 promoter together with immunoblotting revealed the possible involvement of several transcription factors responsive to extracellular and intracellular stressors in the transactivation of the Atf3 gene in Neuro2A cells. ATF3 could be upregulated to play a role in mechanisms underlying mitigation of the neurotoxicity mediated by the endogenous neurotoxin Glu at an early stage after ischemic signal inputs. © 2016 Wiley Periodicals, Inc.

  18. The bZIP repressor proteins, c-Jun dimerization protein 2 and activating transcription factor 3, recruit multiple HDAC members to the ATF3 promoter.

    PubMed

    Darlyuk-Saadon, Ilona; Weidenfeld-Baranboim, Keren; Yokoyama, Kazunari K; Hai, Tsonwin; Aronheim, Ami

    2012-01-01

    JDP2, is a basic leucine zipper (bZIP) protein displaying a high degree of homology with the stress inducible transcription factor, ATF3. Both proteins bind to cAMP and TPA response elements and repress transcription by multiple mechanisms. Histone deacetylases (HDACs) play a key role in gene inactivation by deacetylating lysine residues on histones. Here we describe the association of JDP2 and ATF3 with HDACs 1, 2-6 and 10. Association of HDAC3 and HDAC6 with JDP2 and ATF3 occurs via direct protein-protein interactions. Only part of the N-terminal bZIP motif of JDP2 and ATF3 basic domain is necessary and sufficient for the interaction with HDACs in a manner that is independent of coiled-coil dimerization. Class I HDACs associate with the bZIP repressors via the DAC conserved domain whereas the Class IIb HDAC6 associates through its C-terminal unique binder of ubiquitin Zn finger domain. Both JDP2 and ATF3 are known to bind and repress the ATF3 promoter. MEF cells treated with histone deacetylase inhibitor, trichostatin A (TSA) display enhanced ATF3 transcription. ATF3 enhanced transcription is significantly reduced in MEF cells lacking both ATF3 and JDP2. Collectively, we propose that the recruitment of multiple HDAC members to JDP2 and ATF3 is part of their transcription repression mechanism. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. 77 FR 57590 - Agency Information Collection Activities; Proposed Collection; Comments Requested: ATF...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-18

    ... form is used to evaluate the ATF Distribution Center and the services it provides to the users of ATF...] Agency Information Collection Activities; Proposed Collection; Comments Requested: ATF Distribution Center Survey ACTION: 60-Day notice of information collection under review. The Department of Justice...

  20. ATF7IP-Mediated Stabilization of the Histone Methyltransferase SETDB1 Is Essential for Heterochromatin Formation by the HUSH Complex.

    PubMed

    Timms, Richard T; Tchasovnikarova, Iva A; Antrobus, Robin; Dougan, Gordon; Lehner, Paul J

    2016-10-11

    The histone methyltransferase SETDB1 plays a central role in repressive chromatin processes, but the functional requirement for its binding partner ATF7IP has remained enigmatic. Here, we show that ATF7IP is essential for SETDB1 stability: nuclear SETDB1 protein is degraded by the proteasome upon ablation of ATF7IP. As a result, ATF7IP is critical for repression that requires H3K9 trimethylation by SETDB1, including transgene silencing by the HUSH complex. Furthermore, we show that loss of ATF7IP phenocopies loss of SETDB1 in genome-wide assays. ATF7IP and SETDB1 knockout cells exhibit near-identical defects in the global deposition of H3K9me3, which results in similar dysregulation of the transcriptome. Overall, these data identify a critical functional role for ATF7IP in heterochromatin formation by regulating SETDB1 abundance in the nucleus. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Single-molecule quantification of lipotoxic expression of activating transcription factor 3

    PubMed Central

    Wilson, Dennis W.; Rutledge, John C.

    2014-01-01

    Activating transcription factor 3 (ATF3) is a member of the mammalian activation transcription factor/cAMP, physiologically important in the regulation of pro- and anti-inflammatory target genes. We compared the induction of ATF3 protein as measured by Western blot analysis with single-molecule localization microscopy dSTORM to quantify the dynamics of accumulation of intranuclear ATF3 of triglyceride-rich (TGRL) lipolysis product-treated HAEC (Human Aortic Endothelial Cells). The ATF3 expression rate within the first three hours after treatment with TGRL lipolysis products is about 3500/h. After three hours we detected 33,090 ± 3,491 single-molecule localizations of ATF3. This was accompanied by significant structural changes in the F-actin network of the cells at ~3-fold increased localization precision compared to widefield microscopy after treatment. Additionally, we discovered a cluster size of approximately 384 nanometers of ATF3 molecules. We show for the first time the time course of ATF3 accumulation in the nucleus undergoing lipotoxic injury. Furthermore, we demonstrate ATF3 accumulation associated with increased concentrations of TGRL lipolysis products occurs in large aggregates. PMID:25189785

  2. Construction of a self-cloning sake yeast that overexpresses alcohol acetyltransferase gene by a two-step gene replacement protocol.

    PubMed

    Hirosawa, I; Aritomi, K; Hoshida, H; Kashiwagi, S; Nishizawa, Y; Akada, R

    2004-07-01

    The commercial application of genetically modified industrial microorganisms has been problematic due to public concerns. We constructed a "self-cloning" sake yeast strain that overexpresses the ATF1 gene encoding alcohol acetyltransferase, to improve the flavor profile of Japanese sake. A constitutive yeast overexpression promoter, TDH3p, derived from the glyceraldehyde-3-phosphate dehydrogenase gene from sake yeast was fused to ATF1; and the 5' upstream non-coding sequence of ATF1 was further fused to TDH3p-ATF1. The fragment was placed on a binary vector, pGG119, containing a drug-resistance marker for transformation and a counter-selection marker for excision of unwanted DNA. The plasmid was integrated into the ATF1 locus of a sake yeast strain. This integration constructed tandem repeats of ATF1 and TDH3p-ATF1 sequences, between which the plasmid was inserted. Loss of the plasmid, which occurs through homologous recombination between either the TDH3p downstream ATF1 repeats or the TDH3p upstream repeat sequences, was selected by growing transformants on counter-selective medium. Recombination between the downstream repeats led to reversion to a wild type strain, but that between the upstream repeats resulted in a strain that possessed TDH3p-ATF1 without the extraneous DNA sequences. The self-cloning TDH3p-ATF1 yeast strain produced a higher amount of isoamyl acetate. This is the first expression-controlled self-cloning industrial yeast.

  3. ATF3 Expression in the Corpus Luteum: Possible Role in Luteal Regression†

    PubMed Central

    Mao, Dagan; Hou, Xiaoying; Talbott, Heather; Cushman, Robert; Cupp, Andrea

    2013-01-01

    The present study investigated the induction and possible role of activating transcription factor 3 (ATF3) in the corpus luteum. Postpubertal cattle were treated at midcycle with prostaglandin F2α(PGF) for 0–4 hours. Luteal tissue was processed for immunohistochemistry, in situ hybridization, and isolation of protein and RNA. Ovaries were also collected from midluteal phase and first-trimester pregnant cows. Luteal cells were prepared and sorted by centrifugal elutriation to obtain purified small (SLCs) and large luteal cells (LLCs). Real-time PCR and in situ hybridization showed that ATF3 mRNA increased within 1 hour of PGF treatment in vivo. Western blot and immunohistochemistry demonstrated that ATF3 protein was expressed in the nuclei of LLC within 1 hour and was maintained for at least 4 hours. PGF treatment in vitro increased ATF3 expression only in LLC, whereas TNF induced ATF3 in both SLCs and LLCs. PGF stimulated concentration- and time-dependent increases in ATF3 and phosphorylation of MAPKs in LLCs. Combinations of MAPK inhibitors suppressed ATF3 expression in LLCs. Adenoviral-mediated expression of ATF3 inhibited LH-stimulated cAMP response element reporter luciferase activity and progesterone production in LLCs and SLCs but did not alter cell viability or change the expression or activity of key regulators of progesterone synthesis. In conclusion, the action of PGF in LLCs is associated with the rapid activation of stress-activated protein kinases and the induction of ATF3, which may contribute to the reduction in steroid synthesis during luteal regression. ATF3 appears to affect gonadotropin-stimulated progesterone secretion at a step or steps downstream of PKA signaling and before cholesterol conversion to progesterone. PMID:24196350

  4. PcToll2 positively regulates the expression of antimicrobial peptides by promoting PcATF4 translocation into the nucleus.

    PubMed

    Lan, Jiang-Feng; Zhao, Li-Juan; Wei, Shun; Wang, Yuan; Lin, Li; Li, Xin-Cang

    2016-11-01

    Drosophila Toll and mammalian Toll-like receptors (TLRs) are a family of evolutionarily conserved immune receptors that play a crucial role in the first-line defense against intruded pathogens. Activating transcription factor 4 (ATF4), a member of the ATF/CREB transcription factor family, is an important factor that participates in TLR signaling and other physiological processes. However, in crustaceans, whether ATF4 homologs were involved in TLR signaling remains unclear. In the current study, we identified a Toll homolog PcToll2 and a novel ATF4 homolog PcATF4 from Procambarus clarkii, and analyzed the likely regulatory activity of PcATF4 in PcToll2 signaling. The complete cDNA sequence of PcToll2 was 4175 bp long containing an open reading frame of 2820 bp encoding a 939-amino acid protein, and the cDNA sequence of PcATF4 was 2027 bp long with an open reading frame of 1296 bp encoding a 431-amino acid protein. PcToll2 and human TLR4 shared the high identity and they were grouped into a cluster. Furthermore, PcToll2 had a close relationship with other shrimp TLRs that possessed potential antibacterial activity. PcToll2 was highly expressed in the hemocytes, heart and gills, while PcATF4 mainly distributed in gills. Upon challenge with Vibrio parahemolyticus, PcToll2 and PcATF4 together with the antimicrobial peptides of ALF1 and ALF2 were significantly up-regulated in the hemocytes, and the PcATF4 was translocated into the nucleus. After PcToll2 silencing and challenge with Vibrio, the translocation of PcATF4 into the nucleus was inhibited and the expression of ALF1 and ALF2 was reduced, but the expression of PcDorsal and PcSTAT was not affected. Furthermore, after PcATF4 knockdown and challenge with or without Vibrio, the expression of ALF1 and ALF2 was also decreased while the expression of PcToll2 was upregulated. These results suggested that PcToll2 might regulate the expression of ALF1 and ALF2 by promoting the import of PcATF4, instead of the routine transcription factor PcDorsal, into the nucleus participating in the immune defense against Gram-negative bacteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Incorporating elements of social franchising in government health services improves the quality of infant and young child feeding counselling services at commune health centres in Vietnam.

    PubMed

    Nguyen, Phuong H; Kim, Sunny S; Keithly, Sarah C; Hajeebhoy, Nemat; Tran, Lan M; Ruel, Marie T; Rawat, Rahul; Menon, Purnima

    2014-12-01

    Although social franchising has been shown to enhance the quality of reproductive health services in developing countries, its effect on nutrition services remains unexamined. This study assessed the effects of incorporating elements of social franchising on shaping the quality of infant and young child feeding (IYCF) counselling facilities and services in Vietnam. Process-related data collected 12 months after the launch of the first franchises were used to compare randomly assigned Alive & Thrive-supported health facilities (AT-F, n = 20) with standard facilities (SF, n = 12) across three dimensions of service quality: 'structure', 'process' and 'outcome' that capture the quality of facilities, service delivery, and client perceptions and use, respectively. Data collection included facility assessments (n = 32), staff surveys (n = 96), counselling observations (n = 137), client exit interviews (n = 137) and in-depth interviews with mothers (n = 48). Structure: AT-F were more likely to have an unshared, well-equipped room for nutrition counselling than SF (65.0% vs 10.0%). Compared with SF providers, AT-F staff had better IYCF knowledge (mean score 9.9 vs 8.8, range 0-11 for breastfeeding; mean score 3.6 vs 3.2, range 0-4 for complementary feeding). AT-F providers also demonstrated significantly better interpersonal communication skills (score 9.6 vs 5.1, range 0-13) and offered more comprehensive counselling sessions. Overall utilization of franchises was low (10%). A higher proportion of pregnant women utilized franchise services (48.9%), compared with mothers with children 6-23.9 months (1.4%). There was no quantitative difference in client satisfaction with counselling services between AT-F and SF, but franchise users praised the AT-F for problem solving related to child feeding. Incorporating elements of social franchising significantly enhances the quality of IYCF counselling services within government primary healthcare facilities, particularly their structural and process attributes. Provided that service utilization is improved through demand generation, this model has the potential to impact IYCF practices and child nutrition. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2013; all rights reserved.

  6. Low- and high-order harmonic generation in the extended plasmas produced by laser ablation of zinc and manganese targets

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

    Ganeev, R. A., E-mail: rashid-ganeev@mail.ru; Physical Department, Voronezh State University, Voronezh 394006; Baba, M.

    The systematic studies of the harmonic generation of ultrashort laser pulses in the 5-mm-long Zn and Mn plasmas (i.e., application of nanosecond, picosecond, and femtosecond pulses for ablation, comparison of harmonic generation from atomic, ionic, and cluster-contained species of plasma, variation of plasma length, two-color pump of plasmas, etc.) are presented. The conversion efficiency of the 11th–19th harmonics generated in the Zn plasma was ∼5 × 10{sup −5}. The role of the ionic resonances of Zn near the 9th and 10th harmonics on the enhancement of harmonics is discussed. The enhancement of harmonics was also analyzed using the two-color pump of extendedmore » plasmas, which showed similar intensities of the odd and even harmonics along the whole range of generation. The harmonics up to the 107th order were demonstrated in the case of manganese plasma. The comparison of harmonic generation in the 5-mm-long and commonly used short (≤0.5 mm) plasma plumes showed the advanced properties of extended media.« less

  7. 75 FR 64354 - Agency Information Collection Activities: Proposed Collection; Comments Requested

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-19

    ... of Information Collection Under Review: ATF F 5630.5R, NFA Special Tax Renewal Registration and Return; ATF F 5630.5RC, NFA Special Tax Location Registration Listing; ATF F 5630.7, NFA Special Tax... collection. (2) Title of the Form/Collection: ATF F 5630.5R, NFA Special Tax Renewal Registration and Return...

  8. Two-Color Laser High-Harmonic Generation in Cavitated Plasma Wakefields

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

    Schroeder, Carl; Benedetti, Carlo; Esarey, Eric

    2016-10-03

    A method is proposed for producing coherent x-rays via high-harmonic generation using a laser interacting with highly-stripped ions in cavitated plasma wakefields. Two laser pulses of different colors are employed: a long-wavelength pulse for cavitation and a short-wavelength pulse for harmonic generation. This method enables efficient laser harmonic generation in the sub-nm wavelength regime.

  9. Essential role of eIF5-mimic protein in animal development is linked to control of ATF4 expression

    USDA-ARS?s Scientific Manuscript database

    Translational control of ATF4 through upstream ORFs (uORFs) plays an important role in eukaryotic gene regulation. While ATF4 translation is typically induced by inhibitory phosphorylation of eIF2, ATF4 translation can be also induced by expression of a new translational inhibitor protein, eIF5-mimi...

  10. Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene

    PubMed Central

    Maekawa, Toshio; Kim, Seungjoon; Nakai, Daisuke; Makino, Chieko; Takagi, Tsuyoshi; Ogura, Hiroo; Yamada, Kazuyuki; Chatton, Bruno; Ishii, Shunsuke

    2010-01-01

    Many symptoms induced by isolation rearing of rodents may be relevant to neuropsychiatric disorders, including depression. However, identities of transcription factors that regulate gene expression in response to chronic social isolation stress remain elusive. The transcription factor ATF-7 is structurally related to ATF-2, which is activated by various stresses, including inflammatory cytokines. Here, we report that Atf-7-deficient mice exhibit abnormal behaviours and increased 5-HT receptor 5B (Htr5b) mRNA levels in the dorsal raphe nuclei. ATF-7 silences the transcription of Htr5B by directly binding to its 5′-regulatory region, and mediates histone H3-K9 trimethylation via interaction with the ESET histone methyltransferase. Isolation-reared wild-type (WT) mice exhibit abnormal behaviours that resemble those of Atf-7-deficient mice. Upon social isolation stress, ATF-7 in the dorsal raphe nucleus is phosphorylated via p38 and is released from the Htr5b promoter, leading to the upregulation of Htr5b. Thus, ATF-7 may have a critical role in gene expression induced by social isolation stress. PMID:19893493

  11. Activating transcription factor 4 regulates stearate-induced vascular calcification.

    PubMed

    Masuda, Masashi; Ting, Tabitha C; Levi, Moshe; Saunders, Sommer J; Miyazaki-Anzai, Shinobu; Miyazaki, Makoto

    2012-08-01

    Previously, we reported that stearate, a saturated fatty acid, promotes osteoblastic differentiation and mineralization of vascular smooth muscle cells (VSMC). In this study, we examined the molecular mechanisms by which stearate promotes vascular calcification. ATF4 is a pivotal transcription factor in osteoblastogenesis and endoplasmic reticulum (ER) stress. Increased stearate by either supplementation of exogenous stearic acid or inhibition of stearoyl-CoA desaturase (SCD) by CAY10566 induced ATF4 mRNA, phosphorylated ATF4 protein, and total ATF4 protein. Induction occurred through activation of the PERK-eIF2α pathway, along with increased osteoblastic differentiation and mineralization of VSMCs. Either stearate or the SCD inhibitor but not oleate or other fatty acid treatments also increased ER stress as determined by the expression of p-eIF2α, CHOP, and the spliced form of XBP-1, which were directly correlated with ER stearate levels. ATF4 knockdown by lentiviral ATF4 shRNA blocked osteoblastic differentiation and mineralization induced by stearate and SCD inhibition. Conversely, treatment of VSMCs with an adenovirus containing ATF4 induced vascular calcification. Our results demonstrated that activation of ATF4 mediates vascular calcification induced by stearate.

  12. Activating transcription factor 4 regulates stearate-induced vascular calcification

    PubMed Central

    Masuda, Masashi; Ting, Tabitha C.; Levi, Moshe; Saunders, Sommer J.; Miyazaki-Anzai, Shinobu; Miyazaki, Makoto

    2012-01-01

    Previously, we reported that stearate, a saturated fatty acid, promotes osteoblastic differentiation and mineralization of vascular smooth muscle cells (VSMC). In this study, we examined the molecular mechanisms by which stearate promotes vascular calcification. ATF4 is a pivotal transcription factor in osteoblastogenesis and endoplasmic reticulum (ER) stress. Increased stearate by either supplementation of exogenous stearic acid or inhibition of stearoyl-CoA desaturase (SCD) by CAY10566 induced ATF4 mRNA, phosphorylated ATF4 protein, and total ATF4 protein. Induction occurred through activation of the PERK-eIF2α pathway, along with increased osteoblastic differentiation and mineralization of VSMCs. Either stearate or the SCD inhibitor but not oleate or other fatty acid treatments also increased ER stress as determined by the expression of p-eIF2α, CHOP, and the spliced form of XBP-1, which were directly correlated with ER stearate levels. ATF4 knockdown by lentiviral ATF4 shRNA blocked osteoblastic differentiation and mineralization induced by stearate and SCD inhibition. Conversely, treatment of VSMCs with an adenovirus containing ATF4 induced vascular calcification. Our results demonstrated that activation of ATF4 mediates vascular calcification induced by stearate. PMID:22628618

  13. Efficient second to ninth harmonic generation using megawatt peak power microchip laser.

    PubMed

    Bhandari, R; Tsuji, N; Suzuki, T; Nishifuji, M; Taira, T

    2013-11-18

    We report the design and use of a megawatt peak power Nd:YAG/Cr4+:YAG microchip laser for efficient second to ninth harmonic generation. We show that the sub-nanosecond pulse width region, between 100 ps and 1 ns, is ideally suited for efficient wavelength conversion. Using this feature, we report 85% second harmonic generation efficiency using lithium triborate (LBO), 60% fourth harmonic generation efficiency usingß-barium borate, and 44% IR to UV third harmonic generation efficiency using Type I and Type II LBO. Finally, we report the first demonstration of 118 nm VUV generation in xenon gas using a microchip laser.

  14. Reprogramming cell fate with a genome-scale library of artificial transcription factors.

    PubMed

    Eguchi, Asuka; Wleklinski, Matthew J; Spurgat, Mackenzie C; Heiderscheit, Evan A; Kropornicka, Anna S; Vu, Catherine K; Bhimsaria, Devesh; Swanson, Scott A; Stewart, Ron; Ramanathan, Parameswaran; Kamp, Timothy J; Slukvin, Igor; Thomson, James A; Dutton, James R; Ansari, Aseem Z

    2016-12-20

    Artificial transcription factors (ATFs) are precision-tailored molecules designed to bind DNA and regulate transcription in a preprogrammed manner. Libraries of ATFs enable the high-throughput screening of gene networks that trigger cell fate decisions or phenotypic changes. We developed a genome-scale library of ATFs that display an engineered interaction domain (ID) to enable cooperative assembly and synergistic gene expression at targeted sites. We used this ATF library to screen for key regulators of the pluripotency network and discovered three combinations of ATFs capable of inducing pluripotency without exogenous expression of Oct4 (POU domain, class 5, TF 1). Cognate site identification, global transcriptional profiling, and identification of ATF binding sites reveal that the ATFs do not directly target Oct4; instead, they target distinct nodes that converge to stimulate the endogenous pluripotency network. This forward genetic approach enables cell type conversions without a priori knowledge of potential key regulators and reveals unanticipated gene network dynamics that drive cell fate choices.

  15. ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae.

    PubMed

    Elefteriou, Florent; Benson, M Douglas; Sowa, Hideaki; Starbuck, Michael; Liu, Xiuyun; Ron, David; Parada, Luis F; Karsenty, Gerard

    2006-12-01

    The transcription factor ATF4 enhances bone formation by favoring amino acid import and collagen synthesis in osteoblasts, a function requiring its phosphorylation by RSK2, the kinase inactivated in Coffin-Lowry Syndrome. Here, we show that in contrast, RSK2 activity, ATF4-dependent collagen synthesis, and bone formation are increased in mice lacking neurofibromin in osteoblasts (Nf1(ob)(-/-) mice). Independently of RSK2, ATF4 phosphorylation by PKA is enhanced in Nf1(ob)(-/-) mice, thereby increasing Rankl expression, osteoclast differentiation, and bone resorption. In agreement with ATF4 function in amino acid transport, a low-protein diet decreased bone protein synthesis and normalized bone formation and bone mass in Nf1(ob)(-/-) mice without affecting other organ weight, while a high-protein diet overcame Atf4(-/-) and Rsk2(-/-) mice developmental defects, perinatal lethality, and low bone mass. By showing that ATF4-dependent skeletal dysplasiae are treatable by dietary manipulations, this study reveals a molecular connection between nutrition and skeletal development.

  16. Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

    PubMed Central

    Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

    2012-01-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

  17. Reprogramming cell fate with a genome-scale library of artificial transcription factors

    PubMed Central

    Eguchi, Asuka; Wleklinski, Matthew J.; Spurgat, Mackenzie C.; Heiderscheit, Evan A.; Kropornicka, Anna S.; Vu, Catherine K.; Bhimsaria, Devesh; Swanson, Scott A.; Stewart, Ron; Ramanathan, Parameswaran; Kamp, Timothy J.; Slukvin, Igor; Thomson, James A.; Dutton, James R.; Ansari, Aseem Z.

    2016-01-01

    Artificial transcription factors (ATFs) are precision-tailored molecules designed to bind DNA and regulate transcription in a preprogrammed manner. Libraries of ATFs enable the high-throughput screening of gene networks that trigger cell fate decisions or phenotypic changes. We developed a genome-scale library of ATFs that display an engineered interaction domain (ID) to enable cooperative assembly and synergistic gene expression at targeted sites. We used this ATF library to screen for key regulators of the pluripotency network and discovered three combinations of ATFs capable of inducing pluripotency without exogenous expression of Oct4 (POU domain, class 5, TF 1). Cognate site identification, global transcriptional profiling, and identification of ATF binding sites reveal that the ATFs do not directly target Oct4; instead, they target distinct nodes that converge to stimulate the endogenous pluripotency network. This forward genetic approach enables cell type conversions without a priori knowledge of potential key regulators and reveals unanticipated gene network dynamics that drive cell fate choices. PMID:27930301

  18. Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis.

    PubMed

    Kim, Ji Yeon; Park, Keon Jae; Hwang, Joo-Yeon; Kim, Gyu Hee; Lee, DaeYeon; Lee, Yoo Jeong; Song, Eun Hyun; Yoo, Min-Gyu; Kim, Bong-Jo; Suh, Young Ho; Roh, Gu Seob; Gao, Bin; Kim, Won; Kim, Won-Ho

    2017-08-01

    Non-alcoholic fatty liver disease (NAFLD) contributes to impaired glucose tolerance, leading to type 2 diabetes (T2D); however, the precise mechanisms and target molecules that are involved remain unclear. Activating transcription factor 3 (ATF3) is associated with β-cell dysfunction that is induced by severe stress signals in T2D. We aimed to explore the exact functional role of ATF3 as a mechanistic link between hepatic steatosis and T2D development. Zucker diabetic fatty (ZDF) rats were utilized for animal experiments. An in vivo-jetPEI siRNA delivery system against ATF3 was used for loss-of-function experiments. We analyzed the baseline cross-sectional data derived from the biopsy-proven NAFLD registry (n=322). Human sera and liver tissues were obtained from 43 patients with biopsy-proven NAFLD and from seven healthy participants. ATF3 was highly expressed in the livers of ZDF rats and in human participants with NAFLD and/or T2D. Insulin resistance and hepatic steatosis were associated with increased ATF3 expression and decreased fatty acid oxidation via mitochondrial dysfunction and were attenuated by in vivo ATF3 silencing. Knockdown of ATF3 also ameliorated glucose intolerance, impaired insulin action, and inflammatory responses in ZDF rats. In patients with NAFLD and/or T2D, a significant positive correlation was observed between hepatic ATF3 expression and surrogate markers of T2D, mitochondrial dysfunction, and macrophage infiltration. Increased hepatic ATF3 expression is closely associated with hepatic steatosis and incident T2D; therefore, ATF3 may serve as a potential therapeutic target for NAFLD and hepatic steatosis-induced T2D. Hepatic activating transcription factor 3 (ATF3) may play an important role in oxidative stress-mediated hepatic steatosis and the development of type 2 diabetes (T2D) in a Zucker diabetic fatty (ZDF) rat model and in human patients with non-alcoholic fatty liver disease (NAFLD). Therefore, ATF3 may be a useful biomarker for predicting the progression of NAFLD and the development of T2D. Furthermore, given the significant association between hepatic ATF3 expression and both hepatic steatosis and impaired glucose homeostasis, in vivo ATF3 silencing may be a potential central strategy for preventing and managing NAFLD and T2D. Copyright © 2017 European Association for the Study of the Liver. All rights reserved.

  19. Tailored semiconductors for high-harmonic optoelectronics

    NASA Astrophysics Data System (ADS)

    Sivis, Murat; Taucer, Marco; Vampa, Giulio; Johnston, Kyle; Staudte, André; Naumov, Andrei Yu.; Villeneuve, D. M.; Ropers, Claus; Corkum, P. B.

    2017-07-01

    The advent of high-harmonic generation in gases 30 years ago set the foundation for attosecond science and facilitated ultrafast spectroscopy in atoms, molecules, and solids. We explore high-harmonic generation in the solid state by means of nanostructured and ion-implanted semiconductors. We use wavelength-selective microscopic imaging to map enhanced harmonic emission and show that the generation medium and the driving field can be locally tailored in solids by modifying the chemical composition and morphology. This enables the control of high-harmonic technology within precisely engineered solid targets. We demonstrate customized high-harmonic wave fields with wavelengths down to 225 nanometers (ninth-harmonic order of 2-micrometer laser pulses) and present an integrated Fresnel zone plate target in silicon, which leads to diffraction-limited self-focusing of the generated harmonics down to 1-micrometer spot sizes.

  20. XBP-1 Regulates a Subset of Endoplasmic Reticulum Resident Chaperone Genes in the Unfolded Protein Response

    PubMed Central

    Lee, Ann-Hwee; Iwakoshi, Neal N.; Glimcher, Laurie H.

    2003-01-01

    The mammalian unfolded protein response (UPR) protects the cell against the stress of misfolded proteins in the endoplasmic reticulum (ER). We have investigated here the contribution of the UPR transcription factors XBP-1, ATF6α, and ATF6β to UPR target gene expression. Gene profiling of cell lines lacking these factors yielded several XBP-1-dependent UPR target genes, all of which appear to act in the ER. These included the DnaJ/Hsp40-like genes, p58IPK, ERdj4, and HEDJ, as well as EDEM, protein disulfide isomerase-P5, and ribosome-associated membrane protein 4 (RAMP4), whereas expression of BiP was only modestly dependent on XBP-1. Surprisingly, given previous reports that enforced expression of ATF6α induced a subset of UPR target genes, cells deficient in ATF6α, ATF6β, or both had minimal defects in upregulating UPR target genes by gene profiling analysis, suggesting the presence of compensatory mechanism(s) for ATF6 in the UPR. Since cells lacking both XBP-1 and ATF6α had significantly impaired induction of select UPR target genes and ERSE reporter activation, XBP-1 and ATF6α may serve partially redundant functions. No UPR target genes that required ATF6β were identified, nor, in contrast to XBP-1 and ATF6α, did the activity of the UPRE or ERSE promoters require ATF6β, suggesting a minor role for it during the UPR. Collectively, these results suggest that the IRE1/XBP-1 pathway is required for efficient protein folding, maturation, and degradation in the ER and imply the existence of subsets of UPR target genes as defined by their dependence on XBP-1. Further, our observations suggest the existence of additional, as-yet-unknown, key regulators of the UPR. PMID:14559994

  1. Harmonic generation and parametric decay in the ion cyclotron frequency range

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

    Skiff, F.N.; Wong, K.L.; Ono, M.

    1984-06-01

    Harmonic generation and parametric decay are examined in a toroidal ACT-I plasma using electrostatic plate antennas. The harmonic generation, which is consistent with sheath rectification, is sufficiently strong that the nonlinearly generated harmonic modes themselves decay parametrically. Resonant and nonresonant parametric decay of the second harmonic are observed and compared with uniform pump theory. Resonant decay of lower hybrid waves into lower hybrid waves and slow ion cyclotron waves is seen for the first time. Surprisingly, the decay processes are nonlinearly saturated, indicating absolute instability.

  2. The Loss of Activating Transcription Factor 4 (ATF4) Reduces Bone Toughness and Fracture Toughness

    PubMed Central

    Makowski, Alexander J.; Uppuganti, Sasidhar; Waader, Sandra A.; Whitehead, Jack M.; Rowland, Barbara J.; Granke, Mathilde; Mahadevan-Jansen, Anita; Yang, Xiangli; Nyman, Jeffry S.

    2014-01-01

    Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of the seimportant factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4−/− littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4−/− mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4−/− mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1 Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also maintaining bone toughness and fracture toughness. PMID:24509412

  3. The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness.

    PubMed

    Makowski, Alexander J; Uppuganti, Sasidhar; Wadeer, Sandra A; Whitehead, Jack M; Rowland, Barbara J; Granke, Mathilde; Mahadevan-Jansen, Anita; Yang, Xiangli; Nyman, Jeffry S

    2014-05-01

    Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of these important factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4-/- littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4-/- mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective of age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4-/- mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also in maintaining bone toughness and fracture toughness. Published by Elsevier Inc.

  4. Frontline Science: ATF3 is responsible for the inhibition of TNF-α release and the impaired migration of acute ethanol-exposed monocytes and macrophages.

    PubMed

    Hu, Chaojie; Meng, Xiaoming; Huang, Cheng; Shen, Chenlin; Li, Jun

    2017-03-01

    Binge drinking represses host innate immunity and leads to a high risk of infection. Acute EtOH-pretreated macrophages exhibit a decreased production of proinflammatory mediators in response to LPS. ATF3 is induced and counter-regulates the LPS/TLR4 inflammatory cascade. Here, we investigated the potential role of ATF3 in LPS tolerance in acute ethanol-pretreated macrophages. We found that there was an inverse correlation between ATF3 and LPS-induced TNF-α production in acute ethanol-pretreated murine monocytes and macrophages. The knockdown of ATF3 attenuated the inhibitory effects of acute ethanol treatment on LPS-induced TNF-α production. Furthermore, ChIP assays and co-IP demonstrated that ATF3, together with HDAC1, negatively modulated the transcription of TNF-α. In binge-drinking mice challenged with LPS, an up-regulation of ATF3 and HDAC1 and a concomitant decrease in TNF-α were observed. Given that HDAC1 was concomitantly induced in acute ethanol-exposed monocytes and macrophages, we used the HDACi TSA or silenced HDAC1 to explore the role of HDAC1 in acute ethanol-treated macrophages. Our results revealed that TSA treatment and HDAC1 knockdown prevented acute ethanol-induced ATF3 expression and the inhibition of TNF-α transcription. These data indicated a dual role for HDAC1 in acute ethanol-induced LPS tolerance. Furthermore, we showed that the induction of ATF3 led to the impaired migration of BM monocytes and macrophages. Overall, we present a novel role for ATF3 in the inhibition of LPS-induced TNF-α and in the impairment of monocyte and macrophage migration. © Society for Leukocyte Biology.

  5. Dynamical origin of near- and below-threshold harmonic generation of Cs in an intense mid-infrared laser field.

    PubMed

    Li, Peng-Cheng; Sheu, Yae-Lin; Laughlin, Cecil; Chu, Shih-I

    2015-05-20

    Near- and below-threshold harmonic generation provides a potential approach to generate vacuum-ultraviolet frequency comb. However, the dynamical origin of in these lower harmonics is less understood and largely unexplored. Here we perform an ab initio quantum study of the near- and below-threshold harmonic generation of caesium (Cs) atoms in an intense 3,600-nm mid-infrared laser field. Combining with a synchrosqueezing transform of the quantum time-frequency spectrum and an extended semiclassical analysis, the roles of multiphoton and multiple rescattering trajectories on the near- and below-threshold harmonic generation processes are clarified. We find that the multiphoton-dominated trajectories only involve the electrons scattered off the higher part of the combined atom-field potential followed by the absorption of many photons in near- and below-threshold regime. Furthermore, only the near-resonant below-threshold harmonic is exclusive to exhibit phase locked features. Our results shed light on the dynamic origin of the near- and below-threshold harmonic generation.

  6. Non-phase-matched enhancement of second-harmonic generation in multilayer nonlinear structures with internal reflections.

    PubMed

    Centini, Marco; D'Aguanno, Giuseppe; Sciscione, Letizia; Sibilia, Concita; Bertolotti, Mario; Scalora, Michael; Bloemer, Mark J

    2004-08-15

    Traditional notions of second-harmonic generation rely on phase matching or quasi phase matching to achieve good conversion efficiencies. We present an entirely new concept for efficient second-harmonic generation that is based on the interference of counterpropagating waves in multilayer structures. Conversion efficiencies are an order of magnitude larger than with phase-matched second-harmonic generation in similar multilayer structures.

  7. Second and Third Harmonic Generation in Metal-Based Nanostructures

    DTIC Science & Technology

    2010-01-01

    Prudenzano, D. de Ceglia, N. Akozbek, M.J. Bloemer, P. Ashley, and M. Scalora , "Enhanced transmission and second harmonic generation from...Fazio, C. Sibilia, M. J. Bloemer, and M. Scalora , "Second-harmonic generation from metallodielectric multilayer photonic-band-gap structures", Phys...harmonic generation", Phys. Rev. B 38, 7985 (1988). [50] M. A. Vincenti, D. de Ceglia, M. Buncick, N. Akozbek, M. J. Bloemer, and M. Scalora

  8. Symmetry properties of second harmonics generated by antisymmetric Lamb waves

    NASA Astrophysics Data System (ADS)

    Zhu, Wujun; Xiang, Yanxun; Liu, Chang-Jun; Deng, Mingxi; Xuan, Fu-Zhen

    2018-03-01

    Symmetry properties of second harmonics generated by antisymmetric primary Lamb waves are systematically studied in this work. In theory, the acoustic field of second harmonic Lamb waves is obtained by using the perturbation approximation and normal modal method, and the energy flux transfer from the primary Lamb waves to second harmonics is mainly explored. Symmetry analyses indicate that either the symmetric or antisymmetric Lamb waves can merely generate the symmetric second harmonics. Finite element simulations are performed on the nonlinear Lamb wave propagation of the antisymmetric A0 mode in the low frequency region. The signals of the second harmonics and the symmetric second harmonic s0 mode are found to be exactly equivalent in the time domain. The relative acoustic nonlinearity parameter A2/A12 oscillates with the propagation distance, and the oscillation amplitude and spatial period are well consistent with the theoretical prediction of the A0-s0 mode pair, which means that only the second harmonic s0 mode is generated by the antisymmetric primary A0 mode. Experiments are further conducted to examine the cumulative generation of symmetric second harmonics for the antisymmetric-symmetric mode pair A3-s6. Results show that A2/A12 increases linearly with the propagation distance, which means that the symmetric second harmonic s6 mode is generated cumulatively by the antisymmetric primary A3 mode. The present investigation systematically corroborates the proposed theory that only symmetric second harmonics can be generated accompanying the propagation of antisymmetric primary Lamb waves in a plate.

  9. miR-141-3p functions as a tumor suppressor modulating activating transcription factor 5 in glioma.

    PubMed

    Wang, Mengyuan; Hu, Ming; Li, Zhaohua; Qian, Dongmeng; Wang, Bin; Liu, David X

    2017-09-02

    Glioma is the most common malignant primary brain tumor which arises from the central nervous system. Our studies reported that an anti-apoptotic factor, activating transcription factor 5 (ATF5), is highly expressed in malignant glioma specimens and cell lines. Downregulation by dominant-negetive ATF5 could repress glioma cell proliferation and accelerate apoptosis. Here, we further investigate the upstream factor which regulates ATF5 expression. Bioinformatic analysis showed that ATF5 was a potential target of miR-141-3p. Luciferase reporter assay verified that miR-141-3p specifically targeted the ATF5 3'-UTR in glioma cells. Functional studied suggested that miR-141-3p overexpression inhibited proliferation and promoted apoptosis of glioma cells (U87MG and U251). Xenograft experiments proved the inhibition of miR-141-3p on glioma growth in vivo. Moreover, exogenous ATF5 without 3'-UTR restored the cell proliferation inhibition triggered by miR-141-3p. Taken together, we put forward that miR-141-3p is a new upstream target towards ATF5. It can serve as a crucial tumor suppressor in regulating the ATF5-regulated growth of malignant glioma. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Tunneling ionization and harmonic generation in two-color fields

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

    Kondo, K.; Kobayashi, Y.; Sagisaka, A.

    1996-02-01

    Tunneling ionization and harmonic generation in two-color fields were studied with a fundamental beam ({omega}) and its harmonics (2{omega},3{omega}), which were generated by a 100-fs Ti:sapphire laser. Ion yields of atoms and molecules were successfully controlled by means of a change in the relative phase between {omega} and 3{omega} pulses. Two-color interference was clearly observed in photoelectron spectra and harmonic spectra. In the {omega}{endash}2{omega} field even-order harmonics were observed in which the intensity was almost equal to that of the odd harmonics because of an asymmetric optical field. These results were compared with the quasi-static model for ionization and withmore » the quantum theory for harmonic generation. {copyright} {ital 1996 Optical Society of America.}« less

  11. Generations of even-order harmonics from vibrating H2+ and T2+ in the rising and falling parts of the laser field

    NASA Astrophysics Data System (ADS)

    Feng, Liqiang; Kapteyn, Henry J.; Feng, April Y.

    2018-04-01

    The generations of the even-order harmonics from H2+ and one of its isotope T2+ have been theoretically investigated beyond the Born-Oppenheimer approximation. Normally, the high-order harmonic generation (HHG) only contains odd-order harmonics for the orbital symmetry along the direction of laser polarization. Here, we showed that due to asymmetric harmonic emission (asymmetric half-wave profile), the even-order harmonics can be generated in the rising and the falling part of the laser field. In detail, in the lower initial vibrational state, the even-order harmonics main come from the falling part of the laser field; while as the initial vibrational state increases, the identified even-order harmonics in the falling part of the laser field are decreased; while some other even-order harmonics coming from the rising part of the laser field can be produced. The interesting phenomena have been proved through studying the spatial distributions and the time profiles of the HHG.

  12. Steam Oxidation Testing in the Severe Accident Test Station

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

    Pint, Bruce A.

    After the March 2011 accident at Fukushima Daiichi, Oak Ridge National Laboratory (ORNL) began conducting high temperature steam oxidation testing of candidate materials for accident tolerant fuel (ATF) cladding in August 2011 [1-11]. The ATF concept is to enhance safety margins in light water reactors (LWR) during severe accident scenarios by identifying materials with 100× slower steam oxidation rates compared to current Zr-based alloys. In 2012, the ORNL laboratory equipment was expanded and made available to the entire ATF community as the Severe Accident Test Station (SATS) [4,12]. Compared to the current UO2/Zr-based alloy fuel system, an ATF alternative wouldmore » significantly reduce the rate of heat and hydrogen generation in the core during a coolant-limited severe accident [13-14]. The steam oxidation behavior of candidate materials is a key metric in the evaluation of ATF concepts and also an important input into models [15-17]. However, initial modeling work of FeCrAl cladding has used incomplete information on the physical properties of FeCrAl. Also, the steam oxidation data being collected at 1200°-1700°C is unique as no prior work has considered steam oxidation of alloys at such high temperatures. Also, because many accident scenarios include steadily increasing temperatures, the required data are not traditional isothermal exposures but exposures with varying “ramp” rates. In some cases, the steam oxidation behavior has been surprising and difficult to interpret. Thus, more fundamental information continues to be collected. In addition, more work continues to focus on commercially-manufactured tube material. This report summarizes recent work to characterize the behavior of candidate alloys exposed to high temperature steam, evaluate steam oxidation behavior in various ramp scenarios and continue to collect integral data on FeCrAl compared to conventional Zr-based cladding.« less

  13. Ceapins are a new class of unfolded protein response inhibitors, selectively targeting the ATF6α branch

    PubMed Central

    Gallagher, Ciara M; Garri, Carolina; Cain, Erica L; Ang, Kenny Kean-Hooi; Wilson, Christopher G; Chen, Steven; Hearn, Brian R; Jaishankar, Priyadarshini; Aranda-Diaz, Andres; Arkin, Michelle R; Renslo, Adam R; Walter, Peter

    2016-01-01

    The membrane-bound transcription factor ATF6α plays a cytoprotective role in the unfolded protein response (UPR), required for cells to survive ER stress. Activation of ATF6α promotes cell survival in cancer models. We used cell-based screens to discover and develop Ceapins, a class of pyrazole amides, that block ATF6α signaling in response to ER stress. Ceapins sensitize cells to ER stress without impacting viability of unstressed cells. Ceapins are highly specific inhibitors of ATF6α signaling, not affecting signaling through the other branches of the UPR, or proteolytic processing of its close homolog ATF6β or SREBP (a cholesterol-regulated transcription factor), both activated by the same proteases. Ceapins are first-in-class inhibitors that can be used to explore both the mechanism of activation of ATF6α and its role in pathological settings. The discovery of Ceapins now enables pharmacological modulation all three UPR branches either singly or in combination. DOI: http://dx.doi.org/10.7554/eLife.11878.001 PMID:27435960

  14. ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae

    PubMed Central

    Elefteriou, Florent; Benson, M. Douglas; Sowa, Hideaki; Starbuck, Michael; Liu, Xiuyun; Ron, David; Parada, Luis F.; Karsenty, Gerard

    2009-01-01

    Summary The transcription factor ATF4 enhances bone formation by favoring amino acid import and collagen synthesis in osteoblasts, a function requiring its phosphorylation by RSK2, the kinase inactivated in Coffin-Lowry Syndrome. Here, we show that in contrast, RSK2 activity, ATF4-dependent collagen synthesis, and bone formation are increased in mice lacking neurofibromin in osteoblasts (Nf1ob−/− mice). Independently of RSK2, ATF4 phosphorylation by PKA is enhanced in Nf1ob−/− mice, thereby increasing Rankl expression, osteoclast differentiation, and bone resorption. In agreement with ATF4 function in amino acid transport, a low-protein diet decreased bone protein synthesis and normalized bone formation and bone mass in Nf1ob−/− mice without affecting other organ weight, while a high-protein diet overcame Atf4−/− and Rsk2−/− mice developmental defects, perinatal lethality, and low bone mass. By showing that ATF4-dependent skeletal dysplasiae are treatable by dietary manipulations, this study reveals a molecular connection between nutrition and skeletal development. PMID:17141628

  15. Astrometric Telescope Facility isolation and pointing study

    NASA Technical Reports Server (NTRS)

    Hibble, William; Allen, Terry; Jackson, Louis; Medbery, James; Self, Richard

    1988-01-01

    The Astrometric Telescope Facility (ATF), an optical telescope designed to detect extrasolar planetary systems, is scheduled to be a major user of the Space Station's Payload Pointing System (PPS). However, because the ATF has such a stringent pointing stability specification and requires + or - 180 deg roll about its line of sight, mechanisms to enhance the basic PPS capability are required. The ATF pointing performance achievable by the addition of a magnetic isolation and pointing system (MIPS) between the PPS upper gimbal and the ATF, and separately, by the addition of a passive isolation system between the Space Station and the PPS base was investigated. The candidate MIPS can meet the ATF requirements in the presence of a 0.01 g disturbance. It fits within the available annular region between the PPS and the ATF while meeting power and weight limitations and providing the required roll motion, payload data and power services. By contrast, the passive base isolator system must have an unrealistically low isolation bandwidth on all axes to meet ATF pointing requirements and does not provide roll about the line of sight.

  16. High-harmonic generation in amorphous solids

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

    You, Yong Sing; Yin, Yanchun; Wu, Yi

    High-harmonic generation in isolated atoms and molecules has been widely utilized in extreme ultraviolet photonics and attosecond pulse metrology. Recently, high-harmonic generation has been observed in solids, which could lead to important applications such as all-optical methods to image valance charge density and reconstruct electronic band structures, as well as compact extreme ultraviolet light sources. So far these studies are confined to crystalline solids; therefore, decoupling the respective roles of long-range periodicity and high density has been challenging. Here we report the observation of high-harmonic generation from amorphous fused silica. We also decouple the role of long-range periodicity by comparingmore » harmonics generated from fused silica and crystalline quartz, which contain the same atomic constituents but differ in long-range periodicity. These results advance current understanding of the strong-field processes leading to high-harmonic generation in solids with implications for the development of robust and compact extreme ultraviolet light sources.« less

  17. High-harmonic generation in amorphous solids

    DOE PAGES

    You, Yong Sing; Yin, Yanchun; Wu, Yi; ...

    2017-09-28

    High-harmonic generation in isolated atoms and molecules has been widely utilized in extreme ultraviolet photonics and attosecond pulse metrology. Recently, high-harmonic generation has been observed in solids, which could lead to important applications such as all-optical methods to image valance charge density and reconstruct electronic band structures, as well as compact extreme ultraviolet light sources. So far these studies are confined to crystalline solids; therefore, decoupling the respective roles of long-range periodicity and high density has been challenging. Here we report the observation of high-harmonic generation from amorphous fused silica. We also decouple the role of long-range periodicity by comparingmore » harmonics generated from fused silica and crystalline quartz, which contain the same atomic constituents but differ in long-range periodicity. These results advance current understanding of the strong-field processes leading to high-harmonic generation in solids with implications for the development of robust and compact extreme ultraviolet light sources.« less

  18. Second harmonic generation at fatigue cracks by low-frequency Lamb waves: Experimental and numerical studies

    NASA Astrophysics Data System (ADS)

    Yang, Yi; Ng, Ching-Tai; Kotousov, Andrei; Sohn, Hoon; Lim, Hyung Jin

    2018-01-01

    This paper presents experimental and theoretical analyses of the second harmonic generation due to non-linear interaction of Lamb waves with a fatigue crack. Three-dimensional (3D) finite element (FE) simulations and experimental studies are carried out to provide physical insight into the mechanism of second harmonic generation. The results demonstrate that the 3D FE simulations can provide a reasonable prediction on the second harmonic generated due to the contact nonlinearity at the fatigue crack. The effect of the wave modes on the second harmonic generation is also investigated in detail. It is found that the magnitude of the second harmonic induced by the interaction of the fundamental symmetric mode (S0) of Lamb wave with the fatigue crack is much higher than that by the fundamental anti-symmetric mode (A0) of Lamb wave. In addition, a series of parametric studies using 3D FE simulations are conducted to investigate the effect of the fatigue crack length to incident wave wavelength ratio, and the influence of the excitation frequency on the second harmonic generation. The outcomes show that the magnitude and directivity pattern of the generated second harmonic depend on the fatigue crack length to incident wave wavelength ratio as well as the ratio of S0 to A0 incident Lamb wave amplitude. In summary, the findings of this study can further advance the use of second harmonic generation in damage detection.

  19. Upregulation of Endogenous HMOX1 Expression by a Computer-Designed Artificial Transcription Factor

    PubMed Central

    Guo, Hongfeng; Tian, Yi; Lu, Hai; Wei, Yong; Ying, Dajun

    2010-01-01

    Heme oxygenase-1 (HO-1) is well known as a cytoprotective factor. Research has revealed that it is a promising therapeutic target for cardiovascular diseases. In the current study, an HMOX1 (HO-1 gene) enhancer-specific artificial zinc-finger protein (AZP) was designed using bioinformatical methods. Then, an artificial transcription factor (ATF) was constructed based on the AZP. In the ATF, the p65 functional domain was used as the effector domain (ED), and a nuclear localization sequence (NLS) was also included. We next analyzed the affinity of the ATF to the HMOX1 enhancer and the effect of the ATF on endogenous HMOX1 expression. The results suggest that the ATF could effectively upregulate endogenous HMOX1 expression in ECV304 cells. With further research, the ATF could be developed as a potential drug for cardiovascular diseases. PMID:20706680

  20. Application of mid-infrared pulses for quasi-phase-matching of high-order harmonics in silver plasma.

    PubMed

    Ganeev, Rashid A; Husakou, Anton; Suzuki, Masayuki; Kuroda, Hiroto

    2016-02-22

    We demonstrate the quasi-phase-matching of a group of harmonics generated in Ag multi-jet plasma using tunable pulses in the region of 1160 - 1540 nm and their second harmonic emission. The numerical treatment of this effect includes microscopic description of the harmonic generation, propagation of the pump pulse, and the propagation of the generated harmonics. We obtained more than 30-fold growth of harmonics at the conditions of quasi-phase-matching in the region of 35 nm using eight-jet plasma compared with the case of imperforated plasma.

  1. Mitochondrial ATF2 translocation contributes to apoptosis induction and BRAF inhibitor resistance in melanoma through the interaction of Bim with VDAC1.

    PubMed

    Gao, Zongwei; Shang, Qingjuan; Liu, Zhaoyun; Deng, Chun; Guo, Chunbao

    2015-11-03

    The mitochondrial accumulation of ATF2 is involved in tumor suppressor activities via cytochrome c release in melanoma cells. However, the signaling pathways that connect mitochondrial ATF2 accumulation and cytochrome c release are not well documented. Several melanoma cell lines, B16F10, K1735M2, A375 and A375-R1, were treated with paclitaxel and vemurafenib to test the function of mitochondrial ATF2 and its connection to Bim and voltage-dependent anion channel 1 (VDAC1). Immunoprecipitation analysis was performed to investigate the functional interaction between the involved proteins. VDAC1 oligomerization was evaluated using an EGS-based crosslinking assay. The expression and migration of ATF2 to the mitochondria accounted for paclitaxel stimuli and acquired resistance to BRAF inhibitors. Mitochondrial ATF2 facilitated Bim stabilization through the inhibition of its degradation by the proteasome, thereby promoting cytochrome c release and inducing apoptosis in B16F10 and A375 cells. Studies using B16F10 and A375 cells genetically modified for ATF2 indicated that mitochondrial ATF2 was able to dissociate Bim from the Mcl-1/Bim complex to trigger VDAC1 oligomerization. Immunoprecipitation analysis revealed that Bim interacts with VDAC1, and this interaction was remarkably enhanced during apoptosis. These results reveal that mitochondrial ATF2 is associated with the induction of apoptosis and BRAF inhibitor resistance through Bim activation, which might suggest potential novel therapies for the targeted induction of apoptosis in melanoma therapy.

  2. Mitochondrial ATF2 translocation contributes to apoptosis induction and BRAF inhibitor resistance in melanoma through the interaction of Bim with VDAC1

    PubMed Central

    Deng, Chun; Guo, Chunbao

    2015-01-01

    Background The mitochondrial accumulation of ATF2 is involved in tumor suppressor activities via cytochrome c release in melanoma cells. However, the signaling pathways that connect mitochondrial ATF2 accumulation and cytochrome c release are not well documented. Methods Several melanoma cell lines, B16F10, K1735M2, A375 and A375-R1, were treated with paclitaxel and vemurafenib to test the function of mitochondrial ATF2 and its connection to Bim and voltage-dependent anion channel 1 (VDAC1). Immunoprecipitation analysis was performed to investigate the functional interaction between the involved proteins. VDAC1 oligomerization was evaluated using an EGS-based crosslinking assay. Results The expression and migration of ATF2 to the mitochondria accounted for paclitaxel stimuli and acquired resistance to BRAF inhibitors. Mitochondrial ATF2 facilitated Bim stabilization through the inhibition of its degradation by the proteasome, thereby promoting cytochrome c release and inducing apoptosis in B16F10 and A375 cells. Studies using B16F10 and A375 cells genetically modified for ATF2 indicated that mitochondrial ATF2 was able to dissociate Bim from the Mcl-1/Bim complex to trigger VDAC1 oligomerization. Immunoprecipitation analysis revealed that Bim interacts with VDAC1, and this interaction was remarkably enhanced during apoptosis. Conclusion These results reveal that mitochondrial ATF2 is associated with the induction of apoptosis and BRAF inhibitor resistance through Bim activation, which might suggest potential novel therapies for the targeted induction of apoptosis in melanoma therapy. PMID:26462148

  3. Enhanced third-harmonic generation in silicon nanoparticles driven by magnetic response.

    PubMed

    Shcherbakov, Maxim R; Neshev, Dragomir N; Hopkins, Ben; Shorokhov, Alexander S; Staude, Isabelle; Melik-Gaykazyan, Elizaveta V; Decker, Manuel; Ezhov, Alexander A; Miroshnichenko, Andrey E; Brener, Igal; Fedyanin, Andrey A; Kivshar, Yuri S

    2014-11-12

    We observe enhanced third-harmonic generation from silicon nanodisks exhibiting both electric and magnetic dipolar resonances. Experimental characterization of the nonlinear optical response through third-harmonic microscopy and spectroscopy reveals that the third-harmonic generation is significantly enhanced in the vicinity of the magnetic dipole resonances. The field localization at the magnetic resonance results in two orders of magnitude enhancement of the harmonic intensity with respect to unstructured bulk silicon with the conversion efficiency limited only by the two-photon absorption in the substrate.

  4. Berberine, a natural isoquinoline alkaloid, induces NAG-1 and ATF3 expression in human colorectal cancer cells

    PubMed Central

    Piyanuch, Rojsanga; Sukhthankar, Mugdha; Baek, Seung Joon

    2007-01-01

    Berberine is known to possess a wide variety of pharmacological activities, including pro-apoptotic activity. However, its molecular targets are not elucidated at present. NAG-1 and ATF3 are induced by several dietary compounds associated with pro-apoptotic activity. Berberine induces cell growth arrest, apoptosis, NAG-1, and ATF3 in human colorectal cancer cells. ATF3 induction by berberine is mediated in a p53-dependent manner, whereas NAG-1 induction by berberine is mediated by multiple signaling pathways. Our results suggest that berberine facilitates apoptosis and that NAG-1 and ATF3 expression plays an important role in berberine-induced apoptosis. PMID:17964072

  5. A TAD further: exogenous control of gene activation.

    PubMed

    Mapp, Anna K; Ansari, Aseem Z

    2007-01-23

    Designer molecules that can be used to impose exogenous control on gene transcription, artificial transcription factors (ATFs), are highly desirable as mechanistic probes of gene regulation, as potential therapeutic agents, and as components of cell-based devices. Recently, several advances have been made in the design of ATFs that activate gene transcription (activator ATFs), including reports of small-molecule-based systems and ATFs that exhibit potent activity. However, the many open mechanistic questions about transcriptional activators, in particular, the structure and function of the transcriptional activation domain (TAD), have hindered rapid development of synthetic ATFs. A compelling need thus exists for chemical tools and insights toward a more detailed portrait of the dynamic process of gene activation.

  6. Third harmonic generation in air ambient and laser ablated carbon plasma

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

    Singh, Ravi Pratap, E-mail: ravips@iitk.ac.in; Gupta, Shyam L.; Thareja, Raj K.

    2015-12-15

    We report the third harmonic generation of a nanosecond laser pulse (1.06 μm) in air ambient and in the presence of nanoparticles from laser ablated carbon plasma. Significant decrease in the threshold of third harmonic generation and multi-fold increment in the intensity of generated third harmonic is observed in presence of carbon plasma. The third harmonic in air is due to the quasi-resonant four photon process involving vibrationally excited states of molecular ion of nitrogen due to electron impact ionization and laser pulse. Following optical emission spectroscopic observations we conclude that the presence of C{sub 2} and CN in the ablatedmore » plume play a vital role in the observed third harmonic signals.« less

  7. Resonant second harmonic generation in a gallium nitride two-dimensional photonic crystal on silicon

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

    Zeng, Y.; Roland, I.; Checoury, X.

    We demonstrate second harmonic generation in a gallium nitride photonic crystal cavity embedded in a two-dimensional free-standing photonic crystal platform on silicon. The photonic crystal nanocavity is optically pumped with a continuous-wave laser at telecom wavelengths in the transparency window of the nitride material. The harmonic generation is evidenced by the spectral range of the emitted signal, the quadratic power dependence vs. input power, and the spectral dependence of second harmonic signal. The harmonic emission pattern is correlated to the harmonic polarization generated by the second-order nonlinear susceptibilities χ{sub zxx}{sup (2)}, χ{sub zyy}{sup (2)} and the electric fields of the fundamentalmore » cavity mode.« less

  8. Transfection of gene regulation nanoparticles complexed with pDNA and shRNA controls multilineage differentiation of hMSCs.

    PubMed

    Kim, Hye Jin; Yi, Se Won; Oh, Hyun Jyung; Lee, Jung Sun; Park, Ji Sun; Park, Keun-Hong

    2018-05-29

    Overexpression and knockdown of specific proteins can control stem cell differentiation for therapeutic purposes. In this study, we fabricated RUNX2, SOX9, and C/EBPα plasmid DNAs (pDNAs) and ATF4-targeting shRNA (shATF4) to induce osteogenesis, chondrogenesis, and adipogenesis of human mesenchymal stem cells (hMSCs). The pDNAs and shATF4 were complexed with TRITC-gene regulation nanoparticles (GRN). Osteogenesis-related gene expression was reduced at early (12 h) and late (36 h) time points after co-delivery of shATF4 and SOX9 or C/EBPα pDNA, respectively, and osteogenesis was inhibited in these hMSCs. By contrast, osteogenesis-related genes were highly expressed upon co-delivery of RUNX2 and ATF4 pDNAs. DEX in GRN enhanced chondrogenic differentiation. Expression of osteogenesis-, chondrogenesis-, and adipogenesis-related genes was higher in hMSCs transfected with NPs complexed with RUNX2 and ATF4 pDNAs, shATF4 and SOX9 pDNA, and shATF4 and C/EBPα pDNA for 72 h than in control hMSCs, respectively. Moreover, delivery of these NPs also increased expression of osteogenesis-, chondrogenesis-, and adipogenesis-related proteins. These alterations in expression led to morphological changes, indicating that hMSCs differentiated into osteoblasts, chondrocytes, and adipose cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Tailored semiconductors for high-harmonic optoelectronics.

    PubMed

    Sivis, Murat; Taucer, Marco; Vampa, Giulio; Johnston, Kyle; Staudte, André; Naumov, Andrei Yu; Villeneuve, D M; Ropers, Claus; Corkum, P B

    2017-07-21

    The advent of high-harmonic generation in gases 30 years ago set the foundation for attosecond science and facilitated ultrafast spectroscopy in atoms, molecules, and solids. We explore high-harmonic generation in the solid state by means of nanostructured and ion-implanted semiconductors. We use wavelength-selective microscopic imaging to map enhanced harmonic emission and show that the generation medium and the driving field can be locally tailored in solids by modifying the chemical composition and morphology. This enables the control of high-harmonic technology within precisely engineered solid targets. We demonstrate customized high-harmonic wave fields with wavelengths down to 225 nanometers (ninth-harmonic order of 2-micrometer laser pulses) and present an integrated Fresnel zone plate target in silicon, which leads to diffraction-limited self-focusing of the generated harmonics down to 1-micrometer spot sizes. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  10. An ATF4-ATG5 signaling in hypothalamic POMC neurons regulates obesity.

    PubMed

    Xiao, Yuzhong; Deng, Yalan; Yuan, Feixiang; Xia, Tingting; Liu, Hao; Li, Zhigang; Chen, Shanghai; Liu, Zhixue; Ying, Hao; Liu, Yi; Zhai, Qiwei; Guo, Feifan

    2017-06-03

    ATF4 (activating transcription factor 4) is an important transcription factor that has many biological functions, while its role in hypothalamic POMC (pro-opiomelanocortin-α) neurons in the regulation of energy homeostasis has not been explored. We recently discovered that mice with an Atf4 deletion specific to POMC neurons (PAKO mice) are lean and have higher energy expenditure. Furthermore, these mice are resistant to high-fat diet (HFD)-induced obesity and obesity-related metabolic disorders. Mechanistically, we found the expression of ATG5 (autophagy-related 5) is upregulated in POMC neurons of PAKO mice, and ATF4 regulates ATG5 expression by binding directly to its promoter. Mice with Atf4 and Atg5 double knockout in POMC neurons have reduced energy expenditure and gain more fat mass compared with PAKO mice under a HFD. Finally, the effect of Atf4 knockout in POMC neurons is possibly mediated by enhanced ATG5-dependent macroautophagy/autophagy and α-melanocyte-stimulating hormone (α-MSH) production in the hypothalamus. Together, this work not only identifies a beneficial role for ATF4 in hypothalamic POMC neurons in the regulation of obesity, but also provides a new potential therapeutic target for obesity and obesity-related metabolic diseases.

  11. Regulation of Saccharomyces cerevisiae genetic engineering on the production of acetate esters and higher alcohols during Chinese Baijiu fermentation.

    PubMed

    Li, Wei; Wang, Jian-Hui; Zhang, Cui-Ying; Ma, Hong-Xia; Xiao, Dong-Guang

    2017-06-01

    Acetate esters and higher alcohols greatly influence the quality and flavor profiles of Chinese Baijiu (Chinese liquor). Various mutants have been constructed to investigate the interactions of ATF1 overexpression, IAH1 deletion, and BAT2 deletion on the production of acetate esters and higher alcohols. The results showed that the overexpression of ATF1 under the control of the PGK1 promoter with BAT2 and IAH1 double-gene deletion led to a higher production of acetate esters and a lower production of higher alcohols than the overexpression of ATF1 with IAH1 deletion or overexpression of ATF1 with BAT2 deletion. Moreover, deletion of IAH1 in ATF1 overexpression strains effectively increased the production of isobutyl acetate and isoamyl acetate by reducing the hydrolysis of acetate esters. The decline in the production of higher alcohol by the ATF1 overexpression strains with BAT2 deletion is due to the interaction of ATF1 overexpression and BAT2 deletion. Mutants with varying abilities of producing acetate esters and higher alcohols were developed by genetic engineering. These strains have great potential for industrial application.

  12. Experimental demonstration of efficient and robust second harmonic generation using the adiabatic temperature gradient method

    NASA Astrophysics Data System (ADS)

    Dimova, E.; Steflekova, V.; Karatodorov, S.; Kyoseva, E.

    2018-03-01

    We propose a way of achieving efficient and robust second-harmonic generation. The technique proposed is similar to the adiabatic population transfer in a two-state quantum system with crossing energies. If the phase mismatching changes slowly, e.g., due to a temperature gradient along the crystal, and makes the phase match for second-harmonic generation to occur, then the energy would be converted adiabatically to the second harmonic. As an adiabatic technique, the second-harmonic generation scheme presented is stable to variations in the crystal parameters, as well as in the input light, crystal length, input intensity, wavelength and angle of incidence.

  13. Harmonic generation in metallic, GaAs-filled nanocavities in the enhanced transmission regime at visible and UV wavelengths.

    PubMed

    Vincenti, M A; de Ceglia, D; Roppo, V; Scalora, M

    2011-01-31

    We have conducted a theoretical study of harmonic generation from a silver grating having slits filled with GaAs. By working in the enhanced transmission regime, and by exploiting phase-locking between the pump and its harmonics, we guarantee strong field localization and enhanced harmonic generation under conditions of high absorption at visible and UV wavelengths. Silver is treated using the hydrodynamic model, which includes Coulomb and Lorentz forces, convection, electron gas pressure, plus bulk χ(3) contributions. For GaAs we use nonlinear Lorentz oscillators, with characteristic χ(2) and χ(3) and nonlinear sources that arise from symmetry breaking and Lorentz forces. We find that: (i) electron pressure in the metal contributes to linear and nonlinear processes by shifting/reshaping the band structure; (ii) TE- and TM-polarized harmonics can be generated efficiently; (iii) the χ(2) tensor of GaAs couples TE- and TM-polarized harmonics that create phase-locked pump photons having polarization orthogonal compared to incident pump photons; (iv) Fabry-Perot resonances yield more efficient harmonic generation compared to plasmonic transmission peaks, where most of the light propagates along external metal surfaces with little penetration inside its volume. We predict conversion efficiencies that range from 10(-6) for second harmonic generation to 10(-3) for the third harmonic signal, when pump power is 2 GW/cm2.

  14. The FONT5 Bunch-by-Bunch Position and Angle Feedback System at ATF2

    NASA Astrophysics Data System (ADS)

    Apsimon, R. J.; Bett, D. R.; Burrows, P. N.; Christian, G. B.; Constance, B.; Davis, M. R.; Gerbershagen, A.; Perry, C.; Resta-Lopez, J.

    The FONT5 upstream beam-based feedback system at ATF2 is designed to correct the position and angle jitter at the entrance to the ATF2 final-focus system, and also to demonstrate a prototype intra-train feedback system for the International Linear Collider interaction point. We discuss the hardware, from stripline BPMs to kickers, and RF and digital signal processing, as well as presenting results from the latest beam tests at ATF2.

  15. The analysis of harmonic generation coefficients in the ablative Rayleigh-Taylor instability

    NASA Astrophysics Data System (ADS)

    Lu, Yan; Fan, Zhengfeng; Lu, Xinpei; Ye, Wenhua; Zou, Changlin; Zhang, Ziyun; Zhang, Wen

    2017-10-01

    In this research, we use the numerical simulation method to investigate the generation coefficients of the first three harmonics and the zeroth harmonic in the Ablative Rayleigh-Taylor Instability. It is shown that the interface shifts to the low temperature side during the ablation process. In consideration of the third-order perturbation theory, the first three harmonic amplitudes of the weakly nonlinear regime are calculated and then the harmonic generation coefficients are obtained by curve fitting. The simulation results show that the harmonic generation coefficients changed with time and wavelength. Using the higher-order perturbation theory, we find that more and more harmonics are generated in the later weakly nonlinear stage, which is caused by the negative feedback of the later higher harmonics. Furthermore, extending the third-order theory to the fifth-order theory, we find that the second and the third harmonics coefficients linearly depend on the wavelength, while the feedback coefficients are almost constant. Further analysis also shows that when the fifth-order theory is considered, the normalized effective amplitudes of second and third harmonics can reach about 25%-40%, which are only 15%-25% in the frame of the previous third-order theory. Therefore, the third order perturbation theory is needed to be modified by the higher-order theory when ηL reaches about 20% of the perturbation wavelength.

  16. Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia

    PubMed Central

    Kohl, Susanne; Zobor, Ditta; Chiang, Wei-Chieh; Weisschuh, Nicole; Staller, Jennifer; Menendez, Irene Gonzalez; Chang, Stanley; Beck, Susanne C; Garrido, Marina Garcia; Sothilingam, Vithiyanjali; Seeliger, Mathias W; Stanzial, Franco; Benedicenti, Francesco; Inzana, Francesca; Héon, Elise; Vincent, Ajoy; Beis, Jill; Strom, Tim M; Rudolph, Günther; Roosing, Susanne; den Hollander, Anneke I; Cremers, Frans P M; Lopez, Irma; Ren, Huanan; Moore, Anthony T; Webster, Andrew R; Michaelides, Michel; Koenekoop, Robert K; Zrenner, Eberhart; Kaufman, Randal J; Tsang, Stephen H; Wissinger, Bernd; Lin, Jonathan H

    2015-01-01

    Achromatopsia (ACHM) is an autosomal recessive disorder characterized by color blindness, photophobia, nystagmus and severely reduced visual acuity. Using homozygosity mapping and whole-exome and candidate gene sequencing, we identified ten families carrying six homozygous and two compound-heterozygous mutations in the ATF6 gene (encoding activating transcription factor 6A), a key regulator of the unfolded protein response (UPR) and cellular endoplasmic reticulum (ER) homeostasis. Patients had evidence of foveal hypoplasia and disruption of the cone photoreceptor layer. The ACHM-associated ATF6 mutations attenuate ATF6 transcriptional activity in response to ER stress. Atf6−/− mice have normal retinal morphology and function at a young age but develop rod and cone dysfunction with increasing age. This new ACHM-related gene suggests a crucial and unexpected role for ATF6A in human foveal development and cone function and adds to the list of genes that, despite ubiquitous expression, when mutated can result in an isolated retinal photoreceptor phenotype. PMID:26029869

  17. Simultaneous saccharification and fermentation of Agave tequilana fructans by Kluyveromyces marxianus yeasts for bioethanol and tequila production.

    PubMed

    Flores, Jose-Axel; Gschaedler, Anne; Amaya-Delgado, Lorena; Herrera-López, Enrique J; Arellano, Melchor; Arrizon, Javier

    2013-10-01

    Agave tequilana fructans (ATF) constitute a substrate for bioethanol and tequila industries. As Kluyveromyces marxianus produces specific fructanases for ATF hydrolysis, as well as ethanol, it can perform simultaneous saccharification and fermentation. In this work, fifteen K. marxianus yeasts were evaluated to develop inoculums with fructanase activity on ATF. These inoculums were added to an ATF medium for simultaneous saccharification and fermentation. All the yeasts, showed exo-fructanhydrolase activity with different substrate specificities. The yeast with highest fructanase activity in the inoculums showed the lowest ethanol production level (20 g/l). Five K. marxianus strains were the most suitable for the simultaneous saccharification and fermentation of ATF. The volatile compounds composition was evaluated at the end of fermentation, and a high diversity was observed between yeasts, nevertheless all of them produced high levels of isobutyl alcohol. The simultaneous saccharification and fermentation of ATF with K. marxianus strains has potential for industrial application. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Expression of ATF4 and VEGF in chorionic villus tissue in early spontaneous abortion.

    PubMed

    Chai, Luwei; Ling, Kang; He, Xiaoxi; Yang, Rong

    2013-10-01

    To explore the relationship between early spontaneous abortion (SA) and the expression of activating transcription factor 4 (ATF4) and vascular endothelial growth factor (VEGF). The expression of ATF4 and VEGF protein and mRNA in villi from first trimester spontaneous abortion (SA, n=30) and normal pregnancy (NP, n=30) were detected by immunohistochemistry and fluorescent quantitative polymerase chain reaction (FQ-PCR). Both protein and mRNA expressions of ATF4 and VEGF in the SA group were significantly lower than in the NP group (P<0.01). Their proteins are expressed mainly in syncytiotrophoblast, cytotrophoblast and villous stromal cells. Correlation analysis showed that the expression of ATF4 was positively correlated with that of VEGF in the SA group (r=0.717, P<0.01). Lower expression of ATF4 and VEGF genes in chorionic villus tissue may participate in the pathogenesis of spontaneous abortion. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. ATF3 plays a protective role against toxicity by N-terminal fragment of mutant huntingtin in stable PC12 cell line

    PubMed Central

    Liang, Yideng; Jiang, Haibing; Ratovitski, Tamara; Jie, Chunfa; Nakamura, Masayuki; Hirschhorn, Ricky R.; Wang, Xiaofang; Smith, Wanli W.; Hai, Tsonwin; Poirier, Michelle A.; Ross, Christopher A.

    2009-01-01

    Huntington's disease is a progressive neurodegenerative disorder caused by a polyglutamine expansion near the N-terminus of huntingtin. The mechanisms of polyglutamine neurotoxicity, and cellular responses are not fully understood. We have studied gene expression profiles by cDNA array using an inducible PC12 cell model expressing an N-terminal huntingtin fragment with expanded polyglutamine (Htt-N63-148Q). Mutant huntingtin Htt-N63 induced cell death and increased the mRNA and protein levels of activating transcription factor 3 (ATF3). Mutant Htt-N63 also significantly enhanced ATF3 transcriptional activity by a promoter-based reporter assay. Overexpression of ATF3 protects against mutant Htt-N63 toxicity and knocking down ATF3 expression reduced Htt-N63 toxicity in a stable PC12 cell line. These results indicated that ATF3 plays a critical role in toxicity induced by mutant Htt-N63 and may lead to a useful therapeutic target. PMID:19559011

  20. Chronic ethanol consumption inhibits glucokinase transcriptional activity by Atf3 and triggers metabolic syndrome in vivo.

    PubMed

    Kim, Ji Yeon; Hwang, Joo-Yeon; Lee, Dae Yeon; Song, Eun Hyun; Park, Keon Jae; Kim, Gyu Hee; Jeong, Eun Ae; Lee, Yoo Jeong; Go, Min Jin; Kim, Dae Jin; Lee, Seong Su; Kim, Bong-Jo; Song, Jihyun; Roh, Gu Seob; Gao, Bin; Kim, Won-Ho

    2014-09-26

    Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the underlying mechanism remains largely unknown. Here, we demonstrate that Gck gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure in vivo and in vitro, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from -287 to -158 bp) on the Gck promoter were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the positive effect of Pdx-1 on Gck transcriptional regulation, enhanced recruitment of Hdac1/2 and histone H3 deacetylation, and subsequently augmented the interaction of Hdac1/Pdx-1 on the Gck promoter, which were diminished by Atf3 siRNA. In vivo Atf3-silencing reversed ethanol-mediated Gck down-regulation and β-cell dysfunction, followed by the amelioration of impaired glucose tolerance and insulin resistance. Together, we identified that ethanol-induced Atf3 fosters β-cell dysfunction via Gck down-regulation and that its loss ameliorates metabolic syndrome and could be a potential therapeutic target in treating type 2 diabetes. The Atf3 gene is associated with the induction of type 2 diabetes and alcohol consumption-induced metabolic impairment and thus may be the major negative regulator for glucose homeostasis. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4

    PubMed Central

    Huggins, Christopher J.; Mayekar, Manasi K.; Martin, Nancy; Saylor, Karen L.; Gonit, Mesfin; Jailwala, Parthav; Kasoji, Manjula; Haines, Diana C.; Quiñones, Octavio A.

    2015-01-01

    The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances, and endoplasmic reticulum (ER) stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here, we show that C/EBPγ:ATF4 heterodimers, but not C/EBPβ:ATF4 dimers, are the predominant CARE-binding species in stressed cells. C/EBPγ and ATF4 associate with genomic CAREs in a mutually dependent manner and coregulate many ISR genes. In contrast, the C/EBP family members C/EBPβ and C/EBP homologous protein (CHOP) were largely dispensable for induction of stress genes. Cebpg−/− mouse embryonic fibroblasts (MEFs) proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg−/− mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBPγ-deficient newborns die from atelectasis and respiratory failure, which can be mitigated by in utero exposure to the antioxidant, N-acetyl-cysteine. Cebpg−/− mice on a mixed strain background showed improved viability but, upon aging, developed significantly fewer malignant solid tumors than WT animals. Our findings identify C/EBPγ as a novel antioxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells. PMID:26667036

  2. High-flux soft x-ray harmonic generation from ionization-shaped few-cycle laser pulses

    PubMed Central

    Brahms, Christian; Gregory, Andrew; Tisch, John W. G.; Marangos, Jon P.

    2018-01-01

    Laser-driven high-harmonic generation provides the only demonstrated route to generating stable, tabletop attosecond x-ray pulses but has low flux compared to other x-ray technologies. We show that high-harmonic generation can produce higher photon energies and flux by using higher laser intensities than are typical, strongly ionizing the medium and creating plasma that reshapes the driving laser field. We obtain high harmonics capable of supporting attosecond pulses up to photon energies of 600 eV and a photon flux inside the water window (284 to 540 eV) 10 times higher than previous attosecond sources. We demonstrate that operating in this regime is key for attosecond pulse generation in the x-ray range and will become increasingly important as harmonic generation moves to fields that drive even longer wavelengths. PMID:29756033

  3. Application of organic compounds for high-order harmonic generation of ultrashort pulses

    NASA Astrophysics Data System (ADS)

    Ganeev, R. A.

    2016-02-01

    The studies of the high-order nonlinear optical properties of a few organic compounds (polyvinyl alcohol, polyethylene, sugar, coffee, and leaf) are reported. Harmonic generation in the laser-produced plasmas containing the molecules and large particles of above materials is demonstrated. These studies showed that the harmonic distributions and harmonic cutoffs from organic compound plasmas were similar to those from the graphite ablation. The characteristic feature of observed harmonic spectra was the presence of bluesided lobes near the lower-order harmonics.

  4. Self-Action of Second Harmonic Generation and Longitudinal Temperature Gradient in Nonlinear-Optical Crystals

    NASA Astrophysics Data System (ADS)

    Baranov, A. I.; Konyashkin, A. V.; Ryabushkin, O. A.

    2015-09-01

    Model of second harmonic generation with thermal self-action was developed. Second harmonic generation temperature phase matching curves were measured and calculated for periodically polled lithium niobate crystal. Both experimental and calculated data show asymmetrical shift of temperature tuning curves with pump power.

  5. Reflection second harmonic generation on a z -cut congruent lithium niobate crystal

    NASA Astrophysics Data System (ADS)

    Sono, T. J.; Scott, J. G.; Sones, C. L.; Valdivia, C. E.; Mailis, S.; Eason, R. W.; Frey, J. G.; Danos, L.

    2006-11-01

    Reflection second harmonic generation experiments were performed on z -cut congruent lithium niobate crystals (LiNbO3) to reveal the interfacial layer symmetry as the crystal is rotated around the z axis. To suppress the bulk contribution, the fundamental wavelength was selected to be 532nm , resulting in second harmonic generation at a wavelength within the absorption region of the crystal. The polarity of the direction of the y -axis was determined from second harmonic generation data and used to show that this direction also inverts during domain inversion.

  6. Generation of five phase-locked harmonics by implementing a divide-by-three optical frequency divider.

    PubMed

    Suhaimi, Nurul Sheeda; Ohae, Chiaki; Gavara, Trivikramarao; Nakagawa, Ken'ichi; Hong, Feng-Lei; Katsuragawa, Masayuki

    2015-12-15

    We report the generation of five phase-locked harmonics, f₁:2403  nm, f₂:1201  nm, f₃:801  nm, f₄:600  nm, and f₅:480  nm with an exact frequency ratio of 1:2:3:4:5 by implementing a divide-by-three optical frequency divider in the high harmonic generation process. All five harmonics are generated coaxially with high phase coherence in time and space, which are applicable for various practical uses.

  7. Thermal effects in high-power CW second harmonic generation in Mg-doped stoichiometric lithium tantalate.

    PubMed

    Tovstonog, Sergey V; Kurimura, Sunao; Suzuki, Ikue; Takeno, Kohei; Moriwaki, Shigenori; Ohmae, Noriaki; Mio, Norikatsu; Katagai, Toshio

    2008-07-21

    We investigated thermal behaviors of single-pass second-harmonic generation of continuous wave green radiation with high efficiency by quasi-phase matching in periodically poled Mg-doped stoichiometric lithium tantalate (PPMgSLT). Heat generation turned out to be directly related to the green light absorption in the material. Strong relation between an upper limit of the second harmonic power and confocal parameter was found. Single-pass second-harmonic generation of 16.1 W green power was achieved with 17.6% efficiency in Mg:SLT at room temperature.

  8. Feasibility study of generating ultra-high harmonic radiation with a single stage echo-enabled harmonic generation scheme

    NASA Astrophysics Data System (ADS)

    Zhou, Kaishang; Feng, Chao; Wang, Dong

    2016-10-01

    The echo enabled harmonic generation (EEHG) scheme holds the ability for the generation of fully coherent soft x-ray free-electron laser (FEL) pulses directly from external UV seeding sources. In this paper, we study the feasibility of using a single stage EEHG to generate coherent radiation in the "water window" and beyond. Using the high-order operating modes of the EEHG scheme, intensive numerical simulations have been performed considering various three-dimensional effects. The simulation results demonstrated that coherent soft x-ray radiation at 150th harmonic (1.77 nm) of the seed can be produced by a single stage EEHG. The decreasing of the final bunching factor at the desired harmonic caused by intra beam scattering (IBS) effect has also been analyzed.

  9. Symmetry in circularly polarized molecular high-order harmonic generation with intense bicircular laser pulses

    NASA Astrophysics Data System (ADS)

    Yuan, Kai-Jun; Bandrauk, André D.

    2018-02-01

    We present symmetry effects of laser fields and molecular geometries in circularly polarized high-order harmonic generation by bichromatic counter-rotating circularly polarized laser pulses. Simulations are performed on oriented molecules by numerically solving time-dependent Schrödinger equations. We discuss how electron recollision trajectories by the orthogonal laser field polarizations influence the harmonic polarization by using a time-frequency analysis of harmonics. It is found that orientation-dependent asymmetric ionization in linear molecules due to Coulomb potentials gives rise to a dependence of the polarization on the harmonic frequency. Effects of Coriolis forces are also presented on harmonic generation. Electron recollision trajectories illustrate the effects of the relative symmetry of the field and the molecule, thus paving a method for circularly polarized attosecond pulse generation and molecular orbital imaging in more complex systems.

  10. 78 FR 77494 - Agency Information Collection Activities; Proposed Collection; Comments Requested: ATF Adjunct...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-23

    ... collection. (2) Title of the Form/Collection: ATF Adjunct Instructor Data Form. (3) Agency form number, if...] Agency Information Collection Activities; Proposed Collection; Comments Requested: ATF Adjunct Instructor Data Form ACTION: 60-Day Notice. The Department of Justice (DOJ), Bureau of Alcohol, Tobacco, Firearms...

  11. 27 CFR 646.153 - Authority of appropriate ATF officers to enter business premises.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... REGULATIONS RELATING TO ALCOHOL AND TOBACCO CONTRABAND CIGARETTES Other Provisions Relating to the Distribution of Cigarettes § 646.153 Authority of appropriate ATF officers to enter business premises. Any appropriate ATF officer may enter the business premises of any distributor of cigarettes to inspect the...

  12. 27 CFR 646.153 - Authority of appropriate ATF officers to enter business premises.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... REGULATIONS RELATING TO ALCOHOL AND TOBACCO CONTRABAND CIGARETTES Other Provisions Relating to the Distribution of Cigarettes § 646.153 Authority of appropriate ATF officers to enter business premises. Any appropriate ATF officer may enter the business premises of any distributor of cigarettes to inspect the...

  13. 27 CFR 646.153 - Authority of appropriate ATF officers to enter business premises.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... REGULATIONS RELATING TO ALCOHOL AND TOBACCO CONTRABAND CIGARETTES Other Provisions Relating to the Distribution of Cigarettes § 646.153 Authority of appropriate ATF officers to enter business premises. Any appropriate ATF officer may enter the business premises of any distributor of cigarettes to inspect the...

  14. 27 CFR 646.153 - Authority of appropriate ATF officers to enter business premises.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... REGULATIONS RELATING TO ALCOHOL AND TOBACCO CONTRABAND CIGARETTES Other Provisions Relating to the Distribution of Cigarettes § 646.153 Authority of appropriate ATF officers to enter business premises. Any appropriate ATF officer may enter the business premises of any distributor of cigarettes to inspect the...

  15. Identification of ATF5-Interacting, SH3-Containing Proteins in Breast Cancer Cells

    DTIC Science & Technology

    2010-08-01

    CRE-dependent gene repression on R-Ras, HSP27 , and 14-3-3eta, which contribute to ATF5- mediated cell proliferation in Hep3B cell. (Fig. 5) Page 6...transfected with indicated constructs and mRNA level for R-Ras, HSP27 , and YWHAH(14-3-3eta) was determined by RT-PCR. β-actin was used as control...B23-dependent regulation of ATF5 stability impacts on expression of ATF5 downstream targets R-Ras, HSP27 , and 14-3-3eta, and cell proliferation of

  16. Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation

    PubMed Central

    Grimmer, Matthew R.; Stolzenburg, Sabine; Ford, Ethan; Lister, Ryan; Blancafort, Pilar; Farnham, Peggy J.

    2014-01-01

    Artificial transcription factors (ATFs) and genomic nucleases based on a DNA binding platform consisting of multiple zinc finger domains are currently being developed for clinical applications. However, no genome-wide investigations into their binding specificity have been performed. We have created six-finger ATFs to target two different 18 nt regions of the human SOX2 promoter; each ATF is constructed such that it contains or lacks a super KRAB domain (SKD) that interacts with a complex containing repressive histone methyltransferases. ChIP-seq analysis of the effector-free ATFs in MCF7 breast cancer cells identified thousands of binding sites, mostly in promoter regions; the addition of an SKD domain increased the number of binding sites ∼5-fold, with a majority of the new sites located outside of promoters. De novo motif analyses suggest that the lack of binding specificity is due to subsets of the finger domains being used for genomic interactions. Although the ATFs display widespread binding, few genes showed expression differences; genes repressed by the ATF-SKD have stronger binding sites and are more enriched for a 12 nt motif. Interestingly, epigenetic analyses indicate that the transcriptional repression caused by the ATF-SKD is not due to changes in active histone modifications. PMID:25122745

  17. High-order harmonics measured by the photon statistics of the infrared driving-field exiting the atomic medium.

    PubMed

    Tsatrafyllis, N; Kominis, I K; Gonoskov, I A; Tzallas, P

    2017-04-27

    High-order harmonics in the extreme-ultraviolet spectral range, resulting from the strong-field laser-atom interaction, have been used in a broad range of fascinating applications in all states of matter. In the majority of these studies the harmonic generation process is described using semi-classical theories which treat the electromagnetic field of the driving laser pulse classically without taking into account its quantum nature. In addition, for the measurement of the generated harmonics, all the experiments require diagnostics in the extreme-ultraviolet spectral region. Here by treating the driving laser field quantum mechanically we reveal the quantum-optical nature of the high-order harmonic generation process by measuring the photon number distribution of the infrared light exiting the harmonic generation medium. It is found that the high-order harmonics are imprinted in the photon number distribution of the infrared light and can be recorded without the need of a spectrometer in the extreme-ultraviolet.

  18. High-order harmonics measured by the photon statistics of the infrared driving-field exiting the atomic medium

    PubMed Central

    Tsatrafyllis, N.; Kominis, I. K.; Gonoskov, I. A.; Tzallas, P.

    2017-01-01

    High-order harmonics in the extreme-ultraviolet spectral range, resulting from the strong-field laser-atom interaction, have been used in a broad range of fascinating applications in all states of matter. In the majority of these studies the harmonic generation process is described using semi-classical theories which treat the electromagnetic field of the driving laser pulse classically without taking into account its quantum nature. In addition, for the measurement of the generated harmonics, all the experiments require diagnostics in the extreme-ultraviolet spectral region. Here by treating the driving laser field quantum mechanically we reveal the quantum-optical nature of the high-order harmonic generation process by measuring the photon number distribution of the infrared light exiting the harmonic generation medium. It is found that the high-order harmonics are imprinted in the photon number distribution of the infrared light and can be recorded without the need of a spectrometer in the extreme-ultraviolet. PMID:28447616

  19. High-frequency harmonic imaging of the eye.

    PubMed

    Silverman, Ronald H; Coleman, D Jackson; Ketterling, Jeffrey A; Lizzi, Frederic L

    2005-01-01

    PURPOSE: Harmonic imaging has become a well-established technique for ultrasonic imaging at fundamental frequencies of 10 MHz or less. Ophthalmology has benefited from the use of fundamentals of 20 MHz to 50 MHz. Our aim was to explore the ability to generate harmonics for this frequency range, and to generate harmonic images of the eye. METHODS: The presence of harmonics was determined in both water and bovine vitreous propagation media by pulse/echo and hydrophone at a series of increasing excitation pulse intensities and frequencies. Hydrophone measurements were made at the focal point and in the near- and far-fields of 20 MHz and 40 MHz transducers. Harmonic images of the anterior segment of the rabbit eye were obtained by a combination of analog filtering and digital post-processing. RESULTS: Harmonics were generated nearly identically in both water and vitreous. Hydrophone measurements showed the maximum second harmonic to be -5 dB relative to the 35 MHz fundamental at the focus, while in pulse/echo the maximum harmonic amplitude was -15dB relative to the fundamental. Harmonics were absent in the near-field, but present in the far-field. Harmonic images of the eye showed improved resolution. CONCLUSION: Harmonics can be readily generated at very high frequencies, and at power levels compliant with FDA guidelines for ophthalmology. This technique may yield further improvements to the already impressive resolutions obtainable in this frequency range. Improved imaging of the macular region, in particular, may provide significant improvements in diagnosis of retinal disease.

  20. High-frequency harmonic imaging of the eye

    NASA Astrophysics Data System (ADS)

    Silverman, Ronald H.; Coleman, D. Jackson; Ketterling, Jeffrey A.; Lizzi, Frederic L.

    2005-04-01

    Purpose: Harmonic imaging has become a well-established technique for ultrasonic imaging at fundamental frequencies of 10 MHz or less. Ophthalmology has benefited from the use of fundamentals of 20 MHz to 50 MHz. Our aim was to explore the ability to generate harmonics for this frequency range, and to generate harmonic images of the eye. Methods: The presence of harmonics was determined in both water and bovine vitreous propagation media by pulse/echo and hydrophone at a series of increasing excitation pulse intensities and frequencies. Hydrophone measurements were made at the focal point and in the near- and far-fields of 20 MHz and 40 MHz transducers. Harmonic images of the anterior segment of the rabbit eye were obtained by a combination of analog filtering and digital post-processing. Results: Harmonics were generated nearly identically in both water and vitreous. Hydrophone measurements showed the maximum second harmonic to be -5 dB relative to the 35 MHz fundamental at the focus, while in pulse/echo the maximum harmonic amplitude was -15dB relative to the fundamental. Harmonics were absent in the near-field, but present in the far-field. Harmonic images of the eye showed improved resolution. Conclusion: Harmonics can be readily generated at very high frequencies, and at power levels compliant with FDA guidelines for ophthalmology. This technique may yield further improvements to the already impressive resolutions obtainable in this frequency range. Improved imaging of the macular region, in particular, may provide significant improvements in diagnosis of retinal disease.

  1. Viability of thin wall tube forming of ATF FeCrAl

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

    Maloy, Stuart Andrew; Aydogan, Eda; Anderoglu, Osman

    Fabrication of thin walled tubing of FeCrAl alloys is critical to its success as a candidate enhanced accident-tolerant fuel cladding material. Alloys that are being investigated are Generation I and Generation II FeCrAl alloys produced at ORNL and an ODS FeCrAl alloy, MA-956 produced by Special Metals. Gen I and Gen II FeCrAl alloys were provided by ORNL and MA-956 was provided by LANL (initially produced by Special Metals). Three tube development efforts were undertaken. ORNL led the FeCrAl Gen I and Gen II alloy development and tube processing studies through drawing tubes at Rhenium Corporation. LANL received alloys frommore » ORNL and led tube processing studies through drawing tubes at Century Tubing. PNNL led the development of tube processing studies on MA-956 through pilger processing working with Sandvik Corporation. A summary of the recent progress on tube development is provided in the following report and a separate ORNL report: ORNL/TM-2015/478, “Development and Quality Assessments of Commercial Heat Production of ATF FeCrAl Tubes”.« less

  2. Investigation of Second- and Third-Harmonic Generation in Few-Layer Gallium Selenide by Multiphoton Microscopy

    PubMed Central

    Karvonen, Lasse; Säynätjoki, Antti; Mehravar, Soroush; Rodriguez, Raul D.; Hartmann, Susanne; Zahn, Dietrich R. T.; Honkanen, Seppo; Norwood, Robert A.; Peyghambarian, N.; Kieu, Khanh; Lipsanen, Harri; Riikonen, Juha

    2015-01-01

    Gallium selenide (GaSe) is a layered semiconductor and a well-known nonlinear optical crystal. The discovery of graphene has created a new vast research field focusing on two-dimensional materials. We report on the nonlinear optical properties of few-layer GaSe using multiphoton microscopy. Both second- and third-harmonic generation from few-layer GaSe flakes were observed. Unexpectedly, even the peak at the wavelength of 390 nm, corresponding to the fourth-harmonic generation or the sum frequency generation from third-harmonic generation and pump light, was detected during the spectral measurements in thin GaSe flakes. PMID:25989113

  3. Validation of Genotyping-By-Sequencing Analysis in Populations of Tetraploid Alfalfa by 454 Sequencing

    PubMed Central

    Rocher, Solen; Jean, Martine; Castonguay, Yves; Belzile, François

    2015-01-01

    Genotyping-by-sequencing (GBS) is a relatively low-cost high throughput genotyping technology based on next generation sequencing and is applicable to orphan species with no reference genome. A combination of genome complexity reduction and multiplexing with DNA barcoding provides a simple and affordable way to resolve allelic variation between plant samples or populations. GBS was performed on ApeKI libraries using DNA from 48 genotypes each of two heterogeneous populations of tetraploid alfalfa (Medicago sativa spp. sativa): the synthetic cultivar Apica (ATF0) and a derived population (ATF5) obtained after five cycles of recurrent selection for superior tolerance to freezing (TF). Nearly 400 million reads were obtained from two lanes of an Illumina HiSeq 2000 sequencer and analyzed with the Universal Network-Enabled Analysis Kit (UNEAK) pipeline designed for species with no reference genome. Following the application of whole dataset-level filters, 11,694 single nucleotide polymorphism (SNP) loci were obtained. About 60% had a significant match on the Medicago truncatula syntenic genome. The accuracy of allelic ratios and genotype calls based on GBS data was directly assessed using 454 sequencing on a subset of SNP loci scored in eight plant samples. Sequencing depth in this study was not sufficient for accurate tetraploid allelic dosage, but reliable genotype calls based on diploid allelic dosage were obtained when using additional quality filtering. Principal Component Analysis of SNP loci in plant samples revealed that a small proportion (<5%) of the genetic variability assessed by GBS is able to differentiate ATF0 and ATF5. Our results confirm that analysis of GBS data using UNEAK is a reliable approach for genome-wide discovery of SNP loci in outcrossed polyploids. PMID:26115486

  4. Cyclooxygenase 2 inhibition suppresses tubuloglomerular feedback: roles of thromboxane receptors and nitric oxide

    PubMed Central

    Araujo, Magali; Welch, William J.

    2009-01-01

    Thromboxane (TxA2) and nitric oxide (NO) are potent vasoactive autocoids that modulate tubuloglomerular feedback (TGF). Each is produced in the macula densa (MD) by cyclooxygenase-2 (COX-2) and neuronal nitric oxide synthase (nNOS), respectively. Both enzymes are similarly regulated in the MD and their interaction may be an important factor in the regulation of TGF and glomerular filtration rate. We tested the hypothesis that TGF is modified by the balance between MD nNOS-dependent NO and MD COX-2-dependent TxA2. We measured maximal TGF during perfusion of the loop of Henle (LH) by continuous recording of the proximal tubule stopped flow pressure response to LH perfusion of artificial tubular fluid (ATF) at 0 and 40 nl/min. The response to inhibitors of COX-1 (SC-560), COX-2 [parecoxib (Pxb)], and nNOS (l-NPA) added to the ATF solution was measured in separate nephrons. COX-2 inhibition with Pxb reduced TGF by 46% (ATF + vehicle vs. ATF + Pxb), whereas COX-1 inhibition with SC-560 reduced TGF by only 23%. Pretreatment with intravenous infusion of SQ-29,548, a selective thromboxone/PGH2 receptor (TPR) antagonist, blocked all of the SC-560 effect on TGF, suggesting that this effect was due to activation of TPR. However, SQ-29,548 only partially diminished the effect of Pxb (−66%). Specific inhibition of nNOS with l-NPA increased TGF, as expected. However, the ability of Pxb to reduce TGF was significantly impaired with comicroperfusion of l-NPA. These data suggest that COX-2 modulates TGF by two proconstrictive actions: generation of TxA2 acting on TPR and by simultaneous reduction of NO. PMID:19144694

  5. Unfolded Protein Response and PERK Kinase as a New Therapeutic Target in the Pathogenesis of Alzheimer's Disease.

    PubMed

    Rozpedek, Wioletta; Markiewicz, Lukasz; Diehl, J Alan; Pytel, Dariusz; Majsterek, Ireneusz

    2015-01-01

    Recent evidence suggests that the development of Alzheimer's disease (AD) and related cognitive loss is due to mutations in the Amyloid Precursor Protein (APP) gene on chromosome 21 and increased activation of eukaryotic translation initiation factor-2α (eIF2α) phosphorylation. The high level of misfolded and unfolded proteins loading in Endoplasmic Reticulum (ER) lumen triggers ER stress and as a result Unfolded Protein Response (UPR) pathways are activated. Stress-dependent activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the significant elevation of phospho-eIF2α. That attenuates general translation and, on the other hand, promotes the preferential synthesis of Activating Transcription Factor 4 (ATF4) and secretase β (BACE1) - a pivotal enzyme responsible for the initiation of the amyloidogenic pathway resulting in the generation of the amyloid β (Aβ) variant with high ability to form toxic senile plaques in AD brains. Moreover, excessive, long-term stress conditions may contribute to inducing neuronal death by apoptosis as a result of the overactivated expression of pro-apoptotic proteins via ATF4. These findings allow to infer that dysregulated translation, increased expression of BACE1 and ATF4, as a result of eIF2α phosphorylation, may be a major contributor to structural and functional neuronal loss resulting in memory impairment. Thus, blocking PERK-dependent eIF2α phosphorylation through specific, small-molecule PERK branch inhibitors seems to be a potential treatment strategy for AD individuals. That may contribute to the restoration of global translation rates and reduction of expression of ATF4 and BACE1. Hence, the treatment strategy can block accelerated β -amyloidogenesis by reduction in APP cleaving via the BACE1-dependent amyloidogenic pathway.

  6. 27 CFR 555.202 - Classes of explosive materials.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., except for bulk salutes). (c) Blasting agents. (For example, ammonium nitrate-fuel oil and certain water-gels (see also § 555.11). [T.D. ATF-87, 46 FR 40384, Aug. 7, 1981, as amended by T.D. ATF-293, 55 FR 3722, Feb. 5, 1990; T.D. ATF-400, 63 FR 45003, Aug. 24, 1998] ...

  7. Severe Accident Test Station Activity Report

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

    Pint, Bruce A.; Terrani, Kurt A.

    2015-06-01

    Enhancing safety margins in light water reactor (LWR) severe accidents is currently the focus of a number of international R&D programs. The current UO2/Zr-based alloy fuel system is particularly susceptible since the Zr-based cladding experiences rapid oxidation kinetics in steam at elevated temperatures. Therefore, alternative cladding materials that offer slower oxidation kinetics and a smaller enthalpy of oxidation can significantly reduce the rate of heat and hydrogen generation in the core during a coolant-limited severe accident. In the U.S. program, the high temperature steam oxidation performance of accident tolerant fuel (ATF) cladding solutions has been evaluated in the Severe Accidentmore » Test Station (SATS) at Oak Ridge National Laboratory (ORNL) since 2012. This report summarizes the capabilities of the SATS and provides an overview of the oxidation kinetics of several candidate cladding materials. A suggested baseline for evaluating ATF candidates is a two order of magnitude reduction in the steam oxidation resistance above 1000ºC compared to Zr-based alloys. The ATF candidates are categorized based on the protective external oxide or scale that forms during exposure to steam at high temperature: chromia, alumina, and silica. Comparisons are made to literature and SATS data for Zr-based alloys and other less-protective materials.« less

  8. Driving an Active Vibration Balancer to Minimize Vibrations at the Fundamental and Harmonic Frequencies

    NASA Technical Reports Server (NTRS)

    Holliday, Ezekiel S. (Inventor)

    2014-01-01

    Vibrations of a principal machine are reduced at the fundamental and harmonic frequencies by driving the drive motor of an active balancer with balancing signals at the fundamental and selected harmonics. Vibrations are sensed to provide a signal representing the mechanical vibrations. A balancing signal generator for the fundamental and for each selected harmonic processes the sensed vibration signal with adaptive filter algorithms of adaptive filters for each frequency to generate a balancing signal for each frequency. Reference inputs for each frequency are applied to the adaptive filter algorithms of each balancing signal generator at the frequency assigned to the generator. The harmonic balancing signals for all of the frequencies are summed and applied to drive the drive motor. The harmonic balancing signals drive the drive motor with a drive voltage component in opposition to the vibration at each frequency.

  9. Understanding fifth-harmonic generation in CLBO

    NASA Astrophysics Data System (ADS)

    Patankar, S.; Yang, S. T.; Moody, J. D.; Bayramian, A. J.; Swadling, G. F.; Barker, D.; Datte, P.; Mennerat, G.; Norton, M.; Carr, C. W.; Begishev, I. A.; Bromage, J.; Ross, J. S.

    2018-02-01

    We report on results of fifth harmonic generation in Cesium Lithium Borate (CLBO) using a three-crystal cascaded frequency conversion scheme designed to study the energy balance of the final sum frequency generation stage. The experimental setup independently combines the first and fourth harmonic of a Nd:Glass laser in a 5mm thick CLBO crystal. Energy balance between the incoming and output energy is close to unity when the CLBO is out of phase matching and approximately 80% when the crystal is in phase matching. A detailed analysis of the residual fundamental and fourth harmonic energy indicates 5th harmonic light is being generated but only 26% is unaccounted for. We attribute the missing light to linear transmission loss in the CLBO oven. The ratio of the output to input energy is unity when the missing 5th harmonic is incorporated into the calculations. Two-dimensional plane wave mixing simulations show agreement with the results at lower intensities.

  10. Harmonic magneto-electric response in GaFeO3

    NASA Astrophysics Data System (ADS)

    Naiya, Amit Kumar; Awasthi, A. M.

    2018-04-01

    GaFeO3 is a well-known multiferroic material. Like optical second harmonic generation, it also generates radio frequency (RF) second harmonic due to its non-centrosymmetric orthorhombic structure. The harmonic RF response also features a magneto-electric character comparable in prominence to that of the fundamental response. We measured complex parts of the fundamental and the second harmonic over 80 K to 300 K. The second harmonic permittivity and its phase angle change sign at the spin glass transition temperature Tg = 200 K and becomes dispersive above ˜280 K.

  11. Extending laser plasma accelerators into the mid-IR spectral domain with a next-generation ultra-fast CO 2 laser

    DOE PAGES

    Pogorelsky, I. V.; Babzien, M.; Ben-Zvi, I.; ...

    2016-01-20

    Here we discuss how expanding the scope of relativistic plasma research to wavelengths longer than λ/≈0.8₋1.1μm covered by conventional mode-locked solid-state lasers would offer attractive opportunities due to the quadratic scaling of the ponderomotive electron energy and critical plasma density with λ. Answering this quest, a next-generation mid-IR laser project is being advanced at the BNL ATF as a part of the user facility upgrade. We discuss the technical approach to this conceptually new 100 TW, 100 fs, λ=9₋11 μm CO 2 laser BESTIA (Brookhaven Experimental Supra-Terawatt Infrared at ATF) that encompasses several innovations applied for the first time tomore » molecular gas lasers. BESTIA will enable new regimes of laser plasma accelerators. One for example is shock-wave ion acceleration from gas jets. We review ongoing efforts to achieve stable, monoenergetic proton acceleration by dynamically shaping the plasma density profile from a hydrogen gas target with laser-produced blast waves. At its full power, 100 TW BESTIA promises to achieve proton beams at energy exceeding 200 MeV. In addition to ion acceleration in over-critical plasma, the ultra-intense mid-IR laser BESTIA will open new opportunities in driving wakefields in tenuous plasmas, expanding the landscape of Laser Wake Field Accelerator (LWFA) studies into unexplored long-wavelength spectral domain. Simple wavelength scaling suggests that a 100-TW CO2 laser beam will be capable to efficiently generate plasma “bubbles” thousand times bigger in volume compared to a near-IR solid state laser of an equivalent power. Combined with a femtosecond electron linac available at the ATF, this wavelength scaling will facilitate study of external seeding and staging of LWFA.« less

  12. v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element.

    PubMed

    Xie, W; Fletcher, B S; Andersen, R D; Herschman, H R

    1994-10-01

    We recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factors and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5' of the TIS10/PGS2 transcription start site that mediates pp60v-src induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E-box (CACGTG) sequences. Gel shift-oligonucleotide competition experiments with nuclear extracts from cells stably transfected with a temperature-sensitive v-src gene demonstrate that the CGTCACGTG sequence can bind proteins at both the ATF/CRE and E-box sequences. Dominant-negative CREB and Myc proteins that bind DNA, but do not transactivate, block v-src induction of a luciferase reporter driven by the first 80 nucleotides of the TIS10/PGS2 promoter. Mutational analysis distinguishes which TIS10/PGS2 cis-acting element mediates pp60v-src induction. E-box mutation has no effect on the fold induction in response to pp60v-src. In contrast, ATF/CRE mutation attenuates the pp60v-src response. Antibody supershift and methylation interference experiments demonstrate that CREB and at least one other ATF transcription factor in these extracts bind to the TIS10/PGS2 ATF/CRE element. Expression of a dominant-negative ras gene also blocks TIS10/PGS2 induction by v-src. Our data suggest that Ras mediates pp60v-src activation of an ATF transcription factor, leading to induced TIS10/PGS2 expression via the ATF/CRE element of the TIS10/PGS2 promoter. This is the first description of v-src activation of gene expression via an ATF/CRE element.

  13. Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response.

    PubMed

    Haze, K; Okada, T; Yoshida, H; Yanagi, H; Yura, T; Negishi, M; Mori, K

    2001-04-01

    Eukaryotic cells control the levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element consisting of 19 nt (CCAATN(9)CCACG), the CCACG part of which is considered to provide specificity. We recently identified the basic leucine zipper (bZIP) protein ATF6 as a mammalian UPR-specific transcription factor; ATF6 is activated by ER stress-induced proteolysis and binds directly to CCACG. Here we report that eukaryotic cells express another bZIP protein closely related to ATF6 in both structure and function. This protein encoded by the G13 (cAMP response element binding protein-related protein) gene is constitutively synthesized as a type II transmembrane glycoprotein anchored in the ER membrane and processed into a soluble form upon ER stress as occurs with ATF6. The proteolytic processing of ATF6 and the G13 gene product is accompanied by their relocation from the ER to the nucleus; their basic regions seem to function as a nuclear localization signal. Overexpression of the soluble form of the G13 product constitutively activates the UPR, whereas overexpression of a mutant lacking the activation domain exhibits a strong dominant-negative effect. Furthermore, the soluble forms of ATF6 and the G13 gene product are unable to bind to several point mutants of the cis-acting ER stress response element in vitro that hardly respond to ER stress in vivo. We thus concluded that the two related bZIP proteins are crucial transcriptional regulators of the mammalian UPR, and propose calling the ATF6 gene product ATF6alpha and the G13 gene product ATF6beta.

  14. Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

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

    Srivastava, Ritesh K.; Li, Changzhao

    Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4{sup +/+} wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4{sup +/−} heterozygous mice. To confirm thesemore » observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca{sup ++} homeostasis. ATO induces Ca{sup ++}-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca{sup ++} homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4{sup +/−} mice. • Changes in macrophage functions can be attenuated by Ca{sup ++} homeostasis regulators.« less

  15. Solid-state harmonics beyond the atomic limit.

    PubMed

    Ndabashimiye, Georges; Ghimire, Shambhu; Wu, Mengxi; Browne, Dana A; Schafer, Kenneth J; Gaarde, Mette B; Reis, David A

    2016-06-23

    Strong-field laser excitation of solids can produce extremely nonlinear electronic and optical behaviour. As recently demonstrated, this includes the generation of high harmonics extending into the vacuum-ultraviolet and extreme-ultraviolet regions of the electromagnetic spectrum. High harmonic generation is shown to occur fundamentally differently in solids and in dilute atomic gases. How the microscopic mechanisms in the solid and the gas differ remains a topic of intense debate. Here we report a direct comparison of high harmonic generation in the solid and gas phases of argon and krypton. Owing to the weak van der Waals interaction, rare (noble)-gas solids are a near-ideal medium in which to study the role of high density and periodicity in the generation process. We find that the high harmonic generation spectra from the rare-gas solids exhibit multiple plateaus extending well beyond the atomic limit of the corresponding gas-phase harmonics measured under similar conditions. The appearance of multiple plateaus indicates strong interband couplings involving multiple single-particle bands. We also compare the dependence of the solid and gas harmonic yield on laser ellipticity and find that they are similar, suggesting the importance of electron-hole recollision in these solids. This implies that gas-phase methods such as polarization gating for attosecond pulse generation and orbital tomography could be realized in solids.

  16. Enhanced second-harmonic generation from resonant GaAs gratings.

    PubMed

    de Ceglia, D; D'Aguanno, G; Mattiucci, N; Vincenti, M A; Scalora, M

    2011-03-01

    We theoretically study second harmonic generation in nonlinear, GaAs gratings. We find large enhancement of conversion efficiency when the pump field excites the guided mode resonances of the grating. Under these circumstances the spectrum near the pump wavelength displays sharp resonances characterized by dramatic enhancements of local fields and favorable conditions for second-harmonic generation, even in regimes of strong linear absorption at the harmonic wavelength. In particular, in a GaAs grating pumped at 1064 nm, we predict second-harmonic conversion efficiencies approximately 5 orders of magnitude larger than conversion rates achievable in either bulk or etalon structures of the same material.

  17. Atf6 plays protective and pathologic roles in fatty liver disease due to endoplasmic reticulum stress

    PubMed Central

    Cinaroglu, Ayca; Gao, Chuan; Imrie, Dru; Sadler, Kirsten C.

    2011-01-01

    Many etiologies of fatty liver disease (FLD) are associated with hyper-activation of one of the three pathways that comprise the unfolded protein response (UPR), a harbinger of endoplasmic reticulum (ER) stress. The UPR is mediated by pathways initiated by PERK, IRE1a/XBP1and ATF6, and each of these pathways have been implicated as either protective or pathological in FLD. We use zebrafish with FLD and hepatic ER stress to explore the relationship between Atf6 and steatosis. Mutation of the foie gras (foigr) gene causes FLD and hepatic ER stress. Prolonged treatment of wild-type larvae with a dose of tunicamycin that causes chronic ER stress phenocopies foigr. In contrast, acute exposure to a high dose of tunicamycin robustly activates the UPR but is less effective at inducing steatosis. The Srebp transcription factors are not required for steatosis in any of these models. Instead, depleting larvae of active Atf6 either through mbtps1 mutation or atf6 morpholino injection protects against steatosis caused by chronic ER stress whereas it exacerbates steatosis caused by acute tunicamycin treatment. Conclusion ER stress causes FLD. Loss of Atf6 prevents steatosis caused by chronic ER stress but can also potentiate steatosis caused by acute ER stress. This demonstrates that Atf6 can play both protective and pathological roles in FLD. PMID:21538441

  18. Deep-subwavelength waveguiding via inhomogeneous second-harmonic generation.

    PubMed

    Roppo, Vito; Vincenti, Maria Antonietta; de Ceglia, Domenico; Scalora, Michael

    2012-08-01

    We theoretically investigate second-harmonic generation in extremely narrow, subwavelength semiconductor and dielectric waveguides. We discuss a guiding mechanism characterized by the inhibition of diffraction and the suppression of cutoff limits in the context of a light trapping phenomenon that sets in under conditions of general phase and group velocity mismatch between the fundamental and the generated harmonic.

  19. The role of ferroelectric domain structure in second harmonic generation in random quadratic media.

    PubMed

    Roppo, Vito; Wang, W; Kalinowski, K; Kong, Y; Cojocaru, C; Trull, J; Vilaseca, R; Scalora, M; Krolikowski, W; Kivshar, Yu

    2010-03-01

    We study theoretically and numerically the second harmonic generation in a nonlinear crystal with random distribution of ferroelectric domains. We show that the specific features of disordered domain structure greatly affect the emission pattern of the generated harmonics. This phenomena can be used to characterize the degree of disorder in nonlinear photonic structures.

  20. High-harmonic generation by two-color mixing of circularly polarized laser fields

    NASA Astrophysics Data System (ADS)

    Milošević, D. B.; Becker, W.; Kopold, R.

    2000-06-01

    Dipole selection rules prevent harmonic generation by an atom in a circularly polarized laser field. However, this is not the case for a superposition of several circularly polarized fields, such as two circularly polarized fields with frequencies ω and 2ω that corotate or counter-rotate in the same plane. Harmonic generation in this environment has been observed and, in fact, found to be very intense in the counter-rotating case [1]. In a certain frequency region, the harmonics may be stronger than those radiated in a linearly polarized field of either frequency. The selection rules dictate that the harmonics are circularly polarized with a helicity that alternates from one harmonic to the next. Besides their practical interest, these harmonics are also intriguing from a fundamental point of view: the standard simple-man picture does not apply since orbits that start with zero velocity in this field almost never return to their point of departure. In terms of quantum trajectories, we discuss the mechanism that generates these harmonics. In several interesting ways, it is complementary to the case of linear polarization. [1] H. Eichmann et al., Phys. Rev. A 51, R3414 (1995)

  1. Directional enhancement of selected high-order-harmonics from intense laser irradiated blazed grating targets.

    PubMed

    Zhang, Guobo; Chen, Min; Liu, Feng; Yuan, Xiaohui; Weng, Suming; Zheng, Jun; Ma, Yanyun; Shao, Fuqiu; Sheng, Zhengming; Zhang, Jie

    2017-10-02

    Relativistically intense laser solid target interaction has been proved to be a promising way to generate high-order harmonics, which can be used to diagnose ultrafast phenomena. However, their emission direction and spectra still lack tunability. Based upon two-dimensional particle-in-cell simulations, we show that directional enhancement of selected high-order-harmonics can be realized using blazed grating targets. Such targets can select harmonics with frequencies being integer times of the grating frequency. Meanwhile, the radiation intensity and emission area of the harmonics are increased. The emission direction is controlled by tailoring the local blazed structure. Theoretical and electron dynamics analysis for harmonics generation, selection and directional enhancement from the interaction between multi-cycle laser and grating target are carried out. These studies will benefit the generation and application of laser plasma-based high order harmonics.

  2. Theoretical analysis of high-order harmonic generation from a coherent superposition of states

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

    Milosevic, Dejan B.; Max-Born-Institut, Max-Born-Strasse 2a, Berlin, 12489

    2006-02-15

    A quantum theory of high-order harmonic generation by a strong laser field in the presence of more bound states is formulated. The obtained numerical and analytical results for a two-state hydrogenlike atom model show that the harmonic spectrum consists of two parts: a usual single-state harmonic spectrum of odd harmonics having the energies (2k+1){omega} and a resonant part with the peaks around the excitation energy {delta}{omega}. The energy of the harmonics in the resonant part of the spectrum is equal to {delta}{omega}{+-}{omega}, {delta}{omega}{+-}3{omega}, .... For energies higher than the excitation energy, the resonant part forms a plateau, followed by amore » cutoff. The emission rate of the harmonics in this resonant plateau is many orders of magnitude higher than that of the harmonics generated in the presence of the ground state alone. The influence of the depletion of the initial states, as well as of the pulse shape and intensity, is analyzed.« less

  3. Generation of high-intensity sub-30 as pulses by inhomogeneous polarization gating technology in bowtie-shaped nanostructure

    NASA Astrophysics Data System (ADS)

    Feng, Liqiang; Feng, A. Yuanzi

    2018-04-01

    The generation of high-order harmonics and single attosecond pulses (SAPs) from He atom driven by the inhomogeneous polarization gating technology in a bowtie-shaped nanostructure is theoretically investigated. The results show that by the proper addition of bowtie-shaped nanostructure along the driven laser polarization direction, the harmonic emission becomes sensitive to the position of the laser field, and the harmonics emitted at the maximum orders that generate SAPs occur only at one side of the region inside the nanostructure. As a result, not only the harmonic cutoff can be extended, but also the modulations of the harmonics can be decreased, showing a carrier envelope phase independent harmonic cutoff with a bandwidth of 310 eV. Further, with the proper introduction of an ultraviolet pulse, the harmonic yield can be enhanced by 2 orders of magnitude. Finally, by the Fourier transformation of the selected harmonics, some SAPs with a full width at half maximum of sub-30 as can be obtained.

  4. High-order nonlinear optical processes in ablated carbon-containing materials: Recent approaches in development of the nonlinear spectroscopy using harmonic generation in the extreme ultraviolet range

    NASA Astrophysics Data System (ADS)

    Ganeev, R. A.

    2017-08-01

    The nonlinear spectroscopy using harmonic generation in the extreme ultraviolet range became a versatile tool for the analysis of the optical, structural and morphological properties of matter. The carbon-contained materials have shown the advanced properties among other studied species, which allowed both the definition of the role of structural properties on the nonlinear optical response and the analysis of the fundamental features of carbon as the attractive material for generation of coherent short-wavelength radiation. We review the studies of the high-order harmonic generation by focusing ultrashort pulses into the plasmas produced during laser ablation of various organic compounds. We discuss the role of ionic transitions of ablated carbon-containing molecules on the harmonic yield. We also show the similarities and distinctions of the harmonic and plasma spectra of organic compounds and graphite. We discuss the studies of the generation of harmonics up to the 27th order (λ = 29.9 nm) of 806 nm radiation in the boron carbide plasma and analyze the advantages and disadvantages of this target compared with the ingredients comprising B4C (solid boron and graphite) by comparing plasma emission and harmonic spectra from three species. We also show that the coincidence of harmonic and plasma emission wavelengths in most cases does not cause the enhancement or decrease of the conversion efficiency of this harmonic.

  5. Human cytomegalovirus inhibits apoptosis by regulating the activating transcription factor 5 signaling pathway in human malignant glioma cells

    PubMed Central

    WANG, TONGMEI; QIAN, DONGMENG; HU, MING; LI, LING; ZHANG, LI; CHEN, HAO; YANG, RUI; WANG, BIN

    2014-01-01

    The activating transcription factor 5 (ATF5), also termed ATFx, is a member of the ATF/cAMP response element-binding protein (CREB) family of basic zipper proteins. ATF5 is an anti-apoptotic protein that is highly expressed in malignant glioma and is essential for glioma cell survival. Accumulating evidence indicates that human malignant gliomas are universally infected with human cytomegalovirus (HCMV). Recent studies have shown that HCMV may be resistant to the induction of apoptosis by disrupting cellular pathways in glioblastoma. To investigate the potential anti-apoptotic function of HCMV in glioma, malignant U87 glioma cells were infected with HCMV. The present study showed that HCMV infection suppressed apoptosis in glioblastoma U87 cells by regulating the expression of ATF5. Furthermore, in glioblastoma U87 cells, HCMV infection induced cellular proliferation in parallel with an increase in the expression level of ATF5 and B-cell lymphoma/leukemia-2 to Bcl-2-associated X protein ratio. Loss of ATF5 function was achieved using a dominant-negative form of ATF5 in U87 cells, whereby cells appeared to grow marginally following HCMV infection when compared with the control. However, the anti-apoptotic ability was appeared to decline in the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. These results indicate that ATF5 signaling pathways may be important in the anti-apoptotic activity of HCMV-infected glioblastoma cells; therefore, the anti-apoptotic molecular mechanisms of HCMV in human glioblastoma cells were investigated in the current study. Prevention of HCMV infection may present a potential and promising approach for the treatment of malignant gliomas. PMID:25120656

  6. Antibiotic treatment failure when consulting patients with respiratory tract infections in general practice. A qualitative study to explore Danish general practitioners' perspectives.

    PubMed

    Bordado Sköld, Margrethe; Aabenhus, Rune; Guassora, Ann Dorrit; Mäkelä, Marjukka

    2017-12-01

    Prescribing antibiotics for acute respiratory tract infections (RTIs) is common in primary healthcare although most of these infections are of viral origin and antibiotics may not be helpful. Some of these prescriptions will not be associated with a quick recovery, and might be regarded as cases of antibiotic treatment failure (ATF). We studied antibiotic treatment failure in patients with acute RTIs from a general practitioner (GP) perspective, aiming to explore (i) GPs' views of ATF in primary care; (ii) how ATF influences the doctor-patient relationship; and (iii) GPs' understanding of patients' views of ATF. Qualitative study based on semi-structured, recorded interviews of 18 GPs between August and October 2012. The interviews started with discussion of a unique case of acute RTI involving ATF, followed by a more general reflection of the topic. Interviews were analysed using qualitative content analysis. In patients with acute RTIs, GPs proposed and agreed to a medical definition of antibiotic treatment failure but believed patients' views to differ significantly from this medical definition. GPs thought ATF affected their daily work only marginally. GPs used many communicative tools to maintain trust with patients in cases of ATF, but they did not consider such incidents to affect the doctor-patient relationship adversely. These findings suggest a possible communication gap between doctors and patients, partly due to a narrow medical definition of ATF. Studies describing patients' views are still missing. General practitioners' experiences and views on antibiotic treatment failure in acute respiratory infections or its effects on the doctor-patient relationship have not been studied previously.

  7. Comparison of Fine Structures of Electron Cyclotron Harmonic Emissions in Aurora

    NASA Astrophysics Data System (ADS)

    Labelle, J. W.; Dundek, M.

    2015-12-01

    Recent discoveries of emissions at four and five times the electron cyclotron frequency in aurora occuring under daylit conditions motivated the modification of radio receivers at South Pole Station, Antarctica, to measure fine structure of such emissions during two consecutive austral summers, 2013-4 and 2014-5. The experiment recorded 347 emission events over 376 days of observation. The seasonal distribution of these events revealed that successively higher harmonics require higher solar zenith angles for occurrence, as expected if they are generated at locations where the upper hybrid frequency matches the cyclotron harmonic, which for higher harmonics requires higher electron densities which are associated with higher solar zenith angles. Detailed examination of 21 cases in which two harmonics occur simultaneously showed that only rarely, about ten percent of the time, are the frequencies of the fine structures of the emissions in exact integer ratio (e.g., 3:2, 4:3, or 5:4 depending on which combination of harmonics is observed). In the remaining approximately ninety percent of the cases, the higher harmonic occurred at a lower ratio than the appropriate integer ratio, as expected if the harmonics are generated independently at their separate matching conditions in the bottomside ionosphere, where the upper hybrid frequency increases with altitude while the gyroharmonics decrease with altitude. (The bottomside is the most likely source of the emissions, since from there the mode converted Z-modes have access to ground-level.) Taken together, these results suggest that the dominant mechanism for the higher harmonics is independent generation at locations where the upper hybrid frequency matches each harmonic, i.e., at a separate source altitude for each harmonic. Generation of higher harmonics through coalescence of lower harmonic waves explains at most a small minority of events.

  8. 8-Oxo-2'-deoxyguanosine ameliorates UVB-induced skin damage in hairless mice by scavenging reactive oxygen species and inhibiting MMP expression.

    PubMed

    Lee, Jin-Ku; Ko, Seong-Hee; Ye, Sang-Kyu; Chung, Myung-Hee

    2013-04-01

    Skin is uniquely vulnerable to damage caused by reactive oxygen species (ROS), which are most commonly produced in response to ultraviolet (UV) light. ROS generated at injury sites play an important role in modulating the inflammatory response. Besides inhibiting Rac, 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) has also shown notable antioxidant action. We tested whether 8-oxo-dG could protect skin from UVB-induced damage by scavenging ROS. HaCaT cells and hairless mice were irradiated with 15 and 180 mJ/cm(2) narrow-spectrum UVB, respectively. ROS generation was detected through incubation with DCFDA and confocal microscopy. Western blot analyses and immunohistochemistry were performed to verify the activities of ERK, JNK, p38, ATF-2, and c-Jun, and the expression of matrix metalloproteinases (MMPs), in UVB-irradiated HaCaT cells and murine skin. Hydrogen peroxide production and protein carbonyl concentrations were measured in UVB-damaged mouse skin. MMP-1 and MMP-9 expression in UVB-irradiated HaCaT cells was measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). In UVB-irradiated HaCaT cells, 8-oxo-dG inhibited ROS production, subsequent activation of mitogen-activated protein kinase (MAPK), ATF-2, and c-Jun, and MMP expression. It also prevented UV-induced skin reactions in hairless mice, inhibiting the increase in protein carbonyl content, activation of MAPKs, ATF-2, and c-Jun, the increases in MMP-9 and -13 expression, and epidermal hyperplasia. 8-oxo-dG can be considered an endogenous antioxidant and its potent antioxidant activity might be a beneficial property that could be exploited to protect skin from ROS-associated photodamage. Copyright © 2013. Published by Elsevier Ireland Ltd.

  9. Decursin enhances TRAIL-induced apoptosis through oxidative stress mediated- endoplasmic reticulum stress signalling in non-small cell lung cancers.

    PubMed

    Kim, Jaekwang; Yun, Miyong; Kim, Eun-Ok; Jung, Deok-Beom; Won, Gunho; Kim, Bonglee; Jung, Ji Hoon; Kim, Sung-Hoon

    2016-03-01

    The TNF-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its remarkable ability to selectively kill tumour cells. However, because most tumours exhibit resistance to TRAIL-induced apoptosis, the development of combination therapies to overcome resistance to TRAIL is required for effective cancer therapy. Cell viability and possible synergy between the plant pyranocoumarin decursin and TRAIL was measured by MTT assay and calcusyn software. Reactive oxygen species (ROS) and apoptosis were measured using dichlorodihydrofluorescein and annexin/propidium iodide in cell flow cytometry. Changes in protein levels were assessed with Western blotting. Combining decursin and TRAIL markedly decreased cell viability and increased apoptosis in TRAIL-resistant non-small-cell lung cancer (NSCLC) cell lines. Decursin induced expression of the death receptor 5 (DR5). Inhibition of DR5 attenuated apoptotic cell death in decursin + TRAIL treated NSCLC cell lines. Interestingly, induction of DR5 and CCAAT/enhancer-binding protein homologues protein by decursin was mediated through selective induction of the pancreatic endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) branch of the endoplasmic reticulum stress response pathway. Furthermore, enhancement of PERK/ATF4 signalling by decursin was mediated by ROS generation in NSCLC cell lines, but not in normal human lung cells. Decursin also markedly down-regulated expression of survivin and Bcl-xL in TRAIL-resistant NSCLC cells. ROS generation by decursin selectively activated the PERK/ATF4 axis of the endoplasmic reticulum stress signalling pathway, leading to enhanced TRAIL sensitivity in TRAIL-resistant NSCLC cell lines, partly via up-regulation of DR5. © 2015 The British Pharmacological Society.

  10. Decursin enhances TRAIL‐induced apoptosis through oxidative stress mediated‐ endoplasmic reticulum stress signalling in non‐small cell lung cancers

    PubMed Central

    Kim, Jaekwang; Yun, Miyong; Kim, Eun‐Ok; Jung, Deok‐Beom; Won, Gunho; Kim, Bonglee; Jung, Ji Hoon

    2016-01-01

    Background and Purpose The TNF‐related apoptosis‐inducing ligand (TRAIL) is a promising anticancer agent due to its remarkable ability to selectively kill tumour cells. However, because most tumours exhibit resistance to TRAIL‐induced apoptosis, the development of combination therapies to overcome resistance to TRAIL is required for effective cancer therapy. Experimental Approach Cell viability and possible synergy between the plant pyranocoumarin decursin and TRAIL was measured by MTT assay and calcusyn software. Reactive oxygen species (ROS) and apoptosis were measured using dichlorodihydrofluorescein and annexin/propidium iodide in cell flow cytometry. Changes in protein levels were assessed with Western blotting. Key Results Combining decursin and TRAIL markedly decreased cell viability and increased apoptosis in TRAIL‐resistant non‐small‐cell lung cancer (NSCLC) cell lines. Decursin induced expression of the death receptor 5 (DR5). Inhibition of DR5 attenuated apoptotic cell death in decursin + TRAIL treated NSCLC cell lines. Interestingly, induction of DR5 and CCAAT/enhancer‐binding protein homologues protein by decursin was mediated through selective induction of the pancreatic endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) branch of the endoplasmic reticulum stress response pathway. Furthermore, enhancement of PERK/ATF4 signalling by decursin was mediated by ROS generation in NSCLC cell lines, but not in normal human lung cells. Decursin also markedly down‐regulated expression of survivin and Bcl‐xL in TRAIL‐resistant NSCLC cells. Conclusions and Implications ROS generation by decursin selectively activated the PERK/ATF4 axis of the endoplasmic reticulum stress signalling pathway, leading to enhanced TRAIL sensitivity in TRAIL‐resistant NSCLC cell lines, partly via up‐regulation of DR5. PMID:26661339

  11. Multi-Orbital contributions in High Harmonic Generation

    NASA Astrophysics Data System (ADS)

    Guehr, Markus

    2009-05-01

    The high harmonic spectrum generated from atoms or molecules in a strong laser field contains information about the electronic structure of the generation medium. In the high harmonic generation (HHG) process, a free electron wave packet tunnel-ionizes from the molecular orbital in a strong laser field. After being accelerated by the laser electric field, the free electron wave packet coherently recombines to the orbital from which is was initially ionized, thereby emitting the harmonic spectrum. Interferences between the free electron wave packet and the molecular orbital will shape the spectrum in a characteristic way. These interferences have been used to tomographically image the highest occupied molecular orbital (HOMO) of N2 [1]. Molecular electronic states energetically below the HOMO should contribute to laser-driven high harmonic generation (HHG), but this behavior has not been observed previously. We have observed evidence of HHG from multiple orbitals in aligned N2 [2]. The tunneling ionization (and therefore the harmonic generation) is most efficient if the orbital has a large extension in the direction of the harmonic generation polarization. The HOMO with its σg symmetry therefore dominates the harmonic spectrum if the molecular axis is parallel to the harmonic generation polarization, the lower bound πu HOMO-1 dominates in the perpendicular case. The HOMO contributions appear as a regular plateau with a cutoff in the HHG spectrum. In contrast, the HOMO-1 signal is strongly peaked in the cutoff region. We explain this by semi-classical simulations of the recombination process that show constructive interferences between the HOMO-1 and the recombining wave packet in the cutoff region. The ability to monitor several orbitals opens the route to imaging coherent superpositions of electronic orbitals. [1] J. Itatani et al., Nature 432, 867 (2004)[2] B. K. McFarland, J. P. Farrell, P. H. Bucksbaum and M. Gühr, Science 322, 1232 (2008)

  12. High-order harmonic generation from a two-dimensional band structure

    NASA Astrophysics Data System (ADS)

    Jin, Jian-Zhao; Xiao, Xiang-Ru; Liang, Hao; Wang, Mu-Xue; Chen, Si-Ge; Gong, Qihuang; Peng, Liang-You

    2018-04-01

    In the past few years, harmonic generation in solids has attracted tremendous attention. Recently, some experiments of two-dimensional (2D) monolayer or few-layer materials have been carried out. These studies demonstrated that harmonic generation in the 2D case shows a strong dependence on the laser's orientation and ellipticity, which calls for a quantitative theoretical interpretation. In this work, we carry out a systematic study on the harmonic generation from a 2D band structure based on a numerical solution to the time-dependent Schrödinger equation. By comparing with the 1D case, we find that the generation dynamics can have a significant difference due to the existence of many crossing points in the 2D band structure. In particular, the higher conduction bands can be excited step by step via these crossing points and the total contribution of the harmonic is given by the mixing of transitions between different clusters of conduction bands to the valence band. We also present the orientation dependence of the harmonic yield on the laser polarization direction.

  13. Highly coherent vacuum ultraviolet radiation at the 15th harmonic with echo-enabled harmonic generation technique

    NASA Astrophysics Data System (ADS)

    Hemsing, E.; Dunning, M.; Hast, C.; Raubenheimer, T. O.; Weathersby, S.; Xiang, D.

    2014-07-01

    X-ray free-electron lasers are enabling access to new science by producing ultrafast and intense x rays that give researchers unparalleled power and precision in examining the fundamental nature of matter. In the quest for fully coherent x rays, the echo-enabled harmonic generation technique is one of the most promising methods. In this technique, coherent radiation at the high harmonic frequencies of two seed lasers is generated from the recoherence of electron beam phase space memory. Here we report on the generation of highly coherent and stable vacuum ultraviolet radiation at the 15th harmonic of an infrared seed laser with this technique. The experiment demonstrates two distinct advantages that are intrinsic to the highly nonlinear phase space gymnastics of echo-enabled harmonic generation in a new regime, i.e., high frequency up-conversion efficiency and insensitivity to electron beam phase space imperfections. Our results allow comparison and confirmation of predictive models and scaling laws, and mark a significant step towards fully coherent x-ray free-electron lasers that will open new scientific research.

  14. Harmonics Generation by Surface Plasmon Polaritons on Single Nanowires.

    PubMed

    de Hoogh, Anouk; Opheij, Aron; Wulf, Matthias; Rotenberg, Nir; Kuipers, L

    2016-08-17

    We present experimental observations of visible wavelength second- and third-harmonic generation on single plasmonic nanowires of variable widths. We identify that near-infrared surface plasmon polaritons, which are guided along the nanowire, act as the source of the harmonics generation. We discuss the underlying mechanism of this nonlinear process, using a combination of spatially resolved measurements and numerical simulations to show that the visible harmonics are generated via a combination of both local and propagating plasmonic modes. Our results provide the first demonstration of nanoscale nonlinear optics with guided, propagating plasmonic modes on a lithographically defined chip, opening up new routes toward integrated optical circuits for information processing.

  15. Wiggler magnetic field assisted third harmonic generation in expanding clusters

    NASA Astrophysics Data System (ADS)

    Vij, Shivani

    2018-04-01

    A simple theoretical model is constructed to study the wiggler magnetic field assisted third harmonic generation of intense short pulse laser in a cluster in its expanding phase. The ponderomotive force of laser causes density perturbations in cluster electron density which couples with wiggler magnetic field to produce a nonlinear current that generates transverse third harmonic. An intense short pulse laser propagating through a gas embedded with atomic clusters, converts it into hot plasma balls via tunnel ionization. Initially, the electron plasma frequency inside the clusters ω pe > \\sqrt{3}{ω }1 (with ω 1 being the frequency of the laser). As the cluster expands under Coulomb force and hydrodynamic pressure, ω pe decreases to \\sqrt{3}{ω }1. At this time, there is resonant enhancement in the efficiency of the third harmonic generation. The efficiency of third harmonic generation is enhanced due to cluster plasmon resonance and by phase matching due to wiggler magnetic field. The effect of cluster size on the expansion rate is studied to observe that the clusters of different radii would expand differently. The impact of laser intensity and wiggler magnetic field on the efficiency of third harmonic generation is also explored.

  16. Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells.

    PubMed

    Jeong, Kwon; Kim, Kiyoon; Kim, Hunsung; Oh, Yoojung; Kim, Seong-Jin; Jo, Yunhee; Choe, Wonchae

    2015-06-01

    Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, it was demonstrated that CypB is transcriptionally regulated by hypoxia-mediated activation of transcription factor 6 (ATF6), an ER stress transcription factor. Subsequently, the effects of ATF6 on CypB promoter activity were investigated and an ATF6-responsive region in the promoter was identified. Hypoxia and ATF6 expression each increased CypB promoter activity. Collectively, these results demonstrate that ATF6 positively regulates the expression of CypB by binding to an ATF6-responsive region in the promoter, which may play an important role in the attenuation of apoptosis in the adaption to hypoxia. These results suggest that CypB may be a key molecule in the adaptation of cells to hypoxic conditions.

  17. Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells

    PubMed Central

    JEONG, KWON; KIM, KIYOON; KIM, HUNSUNG; OH, YOOJUNG; KIM, SEONG-JIN; JO, YUNHEE; CHOE, WONCHAE

    2015-01-01

    Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, it was demonstrated that CypB is transcriptionally regulated by hypoxia-mediated activation of transcription factor 6 (ATF6), an ER stress transcription factor. Subsequently, the effects of ATF6 on CypB promoter activity were investigated and an ATF6-responsive region in the promoter was identified. Hypoxia and ATF6 expression each increased CypB promoter activity. Collectively, these results demonstrate that ATF6 positively regulates the expression of CypB by binding to an ATF6-responsive region in the promoter, which may play an important role in the attenuation of apoptosis in the adaption to hypoxia. These results suggest that CypB may be a key molecule in the adaptation of cells to hypoxic conditions. PMID:26137159

  18. Boric acid induces cytoplasmic stress granule formation, eIF2α phosphorylation, and ATF4 in prostate DU-145 cells.

    PubMed

    Henderson, Kimberly A; Kobylewski, Sarah E; Yamada, Kristin E; Eckhert, Curtis D

    2015-02-01

    Dietary boron intake is associated with reduced prostate and lung cancer risk and increased bone mass. Boron is absorbed and circulated as boric acid (BA) and at physiological concentrations is a reversible competitive inhibitor of cyclic ADP ribose, the endogenous agonist of the ryanodine receptor calcium (Ca(+2)) channel, and lowers endoplasmic reticulum (ER) [Ca(2+)]. Low ER [Ca(2+)] has been reported to induce ER stress and activate the eIF2α/ATF4 pathway. Here we report that treatment of DU-145 prostate cells with physiological levels of BA induces ER stress with the formation of stress granules and mild activation of eIF2α, GRP78/BiP, and ATF4. Mild activation of eIF2α and its downstream transcription factor, ATF4, enables cells to reconfigure gene expression to manage stress conditions and mild activation of ATF4 is also required for the differentiation of osteoblast cells. Our results using physiological levels of boric acid identify the eIF2α/ATF pathway as a plausible mode of action that underpins the reported health effects of dietary boron.

  19. Seismic and Aseismic Behavior of the Altotiberina Low-angle Normal Fault System (Northern Apennines, Italy) through High-resolution Earthquake Locations and Repeating Events

    NASA Astrophysics Data System (ADS)

    Valoroso, L.; Chiaraluce, L.

    2017-12-01

    Low-angle normal faults (dip < 30°) are geologically widely documented and considered responsible for accommodating the crustal extension within the brittle crust although their mechanical behavior and seismogenic potential is enigmatic. We study the anatomy and slip-behavior of the actively slipping Altotiberina low-angle (ATF) normal fault system using a high-resolution 5-years-long (2010-2014) earthquake catalogue composed of 37k events (ML<3.9 and completeness magnitude MC=0.5 ML), recorded by a dense permanent seismic network of the Altotiberina Near Fault Observatory (TABOO). The seismic activity defines the fault system dominated at depth by the low-angle ATF surface (15-20°) coinciding to the ATF geometry imaged through seismic reflection data. The ATF extends for 50km along-strike and between 4-5 to 16km of depth. Seismicity also images the geometry of a set of higher angle faults (35-50°) located in the ATF hanging-wall (HW). The ATF-related seismicity accounts for 10% of the whole seismicity (3,700 events with ML<2.4), occurring at a remarkably constant rate of 2.2 events/day. This seismicity describes an about 1.5-km-thick fault zone composed by multiple sub-parallel slipping planes. The remaining events are instead organized in multiple mainshocks (MW>3) seismic sequences lasting from weeks to months, activating a contiguous network of 3-5-km-long syn- and antithetic fault segments within the ATF-HW. The space-time evolution of these minor sequences is consistent with subsequence failures promoted by fluid flow. The ATF-seismicity pattern includes 97 clusters of repeating events (RE) made of 299 events with ML<1.9. RE are located around locked patches identified by geodetic modeling, suggesting a mixed-mode (stick-slip and stable-sliding) slip-behavior along the fault plane in accommodating most of the NE-trending tectonic deformation with creeping dominating below 5 km depth. Consistently, the seismic moment released by the ATF-seismicity accounts for a small portion (30%) of the geodetic one. The rate of occurrence of RE, mostly composed by doublets with short inter-event time (e.g. hours), appears to modulate the seismic release of the ATF-HW, suggesting that creeping may drive the strain partitioning of the system.

  20. Inhibition of linear absorption in opaque materials using phase-locked harmonic generation.

    PubMed

    Centini, Marco; Roppo, Vito; Fazio, Eugenio; Pettazzi, Federico; Sibilia, Concita; Haus, Joseph W; Foreman, John V; Akozbek, Neset; Bloemer, Mark J; Scalora, Michael

    2008-09-12

    We theoretically predict and experimentally demonstrate inhibition of linear absorption for phase and group velocity mismatched second- and third-harmonic generation in strongly absorbing materials, GaAs, in particular, at frequencies above the absorption edge. A 100-fs pump pulse tuned to 1300 nm generates 650 and 435 nm second- and third-harmonic pulses that propagate across a 450-microm-thick GaAs substrate without being absorbed. We attribute this to a phase-locking mechanism that causes the pump to trap the harmonics and to impress on them its dispersive properties.

  1. Role of phase matching in pulsed second-harmonic generation: Walk-off and phase-locked twin pulses in negative-index media

    NASA Astrophysics Data System (ADS)

    Roppo, Vito; Centini, Marco; Sibilia, Concita; Bertolotti, Mario; de Ceglia, Domenico; Scalora, Michael; Akozbek, Neset; Bloemer, Mark J.; Haus, Joseph W.; Kosareva, Olga G.; Kandidov, Valery P.

    2007-09-01

    The present investigation is concerned with the study of pulsed second-harmonic generation under conditions of phase and group velocity mismatch, and generally low conversion efficiencies and pump intensities. In positive-index, nonmetallic materials, we generally find qualitative agreement with previous reports regarding the presence of a double-peaked second harmonic signal, which comprises a pulse that walks off and propagates at the nominal group velocity one expects at the second-harmonic frequency, and a second pulse that is “captured” and propagates under the pump pulse. We find that the origin of the double-peaked structure resides in a phase-locking mechanism that characterizes not only second-harmonic generation, but also χ(3) processes and third-harmonic generation. The phase-locking mechanism that we describe occurs for arbitrarily small pump intensities, and so it is not a soliton effect, which usually relies on a threshold mechanism, although multicolor solitons display similar phase locking characteristics. Thus, in second harmonic generation a phase-matched component is always generated, even under conditions of material phase mismatch: This component is anomalous, because the material does not allow energy exchange between the pump and the second-harmonic beam. On the other hand, if the material is phase matched, phase locking and phase matching are indistinguishable, and the conversion process becomes efficient. We also report a similar phase-locking phenomenon in negative index materials. A spectral analysis of the pump and the generated signals reveals that the phase-locking phenomenon causes the forward moving, phase-locked second-harmonic pulse to experience the same negative index as the pump pulse, even though the index of refraction at the second-harmonic frequency is positive. Our analysis further shows that the reflected second-harmonic pulse generated at the interface and the forward-moving, phase-locked pulse appear to be part of the same pulse initially generated at the surface, part of which is immediately back-reflected, while the rest becomes trapped and dragged along by the pump pulse. These pulses thus constitute twin pulses generated at the interface, having the same negative wave vector, but propagating in opposite directions. Almost any break of the longitudinal symmetry, even an exceedingly small χ(2) discontinuity, releases the trapped pulse which then propagates in the backward direction. These dynamics are indicative of very rich and intricate interactions that characterize ultrashort pulse propagation phenomena.

  2. Role of phase matching in pulsed second-harmonic generation: Walk-off and phase-locked twin pulses in negative-index media

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

    Roppo, Vito; Centini, Marco; Sibilia, Concita

    The present investigation is concerned with the study of pulsed second-harmonic generation under conditions of phase and group velocity mismatch, and generally low conversion efficiencies and pump intensities. In positive-index, nonmetallic materials, we generally find qualitative agreement with previous reports regarding the presence of a double-peaked second harmonic signal, which comprises a pulse that walks off and propagates at the nominal group velocity one expects at the second-harmonic frequency, and a second pulse that is 'captured' and propagates under the pump pulse. We find that the origin of the double-peaked structure resides in a phase-locking mechanism that characterizes not onlymore » second-harmonic generation, but also {chi}{sup (3)} processes and third-harmonic generation. The phase-locking mechanism that we describe occurs for arbitrarily small pump intensities, and so it is not a soliton effect, which usually relies on a threshold mechanism, although multicolor solitons display similar phase locking characteristics. Thus, in second harmonic generation a phase-matched component is always generated, even under conditions of material phase mismatch: This component is anomalous, because the material does not allow energy exchange between the pump and the second-harmonic beam. On the other hand, if the material is phase matched, phase locking and phase matching are indistinguishable, and the conversion process becomes efficient. We also report a similar phase-locking phenomenon in negative index materials. A spectral analysis of the pump and the generated signals reveals that the phase-locking phenomenon causes the forward moving, phase-locked second-harmonic pulse to experience the same negative index as the pump pulse, even though the index of refraction at the second-harmonic frequency is positive. Our analysis further shows that the reflected second-harmonic pulse generated at the interface and the forward-moving, phase-locked pulse appear to be part of the same pulse initially generated at the surface, part of which is immediately back-reflected, while the rest becomes trapped and dragged along by the pump pulse. These pulses thus constitute twin pulses generated at the interface, having the same negative wave vector, but propagating in opposite directions. Almost any break of the longitudinal symmetry, even an exceedingly small {chi}{sup (2)} discontinuity, releases the trapped pulse which then propagates in the backward direction. These dynamics are indicative of very rich and intricate interactions that characterize ultrashort pulse propagation phenomena.« less

  3. Optical harmonic generator

    DOEpatents

    Summers, M.A.; Eimerl, D.; Boyd, R.D.

    1982-06-10

    A pair of uniaxial birefringent crystal elements are fixed together to form a serially arranged, integral assembly which, alternatively, provides either a linearly or elliptically polarized second-harmonic output wave or a linearly polarized third-harmonic output wave. The extraordinary or e directions of the crystal elements are oriented in the integral assembly to be in quadrature (90/sup 0/). For a second-harmonic generation in the Type-II-Type-II angle tuned case, the input fundamental wave has equal amplitude o and e components. For a third-harmonic generation, the input fundamental wave has o and e components whose amplitudes are in a ratio of 2:1 (o:e reference first crystal). In the typical case of a linearly polarized input fundamental wave this can be accomplished by simply rotating the crystal assembly about the input beam direction by 10/sup 0/. For both second and third harmonic generation input precise phase-matching is achieved by tilting the crystal assembly about its two sensitive axeses (o).

  4. High-order-harmonic generation from H2+ molecular ions near plasmon-enhanced laser fields

    NASA Astrophysics Data System (ADS)

    Yavuz, I.; Tikman, Y.; Altun, Z.

    2015-08-01

    Simulations of plasmon-enhanced high-order-harmonic generation are performed for a H2+ molecular cation near the metallic nanostructures. We employ the numerical solution of the time-dependent Schrödinger equation in reduced coordinates. We assume that the main axis of H2+ is aligned perfectly with the polarization direction of the plasmon-enhanced field. We perform systematic calculations on plasmon-enhanced harmonic generation based on an infinite-mass approximation, i.e., pausing nuclear vibrations. Our simulations show that molecular high-order-harmonic generation from plasmon-enhanced laser fields is possible. We observe the dispersion of a plateau of harmonics when the laser field is plasmon enhanced. We find that the maximum kinetic energy of the returning electron follows 4 Up . We also find that when nuclear vibrations are enabled, the efficiency of the harmonics is greatly enhanced relative to that of static nuclei. However, the maximum kinetic energy 4 Up is largely maintained.

  5. Optical harmonic generator

    DOEpatents

    Summers, Mark A.; Eimerl, David; Boyd, Robert D.

    1985-01-01

    A pair of uniaxial birefringent crystal elements are fixed together to form a serially arranged, integral assembly which, alternatively, provides either a linearly or elliptically polarized second-harmonic output wave or a linearly polarized third-harmonic output wave. The "extraordinary" or "e" directions of the crystal elements are oriented in the integral assembly to be in quadrature (90.degree.). For a second-harmonic generation in the Type-II-Type-II angle tuned case, the input fundamental wave has equal amplitude "o" and "e" components. For a third-harmonic generation, the input fundamental wave has "o" and "e" components whose amplitudes are in a ratio of 2:1 ("o":"e" reference first crystal). In the typical case of a linearly polarized input fundamental wave this can be accomplished by simply rotating the crystal assembly about the input beam direction by 10.degree.. For both second and third harmonic generation input precise phase-matching is achieved by tilting the crystal assembly about its two sensitive axes ("o").

  6. Unravelling the dynamical origin of below- and near-threshold harmonic generation of H 2 + in an intense NIR laser field

    DOE PAGES

    Heslar, John; Chu, Shih-I.

    2016-11-24

    Recently, the study of near- and below- threshold regime harmonics as a potential source of intense coherent vacuum-ultraviolet radiation has received considerable attention. However, the dynamical origin of these lower harmonics, particularly for the molecular systems, is less understood and largely unexplored. Here we perform the first fully ab initio and high precision 3D quantum study of the below- and near-threshold harmonic generation of H 2 + molecules in an intense 800-nm near-infrared (NIR) laser field. Furthermore, combining with a synchrosqueezing transform of the quantum time-frequency spectrum and an extended semiclassical analysis, we explore in-depth the roles of various quantummore » trajectories, including short- and long trajectories, multiphoton trajectories, resonance-enhanced trajectories, and multiple rescattering trajectories of the below- and near- threshold harmonic generation processes. Our results shed new light on the dynamical origin of the below- and near-threshold harmonic generation and various quantum trajectories for diatomic molecules for the first time.« less

  7. Saccharomyces cerevisiae Atf1p is an alcohol acetyltransferase and a thioesterase in vitro.

    PubMed

    Nancolas, Bethany; Bull, Ian D; Stenner, Richard; Dufour, Virginie; Curnow, Paul

    2017-06-01

    The alcohol-O-acyltransferases are bisubstrate enzymes that catalyse the transfer of acyl chains from an acyl-coenzyme A (CoA) donor to an acceptor alcohol. In the industrial yeast Saccharomyces cerevisiae this reaction produces acyl esters that are an important influence on the flavour of fermented beverages and foods. There is also a growing interest in using acyltransferases to produce bulk quantities of acyl esters in engineered microbial cell factories. However, the structure and function of the alcohol-O-acyltransferases remain only partly understood. Here, we recombinantly express, purify and characterize Atf1p, the major alcohol acetyltransferase from S. cerevisiae. We find that Atf1p is promiscuous with regard to the alcohol cosubstrate but that the acyltransfer activity is specific for acetyl-CoA. Additionally, we find that Atf1p is an efficient thioesterase in vitro with specificity towards medium-chain-length acyl-CoAs. Unexpectedly, we also find that mutating the supposed catalytic histidine (H191) within the conserved HXXXDG active site motif only moderately reduces the thioesterase activity of Atf1p. Our results imply a role for Atf1p in CoA homeostasis and suggest that engineering Atf1p to reduce the thioesterase activity could improve product yields of acetate esters from cellular factories. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd.

  8. Regulatory interplay of Cockayne syndrome B ATPase and stress-response gene ATF3 following genotoxic stress.

    PubMed

    Kristensen, Ulrik; Epanchintsev, Alexey; Rauschendorf, Marc-Alexander; Laugel, Vincent; Stevnsner, Tinna; Bohr, Vilhelm A; Coin, Frédéric; Egly, Jean-Marc

    2013-06-18

    Cockayne syndrome type B ATPase (CSB) belongs to the SwItch/Sucrose nonfermentable family. Its mutations are linked to Cockayne syndrome phenotypes and classically are thought to be caused by defects in transcription-coupled repair, a subtype of DNA repair. Here we show that after UV-C irradiation, immediate early genes such as activating transcription factor 3 (ATF3) are overexpressed. Although the ATF3 target genes, including dihydrofolate reductase (DHFR), were unable to recover RNA synthesis in CSB-deficient cells, transcription was restored rapidly in normal cells. There the synthesis of DHFR mRNA restarts on the arrival of RNA polymerase II and CSB and the subsequent release of ATF3 from its cAMP response element/ATF target site. In CSB-deficient cells ATF3 remains bound to the promoter, thereby preventing the arrival of polymerase II and the restart of transcription. Silencing of ATF3, as well as stable introduction of wild-type CSB, restores RNA synthesis in UV-irradiated CSB cells, suggesting that, in addition to its role in DNA repair, CSB activity likely is involved in the reversal of inhibitory properties on a gene-promoter region. We present strong experimental data supporting our view that the transcriptional defects observed in UV-irradiated CSB cells are largely the result of a permanent transcriptional repression of a certain set of genes in addition to some defect in DNA repair.

  9. Quasi-phase-matching of high-order harmonics in plasma plumes: theory and experiment.

    PubMed

    Strelkov, V V; Ganeev, R A

    2017-09-04

    We theoretically analyze the phase-matching of high-order harmonic generation (HHG) in multi-jet plasmas and find the harmonic orders for which the quasi-phase-matching (QPM) is achieved depending on the parameters of the plasma and the generating beam. HHG by single- and two-color generating fields is analyzed. The QMP is studied experimentally for silver, indium and manganese plasmas using near IR and mid-IR laser fields. The theory is validated by comparison with our experimental observations, as well as published experimental data. In particular, the plasma densities and the harmonic phase coefficients reconstructed from the observed harmonic spectra using our theory agree with the corresponding parameters found using other methods. Our theory allows defining the plasma jet and the generating field properties, which can maximize the HHG efficiency due to QPM.

  10. Harmonic generation with a dual frequency pulse.

    PubMed

    Keravnou, Christina P; Averkiou, Michalakis A

    2014-05-01

    Nonlinear imaging was implemented in commercial ultrasound systems over the last 15 years offering major advantages in many clinical applications. In this work, pulsing schemes coupled with a dual frequency pulse are presented. The pulsing schemes considered were pulse inversion, power modulation, and power modulated pulse inversion. The pulse contains a fundamental frequency f and a specified amount of its second harmonic 2f. The advantages and limitations of this method were evaluated with both acoustic measurements of harmonic generation and theoretical simulations based on the KZK equation. The use of two frequencies in a pulse results in the generation of the sum and difference frequency components in addition to the other harmonic components. While with single frequency pulses, only power modulation and power modulated pulse inversion contained odd harmonic components, with the dual frequency pulse, pulse inversion now also contains odd harmonic components.

  11. Generation and Analysis of Subpicosecond Double Electron Bunch at the Brookhaven Accelerator Test Facility

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

    Babzien, M.; Kusche, K.; Yakimenko, V.

    2011-08-09

    Two compressed electron beam bunches from a single 60-MeV bunch have been generated in a reproducible manner during compression in the magnetic chicane - 'dog leg' arrangement at ATF. Measurements indicate they have comparable bunch lengths ({approx}100-200 fs) and are separated in energy by {approx}1.8 MeV with the higher-energy bunch preceding the lower-energy bunch by 0.5-1 ps. Some simulation results for analyzing the double-bunch formation process are also presented.

  12. 49 CFR 40.225 - What form is used for an alcohol test?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What form is used for an alcohol test? 40.225... Testing § 40.225 What form is used for an alcohol test? (a) The DOT Alcohol Testing Form (ATF) must be used for every DOT alcohol test. The ATF must be a three-part carbonless manifold form. The ATF is...

  13. 49 CFR 40.225 - What form is used for an alcohol test?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false What form is used for an alcohol test? 40.225... Testing § 40.225 What form is used for an alcohol test? (a) The DOT Alcohol Testing Form (ATF) must be used for every DOT alcohol test. The ATF must be a three-part carbonless manifold form. The ATF is...

  14. 49 CFR 40.225 - What form is used for an alcohol test?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false What form is used for an alcohol test? 40.225... Testing § 40.225 What form is used for an alcohol test? (a) The DOT Alcohol Testing Form (ATF) must be used for every DOT alcohol test. The ATF must be a three-part carbonless manifold form. The ATF is...

  15. 49 CFR 40.225 - What form is used for an alcohol test?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false What form is used for an alcohol test? 40.225... Testing § 40.225 What form is used for an alcohol test? (a) The DOT Alcohol Testing Form (ATF) must be used for every DOT alcohol test. The ATF must be a three-part carbonless manifold form. The ATF is...

  16. 49 CFR 40.225 - What form is used for an alcohol test?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false What form is used for an alcohol test? 40.225... Testing § 40.225 What form is used for an alcohol test? (a) The DOT Alcohol Testing Form (ATF) must be used for every DOT alcohol test. The ATF must be a three-part carbonless manifold form. The ATF is...

  17. High-order harmonic generation in solid slabs beyond the single-active-electron approximation

    NASA Astrophysics Data System (ADS)

    Hansen, Kenneth K.; Deffge, Tobias; Bauer, Dieter

    2017-11-01

    High-harmonic generation by a laser-driven solid slab is simulated using time-dependent density functional theory. Multiple harmonic plateaus up to very high harmonic orders are observed already at surprisingly low field strengths. The full all-electron harmonic spectra are, in general, very different from those of any individual Kohn-Sham orbital. Freezing the Kohn-Sham potential instead is found to be a good approximation for the laser intensities and harmonic orders considered. The origins of the plateau cutoffs are explained in terms of band gaps that can be reached by Kohn-Sham electrons and holes moving through the band structure.

  18. Modular approach to achieving the next-generation X-ray light source

    NASA Astrophysics Data System (ADS)

    Biedron, S. G.; Milton, S. V.; Freund, H. P.

    2001-12-01

    A modular approach to the next-generation light source is described. The "modules" include photocathode, radio-frequency, electron guns and their associated drive-laser systems, linear accelerators, bunch-compression systems, seed laser systems, planar undulators, two-undulator harmonic generation schemes, high-gain harmonic generation systems, nonlinear higher harmonics, and wavelength shifting. These modules will be helpful in distributing the next-generation light source to many more laboratories than the current single-pass, high-gain free-electron laser designs permit, due to both monetary and/or physical space constraints.

  19. Periodically poled potassium niobate for second-harmonic generation at 463 nm.

    PubMed

    Meyn, J P; Klein, M E; Woll, D; Wallenstein, R; Rytz, D

    1999-08-15

    We report on the fabrication and characterization of quasi-phase-matched potassium niobate crystals for second-harmonic generation. Periodic 30-mum -pitch antiparallel ferroelectric domains are fabricated by means of poling in an electrical field. Both birefrigence and periodic phase shift of the generated second harmonic contribute to phase matching when the d(31) nonlinear optical tensor element is used. 3.8 mW of second-harmonic radiation at 463 nm is generated by frequency doubling of the output of master-oscillator power-amplifier diode laser in a 5-mm-long crystal. The measured effective nonlinear coefficient is 3.7pm/V. The measured spectral acceptance bandwidth of 0.25 nm corresponds to the theoretical value.

  20. Three-dimensional image formation in fiber-optical second-harmonic-generation microscopy.

    PubMed

    Gu, Min; Fu, Ling

    2006-02-06

    Three-dimensional (3-D) image formation in fiber-optical second-harmonic-generation microscopy is revealed to be purely coherent and therefore can be described by a 3-D coherent transfer function (CTF) that exhibits the same spatial frequency passband as that of fiber-optical reflection-mode non-fluorescence microscopy. When the numerical aperture of the fiber is much larger than the angle of convergence of the illumination on the fiber aperture, the performance of fiber-optical second-harmonic-generation microscopy behaves as confocal second-harmonic-generation microscopy. The dependence of axial resolution on fiber coupling parameters shows an improvement of approximately 7%, compared with that in fiber-optical two-photon fluorescence microscopy.

  1. Linking high harmonics from gases and solids.

    PubMed

    Vampa, G; Hammond, T J; Thiré, N; Schmidt, B E; Légaré, F; McDonald, C R; Brabec, T; Corkum, P B

    2015-06-25

    When intense light interacts with an atomic gas, recollision between an ionizing electron and its parent ion creates high-order harmonics of the fundamental laser frequency. This sub-cycle effect generates coherent soft X-rays and attosecond pulses, and provides a means to image molecular orbitals. Recently, high harmonics have been generated from bulk crystals, but what mechanism dominates the emission remains uncertain. To resolve this issue, we adapt measurement methods from gas-phase research to solid zinc oxide driven by mid-infrared laser fields of 0.25 volts per ångström. We find that when we alter the generation process with a second-harmonic beam, the modified harmonic spectrum bears the signature of a generalized recollision between an electron and its associated hole. In addition, we find that solid-state high harmonics are perturbed by fields so weak that they are present in conventional electronic circuits, thus opening a route to integrate electronics with attosecond and high-harmonic technology. Future experiments will permit the band structure of a solid to be tomographically reconstructed.

  2. Spatial properties of odd and even low order harmonics generated in gas.

    PubMed

    Lambert, G; Andreev, A; Gautier, J; Giannessi, L; Malka, V; Petralia, A; Sebban, S; Stremoukhov, S; Tissandier, F; Vodungbo, B; Zeitoun, Ph

    2015-01-14

    High harmonic generation in gases is developing rapidly as a soft X-ray femtosecond light-source for applications. This requires control over all the harmonics characteristics and in particular, spatial properties have to be kept very good. In previous literature, measurements have always included several harmonics contrary to applications, especially spectroscopic applications, which usually require a single harmonic. To fill this gap, we present here for the first time a detailed study of completely isolated harmonics. The contribution of the surrounding harmonics has been totally suppressed using interferential filtering which is available for low harmonic orders. In addition, this allows to clearly identify behaviors of standard odd orders from even orders obtained by frequency-mixing of a fundamental laser and of its second harmonic. Comparisons of the spatial intensity profiles, of the spatial coherence and of the wavefront aberration level of 5ω at 160 nm and 6ω at 135 nm have then been performed. We have established that the fundamental laser beam aberrations can cause the appearance of a non-homogenous donut-shape in the 6ω spatial intensity distribution. This undesirable effect can be easily controlled. We finally conclude that the spatial quality of an even harmonic can be as excellent as in standard generation.

  3. Larval hemolymph of rhinoceros beetle, Allomyrina dichotoma, enhances insulin secretion through ATF3 gene expression in INS-1 pancreatic β-cells.

    PubMed

    Kim, Seung-Whan; Suh, Hyun-Woo; Yoo, Bo-Kyung; Kwon, Kisang; Yu, Kweon; Choi, Ji-Young; Kwon, O-Yu

    2018-05-22

    In this study, we show that INS-1 pancreatic β-cells treated for 2 h with hemolymph of larvae of rhinoceros beetle, Allomyrina dichotoma, secreted about twice as much insulin compared to control cells without such treatment. Activating transcription factor 3 (ATF3) was the highest upregulated gene in DNA chip analysis. The A. dichotoma hemolymph dose-dependently induced increased expression levels of genes encoding ATF3 and insulin. Conversely, treatment with ATF3 siRNA inhibited expression levels of both genes and curbed insulin secretion. These results suggest that the A. dichotoma hemolymph has potential for treating and preventing diabetes or diabetes-related complications.

  4. Observation of High-Harmonic Generation from an Atomically Thin Semiconductor [Observation of High Harmonics from and Atomically Thin Semiconductor

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

    Liu, Hanzhe; Li, Yilei; You, Yongsing

    We report the observation of nonperturbative high-harmonic generation from monolayer MoS 2. Here, the yield is higher in monolayer compared to a single layer of the bulk, an effect attributed to strong electron-hole interactions in the monolayer.

  5. Observation of High-Harmonic Generation from an Atomically Thin Semiconductor [Observation of High Harmonics from and Atomically Thin Semiconductor

    DOE PAGES

    Liu, Hanzhe; Li, Yilei; You, Yongsing; ...

    2016-01-01

    We report the observation of nonperturbative high-harmonic generation from monolayer MoS 2. Here, the yield is higher in monolayer compared to a single layer of the bulk, an effect attributed to strong electron-hole interactions in the monolayer.

  6. High order harmonic generation in rare gases

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

    Budil, Kimberly Susan

    1994-05-01

    The process of high order harmonic generation in atomic gases has shown great promise as a method of generating extremely short wavelength radiation, extending far into the extreme ultraviolet (XUV). The process is conceptually simple. A very intense laser pulse (I ~10 13-10 14 W/cm 2) is focused into a dense (~10 17 particles/cm 3) atomic medium, causing the atoms to become polarized. These atomic dipoles are then coherently driven by the laser field and begin to radiate at odd harmonics of the laser field. This dissertation is a study of both the physical mechanism of harmonic generation as wellmore » as its development as a source of coherent XUV radiation. Recently, a semiclassical theory has been proposed which provides a simple, intuitive description of harmonic generation. In this picture the process is treated in two steps. The atom ionizes via tunneling after which its classical motion in the laser field is studied. Electron trajectories which return to the vicinity of the nucleus may recombine and emit a harmonic photon, while those which do not return will ionize. An experiment was performed to test the validity of this model wherein the trajectory of the electron as it orbits the nucleus or ion core is perturbed by driving the process with elliptically, rather than linearly, polarized laser radiation. The semiclassical theory predicts a rapid turn-off of harmonic production as the ellipticity of the driving field is increased. This decrease in harmonic production is observed experimentally and a simple quantum mechanical theory is used to model the data. The second major focus of this work was on development of the harmonic "source". A series of experiments were performed examining the spatial profiles of the harmonics. The quality of the spatial profile is crucial if the harmonics are to be used as the source for experiments, particularly if they must be refocused.« less

  7. Perturbing laser field dependent high harmonic phase modulations

    NASA Astrophysics Data System (ADS)

    Li, Zhengyan; Kong, Fanqi; Brown, Graham; Hammond, TJ; Ko, Dong-Hyuk; Zhang, Chunmei; Corkum, P. B.

    2018-06-01

    A perturbing laser pulse modulates and controls the phase of the high harmonic radiation driven by an intense fundamental pulse. Thus, a structured wave front can impress a specific spatial phase onto the generated high harmonic wave front. This modulation procedure leads to all-optical spatial light modulators for VUV or XUV radiation created by high harmonic generation. Here, through theoretical analysis and experiment, we study the correlation between the high harmonic phase modulations and the perturbing laser field amplitude and phase, providing guidelines for practical high harmonic spatial light modulators. In addition, we show that the petahertz optical oscilloscope for measuring electric fields of a perturbing beam is most robust using low order harmonics, far from the cut-off.

  8. Double optical gating of high-order harmonic generation with carrier-envelope phase stabilized lasers.

    PubMed

    Mashiko, Hiroki; Gilbertson, Steve; Li, Chengquan; Khan, Sabih D; Shakya, Mahendra M; Moon, Eric; Chang, Zenghu

    2008-03-14

    We demonstrated a novel optical switch to control the high-order harmonic generation process so that single attosecond pulses can be generated with multiple-cycle pulses. The technique combines two powerful optical gating methods: polarization gating and two-color gating. An extreme ultraviolet supercontinuum supporting 130 as was generated with neon gas using 9 fs laser pulses. We discovered a unique dependence of the harmonic spectra on the carrier-envelope phase of the laser fields, which repeats every 2 pi radians.

  9. Double Optical Gating of High-Order Harmonic Generation with Carrier-Envelope Phase Stabilized Lasers

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

    Mashiko, Hiroki; Gilbertson, Steve; Li, Chengquan

    2008-03-14

    We demonstrated a novel optical switch to control the high-order harmonic generation process so that single attosecond pulses can be generated with multiple-cycle pulses. The technique combines two powerful optical gating methods: polarization gating and two-color gating. An extreme ultraviolet supercontinuum supporting 130 as was generated with neon gas using 9 fs laser pulses. We discovered a unique dependence of the harmonic spectra on the carrier-envelope phase of the laser fields, which repeats every 2{pi} radians.

  10. Quantum description of the high-order harmonic generation in multiphoton and tunneling regimes

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

    Perez-Hernandez, J. A.; Plaja, L.

    2007-08-15

    We employ a recently developed S-matrix approach [L. Plaja and J. A. Perez-Hernandez, Opt. Express 15, 3629 (2007)] to investigate the process of harmonic generation in tunnel and multiphoton ionization regimes. In contrast with most of the previous approaches, this model is developed without the stationary phase approximation and including the relevant continuum-continuum transitions. Therefore, it provides a full quantum description of the harmonic generation process in these two ionization regimes, with a good quantitative accuracy with the exact results of the time-dependent Schroedinger equation. We show how this model can be used to investigate the contribution of the electronicmore » population ionized at different times, thus giving a time-resolved description that, up to now, was reserved only to semiclassical models. In addition, we will show some aspects of harmonic generation beyond the semiclassical predictions as, for instance, the emission of radiation while the electron is leaving the parent ion and the generation of harmonics in semiclassically forbidden situations.« less

  11. Dynamics of short pulses and phase matched second harmonic generation in negative index materials.

    PubMed

    Scalora, Michael; D'Aguanno, Giuseppe; Bloemer, Mark; Centini, Marco; de Ceglia, Domenico; Mattiucci, Nadia; Kivshar, Yuri S

    2006-05-29

    We study pulsed second harmonic generation in metamaterials under conditions of significant absorption. Tuning the pump in the negative index range, a second harmonic signal is generated in the positive index region, such that the respective indices of refraction have the same magnitudes but opposite signs. This insures that a forward-propagating pump is exactly phase matched to the backward-propagating second harmonic signal. Using peak intensities of ~500 MW/cm(2), assuming chi((2))~80pm/V, we predict conversion efficiencies of 12% and 0.2% for attenuation lengths of 50 and 5microm, respectively.

  12. Spin current and second harmonic generation in non-collinear magnetic systems: the hydrodynamic model

    NASA Astrophysics Data System (ADS)

    Karashtin, E. A.; Fraerman, A. A.

    2018-04-01

    We report a theoretical study of the second harmonic generation in a noncollinearly magnetized conductive medium with equilibrium spin current. The hydrodynamic model is used to unravel the mechanism of a novel effect of the double frequency signal generation that is attributed to the spin current. According to our calculations, this second harmonic response appears due to the ‘non-adiabatic’ spin polarization of the conduction electrons induced by the oscillations in the non-uniform magnetization forced by the electric field of the electromagnetic wave. Together with the linear velocity response this leads to the generation of the double frequency spin current. This spin current is converted to the electric current via the inverse spin Hall effect, and the double-frequency electric current emits the second harmonic radiation. Possible experiment for detection of the new second harmonic effect is proposed.

  13. Photovoltaic power converter system with a controller configured to actively compensate load harmonics

    DOEpatents

    de Rooij, Michael Andrew; Steigerwald, Robert Louis; Delgado, Eladio Clemente

    2008-12-16

    Photovoltaic power converter system including a controller configured to reduce load harmonics is provided. The system comprises a photovoltaic array and an inverter electrically coupled to the array to generate an output current for energizing a load connected to the inverter and to a mains grid supply voltage. The system further comprises a controller including a first circuit coupled to receive a load current to measure a harmonic current in the load current. The controller includes a second circuit to generate a fundamental reference drawn by the load. The controller further includes a third circuit for combining the measured harmonic current and the fundamental reference to generate a command output signal for generating the output current for energizing the load connected to the inverter. The photovoltaic system may be configured to compensate harmonic currents that may be drawn by the load.

  14. High-harmonic generation in ZnO driven by self-compressed mid-infrared pulses

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

    Gholam-Mirzaei, Shima; Beetar, John E.; Chacon, Alexis

    Progress in attosecond science has relied on advancements in few-cycle pulse generation technology and its application to high-order harmonic generation. Traditionally, self-phase modulation in bulk solids has been used for the compression of moderate-energy pulses, additionally exhibiting favorable dispersion properties for mid-infrared (mid-IR) pulses. For this study, we use the anomalous dispersion of Y 3Al 5O 12 (YAG) to self-compress many-cycle pulses from a 50 kHz mid-IR OPA down to produce sub-three-cycle 10 μJ pulses and further use them to generate high-order harmonics in a ZnO crystal. In agreement with theoretical predictions, we observe a boost in the harmonic yieldmore » by a factor of two, and spectral broadening of above-gap harmonics, compared to longer driving pulses. The enhanced yield results from an increase in the intensity for the self-compressed pulses.« less

  15. High-harmonic generation in ZnO driven by self-compressed mid-infrared pulses

    DOE PAGES

    Gholam-Mirzaei, Shima; Beetar, John E.; Chacon, Alexis; ...

    2018-02-20

    Progress in attosecond science has relied on advancements in few-cycle pulse generation technology and its application to high-order harmonic generation. Traditionally, self-phase modulation in bulk solids has been used for the compression of moderate-energy pulses, additionally exhibiting favorable dispersion properties for mid-infrared (mid-IR) pulses. For this study, we use the anomalous dispersion of Y 3Al 5O 12 (YAG) to self-compress many-cycle pulses from a 50 kHz mid-IR OPA down to produce sub-three-cycle 10 μJ pulses and further use them to generate high-order harmonics in a ZnO crystal. In agreement with theoretical predictions, we observe a boost in the harmonic yieldmore » by a factor of two, and spectral broadening of above-gap harmonics, compared to longer driving pulses. The enhanced yield results from an increase in the intensity for the self-compressed pulses.« less

  16. Polarization control of high order harmonics in the EUV photon energy range.

    PubMed

    Vodungbo, Boris; Barszczak Sardinha, Anna; Gautier, Julien; Lambert, Guillaume; Valentin, Constance; Lozano, Magali; Iaquaniello, Grégory; Delmotte, Franck; Sebban, Stéphane; Lüning, Jan; Zeitoun, Philippe

    2011-02-28

    We report the generation of circularly polarized high order harmonics in the extreme ultraviolet range (18-27 nm) from a linearly polarized infrared laser (40 fs, 0.25 TW) focused into a neon filled gas cell. To circularly polarize the initially linearly polarized harmonics we have implemented a four-reflector phase-shifter. Fully circularly polarized radiation has been obtained with an efficiency of a few percents, thus being significantly more efficient than currently demonstrated direct generation of elliptically polarized harmonics. This demonstration opens up new experimental capabilities based on high order harmonics, for example, in biology and materials science. The inherent femtosecond time resolution of high order harmonic generating table top laser sources renders these an ideal tool for the investigation of ultrafast magnetization dynamics now that the magnetic circular dichroism at the absorption M-edges of transition metals can be exploited.

  17. Role of antenna modes and field enhancement in second harmonic generation from dipole nanoantennas.

    PubMed

    de Ceglia, Domenico; Vincenti, Maria Antonietta; De Angelis, Costantino; Locatelli, Andrea; Haus, Joseph W; Scalora, Michael

    2015-01-26

    We study optical second harmonic generation from metallic dipole antennas with narrow gaps. Enhancement of the fundamental-frequency field in the gap region plays a marginal role on conversion efficiency. In the symmetric configuration, i.e., with the gap located at the center of the antenna axis, reducing gap size induces a significant red-shift of the maximum conversion efficiency peak. Either enhancement or inhibition of second-harmonic emission may be observed as gap size is decreased, depending on the antenna mode excited at the harmonic frequency. The second-harmonic signal is extremely sensitive to the asymmetry introduced by gap's displacements with respect to the antenna center. In this situation, second-harmonic light can couple to all the available antenna modes. We perform a multipolar analysis that allows engineering the far-field SH emission and find that the interaction with quasi-odd-symmetry modes generates radiation patterns with a strong dipolar component.

  18. Harmonic generation by yeast cells in response to low-frequency electric fields

    NASA Astrophysics Data System (ADS)

    Nawarathna, D.; Claycomb, J. R.; Cardenas, G.; Gardner, J.; Warmflash, D.; Miller, J. H., Jr.; Widger, W. R.

    2006-05-01

    We report on harmonic generation by budding yeast cells (Saccharomyces cerevisiae, 108cells/ml ) in response to sinusoidal electric fields with amplitudes ranging from zero to 5V/cm in the frequency range 10-300Hz . The cell-generated harmonics are found to exhibit strong amplitude and frequency dependence. Sodium metavanadate, an inhibitor of the proton pump known as H+ -ATPase, and glucose, a substrate of H+ -ATPase, are found to increase harmonic production at low amplitudes while reducing it at large amplitudes. This P-type proton pump can be driven by an oscillatory transmembrane potential, and its nonlinear response is believed to be largely responsible for harmonic production at low frequencies in yeast cells. We find that the observed harmonics show dramatic changes with time and in their field and frequency dependence after perturbing the system by adding an inhibitor, substrate, or membrane depolarizer to the cell suspension.

  19. The shift of harmonics with different initial vibrational states in the H{}_{2}^{+} molecular ion

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Pan, Xue-Fei; Xu, Tong-Tong; Liu, Xue-Shen

    2017-05-01

    Molecular high-order harmonic generation of H{}2+ and its isotopes is investigated by numerical simulations of the non-Born-Oppenheimer time-dependent Schrödinger equations. The general characteristic of the typical high-order harmonic generation (HHG) spectra for the H{}2+ molecule indicates that only the odd harmonics can be generated. Here we show that how the initial vibrational states and nuclear dynamics break down this standard characteristic, i.e. a redshift or blueshift of the harmonics appears. We investigate the effect of the initial vibrational states on the redshift or blueshift of the HHG spectrum under trapezoidal laser pulses. The ionization probability and time-frequency analysis are used to illustrate the physical mechanism of the shift of the harmonics. We also show the HHG spectra from the different isotopes of H2+ molecule with different initial vibrational states.

  20. Bi-harmonic cantilever design for improved measurement sensitivity in tapping-mode atomic force microscopy.

    PubMed

    Loganathan, Muthukumaran; Bristow, Douglas A

    2014-04-01

    This paper presents a method and cantilever design for improving the mechanical measurement sensitivity in the atomic force microscopy (AFM) tapping mode. The method uses two harmonics in the drive signal to generate a bi-harmonic tapping trajectory. Mathematical analysis demonstrates that the wide-valley bi-harmonic tapping trajectory is as much as 70% more sensitive to changes in the sample topography than the standard single-harmonic trajectory typically used. Although standard AFM cantilevers can be driven in the bi-harmonic tapping trajectory, they require large forcing at the second harmonic. A design is presented for a bi-harmonic cantilever that has a second resonant mode at twice its first resonant mode, thereby capable of generating bi-harmonic trajectories with small forcing signals. Bi-harmonic cantilevers are fabricated by milling a small cantilever on the interior of a standard cantilever probe using a focused ion beam. Bi-harmonic drive signals are derived for standard cantilevers and bi-harmonic cantilevers. Experimental results demonstrate better than 30% improvement in measurement sensitivity using the bi-harmonic cantilever. Images obtained through bi-harmonic tapping exhibit improved sharpness and surface tracking, especially at high scan speeds and low force fields.

  1. Joint Doctrine for Amphibious Embarkation

    DTIC Science & Technology

    1993-04-16

    remain unopposed through the arrival and assembly phase. 6. Greater Dispersion of Shipping a. The vulnerability of the amphibious task force ( ATF ... ATF to seaward of the landing beach from which assault shipping is phased into the transport area for selective or general offloading by...depends in large measure on the manner in which the ships have been loaded. Proper loading increases the inherent flexibility of the ATF and is a key

  2. Efficient 2(nd) and 4(th) harmonic generation of a single-frequency, continuous-wave fiber amplifier.

    PubMed

    Sudmeyer, Thomas; Imai, Yutaka; Masuda, Hisashi; Eguchi, Naoya; Saito, Masaki; Kubota, Shigeo

    2008-02-04

    We demonstrate efficient cavity-enhanced second and fourth harmonic generation of an air-cooled, continuous-wave (cw), single-frequency 1064 nm fiber-amplifier system. The second harmonic generator achieves up to 88% total external conversion efficiency, generating more than 20-W power at 532 nm wavelength in a diffraction-limited beam (M(2) < 1.05). The nonlinear medium is a critically phase-matched, 20-mm long, anti-reflection (AR) coated LBO crystal operated at 25 degrees C. The fourth harmonic generator is based on an AR-coated, Czochralski-grown beta-BaB(2)O(4) (BBO) crystal optimized for low loss and high damage threshold. Up to 12.2 W of 266-nm deep-UV (DUV) output is obtained using a 6-mm long critically phase-matched BBO operated at 40 degrees C. This power level is more than two times higher than previously reported for cw 266-nm generation. The total external conversion efficiency from the fundamental at 1064 nm to the fourth harmonic at 266 nm is >50%.

  3. ATF1 Modulates the Heat Shock Response by Regulating the Stress-Inducible Heat Shock Factor 1 Transcription Complex

    PubMed Central

    Takii, Ryosuke; Fujimoto, Mitsuaki; Tan, Ke; Takaki, Eiichi; Hayashida, Naoki; Nakato, Ryuichiro; Shirahige, Katsuhiko

    2014-01-01

    The heat shock response is an evolutionally conserved adaptive response to high temperatures that controls proteostasis capacity and is regulated mainly by an ancient heat shock factor (HSF). However, the regulation of target genes by the stress-inducible HSF1 transcription complex has not yet been examined in detail in mammalian cells. In the present study, we demonstrated that HSF1 interacted with members of the ATF1/CREB family involved in metabolic homeostasis and recruited them on the HSP70 promoter in response to heat shock. The HSF1 transcription complex, including the chromatin-remodeling factor BRG1 and lysine acetyltransferases p300 and CREB-binding protein (CBP), was formed in a manner that was dependent on the phosphorylation of ATF1. ATF1-BRG1 promoted the establishment of an active chromatin state and HSP70 expression during heat shock, whereas ATF1-p300/CBP accelerated the shutdown of HSF1 DNA-binding activity during recovery from acute stress, possibly through the acetylation of HSF1. Furthermore, ATF1 markedly affected the resistance to heat shock. These results revealed the unanticipated complexity of the primitive heat shock response mechanism, which is connected to metabolic adaptation. PMID:25312646

  4. Role for Human Mediator Subunit MED25 in Recruitment of Mediator to Promoters by Endoplasmic Reticulum Stress-responsive Transcription Factor ATF6α*

    PubMed Central

    Sela, Dotan; Conkright, Juliana J.; Chen, Lu; Gilmore, Joshua; Washburn, Michael P.; Florens, Laurence; Conaway, Ronald C.; Conaway, Joan Weliky

    2013-01-01

    Transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. In response to ER stress, ATF6α translocates from its site of latency in the ER membrane to the nucleus, where it activates RNA polymerase II transcription of ER stress response genes upon binding sequence-specifically to ER stress response enhancer elements (ERSEs) in their promoter-regulatory regions. In a recent study, we demonstrated that ATF6α activates transcription of ER stress response genes by a mechanism involving recruitment to ERSEs of the multisubunit Mediator and several histone acetyltransferase (HAT) complexes, including Spt-Ada-Gcn5 (SAGA) and Ada-Two-A-containing (ATAC) (Sela, D., Chen, L., Martin-Brown, S., Washburn, M.P., Florens, L., Conaway, J.W., and Conaway, R.C. (2012) J. Biol. Chem. 287, 23035–23045). In this study, we extend our investigation of the mechanism by which ATF6α supports recruitment of Mediator to ER stress response genes. We present findings arguing that Mediator subunit MED25 plays a critical role in this process and identify a MED25 domain that serves as a docking site on Mediator for the ATF6α transcription activation domain. PMID:23864652

  5. Down-regulation of ATF2 in the inhibition of T-2-toxin-induced chondrocyte apoptosis by selenium chondroitin sulfate nanoparticles

    NASA Astrophysics Data System (ADS)

    Han, Jing; Guo, Xiong

    2013-12-01

    Selenium chondroitin sulfate nanoparticles (SeCS) with a size range of 30-200 nm were obtained in our previous study. Meanwhile, the up-regulated expression of ATF2 mRNA and protein levels could be observed in the cartilage from Kashin-Beck disease (KBD) patients. In this paper, we investigated the inhibition effect of SeCS on T-2-toxin-induced apoptosis of chondrocyte from KBD patients. Here, we found that when the chondrocytes were treated with T-2 toxin, the chondrocyte apoptosis performed in a concentration-dependent manner. The apoptosis of chondrocyte induced by T-2 toxin involved the increased levels of ATF2, JNK and p38 mRNAs and related protein expression. SeCS could partly block the T-2-toxin-induced chondrocyte apoptosis by decreasing the expression of ATF2, JNK and p38 mRNAs and p-JNK, p-38, ATF2 and p-ATF2 proteins. JNK and p38 pathways involved in the apoptosis of chondrocyte induced by T-2 toxin, and SeCS was efficient in the inhibition of chondrocyte apoptosis by T-2 toxin. These results suggested that SeCS had a potential for further prevention and treatment for KBD as well as other selenium deficiency disease.

  6. Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.

    PubMed

    Sela, Dotan; Chen, Lu; Martin-Brown, Skylar; Washburn, Michael P; Florens, Laurence; Conaway, Joan Weliky; Conaway, Ronald C

    2012-06-29

    The basic leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence specifically to ER stress response enhancer elements in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (SAGA) and Ada-Two-A-containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.

  7. Role of ATF4 in skeletal muscle atrophy.

    PubMed

    Adams, Christopher M; Ebert, Scott M; Dyle, Michael C

    2017-05-01

    Here, we discuss recent work focused on the role of activating transcription factor 4 (ATF4) in skeletal muscle atrophy. Muscle atrophy involves and requires widespread changes in skeletal muscle gene expression; however, the transcriptional regulatory proteins responsible for those changes are not yet well defined. Recent work indicates that some forms of muscle atrophy require ATF4, a stress-inducible bZIP transcription factor subunit that helps to mediate a broad range of stress responses in mammalian cells. ATF4 expression in skeletal muscle fibers is sufficient to induce muscle fiber atrophy and required for muscle atrophy during several stress conditions, including aging, fasting, and limb immobilization. By helping to activate specific genes in muscle fibers, ATF4 contributes to the expression of numerous mRNAs, including at least two mRNAs (Gadd45a and p21) that encode mediators of muscle fiber atrophy. Gadd45a promotes muscle fiber atrophy by activating the protein kinase MEKK4. p21 promotes atrophy by reducing expression of spermine oxidase, a metabolic enzyme that helps to maintain muscle fiber size under nonstressed conditions. In skeletal muscle fibers, ATF4 is critical component of a complex and incompletely understood molecular signaling network that causes muscle atrophy during aging, fasting, and immobilization.

  8. Detection of cerebrospinal fluid leakage by specific measurement of transferrin glycoforms.

    PubMed

    Kwon, Seok-Joon; Zhang, Fuming; Dordick, Jonathan S; Sonstein, William J; Linhardt, Robert J

    2015-10-01

    A simple and rapid detection of cerebrospinal fluid (CSF) leakage would benefit spine surgeons making critical postoperative decisions on patient care. We have assessed novel approaches to selectively determine CSF β2-transferrin (β2TF), an asialo-transferrin (aTF) biomarker, without interference from serum sialo-transferrin (sTF) in test samples. First, we performed mild periodate oxidation to selectively generate aldehyde groups in sTF for capture with magnetic hydrazide microparticles, and selective removal with a magnetic separator. Using this protocol sTF was selectively removed from mixtures of CSF and serum containing CSF aTF (β2TF) and serum sTF, respectively. Second, a two-step enzymatic method was developed with neuraminidase and galactose oxidase for generating aldehyde groups in sTF present in CSF and serum mixtures for magnetic hydrazide microparticle capture. After selectively removing sTF from mixtures of CSF and serum, ELISA could detect significant TF signal only in CSF, while the TF signal in serum was negligible. The new approach for selective removal of only sTF in test samples will be promising for the required intervention by a spine surgeon. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. A magnetic isolation and pointing system for the astrometric telescope facility

    NASA Technical Reports Server (NTRS)

    Smith, Marcie; Hibble, William; Wolke, Patrick J.

    1993-01-01

    The astrometric telescope facility (ATF), a 20-meter telescope designed for long-term detection and observation of planetary systems outside of the solar system, is scheduled to be a major user of the Space Station's payload pointing system (PPS) capabilities. However, because the ATF has such a stringent pointing stability specification (as low as 0.01 arcsec error over the frequency range from 5 to 200 hertz) and requires +/- 180-degree roll rotation around the telescope's line of sight, the ATF's utilization of the PPS requires the addition of a mechanism or mechanisms to enhance the basic PPS capabilities. The results of a study conducted to investigate the ATF pointing performance achievable by the addition of a magnetic isolation and pointing (MIPS) system between the PPS upper gimbal and the ATF, and separately, by the addition of a passive isolation system between the Space Station and the PPS base are presented. In addition, the study produced requirements on magnetic force and gap motion as a function of the level of Space Station disturbance. These results were used to support the definition of a candidate MIPS. Pointing performance results from the study indicate that a MIPS can meet the ATF pointing requirements in the presence of a PPS base transitional acceleration of up to 0.018g, with reasonable restrictions placed on the isolation and pointing bandwidths. By contrast, the passive base isolator system must have an unrealistically low isolation bandwidth on all axes (less than 0.1 hertz) to meet ATF pointing requirements. The candidate MIPS is based on an assumed base translational disturbance of 0.01g. The system fits within the available annular region between the PPS and ATF while meeting power and weight limitations and providing the required payload roll motion. Payload data and power services are provided by noncontacting transfer devices.

  10. Nonlinear Metasurface for Simultaneous Control of Spin and Orbital Angular Momentum in Second Harmonic Generation.

    PubMed

    Li, Guixin; Wu, Lin; Li, King F; Chen, Shumei; Schlickriede, Christian; Xu, Zhengji; Huang, Siya; Li, Wendi; Liu, Yanjun; Pun, Edwin Y B; Zentgraf, Thomas; Cheah, Kok W; Luo, Yu; Zhang, Shuang

    2017-12-13

    The spin and orbital angular momentum (SAM and OAM) of light is providing a new gateway toward high capacity and robust optical communications. While the generation of light with angular momentum is well studied in linear optics, its further integration into nonlinear optical devices will open new avenues for increasing the capacity of optical communications through additional information channels at new frequencies. However, it has been challenging to manipulate the both SAM and OAM of nonlinear signals in harmonic generation processes with conventional nonlinear materials. Here, we report the generation of spin-controlled OAM of light in harmonic generations by using ultrathin photonic metasurfaces. The spin manipulation of OAM mode of harmonic waves is experimentally verified by using second harmonic generation (SHG) from gold meta-atom with 3-fold rotational symmetry. By introducing nonlinear phase singularity into the metasurface devices, we successfully generate and measure the topological charges of spin-controlled OAM mode of SHG through an on-chip metasurface interferometer. The nonlinear photonic metasurface proposed in this work not only opens new avenues for manipulating the OAM of nonlinear optical signals but also benefits the understanding of the nonlinear spin-orbit interaction of light in nanoscale devices.

  11. Prediction of Metastasis Using Second Harmonic Generation

    DTIC Science & Technology

    2016-07-01

    extracellular matrix through which metastasizing cells must travel. We and others have demonstrated that tumor collagen structure, as measured with the...algorithm using separate training and validation sets, etc. Keywords: metastasis, overtreatment, extracellular matrix , collagen , second harmonic...optical process called second harmonic generation (SHG), influences tumor metastasis. This suggests that collagen structure may provide prognostic

  12. Effects of Energy Chirp on Echo-Enabled Harmonic Generation Free-Electron Lasers

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

    Huang, Z.; Ratner, D.; Stupakov, G.

    2009-02-23

    We study effects of energy chirp on echo-enabled harmonic generation (EEHG). Analytical expressions are compared with numerical simulations for both harmonic and bunching factors. We also discuss the EEHG free-electron laser bandwidth increase due to an energy-modulated beam and its pulse length dependence on the electron energy chirp.

  13. The control of electron quantum trajectories on the high-order harmonic generation of CO and N2 molecules in the presence of a low frequency field.

    PubMed

    Koushki, A M; Sadighi-Bonabi, R; Mohsen-Nia, M; Irani, E

    2018-04-14

    In the present work, an efficient method is theoretically investigated for extending high-order harmonics and ultrashort attosecond pulse generation in N 2 and CO molecules by using the time-dependent density functional theory approach. Our results show that by utilizing chirped laser field in the presence of a low frequency field, not only is the harmonic cutoff extended remarkably but also the single short quantum trajectory is selected to contribute to the harmonic spectra. When a low frequency field is added to the two-color chirped laser field, the long quantum trajectories are suppressed and only the short quantum trajectories contribute to the higher harmonic emission mechanism. As a result, the spectral modulation is significantly decreased and an intense ultrashort pulse can be generated from the supercontinuum region of high harmonics. With such a scheme, the isolated ultrashort attosecond pulses can be generated in length, velocity, and acceleration gauges. Furthermore, these results are explained by using the classical and quantum time-frequency analyses.

  14. The control of electron quantum trajectories on the high-order harmonic generation of CO and N2 molecules in the presence of a low frequency field

    NASA Astrophysics Data System (ADS)

    Koushki, A. M.; Sadighi-Bonabi, R.; Mohsen-Nia, M.; Irani, E.

    2018-04-01

    In the present work, an efficient method is theoretically investigated for extending high-order harmonics and ultrashort attosecond pulse generation in N2 and CO molecules by using the time-dependent density functional theory approach. Our results show that by utilizing chirped laser field in the presence of a low frequency field, not only is the harmonic cutoff extended remarkably but also the single short quantum trajectory is selected to contribute to the harmonic spectra. When a low frequency field is added to the two-color chirped laser field, the long quantum trajectories are suppressed and only the short quantum trajectories contribute to the higher harmonic emission mechanism. As a result, the spectral modulation is significantly decreased and an intense ultrashort pulse can be generated from the supercontinuum region of high harmonics. With such a scheme, the isolated ultrashort attosecond pulses can be generated in length, velocity, and acceleration gauges. Furthermore, these results are explained by using the classical and quantum time-frequency analyses.

  15. Phase-matched second- and third-harmonic generation in plasmas with density ripple

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

    Dahiya, Deepak; Sajal, Vivek; Sharma, A. K.

    The generation of second and third harmonics by the interaction of an ultrashort laser pulse with underdense plasma having a density ripple is studied at intensities I{lambda}{sup 2}=10{sup 16}-10{sup 19} W cm{sup -2} {mu}m{sup 2} using fully relativistic two-dimensional particle-in-cell simulations with high spectral resolution. A theoretical model is developed for second- and third-harmonic conversion efficiencies. When the laser is plane polarized in the simulation plane even and odd harmonics are excited in the same polarization as the laser polarization. The highest efficiency of generation of a specific harmonic occurs when the ripple wave vector value k{sub q} satisfies phase-matchingmore » conditions. The efficiency of phase-matched harmonic generation is an order of magnitude higher than the one without phase matching. The efficiency increases rapidly in weak and moderate relativistic regime and tends to saturate in strong relativistic regime. At moderately relativistic intensities and low plasma densities, the simulation and recent experimental results are fairly reproduced by an analytical theory.« less

  16. Influence of micro- and macro-processes on the high-order harmonic generation in laser-produced plasma

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

    Ganeev, R. A., E-mail: rashid-ganeev@mail.ru; Physical Department, Voronezh State University, Voronezh 394006

    We compare the resonance-induced enhancement of single harmonic and the quasi-phase-matching-induced enhancement of the group of harmonics during propagation of the tunable mid-infrared femtosecond pulses through the perforated laser-produced indium plasma. We show that the enhancement of harmonics using the macro-process of quasi-phase-matching is comparable with the one using micro-process of resonantly enhanced harmonic. These studies show that joint implementation of the two methods of the increase of harmonic yield could be a useful tool for generation of strong short-wavelength radiation in different spectral regions. We compare these effects in indium, as well as in other plasmas.

  17. SPECIAL ISSUE DEVOTED TO THE 80TH BIRTHDAY OF S.A. AKHMANOV: Selective generation of a higher harmonic in plasma

    NASA Astrophysics Data System (ADS)

    Kulagin, I. A.; Usmanov, T.

    2009-07-01

    It is shown for the first time that the use of autoionisation states for phase matching leads to the efficient selection of a single harmonic generated in a plateau region in plasma. The selected harmonic frequency can be tuned by changing the relative concentration of plasma components and tuning the fundamental radiation frequency. It is shown that the contrast of the selected harmonic can exceed 104.

  18. Harmonic generation in magnetized quantum plasma

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

    Kumar, Punit; Singh, Abhisek Kumar; Singh, Shiv

    2016-05-06

    A study of second harmonic generation by propagation of a linearly polarized electromagnetic wave through homogeneous high density quantum plasma in the presence of transverse magnetic field. The nonlinear current density and dispersion relations for the fundamental and second harmonic frequencies have been obtained using the recently developed quantum hydrodynamic (QHD) model. The effect of quantum Bohm potential, Fermi pressure and the electron spin have been taken into account. The second harmonic is found to be less dispersed than the first.

  19. Sensing new chemicals with bacterial transcription factors.

    PubMed

    Libis, Vincent; Delépine, Baudoin; Faulon, Jean-Loup

    2016-10-01

    Bacteria rely on allosteric transcription factors (aTFs) to sense a wide range of chemicals. The variety of effectors has contributed in making aTFs the most used input system in synthetic biological circuits. Considering their enabling role in biotechnology, an important question concerns the size of the chemical space that can potentially be detected by these biosensors. From digging into the ever changing repertoire of natural regulatory circuits, to advances in aTF engineering, we review here different strategies that are pushing the boundaries of this chemical space. We also review natural and synthetic cases of indirect sensing, where aTFs work in combination with metabolism to enable detection of new molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. How classical gluon fields generate odd azimuthal harmonics for the two-gluon correlation function in high-energy collisions

    NASA Astrophysics Data System (ADS)

    Kovchegov, Yuri V.; Skokov, Vladimir V.

    2018-05-01

    We show that, in the saturation/color glass condensate framework, odd azimuthal harmonics of the two-gluon correlation function with a long-range separation in rapidity are generated by the higher-order saturation corrections in the interactions with the projectile and the target. At the very least, the odd harmonics require three scatterings in the projectile and three scatterings in the target. We derive the leading-order expression for the two-gluon production cross section which generates odd harmonics: the expression includes all-order interactions with the target and three interactions with the projectile. We evaluate the obtained expression both analytically and numerically, confirming that the odd-harmonics contribution to the two-gluon production in the saturation framework is nonzero.

  1. Generation of µW level plateau harmonics at high repetition rate.

    PubMed

    Hädrich, S; Krebs, M; Rothhardt, J; Carstens, H; Demmler, S; Limpert, J; Tünnermann, A

    2011-09-26

    The process of high harmonic generation allows for coherent transfer of infrared laser light to the extreme ultraviolet spectral range opening a variety of applications. The low conversion efficiency of this process calls for optimization or higher repetition rate intense ultrashort pulse lasers. Here we present state-of-the-art fiber laser systems for the generation of high harmonics up to 1 MHz repetition rate. We perform measurements of the average power with a calibrated spectrometer and achieved µW harmonics between 45 nm and 61 nm (H23-H17) at a repetition rate of 50 kHz. Additionally, we show the potential for few-cycle pulses at high average power and repetition rate that may enable water-window harmonics at unprecedented repetition rate. © 2011 Optical Society of America

  2. Nonlinear viscous higher harmonics generation due to incident and reflecting internal wave beam collision

    NASA Astrophysics Data System (ADS)

    Aksu, Anil A.

    2017-09-01

    In this paper, we have considered the non-linear effects arising due to the collision of incident and reflected internal wave beams. It has already been shown analytically [Tabaei et al., "Nonlinear effects in reflecting and colliding internal wave beams," J. Fluid Mech. 526, 217-243 (2005)] and numerically [Rodenborn et al., "Harmonic generation by reflecting internal waves," Phys. Fluids 23, 026601 (2011)] that the internal wave beam collision generates the higher harmonics and mean flow in a linear stratification. In this paper, similar to previous analytical work, small amplitude wave theory is employed; however, it is formulated from energetics perspective which allows considering internal wave beams as the product of slowly varying amplitude and fast complex exponential. As a result, the mean energy propagation equation for the second harmonic wave is obtained. Finally, a similar dependence on the angle of incidence is obtained for the non-linear energy transfer to the second harmonic with previous analyses. A possible physical mechanism for this angle dependence on the second harmonic generation is also discussed here. In addition to previous studies, the viscous effects are also included in the mean energy propagation equation for the incident, the reflecting, and the second harmonic waves. Moreover, even though the mean flow obtained here is only confined to the interaction region, it is also affected by viscosity via the decay in the incident and the reflecting internal wave beams. Furthermore, a framework for the non-linear harmonic generation in non-linear stratification is also proposed here.

  3. Generation of five phase-locked harmonics in the continuous wave regime and its potential application to arbitrary optical waveform synthesis

    NASA Astrophysics Data System (ADS)

    Suhaimi, N. Sheeda; Ohae, C.; Gavara, T.; Nakagawa, K.; Hong, F.-L.; Katsuragawa, M.

    2017-08-01

    We have successfully generated a new broadband coherent light source in the continuous wave (CW) regime which is an ensemble of multi-harmonic radiations (2403, 1201, 801, 600 and 480 nm) by implementing a frequency dividing technology. The system is uniquely designed that all the harmonics are generated and propagate coaxially which gives the advantage of robustly maintaining the phase coherence among the harmonics. The highlight is its huge potential for the arbitrary optical waveform synthesis in the CW regime which has not been performed yet due to the limitation of the existing light source.

  4. RIA simulation tests using driver tube for ATF cladding

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

    Cinbiz, Mahmut N.; Brown, N. R.; Lowden, R. R.

    Pellet-cladding mechanical interaction (PCMI) is a potential failure mechanism for accident-tolerant fuel (ATF) cladding candidates during a reactivity-initiated accident (RIA). This report summarizes Fiscal Year (FY) 2017 research activities that were undertaken to evaluate the PCMI-like hoop-strain-driven mechanical response of ATF cladding candidates. To achieve various RIA-like conditions, a modified-burst test (MBT) device was developed to produce different mechanical pulses. The calibration of the MBT instrument was accomplished by performing mechanical tests on unirradiated Generation-I iron-chromium-aluminum (FeCrAl) alloy samples. Shakedown tests were also conducted in both FY 2016 and FY 2017 using unirradiated hydrided ZIRLO™ tube samples. This milestone reportmore » focuses on testing of ATF materials, but the benchmark tests with hydrided ZIRLO™ tube samples are documented in a recent journal article.a For the calibration and benchmark tests, the hoop strain was monitored using strain gauges attached to the sample surface in the hoop direction. A novel digital image correlation (DIC) system composed of a single high-speed camera and an array of six mirrors was developed for the MBT instrument to better resolve the failure behavior of samples and to provide useful data for validation of high-fidelity modeling and simulation tools. The DIC system enable a 360° view of a sample’s outer surface. This feature was added to the instrument to determine the precise failure location on a sample’s surface for strain predictions. The DIC system was tested on several silicon carbide fiber/silicon carbide matrix (SiC/SiC) composite tube samples at various pressurization rates of the driver tube (which correspond to the strain rates for the samples). The hoop strains for various loading conditions were determined for the SiC/SiC composite tube samples. Future work is planned to enhance understanding of the failure behavior of the ATF cladding candidates of age-hardened FeCrAl alloys and SiC/SiC composites in detail during RIA conditions informed by the computational studies performed under the US Department of Energy Office of Nuclear Energy Advanced Fuels Campaign. The testing instrument and the new DIC system will be further developed to reach different stress-state conditions and to perform tests at elevated temperatures.« less

  5. Effects of electron relaxation on multiple harmonic generation from metal surfaces with femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Karatzas, N. E.; Georges, A. T.

    2006-11-01

    Calculations are presented for the first four (odd and even) harmonics of an 800 nm laser from a gold surface, with pulse widths ranging from 100 down to 14 fs. For peak laser intensities above 1 GW/cm 2 the harmonics are enhanced because of a partial depletion of the initial electron states. At 10 11 W/cm 2 of peak laser intensity the calculated conversion efficiency for 2nd-harmonic generation is 3 × 10 -9, while for the 5th-harmonic it is 10 -10. The generated harmonic pulses are broadened and delayed relative to the laser pulse because of the finite relaxation times of the excited electronic states. The finite electron relaxation times cause also the broadening of the autocorrelations of the laser pulses obtained from surface harmonic generation by two time-delayed identical pulses. Comparison with recent experimental results shows that the response time of an autocorrelator using nonlinear optical processes in a gold surface is shorter than the electron relaxation times. This seems to indicate that for laser pulses shorter than ˜30 fs, the fast nonresonant channel for multiphoton excitation via continuum-continuum transitions in metals becomes important as the resonant channel becomes slow (relative to the laser pulse) and less efficient.

  6. Generation and manipulation of attosecond light pulses

    NASA Astrophysics Data System (ADS)

    Gaarde, Mette

    2006-05-01

    Attosecond pulses of light can be generated in the extremely non-linear interactions between an ultrashort, intense laser pulse and a gas of atoms, via the process of high harmonic generation [1,2]. In one approach, a number of odd harmonics of rougly equal strength are combined to form a train of sub-femtosecond pulses. If the harmonics are locked in phase to each other, the train will consist of the emission of one attosecond pulse every half cycle of the driving laser field [1,3]. It is in general not trivial to ensure that the harmonics are phase-locked as they are generated with intrinsically different phases. These phases originate in the strong field dynamics of the light-matter interaction [4].We will discuss different ways of generating and manipulating attosecond pulses via high harmonic generation. We will show how the harmonics can be phase-locked and better synchronized so as to form optimal pulse trains [3]. We will also show that it is possible to generate trains of pulses separated by a full laser cycle, by combining the driving laser field with its second harmonic [5]. The strong field continuum dynamics driven by the two-color field is very different from that of the one-color field and varies strongly with the delay between the two laser fields [6]. (1) P. M. Paul et al, Science 292, 1689 (2001).(2) M. Hentschel et al, Nature 414, 509 (2001).(3) R. Lopez-Martens et al, PRL 94, 033001 (2005).(4) P. Antoine, A. L'Huillier, and M. Lewenstein, PRL 77, 1234 (1996).(5) J. Mauritsson et al, in preparation (2006).(6) M. B. Gaarde et al, in preparation (2006).

  7. Bernstein wave aided laser third harmonic generation in a plasma

    NASA Astrophysics Data System (ADS)

    Tyagi, Yachna; Tripathi, Deepak; Kumar, Ashok

    2016-09-01

    The process of Bernstein wave aided resonant third harmonic generation of laser in a magnetized plasma is investigated. The extra-ordinary mode (X-mode) laser of frequency ω 0 and wave number k → 0 , travelling across the magnetic field in a plasma, exerts a second harmonic ponderomotive force on the electrons imparting them an oscillatory velocity v → 2 ω0 , 2 k → 0 . This velocity beats with the density perturbation due to the Bernstein wave to produce a density perturbation at cyclotron frequency shifted second harmonic. The density perturbation couples with the oscillatory velocity v → ω0 , k → 0 of X-mode of the laser to produce the cyclotron frequency shifted third harmonic current density leading to harmonic radiation. The phase matching condition for the up shifted frequency is satisfied when the Bernstein wave is nearly counter-propagating to the laser. As the transverse wave number of the Bernstein wave is large, it is effective in the phase matched third harmonic generation, when the laser frequency is not too far from the upper hybrid frequency.

  8. Investigation on the relationship between overpressure and sub-harmonic response from encapsulated microbubbles

    NASA Astrophysics Data System (ADS)

    Wu, Jun; Fan, Ting-Bo; Xu, Di; Zhang, Dong

    2014-10-01

    Sub-harmonic component generated from microbubbles is proven to be potentially used in noninvasive blood pressure measurement. Both theoretical and experimental studies are performed in the present work to investigate the dependence of the sub-harmonic generation on the overpressure with different excitation pressure amplitudes and pulse lengths. With 4-MHz ultrasound excitation at an applied acoustic pressure amplitude of 0.24 MPa, the measured sub-harmonic amplitude exhibits a decreasing change as overpressure increases; while non-monotonic change is observed for the applied acoustic pressures of 0.36 MPa and 0.48 MPa, and the peak position in the curve of the sub-harmonic response versus the overpressure shifts toward higher overpressure as the excitation pressure amplitude increases. Furthermore, the exciting pulse with long duration could lead to a better sensitivity of the sub-harmonic response to overpressure. The measured results are explained by the numerical simulations based on the Marmottant model. The numerical simulations qualitatively accord with the measured results. This work might provide a preliminary proof for the optimization of the noninvasive blood pressure measurement through using sub-harmonic generation from microbubbles.

  9. Automatic computation and solution of generalized harmonic balance equations

    NASA Astrophysics Data System (ADS)

    Peyton Jones, J. C.; Yaser, K. S. A.; Stevenson, J.

    2018-02-01

    Generalized methods are presented for generating and solving the harmonic balance equations for a broad class of nonlinear differential or difference equations and for a general set of harmonics chosen by the user. In particular, a new algorithm for automatically generating the Jacobian of the balance equations enables efficient solution of these equations using continuation methods. Efficient numeric validation techniques are also presented, and the combined algorithm is applied to the analysis of dc, fundamental, second and third harmonic response of a nonlinear automotive damper.

  10. Enhancement and inhibition of second-harmonic generation and absorption in a negative index cavity.

    PubMed

    de Ceglia, Domenico; D'Orazio, Antonella; De Sario, Marco; Petruzzelli, Vincenzo; Prudenzano, Francesco; Centini, Marco; Cappeddu, Mirko G; Bloemer, Mark J; Scalora, Michael

    2007-02-01

    We study second-harmonic generation in a negative-index material cavity. The transmission spectrum shows a bandgap between the electric and magnetic plasma frequencies. The nonlinear process is made efficient by local phase-matching conditions between a forward-propagating pump and a backward-propagating second-harmonic signal. By simultaneously exciting the cavity with counterpropagating pulses, and by varying their relative phase difference, one is able to enhance or inhibit linear absorption and the second-harmonic conversion efficiency.

  11. SYNCHROTRON RADIATION, FREE ELECTRON LASER, APPLICATION OF NUCLEAR TECHNOLOGY, ETC.: Operating the SDUV-FEL with the echo-enabled harmonic generation scheme

    NASA Astrophysics Data System (ADS)

    Chen, Jian-Hui; Deng, Hai-Xiao; Gu, Qiang; Li, Dong-Guo; Wang, Dong; Zhang, Meng; Zhao, Zhen-Tang

    2009-08-01

    Using the recently proposed echo-enabled harmonic generation (EEHG) free-electron laser (FEL) scheme, it is shown that operating the Shanghai deep ultraviolet FEL (SDUV-FEL) with single-stage to higher harmonics is very promising, with higher frequency up-conversion efficiency, higher harmonic selectivity and lower power requirement of the seed laser. The considerations on a proof-of-principle experiment and expected performance in SDUV-FEL are given.

  12. Control of Laser High-Harmonic Generation with Counterpropagating Light

    NASA Astrophysics Data System (ADS)

    Voronov, S. L.; Kohl, I.; Madsen, J. B.; Simmons, J.; Terry, N.; Titensor, J.; Wang, Q.; Peatross, J.

    2001-09-01

    Relatively weak counterpropagating light is shown to disrupt the emission of laser high-harmonic generation. Harmonic orders ranging from the teens to the low thirties produced by a 30-femtosecond pulse in a narrow argon jet are ``shut down'' with a contrast as high as 2 orders of magnitude by a chirped 1-picosecond counterpropagating laser pulse (60 times less intense). Alternatively, under poor phase-matching conditions, the counterpropagating light boosts harmonic production by similar contrast through quasiphase matching where out-of-phase emission is suppressed.

  13. Activation of the unfolded protein response during anoxia exposure in the turtle Trachemys scripta elegans.

    PubMed

    Krivoruchko, Anastasia; Storey, Kenneth B

    2013-02-01

    Red-eared slider turtles, Trachemys scripta elegans, can survive for several weeks without oxygen when submerged in cold water. We hypothesized that anaerobiosis is aided by adaptive up-regulation of the unfolded protein response (UPR), a stress-responsive pathway that is activated by accumulation of unfolded proteins in the endoplasmic reticulum (ER) and functions to restore ER homeostasis. RT-PCR, western immunoblotting and DNA-binding assays were used to quantify the responses and/or activation status of UPR-responsive genes and proteins in turtle tissues after animal exposure to 5 or 20 h of anoxic submergence at 4 °C. The phosphorylation state of protein kinase-like ER kinase (PERK) (a UPR-regulated kinase) and eukaryotic initiation factor 2 (eIF2α) increased by 1.43-2.50 fold in response to anoxia in turtle heart, kidney, and liver. Activation of the PERK-regulated transcription factor, activating transcription factor 4 (ATF4), during anoxia was documented by elevated atf4 transcripts and total ATF4 protein (1.60-2.43 fold), increased nuclear ATF4 content, and increased DNA-binding activity (1.44-2.32 fold). ATF3 and GADD34 (downstream targets of ATF4) also increased by 1.38-3.32 fold in heart and liver under anoxia, and atf3 transcripts were also elevated in heart. Two characteristic chaperones of the UPR, GRP78, and GRP94, also responded positively to anoxia with strong increases in both the transcript and protein levels. The data demonstrate that the UPR is activated in turtle heart, kidney, and liver in response to anoxia, suggesting that this pathway mediates an integrated stress response to protect tissues during oxygen deprivation.

  14. NONLINEAR OPTICS PHENOMENA: Second harmonic generation from DF laser radiation in ZnGeP2

    NASA Astrophysics Data System (ADS)

    Andreev, Yu M.; Velikanov, S. D.; Yerutin, A. S.; Zapol'skiĭ, A. F.; Konkin, D. V.; Mishkin, S. N.; Smirnov, S. V.; Frolov, Yu N.; Shchurov, V. V.

    1992-11-01

    We have succeeded in generating the second harmonic of the radiation from a DF laser for the first time, using single crystals of ZnGeP2. For crystals with lengths of 10.1 and 13.6 mm, the overall external efficiencies of the entire oscillator system were 4 and 6.2%. The internal efficiencies of second-harmonic generation in the crystals were 7.6 and 11.8%, respectively.

  15. miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2.

    PubMed

    Gao, Ming; Liu, Yun; Chen, Yue; Yin, Chunyang; Chen, Jane-Jane; Liu, Sijin

    2016-03-01

    Nuclear factor (erythroid-derived 2) like 2 (Nrf2) is a key regulator in protecting cells against stress by targeting many anti-stress response genes. Recent evidence also reveals that Nrf2 functions partially by targeting mircroRNAs (miRNAs). However, the understanding of Nrf2-mediated cytoprotection through miRNA-dependent mechanisms is largely unknown. In the current study, we identified a direct Nrf2 targeting miRNA, miR-214, and demonstrated a protective role of miR-214 in erythroid cells against oxidative stresses generated by radiation, excess iron and arsenic (As) exposure. miR-214 expression was transcriptionally repressed by Nrf2 through a canonical antioxidant response element (ARE) within its promoter region, and this repression is ROS-dependence. The suppression of miR-214 by Nrf2 could antagonize oxidative stress-induced cell death in erythroid cells by two ways. First, miR-214 directly targeted ATF4, a crucial transcriptional factor involved in anti-stress responses, down regulation of miR-214 releases the repression of ATF4 translation and leads to increased ATF4 protein content. Second, miR-214 was able to prevent cell death by targeting EZH2, the catalytic core component of PRC2 complex that is responsible for tri-methylation reaction at lysine 27 (K27) of histone 3 (H3) (H3K27me3), by which As-induced miR-214 reduction resulted in an increased global H3K27me3 level and a compromised overexpression of a pro-apoptotic gene Bim. These two pathways downstream of miR-214 synergistically cooperated to antagonize erythroid cell death upon oxidative stress. Our combined data revealed a protective role of miR-214 signaling in erythroid cells against oxidative stress, and also shed new light on Nrf2-mediated cytoprotective machinery. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Wake-field and space charge effects on high brightness beams calculations and measured results for the laser driven photoelectrons at BNL-ATF

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

    Parsa, Z.

    1993-05-01

    We discuss the formalism used to study the effects of the interactions between the highly charged particles and the fields in the accelerating structure, including space charge and wake fields. Some of our calculations and numerical simulation results obtained for the Brookhaven National Laboratory (BNL) high-brightness photoelectron beam at the Accelerator Test Facility (ATF) and the measured data at ATF are also included.

  17. Imaging with Second-Harmonic Generation Nanoparticles

    NASA Astrophysics Data System (ADS)

    Hsieh, Chia-Lung

    Second-harmonic generation nanoparticles show promise as imaging probes due to their coherent and stable signal with a broad flexibility in the choice of excitation wavelength. In this thesis, we developed and demonstrated barium titanate nanoparticles as second-harmonic radiation imaging probes. We studied the absolute second-harmonic generation efficiency of the nanoparticles on single-particle level. The polarization dependent second-harmonic signal of single nanoparticles was studied in detail. From the measured polar response, we were able to find the orientation of the nanoparticle. We developed a biochemical interface for using the second-harmonic nanoprobes as biomarkers, including in vitro cellular imaging and in vivo live animal imaging. The nanoparticles were surface functionalized with primary amine groups for stable colloidal dispersion. We achieved specific labeling of the second-harmonic nanoprobes via immunostaining where the antibodies were covalently conjugated onto the nanoparticles. We observed no toxicity of the functionalized nanoparticles to biological cells. The coherent second-harmonic signal radiated from the nanoparticles offers opportunities for new imaging techniques. Using interferometric detection, namely harmonic holography, both amplitude and phase of the second-harmonic field can be captured. Through digital beam propagation, three-dimensional field distribution, reflecting three-dimensional distribution of the nanoparticles, can be reconstructed. We achieved a scan-free three-dimensional imaging of nanoparticles in biological cells with sub-micron spatial resolution by using the harmonic holographic microscope. We further exploited the coherent second-harmonic signal for imaging through scattering media by performing optical phase conjugation of the second-harmonic signal. We demonstrated an all-digital optical phase conjugation of the second-harmonic signal originated from a nanoparticle by combining harmonic holography and dynamic computer generated holography using a spatial light modulator. The phase-conjugated second-harmonic scattered field retraced the scattering trajectory and formed a clean focus on the nanoparticle placed inside a scattering medium. The nanoparticle acted as a beacon of light; it helped us find the tailored wavefront for concentrating light at the nanoparticle inside the scattering medium. We also demonstrated imaging through a thin scattering medium by raster-scanning the phase-conjugated focus in the vicinity of the beacon nanoparticle, in which a clear image of a target placed behind a ground glass diffuser was obtained.

  18. Kerr-like behaviour of second harmonic generation in the far-off resonant regime

    NASA Astrophysics Data System (ADS)

    Peřinová, Vlasta; Lukš, Antonín; Křepelka, Jaromír; Leoński, Wiesław; Peřina, Jan

    2018-05-01

    We separate the Kerr-like behaviour of the second-harmonic generation in the far-off resonant regime from the oscillations caused by the time-dependence of the interaction energy. To this purpose, we consider the approximation obtained from the exact dynamics by the method of small rotations. The Floquet-type decomposition of the approximate dynamics comprises the Kerr-like dynamics and oscillations of the same order of magnitude as those assumed for the exact dynamics of the second-harmonic generation. We have found that a superposition of two states of concentrated quantum phase arises in the fundamental mode in the second-harmonic generation in the far-off resonant limit at a later time than a superposition of two coherent states in the corresponding Kerr medium and the difference is larger for higher initial coherent amplitudes. The quantum phase fluctuation is higher for the same initial coherent amplitudes in the fundamental mode in the second-harmonic generation in the far-off resonant limit than in the corresponding Kerr medium and the difference is larger for higher initial coherent amplitudes.

  19. Kolakoski sequence as an element to radiate giant forward and backward second harmonic signals

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

    Parvini, T. S.; Tehranchi, M. M., E-mail: m-hamidi@sbu.ac.ir, E-mail: teranchi@sbu.ac.ir; Laser and Plasma Research Institute, Shahid Beheshti University, Tehran

    2015-11-14

    We propose a novel type of aperiodic one-dimensional photonic crystal structures which can be used for generating giant forward and backward second harmonic signals. The studied structure is formed by stacking together the air and nonlinear layers according to the Kolakoski self-generation scheme in which each nonlinear layer contains a pair of antiparallel 180° poled LiNbO{sub 3} crystal layers. For different generation stages of the structure, conversion efficiencies of forward and backward second harmonic waves have been calculated by nonlinear transfer matrix method. Numerical simulations show that conversion efficiencies in the Kolakoski-based multilayer are larger than the perfect ones formore » at least one order of magnitude. Especially for 33rd and 39th generation stages, forward second harmonic wave are 42 and 19 times larger, respectively. In this paper, we validate the strong fundamental field enhancement and localization within Kolakoski-based multilayer due to periodicity breaking which consequently leads to very strong radiation of backward and forward second harmonic signals. Following the applications of analogous aperiodic structures, we expect that Kolakosi-based multilayer can play a role in optical parametric devices such as multicolor second harmonic generators with high efficiency.« less

  20. Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation

    PubMed Central

    Plate, Lars; Cooley, Christina B; Chen, John J; Paxman, Ryan J; Gallagher, Ciara M; Madoux, Franck; Genereux, Joseph C; Dobbs, Wesley; Garza, Dan; Spicer, Timothy P; Scampavia, Louis; Brown, Steven J; Rosen, Hugh; Powers, Evan T; Walter, Peter; Hodder, Peter; Wiseman, R Luke; Kelly, Jeffery W

    2016-01-01

    Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases. DOI: http://dx.doi.org/10.7554/eLife.15550.001 PMID:27435961

  1. BNL ATF II beamlines design

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

    Fedurin, M.; Jing, Y.; Stratakis, D.

    The Brookhaven National Laboratory. Accelerator Test Facility (BNL ATF) is currently undergoing a major upgrade (ATF-II). Together with a new location and much improved facilities, the ATF will see an upgrade in its major capabilities: electron beam energy and quality and CO 2 laser power. The electron beam energy will be increased in stages, first to 100-150 MeV followed by a further increase to 500 MeV. Combined with the planned increase in CO 2 laser power (from 1-100 TW), the ATF-II will be a powerful tool for Advanced Accelerator research. A high-brightness electron beam, produced by a photocathode gun, willmore » be accelerated and optionally delivered to multiple beamlines. Besides the energy range (up to a possible 500 MeV in the final stage) the electron beam can be tailored to each experiment with options such as: small transverse beam size (<10 um), short bunch length (<100 fsec) and, combined short and small bunch options. This report gives a detailed overview of the ATFII capabilities and beamlines configuration.« less

  2. Thermal aging of melt-spun NdFeB magnetic powder in hydrogen

    NASA Astrophysics Data System (ADS)

    Pinkerton, Frederick E.; Balogh, Michael P.; Ellison, Nicole; Foto, Aldo; Sechan, Martin; Tessema, Misle M.; Thompson, Margarita P.

    2016-11-01

    High energy product neodymium-iron-boron (NdFeB) magnets are the premier candidate for demanding electrified vehicle traction motor applications. Injection molded (IM) or compression molded (CM) magnets made using NdFeB powders are promising routes to improve motor efficiency, cost, and manufacturability. However, IM and CM NdFeB magnets are susceptible to substantial thermal aging losses at motor operating temperatures when exposed to the automatic transmission fluid (ATF) used as a lubricant and cooling medium. The intrinsic coercivity Hci of NdFeB IM and CM magnets degrades by as much as 18% when aged for 1000 h in ATF at 150 °C, compared to a 3% loss when aged in air. Here we report aging studies of rapidly quenched NdFeB powder in air, ATF, and H2 gas. Expansion of the NdFeB crystal lattice in both ATF and H2 identified hydrogen dissociated from the ATF during aging and diffused into the primary NdFeB phase as the probable cause of the coercivity loss of IM and CM magnets.

  3. Phospho-mimicking Atf1 mutants bypass the transcription activating function of the MAP kinase Sty1 of fission yeast.

    PubMed

    Sánchez-Mir, Laura; Salat-Canela, Clàudia; Paulo, Esther; Carmona, Mercè; Ayté, José; Oliva, Baldo; Hidalgo, Elena

    2018-02-01

    Stress-dependent activation of signaling cascades is often mediated by phosphorylation events, but the exact nature and role of these phosphorelays are frequently poorly understood. Here, we review which are the consequences of the stress-dependent phosphorylation of a transcription factor on gene activation. In fission yeast, the MAP kinase Sty1 is activated upon several environmental hazards and promotes cell adaptation and survival, greatly through activation of a gene program mediated by the transcription factor Atf1. Although described decades ago, the role of the phosphorylation of Atf1 by Sty1 is still a matter of debate. We present here a brief review of recent data, obtained through the characterization of several phosphorylation mutant derivatives of Atf1, demonstrating that Atf1 phosphorylation does not stabilize the factor nor stimulates its binding to DNA. Rather, it provides a structural platform of interaction with the transcriptional machinery. Based on these findings, future work will establish how this phosphorylated trans-activation domain promotes the massive gene expression shift allowing cellular adaptation to stress.

  4. Glucose Deprivation Induces ATF4-Mediated Apoptosis through TRAIL Death Receptors

    PubMed Central

    Iurlaro, Raffaella; Püschel, Franziska; León-Annicchiarico, Clara Lucía; O'Connor, Hazel; Martin, Seamus J.; Palou-Gramón, Daniel; Lucendo, Estefanía

    2017-01-01

    ABSTRACT Metabolic stress occurs frequently in tumors and in normal tissues undergoing transient ischemia. Nutrient deprivation triggers, among many potential cell death-inducing pathways, an endoplasmic reticulum (ER) stress response with the induction of the integrated stress response transcription factor ATF4. However, how this results in cell death remains unknown. Here we show that glucose deprivation triggered ER stress and induced the unfolded protein response transcription factors ATF4 and CHOP. This was associated with the nontranscriptional accumulation of TRAIL receptor 1 (TRAIL-R1) (DR4) and with the ATF4-mediated, CHOP-independent induction of TRAIL-R2 (DR5), suggesting that cell death in this context may involve death receptor signaling. Consistent with this, the ablation of TRAIL-R1, TRAIL-R2, FADD, Bid, and caspase-8 attenuated cell death, although the downregulation of TRAIL did not, suggesting ligand-independent activation of TRAIL receptors. These data indicate that stress triggered by glucose deprivation promotes the ATF4-dependent upregulation of TRAIL-R2/DR5 and TRAIL receptor-mediated cell death. PMID:28242652

  5. Mechanism of equivalent electric dipole oscillation for high-order harmonic generation from grating-structured solid-surface by femtosecond laser pulse

    NASA Astrophysics Data System (ADS)

    Wang, Yang; Song, Hai-Ying; Liu, H. Y.; Liu, Shi-Bing

    2017-07-01

    We theoretically study high-order harmonic generation (HHG) from relativistically driven overdense plasma targets with rectangularly grating-structured surfaces by femtosecond laser pulses. Our particle-in-cell (PIC) simulations show that, under the conditions of low laser intensity and plasma density, the harmonics emit principally along small angles deviating from the target surface. Further investigation of the surface electron dynamics reveals that the electron bunches are formed by the interaction between the laser field and the target surface, giving rise to the oscillation of equivalent electric-dipole (OEED), which enhances specific harmonic orders. Our work helps understand the mechanism of harmonic emissions from grating targets and the distinction from the planar harmonic scheme.

  6. Computer model for harmonic ultrasound imaging.

    PubMed

    Li, Y; Zagzebski, J A

    2000-01-01

    Harmonic ultrasound imaging has received great attention from ultrasound scanner manufacturers and researchers. In this paper, we present a computer model that can generate realistic harmonic images. In this model, the incident ultrasound is modeled after the "KZK" equation, and the echo signal is modeled using linear propagation theory because the echo signal is much weaker than the incident pulse. Both time domain and frequency domain numerical solutions to the "KZK" equation were studied. Realistic harmonic images of spherical lesion phantoms were generated for scans by a circular transducer. This model can be a very useful tool for studying the harmonic buildup and dissipation processes in a nonlinear medium, and it can be used to investigate a wide variety of topics related to B-mode harmonic imaging.

  7. Computer model for harmonic ultrasound imaging.

    PubMed

    Li, Y; Zagzebski, J A

    2000-01-01

    Harmonic ultrasound imaging has received great attention from ultrasound scanner manufacturers and researchers. Here, the authors present a computer model that can generate realistic harmonic images. In this model, the incident ultrasound is modeled after the "KZK" equation, and the echo signal is modeled using linear propagation theory because the echo signal is much weaker than the incident pulse. Both time domain and frequency domain numerical solutions to the "KZK" equation were studied. Realistic harmonic images of spherical lesion phantoms were generated for scans by a circular transducer. This model can be a very useful tool for studying the harmonic buildup and dissipation processes in a nonlinear medium, and it can be used to investigate a wide variety of topics related to B-mode harmonic imaging.

  8. Nonlinear optical effects of opening a gap in graphene

    NASA Astrophysics Data System (ADS)

    Carvalho, David N.; Biancalana, Fabio; Marini, Andrea

    2018-05-01

    Graphene possesses remarkable electronic, optical, and mechanical properties that have taken the research of two-dimensional relativistic condensed matter systems to prolific levels. However, the understanding of how its nonlinear optical properties are affected by relativisticlike effects has been broadly uncharted. It has been recently shown that highly nontrivial currents can be generated in free-standing samples, notably leading to the generation of even harmonics. Since graphene monolayers are centrosymmetric media, for which such harmonic generation at normal incidence is deemed inaccessible, this light-driven phenomenon is both startling and promising. More realistically, graphene samples are often deposited on a dielectric substrate, leading to additional intricate interactions. Here, we present a treatment to study this instance by gapping the spectrum and we show this leads to the appearance of a Berry phase in the carrier dynamics. We analyze the role of such a phase in the generated nonlinear current and conclude that it suppresses odd-harmonic generation. The pump energy can be tuned to the energy gap to yield interference among odd harmonics mediated by interband transitions, allowing even harmonics to be generated. Our results and general methodology pave the way for understanding the role of gap opening in the nonlinear optics of two-dimensional lattices.

  9. Selective suppression of high-order harmonics within phase-matched spectral regions.

    PubMed

    Lerner, Gavriel; Diskin, Tzvi; Neufeld, Ofer; Kfir, Ofer; Cohen, Oren

    2017-04-01

    Phase matching in high-harmonic generation leads to enhancement of multiple harmonics. It is sometimes desired to control the spectral structure within the phase-matched spectral region. We propose a scheme for selective suppression of high-order harmonics within the phase-matched spectral region while weakly influencing the other harmonics. The method is based on addition of phase-mismatched segments within a phase-matched medium. We demonstrate the method numerically in two examples. First, we show that one phase-mismatched segment can significantly suppress harmonic orders 9, 15, and 21. Second, we show that two phase-mismatched segments can efficiently suppress circularly polarized harmonics with one helicity over the other when driven by a bi-circular field. The new method may be useful for various applications, including the generation of highly helical bright attosecond pulses.

  10. Enhanced second-harmonic-generation detection of collagen by means of optical wavefront shaping

    NASA Astrophysics Data System (ADS)

    Thompson, Jonathan V.; Throckmorton, Graham A.; Hokr, Brett H.; Yakovlev, Vladislav V.

    2016-03-01

    Second-harmonic generation (SHG) has proven to be an effective method to both image and detect structural variations in fibrillar collagen. The ability to detect these differences is especially useful in studying diseases like cancer and fibrosis.1 SHG techniques have historically been limited by their ability to penetrate and image through strongly scattering tissues. Recently, optical wavefront shaping has enabled light to be focused through highly scattering media such as biological tissue.2-4 This technology also enables us to examine the dependence of second harmonic generation on the spatial phase of the pump laser. Here, we demonstrate that wavefront shaping can be used to enhance the generation of second harmonic light from collagen fibrils even when scattering is low or non-existent.

  11. When gluons go odd: how classical gluon fields generate odd azimuthal harmonics for the two-gluon correlation function in high-energy collisions

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

    Kovchegov, Yuri V.; Skokov, Vladimir V.

    We show that, in the saturation/Color Glass Condensate framework, odd azimuthal harmonics of the two-gluon correlation function with a long-range separation in rapidity are generated by the higher-order saturation corrections in the interactions with the projectile and the target. At the very least, the odd harmonics require three scatterings in the projectile and three scatterings in the target. We derive the leading-order expression for the two-gluon production cross section which generates odd harmonics: the expression includes all-order interactions with the target and three interactions with the projectile. Here, we evaluate the obtained expression both analytically and numerically, confirming that themore » odd-harmonics contribution to the two-gluon production in the saturation framework is non-zero.« less

  12. When gluons go odd: how classical gluon fields generate odd azimuthal harmonics for the two-gluon correlation function in high-energy collisions

    DOE PAGES

    Kovchegov, Yuri V.; Skokov, Vladimir V.

    2018-04-30

    We show that, in the saturation/Color Glass Condensate framework, odd azimuthal harmonics of the two-gluon correlation function with a long-range separation in rapidity are generated by the higher-order saturation corrections in the interactions with the projectile and the target. At the very least, the odd harmonics require three scatterings in the projectile and three scatterings in the target. We derive the leading-order expression for the two-gluon production cross section which generates odd harmonics: the expression includes all-order interactions with the target and three interactions with the projectile. Here, we evaluate the obtained expression both analytically and numerically, confirming that themore » odd-harmonics contribution to the two-gluon production in the saturation framework is non-zero.« less

  13. Polarization anisotropy in fiber-optic second harmonic generation microscopy.

    PubMed

    Fu, Ling; Gu, Min

    2008-03-31

    We report the investigation and implementation of a compact second harmonic generation microscope that uses a single-mode fiber coupler and a double-clad photonic crystal fiber. Second harmonic polarization anisotropy through the fiber-optic microscope systems is quantitatively measured with KTP microcrystals, fish scale and rat tail tendon. It is demonstrated that the polarized second harmonic signals can be excited and collected through the single-mode fiber coupler to analyze the molecular orientations of structural proteins. It has been discovered that a double-clad photonic crystal fiber can preserve the linear polarization in the core, although a depolarization effect is observed in the inner cladding region. The feasibility of polarization anisotropy measurements in fiber-optic second harmonic generation microscopy will benefit the in vivo study of collagen-related diseases with a compact imaging probe.

  14. Investigation of phase matching for third-harmonic generation in silicon slow light photonic crystal waveguides using Fourier optics.

    PubMed

    Monat, Christelle; Grillet, Christian; Corcoran, Bill; Moss, David J; Eggleton, Benjamin J; White, Thomas P; Krauss, Thomas F

    2010-03-29

    Using Fourier optics, we retrieve the wavevector dependence of the third-harmonic (green) light generated in a slow light silicon photonic crystal waveguide. We show that quasi-phase matching between the third-harmonic signal and the fundamental mode is provided in this geometry by coupling to the continuum of radiation modes above the light line. This process sustains third-harmonic generation with a relatively high efficiency and a substantial bandwidth limited only by the slow light window of the fundamental mode. The results give us insights into the physics of this nonlinear process in the presence of strong absorption and dispersion at visible wavelengths where bandstructure calculations are problematic. Since the characteristics (e.g. angular pattern) of the third-harmonic light primarily depend on the fundamental mode dispersion, they could be readily engineered.

  15. Contribution of the magnetic resonance to the third harmonic generation from a fishnet metamaterial

    NASA Astrophysics Data System (ADS)

    Reinhold, J.; Shcherbakov, M. R.; Chipouline, A.; Panov, V. I.; Helgert, C.; Paul, T.; Rockstuhl, C.; Lederer, F.; Kley, E.-B.; Tünnermann, A.; Fedyanin, A. A.; Pertsch, T.

    2012-09-01

    We investigate experimentally and theoretically the third harmonic generated by a double-layer fishnet metamaterial. To unambiguously disclose most notably the influence of the magnetic resonance, the generated third harmonic was measured as a function of the angle of incidence. It is shown experimentally and numerically that when the magnetic resonance is excited by a pump beam, the angular dependence of the third harmonic signal has a local maximum at an incidence angle of θ≃20∘. This maximum is shown to be a fingerprint of the antisymmetric distribution of currents in the gold layers. An analytical model based on the nonlinear dynamics of the electrons inside the gold shows excellent agreement with experimental and numerical results. This clearly indicates the difference in the third harmonic angular pattern at electric and magnetic resonances of the metamaterial.

  16. Selection rules for harmonic generation in solids

    NASA Astrophysics Data System (ADS)

    Moiseyev, Nimrod

    2015-05-01

    High-order harmonic generation (HHG) in a bulk crystal was first observed in 2011 [S. Ghimire, A. D. DiChiara, E. Sistrunk, P. Agostini, L. F. DiMauro, and D. A. Reis, Nat. Phys. 7, 138 (2011), 10.1038/nphys1847]. Only odd-order harmonics were observed as expected on the basis of the selection rules in solids, which were derived when only the interband currents were taken into consideration. Here we study HHG in solids when the intraband currents are taken into consideration as well. We show that the dynamical selection rules are broken in solids and the possibility of generation of even-order harmonics cannot be excluded on the basis of the dynamical symmetry analysis. However, a simple analysis of the expression we obtained for the amplitude of the emitted high-order harmonics shows, without the need to carry out numerical calculations, that the even-order harmonics are suppressed due to the localization of the field-free one-electron density probability on the atoms in the solids.

  17. High-harmonic generation by quantum-dot nanorings

    NASA Astrophysics Data System (ADS)

    Bâldea, Ioan; Gupta, Ashish K.; Cederbaum, Lorenz S.; Moiseyev, Nimrod

    2004-06-01

    Exact numerical results are obtained within the extended Hubbard Hamiltonian for nanorings consisting of Ag quantum dots (QD’s) with C6v symmetry which interact with a circularly polarized light. The results show that the high-harmonic generation (HHG) spectra obtained from such artificial “molecules” are more pronounced than the HHG spectra obtained from a real molecule such as benzene. Our studies show that the HHG spectra obtained from the QD nanorings consist of two plateaus while only one plateau appears for benzene. The role of electron correlations in the generation of the high-order harmonics is studied, and it is shown that it can increase the intensity of the high-order harmonics. Mainly affected are the harmonics which are located in the second plateau. Selection rules for the produced high harmonics and a new “synergetic” selection rule for the symmetry of the states contributing to the HHG spectrum, a combined effect of spatial and charge conjugation symmetries, are discussed.

  18. Simulation prediction and experiment setup of vacuum laser acceleration at Brookhaven National Lab-Accelerator Test Facility

    NASA Astrophysics Data System (ADS)

    Shao, L.; Cline, D.; Ding, X.; Ho, Y. K.; Kong, Q.; Xu, J. J.; Pogorelsky, I.; Yakimenko, V.; Kusche, K.

    2013-02-01

    This paper presents the pre-experiment plan and prediction of the first stage of vacuum laser acceleration (VLA) collaborating by UCLA, Fudan University and ATF-BNL. This first stage experiment is a proof-of-principle to support our previously posted novel VLA theory. Simulations show that based on ATF's current experimental conditions the electron beam with initial energy of 15 MeV can get net energy gain from an intense CO2 laser beam. The difference in electron beam energy spread is observable by the ATF beam line diagnostics system. Further, this energy spread expansion effect increases along with an increase in laser intensity. The proposal has been approved by the ATF committee and the experiment will be our next project.

  19. Observations of z-dependent microbunching harmonic intensities using COTR in a SASE FEL.

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

    Lumpkin, A. H.; Biedron, S. G.; Dejus, R. J.

    The nonlinear generation of harmonics in a self-amplified spontaneous emission (SASE) free-electron laser (FEL) continues to be of interest. Complementary to such studies is the search for information on the electron beam microbunching harmonic components, which are revealed by coherent optical transition radiation (COTR) experiments. An initial z-dependent set of data has been obtained with the fundamental at 530 nm and the second harmonic at 265 nm. The latter data were collected after every other undulator in a nine-undulator string. These results are compared to estimates based on GINGER and an analytical model for nonlinear harmonic generation.

  20. Comparison of light harmonic generation in Al and Ge consisted silicate materials

    NASA Astrophysics Data System (ADS)

    Smirnov, Vitaly A.; Vostrikova, Liubov I.

    2018-04-01

    The silicate materials are perspective for different areas of laser physics and photonics. In this paper the comparison of the nonlinear conversion with the generation of the light harmonic in Al- and Ge-containing silicate materials is presented. The peculiarities of the processes of the light harmonic generation in dependence on the concentrations of the chemical components are discussed and the influences of the additional small inclusion of the elements of fifth group and the rare-earth elements are estimated.

  1. Generation of intense high-order vortex harmonics.

    PubMed

    Zhang, Xiaomei; Shen, Baifei; Shi, Yin; Wang, Xiaofeng; Zhang, Lingang; Wang, Wenpeng; Xu, Jiancai; Yi, Longqiong; Xu, Zhizhan

    2015-05-01

    This Letter presents for the first time a scheme to generate intense high-order optical vortices that carry orbital angular momentum in the extreme ultraviolet region based on relativistic harmonics from the surface of a solid target. In the three-dimensional particle-in-cell simulation, the high-order harmonics of the high-order vortex mode is generated in both reflected and transmitted light beams when a linearly polarized Laguerre-Gaussian laser pulse impinges on a solid foil. The azimuthal mode of the harmonics scales with its order. The intensity of the high-order vortex harmonics is close to the relativistic region, with the pulse duration down to attosecond scale. The obtained intense vortex beam possesses the combined properties of fine transversal structure due to the high-order mode and the fine longitudinal structure due to the short wavelength of the high-order harmonics. In addition to the application in high-resolution detection in both spatial and temporal scales, it also presents new opportunities in the intense vortex required fields, such as the inner shell ionization process and high energy twisted photons generation by Thomson scattering of such an intense vortex beam off relativistic electrons.

  2. Frequency-doubled microwave waveforms generation using a dual-polarization quadrature phase shift keying modulator driven by a single frequency radio frequency signal

    NASA Astrophysics Data System (ADS)

    Zhu, Zihang; Zhao, Shanghong; Li, Xuan; Qu, Kun; Lin, Tao

    2018-01-01

    A photonic approach to generate frequency-doubled microwave waveforms using an integrated dual-polarization quadrature phase shift keying (DP-QPSK) modulator driven by a sinusoidal radio frequency (RF) signal is proposed. By adjusting the dc bias points of the DP-QPSK modulator, the obtained second-order and six-order harmonics are in phase while the fourth-order harmonics are complementary when the orthogonal polarized outputs of the modulator are photodetected. After properly setting the modulation indices of the modulator, the amplitude of the second-order harmonic is 9 times of that of the six-order harmonic, indicating a frequency-doubled triangular waveform is generated. If a broadband 90° microwave phase shifter is attached after the photodetector (PD) to introduce a 90° phase shift, a frequency-doubled square waveform can be obtained after adjusting the amplitude of the second-order harmonic 3 times of that of the six-order harmonic. The proposal is first theoretically analyzed and then validated by simulation. Simulation results show that a 10 GHz triangular and square waveform sequences are successfully generated from a 5 GHz sinusoidal RF drive signal.

  3. Frequency doubling in poled polymers using anomalous dispersion phase-matching

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

    Kowalczyk, T.C.; Singer, K.D.; Cahill, P.A.

    1995-10-01

    The authors report on a second harmonic generation in a poled polymer waveguide using anomalous dispersion phase-matching. Blue light ({lambda} = 407 nm) was produced by phase-matching the lowest order fundamental and harmonic modes over a distance of 32 {micro}m. The experimental conversion efficiency was {eta} = 1.2 {times} 10{sup {minus}4}, in agreement with theory. Additionally, they discuss a method of enhancing the conversion efficiency for second harmonic generation using anomalous dispersion phase-matching to optimize Cerenkov second harmonic generation. The modeling shows that a combination of phase-matching techniques creates larger conversion efficiencies and reduces critical fabrication requirements of the individualmore » phase-matching techniques.« less

  4. Aberrant hypertrophy in Smad3-deficient murine chondrocytes is rescued by restoring transforming growth factor beta-activated kinase 1/activating transcription factor 2 signaling: a potential clinical implication for osteoarthritis.

    PubMed

    Li, Tian-Fang; Gao, Lin; Sheu, Tzong-Jen; Sampson, Erik R; Flick, Lisa M; Konttinen, Yrjö T; Chen, Di; Schwarz, Edward M; Zuscik, Michael J; Jonason, Jennifer H; O'Keefe, Regis J

    2010-08-01

    To investigate the biologic significance of Smad3 in the progression of osteoarthritis (OA), the crosstalk between Smad3 and activating transcription factor 2 (ATF-2) in the transforming growth factor beta (TGFbeta) signaling pathway, and the effects of ATF-2 overexpression and p38 activation in chondrocyte differentiation. Joint disease in Smad3-knockout (Smad3(-/-)) mice was examined by microfocal computed tomography and histologic analysis. Numerous in vitro methods including immunostaining, real-time polymerase chain reaction, Western blotting, an ATF-2 DNA-binding assay, and a p38 kinase activity assay were used to study the various signaling responses and protein interactions underlying the altered chondrocyte phenotype in Smad3(-/-) mice. In Smad3(-/-) mice, an end-stage OA phenotype gradually developed. TGFbeta-activated kinase 1 (TAK1)/ATF-2 signaling was disrupted in Smad3(-/-) mouse chondrocytes at the level of p38 MAP kinase (MAPK) activation, resulting in reduced ATF-2 phosphorylation and transcriptional activity. Reintroduction of Smad3 into Smad3(-/-) cells restored the normal p38 response to TGFbeta. Phosphorylated p38 formed a complex with Smad3 by binding to a portion of Smad3 containing both the MAD homology 1 and linker domains. Additionally, Smad3 inhibited the dephosphorylation of p38 by MAPK phosphatase 1 (MKP-1). Both ATF-2 overexpression and p38 activation repressed type X collagen expression in wild-type and Smad3(-/-) chondrocytes. P38 was detected in articular cartilage and perichondrium; articular and sternal chondrocytes expressed p38 isoforms alpha, beta, and gamma, but not delta. Smad3 is involved in both the onset and progression of OA. Loss of Smad3 abrogates TAK1/ATF-2 signaling, most likely by disrupting the Smad3-phosphorylated p38 complex, thereby promoting p38 dephosphorylation and inactivation by MKP-1. ATF-2 and p38 activation inhibit chondrocyte hypertrophy. Modulation of p38 isoform activity may provide a new therapeutic approach for OA.

  5. Harmonic arbitrary waveform generator

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

    Roberts, Brock Franklin

    2017-11-28

    High frequency arbitrary waveforms have applications in radar, communications, medical imaging, therapy, electronic warfare, and charged particle acceleration and control. State of the art arbitrary waveform generators are limited in the frequency they can operate by the speed of the Digital to Analog converters that directly create their arbitrary waveforms. The architecture of the Harmonic Arbitrary Waveform Generator allows the phase and amplitude of the high frequency content of waveforms to be controlled without taxing the Digital to Analog converters that control them. The Harmonic Arbitrary Waveform Generator converts a high frequency input, into a precision, adjustable, high frequency arbitrarymore » waveform.« less

  6. Ince-gauss based multiple intermodal phase-matched third-harmonic generations in a step-index silica optical fiber

    NASA Astrophysics Data System (ADS)

    Borne, Adrien; Katsura, Tomotaka; Félix, Corinne; Doppagne, Benjamin; Segonds, Patricia; Bencheikh, Kamel; Levenson, Juan Ariel; Boulanger, Benoit

    2016-01-01

    Several third-harmonic generation processes were performed in a single step-index germanium-doped silica optical fiber under intermodal phase-matching conditions. The nanosecond fundamental beam range between 1400 and 1600 nm. The transverse distributions of the energy were successfully modeled in the form of Ince-Gauss modes, pointing out some ellipticity of fiber core. From these experiments and theoretical calculations, we discuss the implementation of frequency degenerated triple photon generation that shares the same phase-matching condition as third-harmonic generation, which is its reverse process.

  7. Physiological and harmonic components in neural and muscular coherence in Parkinsonian tremor.

    PubMed

    Wang, Shouyan; Aziz, Tipu Z; Stein, John F; Bain, Peter G; Liu, Xuguang

    2006-07-01

    To differentiate physiological from harmonic components in coherence analysis of the tremor-related neural and muscular signals by comparing power, cross-power and coherence spectra. Influences of waveform, burst-width and additional noise on generating harmonic peaks in the power, cross-power and coherence spectra were studied using simulated signals. The local field potentials (LFPs) of the subthalamic nucleus (STN) and the EMGs of the contralateral forearm muscles in PD patients with rest tremor were analysed. (1) Waveform had significant effect on generating harmonics; (2) noise significantly decreased the coherence values in a frequency-dependent fashion; and (3) cross-spectrum showed high resistance to harmonics. Among six examples of paired LFP-EMG signals, significant coherence appeared at the tremor frequency only, both the tremor and double tremor frequencies and the double-tremor frequency only. In coherence analysis of neural and muscular signals, distortion in waveform generates significant harmonic peaks in the coherence spectra and the coherence values of both physiological and harmonic components are modulated by extra noise or non-tremor related activity. The physiological or harmonic nature of a coherence peak at the double tremor frequency may be differentiated when the coherence spectra are compared with the power and in particular the cross-power spectra.

  8. Frequency modulation of high-order harmonic generation in an orthogonally polarized two-color laser field.

    PubMed

    Li, Guicun; Zheng, Yinghui; Ge, Xiaochun; Zeng, Zhinan; Li, Ruxin

    2016-08-08

    We have experimentally investigated the frequency modulation of high-order harmonics in an orthogonally polarized two-color laser field consisting of a mid-infrared 1800nm fundamental pulse and its second harmonic pulse. It is demonstrated that the high harmonic spectra can be fine-tuned as we slightly change the relative delay of the two-color laser pulses. By analyzing the relative frequency shift of each harmonic at different two-color delays, the nonadiabatic spectral shift induced by the rapid variation of the intensity-dependent intrinsic dipole phase can be distinguished from the blueshift induced by the change of the refractive index during self-phase modulation (SPM). Our comprehensive analysis shows that the frequency modulation pattern is a reflection of the average emission time of high-order harmonic generation (HHG), thus offering a simple method to fine-tune the spectra of the harmonics on a sub-cycle time scale.

  9. Nickel chloride (NiCl2) in hepatic toxicity: apoptosis, G2/M cell cycle arrest and inflammatory response

    PubMed Central

    Guo, Hongrui; Cui, Hengmin; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Zhao, Ling; Chen, Kejie; Deng, Jie

    2016-01-01

    Up to now, the precise mechanism of Ni toxicology is still indistinct. Our aim was to test the apoptosis, cell cycle arrest and inflammatory response mechanism induced by NiCl2 in the liver of broiler chickens. NiCl2 significantly increased hepatic apoptosis. NiCl2 activated mitochondria-mediated apoptotic pathway by decreasing Bcl-2, Bcl-xL, Mcl-1, and increasing Bax, Bak, caspase-3, caspase-9 and PARP mRNA expression. In the Fas-mediated apoptotic pathway, mRNA expression levels of Fas, FasL, caspase-8 were increased. Also, NiCl2 induced ER stress apoptotic pathway by increasing GRP78 and GRP94 mRNA expressions. The ER stress was activated through PERK, IRE1 and ATF6 pathways, which were characterized by increasing eIF2α, ATF4, IRE1, XBP1 and ATF6 mRNA expressions. And, NiCl2 arrested G2/M phase cell cycle by increasing p53, p21 and decreasing cdc2, cyclin B mRNA expressions. Simultaneously, NiCl2 increased TNF-α, IL-1β, IL-6, IL-8 mRNA expressions through NF-κB activation. In conclusion, NiCl2 induces apoptosis through mitochondria, Fas and ER stress-mediated apoptotic pathways and causes cell cycle G2/M phase arrest via p53-dependent pathway and generates inflammatory response by activating NF-κB pathway. PMID:27824316

  10. Surface plasma wave assisted second harmonic generation of laser over a metal film

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

    Chauhan, Santosh; Parashar, J., E-mail: j.p.parashar@gmail.com

    2015-01-15

    Second harmonic generation of laser mode converted surface plasma wave (SPW) over a corrugated metal film is studied. The laser, impinged on the metal film, under attenuated total reflection configuration, excites SPW over the metal–vacuum interface. The excited SPW extends over a much wider surface area than the laser spot cross-section. It exerts a second harmonic ponderomotive force on metal electrons, imparting them velocity that beats with the surface ripple to produce a nonlinear current, driving resonant second harmonic surface plasma wave.

  11. Measurement of optical-beat frequency in a photoconductive terahertz-wave generator using microwave higher harmonics.

    PubMed

    Murasawa, Kengo; Sato, Koki; Hidaka, Takehiko

    2011-05-01

    A new method for measuring optical-beat frequencies in the terahertz (THz) region using microwave higher harmonics is presented. A microwave signal was applied to the antenna gap of a photoconductive (PC) device emitting a continuous electromagnetic wave at about 1 THz by the photomixing technique. The microwave higher harmonics with THz frequencies are generated in the PC device owing to the nonlinearity of the biased photoconductance, which is briefly described in this article. Thirteen nearly periodic peaks in the photocurrent were observed when the microwave was swept from 16 to 20 GHz at a power of -48 dBm. The nearly periodic peaks are generated by the homodyne detection of the optical beat with the microwave higher harmonics when the frequency of the harmonics coincides with the optical-beat frequency. Each peak frequency and its peak width were determined by fitting a Gaussian function, and the order of microwave harmonics was determined using a coarse (i.e., lower resolution) measurement of the optical-beat frequency. By applying the Kalman algorithm to the peak frequencies of the higher harmonics and their standard deviations, the optical-beat frequency near 1 THz was estimated to be 1029.81 GHz with the standard deviation of 0.82 GHz. The proposed method is applicable to a conventional THz-wave generator with a photomixer.

  12. Intensity distributions and isolated attosecond pulse generation from molecular high-order harmonic generation in H2+ driven by nonhomogeneous field

    NASA Astrophysics Data System (ADS)

    Feng, Liqiang; Chu, Tianshu

    2017-10-01

    Intensity distributions and isolated attosecond pulse generation from the molecular high-order harmonic generation (MHHG) in H2+ and T2+ driven by the nonhomogeneous field have been theoretically investigated. (i) Generally speaking, the intensities of the harmonics driven by the homogeneous field can be enhanced as the initial vibrational state increases and much more intense harmonics can be obtained from the light nuclei. However, with the introduction of the nonhomogeneous effect, the enhanced ratios of the harmonic yields are decreased as the initial vibrational state increases. Moreover, the intensities of the harmonics from H2+ and T2+ are very sensitive to the nonhomogeneous effect of the laser field. (ii) The contributions of the MHHG from the two-H nuclei present the periodic variation as a function of the laser phase for the case of the symmetric nonhomogeneous field. However, for the case of the positive and the negative asymmetric nonhomogeneous fields, the left-H and the right-H play the dominating role in the MHHG, respectively. Moreover, as the angle between the laser polarization direction and the molecular axis increases, the intensity differences of the harmonics from the two-H nuclei are increased. (iii) By properly adding a half-cycle pulse into the positive asymmetric nonhomogeneous field, a supercontinuum with the bandwidth of 279 eV and an isolated 25 as pulse can be obtained.

  13. Early implementation of SiC cladding fuel performance models in BISON

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

    Powers, Jeffrey J.

    2015-09-18

    SiC-based ceramic matrix composites (CMCs) [5–8] are being developed and evaluated internationally as potential LWR cladding options. These development activities include interests within both the DOE-NE LWR Sustainability (LWRS) Program and the DOE-NE Advanced Fuels Campaign. The LWRS Program considers SiC ceramic matrix composites (CMCs) as offering potentially revolutionary gains as a cladding material, with possible benefits including more efficient normal operating conditions and higher safety margins under accident conditions [9]. Within the Advanced Fuels Campaign, SiC-based composites are a candidate ATF cladding material that could achieve several goals, such as reducing the rates of heat and hydrogen generation duemore » to lower cladding oxidation rates in HT steam [10]. This work focuses on the application of SiC cladding as an ATF cladding material in PWRs, but these work efforts also support the general development and assessment of SiC as an LWR cladding material in a much broader sense.« less

  14. Atomic-like high-harmonic generation from two-dimensional materials.

    PubMed

    Tancogne-Dejean, Nicolas; Rubio, Angel

    2018-02-01

    The generation of high-order harmonics from atomic and molecular gases enables the production of high-energy photons and ultrashort isolated pulses. Obtaining efficiently similar photon energy from solid-state systems could lead, for instance, to more compact extreme ultraviolet and soft x-ray sources. We demonstrate from ab initio simulations that it is possible to generate high-order harmonics from free-standing monolayer materials, with an energy cutoff similar to that of atomic and molecular gases. In the limit in which electrons are driven by the pump laser perpendicularly to the monolayer, they behave qualitatively the same as the electrons responsible for high-harmonic generation (HHG) in atoms, where their trajectories are described by the widely used semiclassical model, and exhibit real-space trajectories similar to those of the atomic case. Despite the similarities, the first and last steps of the well-established three-step model for atomic HHG are remarkably different in the two-dimensional materials from gases. Moreover, we show that the electron-electron interaction plays an important role in harmonic generation from monolayer materials because of strong local-field effects, which modify how the material is ionized. The recombination of the accelerated electron wave packet is also found to be modified because of the infinite extension of the material in the monolayer plane, thus leading to a more favorable wavelength scaling of the harmonic yield than in atomic HHG. Our results establish a novel and efficient way of generating high-order harmonics based on a solid-state device, with an energy cutoff and a more favorable wavelength scaling of the harmonic yield similar to those of atomic and molecular gases. Two-dimensional materials offer a unique platform where both bulk and atomic HHG can be investigated, depending on the angle of incidence. Devices based on two-dimensional materials can extend the limit of existing sources.

  15. Spherical harmonic analysis of a model-generated climatology

    NASA Technical Reports Server (NTRS)

    Christidis, Z. D.; Spar, J.

    1981-01-01

    Monthly mean fields of 850 mb temperature (T850), 500 mb geopotential height (G500) and sea level pressure (SLP) were generated in the course of a five-year climate simulation run with a global general circulation model. Both the model-generated climatology and an observed climatology were subjected to spherical harmonic analysis, with separate analyses of the globe and the Northern Hemisphere. Comparison of the dominant harmonics of the two climatologies indicates that more than 95% of the area-weighted spatial variance of G500 and more than 90% of that of T850 are explained by fewer than three components, and that the model adequately simulates these large-scale characteristics. On the other hand, as many as 25 harmonics are needed to explain 95% of the observed variance of SLP, and the model simulation of this field is much less satisfactory. The model climatology is also evaluated in terms of the annual cycles of the dominant harmonics.

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

    Heslar, John; Chu, Shih-I.

    Recently, the study of near- and below- threshold regime harmonics as a potential source of intense coherent vacuum-ultraviolet radiation has received considerable attention. However, the dynamical origin of these lower harmonics, particularly for the molecular systems, is less understood and largely unexplored. Here we perform the first fully ab initio and high precision 3D quantum study of the below- and near-threshold harmonic generation of H 2 + molecules in an intense 800-nm near-infrared (NIR) laser field. Furthermore, combining with a synchrosqueezing transform of the quantum time-frequency spectrum and an extended semiclassical analysis, we explore in-depth the roles of various quantummore » trajectories, including short- and long trajectories, multiphoton trajectories, resonance-enhanced trajectories, and multiple rescattering trajectories of the below- and near- threshold harmonic generation processes. Our results shed new light on the dynamical origin of the below- and near-threshold harmonic generation and various quantum trajectories for diatomic molecules for the first time.« less

  17. Extending the high-order-harmonic spectrum using surface plasmon polaritons

    NASA Astrophysics Data System (ADS)

    Ebadian, H.; Mohebbi, M.

    2017-08-01

    Nanoparticle assisted high-order-harmonic generation by low-intensity ultrashort laser pulses in hydrogen atomic gas is studied. This work is based on surface plasmon-polariton coupling in metal-insulator-metal structures. The necessary laser intensity is provided by enhancement of the incident laser power in the vicinity of bowtie nanoparticles installed on an insulator-metal structure. The inhomogeneous electric field distribution in the Au nanobowtie gap region is investigated. Simulations show that the insulator layer installed on the Au metal film that supports the plasmon-polariton interactions has a dramatic effect on the field enhancement factor. High-order-harmonic generation cutoffs for different arrangements are calculated and results show that the metal-insulator-metal structure is an excellent device for high-order-harmonic generation purposes. Also, the harmonic cutoff order is extended to more than 170, which is a considerable value and will be an efficient source for extreme ultraviolet radiation.

  18. Simultaneously phase-matched second- and third-harmonic generation from 1.55 microm radiation in annealed proton-exchanged periodically poled lithium niobate waveguides.

    PubMed

    Marangoni, M; Lobino, M; Ramponi, R

    2006-09-15

    Third-harmonic generation (THG) in the cw regime from C-band radiation was achieved in annealed proton-exchanged periodically poled lithium niobate (PPLN) waveguides. By suitable design of fabrication parameters and operating conditions, quasi-phase-matching (QPM) is obtained simultaneously for the second-harmonic generation process (omega-->2omega, first-order QPM) and for the sum-frequency-generation process (omega+2omega-->3omega, third-order QPM), which provides the third harmonic of the pump field. The high overlap between the field profiles of the interacting modes--TM00 at omega and TM10 at 2omega and 3omega--results in what is believed to be the highest ever reported normalized conversion efficiency for THG from telecommunication wavelengths, equal to 0.72%W(-2) cm(-4).

  19. Low-frequency approximation for high-order harmonic generation by a bicircular laser field

    NASA Astrophysics Data System (ADS)

    Milošević, D. B.

    2018-01-01

    We present low-frequency approximation (LFA) for high-order harmonic generation (HHG) process. LFA represents the lowest-order term of an expansion of the final-state interaction matrix element in powers of the laser-field frequency ω . In this approximation the plane-wave recombination matrix element which appears in the strong-field approximation is replaced by the exact laser-free recombination matrix element calculated for the laser-field dressed electron momenta. First, we have shown that the HHG spectra obtained using the LFA agree with those obtained solving the time-dependent Schrödinger equation. Next, we have applied this LFA to calculate the HHG rate for inert gases exposed to a bicircular field. The bicircular field, which consists of two coplanar counter-rotating fields having different frequencies (usually ω and 2 ω ), is presently an important subject of scientific research since it enables efficient generation of circularly polarized high-order harmonics (coherent soft x rays). Analyzing the photorecombination matrix element we have found that the HHG rate can efficiently be calculated using the angular momentum basis with the states oriented in the direction of the bicircular field components. Our numerical results show that the HHG rate for atoms having p ground state, for higher high-order harmonic energies, is larger for circularly polarized harmonics having the helicity -1 . For lower energies the harmonics having helicity +1 prevails. The transition between these two harmonic energy regions can appear near the Cooper minimum, which, in the case of Ar atoms, makes the selection of high-order harmonics having the same helicity much easier. This is important for applications (for example, for generation of attosecond pulse trains of circularly polarized harmonics).

  20. 75 FR 54183 - Agency Information Collection Activities: Proposed Collection; Comments Requested

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ... other technological collection techniques or other forms of information technology, e.g., permitting... teach ATF courses. The information is necessary in order for ATF training programs to verify and defend...

  1. Letter Report Documenting Progress of Second Generation ATF FeCrAl Alloy Fabrication

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

    Yamamoto, Y.; Yang, Y.; Field, K. G.

    2014-06-10

    Development of the 2nd generation ATF FeCrAl alloy has been initiated, and a candidate alloy was selected for trial tube fabrication through hot-extrusion and gun-drilling processes. Four alloys based on Fe-13Cr-4.5Al-0.15Y in weight percent were newly cast with minor alloying additions of Mo, Si, Nb, and C to promote solid-solution and second-phase precipitate strengthening. The alloy compositions were selected with guidance from computational thermodynamic tools. The lab-scale heats of ~ 600g were arc-melted and drop-cast, homogenized, hot-forged and -rolled, and then annealed producing plate shape samples. An alloy with Mo and Nb additions (C35MN) processed at 800°C exhibits very finemore » sub-grain structure with the sub-grain size of 1-3μm which exhibited more than 25% better yield and tensile strengths together with decent ductility compared to the other FeCrAl alloys at room temperature. It was found that the Nb addition was key to improving thermal stability of the fine sub-grain structure. Optimally, grains of less than 30 microns are desired, with grains up to and order of magnitude in desired produced through Nb addition. Scale-up effort of the C35MN alloy was made in collaboration with a commercial cast company who has a capability of vacuum induction melting. A 39lb columnar ingot with ~81mm diameter and ~305mm height (with hot-top) was commercially cast, homogenized, hot-extruded, and annealed providing 10mm-diameter bar-shape samples with the fine sub-grain structure. This commercial heat proved consistent with materials produced at ORNL at the lab-scale. Tubes and end caps were machined from the bar sample and provided to another work package for the ATF-1 irradiation campaign in the milestone M3FT-14OR0202251.« less

  2. The involvement of ATF4 and S-opsin in retinal photoreceptor cell damage induced by blue LED light.

    PubMed

    Ooe, Emi; Tsuruma, Kazuhiro; Kuse, Yoshiki; Kobayashi, Saori; Shimazawa, Masamitsu; Hara, Hideaki

    2017-01-01

    Blue light is a high-energy emitting light with a short wavelength in the visible light spectrum. Blue light induces photoreceptor apoptosis and causes age-related macular degeneration or retinitis pigmentosa. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress induced by blue light-emitting diode (LED) light exposure in murine photoreceptor cells. The murine photoreceptor cell line was incubated and exposed to blue LED light (464 nm blue LED light, 450 lx, 3 to 24 h). The expression of the factors involved in the unfolded protein response pathway was examined using quantitative real-time reverse transcription (RT)-PCR and immunoblot analysis. The aggregation of short-wavelength opsin (S-opsin) in the murine photoreceptor cells was observed with immunostaining. The effect of S-opsin knockdown on ATF4 expression in the murine photoreceptor cell line was also investigated. Exposure to blue LED light increased the bip , atf4 , and grp94 mRNA levels, induced the expression of ATF4 protein, and increased the levels of ubiquitinated proteins. Exposure to blue LED light in combination with ER stress inducers (tunicamycin and dithiothreitol) induced the aggregation of S-opsin. S-opsin mRNA knockdown prevented the induction of ATF4 expression in response to exposure to blue LED light. These findings indicate that the aggregation of S-opsin induced by exposure to blue LED light causes ER stress, and ATF4 activation in particular.

  3. Current-driven second-harmonic domain wall resonance in ferromagnetic metal/nonmagnetic metal bilayers: A field-free method for spin Hall angle measurements

    NASA Astrophysics Data System (ADS)

    Hajiali, M. R.; Hamdi, M.; Roozmeh, S. E.; Mohseni, S. M.

    2017-10-01

    We study the ac current-driven domain wall motion in bilayer ferromagnetic metal (FM)/nonmagnetic metal (NM) nanowires. The solution of the modified Landau-Lifshitz-Gilbert equation including all the spin transfer torques is used to describe motion of the domain wall in the presence of the spin Hall effect. We show that the domain wall center has a second-harmonic frequency response in addition to the known first-harmonic excitation. In contrast to the experimentally observed second-harmonic response in harmonic Hall measurements of spin-orbit torque in magnetic thin films, this second-harmonic response directly originates from spin-orbit torque driven domain wall dynamics. Based on the spin current generated by domain wall dynamics, the longitudinal spin motive force generated voltage across the length of the nanowire is determined. The second-harmonic response introduces additionally a practical field-free and all-electrical method to probe the effective spin Hall angle for FM/NM bilayer structures that could be applied in experiments. Our results also demonstrate the capability of utilizing FM/NM bilayer structures in domain wall based spin-torque signal generators and resonators.

  4. Optimization of multi-color laser waveform for high-order harmonic generation

    NASA Astrophysics Data System (ADS)

    Jin, Cheng; Lin, C. D.

    2016-09-01

    With the development of laser technologies, multi-color light-field synthesis with complete amplitude and phase control would make it possible to generate arbitrary optical waveforms. A practical optimization algorithm is needed to generate such a waveform in order to control strong-field processes. We review some recent theoretical works of the optimization of amplitudes and phases of multi-color lasers to modify the single-atom high-order harmonic generation based on genetic algorithm. By choosing different fitness criteria, we demonstrate that: (i) harmonic yields can be enhanced by 10 to 100 times, (ii) harmonic cutoff energy can be substantially extended, (iii) specific harmonic orders can be selectively enhanced, and (iv) single attosecond pulses can be efficiently generated. The possibility of optimizing macroscopic conditions for the improved phase matching and low divergence of high harmonics is also discussed. The waveform control and optimization are expected to be new drivers for the next wave of breakthrough in the strong-field physics in the coming years. Project supported by the Fundamental Research Funds for the Central Universities of China (Grant No. 30916011207), Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U. S. Department of Energy (Grant No. DE-FG02-86ER13491), and Air Force Office of Scientific Research, USA (Grant No. FA9550-14-1-0255).

  5. Second harmonic generation by self-focusing of intense hollow Gaussian laser beam in collisionless plasma

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

    Purohit, Gunjan, E-mail: gunjan75@gmail.com; Rawat, Priyanka; Gauniyal, Rakhi

    2016-01-15

    The effect of self focused hollow Gaussian laser beam (HGLB) (carrying null intensity in center) on the excitation of electron plasma wave (EPW) and second harmonic generation (SHG) has been investigated in collisionless plasma, where relativistic-ponderomotive and only relativistic nonlinearities are operative. The relativistic change of electron mass and the modification of the background electron density due to ponderomotive nonlinearity lead to self-focusing of HGLB in plasma. Paraxial ray theory has been used to derive coupled equations for the self focusing of HGLB in plasma, generation of EPW, and second harmonic. These coupled equations are solved analytically and numerically tomore » study the laser intensity in the plasma, electric field associated with the excited EPW, and the power of SHG. Second harmonic emission is generated due to nonlinear coupling between incident HGLB and EPW satisfying the proper phase matching conditions. The results show that the effect of including the ponderomotive nonlinearity is significant on the generation of EPW and second harmonic. The electric field associated with EPW and the power of SHG are found to be highly sensitive to the order of the hollow Gaussian beam.« less

  6. Tocotrienol-Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence-Associated Oxidative Stress in Human Myoblasts

    PubMed Central

    Wan Ngah, Wan Zurinah; Abdul Karim, Norwahidah

    2017-01-01

    During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF) modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants (α-tocopherol (ATF) and N-acetyl-cysteine (NAC)). Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS) generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPX1) was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts. PMID:28243354

  7. Brookhaven National Laboratory's Accelerator Test Facility: research highlights and plans

    NASA Astrophysics Data System (ADS)

    Pogorelsky, I. V.; Ben-Zvi, I.

    2014-08-01

    The Accelerator Test Facility (ATF) at Brookhaven National Laboratory has served as a user facility for accelerator science for over a quarter of a century. In fulfilling this mission, the ATF offers the unique combination of a high-brightness 80 MeV electron beam that is synchronized to a 1 TW picosecond CO2 laser. We unveil herein our plan to considerably expand the ATF's floor space with an upgrade of the electron beam's energy to 300 MeV and the CO2 laser's peak power to 100 TW. This upgrade will propel the ATF even further to the forefront of research on advanced accelerators and radiation sources, supporting the most innovative ideas in this field. We discuss emerging opportunities for scientific breakthroughs, including the following: plasma wakefield acceleration studies in research directions already active at the ATF; laser wakefield acceleration (LWFA), where the longer laser wavelengths are expected to engender a proportional increase in the beam's charge while our linac will assure, for the first time, the opportunity to undertake detailed studies of seeding and staging of the LWFA; proton acceleration to the 100-200 MeV level, which is essential for medical applications; and others.

  8. ATF6α regulates morphological changes associated with senescence in human fibroblasts

    PubMed Central

    Martin, Nathalie; Saas, Laure; Cormenier, Johanna; Malaquin, Nicolas; Huot, Ludovic; Slomianny, Christian; Bouali, Fatima; Vercamer, Chantal; Hot, David; Pourtier, Albin; Chevet, Eric; Abbadie, Corinne; Pluquet, Olivier

    2016-01-01

    Cellular senescence is known as an anti-tumor barrier and is characterized by a number of determinants including cell cycle arrest, senescence associated β-galactosidase activity and secretion of pro-inflammatory mediators. Senescent cells are also subjected to enlargement, cytoskeleton-mediated shape changes and organelle alterations. However, the underlying molecular mechanisms responsible for these last changes remain still uncharacterized. Herein, we have identified the Unfolded Protein Response (UPR) as a player controlling some morphological aspects of the senescent phenotype. We show that senescent fibroblasts exhibit ER expansion and mild UPR activation, but conserve an ER stress adaptive capacity similar to that of exponentially growing cells. By genetically invalidating the three UPR sensors in senescent fibroblasts, we demonstrated that ATF6α signaling dictates senescence-associated cell shape modifications. We also show that ER expansion and increased secretion of the pro-inflammatory mediator IL6 were partly reversed by silencing ATF6α in senescent cells. Moreover, ATF6α drives the increase of senescence associated-β-galactosidase activity. Collectively, these findings unveil a novel and central role for ATF6α in the establishment of morphological features of senescence in normal human primary fibroblasts. PMID:27563820

  9. ATF6α regulates morphological changes associated with senescence in human fibroblasts.

    PubMed

    Druelle, Clémentine; Drullion, Claire; Deslé, Julie; Martin, Nathalie; Saas, Laure; Cormenier, Johanna; Malaquin, Nicolas; Huot, Ludovic; Slomianny, Christian; Bouali, Fatima; Vercamer, Chantal; Hot, David; Pourtier, Albin; Chevet, Eric; Abbadie, Corinne; Pluquet, Olivier

    2016-10-18

    Cellular senescence is known as an anti-tumor barrier and is characterized by a number of determinants including cell cycle arrest, senescence associated β-galactosidase activity and secretion of pro-inflammatory mediators. Senescent cells are also subjected to enlargement, cytoskeleton-mediated shape changes and organelle alterations. However, the underlying molecular mechanisms responsible for these last changes remain still uncharacterized. Herein, we have identified the Unfolded Protein Response (UPR) as a player controlling some morphological aspects of the senescent phenotype. We show that senescent fibroblasts exhibit ER expansion and mild UPR activation, but conserve an ER stress adaptive capacity similar to that of exponentially growing cells. By genetically invalidating the three UPR sensors in senescent fibroblasts, we demonstrated that ATF6α signaling dictates senescence-associated cell shape modifications. We also show that ER expansion and increased secretion of the pro-inflammatory mediator IL6 were partly reversed by silencing ATF6α in senescent cells. Moreover, ATF6α drives the increase of senescence associated-β-galactosidase activity. Collectively, these findings unveil a novel and central role for ATF6α in the establishment of morphological features of senescence in normal human primary fibroblasts.

  10. 4E-BP is a target of the GCN2–ATF4 pathway during Drosophila development and aging

    PubMed Central

    Park, Jung-Eun; Zeng, Xiaomei

    2017-01-01

    Reduced amino acid availability attenuates mRNA translation in cells and helps to extend lifespan in model organisms. The amino acid deprivation–activated kinase GCN2 mediates this response in part by phosphorylating eIF2α. In addition, the cap-dependent translational inhibitor 4E-BP is transcriptionally induced to extend lifespan in Drosophila melanogaster, but through an unclear mechanism. Here, we show that GCN2 and its downstream transcription factor, ATF4, mediate 4E-BP induction, and GCN2 is required for lifespan extension in response to dietary restriction of amino acids. The 4E-BP intron contains ATF4-binding sites that not only respond to stress but also show inherent ATF4 activity during normal development. Analysis of the newly synthesized proteome through metabolic labeling combined with click chemistry shows that certain stress-responsive proteins are resistant to inhibition by 4E-BP, and gcn2 mutant flies have reduced levels of stress-responsive protein synthesis. These results indicate that GCN2 and ATF4 are important regulators of 4E-BP transcription during normal development and aging. PMID:27979906

  11. Sensitivity of echo enabled harmonic generation to sinusoidal electron beam energy structure

    DOE PAGES

    Hemsing, E.; Garcia, B.; Huang, Z.; ...

    2017-06-19

    Here, we analytically examine the bunching factor spectrum of a relativistic electron beam with sinusoidal energy structure that then undergoes an echo-enabled harmonic generation (EEHG) transformation to produce high harmonics. The performance is found to be described primarily by a simple scaling parameter. The dependence of the bunching amplitude on fluctuations of critical parameters is derived analytically, and compared with simulations. Where applicable, EEHG is also compared with high gain harmonic generation (HGHG) and we find that EEHG is generally less sensitive to several types of energy structure. In the presence of intermediate frequency modulations like those produced by themore » microbunching instability, EEHG has a substantially narrower intrinsic bunching pedestal.« less

  12. 27 CFR 21.33 - Formula No. 2-B.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... crude drugs. 342.Processing glandular products, vitamins, hormones, and yeasts. 343.Processing... the appropriate TTB officer. [T.D. ATF-133, 48 FR 24673, June 2, 1983, as amended by T.D. ATF-442, 66...

  13. Effects of electromagnetic fields on the nonlinear optical properties of asymmetric double quantum well under intense laser field

    NASA Astrophysics Data System (ADS)

    Yesilgul, U.; Sari, H.; Ungan, F.; Martínez-Orozco, J. C.; Restrepo, R. L.; Mora-Ramos, M. E.; Duque, C. A.; Sökmen, I.

    2017-03-01

    In this study, the effects of electric and magnetic fields on the optical rectification and second and third harmonic generation in asymmetric double quantum well under the intense non-resonant laser field is theoretically investigated. We calculate the optical rectification and second and third harmonic generation within the compact density-matrix approach. The theoretical findings show that the influence of electric, magnetic, and intense laser fields leads to significant changes in the coefficients of nonlinear optical rectification, second and third harmonic generation.

  14. Transmit beamforming for optimal second-harmonic generation.

    PubMed

    Hoilund-Kaupang, Halvard; Masoy, Svein-Erik

    2011-08-01

    A simulation study of transmit ultrasound beams from several transducer configurations is conducted to compare second-harmonic imaging at 3.5 MHz and 11 MHz. Second- harmonic generation and the ability to suppress near field echoes are compared. Each transducer configuration is defined by a chosen f-number and focal depth, and the transmit pressure is estimated to not exceed a mechanical index of 1.2. The medium resembles homogeneous muscle tissue with nonlinear elasticity and power-law attenuation. To improve computational efficiency, the KZK equation is utilized, and all transducers are circular-symmetric. Previous literature shows that second-harmonic generation is proportional to the square of the transmit pressure, and that transducer configurations with different transmit frequencies, but equal aperture and focal depth in terms of wavelengths, generate identical second-harmonic fields in terms of shape. Results verify this for a medium with attenuation f1. For attenuation f1.1, deviations are found, and the high frequency subsequently performs worse than the low frequency. The results suggest that high frequencies are less able to suppress near-field echoes in the presence of a heterogeneous body wall than low frequencies.

  15. Multilevel perspective on high-order harmonic generation in solids

    NASA Astrophysics Data System (ADS)

    Wu, Mengxi; Browne, Dana A.; Schafer, Kenneth J.; Gaarde, Mette B.

    2016-12-01

    We investigate high-order harmonic generation in a solid, modeled as a multilevel system dressed by a strong infrared laser field. We show that the cutoff energies and the relative strengths of the multiple plateaus that emerge in the harmonic spectrum can be understood both qualitatively and quantitatively by considering a combination of adiabatic and diabatic processes driven by the strong field. Such a model was recently used to interpret the multiple plateaus exhibited in harmonic spectra generated by solid argon and krypton [G. Ndabashimiye et al., Nature 534, 520 (2016), 10.1038/nature17660]. We also show that when the multilevel system originates from the Bloch state at the Γ point of the band structure, the laser-dressed states are equivalent to the Houston states [J. B. Krieger and G. J. Iafrate, Phys. Rev. B 33, 5494 (1986), 10.1103/PhysRevB.33.5494] and will therefore map out the band structure away from the Γ point as the laser field increases. This leads to a semiclassical three-step picture in momentum space that describes the high-order harmonic generation process in a solid.

  16. Bright high-repetition-rate source of narrowband extreme-ultraviolet harmonics beyond 22 eV

    PubMed Central

    Wang, He; Xu, Yiming; Ulonska, Stefan; Robinson, Joseph S.; Ranitovic, Predrag; Kaindl, Robert A.

    2015-01-01

    Novel table-top sources of extreme-ultraviolet light based on high-harmonic generation yield unique insight into the fundamental properties of molecules, nanomaterials or correlated solids, and enable advanced applications in imaging or metrology. Extending high-harmonic generation to high repetition rates portends great experimental benefits, yet efficient extreme-ultraviolet conversion of correspondingly weak driving pulses is challenging. Here, we demonstrate a highly-efficient source of femtosecond extreme-ultraviolet pulses at 50-kHz repetition rate, utilizing the ultraviolet second-harmonic focused tightly into Kr gas. In this cascaded scheme, a photon flux beyond ≈3 × 1013 s−1 is generated at 22.3 eV, with 5 × 10−5 conversion efficiency that surpasses similar harmonics directly driven by the fundamental by two orders-of-magnitude. The enhancement arises from both wavelength scaling of the atomic dipole and improved spatio-temporal phase matching, confirmed by simulations. Spectral isolation of a single 72-meV-wide harmonic renders this bright, 50-kHz extreme-ultraviolet source a powerful tool for ultrafast photoemission, nanoscale imaging and other applications. PMID:26067922

  17. Echo-Enabled X-Ray Vortex Generation

    NASA Astrophysics Data System (ADS)

    Hemsing, E.; Marinelli, A.

    2012-11-01

    A technique to generate high-brightness electromagnetic vortices with tunable topological charge at extreme ultraviolet and x-ray wavelengths is described. Based on a modified version of echo-enabled harmonic generation for free-electron lasers, the technique uses two lasers and two chicanes to produce high-harmonic microbunching of a relativistic electron beam with a corkscrew distribution that matches the instantaneous helical phase structure of the x-ray vortex. The strongly correlated electron distribution emerges from an efficient three-dimensional recoherence effect in the echo-enabled harmonic generation transport line and can emit fully coherent vortices in a downstream radiator for access to new research in x-ray science.

  18. Waveforms for optimal sub-keV high-order harmonics with synthesized two- or three-colour laser fields.

    PubMed

    Jin, Cheng; Wang, Guoli; Wei, Hui; Le, Anh-Thu; Lin, C D

    2014-05-30

    High-order harmonics extending to the X-ray region generated in a gas medium by intense lasers offer the potential for providing tabletop broadband light sources but so far are limited by their low conversion efficiency. Here we show that harmonics can be enhanced by one to two orders of magnitude without an increase in the total laser power if the laser's waveform is optimized by synthesizing two- or three-colour fields. The harmonics thus generated are also favourably phase-matched so that radiation is efficiently built up in the gas medium. Our results, combined with the emerging intense high-repetition MHz lasers, promise to increase harmonic yields by several orders to make harmonics feasible in the near future as general bright tabletop light sources, including intense attosecond pulses.

  19. Raman parametric excitation effect upon the third harmonic generation by a metallic nanoparticle lattice

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

    Sepehri Javan, N., E-mail: sepehri-javan@uma.ac.ir

    2015-08-21

    This work is a theoretical study on third harmonic generation in the nonlinear propagation of an intense laser pulse through a periodic three-dimensional lattice of nanoparticles. Using a perturbative method, the nonlinear equations that describe the laser–nanoparticle interaction in the weakly relativistic regime are derived. Additionally, the nonlinear dispersion relation and the amplitude of the third harmonic are obtained. Finally, the effects of the nanoparticle radius and separation length, the distribution of the nanoparticle electron density, and the laser frequency upon the third harmonic efficiency are investigated. In addition to the expected resonance that occurs when the third harmonic resonatesmore » with the plasmon wave, another resonance appears when the nonlinear interaction of the fundamental mode with the third harmonic excites a longitudinal collective plasmon wave via the parametric Raman mechanism.« less

  20. Calibration of a high harmonic spectrometer by laser induced plasma emission.

    PubMed

    Farrell, J P; McFarland, B K; Bucksbaum, P H; Gühr, M

    2009-08-17

    We present a method that allows for a convenient switching between high harmonic generation (HHG) and accurate calibration of the vacuum ultraviolet (VUV) spectrometer used to analyze the harmonic spectrum. The accurate calibration of HHG spectra is becoming increasingly important for the determination of electronic structures. The wavelength of the laser harmonics themselves depend on the details of the harmonic geometry and phase matching, making them unsuitable for calibration purposes. In our calibration mode, the target resides directly at the focus of the laser, thereby enhancing plasma emission and suppressing harmonic generation. In HHG mode, the source medium resides in front or after the focus, showing enhanced HHG and no plasma emission lines. We analyze the plasma emission and use it for a direct calibration of our HHG spectra. (c) 2009 Optical Society of America

  1. Quantum Path Control of Harmonic Emission and Isolated Attosecond Pulse Generation by Using the Asymmetric Inhomogeneous Mid-Infrared Field

    NASA Astrophysics Data System (ADS)

    Feng, L. Q.; Li, W. L.; Castle, R. S.

    2018-03-01

    High-order harmonic generation (HHG) from the He atom driven by the asymmetric inhomogeneous mid-infrared field, produced by a metallic nanostructure, has been investigated. It is found that due to the asymmetric enhancement of the laser intensity in space, not only the harmonic cutoff can be extended, but also the single harmonic emission event with the single short quantum path contribution can be obtained. Further, by properly adding a terahertz (THz) controlling pulse, the harmonic cutoff can be further extended, showing a 1208 eV super-bandwidth with the intensity enhancement of two orders of magnitude. Finally, by properly superposing the harmonics, a series of the isolated 33 as pulses with the photon energies from 123 eV (10 nm) to 1256 eV (1 nm) can be obtained.

  2. Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease.

    PubMed

    Sun, Xiaotian; Aimé, Pascaline; Dai, David; Ramalingam, Nagendran; Crary, John F; Burke, Robert E; Greene, Lloyd A; Levy, Oren A

    2018-05-01

    Reduced function of parkin appears to be a central pathogenic event in Parkinson disease (PD). Increasing parkin levels enhances survival in models of PD-related neuronal death and is a promising therapeutic objective. Previously, we demonstrated that the transcription factor ATF4 promotes survival in response to PD-mimetic stressors by maintaining parkin levels. ATF4 translation is up-regulated by phosphorylation of the translation initiation factor eIF2α. The small molecule guanabenz enhances eIF2α phosphorylation by blocking the function of GADD34, a regulatory protein that promotes eIF2α dephosphorylation. We tested the hypothesis that guanabenz, by inhibiting GADD34 and consequently increasing eIF2α phosphorylation and elevating ATF4, would improve survival in models of PD by up-regulating parkin. We found that GADD34 is strongly induced by 6-OHDA, and that GADD34 localization is dramatically altered in dopaminergic substantia nigra neurons in PD cases. We further demonstrated that guanabenz attenuates 6-hydroxydopamine (6-OHDA) induced cell death of differentiated PC12 cells and primary ventral midbrain dopaminergic neurons in culture, and of dopaminergic neurons in the substantia nigra of mice. In culture models, guanabenz also increases eIF2α phosphorylation and ATF4 and parkin levels in response to 6-OHDA. Furthermore, if either ATF4 or parkin is silenced, then the protective effect of guanabenz is lost. We also found similar results in a distinct model of neuronal death: primary cultures of cortical neurons treated with the topoisomerase I inhibitor camptothecin, in which guanabenz limited camptothecin-induced neuronal death in an ATF4- and parkin-dependent manner. In summary, our data suggest that guanabenz and other GADD34 inhibitors could be used as therapeutic agents to boost parkin levels and thereby slow neurodegeneration in PD and other neurodegenerative conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Effects of lateral variations of crustal rheology on the occurrence of post-orogenic normal faults: The Alto Tiberina Fault (Northern Apennines, Central Italy)

    NASA Astrophysics Data System (ADS)

    Pauselli, Cristina; Ranalli, Giorgio

    2017-11-01

    The Northern Apennines (NA) are characterized by formerly compressive structures partly overprinted by subsequent extensional structures. The area of extensional tectonics migrated eastward since the Miocene. The youngest and easternmost major expression of extension is the Alto Tiberina Fault (ATF). We estimate 2D rheological profiles across the NA, and conclude that lateral rheological crustal variations have played an important role in the formation of the ATF and similar previously active faults to the west. Lithospheric delamination and mantle degassing resulted in an easterly-migrating extension-compression boundary, coinciding at present with the ATF, where (i) the thickness of the upper crust brittle layer reaches a maximum; (ii) the critical stress difference required to initiate faulting at the base of the brittle layer is at a minimum; and (iii) the total strengths of both the brittle layer and the whole lithosphere are at a minimum. Although the location of the fault is correlated with lithospheric rheological properties, the rheology by itself does not account for the low dip ( 20°) of the ATF. Two hypotheses are considered: (a) the low dip of the ATF is related to a rotation of the stress tensor at the time of initiation of the fault, caused by a basal shear stress ( 100 MPa) possibly related to corner flow associated with delamination; or (b) the low dip is associated to low values of the friction coefficient (≤ 0.5) coupled with high pore pressures related to mantle degassing. Our results establishing the correlation between crustal rheology and the location of the ATF are relatively robust, as we have examined various possible compositions and rheological parameters. They also provide possible general indications on the mechanisms of localized extension in post-orogenic extensional setting. The hypotheses to account for the low dip of the ATF, on the other hand, are intended simply to suggest possible solutions worthy of further study.

  4. QED effects induced harmonics generation in extreme intense laser foil interaction

    NASA Astrophysics Data System (ADS)

    Yu, J. Y.; Yuan, T.; Liu, W. Y.; Chen, M.; Luo, W.; Weng, S. M.; Sheng, Z. M.

    2018-04-01

    A new mechanism of harmonics generation (HG) induced by quantum electrodynamics (QED) effects in extreme intense laser foil interaction is found and investigated by particle-in-cell (PIC) simulations. When two laser pulses with identical intensities of 1.6× {10}24 {{W}} {{{cm}}}-2 are counter-incident on a thin foil target, harmonics emission is observed in their reflected electromagnetic waves. Such harmonics radiation is excited due to transversely oscillating electric currents coming from the vibration of QED effect generated {e}-{e}+ pairs. The effects of laser intensity and polarization were studied. By distinguishing the cascade depth of generated photons and pairs, the influence of QED cascades on HG was analyzed. Although the current HG is not an efficient way for radiation source applications, it may provide a unique way to detect the QED processes in the near future ultra-relativistic laser solid interactions.

  5. Theoretical study of high-order harmonic generation from the hydrogen molecular ion with a dichromatic spatially inhomogeneous field

    NASA Astrophysics Data System (ADS)

    Xu, Xiao-Hu; Wang, Yan-Jun; Miao, Xiang-Yang

    2018-05-01

    We theoretically investigate the enhancement of high-order harmonic generation by numerically solving the non-Born-Oppenheimer time-dependent Schrödinger equation from the hydrogen molecular ion in a dichromatic inhomogeneous laser field. An ultrabroad supercontinuum up to 300 orders spectral width is generated. It is found that not only the inhomogeneity, but also the dichromatic field contributes to the significant extension of the harmonic cutoff compared with a monochromatic inhomogeneous laser field. Meanwhile, the long quantum paths can be suppressed and short ones can be enhanced by selecting optimized inhomogeneous parameter β, intensity and carrier envelope phase of the dichromatic inhomogeneous laser field. Furthermore, by superposing a properly selected range of the harmonic spectrum in the continuum region, an isolated 29-as pulse is generated. Both the classical theory and quantum time-frequency analysis are adopted to explain the physical mechanism.

  6. Extreme Ultraviolet Fractional Orbital Angular Momentum Beams from High Harmonic Generation

    PubMed Central

    Turpin, Alex; Rego, Laura; Picón, Antonio; San Román, Julio; Hernández-García, Carlos

    2017-01-01

    We investigate theoretically the generation of extreme-ultraviolet (EUV) beams carrying fractional orbital angular momentum. To this end, we drive high-order harmonic generation with infrared conical refraction (CR) beams. We show that the high-order harmonic beams emitted in the EUV/soft x-ray regime preserve the characteristic signatures of the driving beam, namely ringlike transverse intensity profile and CR-like polarization distribution. As a result, through orbital and spin angular momentum conservation, harmonic beams are emitted with fractional orbital angular momentum, and they can be synthesized into structured attosecond helical beams –or “structured attosecond light springs”– with rotating linear polarization along the azimuth. Our proposal overcomes the state of the art limitations for the generation of light beams far from the visible domain carrying non-integer orbital angular momentum and could be applied in fields such as diffraction imaging, EUV lithography, particle trapping, and super-resolution imaging. PMID:28281655

  7. Efficient nonlinear optical conversion of 1.319-micron laser radiation

    NASA Astrophysics Data System (ADS)

    Byer, Robert L.; Eckardt, Robert C.

    1993-01-01

    The accomplishments of this program are in the development and application of periodically poled nonlinear optical materials for nonlinear frequency-conversion. We have demonstrated the use of periodically poled lithium niobate (PPLN) as a bulk material for external resonant cavity second-harmonic generation with continuous-wave (cw) output power of 1.7 W. Work that is following this investigation is showing that planar waveguides of PPLN may well be the most satisfactory method of generation of 10's of mW of the 659-nm harmonic of the 1.32-micrometer Nd:YAG laser. We encountered major obstacles obtaining multilayer dielectric coatings necessary to pursue our proposed design of monolithic bulk optical harmonic generators. Additional alternative approaches such as discrete component resonant second harmonic generation employing single domain and periodically poled bulk crystals and monolithic single domain resonators formed by total internal reflection remain under investigation.

  8. Efficient second harmonic generation by para-nitroaniline embedded in electro-spun polymeric nanofibres

    NASA Astrophysics Data System (ADS)

    Gonçalves, Hugo; Saavedra, Inês; Ferreira, Rute AS; Lopes, PE; de Matos Gomes, Etelvina; Belsley, Michael

    2018-03-01

    Intense well polarized second harmonic light was generated by poly(methyl methacrylate) nanofibres with embedded para-nitroaniline nanocrystals. Subwavelength diameter fibres were electro-spun using a 1:2 weight ratio of chromophore to polymer. Analysis of the generated second harmonic light indicates that the para-nitroaniline molecules, which nominally crystalize in the centrosymmetric space group, were organized into noncentrosymmetric structures leading to a second order susceptibility dominated by a single tensor element. Under the best deposition conditions, the nanofibrers display an effective nonlinear optical susceptibility approximately two orders of magnitude greater than that of potassium dihydrogen phosphate. Generalizing this approach to a broad range of organic molecules with strong individual molecular second order nonlinear responses, but which nominally form centrosymmetric organic crystals, could open a new pathway for the fabrication of efficient sub-micron sized second harmonic light generators.

  9. Spherical harmonic analysis of a synoptic climatology generated with a global general circulation model

    NASA Technical Reports Server (NTRS)

    Christidis, Z. D.; Spar, J.

    1980-01-01

    Spherical harmonic analysis was used to analyze the observed climatological (C) fields of temperature at 850 mb, geopotential height at 500 mb, and sea level pressure. The spherical harmonic method was also applied to the corresponding "model climatological" fields (M) generated by a general circulation model, the "GISS climate model." The climate model was initialized with observed data for the first of December 1976 at 00. GMT and allowed to generate five years of meteorological history. Monthly means of the above fields for the five years were computed and subjected to spherical harmonic analysis. It was found from the comparison of the spectral components of both sets, M and C, that the climate model generated reasonable 500 mb geopotential heights. The model temperature field at 850 mb exhibited a generally correct structure. However, the meridional temperature gradient was overestimated and overheating of the continents was observed in summer.

  10. High-harmonic and single attosecond pulse generation using plasmonic field enhancement in ordered arrays of gold nanoparticles with chirped laser pulses.

    PubMed

    Yang, Ying-Ying; Scrinzi, Armin; Husakou, Anton; Li, Qian-Guang; Stebbings, Sarah L; Süßmann, Frederik; Yu, Hai-Juan; Kim, Seungchul; Rühl, Eckart; Herrmann, Joachim; Lin, Xue-Chun; Kling, Matthias F

    2013-01-28

    Coherent XUV sources, which may operate at MHz repetition rate, could find applications in high-precision spectroscopy and for spatio-time-resolved measurements of collective electron dynamics on nanostructured surfaces. We theoretically investigate utilizing the enhanced plasmonic fields in an ordered array of gold nanoparticles for the generation of high-harmonic, extreme-ultraviolet (XUV) radiation. By optimization of the chirp of ultrashort laser pulses incident on the array, our simulations indicate a potential route towards the temporal shaping of the plasmonic near-field and, in turn, the generation of single attosecond pulses. The inherent effects of inhomogeneity of the local fields on the high-harmonic generation are analyzed and discussed. While taking the inhomogeneity into account does not affect the optimal chirp for the generation of a single attosecond pulse, the cut-off energy of the high-harmonic spectrum is enhanced by about a factor of two.

  11. The detection of planetary systems from Space Station - A star observation strategy

    NASA Technical Reports Server (NTRS)

    Mascy, Alfred C.; Nishioka, Ken; Jorgensen, Helen; Swenson, Byron L.

    1987-01-01

    A 10-20-yr star-observation program for the Space Station Astrometric Telescope Facility (ATF) is proposed and evaluated by means of computer simulations. The primary aim of the program is to detect stars with planetary systems by precise determination of their motion relative to reference stars. The designs proposed for the ATF are described and illustrated; the basic parameters of the 127 stars selected for the program are listed in a table; spacecraft and science constraints, telescope slewing rates, and the possibility of limiting the program sample to stars near the Galactic equator are discussed; and the effects of these constraints are investigated by simulating 1 yr of ATF operation. Viewing all sky regions, the ATF would have 81-percent active viewing time, observing each star about 200 times (56 h) per yr; only small decrements in this performance would result from limiting the viewing field.

  12. Engineering an allosteric transcription factor to respond to new ligands.

    PubMed

    Taylor, Noah D; Garruss, Alexander S; Moretti, Rocco; Chan, Sum; Arbing, Mark A; Cascio, Duilio; Rogers, Jameson K; Isaacs, Farren J; Kosuri, Sriram; Baker, David; Fields, Stanley; Church, George M; Raman, Srivatsan

    2016-02-01

    Genetic regulatory proteins inducible by small molecules are useful synthetic biology tools as sensors and switches. Bacterial allosteric transcription factors (aTFs) are a major class of regulatory proteins, but few aTFs have been redesigned to respond to new effectors beyond natural aTF-inducer pairs. Altering inducer specificity in these proteins is difficult because substitutions that affect inducer binding may also disrupt allostery. We engineered an aTF, the Escherichia coli lac repressor, LacI, to respond to one of four new inducer molecules: fucose, gentiobiose, lactitol and sucralose. Using computational protein design, single-residue saturation mutagenesis or random mutagenesis, along with multiplex assembly, we identified new variants comparable in specificity and induction to wild-type LacI with its inducer, isopropyl β-D-1-thiogalactopyranoside (IPTG). The ability to create designer aTFs will enable applications including dynamic control of cell metabolism, cell biology and synthetic gene circuits.

  13. Engineering an allosteric transcription factor to respond to new ligands

    PubMed Central

    Taylor, Noah D; Garruss, Alexander S; Moretti, Rocco; Chan, Sum; Arbing, Mark A; Cascio, Duilio; Rogers, Jameson K; Isaacs, Farren J; Kosuri, Sriram; Baker, David; Fields, Stanley; Church, George M; Raman, Srivatsan

    2016-01-01

    Genetic regulatory proteins inducible by small molecules are useful synthetic biology tools as sensors and switches. Bacterial allosteric transcription factors (aTFs) are a major class of regulatory proteins, but few aTFs have been redesigned to respond to new effectors beyond natural aTF-inducer pairs. Altering inducer specificity in these proteins is difficult because substitutions that affect inducer binding may also disrupt allostery. We engineered an aTF, the Escherichia coli lac repressor, LacI, to respond to one of four new inducer molecules: fucose, gentiobiose, lactitol or sucralose. Using computational protein design, single-residue saturation mutagenesis or random mutagenesis, along with multiplex assembly, we identified new variants comparable in specificity and induction to wild-type LacI with its inducer, isopropyl β-D-1-thiogalactopyranoside (IPTG). The ability to create designer aTFs will enable applications including dynamic control of cell metabolism, cell biology and synthetic gene circuits. PMID:26689263

  14. On-the-Fly Control of High-Harmonic Generation Using a Structured Pump Beam

    NASA Astrophysics Data System (ADS)

    Hareli, Liran; Lobachinsky, Lilya; Shoulga, Georgiy; Eliezer, Yaniv; Michaeli, Linor; Bahabad, Alon

    2018-05-01

    We demonstrate experimentally a relatively simple yet powerful all-optical enhancement and control technique for high harmonic generation. This is achieved by using as a pump beam two different spatial optical modes interfering together to realize tunable periodic quasi-phase matching of the interaction. With this technique, we demonstrate on-the-fly quasi-phase matching of harmonic orders 29-41 at ambient gas pressure levels of 50 and 100 Torr, where an up to 100-fold enhancement of the emission is observed. The technique is scalable to different harmonic orders and ambient pressure conditions.

  15. Second-harmonic generation of practical Bessel beams

    NASA Astrophysics Data System (ADS)

    Huang, Jin H.; Ding, Desheng; Hsu, Yin-Sung

    2009-11-01

    A fast Gaussian expansion approach is used to investigate fundamental and second-harmonic generation in practical Bessel beams of finite aperture. The analysis is based on the integral solutions of the KZK equation under the quasilinear approximation. The influence of the medium's attenuation on the beam profile is considered. Analysis results show that the absorption parameter has a significant effect on the far-field beam profile of the second harmonic. Under certain circumstances, the second harmonic of a practical Bessel beam still has the main properties of an ideal Bessel beam of infinite aperture when it propagates within its depth of field.

  16. On-the-Fly Control of High-Harmonic Generation Using a Structured Pump Beam.

    PubMed

    Hareli, Liran; Lobachinsky, Lilya; Shoulga, Georgiy; Eliezer, Yaniv; Michaeli, Linor; Bahabad, Alon

    2018-05-04

    We demonstrate experimentally a relatively simple yet powerful all-optical enhancement and control technique for high harmonic generation. This is achieved by using as a pump beam two different spatial optical modes interfering together to realize tunable periodic quasi-phase matching of the interaction. With this technique, we demonstrate on-the-fly quasi-phase matching of harmonic orders 29-41 at ambient gas pressure levels of 50 and 100 Torr, where an up to 100-fold enhancement of the emission is observed. The technique is scalable to different harmonic orders and ambient pressure conditions.

  17. Possible role of cochlear nonlinearity in the detection of mistuning of a harmonic component in a harmonic complex

    NASA Astrophysics Data System (ADS)

    Stoelinga, Christophe; Heo, Inseok; Long, Glenis; Lee, Jungmee; Lutfi, Robert; Chang, An-Chieh

    2015-12-01

    The human auditory system has a remarkable ability to "hear out" a wanted sound (target) in the background of unwanted sounds. One important property of sound which helps us hear-out the target is inharmonicity. When a single harmonic component of a harmonic complex is slightly mistuned, that component is heard to separate from the rest. At high harmonic numbers, where components are unresolved, the harmonic segregation effect is thought to result from detection of modulation of the time envelope (roughness cue) resulting from the mistuning. Neurophysiological research provides evidence that such envelope modulations are represented early in the auditory system, at the level of the auditory nerve. When the mistuned harmonic is a low harmonic, where components are resolved, the harmonic segregation is attributed to more centrally-located auditory processes, leading harmonic components to form a perceptual group heard separately from the mistuned component. Here we consider an alternative explanation that attributes the harmonic segregation to detection of modulation when both high and low harmonic numbers are mistuned. Specifically, we evaluate the possibility that distortion products in the cochlea generated by the mistuned component introduce detectable beating patterns for both high and low harmonic numbers. Distortion product otoacoustic emissions (DPOAEs) were measured using 3, 7, or 12-tone harmonic complexes with a fundamental frequency (F0) of 200 or 400 Hz. One of two harmonic components was mistuned at each F0: one when harmonics are expected to be resulted and the other from unresolved harmonics. Many non-harmonic DPOAEs are present whenever a harmonic component is mistuned. These non-harmonic DPOAEs are often separated by the amount of the mistuning (ΔF). This small frequency difference will generate a slow beating pattern at ΔF, because this beating is only present when a harmonic component is mistuned, it could provide a cue for behavioral detection of harmonic complex mistuning and may also be associated with the modulation of auditory nerve responses.

  18. TGRL Lipolysis Products Induce Stress Protein ATF3 via the TGF-β Receptor Pathway in Human Aortic Endothelial Cells

    PubMed Central

    Eiselein, Larissa; Nyunt, Tun; Lamé, Michael W.; Ng, Kit F.; Wilson, Dennis W.; Rutledge, John C.; Aung, Hnin H.

    2015-01-01

    Studies have suggested a link between the transforming growth factor beta 1 (TGF-β1) signaling cascade and the stress-inducible activating transcription factor 3 (ATF3). We have demonstrated that triglyceride-rich lipoproteins (TGRL) lipolysis products activate MAP kinase stress associated JNK/c-Jun pathways resulting in up-regulation of ATF3, pro-inflammatory genes and induction of apoptosis in human aortic endothelial cells. Here we demonstrate increased release of active TGF-β at 15 min, phosphorylation of Smad2 and translocation of co-Smad4 from cytosol to nucleus after a 1.5 h treatment with lipolysis products. Activation and translocation of Smad2 and 4 was blocked by addition of SB431542 (10 μM), a specific inhibitor of TGF-β-activin receptor ALKs 4, 5, 7. Both ALK receptor inhibition and anti TGF-β1 antibody prevented lipolysis product induced up-regulation of ATF3 mRNA and protein. ALK inhibition prevented lipolysis product-induced nuclear accumulation of ATF3. ALKs 4, 5, 7 inhibition also prevented phosphorylation of c-Jun and TGRL lipolysis product-induced p53 and caspase-3 protein expression. These findings demonstrate that TGRL lipolysis products cause release of active TGF-β and lipolysis product-induced apoptosis is dependent on TGF-β signaling. Furthermore, signaling through the stress associated JNK/c-Jun pathway is dependent on TGF-β signaling suggesting that TGF-β signaling is necessary for nuclear accumulation of the ATF3/cJun transcription complex and induction of pro-inflammatory responses. PMID:26709509

  19. 27 CFR 479.104 - Registration of firearms by certain governmental entities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS... by T.D. ATF-241, 51 FR 39633, Oct. 29, 1986; T.D. ATF-270, 53 FR 10510, Mar. 31, 1988] Machine Guns ...

  20. 27 CFR 479.104 - Registration of firearms by certain governmental entities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS... by T.D. ATF-241, 51 FR 39633, Oct. 29, 1986; T.D. ATF-270, 53 FR 10510, Mar. 31, 1988] Machine Guns ...

  1. Distinct Residues Contribute to Motility Repression and Autoregulation in the Proteus mirabilis Fimbria-Associated Transcriptional Regulator AtfJ.

    PubMed

    Bode, Nadine J; Chan, Kun-Wei; Kong, Xiang-Peng; Pearson, Melanie M

    2016-08-01

    Proteus mirabilis contributes to a significant number of catheter-associated urinary tract infections, where coordinated regulation of adherence and motility is critical for ascending disease progression. Previously, the mannose-resistant Proteus-like (MR/P) fimbria-associated transcriptional regulator MrpJ has been shown to both repress motility and directly induce the transcription of its own operon; in addition, it affects the expression of a wide range of cellular processes. Interestingly, 14 additional mrpJ paralogs are included in the P. mirabilis genome. Looking at a selection of MrpJ paralogs, we discovered that these proteins, which consistently repress motility, also have nonidentical functions that include cross-regulation of fimbrial operons. A subset of paralogs, including AtfJ (encoded by the ambient temperature fimbrial operon), Fim8J, and MrpJ, are capable of autoinduction. We identified an element of the atf promoter extending from 487 to 655 nucleotides upstream of the transcriptional start site that is responsive to AtfJ, and we found that AtfJ directly binds this fragment. Mutational analysis of AtfJ revealed that its two identified functions, autoregulation and motility repression, are not invariably linked. Residues within the DNA-binding helix-turn-helix domain are required for motility repression but not necessarily autoregulation. Likewise, the C-terminal domain is dispensable for motility repression but is essential for autoregulation. Supported by a three-dimensional (3D) structural model, we hypothesize that the C-terminal domain confers unique regulatory capacities on the AtfJ family of regulators. Balancing adherence with motility is essential for uropathogens to successfully establish a foothold in their host. Proteus mirabilis uses a fimbria-associated transcriptional regulator to switch between these antagonistic processes by increasing fimbrial adherence while simultaneously downregulating flagella. The discovery of multiple related proteins, many of which also function as motility repressors, encoded in the P. mirabilis genome has raised considerable interest as to their functionality and potential redundancy in this organism. This study provides an important advance in this field by elucidating the nonidentical effects of these paralogs on a molecular level. Our mechanistic studies of one member of this group, AtfJ, shed light on how these differing functions may be conferred despite the limited sequence variety exhibited by the paralogous proteins. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

    Brown, Nicholas; Burns, Joseph R.

    The aftermath of the Tōhoku earthquake and the Fukushima accident has led to a global push to improve the safety of existing light water reactors. A key component of this initiative is the development of nuclear fuel and cladding materials with potentially enhanced accident tolerance, also known as accident-tolerant fuels (ATF). These materials are intended to improve core fuel and cladding integrity under beyond design basis accident conditions while maintaining or enhancing reactor performance and safety characteristics during normal operation. To complement research that has already been carried out to characterize ATF neutronics, the present study provides an initial investigationmore » of the sensitivity and uncertainty of ATF systems responses to nuclear cross section data. ATF concepts incorporate novel materials, including SiC and FeCrAl cladding and high density uranium silicide composite fuels, in turn introducing new cross section sensitivities and uncertainties which may behave differently from traditional fuel and cladding materials. In this paper, we conducted sensitivity and uncertainty analysis using the TSUNAMI-2D sequence of SCALE with infinite lattice models of ATF assemblies. Of all the ATF materials considered, it is found that radiative capture in 56Fe in FeCrAl cladding is the most significant contributor to eigenvalue uncertainty. 56Fe yields significant potential eigenvalue uncertainty associated with its radiative capture cross section; this is by far the largest ATF-specific uncertainty found in these cases, exceeding even those of uranium. We found that while significant new sensitivities indeed arise, the general sensitivity behavior of ATF assemblies does not markedly differ from traditional UO2/zirconium-based fuel/cladding systems, especially with regard to uncertainties associated with uranium. We assessed the similarity of the IPEN/MB-01 reactor benchmark model to application models with FeCrAl cladding. We used TSUNAMI-IP to calculate similarity indices of the application model and IPEN/MB-01 reactor benchmark model. This benchmark was selected for its use of SS304 as a cladding and structural material, with significant 56Fe content. The similarity indices suggest that while many differences in reactor physics arise from differences in design, sensitivity to and behavior of 56Fe absorption is comparable between systems, thus indicating the potential for this benchmark to reduce uncertainties in 56Fe radiative capture cross sections.« less

  3. Helicity-Selective Enhancement and Polarization Control of Attosecond High Harmonic Waveforms Driven by Bichromatic Circularly Polarized Laser Fields.

    PubMed

    Dorney, Kevin M; Ellis, Jennifer L; Hernández-García, Carlos; Hickstein, Daniel D; Mancuso, Christopher A; Brooks, Nathan; Fan, Tingting; Fan, Guangyu; Zusin, Dmitriy; Gentry, Christian; Grychtol, Patrik; Kapteyn, Henry C; Murnane, Margaret M

    2017-08-11

    High harmonics driven by two-color counterrotating circularly polarized laser fields are a unique source of bright, circularly polarized, extreme ultraviolet, and soft x-ray beams, where the individual harmonics themselves are completely circularly polarized. Here, we demonstrate the ability to preferentially select either the right or left circularly polarized harmonics simply by adjusting the relative intensity ratio of the bichromatic circularly polarized driving laser field. In the frequency domain, this significantly enhances the harmonic orders that rotate in the same direction as the higher-intensity driving laser. In the time domain, this helicity-dependent enhancement corresponds to control over the polarization of the resulting attosecond waveforms. This helicity control enables the generation of circularly polarized high harmonics with a user-defined polarization of the underlying attosecond bursts. In the future, this technique should allow for the production of bright highly elliptical harmonic supercontinua as well as the generation of isolated elliptically polarized attosecond pulses.

  4. Handling Nonlinearities in ELF/VLF Generation Using Modulated Heating at HAARP

    NASA Astrophysics Data System (ADS)

    Jin, G.; Spasojevic, M.; Cohen, M.; Inan, U. S.

    2011-12-01

    George Jin Maria Spasojevic Morris Cohen Umran Inan Stanford University Modulated HF heating of the D-region ionosphere near the auroral electrojet can generate extremely low frequency (ELF) waves in the kilohertz range. This process is nonlinear and generates harmonics at integer multiples of the ELF modulation frequency. The nonlinear distortion has implications for any communications applications since the harmonics contain a substantial fraction of the signal power and use up bandwidth. We examine two techniques for handling the nonlinearity. First we modulate the HF heating with a non-sinusoidal envelope designed to create a sinusoidal change in the Hall conductivity at a particular altitude in the ionosphere to minimize any generated harmonics. The modulation waveform is generated by inverting a numerical HF heating model, starting from the desired conductivity time series, and obtaining the HF power envelope that will result in that conductivity. The second technique attempts to use the energy in the harmonics to improve bit error rates when digital modulation is applied to the ELF carrier. In conventional quadrature phase-shift keying (QPSK), where a ELF carrier is phase-shifted by 0°, 90°, 180°, and 270° in order to transmit a pair of bits, the even harmonics cannot distinguish between the four possible shifts. By using different phase values, all the energy in the harmonics can contribute to determining the phase of the carrier and thus improve the bit error rate.

  5. Thermally and electrically controllable multiple high harmonics generation by harmonically driven quasi-two-dimensional electron gas

    NASA Astrophysics Data System (ADS)

    Maglevanny, I. I.; Smolar, V. A.; Karyakina, T. I.

    2018-06-01

    In this paper, we consider the activation processes in nonlinear meta-stable system based on a lateral (quasi-two-dimensional) superlattice and study the dynamics of such a system externally driven by a harmonic force. The internal control parameters are the longitudinal applied electric field and the sample temperature. The spontaneous transverse electric field is considered as an order parameter. The forced violations of order parameter are considered as a response of a system to periodic driving. We investigate the cooperative effects of self-organization and high harmonic forcing from the viewpoint of catastrophe theory and show the possibility of generation of third and higher odd harmonics in output signal that lead to distortion of its wave front. A higher harmonics detection strategy is further proposed and explained in detail by exploring the influences of system parameters on the response output of the system that are discussed through numerical simulations.

  6. Electromagnetic probes of molecular motors in the electron transport chains of mitochondria and chloroplasts

    NASA Astrophysics Data System (ADS)

    Miller, J. H., Jr.; Nawarathna, D.; Vajrala, V.; Gardner, J.; Widger, W. R.

    2005-12-01

    We report on measurements of harmonics generated by whole cells, mitochondria, and chloroplasts in response to applied sinusoidal electric fields. The frequency- and amplitude-dependence of the induced harmonics exhibit features that correlate with physiological processes. Budding yeast (S. cerevisiae) cells produce numerous harmonics, the amplitudes of which depend strongly on frequency. When the second or third harmonic amplitude is plotted vs. applied frequency, we observe two peaks, around 3 kHz and 12 kHz, which are suppressed by respiratory inhibitors. We observe similar peaks when measuring the harmonic response of B. indicas, a relative of the mitochondrial ancestor. In uncoupled mitochondria, in which most of the electron transport chain is active but the ATP-synthase molecular turbine is inactive, only one (lower frequency) of the two peaks is present. Finally, we find that harmonics generated by chloroplasts depend dramatically on incident light, and vanish in the absence of light.

  7. High harmonic generation in underdense plasmas by intense laser pulses with orbital angular momentum

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

    Mendonça, J. T., E-mail: josetitomend@gmail.com; Vieira, J., E-mail: jorge.vieira@ist.utl.pt

    We study high harmonic generation produced by twisted laser pulses, with orbital angular momentum in the relativistic regime, for pulse propagation in underdense plasma. We consider fast time scale processes associated with an ultra-short pulse, where the ion motion can be neglected. We use both analytical models and numerical simulations using a relativistic particle-in-cell code. The present description is valid for relativistic laser intensities, when the normalized field amplitude is much larger than one, a ≫ 1. We also discuss two distinct processes associated with linear and circular polarization. Using both analytical solutions and particle-in-cell simulations, we are able tomore » show that, for laser pulses in a well defined Laguerre-Gauss mode, angular momentum conservation is observed during the process of harmonic generation. Intensity modulation of the harmonic spectrum is also verified, as imposed by the nonlinear time-scale for energy transfer between different harmonics.« less

  8. Mode matching in multiresonant plasmonic nanoantennas for enhanced second harmonic generation

    NASA Astrophysics Data System (ADS)

    Celebrano, Michele; Wu, Xiaofei; Baselli, Milena; Großmann, Swen; Biagioni, Paolo; Locatelli, Andrea; de Angelis, Costantino; Cerullo, Giulio; Osellame, Roberto; Hecht, Bert; Duò, Lamberto; Ciccacci, Franco; Finazzi, Marco

    2015-05-01

    Boosting nonlinear frequency conversion in extremely confined volumes remains a challenge in nano-optics research, but can enable applications in nanomedicine, photocatalysis and background-free biosensing. To obtain brighter nonlinear nanoscale sources, approaches that enhance the electromagnetic field intensity and counter the lack of phase matching in nanoplasmonic systems are often employed. However, the high degree of symmetry in the crystalline structure of plasmonic materials (metals in particular) and in nanoantenna designs strongly quenches second harmonic generation. Here, we describe doubly-resonant single-crystalline gold nanostructures with no axial symmetry displaying spatial mode overlap at both the excitation and second harmonic wavelengths. The combination of these features allows the attainment of a nonlinear coefficient for second harmonic generation of ˜5 × 10-10 W-1, enabling a second harmonic photon yield higher than 3 × 106 photons per second. Theoretical estimations point toward the use of our nonlinear plasmonic nanoantennas as efficient platforms for label-free molecular sensing.

  9. Ultrafast third-harmonic generation from textured aluminum nitride-sapphire interfaces

    NASA Astrophysics Data System (ADS)

    Stoker, D. S.; Baek, J.; Wang, W.; Kovar, D.; Becker, M. F.; Keto, J. W.

    2006-05-01

    We measured and modeled third-harmonic generation (THG) from an AlN thin film on sapphire using a time-domain approach appropriate for ultrafast lasers. Second-harmonic measurements indicated that polycrystalline AlN contains long-range crystal texture. An interface model for third-harmonic generation enabled an analytical representation of scanning THG ( z -scan) experiments. Using it and accounting for Fresnel reflections, we measured the AlN -sapphire susceptibility ratio and estimated the susceptibility for aluminum nitride, χxxxx(3)(3ω;ω,ω,ω)=1.52±0.25×10-13esu . The third-harmonic (TH) spectrum strongly depended on the laser focus position and sample thickness. The amplitude and phase of the frequency-domain interference were fit to the Fourier transform of the calculated time-domain field to improve the accuracy of several experimental parameters. We verified that the model works well for explaining TH signal amplitudes and spectral phase. Some anomalous features in the TH spectrum were observed, which we attributed to nonparaxial effects.

  10. Strong-field control and enhancement of chiral response in bi-elliptical high-order harmonic generation: an analytical model

    NASA Astrophysics Data System (ADS)

    Ayuso, David; Decleva, Piero; Patchkovskii, Serguei; Smirnova, Olga

    2018-06-01

    The generation of high-order harmonics in a medium of chiral molecules driven by intense bi-elliptical laser fields can lead to strong chiroptical response in a broad range of harmonic numbers and ellipticities (Ayuso et al 2018 J. Phys. B: At. Mol. Opt. Phys. 51 06LT01). Here we present a comprehensive analytical model that can describe the most relevant features arising in the high-order harmonic spectra of chiral molecules driven by strong bi-elliptical fields. Our model recovers the physical picture underlying chiral high-order harmonic generation (HHG) based on ultrafast chiral hole motion and identifies the rotationally invariant molecular pseudoscalars responsible for chiral dynamics. Using the chiral molecule propylene oxide as an example, we show that one can control and enhance the chiral response in bi-elliptical HHG by tailoring the driving field, in particular by tuning its frequency, intensity and ellipticity, exploiting a suppression mechanism of achiral background based on the linear Stark effect.

  11. New modified multi-level residue harmonic balance method for solving nonlinearly vibrating double-beam problem

    NASA Astrophysics Data System (ADS)

    Rahman, Md. Saifur; Lee, Yiu-Yin

    2017-10-01

    In this study, a new modified multi-level residue harmonic balance method is presented and adopted to investigate the forced nonlinear vibrations of axially loaded double beams. Although numerous nonlinear beam or linear double-beam problems have been tackled and solved, there have been few studies of this nonlinear double-beam problem. The geometric nonlinear formulations for a double-beam model are developed. The main advantage of the proposed method is that a set of decoupled nonlinear algebraic equations is generated at each solution level. This heavily reduces the computational effort compared with solving the coupled nonlinear algebraic equations generated in the classical harmonic balance method. The proposed method can generate the higher-level nonlinear solutions that are neglected by the previous modified harmonic balance method. The results from the proposed method agree reasonably well with those from the classical harmonic balance method. The effects of damping, axial force, and excitation magnitude on the nonlinear vibrational behaviour are examined.

  12. Long-term operation of surface high-harmonic generation from relativistic oscillating mirrors using a spooling tape

    DOE PAGES

    Bierbach, Jana; Yeung, Mark; Eckner, Erich; ...

    2015-05-01

    Surface high-harmonic generation in the relativistic regime is demonstrated as a source of extreme ultra-violet (XUV) pulses with extended operation time. Relativistic high-harmonic generation is driven by a frequency-doubled high-power Ti:Sapphire laser focused to a peak intensity of 3·1019 W/cm2 onto spooling tapes. We demonstrate continuous operation over up to one hour runtime at a repetition rate of 1 Hz. Harmonic spectra ranging from 20 eV to 70 eV (62 nm to 18 nm) were consecutively recorded by an XUV spectrometer. An average XUV pulse energy in the µJ range is measured. With the presented setup, relativistic surface high-harmonic generationmore » becomes a powerful source of coherent XUV pulses that might enable applications in, e.g. attosecond laser physics and the seeding of free-electron lasers, when the laser issues causing 80-% pulse energy fluctuations are overcome.« less

  13. Improved control strategy for PI-R current of DFIG considering voltage and current harmonics compensation

    NASA Astrophysics Data System (ADS)

    Song, S. Y.; Liu, Q. H.; Zhao, Y. N.; Liu, S. Y.

    2016-08-01

    With the rapid development of wind power generation, the related research of wind power control and integration issues has attracted much attention, and the focus of the research are shifting away from the ideal power grid environment to the actual power grid environment. As the main stream wind turbine generator, a doubly-fed induction generator (DFIG) is connected to the power grid directly by its stator, so it is particularly sensitive to the power grid. This paper studies the improvement of DFIG control technology in the power grid harmonic environment. Based on the DFIG dynamic model considering the power grid harmonic environment, this paper introduces the shortcomings of the common control strategy of DFIG, and puts forward the enhanced method. The decoupling control of the system is realized by compensating the coupling between the rotor harmonic voltage and harmonic current, improving the control performance. In addition, the simulation experiments on PSCAD/EMTDC are carried out to verify the correctness and effectiveness of the improved scheme.

  14. Role of initial coherence in the generation of harmonics and sidebands from a strongly driven two-level atom

    NASA Astrophysics Data System (ADS)

    Gauthey, F. I.; Keitel, C. H.; Knight, P. L.; Maquet, A.

    1995-07-01

    We investigate the coherent and incoherent contributions of the scattering spectrum of strongly driven two-level atoms as a function of the initial preparation of the atomic system. The initial ``phasing'' of the coherent superposition of the excited and ground states is shown to influence strongly the generation of both harmonics and hyper-Raman lines. In particular, we point out conditions under which harmonic generation can be inhibited at the expense of the hyper-Raman lines. Our numerical findings are supported by approximate analytical evaluation in the dressed state picture.

  15. Large enhancement of interface second-harmonic generation near the zero-n(-) gap of a negative-index Bragg grating.

    PubMed

    D'Aguanno, Giuseppe; Mattiucci, Nadia; Bloemer, Mark J; Scalora, Michael

    2006-03-01

    We predict a large enhancement of interface second-harmonic generation near the zero-n(-) gap of a Bragg grating made of alternating layers of negative- and positive-index materials. Field localization and coherent oscillations of the nonlinear dipoles located at the structure's interfaces conspire to yield conversion efficiencies at least an order of magnitude greater than those achievable in the same length of nonlinear, phase-matched bulk material. These findings thus point to a new class of second-harmonic-generation devices made of standard centrosymmetric materials.

  16. Efficient forward second-harmonic generation from planar archimedean nanospirals

    DOE PAGES

    Davidson, II, Roderick B.; Ziegler, Jed I.; Vargas, Guillermo; ...

    2015-05-01

    Here, the enhanced electric field at plasmonic resonances in nanoscale antennas can lead to efficient harmonic generation, especially when the plasmonic geometry is asymmetric on either inter-particle or intra-particle levels. The planar Archimedean nanospiral offers a unique geometrical asymmetry for second-harmonic generation (SHG) because the SHG results neither from arranging centrosymmetric nanoparticles in asymmetric groupings, nor from non-centrosymmetric nanoparticles that retain a local axis of symmetry. Here, we report forward SHG from planar arrays of Archimedean nanospirals using 15 fs pulses from a Ti:sapphire oscillator tuned to 800 nm wavelength.

  17. Second harmonic generation in photonic crystal cavities in (111)-oriented GaAs

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

    Buckley, Sonia, E-mail: bucklesm@stanford.edu; Radulaski, Marina; Vučković, Jelena

    2013-11-18

    We demonstrate second harmonic generation at telecommunications wavelengths in photonic crystal cavities in (111)-oriented GaAs. We fabricate 30 photonic crystal structures in both (111)- and (100)-oriented GaAs and observe an increase in generated second harmonic power in the (111) orientation, with the mean power increased by a factor of 3, although there is a large scatter in the measured values. We discuss possible reasons for this increase, in particular, the reduced two photon absorption for transverse electric modes in (111) orientation, as well as a potential increase due to improved mode overlap.

  18. Quasi-phase-matched second-harmonic generation of 532 nm radiation in 25 degrees -rotated, x-cut, near-stoichiometric, lithium tantalate fabricated by vapor transport equilibration.

    PubMed

    Hum, D S; Route, R K; Fejer, M M

    2007-04-15

    Quasi-phase-matched second-harmonic generation of 532 nm radiation in 25 degrees -rotated, x-cut, near-stoichiometric lithium tantalate has been performed. Using a face-normal topology for frequency conversion applications allows scalable surface area to avoid surface and volume damage in high-power interactions. First-order, quasi-phase-matched second-harmonic generation was achieved using near-stoichiometric lithium tantalate fabricated by vapor transport equilibration. These crystals supported 1 J of 1064 nm radiation and generated 21 mJ of 532 nm radiation from a 7 ns, Q-switched Nd:YAG laser within a factor of 4.2 of expectation.

  19. Design of bunch compressing system with suppression of coherent synchrotron radiation for ATF upgrade

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

    Jing, Yichao; Fedurin, Mikhail; Stratakis, Diktys

    2015-05-03

    One of the operation modes for Accelerator Test Facility (ATF) upgrade is to provide high peak current, high quality electron beam for users. Such operation requires a bunch compressing system with a very large compression ratio. The CSR originating from the strong compressors generally could greatly degrade the quality of the electron beam. In this paper, we present our design for the entire bunch compressing system that will limit the effect of CSR on the e-beam’s quality. We discuss and detail the performance from the start to end simulation of such a compressor for ATF.

  20. Compact single-pass X-ray FEL with harmonic multiplication cascades

    NASA Astrophysics Data System (ADS)

    Zhukovsky, K.

    2018-07-01

    The generation of X-ray radiation in cascaded single-pass free electron laser (FEL), which amplifies high harmonics of a two-frequency undulator, is studied. Power dynamics of FEL harmonics is explored with the help of the phenomenological model of a single pass FEL. The model describes both linear and non-linear harmonic generation, starting from a coherent seed laser and initial shot noise with account for main loss factors for each harmonic in each cascade individually: the energy spread and beam divergence, the coupling losses between FEL cascades, the diffraction etc. The model was validated with the experiment and with relevant 3-D simulations. It is employed for modeling the cascaded FELs with harmonic multiplication and analyzing the evolution of FEL harmonic power with the aim to obtain the maximum high harmonic power in the X-ray band at the shortest possible FEL length with the lowest possible seed frequency. The advantages of two-frequency undulators in HGHG FELs are elucidated. The requirements for the electron beam are studied; the need for low energy spread is evidenced: our evaluations yield σe < 2 × 10-4. Several cascaded HGHG FELs with two-frequency undulators are modeled. Generation of soft X-ray radiation at λ = 2 . 71 nm, reaching ∼50 MW power with I0 ∼ 100 A in a cascaded FEL at just 40 m with 13.51 nm seed, matching peak reflectivity of Mo/Si, is demonstrated. The generation of 40 MW radiation power at λ = 2 . 27 nm with the beam current I0 ∼ 100 A, energy E = 950 MeV and the energy spread σe = 2 × 10-4 is studied, using second and third harmonics in three-stage 45 m long FEL. The multistage FEL is modeled for generating radiation in nanometer band: ∼40 MW power at λ ∼ 2 . 6 nm with I0 ∼ 175 A current in just ∼40 m long FEL with commercially available F2 excimer UV laser seed at 157 nm. The peak radiation power rises to ∼0.5 GW for ∼1 kA beam current.

  1. Balancing Vibrations at Harmonic Frequencies by Injecting Harmonic Balancing Signals into the Armature of a Linear Motor/Alternator Coupled to a Stirling Machine

    NASA Technical Reports Server (NTRS)

    Holliday, Ezekiel S. (Inventor)

    2014-01-01

    Vibrations at harmonic frequencies are reduced by injecting harmonic balancing signals into the armature of a linear motor/alternator coupled to a Stirling machine. The vibrations are sensed to provide a signal representing the mechanical vibrations. A harmonic balancing signal is generated for selected harmonics of the operating frequency by processing the sensed vibration signal with adaptive filter algorithms of adaptive filters for each harmonic. Reference inputs for each harmonic are applied to the adaptive filter algorithms at the frequency of the selected harmonic. The harmonic balancing signals for all of the harmonics are summed with a principal control signal. The harmonic balancing signals modify the principal electrical drive voltage and drive the motor/alternator with a drive voltage component in opposition to the vibration at each harmonic.

  2. Steam Oxidation Testing in the Severe Accident Test Station

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

    Pint, Bruce A.; McMurray, Jake W.

    2016-08-01

    Since 2011, Oak Ridge National Laboratory (ORNL) has been conducting high temperature steam oxidation testing of candidate alloys for accident tolerant fuel (ATF) cladding. These concepts are designed to enhance safety margins in light water reactors (LWR) during severe accident scenarios. In the US ATF community, the Severe Accident Test Station (SATS) has been evaluating candidate materials (including coatings) since 2012. Compared to the current UO 2/Zr-based alloy fuel system, alternative cladding materials need to offer slower oxidation kinetics and a smaller enthalpy of oxidation in order to significantly reduce the rate of heat and hydrogen generation in the coremore » during a coolant-limited severe accident. The steam oxidation behavior of candidate materials is a key metric in the evaluation of ATF concepts and also an important input into models. However, prior modeling work of FeCrAl cladding has used incomplete information on the physical properties of FeCrAl. Also, the steam oxidation data being collected at 1200°-1700°C is unique as no prior work has considered steam oxidation of alloys at such high temperatures. In some cases, the results have been difficult to interpret and more fundamental information is needed such as the stability of alumina in flowing steam at 1400°-1500°C. This report summarizes recent work to measure the steam oxidation kinetics of candidate alloys, the evaporation rate of alumina in steam and the development of integral data on FeCrAl compared to conventional Zr-based cladding.« less

  3. Nonlinear harmonic generation in distributed optical klystrons

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

    H.P. Freund; George R. Neil

    2001-12-01

    A distributed optical klystron has the potential for dramatically shortening the total interaction length in high-gain free-electron lasers (INP 77-59, Novosibirsk, 1977; Nucl. Instr. and Meth A 304 (1991) 463) in comparison to a single-wiggler-segment configuration. This shortening can be even more dramatic if a nonlinear harmonic generation mechanism is used to reach the desired wavelength. An example operating at a 4.5{angstrom} fundamental and a 1.5{angstrom} harmonic is discussed.

  4. Second harmonic generation in a molecular magnetic chain

    NASA Astrophysics Data System (ADS)

    Cavigli, L.; Sessoli, R.; Gurioli, M.; Bogani, L.

    2006-05-01

    A setup for the determination of all the components of the second harmonic generation tensor in molecular materials is presented. It allows overcoming depletion problems, which one can expect to be common in molecular systems. A preliminary characterization of the nonlinear properties of the single chain magnet CoPhOMe is carried out. We observe a high second harmonic signal, comparable to that of urea, and show that the bulk contributions are dominant over the surface ones.

  5. Field localization and enhancement of phase-locked second- and third-order harmonic generation in absorbing semiconductor cavities

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

    Roppo, V.; Charles M. Bowden Research Facility, US Army RDECOM, Redstone Arsenal, Alabama 35803; Cojocaru, C.

    We predict and experimentally observe the enhancement by three orders of magnitude of phase mismatched second and third harmonic generation in a GaAs cavity at 650 and 433 nm, respectively, well above the absorption edge. Phase locking between the pump and the harmonics changes the effective dispersion of the medium and inhibits absorption. Despite hostile conditions the harmonics resonate inside the cavity and become amplified leading to relatively large conversion efficiencies. Field localization thus plays a pivotal role despite the presence of absorption, and ushers in a new class of semiconductor-based devices in the visible and uv ranges.

  6. Second harmonic generation: Effects of the multiple reflections of the fundamental and the second harmonic waves on the Maker fringes

    NASA Astrophysics Data System (ADS)

    Tellier, Gildas; Boisrobert, Christian

    2007-11-01

    The Maker fringes technique is commonly used for the determination of nonlinear optical coefficients. In this article, we present a new formulation of Maker fringes in parallel-surface samples, using boundary conditions taking into account the anisotropy of the crystal, the refractive-index dispersion, and the reflections of the fundamental and the second harmonic waves inside the material. Complete expressions for the generated second harmonic intensity are given for birefringent crystals for the case of no pump depletion. A comparison between theory and experimental results is made, showing the accuracy of our theoretical expressions.

  7. Enhanced attosecond pulse generation in the vacuum ultraviolet using a two-colour driving field for high harmonic generation

    NASA Astrophysics Data System (ADS)

    Matía-Hernando, P.; Witting, T.; Walke, D. J.; Marangos, J. P.; Tisch, J. W. G.

    2018-03-01

    High-harmonic radiation in the extreme ultraviolet and soft X-ray spectral regions can be used to generate attosecond pulses and to obtain structural and dynamic information in atoms and molecules. However, these sources typically suffer from a limited photon flux. An additional issue at lower photon energies is the appearance of satellites in the time domain, stemming from insufficient temporal gating and the spectral filtering required for the isolation of attosecond pulses. Such satellites limit the temporal resolution. The use of multi-colour driving fields has been proven to enhance the harmonic yield and provide additional control, using the relative delays between the different spectral components for waveform shaping. We describe here a two-colour high-harmonic source that combines a few-cycle near-infrared pulse with a multi-cycle second harmonic pulse, with both relative phase and carrier-envelope phase stabilization. We observe strong modulations in the harmonic flux, and present simulations and experimental results supporting the suppression of satellites in sub-femtosecond pulses at 20 eV compared to the single colour field case, an important requirement for attosecond pump-probe measurements.

  8. Method and apparatus for reducing spacecraft instrument induced jitter via multifrequency cancellation

    NASA Technical Reports Server (NTRS)

    Liu, Ketao (Inventor); Uetrecht, David S. (Inventor)

    2002-01-01

    A method, apparatus, article of manufacture, and a memory structure for compensating for instrument induced spacecraft jitter is disclosed. The apparatus comprises a spacecraft control processor for producing an actuator command signal, a signal generator, for producing a cancellation signal having at least one harmonic having a frequency and an amplitude substantially equal to that of a disturbance harmonic interacting with a spacecraft structural resonance and a phase substantially out of phase with the disturbance harmonic interacting with the spacecraft structural resonance, and at least one spacecraft control actuator, communicatively coupled to the spacecraft control processor and the signal generator for inducing satellite motion according to the actuator command signal and the cancellation signal. The method comprises the steps of generating a cancellation signal having at least one harmonic having a frequency and an amplitude substantially equal to that of a disturbance harmonic interacting with a spacecraft structural resonance and a phase substantially out of phase with the disturbance harmonic interacting with the spacecraft structural resonance, and providing the cancellation signal to a spacecraft control actuator. The apparatus comprises a storage device tangibly embodying the method steps described above.

  9. Effect of skew angle on second harmonic guided wave measurement in composite plates

    NASA Astrophysics Data System (ADS)

    Cho, Hwanjeong; Choi, Sungho; Lissenden, Cliff J.

    2017-02-01

    Waves propagating in anisotropic media are subject to skewing effects due to the media having directional wave speed dependence, which is characterized by slowness curves. Likewise, the generation of second harmonics is sensitive to micro-scale damage that is generally not detectable from linear features of ultrasonic waves. Here, the effect of skew angle on second harmonic guided wave measurement in a transversely isotropic lamina and a quasi-isotropic laminate are numerically studied. The strain energy density function for a nonlinear transversely isotropic material is formulated in terms of the Green-Lagrange strain invariants. The guided wave mode pairs for cumulative second harmonic generation in the plate are selected in accordance with the internal resonance criteria - i.e., phase matching and non-zero power flux. Moreover, the skew angle dispersion curves for the mode pairs are obtained from the semi-analytical finite element method using the derivative of the slowness curve. The skew angles of the primary and secondary wave modes are calculated and wave propagation simulations are carried out using COMSOL. Numerical simulations revealed that the effect of skew angle mismatch can be significant for second harmonic generation in anisotropic media. The importance of skew angle matching on cumulative second harmonic generation is emphasized and the accompanying issue of the selection of internally resonant mode pairs for both a unidirectional transversely isotropic lamina and a quasi-isotropic laminate is demonstrated.

  10. High-Harmonic Generation in Solids with and without Topological Edge States

    NASA Astrophysics Data System (ADS)

    Bauer, Dieter; Hansen, Kenneth K.

    2018-04-01

    High-harmonic generation in the two topological phases of a finite, one-dimensional, periodic structure is investigated using a self-consistent time-dependent density functional theory approach. For harmonic photon energies smaller than the band gap, the harmonic yield is found to differ by up to 14 orders of magnitude for the two topological phases. This giant topological effect is explained by the degree of destructive interference in the harmonic emission of all valence-band (and edge-state) electrons, which strongly depends on whether or not topological edge states are present. The combination of strong-field laser physics with topological condensed matter opens up new possibilities to electronically control strong-field-based light or particle sources or—conversely—to steer by all optical means topological electronics.

  11. Enhancement of high harmonics from plasmas using two-color pump and chirp variation of 1 kHz Ti:sapphire laser pulses.

    PubMed

    Ganeev, R A; Hutchison, C; Zaïr, A; Witting, T; Frank, F; Okell, W A; Tisch, J W G; Marangos, J P

    2012-01-02

    We have investigated resonance effects in high-order harmonic generation (HHG) within laser-produced plasmas. We demonstrate a significantly improved harmonic yield by using two-color pump-induced enhancement and a 1 kHz pulse repetition rate. Together with an increased HHG output, the even harmonics in the cutoff region were enhanced with respect to odd harmonics. We report the observation of a resonance-induced growth in intensity of 20th harmonic in silver plasma (2×), 26th harmonic in vanadium plasma (4×), and 28th harmonic in chromium plasma (5×).

  12. 77 FR 70467 - Agency Information Collection Activities: Proposed Collection; Comments Requested; ATF...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-26

    ... DEPARTMENT OF JUSTICE Bureau of Alcohol, Tobacco, Firearms and Explosives [OMB Number 1140-0001] Agency Information Collection Activities: Proposed Collection; Comments Requested; ATF Distribution Center Contractor Survey ACTION: 30-day notice. The Department of Justice (DOJ), Bureau of Alcohol...

  13. Dispersion tuning in sub-micron tapers for third-harmonic and photon triplet generation.

    PubMed

    Hammer, Jonas; Cavanna, Andrea; Pennetta, Riccardo; Chekhova, Maria V; Russell, Philip St J; Joly, Nicolas Y

    2018-05-15

    Precise control of the dispersion landscape is of crucial importance if optical fibers are to be successfully used for the generation of three-photon states of light-the inverse of third-harmonic generation (THG). Here we report gas-tuning of intermodal phase-matched THG in sub-micron-diameter tapered optical fiber. By adjusting the pressure of the surrounding argon gas up to 50 bars, intermodally phase-matched third-harmonic light can be generated for pump wavelengths within a 15 nm range around 1.38 μm. We also measure the infrared fluorescence generated in the fiber when pumped in the visible and estimate that the accidental coincidence rate in this signal is lower than the predicted detection rate of photon triplets.

  14. Strong second harmonic generation in two-dimensional ferroelectric IV-monochalcogenides

    NASA Astrophysics Data System (ADS)

    Panday, Suman Raj; Fregoso, Benjamin M.

    2017-11-01

    The two-dimensional ferroelectrics GeS, GeSe, SnS and SnSe are expected to have large spontaneous in-plane electric polarization and enhanced shift-current response. Using density functional methods, we show that these materials also exhibit the largest effective second harmonic generation reported so far. It can reach magnitudes up to 10~nm~V-1 which is about an order of magnitude larger than that of prototypical GaAs. To rationalize this result we model the optical response with a simple one-dimensional two-band model along the spontaneous polarization direction. Within this model the second-harmonic generation tensor is proportional to the shift-current response tensor. The large shift current and second harmonic responses of GeS, GeSe, SnS and SnSe make them promising non-linear materials for optoelectronic applications.

  15. Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats.

    PubMed

    Fang, Jian-Qiao; Du, Jun-Ying; Liang, Yi; Fang, Jun-Fan

    2013-03-22

    Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat's paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats.

  16. Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats

    PubMed Central

    2013-01-01

    Background Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. Results EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat’s paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. Conclusions The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats. PMID:23517865

  17. Mutation of ATF6 causes autosomal recessive achromatopsia.

    PubMed

    Ansar, Muhammad; Santos-Cortez, Regie Lyn P; Saqib, Muhammad Arif Nadeem; Zulfiqar, Fareeha; Lee, Kwanghyuk; Ashraf, Naeem Mahmood; Ullah, Ehsan; Wang, Xin; Sajid, Sundus; Khan, Falak Sher; Amin-ud-Din, Muhammad; Smith, Joshua D; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Hameed, Abdul; Riazuddin, Saima; Ahmed, Zubair M; Ahmad, Wasim; Leal, Suzanne M

    2015-09-01

    Achromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3, CNGB3, GNAT2, PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1-q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Glyfs*8) was identified, which completely segregates with the ACHM phenotype within the family. The frameshift variant was absent in public variant databases, in 130 exomes from unrelated Pakistani individuals, and in 235 ethnically matched controls. The variant is predicted to result in a truncated protein that lacks the DNA binding and transmembrane domains and therefore affects the function of ATF6 as a transcription factor that initiates the unfolded protein response during endoplasmic reticulum (ER) stress. Immunolabeling with anti-ATF6 antibodies showed localization throughout the mouse neuronal retina, including retinal pigment epithelium, photoreceptor cells, inner nuclear layer, inner and outer plexiform layers, with a more prominent signal in retinal ganglion cells. In contrast to cytoplasmic expression of wild-type protein, in heterologous cells ATF6 protein with the p.Glu119Glyfs*8 variant is mainly confined to the nucleus. Our results imply that response to ER stress as mediated by the ATF6 pathway is essential for color vision in humans.

  18. Towards improved NDE and SHM methodologies incorporating nonlinear structural features

    NASA Astrophysics Data System (ADS)

    Chillara, Vamshi Krishna

    Ultrasound is widely employed in Nondestructive Evaluation (NDE) and Structural Health Monitoring (SHM) applications to detect and characterize damage/defects in materials. In particular, ultrasonic guided waves are considered a foremost candidate for in-situ monitoring applications. Conventional ultrasonic techniques rely on changes/discontinuities in linear elastic material properties, namely the Young's modulus and shear modulus to detect damage. On the other hand, nonlinear ultrasonic techniques that rely on micro-scale nonlinear material/structural behavior are proven to be sensitive to damage induced microstructural changes that precede macro-scale damage and are hence capable of early damage detection. The goal of this thesis is to investigate the capabilities of nonlinear guided waves --- a fusion of nonlinear ultrasonic techniques with the guided wave methodologies for early damage detection. To that end, the thesis focuses on two important aspects of the problem: 1. Wavemechanics - deals with ultrasonic guided wave propagation in nonlinear waveguides; 2. Micromechanics - deals with correlating ultrasonic response with micro-scale nonlinear material behavior. For the development of efficient NDE and SHM methodologies that incorporate nonlinear structural features, a detailed understanding of the above aspects is indispensable. In this thesis, the wavemechanics aspect of the problem is dealt with from both theoretical and numerical standpoints. A generalized theoretical framework is developed to study higher harmonic guided waves in plates. This was employed to study second harmonic guided waves in pipes using a large-radius asymptotic approximation. Second harmonic guided waves in plates are studied from a numerical standpoint. Theoretical predictions are validated and some key aspects of higher harmonic generation in waveguides are outlined. Finally, second harmonic guided waves in plates with inhomogeneous and localized nonlinearities are studied and some important aspects of guided wave mode selection are addressed. The other part of the work focused on developing a micromechanics based understanding of ultrasonic higher harmonic generation. Three important aspects of micro-scale material behavior, namely tension-compression asymmetry, shearnormal coupling and deformation induced asymmetry are identified and their role in ultrasonic higher harmonic generation is discussed. Tension-compression asymmetry is identified to cause second (even) harmonic generation in materials. Then, shearnormal coupling is identified to cause generation of secondary waves of different polarity than the primary waves. In addition, deformation induced anisotropy due to the presence of residual stress/strain and its contribution to ultrasonic higher harmonic generation is qualitatively discussed. Also, the tension-compression asymmetry in the material is quantified using an energy based measure. The above measure is employed to develop a homogenization based approach amenable to multi-scale analysis to correlate microstructure with ultrasonic higher harmonic generation. Finally, experimental investigations concerning third harmonic SH wave generation in plates are carried out and the effect of load and temperature changes on nonlinear ultrasonic measurements are discussed in the context of SHM. It was found that while nonlinear ultrasound is sensitive to micro-scale damage, the relative nonlinearity parameter may not always be the best measure to quantify the nonlinearity as it is subject to spurious effects from changes in environmental factors such as loads and temperature.

  19. Ultrafast Plasmonic Control of Second Harmonic Generation

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

    Davidson, Roderick B.; Yanchenko, Anna; Ziegler, Jed I.

    Efficient frequency conversion techniques are crucial to the development of plasmonic metasurfaces for information processing and signal modulation. In principle, nanoscale electric-field confinement in nonlinear materials enables higher harmonic conversion efficiencies per unit volume than those attainable in bulk materials. Here we demonstrate efficient second-harmonic generation (SHG) in a serrated nanogap plasmonic geometry that generates steep electric field gradients on a dielectric metasurface. An ultrafast control pulse is used to control plasmon-induced electric fields in a thin-film material with inversion symmetry that, without plasmonic enhancement, does not exhibit an even-order nonlinear optical response. The temporal evolution of the plasmonic near-fieldmore » is characterized with ~100 as resolution using a novel nonlinear interferometric technique. The serrated nanogap is a unique platform in which to investigate optically controlled, plasmonically enhanced harmonic generation in dielectric materials on an ultrafast time scale. Lastly, this metamaterial geometry can also be readily extended to all-optical control of other nonlinear phenomena, such as four-wave mixing and sum- and difference-frequency generation, in a wide variety of dielectric materials.« less

  20. Ultrafast Plasmonic Control of Second Harmonic Generation

    DOE PAGES

    Davidson, Roderick B.; Yanchenko, Anna; Ziegler, Jed I.; ...

    2016-06-01

    Efficient frequency conversion techniques are crucial to the development of plasmonic metasurfaces for information processing and signal modulation. In principle, nanoscale electric-field confinement in nonlinear materials enables higher harmonic conversion efficiencies per unit volume than those attainable in bulk materials. Here we demonstrate efficient second-harmonic generation (SHG) in a serrated nanogap plasmonic geometry that generates steep electric field gradients on a dielectric metasurface. An ultrafast control pulse is used to control plasmon-induced electric fields in a thin-film material with inversion symmetry that, without plasmonic enhancement, does not exhibit an even-order nonlinear optical response. The temporal evolution of the plasmonic near-fieldmore » is characterized with ~100 as resolution using a novel nonlinear interferometric technique. The serrated nanogap is a unique platform in which to investigate optically controlled, plasmonically enhanced harmonic generation in dielectric materials on an ultrafast time scale. Lastly, this metamaterial geometry can also be readily extended to all-optical control of other nonlinear phenomena, such as four-wave mixing and sum- and difference-frequency generation, in a wide variety of dielectric materials.« less

  1. Large enhancement of second harmonic generation from transition-metal dichalcogenide monolayer on grating near bound states in the continuum.

    PubMed

    Wang, Tiecheng; Zhang, Shihao

    2018-01-08

    Second harmonic generation from the two-layer structure where a transition-metal dichalcogenide monolayer is put on a one-dimensional grating has been studied. This grating supports bound states in the continuum which have no leakage lying within the continuum of radiation modes, we can enhance the second harmonic generation from the transition-metal dichalcogenide monolayer by more than four orders of magnitude based on the critical field enhancement near the bound states in the continuum. In order to complete this calculation, the scattering matrix theory has been extended to include the nonlinear effect and the scattering matrix of a two-dimensional material including nonlinear terms; furthermore, two methods to observe the bound states in the continuum are considered, where one is tuning the thickness of the grating and the other is changing the incident angle of the electromagnetic wave. We have also discussed various modulation of the second harmonic generation enhancement by adjusting the azimuthal angle of the transition-metal dichalcogenide monolayer.

  2. Non-critical phase-matching fourth harmonic generation of a 1053-nm laser in an ADP crystal

    PubMed Central

    Ji, Shaohua; Wang, Fang; Zhu, Lili; Xu, Xinguang; Wang, Zhengping; Sun, Xun

    2013-01-01

    In current inertial confinement fusion (ICF) facilities, KDP and DKDP crystals are the second harmonic generation (SHG) and third harmonic generation (THG) materials for the Nd:glass laser (1053 nm). Based on the trend for the development of short wavelengths for ICF driving lasers, technical solutions for fourth harmonic generation (FHG) will undoubtedly attract more and more attention. In this paper, the rapid growth of an ADP crystal and non-critical phase-matching (NCPM) FHG of a 1053-nm laser using an ADP crystal are reported. The NCPM temperature is 33.7°C. The conversion efficiency from 526 to 263 nm is 70%, and the angular acceptance range is 55.4 mrad; these results are superior to those for the DKDP crystals. This research has shown that ADP crystals will be a competitive candidate in future ICF facilities when the utilisation of high-energy, high-efficiency UV lasers at wavelengths shorter than the present 351 nm is of interest. PMID:23549389

  3. Below-threshold harmonic generation from strong non-uniform fields

    NASA Astrophysics Data System (ADS)

    Yavuz, I.

    2017-10-01

    Strong-field photoemission below the ionization threshold is a rich/complex region where atomic emission and harmonic generation may coexist. We studied the mechanism of below-threshold harmonics (BTH) from spatially non-uniform local fields near the metallic nanostructures. Discrete harmonics are generated due to the broken inversion symmetry, suggesting enriched coherent emission in the vuv frequency range. Through the numerical solution of the time-dependent Schrödinger equation, we investigate wavelength and intensity dependence of BTH. Wavelength dependence identifies counter-regular resonances; individual contributions from the multi-photon emission and channel-closing effects due to quantum path interferences. In order to understand the underlying mechanism of BTH, we devised a generalized semi-classical model, including the influence of Coulomb and non-uniform field interactions. As in uniform fields, Coulomb potential in non-uniform fields is the determinant of BTH; we observed that the generation of BTH are due to returning trajectories with negative energies. Due to large distance effectiveness of the non-uniformity, only long trajectories are noticeably affected.

  4. Non-critical phase-matching fourth harmonic generation of a 1053-nm laser in an ADP crystal.

    PubMed

    Ji, Shaohua; Wang, Fang; Zhu, Lili; Xu, Xinguang; Wang, Zhengping; Sun, Xun

    2013-01-01

    In current inertial confinement fusion (ICF) facilities, KDP and DKDP crystals are the second harmonic generation (SHG) and third harmonic generation (THG) materials for the Nd:glass laser (1053 nm). Based on the trend for the development of short wavelengths for ICF driving lasers, technical solutions for fourth harmonic generation (FHG) will undoubtedly attract more and more attention. In this paper, the rapid growth of an ADP crystal and non-critical phase-matching (NCPM) FHG of a 1053-nm laser using an ADP crystal are reported. The NCPM temperature is 33.7°C. The conversion efficiency from 526 to 263 nm is 70%, and the angular acceptance range is 55.4 mrad; these results are superior to those for the DKDP crystals. This research has shown that ADP crystals will be a competitive candidate in future ICF facilities when the utilisation of high-energy, high-efficiency UV lasers at wavelengths shorter than the present 351 nm is of interest.

  5. Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice

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

    Trindade, Sandra; Rijo-Ferreira, Filipa; Carvalho, Tania

    Trypanosoma brucei is an extracellular parasite that causes sleeping sickness. In mammalian hosts, trypanosomes are thought to exist in two major niches: early in infection, they populate the blood; later, they breach the blood-brain barrier. Working with a well-established mouse model, we discovered that adipose tissue constitutes a third major reservoir for T. brucei. Parasites from adipose tissue, here termed adipose tissue forms (ATFs), can replicate and were capable of infecting a naive animal. ATFs were transcriptionally distinct from bloodstream forms, and the genes upregulated included putative fatty acid β-oxidation enzymes. Consistent with this, ATFs were able to utilize exogenousmore » myristate and form β-oxidation intermediates, suggesting that ATF parasites can use fatty acids as an external carbon source. Lastly, these findings identify the adipose tissue as a niche for T. brucei during its mammalian life cycle and could potentially explain the weight loss associated with sleeping sickness.« less

  6. Engineering an allosteric transcription factor to respond to new ligands

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

    Taylor, Noah D.; Garruss, Alexander S.; Moretti, Rocco

    Genetic regulatory proteins inducible by small molecules are useful synthetic biology tools as sensors and switches. Bacterial allosteric transcription factors (aTFs) are a major class of regulatory proteins, but few aTFs have been redesigned to respond to new effectors beyond natural aTF-inducer pairs. Altering inducer specificity in these proteins is difficult because substitutions that affect inducer binding may also disrupt allostery. In this paper, we engineered an aTF, the Escherichia coli lac repressor, LacI, to respond to one of four new inducer molecules: fucose, gentiobiose, lactitol and sucralose. Using computational protein design, single-residue saturation mutagenesis or random mutagenesis, along withmore » multiplex assembly, we identified new variants comparable in specificity and induction to wild-type LacI with its inducer, isopropyl β-D-1-thiogalactopyranoside (IPTG). Finally, the ability to create designer aTFs will enable applications including dynamic control of cell metabolism, cell biology and synthetic gene circuits.« less

  7. Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice

    DOE PAGES

    Trindade, Sandra; Rijo-Ferreira, Filipa; Carvalho, Tania; ...

    2016-05-26

    Trypanosoma brucei is an extracellular parasite that causes sleeping sickness. In mammalian hosts, trypanosomes are thought to exist in two major niches: early in infection, they populate the blood; later, they breach the blood-brain barrier. Working with a well-established mouse model, we discovered that adipose tissue constitutes a third major reservoir for T. brucei. Parasites from adipose tissue, here termed adipose tissue forms (ATFs), can replicate and were capable of infecting a naive animal. ATFs were transcriptionally distinct from bloodstream forms, and the genes upregulated included putative fatty acid β-oxidation enzymes. Consistent with this, ATFs were able to utilize exogenousmore » myristate and form β-oxidation intermediates, suggesting that ATF parasites can use fatty acids as an external carbon source. Lastly, these findings identify the adipose tissue as a niche for T. brucei during its mammalian life cycle and could potentially explain the weight loss associated with sleeping sickness.« less

  8. Fabrication Control Plan for ORNL RH-LOCA ATF Test Specimens to be Irradiated in the ATR

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

    Field, Kevin G.; Howard, Richard; Teague, Michael

    2014-06-01

    The purpose of this fabrication plan is (1) to summarize the design of a set of rodlets that will be fabricated and then irradiated in the Advanced Test Reactor (ATR) and (2) provide requirements for fabrication and acceptance criteria for inspections of the Light Water Reactor (LWR) – Accident Tolerant Fuels (ATF) rodlet components. The functional and operational (F&OR) requirements for the ATF program are identified in the ATF Test Plan. The scope of this document only covers fabrication and inspections of rodlet components detailed in drawings 604496 and 604497. It does not cover the assembly of these items tomore » form a completed test irradiation assembly or the inspection of the final assembly, which will be included in a separate INL final test assembly specification/inspection document. The controls support the requirements that the test irradiations must be performed safely and that subsequent examinations must provide valid results.« less

  9. Bioleaching of two different types of chalcopyrite by Acidithiobacillus ferrooxidans

    NASA Astrophysics Data System (ADS)

    Dong, Ying-bo; Lin, Hai; Fu, Kai-bin; Xu, Xiao-fang; Zhou, Shan-shan

    2013-02-01

    Two different types of chalcopyrite (pyritic chalcopyrite and porphyry chalcopyrite) were bioleached with Acidithiobacillus ferrooxidans ATF6. The bioleaching of the pyritic chalcopyrite and porphyry chalcopyrite is quite different. The copper extraction reaches 46.96% for the pyritic chalcopyrite after 48-d leaching, but it is only 14.50% for the porphyry chalcopyrite. Proper amounts of initial ferrous ions can improve the efficiency of copper extraction for the two different types of chalcopyrite. The optimum dosage of ferrous ions for the pyritic chalcopyrite and porphyry chalcopyrite is different. The adsorption of ATF6 on the pyritic chalcopyrite and porphyry chalcopyrite was also studied in this paper. It is found that ATF6 is selectively adsorbed by the two different types of chalcopyrite; the higher adsorption onto the pyritic chalcopyrite than the porphyry chalcopyrite leads to the higher copper dissolution rate of the pyritic chalcopyrite. In addition, the zeta-potential of chalcopyrite before and after bioleaching further confirms that ATF6 is more easily adsorbed onto the pyritic chalcopyrite.

  10. Engineering an allosteric transcription factor to respond to new ligands

    DOE PAGES

    Taylor, Noah D.; Garruss, Alexander S.; Moretti, Rocco; ...

    2015-12-21

    Genetic regulatory proteins inducible by small molecules are useful synthetic biology tools as sensors and switches. Bacterial allosteric transcription factors (aTFs) are a major class of regulatory proteins, but few aTFs have been redesigned to respond to new effectors beyond natural aTF-inducer pairs. Altering inducer specificity in these proteins is difficult because substitutions that affect inducer binding may also disrupt allostery. In this paper, we engineered an aTF, the Escherichia coli lac repressor, LacI, to respond to one of four new inducer molecules: fucose, gentiobiose, lactitol and sucralose. Using computational protein design, single-residue saturation mutagenesis or random mutagenesis, along withmore » multiplex assembly, we identified new variants comparable in specificity and induction to wild-type LacI with its inducer, isopropyl β-D-1-thiogalactopyranoside (IPTG). Finally, the ability to create designer aTFs will enable applications including dynamic control of cell metabolism, cell biology and synthetic gene circuits.« less

  11. Third harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Squier, Jeffrey A.; Muller, Michiel; Brakenhoff, G. J.; Wilson, Kent R.

    1998-10-01

    Third harmonic generation microscopy is used to make dynamical images of living systems for the first time. A 100 fs excitation pulse at 1.2 æm results in a 400 nm signal which is generated directly within the specimen. Chara plant rhizoids have been imaged, showing dynamic plant activity, and non-fading image characteristics even with continuous viewing, indicating prolonged viability under these THG-imaging conditions.

  12. Broadband dynamic phase matching of high-order harmonic generation by a high-peak-power soliton pump field in a gas-filled hollow photonic-crystal fiber.

    PubMed

    Serebryannikov, Evgenii E; von der Linde, Dietrich; Zheltikov, Aleksei M

    2008-05-01

    Hollow-core photonic-crystal fibers are shown to enable dynamically phase-matched high-order harmonic generation by a gigawatt soliton pump field. With a careful design of the waveguide structure and an appropriate choice of input-pulse and gas parameters, a remarkably broadband phase matching can be achieved for a soliton pump field and a large group of optical harmonics in the soft-x-ray-extreme-ultraviolet spectral range.

  13. Second harmonic generation in gallium phosphide photonic crystal nanocavities with ultralow continuous wave pump power.

    PubMed

    Rivoire, Kelley; Lin, Ziliang; Hatami, Fariba; Masselink, W Ted; Vucković, Jelena

    2009-12-07

    We demonstrate second harmonic generation in photonic crystal nanocavities fabricated in the semiconductor gallium phosphide. We observe second harmonic radiation at 750 nm with input powers of only nanowatts coupled to the cavity and conversion effciency P(out)/P(2)(in,coupled)=430%/W. The large electronic band gap of GaP minimizes absorption loss, allowing effcient conversion. Our results are promising for integrated, low-power light sources and on-chip reduction of input power in other nonlinear processes.

  14. Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake.

    PubMed

    Kobylewski, Sarah E; Henderson, Kimberly A; Yamada, Kristin E; Eckhert, Curtis D

    2017-04-01

    Fruits, nuts, legumes, and vegetables are rich sources of boron (B), an essential plant nutrient with chemopreventive properties. Blood boric acid (BA) levels reflect recent B intake, and men at the US mean intake have a reported non-fasting level of 10 μM. Treatment of DU-145 prostate cancer cells with physiological concentrations of BA inhibits cell proliferation without causing apoptosis and activates eukaryotic initiation factor 2 (eIF2α). EIF2α induces cell differentiation and protects cells by redirecting gene expression to manage endoplasmic reticulum stress. Our objective was to determine the temporal expression of endoplasmic reticulum (ER) stress-activated genes in DU-145 prostate cells treated with 10 μM BA. Immunoblots showed post-treatment increases in eIF2α protein at 30 min and ATF4 and ATF6 proteins at 1 h and 30 min, respectively. The increase in ATF4 was accompanied by an increase in the expression of its downstream genes growth arrest and DNA damage-induced protein 34 (GADD34) and homocysteine-induced ER protein (Herp), but a decrease in GADD153/CCAAT/enhancer-binding protein homologous protein (CHOP), a pro-apoptotic gene. The increase in ATF6 was accompanied by an increase in expression of its downstream genes GRP78/BiP, calreticulin, Grp94, and EDEM. BA did not activate IRE1 or induce cleavage of XBP1 mRNA, a target of IRE1. Low boron status has been associated with increased cancer risk, low bone mineralization, and retinal degeneration. ATF4 and BiP/GRP78 function in osteogenesis and bone remodeling, calreticulin is required for tumor suppressor p53 function and mineralization of teeth, and BiP/GRP78 and EDEM prevent the aggregation of misfolded opsins which leads to retinal degeneration. The identification of BA-activated genes that regulate its phenotypic effects provides a molecular underpinning for boron nutrition and biology.

  15. Comparative transcriptome analysis revealing dormant conidia and germination associated genes in Aspergillus species: an essential role for AtfA in conidial dormancy.

    PubMed

    Hagiwara, Daisuke; Takahashi, Hiroki; Kusuya, Yoko; Kawamoto, Susumu; Kamei, Katsuhiko; Gonoi, Tohru

    2016-05-17

    Fungal conidia are usually dormant unless the extracellular conditions are right for germination. Despite the importance of dormancy, little is known about the molecular mechanism underlying entry to, maintenance of, and exit from dormancy. To gain comprehensive and inter-species insights, transcriptome analyses were conducted across Aspergillus fumigatus, Aspergillus niger, and Aspergillus oryzae. We found transcripts of 687, 694, and 812 genes were enriched in the resting conidia compared with hyphae in A. fumigatus, A. niger, and A. oryzae, respectively (conidia-associated genes). Similarly, transcripts of 766, 1,241, and 749 genes were increased in the 1 h-cultured conidia compared with the resting conidia (germination-associated genes). Among the three Aspergillus species, we identified orthologous 6,172 genes, 91 and 391 of which are common conidia- and germination-associated genes, respectively. A variety of stress-related genes, including the catalase genes, were found in the common conidia-associated gene set, and ribosome-related genes were significantly enriched among the germination-associated genes. Among the germination-associated genes, we found that calA-family genes encoding a thaumatin-like protein were extraordinary expressed in early germination stage in all Aspergillus species tested here. In A. fumigatus 63 % of the common conidia-associated genes were expressed in a bZIP-type transcriptional regulator AtfA-dependent manner, indicating that AtfA plays a pivotal role in the maintenance of resting conidial physiology. Unexpectedly, the precocious expression of the germination-associated calA and an abnormal metabolic activity were detected in the resting conidia of the atfA mutant, suggesting that AtfA was involved in the retention of conidial dormancy. A comparison among transcriptomes of hyphae, resting conidia, and 1 h-grown conidia in the three Aspergillus species revealed likely common factors involved in conidial dormancy. AtfA positively regulates conidial stress-related genes and negatively mediates the gene expressions related to germination, suggesting a major role for AtfA in Aspergillus conidial dormancy.

  16. Probabilistic Harmonic Analysis on Distributed Photovoltaic Integration Considering Typical Weather Scenarios

    NASA Astrophysics Data System (ADS)

    Bin, Che; Ruoying, Yu; Dongsheng, Dang; Xiangyan, Wang

    2017-05-01

    Distributed Generation (DG) integrating to the network would cause the harmonic pollution which would cause damages on electrical devices and affect the normal operation of power system. On the other hand, due to the randomness of the wind and solar irradiation, the output of DG is random, too, which leads to an uncertainty of the harmonic generated by the DG. Thus, probabilistic methods are needed to analyse the impacts of the DG integration. In this work we studied the harmonic voltage probabilistic distribution and the harmonic distortion in distributed network after the distributed photovoltaic (DPV) system integrating in different weather conditions, mainly the sunny day, cloudy day, rainy day and the snowy day. The probabilistic distribution function of the DPV output power in different typical weather conditions could be acquired via the parameter identification method of maximum likelihood estimation. The Monte-Carlo simulation method was adopted to calculate the probabilistic distribution of harmonic voltage content at different frequency orders as well as the harmonic distortion (THD) in typical weather conditions. The case study was based on the IEEE33 system and the results of harmonic voltage content probabilistic distribution as well as THD in typical weather conditions were compared.

  17. High harmonic generation in rare gas solids

    NASA Astrophysics Data System (ADS)

    Reis, David

    2015-05-01

    There has recently been renewed interest in the interaction of strong optical fields with large band-gap solids. The response is known to involve the attosecond dynamics of the electrons and includes the generation of non-perturbative high-order harmonics. However, the detailed mechanism remain a matter of intense debate. Here we report on high harmonic generation in rare gas solids as compared to a dilute gas. The measured spectrum in the solid exhibits a secondary plateau and a subsequent high-energy cut-off that extends well beyond the gas phase, while the ellipticity dependence is simlar to the gas phase and suggests importance of coherent single-site recombination.

  18. Generation of single attosecond pulse within one atomic unit by using multi-cycle inhomogeneous polarization gating technology in bowtie-shaped nanostructure

    NASA Astrophysics Data System (ADS)

    Feng, Liqiang; Liu, Hang

    2018-04-01

    The generations of high-order harmonic spectra and single attosecond pulses (SAPs) driven by the multi-cycle inhomogeneous polarization gating (PG) technology in the bowtie-shaped nanostructure have been theoretically investigated. It is found that by setting the bowtie-shaped nanostructure along the driven laser polarization direction, not only the extension of the harmonic cutoff can be achieved, caused by the surface plasmon polaritons, but also the modulations of the harmonics can be decreased, caused by the PG technology and the inhomogeneous effect. As a result, the contribution of the harmonic plateau is only from one harmonic emission peak with the dominant short quantum path. Further, by properly adding a half-cycle pulse into the driven laser field, the harmonic emission process can be precisely controlled in the half-cycle duration and a supercontinuum with the bandwidth of 263 eV can be obtained. Finally, by directly superposing the harmonics from this supercontinuum, a SAP with the full width at half maximum of 23 as can be obtained, which is shorter than one atomic unit.

  19. Harmonic generation with multiple wiggler schemes

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

    Bonifacio, R.; De Salvo, L.; Pierini, P.

    1995-02-01

    In this paper the authors give a simple theoretical description of the basic physics of the single pass high gain free electron laser (FEL), describing in some detail the FEL bunching properties and the harmonic generation technique with a multiple-wiggler scheme or a high gain optical klystron configuration.

  20. 27 CFR 555.165 - Failure to report theft or loss.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... report a theft of explosive materials in accordance with § 555.30 will be fined under title 18 U.S.C., imprisoned not more than 5 years, or both. [T.D. ATF-87, 46 FR 40384, Aug. 7, 1981, as amended by ATF No. 1...

  1. 27 CFR 555.165 - Failure to report theft or loss.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... report a theft of explosive materials in accordance with § 555.30 will be fined under title 18 U.S.C., imprisoned not more than 5 years, or both. [T.D. ATF-87, 46 FR 40384, Aug. 7, 1981, as amended by ATF No. 1...

  2. 27 CFR 555.165 - Failure to report theft or loss.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... report a theft of explosive materials in accordance with § 555.30 will be fined under title 18 U.S.C., imprisoned not more than 5 years, or both. [T.D. ATF-87, 46 FR 40384, Aug. 7, 1981, as amended by ATF No. 1...

  3. Research on Harmonic Characteristic of Electronic Current Transformer Based on the Rogowski Coil

    NASA Astrophysics Data System (ADS)

    Shen, Diqiu; Hu, Bei; Wang, Xufeng; Zhu, Mingdong; Wang, Liang; Lu, Wenxing

    2017-05-01

    The nonlinear load present in the power system will cause the distortion of AC sine wave and generate the harmonic, which havea severe impact on the accuracy of energy metering and reliability of relay protection. Tosatisfy the requirements of energy metering and relay protection for the new generation of intelligent substation, based on the working principle of Rogowski coil current transformer, mathematical model and transfer characteristics of Rogowski coil sensors were studied in this paper, and frequency response characteristics of Rogowski coil current transformer system were analysed. Finally, the frequency response characteristics of the Rogowski coil current transformer at 2 to 13 harmonics was simulated and experimented. Simulation and experiments show that Rogowski coil current transformer couldmeet 0.2 accuracy requirements of harmonic power measurement of power system, and measure the harmonic components of the grid reliably.

  4. Determination of genetic effects of ATF3 and CDKN1A genes on milk yield and compositions in Chinese Holstein population.

    PubMed

    Han, Bo; Liang, Weijun; Liu, Lin; Li, Yanhua; Sun, Dongxiao

    2017-05-19

    Our previous RNA-sequencing study revealed that the ATF3 and CDKN1A genes were remarkably differentially expressed between the mammary glands of lactating Holstein cows with extremely high and low milk protein and fat percentage so that both of them were considered as candidates for milk composition. Herein, we further verified whether these genes have genetic effects on milk production traits in a Chinese Holstein cow population. By re-sequencing the entire coding and regulatory regions, we identified four SNPs in 5'promoter region, two in exons, seven in 3' un-translated region (UTR), and six in 3'flanking region of ATF3 gene, and one SNP in exon 5, two in 3'UTR, and two in 3'flanking region of CDKN1A gene. Of these, only the SNP, c.271C > T (rs442346530), in exon 5 of CDKN1A gene was predicted to result in an amino acid replacement from arginine to tryptophan. Subsequent genotype-phenotype association analysis revealed that 19 SNPs in ATF3 and 5 SNPs in CDKN1A were evidently associated with 305-days milk yield, fat yield, protein yield, or protein percentage (P = < 0.0001 ~ 0.0494). Whilst, no significant SNPs in ATF3 gene were associated with fat percentage in both first and second lactations (P > 0.05), and only two SNPs of CDKN1A gene, c.271C > T (P = 0.0377) and c.*654C > T (P = 0.0144), were markedly associated with fat percentage in the first lactation. Further, linkage disequilibrium (LD) analyses were conducted among the identified SNPs in ATF3 and/or CDKN1A genes to further confirm the association results. We also observed that the four SNPs, g.72834301C > A, g.72834229C > A, g.72833969A > G, and g.72833562G > T altered the specific transcription factor (TF) binding sites in ATF3 promoter, and one SNP, c.271C > T, changed the CDKN1A protein secondary structure, suggesting they might be the promising potential functional mutations. Our findings first profiled the genetic effects of ATF3 and CDKN1A genes for milk production traits in dairy cattle and will be available for marker-assisted breeding in dairy cattle.

  5. Harmonic reduction by using single-tuned passive filter in plastic processing industry

    NASA Astrophysics Data System (ADS)

    Fahmi, M. I.; Baafai, U.; Hazmi, A.; Nasution, T. H.

    2018-02-01

    The using of non-linear loads generated by industrial machines may result inconsistent harmonics that do not reach the IEEE 519 - 1992 standards. This study discusses the use of single-tuned passive filters in reducing harmonics in the plastics processing industry. The system modeling using matlab / simulink simulation resulted in total harmonic distortion (THD) of 15.55%, can be reduced to 4.77% harmonics in accordance with IEEE 519 - 1992 standards. From the simulation results also seen that single-tuned passive filter can reduce the harmonics of the current 82.23% harmonic that wants to be reduced and also can reduce other orders harmonics between 7% to 8%.

  6. Maximum imaging depth comparison in porcine vocal folds using 776-nm vs. 1552-nm excitation wavelengths

    NASA Astrophysics Data System (ADS)

    Yildirim, Murat; Ferhanoglu, Onur; Kobler, James B.; Zeitels, Steven M.; Ben-Yakar, Adela

    2013-02-01

    Vocal fold scarring is one of the major causes of voice disorders and may arise from overuse or post-surgical wound healing. One promising treatment utilizes the injection of soft biomaterials aimed at restoring viscoelasticity of the outermost vibratory layer of the vocal fold, superficial lamina propria (SLP). However, the density of the tissue and the required injection pressure impair proper localization of the injected biomaterial in SLP. To enhance treatment effectiveness, we are investigating a technique to image and ablate sub-epithelial planar voids in vocal folds using ultrafast laser pulses to better localize the injected biomaterial. It is challenging to optimize the excitation wavelength to perform imaging and ablation at depths suitable for clinical use. Here, we compare maximum imaging depth using two photon autofluorescence and second harmonic generation with third-harmonic generation imaging modalities for healthy porcine vocal folds. We used a home-built inverted nonlinear scanning microscope together with a high repetition rate (2 MHz) ultrafast fiber laser (Raydiance Inc.). We acquired both two-photon autofluorescence and second harmonic generation signals using 776 nm wavelength and third harmonic generation signals using 1552 nm excitation wavelength. We observed that maximum imaging depth with 776 nm wavelength is significantly improved from 114 μm to 205 μm when third harmonic generation is employed using 1552 nm wavelength, without any observable damage in the tissue.

  7. High-order harmonic generation of CO and N2 molecules under linearly- and bi circularly-polarized laser pulses by TD-DFT

    NASA Astrophysics Data System (ADS)

    Koushki, A. M.; Sadighi-Bonabi, R.; Mohsen-Nia, M.; Irani, E.

    2018-07-01

    We present a method for high-order harmonics generation of N2 and CO molecules under two-color circularly polarized counter-rotating laser pulses at frequencies of and 2. Pulse envelope in this investigation is sin-squared and the intensity of each laser beam is with ten-optical cycle (o.c.). We show that an isolated pulse with a pulse duration shorter than 20 attosecond from the superposition of several harmonics can be generated. Both two-color linearly- and bicircularly-polarized laser pulses are considered. Our results have also been compared with the outcomes of the previous theoretical works as well as experiment observations. It is found that for CO molecule, the bicircularly-polarized laser pulses are superior and more efficient, and it can generate narrower attosecond pulses than the linearly-polarized pulses. While for N2 molecule, the two-color linearly-polarized pulses are more efficient, and it can generate narrower attosecond pulses than the bicircularly-polarized pulses. Furthermore, in order to demonstrate the origin of red- and blue-shifts in high-harmonic spectra, the effect of pulse duration on the high-order harmonics spectra is investigated. In addition, to obtain imaging on the temporal dependence of the electron densities, the time dependent electron localization function is used. Moreover, in order to study of the quantum trajectory of electrons, time-frequency analysis is utilized.

  8. Characterization of key triacylglycerol biosynthesis processes in rhodococci

    DOE PAGES

    Amara, Sawsan; Seghezzi, Nicolas; Otani, Hiroshi; ...

    2016-04-29

    In this study, oleaginous microorganisms have considerable potential for biofuel and commodity chemical production. Under nitrogen-limitation, Rhodococcus jostii RHA1 grown on benzoate, an analog of lignin depolymerization products, accumulated triacylglycerols (TAGs) to 55% of its dry weight during transition to stationary phase, with the predominant fatty acids being C16:0 and C17:0. Transcriptomic analyses of RHA1 grown under conditions of N-limitation and N-excess revealed 1,826 dysregulated genes. Genes whose transcripts were more abundant under N-limitation included those involved in ammonium assimilation, benzoate catabolism, fatty acid biosynthesis and the methylmalonyl-CoA pathway. Of the 16 atf genes potentially encoding diacylglycerol O-acyltransferases, atf8 transcriptsmore » were the most abundant during N-limitation (~50-fold more abundant than during N-excess). Consistent with Atf8 being a physiological determinant of TAG accumulation, a Δ atf8 mutant accumulated 70% less TAG than wild-type RHA1 while atf8 overexpression increased TAG accumulation 20%. Genes encoding type-2 phosphatidic acid phosphatases were not significantly expressed. By contrast, three genes potentially encoding phosphatases of the haloacid dehalogenase superfamily and that cluster with, or are fused with other Kennedy pathway genes were dysregulated. Overall, these findings advance our understanding of TAG metabolism in mycolic acid-containing bacteria and provide a framework to engineer strains for increased TAG production.« less

  9. Characterization of key triacylglycerol biosynthesis processes in rhodococci

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

    Amara, Sawsan; Seghezzi, Nicolas; Otani, Hiroshi

    In this study, oleaginous microorganisms have considerable potential for biofuel and commodity chemical production. Under nitrogen-limitation, Rhodococcus jostii RHA1 grown on benzoate, an analog of lignin depolymerization products, accumulated triacylglycerols (TAGs) to 55% of its dry weight during transition to stationary phase, with the predominant fatty acids being C16:0 and C17:0. Transcriptomic analyses of RHA1 grown under conditions of N-limitation and N-excess revealed 1,826 dysregulated genes. Genes whose transcripts were more abundant under N-limitation included those involved in ammonium assimilation, benzoate catabolism, fatty acid biosynthesis and the methylmalonyl-CoA pathway. Of the 16 atf genes potentially encoding diacylglycerol O-acyltransferases, atf8 transcriptsmore » were the most abundant during N-limitation (~50-fold more abundant than during N-excess). Consistent with Atf8 being a physiological determinant of TAG accumulation, a Δ atf8 mutant accumulated 70% less TAG than wild-type RHA1 while atf8 overexpression increased TAG accumulation 20%. Genes encoding type-2 phosphatidic acid phosphatases were not significantly expressed. By contrast, three genes potentially encoding phosphatases of the haloacid dehalogenase superfamily and that cluster with, or are fused with other Kennedy pathway genes were dysregulated. Overall, these findings advance our understanding of TAG metabolism in mycolic acid-containing bacteria and provide a framework to engineer strains for increased TAG production.« less

  10. ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer.

    PubMed

    Shi, Yanhua; Wang, Wei; Yang, Baozhi; Tian, Hongge

    2017-10-01

    Cervical cancer is one of the most common cancers among women worldwide. It is highly lethal yet can be treated when found in early stage. Thus, early detection is of significant important for early diagnosis of cervical cancer. Exosomes have been used as biomarkers in clinical diagnosis. It is unknown that whether blood exosomes associated with cervical cancer can be detected and if these exosomes can accurately represent the developmental stage of cervical cancer. Mouse models were made out of a relapsed cervical cancer patient's tumour sample for original and recurrent cervical cancer, and gene analysis in both tumours and exosomes in these mouse models were performed. We found that activating transcription factor 1 (ATF1) and RAS genes were significantly up-regulated in tumours of both primary and recurrent cervical cancer mouse model, and they can also be detected in the blood exosomes of the mouse model. Our results indicated that ATF1 and RAS could be potential candidate biomarkers for cervical cancer in early diagnosis. ATF1 and RAS genes were found significantly elevated in tumours of primary and recurrent cervical cancer mouse model, and they were also detected in the blood exosomes. Therefore, ATF1 and RAS could be used as a diagnostic marker for cervical cancer in the future. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Nonresonant Local Fields Enhance Second-Harmonic Generation from Metal Nanoislands with Dielectric Cover

    NASA Astrophysics Data System (ADS)

    Chervinskii, Semyon; Koskinen, Kalle; Scherbak, Sergey; Kauranen, Martti; Lipovskii, Andrey

    2018-03-01

    We study second-harmonic generation from gold nanoislands covered with amorphous titanium oxide (TiO2 ) films. As the TiO2 thickness increases, the plasmon resonance of the nanoislands shifts away from the second-harmonic wavelength of 532 nm, diminishing the resonant enhancement of the process at this wavelength. Nevertheless, the second-harmonic signal is enhanced by up to a factor of 45 with increasing TiO2 thickness. This unexpected effect arises from the scaling of local fields at the fundamental wavelength of 1064 nm—which is at the far tail of the resonance—due to a change in the dielectric environment of the nanoislands.

  12. Model of resonant high harmonic generation in multi-electron systems

    NASA Astrophysics Data System (ADS)

    Redkin, P. V.; Ganeev, R. A.

    2017-09-01

    We extend the 4-step analytical model of resonant enhancement of high harmonic generation to the systems possessing resonant transitions of inner-shell electrons. Resonant enhancement is explained by lasing without inversion in a three-level system of ground, excited and shifted resonant states, which are coupled to the fundamental field and its high harmonics. The role of inelastic scattering is studied by simulation of an excited state’s population dynamics. It is shown that maximal gain is achieved when the energy shift between the excited state and resonant state is close to the energy of the fundamental photon. To prove the concept we demonstrate the enhancement of harmonics in the In plasma using different pumps.

  13. Quasi-supercontinuum source in the extreme ultraviolet using multiple frequency combs from high-harmonic generation

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

    Wünsche, Martin; Fuchs, Silvio; Aull, Stefan

    A quasi-supercontinuum source in the extreme ultraviolet (XUV) is demonstrated using a table-top femtosecond laser and a tunable optical parametric amplifier (OPA) as a driver for high-harmonic generation (HHG). The harmonic radiation, which is usually a comb of odd multiples of the fundamental frequency, is generated by near-infrared (NIR) laser pulses from the OPA. A quasi-continuous XUV spectrum in the range of 30 to 100 eV is realized by averaging over multiple harmonic comb spectra with slightly different fundamental frequencies and thus different spectral spacing between the individual harmonics. The driving laser wavelength is swept automatically during an averaging timemore » period. With a total photon flux of 4×10 9 photons/s in the range of 30 eV to 100 eV and 1×10 7 photons/s in the range of 100 eV to 200 eV, the resulting quasi-supercontinuum XUV source is suited for applications such as XUV coherence tomography (XCT) or near-edge absorption fine structure spectroscopy (NEXAFS).« less

  14. Quasi-supercontinuum source in the extreme ultraviolet using multiple frequency combs from high-harmonic generation

    DOE PAGES

    Wünsche, Martin; Fuchs, Silvio; Aull, Stefan; ...

    2017-03-16

    A quasi-supercontinuum source in the extreme ultraviolet (XUV) is demonstrated using a table-top femtosecond laser and a tunable optical parametric amplifier (OPA) as a driver for high-harmonic generation (HHG). The harmonic radiation, which is usually a comb of odd multiples of the fundamental frequency, is generated by near-infrared (NIR) laser pulses from the OPA. A quasi-continuous XUV spectrum in the range of 30 to 100 eV is realized by averaging over multiple harmonic comb spectra with slightly different fundamental frequencies and thus different spectral spacing between the individual harmonics. The driving laser wavelength is swept automatically during an averaging timemore » period. With a total photon flux of 4×10 9 photons/s in the range of 30 eV to 100 eV and 1×10 7 photons/s in the range of 100 eV to 200 eV, the resulting quasi-supercontinuum XUV source is suited for applications such as XUV coherence tomography (XCT) or near-edge absorption fine structure spectroscopy (NEXAFS).« less

  15. Generation of Bright, Spatially Coherent Soft X-Ray High Harmonics in a Hollow Waveguide Using Two-Color Synthesized Laser Pulses.

    PubMed

    Jin, Cheng; Stein, Gregory J; Hong, Kyung-Han; Lin, C D

    2015-07-24

    We investigate the efficient generation of low-divergence high-order harmonics driven by waveform-optimized laser pulses in a gas-filled hollow waveguide. The drive waveform is obtained by synthesizing two-color laser pulses, optimized such that highest harmonic yields are emitted from each atom. Optimization of the gas pressure and waveguide configuration has enabled us to produce bright and spatially coherent harmonics extending from the extreme ultraviolet to soft x rays. Our study on the interplay among waveguide mode, atomic dispersion, and plasma effect uncovers how dynamic phase matching is accomplished and how an optimized waveform is maintained when optimal waveguide parameters (radius and length) and gas pressure are identified. Our analysis should help laboratory development in the generation of high-flux bright coherent soft x rays as tabletop light sources for applications.

  16. Non-contact defect diagnostics in Cz-Si wafers using resonance ultrasonic vibrations

    NASA Astrophysics Data System (ADS)

    Belyaev, A.; Kochelap, V. A.; Tarasov, I.; Ostapenko, S.

    2001-01-01

    A new resonance effect of generation of sub-harmonic acoustic vibrations was applied to characterize defects in as-grown and processed Cz-Si wafers. Ultrasonic vibrations were generated into standard 8″ wafers using an external ultrasonic transducer and their amplitude recorded in a non-contact mode using a scanning acoustic probe. By tuning the frequency, f, of the transducer we observed generation of intense sub-harmonic acoustic mode ("whistle" or w-mode) with f/2 frequency. The characteristics of the w-mode-amplitude dependence, frequency scans, spatial distribution allow a clear distinction versus harmonic vibrations of the same wafer. The origin of sub-harmonic vibrations observed on 8″ Cz-Si wafers is attributed to a parametric resonance of flexural vibrations in thin silicon circular plates. We present evidence that "whistle" effect shows a strong dependence on the wafer's growth and processing history and can be used for quality assurance purposes.

  17. Angular and Intensity Dependent Spectral Modulations in High Harmonics from N2

    NASA Astrophysics Data System (ADS)

    McFarland, Brian; Farrell, Joseph; Bucksbaum, Philip; Guehr, Markus

    2009-05-01

    The spectral amplitude and phase modulation of high harmonics (HHG) in molecules provides important clues to molecular structure and dynamics in strong laser fields. We have studied these effects in aligned N2. Earlier results of HHG experiments claimed that the spectral amplitude modulation was predominantly due to geometrical interference between the recombining electron and the highest occupied molecular orbital (HOMO) [1]. We report evidence that contradicts this simple view. We observe a phase jump accompanied by a spectral minimum for HHG in aligned N2. The minimum shifts to lower harmonics as the angle between the molecular axis and harmonic generation polarization increases, and shifts to higher harmonics with increasing harmonic generation intensity. The features observed cannot be fully explained by a geometrical model. We discuss alternative explanations involving multi orbital effects [2]. [0pt] [1] Lein et al., Phys. Rev. A, 66, 023805 (2002) [2] B. K. McFarland, J. P. Farrell, P. H. Bucksbaum and M. Gühr, Science 322, 1232 (2008)

  18. Acoustic waves in the atmosphere and ground generated by volcanic activity

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

    Ichihara, Mie; Lyons, John; Oikawa, Jun

    2012-09-04

    This paper reports an interesting sequence of harmonic tremor observed in the 2011 eruption of Shinmoe-dake volcano, southern Japan. The main eruptive activity started with ashcloud forming explosive eruptions, followed by lava effusion. Harmonic tremor was transmitted into the ground and observed as seismic waves at the last stage of the effusive eruption. The tremor observed at this stage had unclear and fluctuating harmonic modes. In the atmosphere, on the other hand, many impulsive acoustic waves indicating small surface explosions were observed. When the effusion stopped and the erupted lava began explosive degassing, harmonic tremor started to be transmitted alsomore » to the atmosphere and observed as acoustic waves. Then the harmonic modes became clearer and more stable. This sequence of harmonic tremor is interpreted as a process in which volcanic degassing generates an open connection between the volcanic conduit and the atmosphere. In order to test this hypothesis, a laboratory experiment was performed and the essential features were successfully reproduced.« less

  19. Studying the effect of photodynamic therapy (PDT) to enhance healing of femur fractures using polarimetric second-harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Golaraei, Ahmad; Raja, Vaishnavi; Akens, Margarete K.; Wilson, Brian C.; Barzda, Virginijus

    2017-07-01

    Linear polarization-in, polarization-out second-harmonic generation microscopy was used to study the effect of Photodynamic therapy treatment on enhancing the healing of femur fracture by investigating the ultrastructure of collagen as a major component of bone matrix.

  20. Two-pass-internal second-harmonic generation using a prism coupler.

    NASA Technical Reports Server (NTRS)

    Gonzalez, D. G.; Nieh, S. T. K.; Steier, W. H.

    1973-01-01

    A dispersive quartz prism is used to couple the total second harmonic generated in both directions by an internal cavity frequency doubler. The study shows that the dispersion of air and mirror reflection phase shifts can be compensated for by a slight nonphase match condition in the doubler.

  1. Comparison of fine structures of electron cyclotron harmonic emissions in aurora

    NASA Astrophysics Data System (ADS)

    LaBelle, J.; Dundek, M.

    2015-10-01

    Recent discoveries of higher harmonic cyclotron emissions in aurora occurring under daylight conditions motivated the modification of radio receivers at South Pole Station, Antarctica, to measure fine structure of such emissions during two consecutive austral summers, 2013-2014 and 2014-2015. The experiment recorded 347 emission events over 376 days of observation. The seasonal distribution of these events reveals that successively higher harmonics require higher solar zenith angles for occurrence, as expected if they are generated at the matching condition fuh = Nfce, which for higher N requires higher electron densities which are associated with higher solar zenith angles. This result implies that generation of higher harmonics from lower harmonics via wave-wave processes explains only a minority of events. Detailed examination of 21 cases in which two harmonics occur simultaneously shows that in almost all events the higher harmonic comes from higher altitudes, and only for a small fraction of events is it plausible that the frequencies of the fine structures of the emissions are correlated and in exact integer ratio. This observation puts an upper bound of 15-20% on the fraction of emissions which can be explained by wave-wave interactions involving Z mode waves at fce and, combined with consideration of source altitudes, puts an upper bound of 75% on the fraction explained by coalescence of Z mode waves at 2fce. Taken together, these results suggest that the dominant mechanism for the higher harmonics is independent generation at the matching points fuh = Nfce and that the wave-wave interaction mechanisms explain a relatively small fraction of events.

  2. ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone

    DTIC Science & Technology

    2009-07-01

    formation rate and bone mineral density (severe osteoporosis) that persists throughout life. The expression of both osteocalcin (Ocn) and bone sialoprotein ...established that ATF4 is critical for osteoblast differentiation as demonstrated by dramatically reduced expression of osteocalcin and bone sialoprotein mRNA

  3. Measured thermal and fast neutron fluence rates for ATF-1 holders during ATR cycle 160A

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

    Walker, B. J.; Miller, D. T.

    This report contains the thermal (2200 m/s) and fast (E>1MeV) neutron fluence rate data for the ATF-1 holders located in core for ATR Cycle 160A which were measured by the Radiation Measurements Laboratory (RML).

  4. 78 FR 57415 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ... DEPARTMENT OF JUSTICE Bureau of Alcohol, Tobacco, Firearms and Explosives [OMB Number 1140-NEW] Agency Information Collection Activities; Proposed Collection; Comments Requested: Request for ATF Background Investigation Information ACTION: 60-Day Notice. The Department of Justice (DOJ), Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF),...

  5. Audiometric Predictions Using SFOAE and Middle-Ear Measurements

    PubMed Central

    Ellison, John C.; Keefe, Douglas H.

    2006-01-01

    Objective The goals of the study are to determine how well stimulus-frequency otoacoustic emissions (SFOAEs) identify hearing loss, classify hearing loss as mild or moderate-severe, and correlate with pure-tone thresholds in a population of adults with normal middle-ear function. Other goals are to determine if middle-ear function as assessed by wideband acoustic transfer function (ATF) measurements in the ear canal account for the variability in normal thresholds, and if the inclusion of ATFs improves the ability of SFOAEs to identify hearing loss and predict pure-tone thresholds. Design The total suppressed SFOAE signal and its corresponding noise were recorded in 85 ears (22 normal ears and 63 ears with sensorineural hearing loss) at octave frequencies from 0.5 – 8 kHz using a nonlinear residual method. SFOAEs were recorded a second time in three impaired ears to assess repeatability. Ambient-pressure ATFs were obtained in all but one of these 85 ears, and were also obtained from an additional 31 normal-hearing subjects in whom SFOAE data were not obtained. Pure-tone air-and bone-conduction thresholds and 226-Hz tympanograms were obtained on all subjects. Normal tympanometry and the absence of air-bone gaps were used to screen subjects for normal middle-ear function. Clinical decision theory was used to assess the performance of SFOAE and ATF predictors in classifying ears as normal or impaired, and linear regression analysis was used to test the ability of SFOAE and ATF variables to predict the air-conduction audiogram. Results The ability of SFOAEs to classify ears as normal or hearing impaired was significant at all test frequencies. The ability of SFOAEs to classify impaired ears as either mild or moderate-severe was significant at test frequencies from 0.5 to 4 kHz. SFOAEs were present in cases of severe hearing loss. SFOAEs were also significantly correlated with air-conduction thresholds from 0.5 to 8 kHz. The best performance occurred using the SFOAE signal-to-noise ratio (S/N) as the predictor, and the overall best performance was at 2 kHz. The SFOAE S/N measures were repeatable to within 3.5 dB in impaired ears. The ATF measures explained up to 25% of the variance in the normal audiogram; however, ATF measures did not improve SFOAEs predictors of hearing loss except at 4 kHz. Conclusions In common with other OAE types, SFOAEs are capable of identifying the presence of hearing loss. In particular, SFOAEs performed better than distortion-product and click-evoked OAEs in predicting auditory status at 0.5 kHz; SFOAE performance was similar to that of other OAE types at higher frequencies except for a slight performance reduction at 4 kHz. Because SFOAEs were detected in ears with mild to severe cases of hearing loss they may also provide an estimate of the classification of hearing loss. Although SFOAEs were significantly correlated with hearing threshold, they do not appear to have clinical utility in predicting a specific behavioral threshold. Information on middle-ear status as assessed by ATF measures offered minimal improvement in SFOAE predictions of auditory status in a population of normal and impaired ears with normal middle-ear function. However, ATF variables did explain a significant fraction of the variability in the audiograms of normal ears, suggesting that audiometric thresholds in normal ears are partially constrained by middle-ear function as assessed by ATF tests. PMID:16230898

  6. Periodic acoustic radiation from a low aspect ratio propeller

    NASA Astrophysics Data System (ADS)

    Muench, John David

    An experimental program was conducted with the objective of providing high fidelity measurements of propeller inflow, unsteady blade surface pressures, and discrete acoustic radiation over a wide range of speeds. Anechoic wind tunnel experiments were preformed using the SISUP propeller. The upstream stator blades generate large wake deficits that result in periodic unsteady blade forces that acoustically radiate at blade passing frequency and higher harmonics. The experimental portion of this research successfully measured the inflow velocity, blade span unsteady pressures and directive characteristics of the blade-rate radiated noise associated with this complex propeller geometry while the propeller was operating on design. The spatial harmonic decomposition of the inflow revealed significant coefficients at 8, 16 and 24. The magnitude of the unsteady blade forces scale as U4 and linearly shift in frequency with speed. The magnitude of the discrete frequency acoustic levels associated with blade rate scale as U6 and also shift linearly with speed. At blade-rate, the far-field acoustic directivity has a dipole-like directivity oriented perpendicular to the inflow. At the first harmonic of blade-rate, the far-field directivity is not as well defined. The experimental inflow and blade surface pressure results were used to generate an acoustic prediction at blade rate based on a blade strip theory model developed by Blake (1986). The predicted acoustic levels were compared to the experimental results. The model adequately predicts the measured sound field at blade rate at 120 ft/sec. Radiated noise at blade-rate for 120 ft/s can be described by a dipole, whose orientation is perpendicular to the flow and is generated by the interaction of the rotating propeller with the 8th harmonic of the inflow. At blade-rate for 60 ft/s, the model under predicts measured levels. At the first harmonic of blade-rate, for 120 ft/s, the sound field is described as a combination of dipole sources, one generated by the 16 th harmonic, perpendicular to the inflow, and the other generated by the 12th harmonic of the inflow parallel to the inflow. At the first harmonic of blade-rate for 60 ft/s, the model under predicts measured levels.

  7. Performance of a Combined System Using an X-Ray FEL Oscillator and a High-Gain FEL Amplifier

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

    Gupta, L.; Lindberg, R.; Kim, K. -J.

    The LCLS-II at SLAC will feature a 4 GeV CW superconducting (SC) RF linac [1] that can potentially drive a 5th harmonic X-Ray FEL Oscillator (XFELO) to produce fully coherent, 1 MW photon pulses with a 5 meV bandwidth at 14.4 keV [2]. The XFELO output can serve as the input seed signal for a high-gain FEL amplifier employing fs electron beams from the normal conducting SLAC linac, thereby generating coherent, fs x-ray pulses with TW peak powers using a tapered undulator after saturation [3]. Coherent, intense output at several tens of keV will also be feasible if one considersmore » a harmonic generation scheme. Thus, one can potentially reach the 42 keV photon energy required for the MaRIE project [4] by beginning with an XFELO operating at the 3rd harmonic to produce 14.0 keV photons using a 12 GeV SCRF linac, and then subsequently using the high-gain harmonic generation scheme to generate and amplify the 3th harmonic at 42 keV [5]. We report extensive GINGER simulations that determine an optimized parameter set for the combined system.« less

  8. Complete spatial and temporal locking in phase-mismatched second-harmonic generation.

    PubMed

    Fazio, Eugenio; Pettazzi, Federico; Centini, Marco; Chauvet, Mathieu; Belardini, Alessandro; Alonzo, Massimo; Sibilia, Concita; Bertolotti, Mario; Scalora, Micheal

    2009-03-02

    We experimentally demonstrate simultaneous phase and group velocity locking of fundamental and generated second harmonic pulses in Lithium Niobate, under conditions of material phase mismatch. In phase-mismatched, pulsed second harmonic generation in addition to a reflected signal two forward-propagating pulses are also generated at the interface between a linear and a second order nonlinear material: the first pulse results from the solution of the homogeneous wave equation, and propagates at the group velocity expected from material dispersion; the second pulse is the solution of the inhomogeneous wave equation, is phase-locked and trapped by the pump pulse, and follows the pump trajectory. At normal incidence, the normal and phase locked pulses simply trail each other. At oblique incidence, the consequences can be quite dramatic. The homogeneous pulse refracts as predicted by material dispersion and Snell's law, yielding at least two spatially separate second harmonic spots at the medium's exit. We thus report the first experimental results showing that, at oblique incidence, fundamental and phase-locked second harmonic pulses travel with the same group velocity and follow the same trajectory. This is direct evidence that, at least up to first order, the effective dispersion of the phase-locked pulse is similar to the dispersion of the pump pulse.

  9. On Weyl wormholes supported by massless K-essence

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

    Estevez-Delgado, J.; Zannias, T.

    We show that Weyl wormholes supported by mass-less K-essence can be generated by a pair of axisymmetric harmonic functions. We study properties of space-times generated by harmonic functions describing the exterior potential of a thin conducting disk held at fixed potential. We find that within this family, only a particular subfamily generates wormholes and the resulting wormholes are necessarily spherical. In general, the topology of the space-times generated by an arbitrary pair is multi sheeted.

  10. Multicascade X-Ray Free-Electron Laser with Harmonic Multiplier and Two-Frequency Undulator

    NASA Astrophysics Data System (ADS)

    Zhukovsky, K. V.

    2018-06-01

    The feasibility of generation of powerful x-ray radiation by a cascade free-electron laser (FEL) with amplification of higher harmonics using a two-frequency undulator is studied. To analyze the FEL operation, a complex phenomenological single-pass FEL model is developed and used. It describes linear and nonlinear generation of harmonics in the FEL with seed laser that takes into account initial electron beam noise and describes all main losses of each harmonic in each FEL cascade. The model is also calibrated against and approved by the experimental FEL data and available results of three-dimensional numerical simulation. The electron beam in the undulator is assumed to be matched and focused, and the dynamics of power in the singlepass FEL with cascade harmonic multipliers is investigated to obtain x-ray laser radiation in the FEL having the shortest length, beam energy, and frequency of the seed laser as low as possible. In this context, the advantages of the two-frequency undulator used for generation of harmonics are demonstrated. The evolution of harmonics in a multicascade FEL with multiplication of harmonics is investigated. The operation of the cascade FEL at the wavelength λ = 1.14 nm, generating 30 MW already on 38 m with the seed laser operating at a wavelength of 11.43 nm corresponding to the maximal reflectivity of the multilayered mirror MoRu/Be coating is investigated. In addition, the operation of the multicascade FEL with accessible seed UVlaser operating at a wavelength of 157 nm (F2 excimer UV-laser) and electron beam with energy of 0.5 GeV is investigated. X-ray radiation simulated in it at the wavelength λ 3.9 nm reaches power of 50 MW already at 27 m, which is by two orders of magnitude shorter than 3.4 km of the x-ray FEL recently put into operation in Europe.

  11. Second-harmonic generation in shear wave beams with different polarizations

    NASA Astrophysics Data System (ADS)

    Spratt, Kyle S.; Ilinskii, Yurii A.; Zabolotskaya, Evgenia A.; Hamilton, Mark F.

    2015-10-01

    A coupled pair of nonlinear parabolic equations was derived by Zabolotskaya [1] that model the transverse components of the particle motion in a collimated shear wave beam propagating in an isotropic elastic solid. Like the KZK equation, the parabolic equation for shear wave beams accounts consistently for the leading order effects of diffraction, viscosity and nonlinearity. The nonlinearity includes a cubic nonlinear term that is equivalent to that present in plane shear waves, as well as a quadratic nonlinear term that is unique to diffracting beams. The work by Wochner et al. [2] considered shear wave beams with translational polarizations (linear, circular and elliptical), wherein second-order nonlinear effects vanish and the leading order nonlinear effect is third-harmonic generation by the cubic nonlinearity. The purpose of the current work is to investigate the quadratic nonlinear term present in the parabolic equation for shear wave beams by considering second-harmonic generation in Gaussian beams as a second-order nonlinear effect using standard perturbation theory. In order for second-order nonlinear effects to be present, a broader class of source polarizations must be considered that includes not only the familiar translational polarizations, but also polarizations accounting for stretching, shearing and rotation of the source plane. It is found that the polarization of the second harmonic generated by the quadratic nonlinearity is not necessarily the same as the polarization of the source-frequency beam, and we are able to derive a general analytic solution for second-harmonic generation from a Gaussian source condition that gives explicitly the relationship between the polarization of the source-frequency beam and the polarization of the second harmonic.

  12. Quasi-phase-matching of only even-order high harmonics.

    PubMed

    Diskin, Tzvi; Cohen, Oren

    2014-03-24

    High harmonic spectrum of a quasi-monochromatic pump that interacts with isotropic media consists of only odd-order harmonics. Addition of a secondary pump, e.g. a static field or the second harmonic of the primary pump, can results with generation of both odd and even harmonics of the primary pump. We propose a method for quasi-phase matching of only the even-order harmonics of the primary pump. We formulate a theory for this process and demonstrate it numerically. We also show that it leads to attosecond pulse trains with constant carrier envelop phase and high repetition rate.

  13. Multiple layer optical memory system using second-harmonic-generation readout

    DOEpatents

    Boyd, Gary T.; Shen, Yuen-Ron

    1989-01-01

    A novel optical read and write information storage system is described which comprises a radiation source such as a laser for writing and illumination, the radiation source being capable of radiating a preselected first frequency; a storage medium including at least one layer of material for receiving radiation from the radiation source and capable of being surface modified in response to said radiation source when operated in a writing mode and capable of generating a pattern of radiation of the second harmonic of the preselected frequency when illuminated by the radiation source at the preselected frequency corresponding to the surface modifications on the storage medium; and a detector to receive the pattern of second harmonic frequency generated.

  14. Generation of higher odd harmonics in a defective photonic crystal

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

    Ramanujam, N. R., E-mail: wilsonpra@yahoo.co.in; Wilson, K. S. Joseph

    2015-06-24

    A photonic crystal (AB){sup 2}(DB)(AB){sup 2} with high refractive index medium as silicon and low refractive medium as air is considered. Using the transfer matrix method, the transmission properties as a function of wavelength with photonic band gaps has been obtained. We are able to demonstrate the generation of third, fifth, seventh and ninth harmonics in the present work. We show that if the air medium is removed in the defect, the defect modes are generated but not harmonics. It can be designed to have a frequency conversion, and have a potential for becoming the basis for the next generationmore » of optical devices.« less

  15. Determination of collagen fibril size via absolute measurements of second-harmonic generation signals

    NASA Astrophysics Data System (ADS)

    Bancelin, Stéphane; Aimé, Carole; Gusachenko, Ivan; Kowalczuk, Laura; Latour, Gaël; Coradin, Thibaud; Schanne-Klein, Marie-Claire

    2014-09-01

    The quantification of collagen fibril size is a major issue for the investigation of pathological disorders associated with structural defects of the extracellular matrix. Second-harmonic generation microscopy is a powerful technique to characterize the macromolecular organization of collagen in unstained biological tissues. Nevertheless, due to the complex coherent building of this nonlinear optical signal, it has never been used to measure fibril diameter so far. Here we report absolute measurements of second-harmonic signals from isolated fibrils down to 30 nm diameter, via implementation of correlative second-harmonic-electron microscopy. Moreover, using analytical and numerical calculations, we demonstrate that the high sensitivity of this technique originates from the parallel alignment of collagen triple helices within fibrils and the subsequent constructive interferences of second-harmonic radiations. Finally, we use these absolute measurements as a calibration for ex vivo quantification of fibril diameter in the Descemet’s membrane of a diabetic rat cornea.

  16. The harmonic state of quantum cascade lasers: origin, control, and prospective applications [Invited].

    PubMed

    Piccardo, Marco; Chevalier, Paul; Mansuripur, Tobias S; Kazakov, Dmitry; Wang, Yongrui; Rubin, Noah A; Meadowcroft, Lauren; Belyanin, Alexey; Capasso, Federico

    2018-04-16

    The recently discovered ability of the quantum cascade laser to produce a harmonic frequency comb has attracted new interest in these devices for both applications and fundamental laser physics. In this review we present an extensive experimental phenomenology of the harmonic state, including its appearance in mid-infrared and terahertz quantum cascade lasers, studies of its destabilization induced by delayed optical feedback, and the assessment of its frequency comb nature. A theoretical model explaining its origin as due to the mutual interaction of population gratings and population pulsations inside the laser cavity will be described. We explore different approaches to control the spacing of the harmonic state, such as optical injection seeding and variation of the device temperature. Prospective applications of the harmonic state include microwave and terahertz generation, picosecond pulse generation in the mid-infrared, and broadband spectroscopy.

  17. Ultrashort pulse chirp measurement via transverse second-harmonic generation in strontium barium niobate crystal

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

    Trull, J.; Wang, B.; Parra, A.

    2015-06-01

    Pulse compression in dispersive strontium barium niobate crystal with a random size and distribution of the anti-parallel orientated nonlinear domains is observed via transverse second harmonic generation. The dependence of the transverse width of the second harmonic trace along the propagation direction allows for the determination of the initial chirp and duration of pulses in the femtosecond regime. This technique permits a real-time analysis of the pulse evolution and facilitates fast in-situ correction of pulse chirp acquired in the propagation through an optical system.

  18. Shaping the third-harmonic radiation from silicon nanodimers

    DOE PAGES

    Wang, Lei; Kruk, Sergey; Xu, Lei; ...

    2017-01-23

    Recent progress in the study of resonant light confinement in high-index dielectric nanostructures suggests a new route for achieving efficient control of both electric and magnetic components of light. It also leads to the enhancement of nonlinear effects near electric and magnetic Mie resonances with an engineered radiation directionality. Furthermore we study the third-harmonic generation from dimers composed of pairs of two identical silicon nanoparticles and demonstrate, both numerically and experimentally, that the multipolar harmonic modes generated by the dimers near the Mie resonances allow the shaping of the directionality of nonlinear radiation.

  19. Second-harmonic generation using tailored whispering gallery modes

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

    Dumeige, Yannick; Feron, Patrice

    It has been shown that whispering gallery modes can be used to obtain a combination of modal and geometrical quasi-phase-matching in second-harmonic generation. This could be achieved in isotropic, nonferroelectric, strongly dispersive and highly nonlinear materials such as III-V semiconductors. Unfortunately the poor overlap between the second-harmonic field and second order nonlinear polarization limits the conversion efficiency. In this paper we show that by engineering the refractive index it is possible to increase field overlap and to enhance effective second order nonlinear polarization of semiconductor microdisks.

  20. High Resolution BPM Upgrade for the ATF Damping Ring at KEK

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

    Eddy, N.; Briegel, C.; Fellenz, B.

    2011-08-17

    A beam position monitor (BPM) upgrade at the KEK Accelerator Test Facility (ATF) damping ring has been accomplished, carried out by a KEK/FNAL/SLAC collaboration under the umbrella of the global ILC R&D effort. The upgrade consists of a high resolution, high reproducibility read-out system, based on analog and digital down-conversion techniques, digital signal processing, and also implements a new automatic gain error correction schema. The technical concept and realization as well as results of beam studies are presented. The next generation of linear colliders require ultra-low vertical emittance of <2 pm-rad. The damping ring at the KEK Accelerator Test Facilitymore » (ATF) is designed to demonstrate this mission critical goal. A high resolution beam position monitor (BPM) system for the damping ring is one of the key tools for realizing this goal. The BPM system needs to provide two distnict measurements. First, a very high resolution ({approx}100-200nm) closed-orbit measurement which is averaged over many turns and realized with narrowband filter techniques - 'narrowband mode'. This is needed to monitor and steer the beam along an optimum orbit and to facilitate beam-based alignment to minimize non-linear field effects. Second, is the ability to make turn by turn (TBT) measurements to support optics studies and corrections necessary to achieve the design performance. As the TBT measurement necessitates a wider bandwidth, it is often referred to as 'wideband mode'. The BPM upgrade was initiated as a KEK/SLAC/FNAL collaboration in the frame of the Global Design Initiative of the International Linear Collider. The project was realized and completed using Japan-US funds with Fermilab as the core partner.« less

  1. NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes

    PubMed Central

    2012-01-01

    Background Lipoteichoic acid (LTA) is a component of gram-positive bacterial cell walls and may be elevated in the cerebrospinal fluid of patients suffering from meningitis. Among matrix metalloproteinases (MMPs), MMP-9 has been observed in patients with brain inflammatory diseases and may contribute to the pathology of brain diseases. Moreover, several studies have suggested that increased oxidative stress is implicated in the pathogenesis of brain inflammation and injury. However, the molecular mechanisms underlying LTA-induced redox signal and MMP-9 expression in brain astrocytes remain unclear. Objective Herein we explored whether LTA-induced MMP-9 expression was mediated through redox signals in rat brain astrocytes (RBA-1 cells). Methods Upregulation of MMP-9 by LTA was evaluated by zymographic and RT-PCR analyses. Next, the MMP-9 regulatory pathways were investigated by pretreatment with pharmacological inhibitors or transfection with small interfering RNAs (siRNAs), Western blotting, and chromatin immunoprecipitation (ChIP)-PCR and promoter activity reporter assays. Moreover, we determined the cell functional changes by migration assay. Results These results showed that LTA induced MMP-9 expression via a PKC(α)-dependent pathway. We further demonstrated that PKCα stimulated p47phox/NADPH oxidase 2 (Nox2)-dependent reactive oxygen species (ROS) generation and then activated the ATF2/AP-1 signals. The activated-ATF2 bound to the AP-1-binding site of MMP-9 promoter, and thereby turned on MMP-9 gene transcription. Additionally, the co-activator p300 also contributed to these responses. Functionally, LTA-induced MMP-9 expression enhanced astrocytic migration. Conclusion These results demonstrated that in RBA-1 cells, activation of ATF2/AP-1 by the PKC(α)-mediated Nox(2)/ROS signals is essential for upregulation of MMP-9 and cell migration enhanced by LTA. PMID:22643046

  2. Generation of coherent terahertz radiation in ultrafast laser-gas interactionsa)

    NASA Astrophysics Data System (ADS)

    Kim, Ki-Yong

    2009-05-01

    The generation of intense terahertz radiation in ultrafast laser-gas interactions is studied on a basis of transient electron current model. When an ultrashort pulse laser's fundamental and its second harmonic fields are mixed to ionize a gas, a nonvanishing, directional photoelectron current can be produced, which simultaneously emits terahertz radiation in the far field. Here, the generation mechanism is examined with an analytic derivation and numerical simulations, in which tunneling ionization and subsequent electron motion in the combined laser field play a key role. In the simulations, three types of laser-gas interactions are considered: (i) mixing the fundamental and its second harmonic fields, (ii) mixing nonharmonic, two-color fields, and (iii) focusing single-color, few-cycle pulses. In these interactions, terahertz generation and other nonlinear effects driven by the transient current are investigated. In particular, anticorrelation between terahertz and second (or third) harmonic generation is observed and analyzed.

  3. High-efficency stable 213-nm generation for LASIK application

    NASA Astrophysics Data System (ADS)

    Wang, Zhenglin; Alameh, Kamal; Zheng, Rong

    2005-01-01

    213nm Solid-state laser technology provides an alternative method to replace toxic excimer laser in LASIK system. In this paper, we report a compact fifth harmonic generation system to generate high pulse energy 213nm laser from Q-switched Nd:YAG laser for LASIK application based on three stages harmonic generation procedures. A novel crystal housing was specifically designed to hold the three crystals with each crystal has independent, precise angular adjustment structure and automatic tuning control. The crystal temperature is well maintained at ~130°C to improve harmonic generation stability and crystal operation lifetime. An output pulse energy 35mJ is obtained at 213nm, corresponding to total conversion efficiency ~10% from 1064nm pump laser. In system verification tests, the 213nm output power drops less than 5% after 5 millions pulse shots and no significant damage appears in the crystals.

  4. Cusp-Gun Sixth-Harmonic Slotted Gyrotron

    NASA Astrophysics Data System (ADS)

    Stutzman, R. C.; McDermott, D. B.; Hirata Luhmann, Y., Jr.; Gallagher, D. A.; Spencer, T. A.

    2000-10-01

    A high-harmonic slotted gyrotron has been constructed at UC Davis to be driven by a 70 kV, 3.5 A, axis-encircling electron beam from a Northrop Grumman Cusp gun. The 94 GHz, slotted sixth-harmonic gyrotron is predicted to generate 50 kW with an efficiency of 20%. Using the profile of the adiabatic field reversal from the UC Davis superconducting test-magnet, EGUN simulations predict that an axis-encircling electron beam will be generated with an axial velocity spread of Δ v_z/v_z=10% for the desired velocity ratio of α =v_z/v_z=1.5. The design will also be presented for an 8th-harmonic W-band gyrotron whose magnetic field can be supplied by a lightweight permanent magnet.

  5. Harmonics generation near ion-cyclotron frequency of ECR plasma

    NASA Astrophysics Data System (ADS)

    Chowdhury, Satyajit; Biswas, Subir; Chakrabarti, Nikhil; Pal, Rabindranath

    2017-10-01

    Wave excitation at different frequency regime is employed in the MaPLE device ECR plasma for varied excitation amplitude. At very low amplitude excitation, mainly fundamental frequency mode of the exciter signal frequency comes into play. With the increase in amplitude of applied perturbation, harmonics are generated and dominant over the fundamental frequency mode. There is a fixed critical amplitude of exciter to yield the harmonics and is independent of applied frequency. Observed harmonics and the main frequency mode has propagation characteristics and are discussed here. Exact mode number and propagation nature are also tried to measure in the experiment. Detailed experimental results will be presented. Department of Science and Technology of Government of India (Project No. SB/S2/HEP-005/2014).

  6. Ultraviolet surprise: Efficient soft x-ray high-harmonic generation in multiply ionized plasmas.

    PubMed

    Popmintchev, Dimitar; Hernández-García, Carlos; Dollar, Franklin; Mancuso, Christopher; Pérez-Hernández, Jose A; Chen, Ming-Chang; Hankla, Amelia; Gao, Xiaohui; Shim, Bonggu; Gaeta, Alexander L; Tarazkar, Maryam; Romanov, Dmitri A; Levis, Robert J; Gaffney, Jim A; Foord, Mark; Libby, Stephen B; Jaron-Becker, Agnieszka; Becker, Andreas; Plaja, Luis; Murnane, Margaret M; Kapteyn, Henry C; Popmintchev, Tenio

    2015-12-04

    High-harmonic generation is a universal response of matter to strong femtosecond laser fields, coherently upconverting light to much shorter wavelengths. Optimizing the conversion of laser light into soft x-rays typically demands a trade-off between two competing factors. Because of reduced quantum diffusion of the radiating electron wave function, the emission from each species is highest when a short-wavelength ultraviolet driving laser is used. However, phase matching--the constructive addition of x-ray waves from a large number of atoms--favors longer-wavelength mid-infrared lasers. We identified a regime of high-harmonic generation driven by 40-cycle ultraviolet lasers in waveguides that can generate bright beams in the soft x-ray region of the spectrum, up to photon energies of 280 electron volts. Surprisingly, the high ultraviolet refractive indices of both neutral atoms and ions enabled effective phase matching, even in a multiply ionized plasma. We observed harmonics with very narrow linewidths, while calculations show that the x-rays emerge as nearly time-bandwidth-limited pulse trains of ~100 attoseconds. Copyright © 2015, American Association for the Advancement of Science.

  7. The Ultraviolet Surprise. Efficient Soft X-Ray High Harmonic Generation in Multiply-Ionized Plasmas

    DOE PAGES

    Popmintchev, Dimitar; Hernandez-Garcia, Carlos; Dollar, Franklin; ...

    2015-12-04

    High-harmonic generation is a universal response of matter to strong femtosecond laser fields, coherently upconverting light to much shorter wavelengths. Optimizing the conversion of laser light into soft x-rays typically demands a trade-off between two competing factors. Reduced quantum diffusion of the radiating electron wave function results in emission from each species which is highest when a short-wavelength ultraviolet driving laser is used. But, phase matching—the constructive addition of x-ray waves from a large number of atoms—favors longer-wavelength mid-infrared lasers. We identified a regime of high-harmonic generation driven by 40-cycle ultraviolet lasers in waveguides that can generate bright beams inmore » the soft x-ray region of the spectrum, up to photon energies of 280 electron volts. Surprisingly, the high ultraviolet refractive indices of both neutral atoms and ions enabled effective phase matching, even in a multiply ionized plasma. We observed harmonics with very narrow linewidths, while calculations show that the x-rays emerge as nearly time-bandwidth–limited pulse trains of ~100 attoseconds.« less

  8. Generation of coherent two-color pulses at two adjacent harmonics in a seeded free-electron laser

    NASA Astrophysics Data System (ADS)

    Zhao, Zhouyu; Li, Heting; Jia, Qika

    2018-02-01

    The growing requirements of pump-probe techniques and nonlinear optics experiments greatly promote the studies of two-color free-electron lasers (FELs). We propose a new method to generate coherent two-color pulses in a high-gain harmonic generation (HGHG) FEL. In this scheme, an initial tilted electron beam is sent though the modulator and dispersive section of an HGHG FEL to generate the bunching at harmonics of the seed laser. Then a transverse gradient undulator (TGU) is adopted as the radiator and in such radiator, only two separated fractions of the tilted beam will resonate at two adjacent harmonics of the seed laser and are enabled to emit the coherent two-color pulses simultaneously. The time separation between the two pulses are on the order of hundreds of femtoseconds, and can be precisely controlled by varying the tilted amplitude of the electron beam and/or the transverse gradient of the TGU radiator. Numerical simulations confirm the validity and feasibility of this scheme in the extreme ultraviolet waveband.

  9. Extraction of small boat harmonic signatures from passive sonar.

    PubMed

    Ogden, George L; Zurk, Lisa M; Jones, Mark E; Peterson, Mary E

    2011-06-01

    This paper investigates the extraction of acoustic signatures from small boats using a passive sonar system. Noise radiated from a small boats consists of broadband noise and harmonically related tones that correspond to engine and propeller specifications. A signal processing method to automatically extract the harmonic structure of noise radiated from small boats is developed. The Harmonic Extraction and Analysis Tool (HEAT) estimates the instantaneous fundamental frequency of the harmonic tones, refines the fundamental frequency estimate using a Kalman filter, and automatically extracts the amplitudes of the harmonic tonals to generate a harmonic signature for the boat. Results are presented that show the HEAT algorithms ability to extract these signatures. © 2011 Acoustical Society of America

  10. The Business Benefits of Apprenticeships: The English Employers' Perspective

    ERIC Educational Resources Information Center

    Kenyon, Rod

    2005-01-01

    Purpose - This paper seeks to present the Apprenticeships Task Forces ATFs evaluation of the business case for recruiting and training apprentices. The focus is on whether they provide employers in the UK with a positive return on investment in key performance areas. Design/methodology/approach - The ATF asked nine members, senior executives of…

  11. 75 FR 8528 - Procedures for Transportation Workplace Drug and Alcohol Testing Programs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-25

    ... updated U.S. DOT Alcohol Testing Form (ATF) and the Management Information System (MIS) Data Collection... included a revised U.S. DOT Alcohol Testing Form (ATF) and the Management Information System (MIS) Data...) and Management Information System (MIS) form Federal Register [73 FR 14300] and [73 FR 33140]. There...

  12. 27 CFR 478.99 - Certain prohibited sales or deliveries.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...; (6) Has been discharged from the Armed Forces under dishonorable conditions; (7) Who, having been a... explicitly prohibits the use, attempted use, or threatened use of physical force against such intimate... such ammunition. [T.D. ATF-270, 53 FR 10497, Mar. 31, 1988, as amended by T.D. ATF-363, 60 FR 17454...

  13. 78 FR 2363 - Notification of Deletion of a System of Records; Automated Trust Funds Database

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-11

    ... Database AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Notice of deletion of a system... establishing the Automated Trust Funds (ATF) database system of records. The Federal Information Security... Integrity Act of 1982, Public Law 97-255, provided authority for the system. The ATF database has been...

  14. Measured thermal and fast neutron fluence rates for ATF-1 holders during ATR cycle 158B/159A

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

    Smith, Larry Don; Miller, David Torbet; Walker, Billy Justin

    2016-11-01

    This report contains the thermal (2200 m/s) and fast (E>1MeV) neutron fluence rate data for the ATF-1 holders located in core for ATR Cycle 158B/159A which were measured by the Radiation Measurements Laboratory (RML).

  15. 77 FR 67026 - Agency Information Collection Activities: Proposed Collection; Comments Requested: Report of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-08

    ... Lost ATF Form 5400.30, Intrastate Purchase of Explosives Coupon ACTION: 60-day notice. The Department... the following four points: --Evaluate whether the proposed collection of information is necessary for... or Lost ATF F 5400.30, Intrastate Purchase Explosives Coupon. (3) Agency form number, if any, and the...

  16. 27 CFR 24.32 - Records.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Records. 24.32 Section 24.32 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE... control number 1512-0298) [T.D. ATF-299, 55 FR 24989, June 19, 1990, as amended by T.D. ATF-409, 64 FR...

  17. 27 CFR 18.17 - Retention of documents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Retention of documents. 18.17 Section 18.17 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Budget under control number 1512-0046) [T.D. ATF-104, 47 FR 23921, June 2, 1982, as amended by T.D. ATF...

  18. 27 CFR 24.32 - Records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Records. 24.32 Section 24.32 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE... control number 1512-0298) [T.D. ATF-299, 55 FR 24989, June 19, 1990, as amended by T.D. ATF-409, 64 FR...

  19. 27 CFR 24.60 - General.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false General. 24.60 Section 24.60 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE... Budget under control number 1512-0492) [T.D. ATF-299, 55 FR 24989, June 19, 1990, as amended by T.D. ATF...

  20. 27 CFR 24.60 - General.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false General. 24.60 Section 24.60 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE... Budget under control number 1512-0492) [T.D. ATF-299, 55 FR 24989, June 19, 1990, as amended by T.D. ATF...

  1. 78 FR 59720 - Agency Information Collection Activities: Proposed Collection; Comments Requested; Training...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-27

    ... Request for Non-ATF Employees ACTION: 30-Day notice. The Department of Justice (DOJ), Bureau of Alcohol... information is necessary for the proper performance of the functions of the agency, including whether the... Form/Collection: Training Registration Request for Non-ATF Employees. (3) Agency form number, if any...

  2. 78 FR 45275 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Training...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-26

    ... Request for Non-ATF Employees ACTION: 60-Day notice. The Department of Justice (DOJ), Bureau of Alcohol... performance of the functions of the agency, including whether the information will have practical utility... Request for Non-ATF Employees (3) Agency form number, if any, and the applicable component of the...

  3. Increased Amino Acid Uptake Supports Autophagy-Deficient Cell Survival upon Glutamine Deprivation.

    PubMed

    Zhang, Nan; Yang, Xin; Yuan, Fengjie; Zhang, Luyao; Wang, Yanan; Wang, Lina; Mao, Zebin; Luo, Jianyuan; Zhang, Hongquan; Zhu, Wei-Guo; Zhao, Ying

    2018-06-05

    Autophagy is a protein degradation process by which intracellular materials are recycled for energy homeostasis. However, the metabolic status and energy source of autophagy-defective tumor cells are poorly understood. Here, our data show that amino acid uptake from the extracellular environment is increased in autophagy-deficient cells upon glutamine deprivation. This elevated amino acid uptake results from activating transcription factor 4 (ATF4)-dependent upregulation of AAT (amino acid transporter) gene expression. Furthermore, we identify SIRT6, a NAD + -dependent histone deacetylase, as a corepressor of ATF4 transcriptional activity. In autophagy-deficient cells, activated NRF2 enhances ATF4 transcriptional activity by disrupting the interaction between SIRT6 and ATF4. In this way, autophagy-deficient cells exhibit increased AAT expression and show increased amino acid uptake. Notably, inhibition of amino acid uptake reduces the viability of glutamine-deprived autophagy-deficient cells, but not significantly in wild-type cells, suggesting reliance of autophagy-deficient tumor cells on extracellular amino acid uptake. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease

    PubMed Central

    Naranjo, José R.; Zhang, Hongyu; Villar, Diego; González, Paz; Dopazo, Xose M.; Morón-Oset, Javier; Higueras, Elena; Oliveros, Juan C.; Arrabal, María D.; Prieto, Angela; Cercós, Pilar; González, Teresa; De la Cruz, Alicia; Casado-Vela, Juan; Rábano, Alberto; Valenzuela, Carmen; Gutierrez-Rodriguez, Marta; Li, Jia-Yi; Mellström, Britt

    2016-01-01

    Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HD. PMID:26752648

  5. Interseismic Deformation across the Eastern Altyn Tagh Fault from Insar Measurements

    NASA Astrophysics Data System (ADS)

    Liu, C. J.; Zhao, C. Y.; Ji, L. Y.; Zhang, Z. R.; Sun, H.

    2018-04-01

    As a new type of earth observation technique, InSAR has a lot of advantages, such as all-weather, all-time, high precision, high density, wide coverage and low cost. It has been widely used in deformation monitoring. Taking the eastern segment of Altyn Tagh fault (ATF) as the object of the research, this paper discussed the application of multi-temporal InSAR technology in the field of interseismic deformation monitoring. We measured the interseismic deformation along the eastern section of ATF using three neighboring descending tracks SAR data from the ERS and Envisat missions. The results show that, first, the validation of InSAR results is better than 2.5 mm/yr, the calibration of InSAR results is about 1.06 mm/yr. Second, the fault slip rate in this segment is about 4-7 mm/yr, and is in the locked condition. Third, The InSAR velocity profile across the fault is the clear asymmetry with respect to ATF, it may be the combined effect of northern (NATF) and southern (SATF) branches of ATF.

  6. Role of Atf1 and Pap1 in the induction of the catalase gene of fission yeast schizosaccharomyces pombe.

    PubMed

    Nakagawa, C W; Yamada, K; Mutoh, N

    2000-02-01

    We examined the induction of the catalase gene (ctt1(+)) of fission yeast Schizosaccharomyces pombe in response to several stresses by using mutants of transcription factors (Atf1 and Pap1) and a series of deletion mutants of the ctt1(+) promoter region. A transcription factor, Atf1, and its binding site are necessary for the induction of ctt1(+) by osmotic stress, UV irradiation, and heat shock. Induction by menadione treatment, which produces superoxide anion, required element A, the region from -111 to -90 (numbered with the transcription start site as +1). The factor responsible for the induction of the gene by oxidative stress via element A was identified as the transcription factor Pap1. We also found that Atf1 is activated by menadione treatment in pap1 mutant cells, although it is not activated by menadione treatment in pap1(+) cells. The activity of catalase is not increased in pap1 cells by several stresses, despite mRNA induction, suggesting that Pap1 plays some role in the expression of catalase activity.

  7. Inertial confinement fusion quarterly report, October--December 1992. Volume 3, No. 1

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

    Dixit, S.N.

    1992-12-31

    This report contains papers on the following topics: The Beamlet Front End: Prototype of a new pulse generation system;imaging biological objects with x-ray lasers; coherent XUV generation via high-order harmonic generation in rare gases; theory of high-order harmonic generation; two-dimensional computer simulations of ultra- intense, short-pulse laser-plasma interactions; neutron detectors for measuring the fusion burn history of ICF targets; the recirculator; and lasnex evolves to exploit computer industry advances.

  8. Optical bistability and second-harmonic generation in thin film coupled cavity photonic crystal structures

    NASA Astrophysics Data System (ADS)

    Diao, Liyong

    This thesis deals with design, fabrication and modeling of bistable and multi-stable switching dynamics and second-harmonic generation in two groups of thin film coupled cavity photonic crystal structures. The first component studies optical bistability and multistability in such structures. Optical bistability and multistability are modelled by a nonlinear transfer matrix method. The second component is focused on the modelling and experimental measurement of second-harmonic generation in such structures. It is found that coupled cavity structures can reduce the threshold and index change for bistable operation, but single cavity structures can do the same. However, there is a clear advantage in using coupled cavity structures for multistability in that the threshold for multistability can be reduced. Second-harmonic generation is enhanced by field localization due to the resonant effect at the fundamental wavelength in single and coupled cavity structures by simulated and measured results. The work in this thesis makes three significant contributions. First, in the successful fabrication of thin film coupled cavity structures, the simulated linear transmissions of such structures match those of the fabricated structures almost exactly. Second, the newly defined figure of merit at the maximum transmission point on the bistable curve can be used to compare the material damage tolerance to any other Kerr effect nonlinear gate. Third, the simulated second-harmonic generation agrees excellently with experimental results. More generally optical thin film fabrication has commercial applications in many industry sections, such as electronics, opto-electronics, optical coating, solar cell and MEMS.

  9. Urinary exosomal transcription factors, a new class of biomarkers for renal disease

    PubMed Central

    Zhou, Hua; Cheruvanky, Anita; Hu, Xuzhen; Matsumoto, Takayuki; Hiramatsu, Noriyuki; Cho, Monique E.; Berger, Alexandra; Leelahavanichkul, Asada; Doi, Kent; Chawla, Lakhmir S.; Illei, Gabor G.; Kopp, Jeffrey B.; Balow, James E.; Austin, Howard A.; Yuen, Peter S.T.; Star, Robert A.

    2008-01-01

    Urinary exosomes are excreted from all nephron segments and are a rich source of kidney injury biomarkers. Because exosomes contain intracellular proteins, we asked if transcription factors (TF) can be measured in urinary exosomes. We collected urine from two acute kidney injury (AKI) models (cisplatin or ischemia/reperfusion) and two podocyte injury models (puromycin-treated rats and podocin/Vpr transgenic mice). Human urine was obtained from patients with AKI, focal segmental glomerulosclerosis (FSGS), and matched controls. After isolating urine exosomes by differential centrifugation, activating transcription factor 3 (ATF3) and Wilms Tumor 1 (WT-1) were detected by western blot. ATF3 was continuously detected in urine exosomes 2–24 hr after ischemia/reperfusion and in a biphasic pattern after cisplatin. In both models, urinary ATF3 was detected earlier than serum creatinine. Urinary ATF3 was detected in AKI patients but not in normal subjects or patients with chronic kidney disease (CKD). Urinary WT-1 was detected in animal models before significant glomerular sclerosis. Urinary WT-1 was detected in 9/10 FSGS patients, but not in 8 controls. Transcription factors can be detected in urine exosomes, but not in whole urine. Urinary ATF3 may be a novel renal tubular cell injury biomarker for detecting early AKI, whereas urinary WT-1 may detect early podocyte injury. Urinary exosomal TFs represent a new class of biomarkers for acute and chronic renal diseases and may offer insight into cellular regulatory pathways. PMID:18509321

  10. Measurement of impulse peak insertion loss from two acoustic test fixtures and four hearing protector conditions with an acoustic shock tube

    PubMed Central

    Murphy, William J.; Fackler, Cameron J.; Berger, Elliott H.; Shaw, Peter B.; Stergar, Mike

    2015-01-01

    Impulse peak insertion loss (IPIL) was studied with two acoustic test fixtures and four hearing protector conditions at the E-A-RCAL Laboratory. IPIL is the difference between the maximum estimated pressure for the open-ear condition and the maximum pressure measured when a hearing protector is placed on an acoustic test fixture (ATF). Two models of an ATF manufactured by the French-German Research Institute of Saint-Louis (ISL) were evaluated with high-level acoustic impulses created by an acoustic shock tube at levels of 134 decibels (dB), 150 dB, and 168 dB. The fixtures were identical except that the E-A-RCAL ISL fixture had ear canals that were 3 mm longer than the National Institute for Occupational Safety and Health (NIOSH) ISL fixture. Four hearing protection conditions were tested: Combat Arms earplug with the valve open, ETYPlugs® earplug, TacticalPro headset, and a dual-protector ETYPlugs earplug with TacticalPro earmuff. The IPILs measured for the E-A-RCAL fixture were 1.4 dB greater than the National Institute for Occupational Safety and Health (NIOSH) ISL ATF. For the E-A-RCAL ISL ATF, the left ear IPIL was 2.0 dB greater than the right ear IPIL. For the NIOSH ATF, the right ear IPIL was 0.3 dB greater than the left ear IPIL. PMID:26356380

  11. MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4*

    PubMed Central

    Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai; Wang, Chunxia; Guo, Feifan

    2015-01-01

    Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1 (FOXO1) transcriptional activity. Finally, liver-specific miR-214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. PMID:25657009

  12. Amino Acid Availability Controls TRB3 Transcription in Liver through the GCN2/eIF2α/ATF4 Pathway

    PubMed Central

    Carraro, Valérie; Maurin, Anne-Catherine; Lambert-Langlais, Sarah; Averous, Julien; Chaveroux, Cédric; Parry, Laurent; Jousse, Céline; Örd, Daima; Örd, Tõnis; Fafournoux, Pierre; Bruhat, Alain

    2010-01-01

    In mammals, plasma amino acid concentrations are markedly affected by dietary or pathological conditions. It has been well established that amino acids are involved in the control of gene expression. Up to now, all the information concerning the molecular mechanisms involved in the regulation of gene transcription by amino acid availability has been obtained in cultured cell lines. The present study aims to investigate the mechanisms involved in transcriptional activation of the TRB3 gene following amino acid limitation in mice liver. The results show that TRB3 is up-regulated in the liver of mice fed a leucine-deficient diet and that this induction is quickly reversible. Using transient transfection and chromatin immunoprecipitation approaches in hepatoma cells, we report the characterization of a functional Amino Acid Response Element (AARE) in the TRB3 promoter and the binding of ATF4, ATF2 and C/EBPβ to this AARE sequence. We also provide evidence that only the binding of ATF4 to the AARE plays a crucial role in the amino acid-regulated transcription of TRB3. In mouse liver, we demonstrate that the GCN2/eIF2α/ATF4 pathway is essential for the induction of the TRB3 gene transcription in response to a leucine-deficient diet. Therefore, this work establishes for the first time that the molecular mechanisms involved in the regulation of gene transcription by amino acid availability are functional in mouse liver. PMID:21203563

  13. Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe

    PubMed Central

    Travison, Thomas G.; Vesper, Hubert W.; Orwoll, Eric; Wu, Frederick; Kaufman, Jean Marc; Wang, Ying; Lapauw, Bruno; Fiers, Tom; Matsumoto, Alvin M.

    2017-01-01

    Background: Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men. Objective: To establish harmonized reference ranges for total testosterone in men that can be applied across laboratories by cross-calibrating assays to a reference method and standard. Population: The 9054 community-dwelling men in cohort studies in the United States and Europe: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; and Male Sibling Study of Osteoporosis. Methods: Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method at Centers for Disease Control and Prevention (CDC). Generalized additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values. Normalizing equations, generated using Passing-Bablok regression, were used to generate harmonized values, which were used to derive standardized, age-specific reference ranges. Results: Harmonization procedure reduced intercohort variation between testosterone measurements in men of similar ages. In healthy nonobese men, 19 to 39 years, harmonized 2.5th, 5th, 50th, 95th, and 97.5th percentile values were 264, 303, 531, 852, and 916 ng/dL, respectively. Age-specific harmonized testosterone concentrations in nonobese men were similar across cohorts and greater than in all men. Conclusion: Harmonized normal range in a healthy nonobese population of European and American men, 19 to 39 years, is 264 to 916 ng/dL. A substantial proportion of intercohort variation in testosterone levels is due to assay differences. These data demonstrate the feasibility of generating harmonized reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator. PMID:28324103

  14. Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice.

    PubMed

    Nikonorova, Inna A; Al-Baghdadi, Rana J T; Mirek, Emily T; Wang, Yongping; Goudie, Michael P; Wetstein, Berish B; Dixon, Joseph L; Hine, Christopher; Mitchell, James R; Adams, Christopher M; Wek, Ronald C; Anthony, Tracy G

    2017-04-21

    Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 ( Atf4 ) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Apomorphine prevents LPS-induced IL-23 p19 mRNA expression via inhibition of JNK and ATF4 in HAPI cells.

    PubMed

    Hara, Hirokazu; Kimoto, Dai; Kajita, Miho; Takada, Chisato; Kamiya, Tetsuro; Adachi, Tetsuo

    2017-01-15

    Inflammation has been reported to be closely related to exaggeration of cerebral ischemia and neurodegenerative diseases. Microglia, resident immune cells in the central nervous system, can be activated in response to neuronal injury and produce proinflammatory cytokines, resulting in further aggravation of neuronal injury. Interleukin (IL)-23, which consists of p19 and IL-12 p40 subunits, has been shown to be involved in brain injury associated with neuroinflammation. Apomorphine (Apo), a nonselective dopamine receptor agonist, has been used for clinical therapy of Parkinson's disease. Besides the pharmacological effect, Apo is known to have pleiotropic biological functions. In this study, to elucidate the effect of Apo on lipopolysaccharide (LPS)-induced IL-23 p19 mRNA expression in microglial cell line HAPI cells, we pretreated cells with various concentrations of Apo (10 - 30μM) for 8, 16, and 24h, followed by exposure to LPS (100ng/ml). Pretreatment with Apo dose- and time-dependently suppressed the induction of IL-23 p19 mRNA. However, this effect of Apo was exerted independently of dopamine receptors. JNK and ATF4, an endoplasmic reticulum (ER) stress-inducible transcription factor, were involved in expression of LPS-induced IL-23 p19 mRNA. Pretreatment with Apo (30μM) for 24h inhibited LPS-induced activation of JNK and the nuclear accumulation of ATF4. Thapsigargin (Tg), an ER stress inducer, stimulated IL-23 p19 mRNA expression via an ATF4 dependent mechanism. We also found that Apo inhibited Tg-induced ATF4 accumulation and IL-23 p19 mRNA expression. Taken together, our findings suggest that Apo exerts anti-inflammatory effects through inhibition of JNK and ATF4 signaling pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Very High Density of Chinese Hamster Ovary Cells in Perfusion by Alternating Tangential Flow or Tangential Flow Filtration in WAVE Bioreactor™—Part II: Applications for Antibody Production and Cryopreservation

    PubMed Central

    Clincke, Marie-Françoise; Mölleryd, Carin; Samani, Puneeth K; Lindskog, Eva; Fäldt, Eric; Walsh, Kieron; Chotteau, Véronique

    2013-01-01

    A high cell density perfusion process of monoclonal antibody (MAb) producing Chinese hamster ovary (CHO) cells was developed in disposable WAVE Bioreactor™ using external hollow fiber (HF) filter as cell separation device. Tangential flow filtration (TFF) and alternating tangential flow (ATF) systems were compared and process applications of high cell density perfusion were studied here: MAb production and cryopreservation. Operations by perfusion using microfiltration (MF) or ultrafiltration (UF) with ATF or TFF and by fed-batch were compared. Cell densities higher than 108 cells/mL were obtained using UF TFF or UF ATF. The cells produced comparable amounts of MAb in perfusion by ATF or TFF, MF or UF. MAbs were partially retained by the MF using ATF or TFF but more severely using TFF. Consequently, MAbs were lost when cell broth was discarded from the bioreactor in the daily bleeds. The MAb cell-specific productivity was comparable at cell densities up to 1.3 × 108 cells/mL in perfusion and was comparable or lower in fed-batch. After 12 days, six times more MAbs were harvested using perfusion by ATF or TFF with MF or UF, compared to fed-batch and 28× more in a 1-month perfusion at 108 cells/mL density. Pumping at a recirculation rate up to 2.75 L/min did not damage the cells with the present TFF settings with HF short circuited. Cell cryopreservation at 0.5 × 108 and 108 cells/mL was performed using cells from a perfusion run at 108 cells/mL density. Cell resuscitation was very successful, showing that this system was a reliable process for cell bank manufacturing. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:768–777, 2013 PMID:23436783

  17. Blockade of anoctamin-1 in injured and uninjured nerves reduces neuropathic pain.

    PubMed

    García, Guadalupe; Martínez-Rojas, Vladimir A; Oviedo, Norma; Murbartián, Janet

    2018-06-02

    The aim of this study was to determine the participation of anoctamin-1 in 2 models of neuropathic pain in rats (L5/L6 spinal nerve ligation [SNL] and L5 spinal nerve transection [SNT]). SNL and SNT diminished withdrawal threshold in rats. Moreover, SNL up-regulated anoctamin-1 protein expression in injured L5 and uninjured L4 DRG whereas that it enhanced activating transcription factor 3 (ATF-3) and caspase-3 expression only in injured L5 DRG. In marked contrast, SNT enhanced ATF-3 and caspase-3, but not anoctamin-1, expression in injured L5 DRG but it did not modify anoctamin-1, ATF-3 nor caspase-3 expression in uninjured L4 DRG. Accordingly, repeated (3 times) intrathecal injection of the anoctamin-1 blocker T16A inh-A01 (0.1-1 µg) or MONNA (1-10 µg) partially reverted SNL-induced mechanical allodynia in a dose-dependent manner. In contrast, anoctamin-1 blockers only produced a modest effect in SNT-induced mechanical allodynia. Interestingly, intrathecal injection of T16A inh-A01 (1 µg) or MONNA (10 µg) prevented SNL-induced up-regulation of anoctamin-1, ATF-3 and caspase-3 in injured L5 DRG. Repeated intrathecal injection of T16A inh-A01 or MONNA also reduced SNT-induced up-regulation of ATF-3 in injured L5 DRG. In contrast, T16A inh-A01 and MONNA did not affect SNT-induced up-regulation of caspase-3 expression in L5 DRG. Likewise, gabapentin (100 µg) diminished SNL-induced up-regulation of anoctamin-1, ATF-3 and caspase-3 expression in injured L5 DRG. These data suggest that spinal anoctamin-1 in injured and uninjured DRG participates in the maintenance of neuropathic pain in rats. Our data also indicate that expression of anoctamin-1 in DRG is differentially regulated depending on the neuropathic pain model. Copyright © 2018. Published by Elsevier B.V.

  18. Cytotoxic activity of the twigs of Cinnamomum cassia through the suppression of cell proliferation and the induction of apoptosis in human colorectal cancer cells.

    PubMed

    Park, Gwang Hun; Song, Hun Min; Park, Su Bin; Son, Ho-Jun; Um, Yurry; Kim, Hyun-Seok; Jeong, Jin Boo

    2018-01-25

    Because twigs of Cinnamomum cassia (TC) have been reported to exert anti-cancer activity, the mechanistic study for TC's anti-cancer activity is required. Thus, we elucidated the potential molecular mechanism of TC's anti-proliferative effect and the induction of apoptosis in human colorectal cancer cells. How water extracts form TC (TC-HW) was used in this study. Anti-cell proliferative effect of TC-HW was evaluated by MTT assay. The change of protein or mRNA level by TC-HW was evaluated by Western blot and RT-RCR, respectively. The promoter construct for ATF3, NF-κB, TOP-FLASH or FOP-FLASH was used for the investigation of the transcriptional activity for ATF3, NF-κB or Wnt. siRNA for ATF3 or p65 was used for the knockdown of ATF3 and p65. TC-HW reduced the cell viability in human colorectal cancer cells. TC-HW decreased cyclin D1 protein level through cyclin D1 degradation via GSK3β-dependent threonine-286 (T286) phosphorylation of cyclin D1, indicating that cyclin D1 degradation may contribute to TC-HW-mediated decrease of cyclin D1 protein level. TC-HW downregulated the expression of cyclin D1 mRNA level and inhibited Wnt activation through the downregulation of β-catenin and TCF4 expression, indicating that inhibition of cyclin D1 transcription may also result in TC-HW-mediated decrease of cyclin D1 protein level. In addition, TC-HW was observed to induce apoptosis through ROS-dependent DNA damage. TC-HW-induced ROS increased NF-κB and ATF3 activation, and inhibition of NF-κB and ATF3 activation attenuated TC-HW-mediated apoptosis. Our results suggest that TC-HW may suppress cell proliferation through the downregulation of cyclin D1 via proteasomal degradation and transcriptional inhibition, and may induce apoptosis through ROS-dependent NF-κB and ATF3 activation. These effects of TC-HW may contribute to the reduction of cell viability in human colorectal cancer cells. From these findings, TC-HW has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

  19. Polarization properties of below-threshold harmonics from aligned molecules H2+ in linearly polarized laser fields.

    PubMed

    Dong, Fulong; Tian, Yiqun; Yu, Shujuan; Wang, Shang; Yang, Shiping; Chen, Yanjun

    2015-07-13

    We investigate the polarization properties of below-threshold harmonics from aligned molecules in linearly polarized laser fields numerically and analytically. We focus on lower-order harmonics (LOHs). Our simulations show that the ellipticity of below-threshold LOHs depends strongly on the orientation angle and differs significantly for different harmonic orders. Our analysis reveals that this LOH ellipticity is closely associated with resonance effects and the axis symmetry of the molecule. These results shed light on the complex generation mechanism of below-threshold harmonics from aligned molecules.

  20. Active tectonic extension across the Alto Tiberina normal fault system from GPS data modeling and InSAR velocity maps: new perspectives within TABOO Near Fault Observatory

    NASA Astrophysics Data System (ADS)

    Vadacca, Luigi; Anderlini, Letizia; Casarotti, Emanuele; Serpelloni, Enrico; Chiaraluce, Lauro; Polcari, Marco; Albano, Matteo; Stramondo, Salvatore

    2014-05-01

    The Alto Tiberina fault (ATF) is a low-angle (east-dipping at 15°) normal fault (LANF) 70 km long placed in the Umbria-Marche Apennines (central Italy), characterized by SW-NE oriented extension occurring at rates of 2-3 mm/yr. These rates were measured by continuous GPS stations belonging to several networks, which are denser in the study area thanks to additional sites recently installed in the framework of the INGV national RING network and of the ATF observatory. In this area historical and instrumental earthquakes mainly occur on west-dipping high-angle normal faults. Within this context the ATF has accumulated 2 km of displacement over the past 2 Ma, but at the same time the deformation processes active along this misoriented fault, as well as its mechanical behavior, are still unknown. We tackle this issue by solving for interseismic deformation models obtained by two different methods. At first, through the 2D and 3D finite element modeling, we define the effects of locking depth, synthetic and antithetic fault activity and lithology on the velocity gradient measured along the ATF system. Subsequently through a block modeling approach, we model the GPS velocities by considering the major fault systems as bounds of rotating blocks, while estimating the corresponding geodetic fault slip-rates and maps of heterogeneous fault coupling. Thanks to the latest imaging of the ATF deep structure obtained from seismic profiles, we improve the proposed models by modeling the fault as a complex rough surface to understand where the stress accumulations are located and the interseismic coupling changes. The preliminary results obtained show firstly that the observed extension is mainly accommodated by interseismic deformation on both the ATF and antithetic faults, highlighting the important role of this LANF inside an active tectonic contest. Secondarily, using the ATF surface "topography", we find an interesting correlation between microseismicty and creeping portions of the ATF. Future perspectives within this study is to validate these models using velocity maps and temporal series provided by Differential Interferometric SAR (DInSAR) technique applied to a datasets of ERS 1-2 and ENVISAT SAR images. These data cover a time interval spanning from 1992 to 2010 and have been acquired along both ascending and descending orbit. In addition we will deploy a network of SAR passive Corner Reflectors (CRs) in the proximity of GPS monuments in order to calibrate the results of processing a set of COSMO-SkyMed SAR data and derive velocity maps. Thus the availability of high-resolution data will contribute to understand the mechanics of the LANFs and to evaluate the seismic potential associated to these geologic structures.

  1. High-harmonic spectroscopy of oriented OCS molecules: emission of even and odd harmonics.

    PubMed

    Kraus, P M; Rupenyan, A; Wörner, H J

    2012-12-07

    We study the emission of even and odd high-harmonic orders from oriented OCS molecules. We use an intense, nonresonant femtosecond laser pulse superimposed with its phase-controlled second harmonic field to impulsively align and orient a dense sample of molecules from which we subsequently generate high-order harmonics. The even harmonics appear around the full revivals of the rotational dynamics. We demonstrate perfect coherent control over their intensity through the subcycle delay of the two-color fields. The odd harmonics are insensitive to the degree of orientation, but modulate with the degree of axis alignment, in agreement with calculated photorecombination dipole moments. We further compare the shape of the even and odd harmonic spectra with our calculations and determine the degree of orientation.

  2. Separation of High Order Harmonics with Fluoride Windows

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

    Allison, Tom; van Tilborg, Jeroen; Wright, Travis

    2010-08-02

    The lower orders produced in high order harmonic generation can be effciently temporally separated into monochromatic pulses by propagation in a Fluoride window while still preserving their femtosecond pulse duration. We present calculations for MgF2, CaF2, and LiF windows for the third, fifth, and seventh harmonics of 800 nm. We demonstrate the use of this simple and inexpensive technique in a femtosecond pump/probe experiment using the fifth harmonic.

  3. High-harmonic generation from an atomically thin semiconductor [Observation of high harmonics from an atomically thin semiconductor

    DOE PAGES

    Liu, Hanzhe; Li, Yilei; You, Yong Sing; ...

    2016-11-14

    High-harmonic generation (HHG) in bulk solids permits the exploration of materials in a new regime of strong fields and attosecond timescales. The generation process has been discussed in the context of strongly driven electron dynamics in single-particle bands. Two-dimensional materials exhibit distinctive electronic properties compared to the bulk that could significantly modify the HHG process, including different symmetries, access to individual valleys and enhanced many-body interactions. Here we demonstrate non-perturbative HHG from a monolayer MoS 2 crystal, with even and odd harmonics extending to the 13th order. The even orders are predominantly polarized perpendicular to the pump and are compatiblemore » with the anomalous transverse intraband current arising from the material’s Berry curvature, while the weak parallel component suggests the importance of interband transitions. The odd harmonics exhibit a significant enhancement in efficiency per layer compared to the bulk, which is attributed to correlation effects. In conclusion, the combination of strong many-body Coulomb interactions and widely tunable electronic properties in two-dimensional materials offers a new platform for attosecond physics.« less

  4. Laser waveform control of extreme ultraviolet high harmonics from solids.

    PubMed

    You, Yong Sing; Wu, Mengxi; Yin, Yanchun; Chew, Andrew; Ren, Xiaoming; Gholam-Mirzaei, Shima; Browne, Dana A; Chini, Michael; Chang, Zenghu; Schafer, Kenneth J; Gaarde, Mette B; Ghimire, Shambhu

    2017-05-01

    Solid-state high-harmonic sources offer the possibility of compact, high-repetition-rate attosecond light emitters. However, the time structure of high harmonics must be characterized at the sub-cycle level. We use strong two-cycle laser pulses to directly control the time-dependent nonlinear current in single-crystal MgO, leading to the generation of extreme ultraviolet harmonics. We find that harmonics are delayed with respect to each other, yielding an atto-chirp, the value of which depends on the laser field strength. Our results provide the foundation for attosecond pulse metrology based on solid-state harmonics and a new approach to studying sub-cycle dynamics in solids.

  5. Understanding Collagen Organization in Breast Tumors to Predict and Prevent Metastasis

    DTIC Science & Technology

    2014-09-01

    Harmonic Generation to Image the Extracellular Matrix During Tumor Progression. Invited Perspective Intravital Manuscript Submitted. Sullivan K...harmonic generation (the SHG “F/B ratio”) in thick intact tissue, with a single image scan. This will be necessary for us to pursue our goal of...quantifying matrix changes dynamically, in intact tumor models. The first method determines F/B by generating a series of backscattered images using a series

  6. Generation of lower and upper bands of electrostatic electron cyclotron harmonic waves in the Van Allen radiation belts

    DOE PAGES

    Zhou, Qinghua; Xiao, Fuliang; Yang, Chang; ...

    2017-05-22

    Electrostatic electron cyclotron harmonic (ECH) waves generated by the electron loss cone distribution can produce efficient scattering loss of plasma sheet electrons, which has a significant effect on the dynamics in the outer magnetosphere. Here we report two ECH emission events around the same location L≈ 5.7–5.8, MLT ≈ 12 from Van Allen Probes on 11 February (event A) and 9 January 2014 (event B), respectively. The spectrum of ECH waves was centered at the lower half of the harmonic bands during event A, but the upper half during event B. The observed electron phase space density in both eventsmore » is fitted by the subtracted bi-Maxwellian distribution, and the fitting functions are used to evaluate the local growth rates of ECH waves based on a linear theory for homogeneous plasmas. ECH waves are excited by the loss cone instability of 50 eV–1 keV electrons in the lower half of harmonic bands in the low-density plasmasphere in event A, and 1–10 keV electrons in the upper half of harmonic bands in a relatively high-density region in event B. Here, the current results successfully explain observations and provide a first direct evidence on how ECH waves are generated in the lower and upper half of harmonic frequency bands.« less

  7. Generation of lower and upper bands of electrostatic electron cyclotron harmonic waves in the Van Allen radiation belts

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

    Zhou, Qinghua; Xiao, Fuliang; Yang, Chang

    Electrostatic electron cyclotron harmonic (ECH) waves generated by the electron loss cone distribution can produce efficient scattering loss of plasma sheet electrons, which has a significant effect on the dynamics in the outer magnetosphere. Here we report two ECH emission events around the same location L≈ 5.7–5.8, MLT ≈ 12 from Van Allen Probes on 11 February (event A) and 9 January 2014 (event B), respectively. The spectrum of ECH waves was centered at the lower half of the harmonic bands during event A, but the upper half during event B. The observed electron phase space density in both eventsmore » is fitted by the subtracted bi-Maxwellian distribution, and the fitting functions are used to evaluate the local growth rates of ECH waves based on a linear theory for homogeneous plasmas. ECH waves are excited by the loss cone instability of 50 eV–1 keV electrons in the lower half of harmonic bands in the low-density plasmasphere in event A, and 1–10 keV electrons in the upper half of harmonic bands in a relatively high-density region in event B. Here, the current results successfully explain observations and provide a first direct evidence on how ECH waves are generated in the lower and upper half of harmonic frequency bands.« less

  8. Walk-off reduction, using an external optical plate and Bessel-Gaussian interaction

    NASA Astrophysics Data System (ADS)

    Masoume, Mansouri; Mohsen, Askarbioki; Saeed Ghavami, Sabouri; Alireza, Khorsandi

    2015-02-01

    To reduce the walk-off angle of the extraordinary third-harmonic ultraviolet wave at 355 nm generated by type II KTiOPO4 and type I β-BaB2O4 optical crystals, and the Gaussian output beam of a Q-switched Nd:YAG laser, a simple theoretical model was developed based on a rotatable BK7 plate of variable thickness. By rotating the plate up to 35° along the beam direction, we reduced the walk-off angle up to ˜ 13%. The same phenomenon is predicted by the model, confirming the performance of the model. It is found that, due to the walk-off effect, the intensity profile of the third-harmonic generation beam is slightly degraded. To compensate for the observed phenomena and further reduce the walk-off, we used a combination of a convex lens and an axicon to transform the beam profile of the interacting fundamental and second-harmonic generation waves to the zero-order Bessel-Gaussian form. As a result, the walk-off is decreased to ˜48.81 mrad, providing ˜30% relative reduction. By using the same BK7 plate rotated up to 35° along the third-harmonic beam direction, the walk-off angle is further reduced to 38.9 mrad. Moreover, it is observed that the beam profile of the emerged Bessel-Gaussian third-harmonic generation beam remains unchanged with no degradation.

  9. A Compact Ti:Sapphire Laser With its Third Harmonic Generation (THG) for an Airborne Ozone Differential Absorption Lidar (DIAL) Transmitter

    NASA Technical Reports Server (NTRS)

    Chen, Songsheng; Storm, Mark E.; Marsh, Waverly D.; Petway, Larry B.; Edwards, William C.; Barnes, James C.

    2000-01-01

    A compact and high-pulse-energy Ti:Sapphire laser with its Third Harmonic Generation (THG) has been developed for an airborne ozone differential absorption lidar (DIAL) to study the distributions and concentrations of the ozone throughout the troposphere. The Ti:Sapphire laser, pumped by a frequency-doubled Nd:YAG laser and seeded by a single mode diode laser, is operated either at 867 nm or at 900 nm with a pulse repetition frequency of 20 Hz. High energy laser pulses (more than 110 mJ/pulse) at 867 nm or 900 nm with a desired beam quality have been achieved and utilized to generate its third harmonic at 289nm or 300nm, which are on-line and off-line wavelengths of an airborne ozone DIAL. After being experimentally compared with Beta-Barium Borate (beta - BaB2O4 or BBO) nonlinear crystals, two Lithium Triborate (LBO) crystals (5 x 5 x 20 cu mm) are selected for the Third Harmonic Generation (THG). In this paper, we report the Ti:Sapphire laser at 900 nm and its third harmonic at 300 nm. The desired high ultraviolet (UV) output pulse energy is more than 30 mJ at 300 nm and the energy conversion efficiency from 900 nm to 300 nm is 30%.

  10. Study of Nonlinear Propagation of Ultrashort Laser Pulses and Its Application to Harmonic Generation

    NASA Astrophysics Data System (ADS)

    Weerawarne, Darshana L.

    Laser filamentation, which is one of the exotic nonlinear optical phenomena, is self-guidance of high-power laser beams due to the dynamic balance between the optical Kerr effect (self-focusing) and other nonlinear effects such as plasma defocusing. It has many applications including supercontinuum generation (SCG), high-order harmonic generation (HHG), lightning guiding, stand-off sensing, and rain making. The main focus of this work is on studying odd-order harmonic generation (HG) (i.e., 3o, 5o, 7o, etc., where o is the angular frequency) in centrosymmetric media while a high-power, ultrashort harmonic-driving pulse undergoes nonlinear propagation such as laser filamentation. The investigation of highly-controversial nonlinear indices of refraction by measuring low-order HG in air is carried out. Furthermore, time-resolved (i.e., pump-probe) experiments and significant harmonic enhancements are presented and a novel HG mechanism based on higher-order nonlinearities is proposed to explain the experimental results. C/C++ numerical simulations are used to solve the nonlinear Schrodinger equation (NLSE) which supports the experimental findings. Another project which I have performed is selective sintering using lasers. Short-pulse lasers provide a fascinating tool for material processing, especially when the conventional oven-based techniques fail to process flexible materials for smart energy/electronics applications. I present experimental and theoretical studies on laser processing of nanoparticle-coated flexible materials, aiming to fabricate flexible electronic devices.

  11. High second-harmonic generation of antiferromagnetic/ionic-crystal composite medium with negative refraction

    NASA Astrophysics Data System (ADS)

    Song, Yu-Ling; Ta, Jin-Xing; Wang, Xuan-Zhang

    2012-03-01

    Second harmonic generation (SHG) from a short-period structure composed of alternating antiferromagnetic (AF) and ionic-crystal layers is investigated, where the generated harmonic waves are situated in the far-infrared range and attributed to the magnetically nonlinear interaction in AF layers. The presence of a kind of appropriate ionic-crystal layers in the structure can support negative refraction for the pumping wave and positive refraction for the SH wave, so the SHG is greatly amplified in the vicinity of each AF resonant frequency. For the composite structure FeF2/TlBr, we found that the SH output is about 8 times higher than that of the FeF2 bulk in the same frequency range.

  12. Energy exchange properties during second-harmonic generation in finite one-dimensional photonic band-gap structures with deep gratings.

    PubMed

    D'Aguanno, Giuseppe; Centini, Marco; Scalora, Michael; Sibilia, Concita; Bertolotti, Mario; Bloemer, Mark J; Bowden, Charles M

    2003-01-01

    We study second-harmonic generation in finite, one-dimensional, photonic band-gap structures with large index contrast in the regime of pump depletion and global phase-matching conditions. We report a number of surprising results: above a certain input intensity, field dynamics resemble a multiwave mixing process, where backward and forward components compete for the available energy; the pump field is mostly reflected, revealing a type of optical limiting behavior; and second-harmonic generation becomes balanced in both directions, showing unusual saturation effects with increasing pump intensity. This dynamics was unexpected, and it is bound to influence the way one goes about thinking and designing nonlinear frequency conversion devices in a practical way.

  13. Quasi-phase-matching and second-harmonic generation enhancement in a semiconductor microresonator array using slow-light effects

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

    Dumeige, Yannick

    We theoretically analyze the second-harmonic generation process in a sequence of unidirectionnaly coupled doubly resonant whispering gallery mode semiconductor resonators. By using a convenient design, it is possible to coherently sum the second-harmonic fields generated inside each resonator. We show that resonator coupling allows the bandwidth of the phase-matching curve to be increased with respect to single-resonator configurations simultaneously taking advantage of the resonant feature of the resonators. This quasi-phase-matching technique could be applied to obtain small-footprint nonlinear devices with large bandwidth and limited nonlinear losses. The results are discussed in the framework of the slow-light-effect enhancement of second-order opticalmore » nonlinearities.« less

  14. Self-starting harmonic frequency comb generation in a quantum cascade laser

    NASA Astrophysics Data System (ADS)

    Kazakov, Dmitry; Piccardo, Marco; Wang, Yongrui; Chevalier, Paul; Mansuripur, Tobias S.; Xie, Feng; Zah, Chung-en; Lascola, Kevin; Belyanin, Alexey; Capasso, Federico

    2017-12-01

    Optical frequency combs1,2 establish a rigid phase-coherent link between microwave and optical domains and are emerging as high-precision tools in an increasing number of applications3. Frequency combs with large intermodal spacing are employed in the field of microwave photonics for radiofrequency arbitrary waveform synthesis4,5 and for the generation of terahertz tones of high spectral purity in future wireless communication networks6,7. Here, we demonstrate self-starting harmonic frequency comb generation with a terahertz repetition rate in a quantum cascade laser. The large intermodal spacing caused by the suppression of tens of adjacent cavity modes originates from a parametric contribution to the gain due to temporal modulations of population inversion in the laser8,9. Using multiheterodyne self-detection, the mode spacing of the harmonic comb is shown to be uniform to within 5 × 10-12 parts of the central frequency. This new harmonic comb state extends the range of applications of quantum cascade laser frequency combs10-13.

  15. Anisotropic high-harmonic generation in bulk crystals

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

    You, Yong Sing; Reis, David A.; Ghimire, Shambhu

    2016-11-21

    The microscopic valence electron density determines the optical, electronic, structural and thermal properties of materials. However, current techniques for measuring this electron charge density are limited: for example, scanning tunnelling microscopy is confined to investigations at the surface, and electron diffraction requires very thin samples to avoid multiple scattering. Therefore, an optical method is desirable for measuring the valence charge density of bulk materials. Since the discovery of high-harmonic generation (HHG) in solids, there has been growing interest in using HHG to probe the electronic structure of solids. Here, using single-crystal MgO, we demonstrate that high-harmonic generation in solids ismore » sensitive to interatomic bonding. We find that harmonic efficiency is enhanced (diminished) for semi-classical electron trajectories that connect (avoid) neighbouring atomic sites in the crystal. Finally, these results indicate the possibility of using materials’ own electrons for retrieving the interatomic potential and thus the valence electron density, and perhaps even wavefunctions, in an all-optical setting.« less

  16. 75 FR 48362 - Hearing Procedures Relating to Federal Firearms Licenses (2010R-2T)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-10

    ... Attorney General and the Deputy Attorney General. 28 CFR 0.130(a). ATF has promulgated regulations that... ATF by 28 U.S.C. 599A and 28 CFR 0.130-0.133, the authority to issue notices, conduct licensing... unlicensed person without providing a secure gun storage or safety device. [[Page 48363

  17. 27 CFR 9.49 - Central Delaware Valley.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... starting point of the following boundary description is the summit of Strawberry Hill, which is located in.... (2) Boundary Description: (i) From the summit of Strawberry Hill (475 feet) in a straight line to the... summit of Strawberry Hill (475 feet). [T.D. ATF-168, 49 FR 10117, Mar. 19, 1984, as amended by T.D. ATF...

  18. 27 CFR 9.49 - Central Delaware Valley.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... starting point of the following boundary description is the summit of Strawberry Hill, which is located in.... (2) Boundary Description: (i) From the summit of Strawberry Hill (475 feet) in a straight line to the... summit of Strawberry Hill (475 feet). [T.D. ATF-168, 49 FR 10117, Mar. 19, 1984, as amended by T.D. ATF...

  19. 27 CFR 9.49 - Central Delaware Valley.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... starting point of the following boundary description is the summit of Strawberry Hill, which is located in.... (2) Boundary Description: (i) From the summit of Strawberry Hill (475 feet) in a straight line to the... summit of Strawberry Hill (475 feet). [T.D. ATF-168, 49 FR 10117, Mar. 19, 1984, as amended by T.D. ATF...

  20. 27 CFR 9.49 - Central Delaware Valley.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... starting point of the following boundary description is the summit of Strawberry Hill, which is located in.... (2) Boundary Description: (i) From the summit of Strawberry Hill (475 feet) in a straight line to the... summit of Strawberry Hill (475 feet). [T.D. ATF-168, 49 FR 10117, Mar. 19, 1984, as amended by T.D. ATF...

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